Publications by authors named "Michael Bauer"

777 Publications

Low‑Level Environmental Heavy Metals are Associated with Obesity Among Postmenopausal Women in a Southern State.

Expo Health 2021 Jun 17;13(2):269-280. Epub 2021 Jan 17.

Department of Epidemiology, Fay W. Boozman College of Public Health, University of Arkansas Medical Sciences, 4301 W. Markham St. # 820, Little Rock, AR 72205, USA.

Both arsenic and cadmium are reported to be toxic to humans. The use of saliva as a biomarker of low-level exposures to these elements has not been adequately explored, and the putative relationship between exposure and obesity is unclear. This cross-sectional study aims to investigate the relationship between salivary arsenic and cadmium concentrations and their association with obesity. Arsenic and cadmium concentrations were analyzed in human saliva samples by Inductively Coupled Plasma-Mass Spectrometry on 270 randomly selected women who participated in the Arkansas Rural Community Health Study. Multivariable logistic regression was performed to evaluate the association between heavy metal concentrations and obesity. Stratified logistic regression was performed based on menopausal status. Generalized linear models were used to evaluate weight gain velocity. Significant positive associations were observed in postmenopausal women for both arsenic (OR = 4.43, 95% CI 1.91-10.28) and cadmium (OR = 2.72, 95% CI 1.23-5.99) concentrations, as well as significant trends among tertiles ( < 0.01 and = 0.01, respectively). No relationship with obesity was evident among premenopausal women for either metal. A dose-response relationship was observed between increasing weight gain velocity and increasing metal concentrations. At concentrations well below governmental and industrial standards for acute toxicity, significant associations between obesity and concentration of these heavy metals are evident. The rate at which individuals gain weight is affected by metal concentrations and may play a role in the rapid increase in weight in postmenopausal women. These results might explain, in part, the missing variability in the increasing obesity pandemic in certain population exposed to these environmental toxicants.
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http://dx.doi.org/10.1007/s12403-020-00381-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323941PMC
June 2021

Cardiovascular Effects of Combining Subcutaneous or Intravenous Esketamine and the MAO Inhibitor Tranylcypromine for the Treatment of Depression: A Retrospective Cohort Study.

CNS Drugs 2021 Jul 20. Epub 2021 Jul 20.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Background: (Es)ketamine and monoamine oxidase inhibitors (MAOIs), e.g., tranylcypromine, are therapeutic options for treatment-resistant major depression. Simultaneous administration is currently not recommended because of concern about hypertensive crises.

Objective: Our objective was to evaluate whether changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) during esketamine administration differed between patients who concomitantly received tranylcypromine and those who did not.

Methods: This was a retrospective cohort study utilizing cardiovascular monitoring data from inpatients treated for severe depression in unipolar, bipolar, and schizoaffective disorder. Primary outcomes were change in mean BP and HR during the first hour after intravenous or subcutaneous esketamine administration compared with baseline, controlled for confounders. Secondary analyses quantify differences in absolute BP during esketamine treatment and comparisons of BP peaks, temporal effects, and intraindividual comparisons before and after tranylcypromine initiation.

Results: Our analysis included 509 esketamine administrations in 43 patients, 14 of whom concomitantly received tranylcypromine. Controlling for creatinine and age, mean ± standard deviation (SD) BP changes were significantly increased by concomitant tranylcypromine treatment (ΔSBP: F[1,503] = 86.73, p < 0.001; ΔDBP: F[1,503] = 55.71, p < 0.001), but HR remained unaffected. Mean SBP change during esketamine administration was 2.96 ± 18.11 mmHg in patients receiving tranylcypromine (TCP+) and -8.84 ± 11.31 mmHg in those who did not (TCP-). Changes in DBP were -2.81 ± 11.20 mmHg for TCP+ and -10.77 ± 9.13 mmHg for TCP-. Moreover, we found a significant dose-response relationship between tranylcypromine dose and BP (SBP: B = 0.35, standard error [SE] = 0.12, 95% confidence interval [CI] 0.12-0.60, p = 0.004; adjusted R = 0.11, p = 0.008; DBP: B = 0.21, SE = 0.08, 95% CI 0.06-0.36, p = 0.007; adjusted R = 0.08; p = 0.023).

Conclusions: Although statistically significant changes in BP were identified in patients receiving tranylcypromine and esketamine, these changes were clinically insignificant. Thus, combining esketamine and this MAOI appears to be safe at standard doses. The dose-response relationship calls for caution with higher doses of tranylcypromine.
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http://dx.doi.org/10.1007/s40263-021-00837-6DOI Listing
July 2021

Stealth Effect of Short Polyoxazolines in Graft Copolymers: Minor Changes of Backbone End Group Determine Liver Cell-Type Specificity.

ACS Nano 2021 Jul 16. Epub 2021 Jul 16.

Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany.

Dye-loaded micelles of 10 nm diameter formed from amphiphilic graft copolymers composed of a hydrophobic poly(methyl methacrylate) backbone and hydrophilic poly(2-ethyl-2-oxazoline) side chains with a degree of polymerization of 15 were investigated concerning their cellular interaction and uptake as well as their interaction with local and circulating cells of the reticuloendothelial system in the liver by intravital microscopy. Despite the high molar mass of the individual macromolecules ( ≈ 20 kg mol), backbone end group modification by attachment of a hydrophilic anionic fluorescent probe strongly affected the performance. To understand these effects, the end group was additionally modified by the attachment of four methacrylic acid repeating units. Although various micelles appeared similar in dynamic light scattering and cryo-transmission electron microscopy, changes in the micelles were evident from principal component analysis of the Raman spectra. Whereas an efficient stealth effect was found for micelles formed from polymers with anionically charged or thiol end groups, a hydrophobic end group altered the micelles' structure sufficiently to adapt cell-type specificity and stealth properties in the liver.
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http://dx.doi.org/10.1021/acsnano.1c04213DOI Listing
July 2021

Early detection of bipolar disorders and treatment recommendations for help-seeking adolescents and young adults: Findings of the Early Detection and Intervention Center Dresden.

Int J Bipolar Disord 2021 Jul 2;9(1):23. Epub 2021 Jul 2.

Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.

Background: Early identification and intervention of individuals with risk factors for or subtle prodromal symptoms of bipolar disorders (BD) may improve the illness course and prevent adverse long-term consequences.

Methods: We examined sociodemographic, clinical and psychopathological characteristics of help-seeking adolescents and young adults who consulted the Early Detection and Intervention Center Dresden at the University of Dresden (Germany) and presented with or without pre-defined at-risk criteria for BD. The standardized diagnostic procedure for all help-seeking youth included a comprehensive psychiatric history and a structured clinical interview. When BD at-risk state was suspected, early detection instruments (EPIbipolar, BPSS-FP) were applied. Treatment recommendations were formulated in multi-professional case conferences.

Results: Out of 890 help-seeking persons between 05/2009 and 04/2018, 582 (65%) completed the diagnostic process. Of these, 24 (4%) had manifest BD and 125 (21%) fulfilled at-risk BD criteria (age = 23.9 ± 0.6 years, female = 62%). Of the pre-defined main risk factors, family history for BD was reported in 22% of the at-risk persons, (hypo-)mania risk state in 44%, and increasing cyclothymic mood swings with increased activity in 48%. The most common secondary risk factors were decreased psychosocial functioning (78%), lifetime diagnosis of depressive disorder (67%) and specific sleep/circadian rhythm disturbances (59%). Substance use was very common in subjects at-risk for BD (cannabis = 50%, alcohol = 33%) and highest in patients with BD (cannabis = 75%, alcohol = 40%). Psychiatric treatment history, including psychopharmacological therapy, was similar between the groups, while treatment recommendations differed, with more advice for psychotherapy and antidepressants in the at-risk group with a lifetime diagnosis of depression and more advice for specialized BD treatment including mood stabilizers in patients with BD.

Conclusion: This analysis on the phenomenology of different BD at-risk stages suggests that early detection of individuals presenting with suggested risk factors for the development of BD is feasible in help-seeking young people. Future research should further develop/test stage-specific prevention and early targeted intervention approaches that were described in a naturalistic setting.
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http://dx.doi.org/10.1186/s40345-021-00227-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253866PMC
July 2021

[Erratum to: Mortality in sepsis and septic shock in Germany. Results of a systematic review and meta-analysis].

Anaesthesist 2021 Jun 21. Epub 2021 Jun 21.

Klinik für Anästhesie, operative Intensivmedizin und Schmerztherapie, Vivantes Klinikum Neukölln, Berlin, Deutschland.

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http://dx.doi.org/10.1007/s00101-021-00985-wDOI Listing
June 2021

[Sepsis in German intensive care units-Last position worldwide?… Not so fast].

Anaesthesist 2021 Jun 21. Epub 2021 Jun 21.

Klinik für Anästhesie, operative Intensivmedizin und Schmerztherapie, Vivantes Klinikum Neukölln, Rudower Straße 48, 12351, Berlin, Deutschland.

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http://dx.doi.org/10.1007/s00101-021-00986-9DOI Listing
June 2021

Using Crash Outcome Data Evaluation System (CODES) to examine injury in front vs. rear-seated infants and children involved in a motor vehicle crash in New York State.

Inj Epidemiol 2021 Jun 21;8(1):32. Epub 2021 Jun 21.

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA.

