The Relationship Between Self-Reported Childhood Maltreatment and Mental Health in Substance Use Disorders: A 6-Year Retrospective Analysis.

Objective: This longitudinal cohort study aims to investigate the relationship between self-reported childhood maltreatment (CM) and the retrospective trajectory of substance use, mental health, and satisfaction with life in individuals with substance use disorders.

Methods: One hundred eleven treatment-seeking individuals with substance use disorder were recruited from clinical settings and monitored prospectively for 6 years. The participants' substance use, mental health, and satisfaction with life were assessed using standardized measures.

Traumatic experiences and PTSD symptoms in substance use disorder: A comparison of recovered versus current users.

The aim of this study was to investigate the prevalence of traumatic experiences and symptoms of posttraumatic stress disorder (PTSD) in treatment-seeking individuals with ongoing substance use disorder (SUD) compared to individuals who have recovered from SUD. Patients with SUD recruited from the STAYER study (N = 114) underwent an examination of alcohol and drug use, childhood trauma, negative life events and PTSD symptomatology. In this study, only participants with 12-month concurrent polysubstance use was included.

Factors influencing doctors' counselling on patients' lifestyle habits: a cohort study.

Background: Lifestyle changes are important for prevention and treatment of many common diseases, and doctors have an important role in the lifestyle counselling of patients. It is important to know more about factors influencing lifestyle counselling.

Aim: To investigate the frequency of counselling about physical activity compared to that about alcohol habits; the impact of doctors' own physical activity and alcohol habits on patient counselling about these lifestyle dimensions; and whether perceived mastery of clinical work or vulnerable personality have a confounding or moderating effect on these associations.

Factors associated with low vs increased perceived mastery of clinical work over ten years of practice: a prospective study of Norwegian doctors.

Background: A higher sense of mastery of doctors' clinical work could benefit not only their own mental health but also their work performance and patient care. However, we know little about factors associated with perceived mastery of clinical work among physicians. Our aim was therefore to study characteristics of those with stable low levels and of those with increased levels of mastery over a period of ten years of medical practice.

Pan-NS3 protease inhibitors of hepatitis C virus based on an R-elongated pyrazinone scaffold.

Herein, we present the design and synthesis of 2(1H)-pyrazinone based HCV NS3 protease inhibitors and show that elongated R urea substituents were associated with increased inhibitory potencies over several NS3 protein variants. The inhibitors are believed to rely on β-sheet mimicking hydrogen bonds which are similar over different genotypes and current drug resistant variants and correspond to the β-sheet interactions of the natural peptide substrate. Inhibitor 36, for example, with a urea substituent including a cyclic imide showed balanced nanomolar inhibitory potencies against genotype 1a, both wild-type (K = 30 nM) and R155K (K = 2 nM), and genotype 3a (K = 5 nM).

Medical school predictors of later perceived mastery of clinical work among Norwegian doctors: a cohort study with 10-year and 20-year follow-up.

Objective: Doctors' self-perceived mastery of clinical work might have an impact on their career and patient care, in addition to their own health and well-being. The aim of this study is to identify predictors at medical school of perceived mastery later in doctors' careers.

Design: A cohort of medical students (n=631) was surveyed in the final year of medical school in 1993/1994 (T1), and 10 (T2) and 20 (T3) years later.

Discovery of pyrazinone based compounds that potently inhibit the drug-resistant enzyme variant R155K of the hepatitis C virus NS3 protease.

Herein, we present the design and synthesis of 2(1H)-pyrazinone based HCV NS3 protease inhibitors with variations in the C-terminus. Biochemical evaluation was performed using genotype 1a, both the wild-type and the drug resistant enzyme variant, R155K. Surprisingly, compounds without an acidic sulfonamide retained good inhibition, challenging our previous molecular docking model.

Achiral pyrazinone-based inhibitors of the hepatitis C virus NS3 protease and drug-resistant variants with elongated substituents directed toward the S2 pocket.

Herein we describe the design, synthesis, inhibitory potency, and pharmacokinetic properties of a novel class of achiral peptidomimetic HCV NS3 protease inhibitors. The compounds are based on a dipeptidomimetic pyrazinone glycine P3P2 building block in combination with an aromatic acyl sulfonamide in the P1P1' position. Structure-activity relationship data and molecular modeling support occupancy of the S2 pocket from elongated R(6) substituents on the 2(1H)-pyrazinone core and several inhibitors with improved inhibitory potency down to Ki = 0.

Synthesis and SAR of potent inhibitors of the Hepatitis C virus NS3/4A protease: exploration of P2 quinazoline substituents.

Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series exhibiting macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8-methyl substitution in the P2 cyclopentane dicarboxylic acid series improved on the metabolic stability in human liver microsomes.

Design and synthesis of potent inhibitors of the malaria aspartyl proteases plasmepsin I and II. Use of solid-phase synthesis to explore novel statine motifs.

Picomolar to low nanomolar inhibitors of the two aspartic proteases plasmepsin (Plm) I and II, from the malaria parasite Plasmodium falciparum, have been identified from sets of libraries containing novel statine-like templates modified at the amino and carboxy terminus. The syntheses of the novel statine templates were carried out in solution phase using efficient synthetic routes and resulting in excellent stereochemical control. The most promising statine template was attached to solid support and diversified by use of parallel synthesis.