Mindfulness-Based Interventions for In-Patients With Schizophrenia Spectrum Disorders-A Qualitative Approach

In recent years, mindfulness-based interventions (MBI) have gained clinical relevance in the treatment of patients with schizophrenia spectrum disorders (SSDs). High symptom burden, long durations of hospitalization and high rehospitalization rates demonstrate the severity and cost-intensity of these disorders. MBIs have shown promising treatment outcomes in a small number of trials, primarily taking place in English-speaking countries. The current study aims to explore mechanisms and processes as well as adverse effects of MBIs on in-patients with SSDs in a German university hospital setting. A qualitative design based on inductive thematic analysis accompanied by quantitative assessments was chosen. A semi-structured interview guide was developed by psychiatrists and psychologists to assess patient experiences, perceptions, thoughts, and feelings during and after taking part in a MBI. Twenty-seven interviews were conducted between September 2017 and October 2018 with in-patients who are diagnosed with schizophrenia or schizoaffective disorder. Rater-based questionnaires, such as the Positive and Negative Syndrome Scale (PANSS), Montgomery Asberg Depression Rating Scale (MADRS), and Psychotic Symptom Rating Scales-Auditory Hallucination (PSYRATS-AH) were administered at baseline to collect clinical outcomes. Qualitative analysis revealed two domains: content and function. In the first domain related to content with the core elements "detachment and rumination", "presence and getting lost", "non-judgment and judgment", and effects with "emotions", "cognition", and "symptom changes". A second domain related to function was extracted, including the relevance of perception of context and transfer to everyday life. Overall, improvements concerning cognition, distress, and psychopathology were detected, while no adverse effects, such as increased psychotic symptoms, were revealed. As the first study of its kind, mechanisms, processes, and the safety of MBIs were explored and confirmed in a sample of German in-patients with SSDs. The results of this qualitative study are in line with recent findings on MBIs amongst patients with psychotic disorders from other countries. Results lay the ground for future research to focus on the systematic study of MBIs in large samples, its treatment processes, outcomes, and effectiveness for in-patients with SSDs

Perceived Severity of Stressors in the Intensive Care Unit: A Systematic Review and Semi-Quantitative Analysis of the Literature on the Perspectives of Patients, Health Care Providers and Relatives

The aim of this study was to synthesize quantitative research that identified ranking lists of the most severe stressors of patients in the intensive care unit, as perceived by patients, relatives, and health care professionals (HCP). We conducted a systematic literature search in PubMed, MEDLINE, EMBASE, PsycInfo, CINAHL, and Cochrane Library from 1989 to 15 May 2020. Data were analyzed with descriptive and semi-quantitative methods to yield summarizing ranking lists of the most severe stressors. We synthesized the results of 42 prospective cross-sectional observational studies from different international regions. All investigations had assessed patient ratings. Thirteen studies also measured HCP ratings, and four studies included ratings of relatives. Data indicated that patients rate the severity of stressors lower than HCPs and relatives do. Out of all ranking lists, we extracted 137 stressor items that were most frequently ranked among the most severe stressors. After allocation to four domains, a group of clinical ICU experts sorted these stressors with good to excellent agreement according to their stress levels. Our results may contribute to improve HCPs' and relatives' understanding of patients' perceptions of stressors in the ICU. The synthesized stressor rankings can be used for the development of new assessment instruments of stressors

Novel methods for in vitro modeling of pancreatic cancer reveal important aspects for successful primary cell culture

Background: Pancreatic cancer remains a fatal disease. Experimental systems are needed for personalized treatment strategies, drug testing and to further understand tumor biology. Cell cultures can serve as an excellent preclinical platform, but their generation remains challenging. Methods: Tumor cells from surgically removed pancreatic ductal adenocarcinoma (PDAC) specimens were cultured under novel protocols. Cellular growth and composition were analyzed and culture conditions were continuously optimized. Characterization of cell cultures and primary tumors was performed via hematoxylin and eosin (HE) and immunofluorescence (IF) staining. Results: Protocols for two- and three-dimensional PDAC primary cell cultures could successfully be established. Primary cell culture depended on dissociation techniques, growth factor supplementation and extracellular matrix components containing Matrigel being crucial for the transformation to three-dimensional PDAC organoids. The generated cultures showed to be highly resemblant to established PDAC primary cell cultures. HE and IF staining for cell culture and corresponding primary tumor characterization could successfully be performed. Conclusions: The work presented herein shows novel and effective methods to successfully establish primary PDAC cell cultures in a distinct time frame. Factors contributing to cell growth and differentiation could be identified with important implications for further primary cell culture protocols. The established protocols might serve as novel tools in personalized tumor therapy

