Deciphering Polymer Interactions in Bioconjugates with Different Architectures by Structural Analysis via Time-resolved Limited Proteolysis Mass Spectrometry.

Therapeutic proteins are commonly conjugated with polymers to modulate their pharmacokinetics but often lack a description of the polymer-protein interaction. We deployed limited proteolysis mass spectrometry (LiP-MS) to reveal the interaction of polyethylene glycol (PEG) and PEG alternative polymers with interferon-α2a (IFN). Target conjugates were digested with the specific protease trypsin and a "heavy" 15N-IFN wild type (IFN-WT) for time-resolved quantification of the cleavage dynamics.

US Real-World Effectiveness, Tolerability, and Healthcare Resource Utilization After Addition of Fremanezumab for Preventive Treatment in Patients Using Gepants for Acute Treatment of Migraine: Results From a Retrospective Chart Review.

Introduction: Fremanezumab, a monoclonal antibody (mAb) targeting the calcitonin gene-related peptide (CGRP) pathway, and gepants, small molecule CGRP receptor antagonists, are both approved for the treatment of migraine or its symptoms. This study assessed effectiveness, tolerability, and migraine-related healthcare resource utilization (HCRU) after the addition of fremanezumab for preventive migraine treatment in patients using gepants for acute treatment.

Methods: Data were extracted during a retrospective chart review from electronic medical records from the Dent Neurologic Institute.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Psychosocial Outcomes of Supported Living for People with Severe Mental Illness: A One Year Evaluation of Floating Outreach in Germany.

Supported living plays an important role in the community-based care for people with mental illness. However, support services like floating outreach have hardly been the subject of longer-term research to date, especially with regard to Germany. Thus, the main aim of this prospective observational study was to evaluate the psychosocial outcomes of floating outreach support for non-homeless people with severe mental illness across a one-year period.

Reactions to and Impact of Survivor Online Disclosures: A Qualitative Analysis.

Social reactions to disclosure of sexual victimization play an important role in the process of recovery. The purpose of this qualitative study was to explore the impact of online disclosure of sexual victimization. The sample for this qualitative study ( = 17) focused on participants who shared their experiences with disclosing about their sexual victimization online and the reactions received in these spaces.

Predictors of return to work in people with major depression: Results from a supported employment program in Germany.

Background: Depression is a common mental disorder and is associated with work disability. For the implementation of evidence-based interventions, such as Individual Placement and Support (IPS) for people with depression in Germany, the aim of this study was to investigate client variables that predict return to work.

Methods: The sample consisted of 129 participants, initially treated in a psychiatric hospital due to major depression, who participated in IPS as part of a German clinical trial.

Two Sides of the Same Coin in Female Borderline Personality Disorder: Self-Reported Guilt and Shame and Their Neurofunctional Correlates.

Objective: Patients with borderline personality disorder (BPD) report to be especially prone to social emotions like shame and guilt. At the same time, these emotions seem to play an important role in BPD pathology. The present study aimed to deepen the knowledge about the processes behind shame and guilt in patients with BPD.

A Dutch cost-effectiveness analysis of fremanezumab versus best supportive care in patients with chronic migraine and inadequate response to prior preventive therapy.

Background: Chronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide pathway as a migraine preventive therapy. This study aimed to conduct a cost-effectiveness analysis of fremanezumab from a societal perspective in the Netherlands, using a Markov cohort simulation model.

Somatic Factors Predict On-Road Driving Skills in Older Drivers and Drivers with Mild Cognitive Impairment.

Background: On-road driving skills can be impaired in older drivers and drivers with mild cognitive impairment (MCI) due to different driving-relevant deficits. Among these deficits, somatic factors have received little attention so far.

Methods: In a prospective observational on-road driving study, we examined whether somatic factors can predict on-road driving skills in a mixed sample of healthy older drivers and drivers with MCI (n = 99) and whether the inclusion of age explains additional variance.

An Introductory Guide to Protease Sensitive Linker Design Using Matrix Metalloproteinase 13 as an Example.

