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  1. Article ; Online: Clinical and serological characterization of acute pleuropericarditis suggests an autoinflammatory pathogenesis and highlights risk factors for recurrent attacks.

    Kaudewitz, Dorothee / John, Lukas / Meis, Jan / Frey, Norbert / Lorenz, Hanns-Martin / Leuschner, Florian / Blank, Norbert

    Clinical research in cardiology : official journal of the German Cardiac Society

    2024  

    Abstract: Purpose: We describe the manifestations and course of patients with pleuropericarditis (PP). Serum parameters were analyzed to evaluate the contribution of autoimmune and autoinflammatory mechanisms to PP pathogenesis. Finally, we outline risk factors ... ...

    Abstract Purpose: We describe the manifestations and course of patients with pleuropericarditis (PP). Serum parameters were analyzed to evaluate the contribution of autoimmune and autoinflammatory mechanisms to PP pathogenesis. Finally, we outline risk factors for recurrent PP attacks.
    Methods: Electronic medical records of the University Hospital Heidelberg were screened for PP diagnosis between the years 2009 and 2021. A total of 164 patients were detected and compared to patients suffering from systemic lupus erythematosus (SLE)-associated PP. Follow-up data were collected until January 2023.
    Results: In 57.3% of a total of 164 PP cases, no trigger was identified (idiopathic PP). The clinical manifestations were similar in subgroups with different triggers (idiopathic, post-cardiac injury and post-infectious). None of the patients in the idiopathic-PP (i-PP) group fulfilled the diagnostic criteria of an autoimmune disease and the i-PP group could be clearly discriminated by clinical, epidemiological and serological means from the control cohort of SLE-associated PP. After a median follow-up of 1048 days, the majority of PP patients (72.7%) had at least one PP relapse. Univariate analyses showed that CRP, SAA (serum amyloid A), troponin T, NT-BNP and post-cardiac injury were negatively correlated, while the presence of fever and an idiopathic trigger were positively correlated with recurrence of PP. Multivariate analyses showed that fever, an idiopathic trigger and low SAA values were risk factors for PP recurrence.
    Conclusion: This study highlights that most cases of PP are idiopathic and PP cases with various triggers have an identical clinical phenotype. Our data suggest that the clinical, epidemiological and serological characteristics of idiopathic PP considerably differ from patients with PP caused by autoimmune disease like SLE. We further demonstrate that PP has a high risk of recurrence and identify factors associated with this risk, allowing for a targeted secondary prophylaxis.
    Language English
    Publishing date 2024-02-15
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2213295-8
    ISSN 1861-0692 ; 1861-0684
    ISSN (online) 1861-0692
    ISSN 1861-0684
    DOI 10.1007/s00392-024-02390-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Micropuncture of the kidney: a primer on techniques.

    Lorenz, John N

    Comprehensive Physiology

    2012  Volume 2, Issue 1, Page(s) 621–637

    Abstract: Techniques to evaluate renal function at the single nephron level have been instrumental and indispensible in furthering our understanding of the mammalian kidney. Techniques that were first introduce in the 1920s, and later refined in the 1950s and ... ...

    Abstract Techniques to evaluate renal function at the single nephron level have been instrumental and indispensible in furthering our understanding of the mammalian kidney. Techniques that were first introduce in the 1920s, and later refined in the 1950s and 1960s, permit sophisticated interrogation of glomerular filtration and hemodynamics, and tubular epithelial transport activity. Much of what we know about the physiology and pathophysiology of the kidney has been produced or, to some degree, confirmed by renal micropuncture. While micropuncture is perhaps not as widely employed as before, it remains an essential tool for comprehensive evaluation of kidney function, particularly in this age of genetically pliable experimental models. This review aims to provide a introduction to common methodologies and approaches used to conduct micropuncture experiments. Topics covered include instrumentation and equipment, pipet fabrication techniques, animal preparation, and experimental procedures for evaluating single nephron hemodynamics and tubular function.
    MeSH term(s) Animals ; Electrochemical Techniques/methods ; Feedback, Physiological/physiology ; Glomerular Filtration Rate/physiology ; Hemodynamics ; Kidney/physiology ; Kidney Function Tests/methods ; Kidney Tubules/physiology ; Nephrons/blood supply ; Nephrons/physiology ; Punctures/instrumentation ; Punctures/methods ; Punctures/trends ; Specimen Handling/methods
    Language English
    Publishing date 2012-01
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2040-4603
    ISSN (online) 2040-4603
    DOI 10.1002/cphy.c110035
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Unlocking the Role of sMyBP-C: A Key Player in Skeletal Muscle Development and Growth.

