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  1. Article ; Online: Crystallographic investigation of the ubiquinone binding site of respiratory Complex II and its inhibitors.

    Huang, Li-Shar / Lümmen, Peter / Berry, Edward A

    Biochimica et biophysica acta. Proteins and proteomics

    2021  Volume 1869, Issue 9, Page(s) 140679

    Abstract: The quinone binding site (Q-site) of Mitochondrial Complex II (succinate-ubiquinone oxidoreductase) is the target for a number of inhibitors useful for elucidating the mechanism of the enzyme. Some of these have been developed as fungicides or pesticides, ...

    Abstract The quinone binding site (Q-site) of Mitochondrial Complex II (succinate-ubiquinone oxidoreductase) is the target for a number of inhibitors useful for elucidating the mechanism of the enzyme. Some of these have been developed as fungicides or pesticides, and species-specific Q-site inhibitors may be useful against human pathogens. We report structures of chicken Complex II with six different Q-site inhibitors bound, at resolutions 2.0-2.4 Å. These structures show the common interactions between the inhibitors and their binding site. In every case a carbonyl or hydroxyl oxygen of the inhibitor is H-bonded to Tyr58 in subunit SdhD and Trp173 in subunit SdhB. Two of the inhibitors H-bond Ser39 in subunit SdhC directly, while two others do so via a water molecule. There is a distinct cavity that accepts the 2-substituent of the carboxylate ring in flutolanil and related inhibitors. A hydrophobic "tail pocket" opens to receive a side-chain of intermediate-length inhibitors. Shorter inhibitors fit entirely within the main binding cleft, while the long hydrophobic side chains of ferulenol and atpenin A5 protrude out of the cleft into the bulk lipid region, as presumably does that of ubiquinone. Comparison of mitochondrial and Escherichia coli Complex II shows a rotation of the membrane-anchor subunits by 7° relative to the iron‑sulfur protein. This rotation alters the geometry of the Q-site and the H-bonding pattern of SdhB:His216 and SdhD:Asp57. This conformational difference, rather than any active-site mutation, may be responsible for the different inhibitor sensitivity of the bacterial enzyme.
    MeSH term(s) Amino Acid Sequence/genetics ; Animals ; Benzoquinones ; Binding Sites ; Chickens/genetics ; Electron Transport Complex II/antagonists & inhibitors ; Electron Transport Complex II/metabolism ; Electron Transport Complex II/ultrastructure ; Multienzyme Complexes/genetics ; Multienzyme Complexes/metabolism ; Mutagenesis, Site-Directed ; Quinones/chemistry ; Sequence Alignment ; Sus scrofa/genetics ; Ubiquinone/chemistry ; Ubiquinone/ultrastructure
    Chemical Substances Benzoquinones ; Multienzyme Complexes ; Quinones ; respiratory complex II ; Ubiquinone (1339-63-5) ; quinone (3T006GV98U) ; Electron Transport Complex II (EC 1.3.5.1)
    Language English
    Publishing date 2021-06-03
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2918798-9
    ISSN 1878-1454 ; 1570-9639
    ISSN (online) 1878-1454
    ISSN 1570-9639
    DOI 10.1016/j.bbapap.2021.140679
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  2. Article ; Online: Prevalence of and Annual Conversion Rates to Mild Cognitive Impairment and Dementia: Prospective, Longitudinal Study of an Essential Tremor Cohort.

    Ghanem, Ali / Berry, Diane S / Burkes, Allison / Grill, Natalie / Hall, Talía M / Hart, Kira A / Hernandez, Nora C / Chapman, Silvia / Sharma, Vibhash D / Huey, Edward D / Cosentino, Stephanie A / Louis, Elan D

    Annals of neurology

    2024  

    Abstract: Objective: Despite recent attention to cognitive impairment in essential tremor, few studies examine rates of conversion to diagnoses of mild cognitive impairment and dementia. Development of dementia in essential tremor is associated with loss of ... ...