Background: In New York State (NYS), motor vehicle (MV) injury to child passengers is a leading cause of hospitalization and emergency department (ED) visits in children aged 0-12 years. NYS laws require appropriate child restraints for ages 0-7 years and safety belts for ages 8 and up while traveling in a private passenger vehicle, but do not specify a seating position.

Methods: Factors associated with injury in front-seated (n = 11,212) compared to rear-seated (n = 93,092) passengers aged 0-12 years were examined by age groups 0-3, 4-7 and 8-12 years using the 2012-2014 NYS Crash Outcome Data Evaluation System (CODES). CODES consists of Department of Motor Vehicle (DMV) crash reports linked to ED visits and hospitalizations. The front seat was row 1 and the rear rows 2-3. Vehicle towed from scene and air bag deployed were proxies for crash severity. Injury was dichotomized based on Maximum Abbreviated Injury Severity (MAIS) scores greater than zero. Multivariable logistic regression (odds ratios (OR) with 95% CI) was used to examine factors predictive of injury for the total population and for each age group.

Results: Front-seated children had more frequent injury than those rear-seated (8.46% vs. 4.92%, p < 0.0001). Children in child restraints experienced fewer medically-treated injuries compared to seat belted or unrestrained children (3.80, 6.50 and 13.62%, p < 0.0001 respectively). A higher proportion of children traveling with an unrestrained vs. restrained driver experienced injury (14.50% vs 5.26%, p < 0.0001). After controlling for crash severity, multivariable adjusted predictors of injury for children aged 0-12 years included riding in the front seat (1.20, 1.10-1.31), being unrestrained vs. child restraint (2.13, 1.73-2.62), being restrained in a seat belt vs. child restraint (1.20, 1.11-1.31), and traveling in a car vs. other vehicle type (1.21, 1.14-1.28). Similarly, protective factors included traveling with a restrained driver (0.61, 0.50-0.75), a driver aged < 25 years (0.91, 0.82-0.99), being an occupant of a later vehicle model year 2005-2008 (0.68, 0.53-0.89) or 2009-2015 (0.55, 0.42-0.71) compared to older model years (1970-1993).

Conclusions: Compared to front-seated children, rear-seated children and children in age-appropriate restraints had lower adjusted odds of medically-treated injury.
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http://dx.doi.org/10.1186/s40621-021-00328-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215803PMC
June 2021

Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis?

Mol Psychiatry 2021 Jun 17. Epub 2021 Jun 17.

Zentrums für Apherese- und Hämofiltration am INUS Tagesklinikum, Cham, Germany.

As millions of patients have been infected by SARS-CoV-2 virus a vast number of individuals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called "post-COVID syndrome" or "long-COVID" [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups. Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.
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http://dx.doi.org/10.1038/s41380-021-01148-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209771PMC
June 2021

Lithium: A therapeutic option in Alzheimer's disease and its prodromal stages?

Neurosci Lett 2021 Jun 10:136044. Epub 2021 Jun 10.

Department of Psychiatry, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany.

Experimental data reveal that lithium is capable of attenuating Alzheimer's disease pathology and stimulating adult hippocampal neurogenesis. Clinical studies show procognitive effects in lithium-treated patients with amnestic MCI and Alzheimer's disease. These procognitive effects are associated with changes of CSF biomarkers of Alzheimer's disease. After 3 months of lithium treatment with low lithium levels, a slowing of cognitive decline is observed in patients with Alzheimer's disease. In patients with amnestic MCI with low-dose lithium treatment a trend of a reduced Alzheimer's disease conversion rate and longer cognitive stability was reported. Thus, lithium might be a therapeutic option in the treatment of Alzheimer's disease and its prodromal stages. But its therapeutic efficacy needs further evaluation. Further studies should include head-to-head comparisons with approved dementia treatment options. Due to lithium's therapeutic toxicity a thorough preselection of patients and a closely therapeutic monitoring is necessary. This manuscript is based on a literature review.
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http://dx.doi.org/10.1016/j.neulet.2021.136044DOI Listing
June 2021

[COVID-19 in neurology and psychiatry].

Nervenarzt 2021 06 7;92(6):519-520. Epub 2021 Jun 7.

Klinik und Poliklinik für Psychiatrie und Psychotherapie, Carl Gustav Carus Universitätsklinikum Dresden, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Deutschland.

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http://dx.doi.org/10.1007/s00115-021-01130-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182731PMC
June 2021

Leukocyte Activation Profile Assessed by Raman Spectroscopy Helps Diagnosing Infection and Sepsis.

Crit Care Explor 2021 May 12;3(5):e0394. Epub 2021 May 12.

Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany.

Objectives: Leukocytes are first responders to infection. Their activation state can reveal information about specific host immune response and identify dysregulation in sepsis. This study aims to use the Raman spectroscopic fingerprints of blood-derived leukocytes to differentiate inflammation, infection, and sepsis in hospitalized patients. Diagnostic sensitivity and specificity shall demonstrate the added value of the direct characterization of leukocyte's phenotype.

