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  1. Article ; Online: Interaction of tau with HNRNPA2B1 and N

    Jiang, Lulu / Lin, Weiwei / Zhang, Cheng / Ash, Peter E A / Verma, Mamta / Kwan, Julian / van Vliet, Emily / Yang, Zhuo / Cruz, Anna Lourdes / Boudeau, Samantha / Maziuk, Brandon F / Lei, Shuwen / Song, Jaehyup / Alvarez, Victor E / Hovde, Stacy / Abisambra, Jose F / Kuo, Min-Hao / Kanaan, Nicholas / Murray, Melissa E /
    Crary, John F / Zhao, Jian / Cheng, Ji-Xin / Petrucelli, Leonard / Li, Hu / Emili, Andrew / Wolozin, Benjamin

    Molecular cell

    2021  Volume 81, Issue 20, Page(s) 4209–4227.e12

    Abstract: ... connecting oTau with N ...

    Abstract The microtubule-associated protein tau oligomerizes, but the actions of oligomeric tau (oTau) are unknown. We have used Cry2-based optogenetics to induce tau oligomers (oTau-c). Optical induction of oTau-c elicits tau phosphorylation, aggregation, and a translational stress response that includes stress granules and reduced protein synthesis. Proteomic analysis identifies HNRNPA2B1 as a principle target of oTau-c. The association of HNRNPA2B1 with endogenous oTau was verified in neurons, animal models, and human Alzheimer brain tissues. Mechanistic studies demonstrate that HNRNPA2B1 functions as a linker, connecting oTau with N
    MeSH term(s) Adenosine/analogs & derivatives ; Adenosine/metabolism ; Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Animals ; Case-Control Studies ; Cerebral Cortex/metabolism ; Cerebral Cortex/pathology ; Disease Models, Animal ; Disease Progression ; Female ; HEK293 Cells ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism ; Humans ; Male ; Methylation ; Mice, Inbred C57BL ; Mice, Transgenic ; Middle Aged ; Protein Aggregates ; Protein Aggregation, Pathological ; RNA/genetics ; RNA/metabolism ; RNA Processing, Post-Transcriptional ; Severity of Illness Index ; tau Proteins/genetics ; tau Proteins/metabolism ; Mice
    Chemical Substances Heterogeneous-Nuclear Ribonucleoprotein Group A-B ; MAPT protein, human ; Protein Aggregates ; hnRNP A2 ; tau Proteins ; RNA (63231-63-0) ; N-methyladenosine (CLE6G00625) ; Adenosine (K72T3FS567)
    Language English
    Publishing date 2021-08-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.07.038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Correction to: The Potential of N‑Acetyl‑L‑Cysteine (NAC) in the Treatment of Psychiatric Disorders.

    Bradlow, Richard C J / Berk, Michael / Kalivas, Peter W / Back, Sudie E / Kanaan, Richard A

    CNS drugs

    2022  Volume 36, Issue 5, Page(s) 553

    Language English
    Publishing date 2022-04-28
    Publishing country New Zealand
    Document type Published Erratum
    ZDB-ID 1203800-3
    ISSN 1179-1934 ; 1172-7047
    ISSN (online) 1179-1934
    ISSN 1172-7047
    DOI 10.1007/s40263-022-00925-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The Potential of N-Acetyl-L-Cysteine (NAC) in the Treatment of Psychiatric Disorders.

    Bradlow, Richard C J / Berk, Michael / Kalivas, Peter W / Back, Sudie E / Kanaan, Richard A

    CNS drugs

    2022  Volume 36, Issue 5, Page(s) 451–482

    Abstract: N-acetyl-L-cysteine (NAC) is a compound of increasing interest in the treatment of psychiatric ...