    Abstract Objective: Despite recent attention to cognitive impairment in essential tremor, few studies examine rates of conversion to diagnoses of mild cognitive impairment and dementia. Development of dementia in essential tremor is associated with loss of functional ability and a doubling of mortality rate. This prospective, longitudinal study comprehensively reports the prevalence and incidence of, and the annual rates of conversion to, mild cognitive impairment and dementia in an essential tremor cohort.
    Methods: Patients underwent detailed cognitive assessments and were assigned diagnoses of normal cognition, mild cognitive impairment, or dementia. There were 222 patients at baseline (mean age = 79.3 ± 9.7 years), and 177 patients participated in follow-up evaluations at 18, 36, 54, and 72 months (mean years of observation = 5.1 ± 1.7). Data were compared to those of historical controls and Parkinson disease patients.
    Results: The cumulative prevalence of dementia and average annual conversion rate of mild cognitive impairment to dementia were 18.5% and 12.2%, nearly three times higher than rates in the general population, and approximately one half the magnitude of those reported for Parkinson disease patients. The cumulative prevalence of mild cognitive impairment (26.6%) was almost double that of the general population, but less than that in Parkinson disease populations.
    Interpretation: We present the most complete exposition of the longitudinal trajectory of cognitive impairment in an essential tremor cohort yet presented. The prevalence of and conversion rates to dementia in essential tremor fall between those associated with the natural course of aging and the more pronounced rates observed in Parkinson disease. ANN NEUROL 2024.
    Language English
    Publishing date 2024-04-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80362-5
    ISSN 1531-8249 ; 0364-5134
    ISSN (online) 1531-8249
    ISSN 0364-5134
    DOI 10.1002/ana.26927
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  3. Article: Time-to-Incision for Hip Fractures in a Canadian Level-1 Trauma Centre: Are We Respecting the Guidelines?

    Denis, Antoine / Montreuil, Julien / Reindl, Rudolf / Berry, Gregory K / Harvey, Edward J / Bernstein, Mitchell

    Canadian geriatrics journal : CGJ

    2022  Volume 25, Issue 1, Page(s) 57–65

    Abstract: Background: Surgical intervention within 48 hours is recommended for hip fractures in the elderly in order to reduce post-operative complications and lower mortality rates. The purpose of this retrospective study is to explore the causes of surgical ... ...

    Abstract Background: Surgical intervention within 48 hours is recommended for hip fractures in the elderly in order to reduce post-operative complications and lower mortality rates. The purpose of this retrospective study is to explore the causes of surgical delays for acute geriatric hip fractures.
    Methods: This is a retrospective cohort study involving a total of 109 consecutive geriatric patients who sustained proximal femur fractures ("hip fractures"), who subsequently underwent definitive fixation. Clinical, demographic, and direct costing data were extracted via a modern system and electronic medical records on a centralized data warehouse. Surgical delays and length of stay were analyzed according to clinical variables.
    Results: The established benchmark of a time-to-surgery of less than 48 hours was respected for 63 (57.8%) patients. Patients on oral anticoagulant (ACO) waited significantly longer, on average 58 hours compared to 44 for non-anticoagulated patients (
    Conclusion: Fewer than 60% of patients received surgery within the 48-hour benchmark after being admitted for an acute hip fracture in a Level-1 trauma centre. Patients with more comorbidities waited longer and stayed longer in the hospital after surgery. Implementing strategic, evidence-based changes should be done using this data to improve care of this vulnerable population.
    Language English
    Publishing date 2022-03-02
    Publishing country Canada
    Document type Journal Article
    ISSN 1925-8348
    ISSN 1925-8348
    DOI 10.5770/cgj.25.529
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  4. Article ; Online: Cancellations and delays of emergent orthopedic operations at a Canadian level 1 trauma centre.

    Denis, Antoine / Montreuil, Julien / Harvey, Edward J / Berry, Gregory K / Reindl, Rudolf / Bernstein, Mitchell

    Canadian journal of surgery. Journal canadien de chirurgie

    2022  Volume 65, Issue 3, Page(s) E382–E387

    Abstract: Background: Day-of surgery cancellation (DOSC) is considered to be a very inefficient use of hospital resources and results in emotional stress for the patient. To examine opportunities to minimize the incidence of preventable cancellations - an ... ...