Design: Prospective nonrandomized, single-center, observational phase-II study (DRKS00006265).

Setting: Jena University Hospital, Germany.

Patients: Sixty-one hospitalized patients (19 with sterile inflammation, 23 with infection without organ dysfunction, 18 with sepsis according to Sepsis-3 definition).

Interventions: None (blood withdrawal).

Measurements And Main Results: Individual peripheral blood leukocytes were characterized by Raman spectroscopy. Reference diagnostics included established clinical scores, blood count, and biomarkers (C-reactive protein, procalcitonin and interleukin-6). Binary classification models using Raman data were able to distinguish patients with infection from patients without infection, as well as sepsis patients from patients without sepsis, with accuracies achieved with established biomarkers. Compared with biomarker information alone, an increase of 10% (to 93%) accuracy for the detection of infection and an increase of 18% (to 92%) for detection of sepsis were reached by adding the Raman information. Leukocytes from sepsis patients showed different Raman spectral features in comparison to the patients with infection that point to the special immune phenotype of sepsis patients.

Conclusions: Raman spectroscopy can extract information on leukocyte's activation state in a nondestructive, label-free manner to differentiate sterile inflammation, infection, and sepsis.
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http://dx.doi.org/10.1097/CCE.0000000000000394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162546PMC
May 2021

Do outcomes of psychiatric hospital treatment differ for migrants and non-migrants?

Soc Psychiatry Psychiatr Epidemiol 2021 May 24. Epub 2021 May 24.

Unit for Social & Community Psychiatry, WHO Collaborating Centre for Mental Health Services Development, East London NHS Foundation Trust, Newham Centre for Mental Health, Queen Mary University of London, London, E13 8SP, UK.

Purpose: Providing effective treatment for immigrants is an increasing challenge for mental health services across Europe. Yet, little is known as to whether current practice is associated with different outcomes in migrant and non-migrant patients. We compared outcomes of inpatient psychiatric treatment for migrants and non-migrants in a sample from five European countries.

Methods: Patients with psychotic disorders, affective disorders or anxiety/somatisation disorders admitted to routine psychiatric inpatient treatment were assessed in hospitals in Belgium, Germany, Italy, Poland and the United Kingdom. Treatment outcomes were satisfaction with care during hospitalisation, length of stay, readmission to hospital (any and, specifically, involuntary re-hospitalisation), as well as untoward incidents in a 1-year follow-up period. Outcomes were compared between patients born inside (non-migrants) and outside (migrants) the country of treatment, through mixed regression models.

Results: Across all sites, 985 migrant patients and 6298 non-migrant patients were included. After accounting for the influence of confounding patient characteristics, migrants reported significantly lower treatment satisfaction, but there were no significant differences for length of stay and re-hospitalisations, in general and involuntary ones. Migrants had a lower rate of suicide attempts, but there was no significant difference in other types of untoward incidents in the year following the index admission.

Conclusion: The study suggests that migrants are less satisfied with their hospital treatment, there is no evidence that routine inpatient care as currently provided results overall in poorer objective outcomes for migrants than in non-migrant populations.
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http://dx.doi.org/10.1007/s00127-021-02103-yDOI Listing
May 2021

Divergent Dimethylarginine Dimethylaminohydrolase Isoenzyme Expression in the Central Nervous System.

Cell Mol Neurobiol 2021 May 20. Epub 2021 May 20.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

The endogenous methylated derivative of ʟ-arginine, N,N-dimethyl-ʟ-arginine (asymmetric dimethylarginine, ADMA), an independent risk factor in many diseases, inhibits the activity of nitric oxide synthases and, consequently, modulates the availability of nitric oxide. While most studies on the biological role of ADMA have focused on endothelial and inducible nitric oxide synthases modulation and its contribution to cardiovascular, metabolic, and renal diseases, a role in regulating neuronal nitric oxide synthases and pathologies of the central nervous system is less understood. The two isoforms of dimethylarginine dimethylaminohydrolase (DDAH), DDAH1 and DDAH2, are thought to be the main enzymes responsible for ADMA catabolism. A current impediment is limited knowledge on specific tissue and cellular distribution of DDAH enzymes within the brain. In this study, we provide a detailed characterization of the regional and cellular distribution of DDAH1 and DDAH2 proteins in the adult murine and human brain. Immunohistochemical analysis showed a wide distribution of DDAH1, mapping to multiple cell types, while DDAH2 was detected in a limited number of brain regions and exclusively in neurons. Our results provide key information for the investigation of the pathophysiological roles of the ADMA/DDAH system in neuropsychiatric diseases and pave the way for the development of novel selective therapeutic approaches.
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http://dx.doi.org/10.1007/s10571-021-01101-7DOI Listing
May 2021

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.

