Preservation of biomaterials and cells by freeze-drying : Change of paradigm

Freeze-drying is the most widespread method to preserve protein drugs and vaccines in a dry form facilitating their storage and transportation without the laborious and expensive cold chain. Extending this method for the preservation of natural biomaterials and cells in a dry form would provide similar benefits, but most results in the domain are still below expectations. In this review, rather than consider freeze-drying as a traditional black box we "break it" through a detailed process thinking approach. We discuss freeze-drying from process thinking aspects, introduce the chemical, physical, and mechanical environments important in this process, and present advanced biophotonic process analytical technology. In the end, we review the state of the art in the freezedrying of the biomaterials, extracellular vesicles, and cells. We suggest that the rational design of the experiment and implementation of advanced biophotonic tools are required to successfully preserve the natural biomaterials and cells by freeze-drying. We discuss this change of paradigm with existing literature and elaborate on our perspective based on our new unpublished results.Peer reviewe

Early maladaptive schemas in chronically depressed patients : A preliminary investigation

Background Schema therapy has been proposed as a potentially effective treatment for chronic depression. However, little is known about early maladaptive schemas (EMSs), a key concept in schema therapy, in relation to chronic depression or chronic depression with comorbid personality pathology. The aim of the present study was to compare EMSs between currently chronically depressed patients with comorbid cluster C personality disorder (CDCPD), currently chronically depressed patients (CD), and patients remitted from chronic depression (CDR). Methods Based on data from a naturalistic follow-up study on psychiatric outpatients with major depressive disorder, three groups were formed according to Diagnostic and Statistical Manual of Mental Disorders-IV: CDCPD (n = 15), CD (n = 23), and CDR (n = 13). Groups were compared in terms of background information and measurements for depression (Beck Depression Inventory) and EMSs (Young Schema Questionnaire). Results Patients with CDCPD and CD did not differ in terms of background variables or the severity of depressive symptoms, but patients with CDCPD were more maladaptive with respect to the majority of EMSs. Patients with CDR were less depressed than CDCPD or CD patients, but did not differ in terms of EMSs compared with CD patients. Conclusions Comorbid cluster C personality disorder appears to be associated with more severe EMS endorsement in chronically depressed patients. Remitted patients show similar cognitive vulnerability factors in terms of EMSs compared to those currently chronically depressed. The findings suggest that EMSs may contribute to vulnerability to chronic depression. Focusing on EMSs may be beneficial in the treatment of chronic depression.Peer reviewe

Near-infrared analysis of nanofibrillated cellulose aerogel manufacturing

Biomaterial aerogel fabrication by freeze-drying must be further improved to reduce the costs of lengthy freeze-drying cycles and to avoid the formation of spongy cryogels and collapse of the aerogel structures. Residual water content is a critical quality attribute of the freeze-dried product, which can be monitored in-line with near-infrared (NIR) spectroscopy. Predictive models of NIR have not been previously applied for biomaterials and the models were mostly focused on the prediction of only one formulation at a time. We recorded NIR spectra of different nanofibrillated cellulose (NFC) hydrogel formulations during the secondary drying and set up a partial least square regression model to predict their residual water contents. The model can be generalized to measure residual water of formulations with different NFC concentrations and the excipients, and the NFC fiber concentrations and excipients can be separated with the principal component analysis. Our results provide valuable information about the freeze-drying of biomaterials and aerogel fabrication, and how NIR spectroscopy can be utilized in the optimization of residual water content.Peer reviewe

Global arginine bioavailability ratio is decreased in patients with major depressive disorder

Background: Major depressive disorder (MDD) is characterized by increased oxidative and nitrosative stress. We compared nitric oxide metabolism, i.e., the global arginine bioavailability ratio (GABR) and related serum amino acids, between MDD patients and non-depressed controls, and between remitted and non-remitted MDD patients. Methods: Ninety-nine MDD patients and 253 non-depressed controls, aged 20-71 years, provided background data via questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of ornithine, arginine, citrulline, and symmetric and asymmetric dimethylarginine. GABR was calculated as arginine divided by the sum of ornithine plus citrulline. We compared the above measures between: 1) MDD patients and controls, 2) remitted (n= 33) and non-remitted (n = 45) MDD patients, and 3) baseline and follow-up within the remitted and non-remitted groups. Results: Lower arginine levels (OR 0.98, 95% CI 0.97-0.99) and lower GABR (OR 0.13, 95% CI 0.03-0.50) were associated with the MDD vs. the non-depressed group after adjustments for potential confounders. The remitted group showed a decrease in GABR, arginine, and symmetric dimethylarginine, and an increase in ornithine after the follow-up compared with within-group baseline values. The non-remitted group displayed an increase in arginine and ornithine levels and a decrease in GABR. No significant differences were recorded between the remitted and non-remitted groups. Limitations: The MDD group was not medication-free. Conclusions: Arginine bioavailability may be decreased in MDD. This could impair the production of nitric oxide, and thus add to oxidative stress in the central nervous system.Peer reviewe

Ahdistuneisuushäiriöt : KÄYPÄ HOITO -SUOSITUS (Tiivistelmä)

Käypä hoito -suositus. Tiivistelmä. English summar

Reality of auditory verbal hallucinations

Distortion of the sense of reality, actualized in delusions and hallucinations, is the key feature of psychosis but the underlying neuronal correlates remain largely unknown. We studied 11 highly functioning subjects with schizophrenia or schizoaffective disorder while they rated the reality of auditory verbal hallucinations (AVH) during functional magnetic resonance imaging (fMRI). The subjective reality of AVH correlated strongly and specifically with the hallucination-related activation strength of the inferior frontal gyri (IFG), including the Broca's language region. Furthermore, how real the hallucination that subjects experienced was depended on the hallucination-related coupling between the IFG, the ventral striatum, the auditory cortex, the right posterior temporal lobe, and the cingulate cortex. Our findings suggest that the subjective reality of AVH is related to motor mechanisms of speech comprehension, with contributions from sensory and salience-detection-related brain regions as well as circuitries related to self-monitoring and the experience of agency