    Song, Taejeong / McNamara, James W / Baby, Akhil / Ma, Weikang / Landim-Vieira, Maicon / Natesan, Sankar / Pinto, Jose Renato / Lorenz, John N / Irving, Thomas C / Sadayappan, Sakthivel

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Skeletal muscle is the largest organ in the body, responsible for gross movement and metabolic regulation. Recently, variants in ... ...

    Abstract Skeletal muscle is the largest organ in the body, responsible for gross movement and metabolic regulation. Recently, variants in the
    Language English
    Publishing date 2023-11-30
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.10.23.563591
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: HuR inhibition reduces post-ischemic cardiac remodeling by dampening acute inflammatory gene expression and the innate immune response.

    Slone, Samuel / Anthony, Sarah R / Green, Lisa C / Nieman, Michelle L / Alam, Perwez / Wu, Xiaoqing / Roy, Sudeshna / Aube, Jeffrey / Xu, Liang / Lorenz, John N / Owens, A Phillip / Kanisicak, Onur / Tranter, Michael

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Myocardial ischemia/reperfusion (I/R) injury and the resulting cardiac remodeling is a common cause of heart failure. The RNA binding protein Human Antigen R (HuR) has been previously shown to reduce cardiac remodeling following both I/R and cardiac ... ...

    Abstract Myocardial ischemia/reperfusion (I/R) injury and the resulting cardiac remodeling is a common cause of heart failure. The RNA binding protein Human Antigen R (HuR) has been previously shown to reduce cardiac remodeling following both I/R and cardiac pressure overload, but the full extent of the HuR-dependent mechanisms within cells of the myocardium have yet to be elucidated. In this study, we applied a novel small molecule inhibitor of HuR to define the functional role of HuR in the acute response to I/R injury and gain a better understanding of the HuR-dependent mechanisms during post-ischemic myocardial remodeling. Our results show an early (two hours post-I/R) increase in HuR activity that is necessary for early inflammatory gene expression by cardiomyocytes in response to I/R. Surprisingly, despite the reductions in early inflammatory gene expression at two hours post-I/R, HuR inhibition has no effect on initial infarct size at 24-hours post-I/R. However, in agreement with previously published work, we do see a reduction in pathological remodeling and preserved cardiac function at two weeks post-I/R upon HuR inhibition. RNA-sequencing analysis of neonatal rat ventricular myocytes (NRVMs) at two hours post-LPS treatment to model damage associated molecular pattern (DAMP)-mediated activation of toll like receptors (TLRs) demonstrates a broad HuR-dependent regulation of pro-inflammatory chemokine and cytokine gene expression in cardiomyocytes. We show that conditioned media from NRVMs pre-treated with HuR inhibitor loses the ability to induce inflammatory gene expression in bone marrow derived macrophages (BMDMs) compared to NRVMs treated with LPS alone. Functionally, HuR inhibition in NRVMs also reduces their ability to induce endocrine migration of peripheral blood monocytes
    Language English
    Publishing date 2023-01-18
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.01.17.524420
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Chymase: the other ACE?

    Lorenz, John N

    American journal of physiology. Renal physiology

    2009  Volume 298, Issue 1, Page(s) F35–6

    MeSH term(s) Angiotensin II/metabolism ; Animals ; Chymases/metabolism ; Diabetes Complications/metabolism ; Diabetic Nephropathies/etiology ; Diabetic Nephropathies/metabolism ; Disease Models, Animal ; Humans ; Hypertension/etiology ; Hypertension/metabolism ; Kidney/metabolism ; Mice ; Peptidyl-Dipeptidase A/metabolism ; Receptors, Leptin/genetics ; Receptors, Leptin/metabolism ; Signal Transduction/physiology
    Chemical Substances Receptors, Leptin ; Angiotensin II (11128-99-7) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Chymases (EC 3.4.21.39)
    Language English
    Publishing date 2009-11-18
    Publishing country United States
    Document type Comment ; Editorial ; Research Support, N.I.H., Extramural
    ZDB-ID 603837-2
    ISSN 1522-1466 ; 0363-6127
    ISSN (online) 1522-1466
    ISSN 0363-6127
    DOI 10.1152/ajprenal.00641.2009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Pharmacologic Inhibition of Pain Response to Incomplete Vascular Occlusion Blunts Cardiovascular Preconditioning Response.