Nat Genet 2021 06 17;53(6):817-829. Epub 2021 May 17.

Department of Neuroscience, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
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http://dx.doi.org/10.1038/s41588-021-00857-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192451PMC
June 2021

The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.

Lancet Respir Med 2021 06 6;9(6):622-642. Epub 2021 May 6.

Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-inflammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.
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http://dx.doi.org/10.1016/S2213-2600(21)00218-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102044PMC
June 2021

Chromothripsis as a pathogenic driver of multiple myeloma.

Semin Cell Dev Biol 2021 May 3. Epub 2021 May 3.

Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA. Electronic address:

Analysis of the genetic basis for multiple myeloma (MM) has informed many of our current concepts of the biology that underlies disease initiation and progression. Studying these events in further detail is predicted to deliver important insights into its pathogenesis, prognosis and treatment. Information from whole genome sequencing of structural variation is revealing the role of these events as drivers of MM. In particular, we discuss how the insights we have gained from studying chromothripsis suggest that it can be used to provide information on disease initiation and that, as a consequence, it can be used for the clinical classification of myeloma precursor diseases allowing for early intervention and prognostic determination. For newly diagnosed MM, the integration of information on the presence of chromothripsis has the potential to significantly enhance current risk prediction strategies and to better characterize patients with high-risk disease biology. In this article we summarize the genetic basis for MM and the role played by chromothripsis as a critical pathogenic factor active at early disease phases.
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http://dx.doi.org/10.1016/j.semcdb.2021.04.014DOI Listing
May 2021

Deficits in explicit emotion regulation in bipolar disorder: a systematic review.

Int J Bipolar Disord 2021 May 3;9(1):15. Epub 2021 May 3.

Clinical Psychology and Behavioral Neuroscience, Faculty of Psychology, Technische Universität Dresden, Chemnitzer Str. 46, 01187, Dresden, Germany.

Background: This study aimed to compile and synthesize studies investigating explicit emotion regulation in patients with bipolar disorder and individuals at risk of developing bipolar disorder. The importance of explicit emotion regulation arises from its potential role as a marker for bipolar disorders in individuals at risk and its potent role in therapy for bipolar disorder patients.

Methods: To obtain an exhaustive compilation of studies dealing specifically with explicit emotion regulation in bipolar disorder, we conducted a systematic literature search in four databases. In the 15 studies we included in our review, the emotion-regulation strategies maintenance, distraction, and reappraisal (self-focused and situation-focused) were investigated partly on a purely behavioral level and partly in conjunction with neural measures. The samples used in the identified studies included individuals at increased risk of bipolar disorder, patients with current affective episodes, and patients with euthymic mood state.

Results: In summary, the reviewed studies' results indicate impairments in explicit emotion regulation in individuals at risk for bipolar disorder, patients with manic and depressive episodes, and euthymic patients. These deficits manifest in subjective behavioral measures as well as in neural aberrations. Further, our review reveals a discrepancy between behavioral and neural findings regarding explicit emotion regulation in individuals at risk for bipolar disorders and euthymic patients. While these groups often do not differ significantly in behavioral measures from healthy and low-risk individuals, neural differences are mainly found in frontostriatal networks.

Conclusion: We conclude that these neural aberrations are a potentially sensitive measure of the probability of occurrence and recurrence of symptoms of bipolar disorders and that strengthening this frontostriatal route is a potentially protective measure for individuals at risk and patients who have bipolar disorders.
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http://dx.doi.org/10.1186/s40345-021-00221-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089068PMC
May 2021

Shortwave infrared-absorbing squaraine dyes for all-organic optical upconversion devices.

Sci Technol Adv Mater 2021 Apr 13;22(1):194-204. Epub 2021 Apr 13.

Laboratory for Functional Polymers, Empa, Swiss Federal Laboratories for Materials Science and Technology, Dübendorf, Switzerland.

Shortwave infrared (SWIR) optical sensing and imaging are essential to an increasing number of next-generation applications in communications, process control or medical imaging. An all-organic SWIR upconversion device (OUC) consists of an organic SWIR sensitive photodetector (PD) and an organic light-emitting diode (OLED), connected in series. OUCs directly convert SWIR to visible photons, which potentially provides a low-cost alternative to the current inorganic compound-based SWIR imaging technology. For OUC applications, only few organic materials have been reported with peak absorption past 1000 nm and simultaneous small absorption in the visible. Here, we synthesized a series of thermally stable high-extinction coefficient donor-substituted benz[]indole-capped SWIR squaraine dyes. First, we coupled the phenyl-, carbazole-, and thienyl-substituted benz[]indoles with squaric acid (to obtain the SQ dye family). We then combined these donors with the dicyanomethylene-substituted squaraine acceptor unit, to obtain the dicyanomethylene-functionalized squaraine DCSQ family. In the solid state, the absorbance of all dyes extended considerably beyond 1100 nm. For the carbazole- and thienyl-substituted DCSQ dyes, even the peak absorptions in solution were in the SWIR, at 1008 nm and 1014 nm. We fabricated DCSQ PDs with an external photon-to-current efficiency over 30%. We then combined the PD with a fluorescent OLED and fabricated long-term stable OUCs with peak sensitivity at 1020 nm, extending to beyond 1200 nm. Our OUCs are characterized by a very low dark luminance (<10 cd m at below 6 V) in the absence of SWIR light, and a low turn-on voltage of 2 V when SWIR light is present.
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http://dx.doi.org/10.1080/14686996.2021.1891842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049466PMC
April 2021

