The NADPH Oxidase Inhibitor, Mitoapocynin, Mitigates DFP-Induced Reactive Astrogliosis in a Rat Model of Organophosphate Neurotoxicity.

NADPH oxidase (NOX) is a primary mediator of superoxides, which promote oxidative stress, neurodegeneration, and neuroinflammation after diisopropylfluorophosphate (DFP) intoxication. Although orally administered mitoapocynin (MPO, 10 mg/kg), a mitochondrial-targeted NOX inhibitor, reduced oxidative stress and proinflammatory cytokines in the periphery, its efficacy in the brain regions of DFP-exposed rats was limited. In this study, we encapsulated MPO in polyanhydride nanoparticles (NPs) based on 1,6-bis(p-carboxyphenoxy) hexane (CPH) and sebacic anhydride (SA) for enhanced drug delivery to the brain and compared with a high oral dose of MPO (30 mg/kg).

Ultraviolet Radiation-Induced Mitochondrial Disturbances Are Attenuated by Metabolites of Melatonin in Human Epidermal Keratinocytes.

Melatonin (-acetyl-5-methoxytryptamine) is recognized as an effective antioxidant produced by the pineal gland, brain and peripheral organs, which also has anti-inflammatory, immunomodulatory, and anti-tumour capacities. Melatonin has been reported as a substance that counteracts ultraviolet radiation B (UVB)-induced intracellular disturbances. Nevertheless, the mechanistic actions of related molecules including its kynurenic derivatives (-acetyl--formyl-5-methoxykynurenine (AFMK)), its indolic derivatives (6-hydroxymelatonin (6(OH)MEL) and 5-methoxytryptamine (5-MT)) and its precursor -acetylserotonin (NAS) are only poorly understood.

Peripheral and central effects of NADPH oxidase inhibitor, mitoapocynin, in a rat model of diisopropylfluorophosphate (DFP) toxicity.

Organophosphates (OP) are highly toxic chemical nerve agents that have been used in chemical warfare. Currently, there are no effective medical countermeasures (MCMs) that mitigate the chronic effects of OP exposure. Oxidative stress is a key mechanism underlying OP-induced cell death and inflammation in the peripheral and central nervous systems and is not mitigated by the available MCMs.

Antibody responses elicited by mRNA vaccination in firefighters persist six months and correlate inversely with age and directly with BMI.

Knowledge regarding the sustainability of immune responses after COVID-19 vaccination is important, e.g., to decide whom and when to booster.

Midazolam impacts acetyl-And butyrylcholinesterase genes: An epigenetic explanation for postoperative delirium?

Midazolam is a widely used short-acting benzodiazepine. However, midazolam is also criticized for its deliriogenic potential. Since delirium is associated with a malfunction of the neurotransmitter acetylcholine, midazolam appears to interfere with its proper metabolism, which can be triggered by epigenetic modifications.

Acquired aplastic anemia following SARS-CoV-2 vaccination.

COVID-19 is a potential life-threatening viral disease caused by SARS-CoV-2 and was declared a pandemic by the WHO in March 2020. mRNA-based SARS-CoV-2 vaccines are routinely recommended in immune-compromised patients, including patients with AA, as these patients are at increased risk of contracting COVID-19 and developing a more severe course of disease. Between March 2021 and November 2021 relapse of AA occurred in four (age [median]: 53 years, range 30-84 years) out of 135 patients currently registered at our department and two de novo cases of AA in temporal context to vaccination against SARS-CoV-2, were documented.

The Course of Anti-HBc Antibodies over Time in Immunocompromised Hosts.

Hepatitis B virus infection results in the appearance of anti-HBc antibodies that normally persist lifelong. We analyzed the course of anti-HBc antibodies overtime, focusing on patients with a permanent loss or fluctuating anti-HBc antibodies. From 120,531 patients tested for anti-HBc antibodies (Architect, Abbott) from January 2006 to December 2020, ≥4 serial values were available in 8098 and permanent or intermittent anti-HBc loss was observed in 139 patients.

The impact of COVID-19 on alternative and local food systems and the potential for the sustainability transition: Insights from 13 countries.