    Abstract Background: Day-of surgery cancellation (DOSC) is considered to be a very inefficient use of hospital resources and results in emotional stress for the patient. To examine opportunities to minimize the incidence of preventable cancellations - an indicator of quality of care - we assessed the incidence of and reasons for DOSCs over 3 months among inpatients and outpatients at a trauma orthopedic service.
    Methods: This was a prospective study of 2 cohorts of patients, inpatients and outpatients, scheduled for emergent orthopedic surgery at a Canadian tertiary level 1 trauma centre from Jan. 1 to Mar. 31, 2020. Patient demographic characteristics, injury characteristics, delays until surgery and reasons for DOSCs were recorded.
    Results: A total of 185 patients (100 males and 85 females with a mean age of 54 yr) were included in the study. There were 98 outpatients and 87 inpatients. Seventy-five (40%) of the scheduled procedures in the outpatient group and 34 (30%) of those in the inpatient group were cancelled. In both groups, more than 85% of the cancellations were because of prioritization of a more urgent orthopedic or nonorthopedic surgical case. The average operative delay for the outpatient group was 11.4 days, compared to 3.8 days for the inpatient group (
    Conclusion: High DOSC rates were observed among both outpatients and inpatients. The main reason for delaying surgery was prioritization of a more urgent surgical case. Providing the orthopedic trauma service with a dedicated OR opened 6 days per week, along with extended hours of OR services to 1700 daily, might be effective at minimizing DOSCs.
    MeSH term(s) Appointments and Schedules ; Canada ; Female ; Humans ; Male ; Middle Aged ; Operating Rooms ; Orthopedic Procedures ; Prospective Studies ; Trauma Centers
    Language English
    Publishing date 2022-06-14
    Publishing country Canada
    Document type Journal Article
    ZDB-ID 410651-9
    ISSN 1488-2310 ; 0008-428X
    ISSN (online) 1488-2310
    ISSN 0008-428X
    DOI 10.1503/cjs.009420
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    Zs.A 221: Show issues Location:
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  5. Article ; Online: Hospital episode-of-care costs for hip fractures: an activity-based costing analysis.

    Denis, Antoine / Montreuil, Julien / Bouklouch, Yasser / Reindl, Rudolf / Berry, Gregory K / Harvey, Edward J / Bernstein, Mitchell

    OTA international : the open access journal of orthopaedic trauma

    2023  Volume 6, Issue 4, Page(s) e295

    Abstract: Background: Despite the large impact of hip fracture care on hospital budgets, accurate episode-of-care costs (EOCC) calculations for this injury remains a challenge. The objective of this article was to assess EOCC for geriatric patients with hip ... ...

    Abstract Background: Despite the large impact of hip fracture care on hospital budgets, accurate episode-of-care costs (EOCC) calculations for this injury remains a challenge. The objective of this article was to assess EOCC for geriatric patients with hip fractures using an activity-based costing methodology and identify intraoperative, perioperative, and patient-specific factors associated with higher EOCC.
    Material and methods: This is a retrospective cohort study involving a total of 109 consecutive patients with hip fracture treated surgically at a Canadian level-1 trauma center from April 2018 to February 2019. Clinical and demographic data were extracted through the institution's centralized data warehouse. Data acquisition also included direct and indirect costs per episode of care, adverse events, and precise temporal data.
    Results: The median total EOCC was $13,113 (interquartile range 6658), excluding physician fees. Out of the total cost, 75% was attributed to direct costs, which represented a median expenditure of $9941. The median indirect cost of the EOCC was $3322. Based on the multivariate analysis, patients not operated within the 48 hours guidelines had an increased length of stay by 5.7 days (
    Conclusion: The cost of managing a patient with geriatric hip fracture from arrival in the emergency department to discharge from surgical ward represented $13,113. Main factors influencing the EOCC included adherence to the 48-hour benchmark surgical delay and ASA score. High-quality costing data are vital in assessing health care spending, conducting cost effectiveness analyses, and ultimately in guiding policy decisions.
    Level of evidence: Level III (3), retrospective cohort study.
    Language English
    Publishing date 2023-12-04
    Publishing country United States
    Document type Journal Article
    ISSN 2574-2167
    ISSN (online) 2574-2167
    DOI 10.1097/OI9.0000000000000295
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  6. Article: Crystallographic investigation of the ubiquinone binding site of respiratory Complex II and its inhibitors

    Huang, Li-shar / Lümmen, Peter / Berry, Edward A

    Biochimica et biophysica acta. 2021 Sept., v. 1869, no. 9

    2021  

    Abstract: The quinone binding site (Q-site) of Mitochondrial Complex II (succinate-ubiquinone oxidoreductase) is the target for a number of inhibitors useful for elucidating the mechanism of the enzyme. Some of these have been developed as fungicides or pesticides, ...