Circadian rhythms in septic shock patients

Background: Despite the intensive efforts to improve the diagnosis and therapy of sepsis over the last decade, the mortality of septic shock remains high and causes substantial socioeconomical burden of disease. The function of immune cells is time-of-day-dependent and is regulated by several circadian clock genes. This study aims to investigate whether the rhythmicity of clock gene expression is altered in patients with septic shock. Methods: This prospective pilot study was performed at the university hospital Charite-Universitatsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK). We included 20 patients with septic shock between May 2014 and January 2018, from whom blood was drawn every 4 h over a 24-h period to isolate CD14-positive monocytes and to measure the expression of 17 clock and clock-associated genes. Of these patients, 3 whose samples expressed fewer than 8 clock genes were excluded from the final analysis. A rhythmicity score S-P was calculated, which comprises values between -1 (arrhythmic) and 1 (rhythmic), and expression data were compared to data of a healthy study population additionally. Results: 77% of the measured clock genes showed inconclusive rhythms, i.e., neither rhythmic nor arrhythmic. The clock genes NR1D1, NR1D2 and CRY2 were the most rhythmic, while CLOCK and ARNTL were the least rhythmic. Overall, the rhythmicity scores for septic shock patients were significantly (p < 0.0001) lower (0.23 +/- 0.26) compared to the control group (12 healthy young men, 0.70 +/- 0.18). In addition, the expression of clock genes CRY1, NR1D1, NR1D2, DBP, and PER2 was suppressed in septic shock patients and CRY2 was significantly upregulated compared to controls. Conclusion: Molecular rhythms in immune cells of septic shock patients were substantially altered and decreased compared to healthy young men. The decrease in rhythmicity was clock gene-dependent. The loss of rhythmicity and down-regulation of clock gene expression might be caused by sepsis and might further deteriorate immune responses and organ injury, but further studies are necessary to understand underlying pathophysiological mechanisms

Epithelial cell lines of the cotton rat (<i>Sigmodon hispidus</i>) are highly susceptible in vitro models to zoonotic <i>Bunya-</i>, <i>Rhabdo-</i>, and <i>Flaviviruses</i>

Background: Small mammals such as bats and rodents have been increasingly recognized as reservoirs of novel potentially zoonotic pathogens. However, few in vitro model systems to date allow assessment of zoonotic viruses in a relevant host context. The cotton rat (Sigmodon hispidus) is a New World rodent species that has a long-standing history as an experimental animal model due to its unique susceptibility to human viruses. Furthermore, wild cotton rats are associated with a large variety of known or potentially zoonotic pathogens. Methods: A method for the isolation and culture of airway epithelial cell lines recently developed for bats was applied for the generation of rodent airway and renal epithelial cell lines from the cotton rat. Continuous cell lines were characterized for their epithelial properties as well as for their interferon competence. Susceptibility to members of zoonotic Bunya-, Rhabdo-, and Flaviviridae, in particular Rift Valley fever virus (RVFV), vesicular stomatitis virus (VSV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV) was tested. Furthermore, novel arthropod-derived viruses belonging to the families Bunya-, Rhabdo-, and Mesoniviridae were tested. Results: We successfully established airway and kidney epithelial cell lines from the cotton rat, and characterized their epithelial properties. Cells were shown to be interferon-competent. Viral infection assays showed high-titre viral replication of RVFV, VSV, WNV, and TBEV, as well as production of infectious virus particles. No viral replication was observed for novel arthropod-derived members of the Bunya-, Rhabdo-, and Mesoniviridae families in these cell lines. Conclusion: In the current study, we showed that newly established cell lines from the cotton rat can serve as host-specific in vitro models for viral infection experiments. These cell lines may also serve as novel tools for virus isolation, as well as for the investigation of virus-host interactions in a relevant host species.</p

Bat Airway Epithelial Cells: A Novel Tool for the Study of Zoonotic Viruses

<div><p>Bats have been increasingly recognized as reservoir of important zoonotic viruses. However, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. Further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. The epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. Although several cell lines from bats were established recently, no well-characterized, selectively cultured airway epithelial cells were available so far. Here, primary cells and immortalized cell lines from bats of the two important suborders Yangochiroptera and Yinpterochiroptera, <i>Carollia perspicillata</i> (Seba's short-tailed bat) and <i>Eidolon helvum</i> (Straw-colored fruit bat), were successfully cultured under standardized conditions from both fresh and frozen organ specimens by cell outgrowth of organ explants and by the use of serum-free primary cell culture medium. Cells were immortalized to generate permanent cell lines. Cells were characterized for their epithelial properties such as expression of cytokeratin and tight junctions proteins and permissiveness for viral infection with Rift-Valley fever virus and vesicular stomatitis virus Indiana. These cells can serve as suitable models for the study of bat-borne viruses and complement cell culture models for virus infection in human airway epithelial cells.</p></div

Virus infection studies with vesicular stomatitis virus (VSV) (A, B) and Rift Valley fever virus (RVFV) (C, D), and at MOI of 0.1 (left side) and 0.001 (right side), in subclones of immortalized <i>C. perspicillata</i> airway epithelial cells (subclone 3, designated CarperAEC.B-3) and <i>E. helvum</i> airway epithelial cells (subclone 1, designated EidheAEC.B-1).

<p>Viruses were detected by quantitative real-time RT-PCR. All cells were infectable and able to support replication of RVFV and VSV.</p

Characteristics of bat species chosen for the establishment of bat airway epithelial cells.

<p>Characteristics of bat species chosen for the establishment of bat airway epithelial cells.</p

Viruses associated with the bat species <i>C. perspicillata</i> and <i>E. helvum</i>.

<p>Viruses were detected either as virus isolates, on the basis of genetic sequence, or indirectly by detection of antibodies. Table adapted from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084679#pone.0084679-Luis1" target="_blank">[32]</a>; modified and supplemented. Viruses that have been reported to infect humans are marked with *.</p