The COVID-19 pandemic has been a major stress test for the agri-food system. While most research has analysed the impact of the pandemic on mainstream food systems, this article examines how alternative and local food systems (ALFS) in 13 countries responded in the first months of the crisis. Using primary and secondary data and combining the Multi-Level Perspective with social innovation approaches, we highlight the innovations and adaptations that emerged in ALFS, and how these changes have created or supported the sustainability transition in production and consumption systems.

Performance of the LIAISON SARS-CoV-2 Antigen Assay vs. SARS-CoV-2-RT-PCR.

We aimed to evaluate the LIAISON SARS-CoV-2 antigen assay (DiaSorin), comparing its performance to real-time polymerase chain reaction (RT-PCR) for the detection of SARS-CoV-2 RNA. 182 (110 PCR-positive and 72 PCR-negative) nasopharyngeal swab samples were taken for the detection of SARS-CoV-2. RT-PCR and antigen assay were performed using the same material.

Fast Detection of SARS-CoV-2 RNA Directly from Respiratory Samples Using a Loop-Mediated Isothermal Amplification (LAMP) Test.

The availability of simple SARS-CoV-2 detection methods is crucial to contain the COVID-19 pandemic. This study examined whether a commercial LAMP assay can reliably detect SARS-CoV-2 genomes directly in respiratory samples without having to extract nucleic acids (NA) beforehand. Nasopharyngeal swabs (NPS, = 220) were tested by real-time reverse transcription (RT)-PCR and with the LAMP assay.

LPS-Induced Endotoxemia Evokes Epigenetic Alterations in Mitochondrial DNA That Impacts Inflammatory Response.

Mitochondrial DNA (mtDNA) plays a vital role as a damage-associated molecular pattern in sepsis being able to shape the immune response. Since pathogen recognition receptors of innate immune cells are activated by demethylated DNA only, we set out to investigate the amount of DNA methyltransferase 1 (DNMT1) in mitochondria and the extent of mtDNA methylation in a human endotoxin model. Peripheral blood mononuclear cells of 20 healthy individuals were isolated from whole blood and stimulated with lipopolysaccharide (LPS) for 48 h.

A novel understanding of postoperative complications: In vitro study of the impact of propofol on epigenetic modifications in cholinergic genes.

Background: Propofol is a widely used anaesthetic drug with advantageous operating conditions and recovery profile. However, propofol could have long term effects on neuronal cells and is associated with post-operative delirium (POD). In this context, one of the contributing factors to the pathogenesis of POD is a reduction of cholinesterase activity.

Sequential high-dose alkylating therapy and stem cell support for high-risk stage III breast cancer.

Patients who receive neoadjuvant chemotherapy for locally advanced breast cancer and have four or more ipsilateral axillary lymph nodes involved at surgery are at high risk for recurrence, with a median time to relapse of 18 months. We offered such patients high-dose chemotherapy with stem cell rescue. Patients received cyclophosphamide or paclitaxel and granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells.

Effects of multi-sensory stimulation for people with dementia.

Background: Over recent years multi-sensory stimulation (MSS) has become an increasingly popular approach to care and is used in several centres throughout Europe. This popularity could be explained by the limited alternatives available to staff and a widely held belief that MSS is a friendly and highly humane approach. A randomized controlled trial was therefore essential to evaluate the effectiveness and extent of the benefits of MSS.

Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia.

Patients with anorexia nervosa (AN) often show normal to elevated physical activity levels despite severe weight loss and emaciation. This is seemingly in contrast to the loss of energy and fatigue characteristic of other starvation states associated with weight loss. Despite the fact that historical accounts and clinical case studies of AN have regularly commented on the elevated activity levels, the behavior has become only recently the subject of systematic study.

Effects of the implementation of the Resident Assessment Instrument on gaps between perceived needs and nursing care supply for nursing home residents in the Netherlands.

This study evaluated the effects of the implementation of the Resident Assessment Instrument (RAI) on gaps perceived between residents' needs and nursing care received in Dutch nursing homes. In a controlled group design residents were interviewed before and after the implementation. Most gaps were perceived in the psycho-social area rather than physical or needs with aids and facilities.

