Polychlorinated biphenyls (PCBs) are persistent organic pollutants that bioaccumulate in the body, however, they can be metabolized to more water-soluble products. Although they are more readily excreted than the parent compounds, some of the metabolites are still hydrophobic and may be more available to target tissues, such as the brain. They can also cross the placenta and reach a developing foetus. Much less is known about the toxicity of PCB metabolites than about the parent compounds. In the present study, we have investigated the effects of eight hydroxylated (OH) PCB congeners (2′-OH PCB 3, 4-OH PCB 14, 4-OH PCB 34, 4′-OH PCB 35, 4-OH PCB 36, 4′-OH PCB 36, 4-OH PCB 39, and 4′-OH PCB 68) on reactive oxygen species (ROS) formation and cell viability in rat cerebellar granule cells. We found that, similar to their parent compounds, OH-PCBs are potent ROS inducers with potency 4-OH PCB 14 < 4-OH PCB 36 < 4-OH PCB 34 < 4′-OH PCB 36 < 4′-OH PCB 68 < 4-OH PCB 39 < 4′-OH PCB 35. 4-OH PCB 36 was the most potent cell death inducer, and caused apoptotic or necrotic morphology depending on concentration. Inhibition of ERK1/2 kinase with U0126 reduced both cell death and ROS formation, suggesting that ERK1/2 activation is involved in OH-PCB toxicity. The results indicate that the hydroxylation of PCBs may not constitute a detoxification reaction. Since OH-PCBs like their parent compounds are retained in the body and may be more widely distributed to sensitive tissues, it is important that not only the levels of the parent compounds but also the levels of their metabolites are taken into account during risk assessment of PCBs and related compounds.

Background An aging population with a growing burden of chronic complex illnesses will seriously challenge the public health care system. Consequently, novel and efficacious treatment approaches are highly warranted. Based on our experiences with concentrated treatment formats for other health challenges, we developed a highly concentrated interdisciplinary group rehabilitation approach for chronic illnesses. Objective We aim to explore the acceptability of the intervention and describe potential changes in functional impairment at follow-up. Methods The cornerstones of the intervention are as follows: (1) prepare the patient for change prior to treatment, (2) focus on health promoting microchoices instead of symptoms, and (3) expect the patient to integrate the changes in everyday living with limited hands-on follow-up. The intervention will be delivered to patients with highly diverse primary symptoms, namely patients with low back pain, post–COVID-19 symptoms, anxiety and depression, and type 2 diabetes. Results Recruitment started between August 2020 and January 2021 (according to the illness category). For initial 3-month results, recruitment is expected to be completed by the end of 2021. Conclusions If successful, this study may have a substantial impact on the treatment of low back pain, post–COVID-19 symptoms, anxiety and depression, and type 2 diabetes, which together constitute a major socioeconomic cost. Further, the study may widen the evidence base for the use of the concentrated treatment format in a diverse group of medical conditions. International Registered Report Identifier (IRRID) DERR1-10.2196/32216

Background Pulmonary rehabilitation has been demonstrated to be a highly effective treatment for people with chronic obstructive pulmonary disease (COPD). However, its availability is scarce worldwide, and new and innovative rehabilitation models are highly warranted. Recently, the group behind the present study published a protocol describing a novel concentrated, interdisciplinary group rehabilitation program for patients with chronic illnesses. The current paper describes an extension of this protocol to patients with COPD. Objective The objective of this study is to explore the acceptability of concentrated, interdisciplinary group pulmonary rehabilitation for patients with COPD. The intervention is expected to improve functional status and be highly acceptable to patients. Methods This study will include 50 patients aged over 40 years who fulfill the diagnostic criteria for COPD: a forced expiratory volume at the first second (FEV1) <80% of expected and a FEV1/forced vital capacity ratio below the lower limit of normal according to the Global Lung Function Initiative. An interdisciplinary team consisting of physicians, physiotherapists, psychologists, pharmacists, clinical nutritionists, and nurses will deliver the treatment to groups of 6 to 10 patients over 3 to 4 consecutive days with a 12-month follow-up. The intervention is divided into three distinct phases: (1) pretreatment preparation for change, (2) concentrated rehabilitation, where the patient is coached to focus on making health-promoting microchoices, and (3) integration of the changes into everyday living, aided by digital follow-up and 2 on-site clinical examinations. Statistical significance will be set at α=.05. Results The recruitment period will last from April 2022 until June 2023. Conclusions If successful, this highly novel rehabilitation format might change the way we deliver care for patients with COPD, leading to substantial societal and socioeconomic gains. The study will expand knowledge on the concentrated treatment format as a rehabilitation model for people with COPD. Trial Registration ClinicalTrials.gov NCT05234281; https://clinicaltrials.gov/ct2/show/NCT05234281 International Registered Report Identifier (IRRID) PRR1-10.2196/40700