How do Canadian public health agencies respond to the COVID-19 emergency using social media: a protocol for a case study using content and sentiment analysis.

BMJ Open 2021 04 22;11(4):e041818. Epub 2021 Apr 22.

Department of Computer Sciences, Faculty of Science, Western University, London, Ontario, Canada.

Introduction: Keeping Canadians safe requires a robust public health (PH) system. This is especially true when there is a PH emergency, like the COVID-19 pandemic. Social media, like Twitter and Facebook, is an important information channel because most people use the internet for their health information. The PH sector can use social media during emergency events for (1) PH messaging, (2) monitoring misinformation, and (3) responding to questions and concerns raised by the public. In this study, we ask: what is the Canadian PH risk communication response to the COVID-19 pandemic in the context of social media?

Methods And Analysis: We will conduct a case study using content and sentiment analysis to examine how provinces and provincial PH leaders, and the Public Health Agency of Canada and national public heath leaders, engage with the public using social media during the first wave of the pandemic (1 January-3 September 2020). We will focus specifically on Twitter and Facebook. We will compare findings to a gold standard during the emergency with respect to message content.

Ethics And Dissemination: Western University's research ethics boards confirmed that this study does not require research ethics board review as we are using social media data in the public domain. Using our study findings, we will work with PH stakeholders to collaboratively develop Canadian social media emergency response guideline recommendations for PH and other health system organisations. Findings will also be disseminated through peer-reviewed journal articles and conference presentations.
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http://dx.doi.org/10.1136/bmjopen-2020-041818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068947PMC
April 2021

Draft Genome Sequence of Persistent Klebsiella grimontii AT013-Mero-001, Isolated from Human Feces.

Microbiol Resour Announc 2021 Apr 22;10(16). Epub 2021 Apr 22.

Department of Anaesthesiology and Intensive Care Medicine, University Hospital Jena, Jena, Germany

Here, we report the draft genome sequence of AT013-Mero-001, which was isolated from feces from a sepsis patient treated with meropenem. This isolate is an antibiotic-susceptible but persistent strain.
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http://dx.doi.org/10.1128/MRA.00054-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063637PMC
April 2021

Camostat mesylate therapy in critically ill patients with COVID-19 pneumonia.

Intensive Care Med 2021 06 12;47(6):707-709. Epub 2021 Apr 12.

Department of Anesthesiology and Critical Care Medicine, Al Ain Hospital, SEHA, Abu Dhabi, UAE.

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http://dx.doi.org/10.1007/s00134-021-06395-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041240PMC
June 2021

The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

Institute of Molecular Cell Biology, Jena University Hospital, D-07745 Jena, Germany.

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.
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http://dx.doi.org/10.3390/ijms22052578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961448PMC
March 2021

Internet of things issues related to psychiatry.

Int J Bipolar Disord 2021 Apr 2;9(1):11. Epub 2021 Apr 2.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus Medical Faculty, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.

Background: Internet of Things (IoT) devices for remote monitoring, diagnosis, and treatment are widely viewed as an important future direction for medicine, including for bipolar disorder and other mental illness. The number of smart, connected devices is expanding rapidly. IoT devices are being introduced in all aspects of everyday life, including devices in the home and wearables on the body. IoT devices are increasingly used in psychiatric research, and in the future may help to detect emotional reactions, mood states, stress, and cognitive abilities. This narrative review discusses some of the important fundamental issues related to the rapid growth of IoT devices.

Main Body: Articles were searched between December 2019 and February 2020. Topics discussed include background on the growth of IoT, the security, safety and privacy issues related to IoT devices, and the new roles in the IoT economy for manufacturers, patients, and healthcare organizations.

Conclusions: The use of IoT devices will increase throughout psychiatry. The scale, complexity and passive nature of data collection with IoT devices presents unique challenges related to security, privacy and personal safety. While the IoT offers many potential benefits, there are risks associated with IoT devices, and from the connectivity between patients, healthcare providers, and device makers. Security, privacy and personal safety issues related to IoT devices are changing the roles of manufacturers, patients, physicians and healthcare IT organizations. Effective and safe use of IoT devices in psychiatry requires an understanding of these changes.
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http://dx.doi.org/10.1186/s40345-020-00216-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018992PMC
April 2021

Minimally-invasive mitral valve repair of symmetric and asymmetric Barlow´s disease.