Improvements in the quality of co-ordination of nursing care following implementation of the Resident Assessment Instrument in Dutch nursing homes.

Aim: To study the effect of implementation of the Resident Assessment Instrument (RAI) on the quality of co-ordination of nursing care in Dutch nursing homes.

Background: The Resident Assessment Instrument (RAI) was designed to improve the quality of care and quality of life in nursing homes. Until now, only noncontrolled studies on the effects of implementation of the RAI have been carried out.

The relation between quality of co-ordination of nursing care and quality of life in Dutch nursing homes.

Quality of life of nursing home residents is a critical consideration in international health care policies and health care decisions. Yet, there is little relevant research to support decisions about client-tailored and effective nursing care for this population. Because of the permanency of their stay, the care received affects the quality of daily life.

[The effect of sensory stimulation in the sensory stimulation room on the well-being of demented elderly. A cross-over trial in residents of the R.C. Care Center Bernardus in Amsterdam].

A controlled cross-over experiment was carried out to investigate the effect of snoezelen in the snoezelenroom on the well-being of elderly people with dementia. Seventeen elderly residents from the Bernardus Nursing Home in Amsterdam participated. All were in a very advanced stage of dementia requiring a high level of care and nursing.

[Effect of snoezelen on the behaviour of demented elderly].

A randomised cross-over trial was carried out at nursing home Bernardus in Amsterdam to investigate the effect of 'snoezelen' in a specially furnished room on the well-being of demented elderly people. The behaviour during the experimental intervention 'snoezelen' was compared with the behaviour during the control intervention, consisting of standard activities in the livingroom. Sixteen elderly persons participated in the study.

Invasive pneumococcal infections in children infected with HIV are not associated with splenic dysfunction.

Objectives: Children infected with HIV-1 are more likely to acquire infections associated with the encapsulated bacterial pathogens of childhood than their non-HIV-infected peers. The goal of the current study was to determine what proportion of community-acquired, invasive pneumococcal disease in HIV-infected children could be attributed to splenic dysfunction, as measured by enumerating the number of pocked red blood cells (RBCs) in peripheral blood.

Methods: Splenic reticuloendothelial function was assessed semiquantitatively by examining the morphology of the RBCs of 84 children born to HIV-infected mothers using phase interference microscopy.

Characterization of autoantibodies against the platelet glycoprotein antigens IIb/IIIa in childhood idiopathic thrombocytopenia purpura.

The majority of children with idiopathic thrombocytopenia (ITP) have an acute self-limiting course and no diagnostic test has been identified which will predict the course of thrombocytopenia and detect those with the chronic autoimmune form. The detection of autoantibodies directed against the platelet glycoprotein complex IIB/IIIa, may identify patients with chronic ITP. Serum anti-GP IIb/IIIa antibodies were assessed by the indirect MAIPA assay in 54 children with immune thrompocytopenia at initial presentation along with an additional 7 children previously diagnosed with chronic ITP, to determine if there was a difference in antibody positivity between acute and chronic ITP patients, and whether the identification of antibodies could be used as a predictive test at diagnosis.

Reduced serum haptoglobin values in hemophiliacs receiving monoclonally purified factor VIII concentrates.

Hemophiliacs often have mild anemia, and hemolysis has been suggested as the likely mechanism on the basis of the reduced serum haptoglobin values frequently observed in these patients. It has been suggested that hypohaptoglobinemia results from isohemagglutinins or other contaminating proteins in the infused factor concentrates. The advent and increased utilization of Factor VIII concentrates that are highly purified by use of monoclonal antibodies have provided the opportunity to study whether proteins other than Factor VIII contained in the concentrate induce hemolysis.

The bleeding time may be longer in children than in adults.

The bleeding time, the most frequently performed test reflecting in vivo platelet function, is the duration of blood flow from a standardized incision on the volar surface of the forearm. Normal values have been determined in adult subjects, but with the exception of neonates, data on the range of bleeding time values in pediatric patients are unavailable. Standard hematology textbooks imply that bleeding time values in children are similar to those of adults.