BACKGROUND Pulmonary rehabilitation is demonstrated to be a highly effective treatment for people with chronic obstructive pulmonary disease (COPD). However, the availability is scarce worldwide, and new and innovative rehabilitation models are highly warranted. Recently, the group behind this study published a protocol describing a novel concentrated and interdisciplinary group rehabilitation program for patients with chronic illnesses. The current paper describes an extension of this protocol to patients with COPD. OBJECTIVE The aim with this study is to explore the acceptability of concentrated interdisciplinary group rehabilitation for patients with COPD. The intervention is expected to improve functional status and to be highly acceptable to the patients. METHODS Fifty patients aged >40 years, fulfilling the diagnostic criteria of COPD: a forced expiratory volume at the first second (FEV1) < 80% of expected and a FEV1/forced vital capacity (FVC) below the lower limit of normal of the global lung function initiative (GLI), will be included. An interdisciplinary team consisting of physician and physiotherapists with speciality in pulmonary disorders, psychologist, pharmacist, clinical nutritionist, and nurse will deliver the treatment to groups of 6-10 patients during four consecutive days with 12 months follow-up. The intervention is divided into three distinct phases: 1) pre-treatment preparation for change, 2) concentrated rehabilitation where the patient is coached to focus on making health-promoting micro-choices, and 3) integration of the changes into everyday living aided by digital follow-up and two on-site clinical examinations. RESULTS The recruitment period will last from April 2022 until June 2023. CONCLUSIONS If successful, this highly novel rehabilitation-format might change the way we deliver care for patients with COPD with substantial societal and socio-economic gains. The study will expand the knowledge of the concentrated treatment format as a rehabilitation model for people with COPD. CLINICALTRIAL ClinicalTrials.gov Identifier: NCT05234281 https://www.clinicaltrials.gov/ct2/show/NCT05234281?term=concentrated+rehabilitation&cntry=NO&draw=2&rank=2 Western Norway Regional Committees for Medical and Health Research Ethics (REK 2020/101638)

BACKGROUND An aging population with a growing burden of chronic complex illnesses will seriously challenge the public health care system. Consequently, novel and efficacious treatment approaches are highly warranted. Based on our experiences with concentrated treatment formats for other health challenges, we developed a highly concentrated interdisciplinary group rehabilitation approach for chronic illnesses. OBJECTIVE We aim to explore the acceptability of the intervention and describe potential changes in functional impairment at follow-up. METHODS The cornerstones of the intervention are as follows: (1) prepare the patient for change prior to treatment, (2) focus on health promoting microchoices instead of symptoms, and (3) expect the patient to integrate the changes in everyday living with limited hands-on follow-up. The intervention will be delivered to patients with highly diverse primary symptoms, namely patients with low back pain, post–COVID-19 symptoms, anxiety and depression, and type 2 diabetes. RESULTS Recruitment started between August 2020 and January 2021 (according to the illness category). For initial 3-month results, recruitment is expected to be completed by the end of 2021. CONCLUSIONS If successful, this study may have a substantial impact on the treatment of low back pain, post–COVID-19 symptoms, anxiety and depression, and type 2 diabetes, which together constitute a major socioeconomic cost. Further, the study may widen the evidence base for the use of the concentrated treatment format in a diverse group of medical conditions. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/32216