Clin Res Cardiol 2021 Apr 1. Epub 2021 Apr 1.

Department of Cardiothoracic Surgery, Jena University Hospital, Friedrich-Schiller-University Jena, Am Klinikum 1, 07747, Jena, Germany.

Objectives: Barlow´s disease represents a wide spectrum of mitral valve pathologies associated with regurgitation (MR), excess leaflet tissue, and prolapse. Repair strategies range from complex repairs with annuloplasty plus neochords through resection to annuloplasty-only. The latter requires symmetric prolapse patterns and central regurgitant jets. We aimed to assess repair success and durability, survival, and intraoperative outcomes with symmetric and asymmetric Barlow's disease.

Methods: Between 09/10 and 03/20, 103 patients (of 1939 with mitral valve surgery) presented with Barlow´s disease. All received surgery through mini-thoracotomy with annuloplasty plus neochords (n = 71) or annuloplasty-only (n = 31). One valve was replaced for endocarditis (repair rate: 99%).

Results: Annuloplasty-only patients were older (64 ± 16 vs. 55 ± 11 years, p = 0.008) and presented with higher risk (EuroSCORE II: 4.2 ± 4.9 vs. 1.6 ± 1.7, p = 0.007). Annuloplasty-only patients had shorter cross-clamp times (53 ± 18 min vs. 76 ± 23 min, p < 0.001) and received more tricuspid annuloplasty (15.5% vs. 48.4%, p < 0.001). Operating times were similar (170 ± 41 min vs. 164 ± 35, p = 0.455). In three patients, annuloplasty-only caused intraoperative systolic anterior motion (SAM), which was fully resolved by neochords to the posterior leaflet. There were no conversions to sternotomy or deaths at 30-days. Three patients required reoperation for recurrent MR (at 25 days, 2.8 and 7.8 years). At the latest follow-up, there was no MR in 81.4%, mild in 14.7%, and moderate in 2.9%. Three patients died due to non-cardiac reasons. Surviving patients report the absence of relevant symptoms.

Conclusions: Minimally-invasive Barlow's repair is safe with good durability. Annuloplasty-only may be a simple solution for complex but symmetric pathologies. However, it may carry an increased risk of intraoperative SAM.
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http://dx.doi.org/10.1007/s00392-021-01844-9DOI Listing
April 2021

Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and the correlation with tissue damage.

Elife 2021 03 30;10. Epub 2021 Mar 30.

Institute of Forensic Medicine, Jena University Hospital, Jena, Germany.

Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body and its correlation with tissue damage can aid in understanding the pathophysiology of SARS-CoV-2 infection. We present a detailed mapping of the viral RNA in 61 tissues and organs of 11 deceased patients with COVID-19. The autopsies were performed within the early postmortem interval (between 1.5 and 15 hr, mean: 5.6 hr) to minimize the bias due to viral RNA and tissue degradation. Very high viral loads (>10copies/ml) were detected in most patients' lungs, and the presence of intact viral particles in the lung tissue could be verified by transmission electron microscopy. Interestingly, viral RNA was detected throughout various extrapulmonary tissues and organs without visible tissue damage. The dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis that there is a maladaptive host response with viremia and multiorgan dysfunction.
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http://dx.doi.org/10.7554/eLife.60361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009677PMC
March 2021

Host cystathionine-γ lyase derived hydrogen sulfide protects against Pseudomonas aeruginosa sepsis.

PLoS Pathog 2021 03 26;17(3):e1009473. Epub 2021 Mar 26.