    Abstract N-acetyl-L-cysteine (NAC) is a compound of increasing interest in the treatment of psychiatric disorders. Primarily through its antioxidant, anti-inflammatory, and glutamate modulation activity, NAC has been investigated in the treatment of neurodevelopmental disorders, schizophrenia spectrum disorders, bipolar-related disorders, depressive disorders, anxiety disorders, obsessive compulsive-related disorders, substance-use disorders, neurocognitive disorders, and chronic pain. Whilst there is ample preclinical evidence and theoretical justification for the use of NAC in the treatment of multiple psychiatric disorders, clinical trials in most disorders have yielded mixed results. However, most studies have been underpowered and perhaps too brief, with some evidence of benefit only after months of treatment with NAC. Currently NAC has the most evidence of having a beneficial effect as an adjuvant agent in the negative symptoms of schizophrenia, severe autism, depression, and obsessive compulsive and related disorders. Future research with well-powered studies that are of sufficient length will be critical to better understand the utility of NAC in the treatment of psychiatric disorders.
    MeSH term(s) Acetylcysteine/therapeutic use ; Anxiety Disorders/drug therapy ; Bipolar Disorder/drug therapy ; Humans ; Obsessive-Compulsive Disorder/drug therapy ; Schizophrenia/drug therapy
    Chemical Substances Acetylcysteine (WYQ7N0BPYC)
    Language English
    Publishing date 2022-03-22
    Publishing country New Zealand
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 1203800-3
    ISSN 1179-1934 ; 1172-7047
    ISSN (online) 1179-1934
    ISSN 1172-7047
    DOI 10.1007/s40263-022-00907-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial of adjunctive N-Acetylcysteine for treatment-resistant PTSD.

    Kanaan, Richard A / Oliver, Gina / Dharan, Anita / Sendi, Shahbaz / Maier, Alice / Mohebbi, Mohammadreza / Ng, Chee / Back, Sudie E / Kalivas, Peter / Berk, Michael

    Psychiatry research

    2023  Volume 327, Page(s) 115398

    Abstract: Background: PTSD may involve oxidative stress, and N-acetylcysteine (NAC) may reduce the impact ...

    Abstract Background: PTSD may involve oxidative stress, and N-acetylcysteine (NAC) may reduce the impact of oxidative stress in the brain. This study aims to investigate the efficacy of adjuvant NAC in people with treatment-resistant PTSD.
    Methods: A multicentre, randomised, double-blind, placebo-controlled trial for adults with PTSD unresponsive to first-line treatment. The intervention was either oral NAC 2.7 g/day or placebo for 12 weeks. The primary outcome was change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 12 weeks compared with baseline. Secondary outcomes included depression and substance craving. Follow-up measures were obtained at 16 and 64-weeks.
    Results: 133 patients were assessed, with 105 randomised; 81 participants completed the 12-week trial, 79 completed week-16 follow-up, and 21 completed week-64 follow-up. There were no significant differences between those taking NAC and those taking placebo in CAPS-5 scores at week 12, nor in secondary outcomes. Significant between-group differences were observed at week 64 in craving duration (Cohen's d = 1.61) and craving resistance (Cohen's d = 1.03), both in favour of NAC.
    Conclusion: This was the first multicentre, double-blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. No benefit of NAC was observed in this group beyond that provided by placebo at end of the trial.
    Trial registration: ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004.
    MeSH term(s) Adult ; Humans ; Acetylcysteine/pharmacology ; Acetylcysteine/therapeutic use ; Stress Disorders, Post-Traumatic/drug therapy ; Double-Blind Method ; Treatment Outcome
    Chemical Substances Acetylcysteine (WYQ7N0BPYC)
    Language English
    Publishing date 2023-07-30
    Publishing country Ireland
    Document type Randomized Controlled Trial ; Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 445361-x
    ISSN 1872-7123 ; 1872-7506 ; 0925-4927 ; 0165-1781
    ISSN (online) 1872-7123 ; 1872-7506
    ISSN 0925-4927 ; 0165-1781
    DOI 10.1016/j.psychres.2023.115398
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: N-terminal pro-B-type-natriuretic peptide as a screening tool for pulmonary hypertension in the paediatric population.

    Dasgupta, Soham / Bettermann, Erika / Kelleman, Michael / Kanaan, Usama / Sachdeva, Ritu / Petit, Christopher / Kim, Dennis / Vincent, Robert / Bauser-Heaton, Holly

    Cardiology in the young

    2021  Volume 31, Issue 10, Page(s) 1595–1607

    Abstract: ... simultaneously compared N-terminal pro-B-type-natriuretic peptide (NTproBNP) with cath/echo as a potential ...