Proteases play a crucial role, not only in physiological, but also in pathological processes, such as cancer, inflammation, arthritis, Alzheimer's, and infections, to name but a few. Their ability to cleave peptides can be harnessed for a broad range of biotechnological purposes. To do this efficiently, it is essential to find an amino acid sequence that meets the necessary requirements, including interdependent factors like specificity, selectivity, cleavage kinetics, or synthetic accessibility.

Two Sides of Theory of Mind: Mental State Attribution to Moving Shapes in Paranoid Schizophrenia Is Independent of the Severity of Positive Symptoms.

Background: Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM (undermentalizing) or an increased ToM ability to hyperattribute others' mental states (overmentalizing).

Methods: Mental state attribution was examined in 24 patients diagnosed with schizophrenia (12 acute paranoid (APS) and 12 post-acute paranoid (PPS)) with regard to positive symptoms as well as matched healthy persons using a moving shapes paradigm.

The laboratory parameters-derived CoLab score as an indicator of the host response in ICU COVID-19 patients decreases over time: a prospective cohort study.

The CoLab score was developed and externally validated to rule out COVID-19 among suspected patients presenting at the emergency department. We hypothesized a within-patient decrease in the CoLab score over time in an intensive care unit (ICU) cohort. Such a decrease would create the opportunity to potentially rule out the need for isolation when the infection is overcome.

Real-world Impact of Fremanezumab on Migraine-Related Health Care Resource Utilization in Patients with Comorbidities, Acute Medication Overuse, and/or Unsatisfactory Prior Migraine Preventive Response.

Introduction: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed.

Methods: Data for this US, retrospective claims analysis were obtained from the Merative MarketScan Commercial and supplemental databases.

Reliability and validity of the dynamic risk outcome scales-short version for clients with mild intellectual disabilities or borderline intellectual functioning.

Introduction: This study investigated the reliability and validity of the dynamic risk outcome scales-short version (DROS-SV). This instrument is developed to monitor treatment progress using dynamic risk factors in clients with mild intellectual disabilities or borderline intellectual functioning and behavioural and/or mental health problems.

Method: Data were collected from 264 clients who received Flexible Assertive Community Treatment (FACT), a form of intensive outpatient treatment.

[Everyday Life and Mental Health of Elderly with Cognitive Impairment During the Covid-19 Pandemic].

Objective: The aim is to analyze pandemic-related effects on everyday life and psychosocial health in the understudied vulnerable group of cognitively impaired elderly people living at home.

Methods: Structured telephone interviews in 2020 (n+=+141) and 2021 (n+=+107) were used to survey over-65s with cognitive impairment (MMSE Ø 23.4).

Does mixing inhaler devices lead to unchecked inhaler technique errors in patients with COPD? Findings from the cross-sectional observational MISMATCH study.

Background: Patients with chronic obstructive pulmonary disease (COPD) may be prescribed multiple inhalers that require different techniques for optimal performance. Mixing devices has been associated with poorer COPD outcomes suggesting that it leads to inappropriate inhaler technique. However, empirical evidence is lacking.

A comprehensive view of pregnancy in patients with sickle cell disease in high-income countries: the need for robust data and further decline in morbidity and mortality.

Sickle cell disease is a major public health concern due to its prevalence and associated morbidities. In high-income countries, diagnosis and treatment advancements have extended patient's lives and enabled women to embrace motherhood. Although the provision of care in specialist centres has reduced maternal-fetal complication rates, the mortality rate among pregnant women with sickle cell disease remains disproportionately high.

Hyperglycemia and glucose variability are associated with worse survival in mechanically ventilated COVID-19 patients: the prospective Maastricht Intensive Care Covid Cohort.

Background: Data on hyperglycemia and glucose variability in relation to diabetes mellitus, either known or unknown in ICU-setting in COVID-19, are scarce. We prospectively studied daily glucose variables and mortality in strata of diabetes mellitus and glycosylated hemoglobin among mechanically ventilated COVID-19 patients.

Methods: We used linear-mixed effect models in mechanically ventilated COVID-19 patients to investigate mean and maximum difference in glucose concentration per day over time.