Repeated exposure to chlorpyrifos is associated with a dose-dependent chronic neurobehavioral deficit in adult rats

Organophosphate (OP) chemicals include commonly used pesticides and chemical warfare agents, and mechanistically they are potent inhibitors of the cholinesterase (ChE) enzyme. Epidemiological studies report long-term neuropsychiatric issues, including depression and cognitive impairments in OP-exposed individuals. Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. Multiple laboratory studies have reported on either the long-term behavioral effect of an acute high-dose CPF (30-250 mg/kg) or studied sub-chronic behavioral effects, particularly the motor and cognitive effects of repeated low-dose CPF. However, studies are lacking on chronic mood and depression-related morbidities following repeated CPF doses that would mimic occupationally relevant OP exposures. In this study, adult male rats were injected with CPF (1, 3, 5, or 10 mg/kg/d, s.c.) for 21 consecutive days. Dependent on the CPF dose, ChE activity was inhibited approximately 60-80% in the blood and about 20-50% in the hippocampus at 2-days after the end of CPF exposures. Following a 12-week washout period, a complete recovery of ChE activity was noted. However, CPF-treated rats exhibited a dose-dependent increase in signs related to anhedonia (sucrose preference test), anxiety (open-field and elevated plus-maze), and despair (forced swim test) at this stage. To the best of our knowledge, this could be the first laboratory study that demonstrates a cause-effect relationship between occupational-like CPF exposures in adult rats and the development of long-term depression-related outcomes and could provide an experimental system to study molecular mechanisms underlying environmental OP exposures and the elevated risk for chronic behavioral deficits

Study protocol of a mixed method pragmatic quasi-experimental trial to evaluate the day activity services targeted at older home care clients in Finland

Background: In Finland, the ‘day activity service’ is targeted at older home care clients who are unable to participate in other available activities due to poor health or functional disabilities. The aim of the day activity service is to support home care client’s ability to live at home and to enhance their wellbeing and social inclusion. This mixed method study examines the effectiveness, cost-effectiveness and process of the day activity service. Methods: The target sample size is 200 participants. The intervention group (n = 100) is composed of home care clients who begin to participate in the day activity service. The comparison group (n = 100) are home care clients who do not participate in the day activity service, and whose functioning and care needs are similar to the participants of the intervention group. The primary outcome is social inclusion (ESIS-scale). Secondary outcomes are loneliness (single item and De Jong Gierveld Loneliness Scale) and social care related quality of life (ASCOT). Baseline, three-month and six-month follow-up surveys are gathered from intervention and comparison group participants in order to compare outcomes between groups pre- and post-intervention. Costs of health and social services, based on administrative data, and the costs of the intervention are utilized in examining the cost-effectiveness of the intervention with the above-described measurements. Qualitative data are collected by interviewing the intervention participants (n = 10) and professionals working at the day activity centres and older people’s services (4 focus groups) to explore the perceived outcomes and process of the intervention to find out how and why the intervention is effective or ineffective. Discussion: The study seeks to produce a comprehensive understanding of the effectiveness, cost-effectiveness and implementation process of the day activity service. Trial registration: ISRCTN13146087, Registration date 03/04/2022

Depletion of the chromatin remodeler CHD4 sensitizes AML blasts to genotoxic agents and reduces tumor formation

Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATPase that alters the phasing of nucleosomes on DNA and has recently been implicated in DNA double-stranded break (DSB) repair. Here, we show that depletion of CHD4 in acute myeloid leukemia (AML) blasts induces a global relaxation of chromatin that renders cells more susceptible to DSB formation, while concurrently impeding their repair. Furthermore, CHD4 depletion renders AML blasts more sensitive both in vitro and in vivo to genotoxic agents used in clinical therapy: daunorubicin (DNR) and cytarabine (ara-C). Sensitization to DNR and ara-C is mediated in part by activation of the ataxia-telangiectasia mutated pathway, which is preliminarily activated by a Tip60-dependent mechanism in response to chromatin relaxation and further activated by genotoxic agent–induced DSBs. This sensitization preferentially affects AML cells, as CHD4 depletion in normal CD34+ hematopoietic progenitors does not increase their susceptibility to DNR or ara-C. Unexpectedly, we found that CHD4 is necessary for maintaining the tumor-forming behavior of AML cells, as CHD4 depletion severely restricted the ability of AML cells to form xenografts in mice and colonies in soft agar. Taken together, these results provide evidence for CHD4 as a novel therapeutic target whose inhibition has the potential to enhance the effectiveness of genotoxic agents used in AML therapy

Theranostics in Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: B-10 and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of B-10 in the tumor but also on the organs at risk. It is not yet possible to determine the B-10 concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the B-10 concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake of B-10 from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine the B-10 concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach

Theranostics in Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually: 10B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount of 10B in the tumor but also on the organs at risk. It is not yet possible to determine the 10B concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure the 10B concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake of 10B from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine the 10B concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach

Theranostics in Boron neutron capture therapy

Boron neutron capture therapy (BNCT) has the potential to specifically destroy tumor cells without damaging the tissues infiltrated by the tumor. BNCT is a binary treatment method based on the combination of two agents that have no effect when applied individually:B and thermal neutrons. Exclusively, the combination of both produces an effect, whose extent depends on the amount ofB in the tumor but also on the organs at risk. It is not yet possible to determine theB concentration in a specific tissue using non-invasive methods. At present, it is only possible to measure theB concentration in blood and to estimate the boron concentration in tissues based on the assumption that there is a fixed uptake ofB from the blood into tissues. On this imprecise assumption, BNCT can hardly be developed further. A therapeutic approach, combining the boron carrier for therapeutic purposes with an imaging tool, might allow us to determine theB concentration in a specific tissue using a non-invasive method. This review provides an overview of the current clinical protocols and preclinical experiments and results on how innovative drug development for boron delivery systems can also incorporate concurrent imaging. The last section focuses on the importance of proteomics for further optimization of BNCT, a highly precise and personalized therapeutic approach.E.H.-H. and M.K. gratefully acknowledge support from the DFG (HE 1376/38-1); L.S. received funding from GEFLUC Grenoble Dauphiné Savoie