    Abstract The quinone binding site (Q-site) of Mitochondrial Complex II (succinate-ubiquinone oxidoreductase) is the target for a number of inhibitors useful for elucidating the mechanism of the enzyme. Some of these have been developed as fungicides or pesticides, and species-specific Q-site inhibitors may be useful against human pathogens. We report structures of chicken Complex II with six different Q-site inhibitors bound, at resolutions 2.0–2.4 Å. These structures show the common interactions between the inhibitors and their binding site. In every case a carbonyl or hydroxyl oxygen of the inhibitor is H-bonded to Tyr58 in subunit SdhD and Trp173 in subunit SdhB. Two of the inhibitors H-bond Ser39 in subunit SdhC directly, while two others do so via a water molecule. There is a distinct cavity that accepts the 2-substituent of the carboxylate ring in flutolanil and related inhibitors. A hydrophobic “tail pocket” opens to receive a side-chain of intermediate-length inhibitors. Shorter inhibitors fit entirely within the main binding cleft, while the long hydrophobic side chains of ferulenol and atpenin A5 protrude out of the cleft into the bulk lipid region, as presumably does that of ubiquinone. Comparison of mitochondrial and Escherichia coli Complex II shows a rotation of the membrane-anchor subunits by 7° relative to the iron‑sulfur protein. This rotation alters the geometry of the Q-site and the H-bonding pattern of SdhB:His216 and SdhD:Asp57. This conformational difference, rather than any active-site mutation, may be responsible for the different inhibitor sensitivity of the bacterial enzyme.
    Keywords Escherichia coli ; active sites ; bacterial enzymes ; chickens ; crystallography ; flutolanil ; geometry ; humans ; hydrogen bonding ; hydrophobicity ; lipids ; mitochondria ; mutation ; oxygen ; ubiquinones
    Language English
    Dates of publication 2021-09
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 2918798-9
    ISSN 1878-1454 ; 1570-9639
    ISSN (online) 1878-1454
    ISSN 1570-9639
    DOI 10.1016/j.bbapap.2021.140679
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Cellular transduction mechanisms of adeno-associated viral vectors.

    Berry, Garrett Edward / Asokan, Aravind

    Current opinion in virology

    2016  Volume 21, Page(s) 54–60

    Abstract: Recombinant adeno-associated viral vectors (rAAV) are regarded as promising vehicles for therapeutic gene delivery. Continued development and new strategies are essential to improve the potency of AAV vectors and reduce the effective dose needed for ... ...

    Abstract Recombinant adeno-associated viral vectors (rAAV) are regarded as promising vehicles for therapeutic gene delivery. Continued development and new strategies are essential to improve the potency of AAV vectors and reduce the effective dose needed for clinical efficacy. In this regard, many studies have focused on understanding the cellular transduction mechanisms of rAAV, often with the goal of exploiting this knowledge to increase gene transfer efficiency. Here, we provide an overview of our evolving understanding of rAAV cellular trafficking pathways through the host cell, beginning with cellular entry and ending with transcription of the vector genome. Strategies to exploit this information for improving rAAV transduction are discussed.
    MeSH term(s) Dependovirus/genetics ; Drug Delivery Systems ; Genetic Therapy ; Genetic Vectors ; Humans ; Transduction, Genetic
    Language English
    Publishing date 2016-12
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2611378-8
    ISSN 1879-6265 ; 1879-6257
    ISSN (online) 1879-6265
    ISSN 1879-6257
    DOI 10.1016/j.coviro.2016.08.001
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  8. Book: William Edward Hearn: first Australian economist

    Copland, Douglas Berry / Hearn, William Edward

    the Murtagh Macrossan lectures in the University of Queensland 1935

    1935  

    Author's details by Douglas Berry Copland
    Size 80 S
    Publisher Melbourne University Press. usw
    Publishing place Melbourne
    Document type Book
    Database ECONomics Information System

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  9. Article: Associations Between Relapses and Psychosocial Outcomes in Patients With Schizophrenia in Real-World Settings in the United States.

    Lin, Dee / Joshi, Kruti / Keenan, Alexander / Shepherd, Jason / Bailey, Hollie / Berry, Mia / Wright, Jack / Meakin, Sophie / Benson, Carmela / Kim, Edward

    Frontiers in psychiatry

    2021  Volume 12, Page(s) 695672

    Abstract: Aim: ...

    Abstract Aim:
    Language English
    Publishing date 2021-10-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2021.695672
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  10. Article ; Online: Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent: Final Results from a Phase II Study.

    Wagner, Patrick / Levine, Edward A / Kim, Alex C / Shen, Perry / Fleming, Nicole D / Westin, Shannon N / Berry, Laurel K / Karakousis, Giorgos C / Tanyi, Janos L / Olson, Madeline T / Madajewski, Brian / Ostrander, Brian / Krishnan, Kartik / Balch, Charles M / Bartlett, David L

    Annals of surgical oncology

    2024  

    Abstract: Background: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. ... ...

    Abstract Background: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS.
    Patients and methods: NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance.
    Results: A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients.
    Conclusions: Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.
    Language English
    Publishing date 2024-04-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1200469-8
    ISSN 1534-4681 ; 1068-9265
    ISSN (online) 1534-4681
    ISSN 1068-9265
    DOI 10.1245/s10434-024-15165-4
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