    Abstract Background: Although cardiac catheterisation (cath) is the diagnostic test for pulmonary hypertension, it is an invasive procedure. Echocardiography (echo) is commonly used for the non-invasive diagnosis of pulmonary hypertension but maybe limited by lack of adequate signals. Therefore, emphasis has been placed on biomarkers as a potential diagnostic tool. No prior paediatric studies have simultaneously compared N-terminal pro-B-type-natriuretic peptide (NTproBNP) with cath/echo as a potential diagnostic tool. The aim of this study was to determine if NTproBNP was a reliable diagnostic tool for pulmonary hypertension in this population.
    Methods: Patients were divided into Study (echo evidence/established diagnosis of pulmonary hypertension undergoing cath) and Control (cath for small atrial septal defect/patent ductus arteriosus and endomyocardial biopsy post cardiac transplant) groups. NTproBNP, cath/echo data were obtained.
    Results: Thirty-one patients met inclusion criteria (10 Study, 21 Control). Median NTproBNP was significantly higher in the Study group. Echo parameters including transannular plane systolic excursion z scores, pulmonary artery acceleration time and right ventricular fractional area change were lower in the Study group and correlated negatively with NTproBNP. Receiver operation characteristic curve analysis demonstrated NTproBNP > 389 pg/ml was 87% specific for the diagnosis of pulmonary hypertension with the addition of pulmonary artery acceleration time improving the specificity.
    Conclusions: NTproBNP may be a valuable adjunctive diagnostic tool for pulmonary hypertension in the paediatric population. Echo measures of transannular plane systolic excursion z score, pulmonary artery acceleration time and right ventricular fractional area change had negative correlations with NTproBNP. The utility of NTproBNP as a screening tool for pulmonary hypertension requires validation in a population with unknown pulmonary hypertension status.
    MeSH term(s) Biomarkers ; Child ; Humans ; Hypertension, Pulmonary/diagnosis ; Natriuretic Peptide, Brain/blood ; Peptide Fragments/blood ; Prospective Studies
    Chemical Substances Biomarkers ; Peptide Fragments ; pro-brain natriuretic peptide (1-76) ; Natriuretic Peptide, Brain (114471-18-0)
    Language English
    Publishing date 2021-03-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 1078466-4
    ISSN 1467-1107 ; 1047-9511
    ISSN (online) 1467-1107
    ISSN 1047-9511
    DOI 10.1017/S1047951121000585
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A multi-centre, double-blind, 12-week, randomized, placebo-controlled trial to assess the efficacy of adjunctive N-Acetylcysteine for treatment-resistant PTSD: a study protocol.

    Maier, Alice / Dharan, Anita / Oliver, Gina / Berk, Michael / Redston, Suzy / Back, Sudie E / Kalivas, Peter / Ng, Chee / Kanaan, Richard A

    BMC psychiatry

    2020  Volume 20, Issue 1, Page(s) 397

    Abstract: ... following first-line treatment. Oxidative stress has been implicated in the pathophysiology of PTSD. N ...