    Kirschner, Akiva / Koch, Sheryl E / Robbins, Nathan / Karthik, Felix / Mudigonda, Parvathi / Ramasubramanian, Ranjani / Nieman, Michelle L / Lorenz, John N / Rubinstein, Jack

    Cardiovascular toxicology

    2021  Volume 21, Issue 11, Page(s) 889–900

    Abstract: Complete vascular occlusion to distant tissue prior to an ischemic cardiac event can provide significant cardioprotection via remote ischemic preconditioning (RIPC). Despite understanding its mechanistic basis, its translation to clinical practice has ... ...

    Abstract Complete vascular occlusion to distant tissue prior to an ischemic cardiac event can provide significant cardioprotection via remote ischemic preconditioning (RIPC). Despite understanding its mechanistic basis, its translation to clinical practice has been unsuccessful, likely secondary to the inherent impossibility of predicting (and therefore preconditioning) an ischemic event, as well as the discomfort that is associated with traditional, fully occlusive RIPC stimuli. Our laboratory has previously shown that non-occlusive banding (NOB) via wrapping of a leather band (similar to a traditional Jewish ritual) can elicit an RIPC response in healthy human subjects. This study sought to further the pain-mediated aspect of this observation in a mouse model of NOB with healthy mice that were exposed to treatment with and without lidocaine to inhibit pain sensation prior to ischemia/reperfusion injury. We demonstrated that NOB downregulates key inflammatory markers resulting in a preconditioning response that is partially mediated via pain sensation.
    MeSH term(s) Anesthetics, Local/pharmacology ; Animals ; Cytokines/blood ; Cytokines/genetics ; Disease Models, Animal ; Echocardiography ; Forelimb/blood supply ; Ischemic Preconditioning/methods ; Lidocaine/pharmacology ; Ligation ; Male ; Mice, Inbred C57BL ; Myocardial Infarction/blood ; Myocardial Infarction/diagnostic imaging ; Myocardial Infarction/physiopathology ; Myocardial Infarction/prevention & control ; Myocardial Reperfusion Injury/blood ; Myocardial Reperfusion Injury/diagnostic imaging ; Myocardial Reperfusion Injury/physiopathology ; Myocardial Reperfusion Injury/prevention & control ; Myocardium/metabolism ; Myocardium/pathology ; Pain Threshold/drug effects ; Radial Artery/diagnostic imaging ; Radial Artery/physiology ; Regional Blood Flow ; Time Factors ; Mice
    Chemical Substances Anesthetics, Local ; Cytokines ; Lidocaine (98PI200987)
    Language English
    Publishing date 2021-07-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2036765-X
    ISSN 1559-0259 ; 1530-7905
    ISSN (online) 1559-0259
    ISSN 1530-7905
    DOI 10.1007/s12012-021-09680-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab.

    Chandrakasan, Shanmuganathan / Jordan, Michael B / Baker, Ashley / Behrens, Edward M / Bhatla, Deepika / Chien, May / Eckstein, Olive S / Henry, Michael M / Hermiston, Michelle L / Hinson, Ashley / Leiding, Jennifer W / Oladapo, Abiola / Patel, Sachit A / Pednekar, Priti / Ray, Anish / Dávila Saldaña, Blachy J / Sarangi, Susmita N / Walkovich, Kelly / Yee, John D /
    Zoref-Lorenz, Adi / Allen, Carl E

    Blood advances

    2024  

    Abstract: ... initiation for the entire cohort (n=46) was 73.1%. There were no discontinuations due to adverse events ...

    Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-gamma, is approved in the United States to treat primary HLH (pHLH) in patients with refractory, recurrent, progressive disease or intolerance with conventional HLH. REAL-HLH, a retrospective study, conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between November 20, 2018, and October 31, 2021. Forty-six patients met the pHLH classification criteria. Median (range) age at diagnosis was 1.0 (0.3-21.0) year. Emapalumab was initiated for treating refractory (19/46), recurrent (14/46), or progressive (7/46) pHLH. At initiation, 15/46 patients were in the intensive care unit and 35/46 had received prior HLH-related therapies. Emapalumab treatment resulted in normalization of key laboratory parameters, including chemokine ligand 9 (CXCL9) (24/33; 72.7%), ferritin (20/45; 44.4%), fibrinogen (37/38; 97.4%), platelets (39/46; 84.8%), and absolute neutrophil count (40/45; 88.9%). Forty-two (91.3%) patients were considered eligible for transplant. Pre-transplant survival was 38/42 (90.5%). Thirty-one (73.8%) transplant-eligible patients proceeded to transplant and 23/31 (74.2%) of those transplanted were alive at the end of the follow-up period. Twelve-month survival probability from emapalumab initiation for the entire cohort (n=46) was 73.1%. There were no discontinuations due to adverse events. In conclusion, results from the REAL-HLH study, which describes treatment patterns, effectiveness, and outcomes in patients with pHLH treated with emapalumab in real-world settings, are consistent with the emapalumab pivotal phase 2/3 pHLH trial.
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023012217
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Antenatal consultation and deliberation: adapting to parental preferences.

    Haward, Marlyse F / Lorenz, John M / Janvier, Annie / Fischhoff, Baruch

    Journal of perinatology : official journal of the California Perinatal Association

    2023  Volume 43, Issue 7, Page(s) 895–902

    Abstract: ... Results: Non-clinician participants' (n = 80) perspectives differed regarding: amount and content ...

    Abstract Objective: To analyze and compare perspectives on antenatal consultation and decision-making from participants with varying degrees of prematurity experience and clinician-experts.
    Study design: Open-ended interviews structured around topics previously identified by recognized clinician-experts were conducted with participants having different levels of prematurity experience. Analysis used mixed methods (thematic and mental models analysis). Secondary sub-group comparisons were performed, based on degree of experience.
    Results: Non-clinician participants' (n = 80) perspectives differed regarding: amount and content of information desired, decision-making strategies, and who - parent or clinician - should direct consultations. Most wanted to retain decisional authority, all recognized their emotional limitations and many advocated for deliberation support. Participants worried parents' would regret choosing palliative care contrary to clinicians. Bereaved parents often saw issues differently.
    Conclusions: Parents approach risk and decision-making for extremely premature infants in a personal fashion. They need personalized support tailored to their unique circumstances, decision-making preferences, and emotions.
    MeSH term(s) Infant, Newborn ; Infant ; Humans ; Female ; Pregnancy ; Decision Making ; Parents/psychology ; Infant, Extremely Premature ; Emotions ; Referral and Consultation
    Language English
    Publishing date 2023-02-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645021-0
    ISSN 1476-5543 ; 0743-8346
    ISSN (online) 1476-5543
    ISSN 0743-8346
    DOI 10.1038/s41372-023-01605-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: V2a Neurons Constrain Extradiaphragmatic Respiratory Muscle Activity at Rest.

    Jensen, Victoria N / Seedle, Kari / Turner, Sarah M / Lorenz, John N / Crone, Steven A

    eNeuro

    2019  Volume 6, Issue 4

    Abstract: Breathing requires precise control of respiratory muscles to ensure adequate ventilation. Neurons within discrete regions of the brainstem produce oscillatory activity to control the frequency of breathing. Less is understood about how spinal and ... ...