Survey data of public awareness on climate change and the value of marine and coastal ecosystems

The long-term provision of ocean ecosystem services depends on healthy ecosystems and effective sustainable management. Understanding public opinion about marine and coastal ecosystems is important to guide decision-making and inform specific actions. However, available data on public perceptions on the interlinked effects of climate change, human impacts and the value and management of marine and coastal ecosystems are rare. This dataset presents raw data from an online, self-administered, public awareness survey conducted between November 2021 and February 2022 which yielded 709 responses from 42 countries. The survey was released in four languages (English, French, Spanish and Italian) and consisted of four main parts: (1) perceptions about climate change; (2) perceptions about the value of, and threats to, coasts, oceans and their wildlife, (3) perceptions about climate change response; and (4) socio-demographic information. Participation in the survey was voluntary and all respondents provided informed consent after reading a participant information form at the beginning of the survey. Responses were anonymous unless respondents chose to provide contact information. All identifying information has been removed from the dataset. The dataset can be used to conduct quantitative analyses, especially in the area of public perceptions of the interlinkages between climate change, human impacts and options for sustainable management in the context of marine and coastal ecosystems. The dataset is provided with this article, including a copy of the survey and participant information forms in all four languages, data and the corresponding codebook.This study received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement MaCoBioS (No 869710). The funders had no role in any part of the research process.info:eu-repo/semantics/publishedVersio

Infraspinatus scapular retraction test: a reliable and practical method to assess infraspinatus strength in overhead athletes with scapular dyskinesis

Background Alteration of normal scapulohumeral rhythm due to the fatigue of scapular-stabilizing muscles induces decrease of rotator cuff strength. In this study we analyzed the interobserver and intraobserver realibility of the infraspinatus strength test (IST) and infraspinatus scapular retraction test (ISRT) in 29 overhead athletes with scapular dykinesis, before and after 6 months of scapular musculature rehabilitation. Materials and methods Subjects with magnetic resonance imaging (MRI) findings of labral injuries (2 cases, 5%) and cuff tears (4 cases, 11%) were excluded. Scapular dyskinesis patterns were evaluated according to Kibler et al. (J Shoulder Elbow Surg 11:550-556, 2002). We found a type I dyskinesis in 24 cases (83%) and a type II in 5 cases (17%). Patients were tested by using IST and ISRT and the maximum infraspinatus strength (kg) was registered by a handheld dynamometer. Changes in shoulder IR were measured by using a standard goniometry. Rehabilitation continued for 6 months and was focused on the restoration of scapular muscular control and balance. We used a paired Student t test for the significance of the force values (alpha = 0.01). Intraclass correlation coefficient (ICC) and standard error (SE) were applied to determine the realibility of repeated values collected within testers and between testers. Results Values of ICC close to 1 at baseline and at 6 months indicated a higher interexaminer and intraexaminer realibility. IST force values registered a significant increase at 6 months for both examiners (P<0.01). The mean difference between IST and ISRT values were not significant at 6 months (P>0.01). The increase of glenohumeral internal rotation was significant at 6 months (P<0.01). Conclusion The good realibility and the easy reproducibility make the ISRT an excellent test to assess patients with infraspinatus weakness due to scapular dyskinesis and address them toward an appropriate program of rehabilitation aimed to restore scapular musculature balance and control. \ua9 The Author(s) 2010

Embracing Nature-based Solutions to promote resilient marine and coastal ecosystems

The world is struggling to limit greenhouse gas emissions and reduce the human footprint on nature. We therefore urgently need to think about how to achieve more with actions to address mounting challenges for human health and wellbeing from biodiversity loss, climate change effects, and unsustainable economic and social development. Nature-based Solutions (NBS) have emerged as a systemic approach and an important component of the response to these challenges. In marine and coastal spaces, NBS can contribute to improved environmental health, climate change mitigation and adaptation, and a more sustainable blue economy, if implemented to a high standard. However, NBS have been largely studied for terrestrial – particularly urban – systems, with limited uptake thus far in marine and coastal areas, despite an abundance of opportunities. Here, we provide explanations for this lag and propose the following three research priorities to advance marine and coastal NBS: (1) Improve understanding of marine and coastal biodiversity-ecosystem services relationships to support NBS better designed for rebuilding system resilience and achieving desired ecological outcomes under climate change; (2) Provide scientific guidance on how and where to implement marine and coastal NBS and better coordinate strategies and projects to facilitate their design, effectiveness, and value through innovative synergistic actions; (3) Develop ways to enhance marine and coastal NBS communication, collaboration, ocean literacy and stewardship to raise awareness, co-create solutions with stakeholders, boost public and policy buy-in, and potentially drive a more sustained investment. Research effort in these three areas will help practitioners, policy-makers and society embrace NBS for managing marine and coastal ecosystems for tangible benefits to people and marine life.The study received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement MaCoBioS (contract no 869710), FutureMARES (contract no 869300) and REST-COAST (contract no 101037097).info:eu-repo/semantics/publishedVersio