    Abstract Background: Most patients with Posttraumatic Stress Disorder (PTSD) suffer residual symptoms following first-line treatment. Oxidative stress has been implicated in the pathophysiology of PTSD. N-acetylcysteine (NAC) is a precursor of the brain's primary antioxidant, glutathione, and may diminish oxidative cellular damage. An 8-week pilot study of NAC in veterans with PTSD found that symptoms were significantly reduced in the NAC group compared to placebo. This study aims to confirm these findings with a larger sample in a double-blind, placebo-controlled trial to further explore the efficacy of NAC as an adjunctive therapy in treatment-resistant PTSD.
    Methods: A multicentre, randomised, double-blind, placebo-controlled trial for adult patients who still meet criteria for PTSD following first-line treatment. The intervention comprises either NAC as a fixed dose regime of 2.7 g/day (900 mg three times daily) administered orally for 12 weeks, or placebo. Standard care for PTSD will continue in addition, including other pharmacotherapies. Detailed clinical data will be collected at randomisation and weeks 4, 8, 12, 16, and 64 post-randomisation, with self-report measures completed weekly from baseline to 16 weeks and at 64 weeks post-randomisation. Blood-based biomarkers will be collected at baseline and 12 weeks to assess the mechanism of effect. The primary outcome measure will be change in Clinician-Administered PTSD Scale for DSM-5 at 12 weeks compared with baseline. Secondary outcomes will be change in quality of life, depression, anxiety, substance use and craving, and somatic symptoms. With 126 completed participants (63 per arm), the study is powered at 80% to detect a true difference in the primary outcome measure using a two-tailed analysis with alpha = 0.05, beta = 0.2.
    Discussion: This is the first multicentre, double blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. NAC has an established safety profile, is readily available and easy to administer, and has a favourable tolerability profile, therefore making it an attractive adjunctive therapy. Inclusion of blood analyses to assess potential target engagement biomarkers of oxidative stress and neuroinflammation may help gauge the biological mechanisms of effect of NAC.
    Trial registration: ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004 .
    MeSH term(s) Acetylcysteine/therapeutic use ; Adult ; Double-Blind Method ; Humans ; Pilot Projects ; Quality of Life ; Stress Disorders, Post-Traumatic/drug therapy ; Treatment Outcome
    Chemical Substances Acetylcysteine (WYQ7N0BPYC)
    Language English
    Publishing date 2020-08-06
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ISSN 1471-244X
    ISSN (online) 1471-244X
    DOI 10.1186/s12888-020-02793-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Tau here, tau there, tau almost everywhere: Clarifying the distribution of tau in the adult CNS.

    Kanaan, Nicholas M

    Cytoskeleton (Hoboken, N.J.)

    2023  Volume 81, Issue 1, Page(s) 107–115

    Abstract: The microtubule-associated protein tau has gained significant attention over the last several decades primarily due to its apparent role in the pathogenesis of several diseases, most notably Alzheimer's disease. While the field has focused largely on tau' ...

    Abstract The microtubule-associated protein tau has gained significant attention over the last several decades primarily due to its apparent role in the pathogenesis of several diseases, most notably Alzheimer's disease. While the field has focused largely on tau's potential contributions to disease mechanisms, comparably less work has focused on normal tau physiology. Moreover, as the field has grown, some misconceptions and dogmas regarding normal tau physiology have become engrained in the traditional narrative. Here, one of the most common misconceptions regarding tau, namely its normal cellular/subcellular distribution in the CNS, is discussed. The literature describing the presence of tau in neuronal somata, dendrites, axons and synapses, as well as in glial cells is described. The origins for the erroneous description of tau as an "axon-specific," "axon-enriched" and/or "neuron-specific" protein are discussed as well. The goal of this work is to help address these specific dogmatic misconceptions and provide a concise description of tau's normal cellular/subcellular localization in the adult CNS. This information can help refine our collective understanding of- and hypotheses about tau biology and pathobiology.
    MeSH term(s) Microtubules/metabolism ; Axons ; tau Proteins ; Neurons/metabolism ; Synapses/metabolism
    Chemical Substances tau Proteins
    Language English
    Publishing date 2023-12-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2534372-5
    ISSN 1949-3592 ; 1949-3584
    ISSN (online) 1949-3592
    ISSN 1949-3584
    DOI 10.1002/cm.21820
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Tailored Skull Base Approach to Management of Intracranial Aneurysms.

    Kanaan, Imad N

    Advances and technical standards in neurosurgery

    2022  Volume 44, Page(s) 1–16

    Abstract: Surgical management of intracranial aneurysms (IAs) remains one of the most challenging and dynamic tasks for neurosurgeons. The rivalry between modern time microsurgery and progress in endovascular intervention has provided a great arena for advancement ...