    Abstract Breathing requires precise control of respiratory muscles to ensure adequate ventilation. Neurons within discrete regions of the brainstem produce oscillatory activity to control the frequency of breathing. Less is understood about how spinal and pontomedullary networks modulate the activity of respiratory motor neurons to produce different patterns of activity during different behaviors (i.e., during exercise, coughing, swallowing, vocalizing, or at rest) or following disease or injury. Here, we use a chemogenetic approach to inhibit the activity of glutamatergic V2a neurons in the brainstem and spinal cord of neonatal and adult mice to assess their potential roles in respiratory rhythm generation and patterning respiratory muscle activity. Using whole-body plethysmography (WBP), we show that V2a neuron function is required in neonatal mice to maintain the frequency and regularity of respiratory rhythm. However, silencing V2a neurons in adult mice increases respiratory frequency and ventilation, without affecting regularity. Thus, the excitatory drive provided by V2a neurons is less critical for respiratory rhythm generation in adult compared to neonatal mice. In addition, we used simultaneous EMG recordings of the diaphragm and extradiaphragmatic respiratory muscles in conscious adult mice to examine the role of V2a neurons in patterning respiratory muscle activity. We find that silencing V2a neurons activates extradiaphragmatic respiratory muscles at rest, when they are normally inactive, with little impact on diaphragm activity. Thus, our results indicate that V2a neurons participate in a circuit that serves to constrain the activity of extradiaphragmatic respiratory muscles so that they are active only when needed.
    MeSH term(s) Animals ; Male ; Medulla Oblongata/physiology ; Mice, Transgenic ; Neurons/physiology ; Respiration ; Respiratory Muscles/innervation ; Respiratory Muscles/physiology ; Spinal Cord/physiology
    Language English
    Publishing date 2019-08-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2800598-3
    ISSN 2373-2822 ; 2373-2822
    ISSN (online) 2373-2822
    ISSN 2373-2822
    DOI 10.1523/ENEURO.0492-18.2019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Sexual Exposures Associated With Mpox Infection: California, November 2022 to June 2023.

    Snyder, Robert E / Saadeh, Kayla / Tang, Eric C / Johnson, Kelly A / Holland, Samuel N / Quint, Joshua / Burghardt, Nicole O / Chai, Shua J / Fernando, Roshani / Barrera, Kimberly Gonzalez / Hernandez, Cindy / McManus, Korie / Lorenz, Kieran / Maycott, Jarett / McGinley, John / Lewnard, Joseph A

    The Journal of infectious diseases

    2023  Volume 229, Issue Supplement_2, Page(s) S188–S196

    Abstract: Background: Exposures associated with mpox infection remain imperfectly understood.: Methods: We conducted a case-control study enrolling participants who received molecular tests for mpox/orthopoxvirus in California from November 2022 through June ... ...

    Abstract Background: Exposures associated with mpox infection remain imperfectly understood.
    Methods: We conducted a case-control study enrolling participants who received molecular tests for mpox/orthopoxvirus in California from November 2022 through June 2023. We collected data on behaviors during a 21-day risk period before symptom onset or testing among mpox case patients and test-negative controls.
    Results: Thirteen of 54 case patients (24.1%) and 5 of 117 controls (4.3%) reported sexual exposure to individuals they identified as potential mpox case patients ("index contacts"; odds ratio [OR], 7.7 [95% confidence interval (CI), 2.5-19.3] relative to individuals who did not report exposure to potential mpox case patients). Among these participants, 10 of 13 case patients (76.9%) and 2 of 5 controls (40.0%) reported that their index contacts were not experiencing symptoms visible to participants during sex (OR, 14.9 [95% CI, 3.6-101.8]). Only 3 of 54 case patients (5.6%) reported exposure to symptomatic index contacts. Case patients reported more anal/vaginal sex partners than did controls (adjusted OR, 2.2 [95% CI, 1.0-4.8] for 2-3 partners and 3.8 [1.7-8.8] for ≥4 partners). Male case patients with penile lesions more commonly reported insertive anal/vaginal sex than those without penile lesions (adjusted OR, 9.3 [95% CI, 1.6-54.8]). Case patients with anorectal lesions more commonly reported receptive anal sex than those without anorectal lesions (adjusted OR, 14.4 [95% CI, 1.0-207.3]).
    Conclusions: Sexual exposure to contacts known or suspected to have experienced mpox was associated with increased risk of infection, often when index contacts lacked apparent symptoms. Exposure to more sex partners, including those whom participants did not identify as index contacts, was associated with increased risk of infection in a site-specific manner. While participants' assessment of symptoms in partners may be imperfect, these findings suggest that individuals without visibly prominent mpox symptoms transmit infection.
    MeSH term(s) Female ; Humans ; Male ; HIV Infections ; Case-Control Studies ; Mpox (monkeypox) ; Risk Factors ; Sexual Behavior ; California ; Homosexuality, Male ; Sexual and Gender Minorities
    Language English
    Publishing date 2023-10-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad447
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