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Hydrogen sulfide (H2S) has recently been recognized as a novel gaseous transmitter with several anti-inflammatory properties. The role of host- derived H2S in infections by Pseudomonas aeruginosa was investigated in clinical and mouse models. H2S concentrations and survival was assessed in septic patients with lung infection. Animal experiments using a model of severe systemic multidrug-resistant P. aeruginosa infection were performed using mice with a constitutive knock-out of cystathionine-γ lyase (Cse) gene (Cse-/-) and wild-type mice with a physiological expression (Cse+/+). Experiments were repeated in mice after a) treatment with cyclophosphamide; b) bone marrow transplantation (BMT) from a Cse+/+ donor; c) treatment with H2S synthesis inhibitor aminooxyacetic acid (ΑΟΑΑ) or propargylglycine (PAG) and d) H2S donor sodium thiosulfate (STS) or GYY3147. Bacterial loads and myeloperoxidase activity were measured in tissue samples. The expression of quorum sensing genes (QS) was determined in vivo and in vitro. Cytokine concentration was measured in serum and incubated splenocytes. Patients survivors at day 28 had significantly higher serum H2S compared to non-survivors. A cut- off point of 5.3 μΜ discriminated survivors with sensitivity 92.3%. Mortality after 28 days was 30.9% and 93.7% in patients with H2S higher and less than 5.3 μΜ (p = 7 x 10-6). In mice expression of Cse and application of STS afforded protection against infection with multidrug-resistant P. aeruginosa. Cyclophosphamide pretreatment eliminated the survival benefit of Cse+/+ mice, whereas BMT increased the survival of Cse-/- mice. Cse-/- mice had increased pathogen loads compared to Cse+/+ mice. Phagocytic activity of leukocytes from Cse-/- mice was reduced but was restored after H2S supplementation. An H2S dependent down- regulation of quorum sensing genes of P.aeruginosa could be demonstrated in vivo and in vitro. Endogenous H2S is a potential independent parameter correlating with the outcome of P. aeruginosa. H2S provides resistance to infection by MDR bacterial pathogens.
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http://dx.doi.org/10.1371/journal.ppat.1009473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051778PMC
March 2021

Use of IFNγ/IL10 Ratio for Stratification of Hydrocortisone Therapy in Patients With Septic Shock.

Front Immunol 2021 9;12:607217. Epub 2021 Mar 9.

Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.

Large clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may benefit of hydrocortisone treatment depending on their individual immune response. We performed an exploratory analysis of the database from the international randomized controlled clinical trial Corticosteroid Therapy of Septic Shock (CORTICUS) employing machine learning to a panel of 137 variables collected from the Berlin subcohort comprising 83 patients including demographic and clinical measures, organ failure scores, leukocyte counts and levels of circulating cytokines. The identified theranostic marker was validated against data from a cohort of the Hellenic Sepsis Study Group (HSSG) ( = 246), patients enrolled in the clinical trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT, = 118), and another, smaller clinical trial (Crossover study, = 20). In addition, blood culture experiments and experiments in mouse models were performed to assess biological plausibility. A low serum IFNγ/IL10 ratio predicted increased survival in the hydrocortisone group whereas a high ratio predicted better survival in the placebo group. Using this marker for a decision rule, we applied it to three validation sets and observed the same trend. Experimental studies revealed that IFNγ/IL10 was negatively associated with the load of (heat inactivated) pathogens in spiked human blood and in septic mouse models. Accordingly, an analysis of published IFNγ and IL10 values in bacteremic and non-bacteremic patients with the Systemic Inflammatory Response Syndrome supported this association between the ratio and pathogen burden. We propose IFNγ/IL10 as a molecular marker supporting the decision to administer hydrocortisone to patients in septic shock. Prospective clinical studies are necessary and standard operating procedures need to be implemented, particularly to define a generic threshold. If confirmed, IFNγ/IL10 may become a suitable theranostic marker for an urging clinical need.
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http://dx.doi.org/10.3389/fimmu.2021.607217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985546PMC
July 2021

Mid-German Sepsis Cohort (MSC): a prospective observational study of sepsis survivorship.

BMJ Open 2021 03 17;11(3):e043352. Epub 2021 Mar 17.

Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany

Purpose: The Mid-German Sepsis Cohort (MSC) aims to investigate mid-term and long-term functional disabilities in sepsis survivors from intensive care unit (ICU) discharge until 1 year after. Secondary, post-acute mortality and morbidity, health-related quality of life and healthcare utilisation will be investigated.

Participants: The MSC comprises adult (aged ≥18 years) patients who were treated for (severe) sepsis or septic shock on ICU. The participants were recruited between 15 April 2016 and 30 November 2018 from five German centres. Three thousand two hundred and ten patients with sepsis were identified, of which 1968 survived their ICU stay and were eligible for enrolment in the follow-up cohort. Informed consent for follow-up assessment was provided by 907 patients (46.1% of eligible patients).

Findings To Date: The recruitment of the participants for follow-up assessments and the baseline data collection is completed. Incidence of sepsis was 116.7 patients per 1000 ICU patients. In this cohort profile, we provide an overview of the demographics and the clinical characteristics of both the overall sepsis cohort and the ICU survivors who provided informed consent for follow-up assessment (907 out of 1968 ICU survivors (46.1%)).

Future Plans: The follow-ups are conducted 3, 6 and 12 months after ICU discharge. Another yearly follow-up up to 5 years after ICU discharge is pursued. Several cooperation and satellite projects were initiated. This prospective cohort offers a unique resource for research on long-term sequelae of sepsis survivors.

Trial Registration Number: German Clinical Trials Registry (DRKS00010050).
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http://dx.doi.org/10.1136/bmjopen-2020-043352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978081PMC
March 2021
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