    Abstract Surgical management of intracranial aneurysms (IAs) remains one of the most challenging and dynamic tasks for neurosurgeons. The rivalry between modern time microsurgery and progress in endovascular intervention has provided a great arena for advancement and lead to redefine training concept and referral pattern. Both approaches has its own merits, risks and complications and the best outcome is achieved by case individualization and complimentary multidisciplinary approach.The recent innovation in microscopic and endoscopic tailored skull base approaches, intraoperative 3D and ICG video-angiography, design of high quality aneurysm clips, and refinement of cerebral bypass techniques enhance IAs neurosurgical management and their clinical outcome. The command of tailored skull base approaches should be part of the training curriculum of young generation of neurosurgeons to compliment the emerging treatment options of endovascular intervention.
    MeSH term(s) Humans ; Intracranial Aneurysm/surgery ; Microsurgery ; Neurosurgeons ; Skull Base/surgery ; Surgical Instruments
    Language English
    Publishing date 2022-02-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 189820-6
    ISSN 0095-4829
    ISSN 0095-4829
    DOI 10.1007/978-3-030-87649-4_1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Knowledge, attitudes, and practices related to the prevention of adverse pregnancy outcomes among samples of females in Al-Suwaira city, Wasit Governorate, Iraq.

    Salim, Israa Dawood / Kanaan, Manal Hadi Ghaffoori / Tarek, Ahmad M

    Journal of preventive medicine and hygiene

    2024  Volume 65, Issue 1, Page(s) E17–E24

    Abstract: ... The findings revealed that the majority of participants were between the ages of 20 and 25 (n = 57, 48.3%) and ... had a Bachelor's degree (n = 106, 89.8%).Knowledge gaps were discovered in the areas of the danger ... around pregnancy-related risk factors via internet (n = 38, 32.2%) and university (n = 34, 28.8%).: Conclusions ...

    Abstract Introduction: Adverse pregnancy outcomes pose serious health risks to both periconceptional women and newborns. This study aimed to investigate the levels of knowledge, attitudes, and practice (KAP) toward adverse pregnancy outcomes among women of reproductive age in Al-Suwaira, Wasit governorate, Iraq.
    Methods: During November 2021 to February 2022, cross-sectional research of randomly selected women was performed. The KAP was evaluated with a standard, self-administered questionnaire. The outcomes were described using a descriptive analysis.
    Results: The questionnaire was completed by 118 women. Participants had good knowledge and positive attitudes and practices toward adverse pregnancy outcomes. The findings revealed that the majority of participants were between the ages of 20 and 25 (n = 57, 48.3%) and had a Bachelor's degree (n = 106, 89.8%).Knowledge gaps were discovered in the areas of the danger of pregnancy at a young age of less than 17 years (30.5%), the link between lack of maternal education and poor births (24.6%), and the influence of drug misuse on the fetus (17.8%). The participants learn more around pregnancy-related risk factors via internet (n = 38, 32.2%) and university (n = 34, 28.8%).
    Conclusions: The participants in this study had good knowledge, positive attitude, and positive practice regarding adverse pregnancy outcomes. However, there were some knowledge gaps. Therefore, to raise awareness among local women, it seems advisable to strengthen and strictly apply awareness-raising plans.
    MeSH term(s) Humans ; Female ; Pregnancy ; Health Knowledge, Attitudes, Practice ; Iraq ; Adult ; Cross-Sectional Studies ; Pregnancy Outcome ; Young Adult ; Surveys and Questionnaires ; Adolescent ; Pregnancy Complications
    Language English
    Publishing date 2024-03-31
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 1102926-2
    ISSN 2421-4248 ; 1121-2233
    ISSN (online) 2421-4248
    ISSN 1121-2233
    DOI 10.15167/2421-4248/jpmh2024.65.1.3088
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: AKI and Transaminitis in a Kidney Transplant Patient.

    Lacave, Florian / Kanaan, Nada / Devresse, Arnaud

    Kidney360

    2023  Volume 4, Issue 1, Page(s) 119–120

    MeSH term(s) Humans ; Kidney Transplantation/adverse effects ; Retrospective Studies ; Acute Kidney Injury/diagnosis ; Acute Kidney Injury/etiology ; Patients
    Language English
    Publishing date 2023-02-03
    Publishing country United States
    Document type Journal Article
    ISSN 2641-7650
    ISSN (online) 2641-7650
    DOI 10.34067/KID.0000000000000023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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