Iron-sulfur cluster loss in mitochondrial CISD1 mediates PINK1 loss-of-function phenotypes.

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain. Familial cases of PD are often caused by mutations of PTEN-induced kinase 1 (PINK1) and the ubiquitin ligase Parkin, both pivotal in maintaining mitochondrial quality control. CISD1, a homodimeric mitochondrial iron-sulfur-binding protein, is a major target of Parkin-mediated ubiquitination.

Metabolic activation of WHO-congeners PCB28, 52, and 101 by human CYP2A6: evidence from in vitro and in vivo experiments.

Despite extensive research on the metabolism of polychlorinated biphenyls (PCBs), knowledge gaps persist regarding their isoform-specific biotransformation pathways. This study aimed to elucidate the role of different cytochrome P450 enzymes in PCB metabolism, focusing on WHO-congeners 2,4,4'-trichlorobiphenyl (PCB28), 2,2',5,5'-tetrachlorobiphenyl (PCB52), and 2,2',4,5,5'-pentachlorobiphenyl (PCB101). Utilizing engineered HEK293 cell lines, we investigated the in vitro metabolism of these PCBs by CYP1A2, CYP2C8, CYP2C9, CYP3A4, CYP2A6, and CYP2E1, revealing robust production of hydroxylated metabolites.

Clinical and radiological outcome following trauma-related reverse shoulder arthroplasty.

Background: Reverse shoulder arthroplasty (RSA) is a frequently used therapy for complex proximal humeral fractures and posttraumatic disorders. The present study's purpose was to assess the clinical and radiological outcome of primary and secondary RSA, and to analyze the impact of refixation of the greater tuberosity (GT).

Patients And Methods: 28 patients with primary fracture RSA and 18 patients with RSA due to posttraumatic disorders were examined with a mean clinical follow-up of 2.

Classification and Incidence of Heterotopic Ossifications in Relation to NSAID Prophylaxis after Elbow Trauma.

Heterotopic ossification (HO) after elbow trauma can be responsible for significant motion restrictions. The study's primary aim was to develop a new X-ray-based classification for HO of the elbow. This retrospective study analyzed elbow injury radiographs from 138 patients aged 6-85 years (mean 45.

Nutrimetric Validation of Solanidine as Dietary-Derived CYP2D6 Activity Marker In Vivo.

CYP2D6 is involved in the metabolism of many drugs. Its activity is affected by pharmacogenetic variability leading to highly polymorphic phenotypes between individuals, affecting safety and efficacy of drugs. Recently, solanidine, a steroidal alkaloid from potatoes, and its metabolites, has been identified as a dietary-derived activity marker for CYP2D6.

Clinical Outcome of Carbon Fiber Reinforced Polyetheretherketone Plates in Patients with Proximal Humeral Fracture: One-Year Follow-Up.

Background: Proximal humerus fractures are seen frequently, particularly in older patients. The development of new osteosynthesis materials is being driven by the high complication rates following surgical treatment of proximal humerus fractures. Plate osteosyntheses made of steel, titanium and, for several years now, carbon fiber-reinforced polyetheretherketone (CFR-PEEK) are used most frequently.

Ten years after: findings from the medical surveillance program on Health Effects in High-Level Exposure to PCB (HELPcB).

After the detection of high environmental and occupational exposure to polychlorinated biphenyls (PCBs) in a German recycling company for transformers and capacitors in 2010, the multidisciplinary medical surveillance program "HELPcB" (Health Effects in High-Level Exposure to PCB) was established for former PCB-exposed workers of the company, their family members, employees of surrounding companies, and area residents to investigate potential adverse health effects by PCB exposure in a longitudinal study approach with up to seven examination time points between 2010 and 2019. More than 300 individuals were enrolled into the program. Assessments particularly included plasma and urine concentrations of PCB congeners and their metabolites, clinical laboratory parameters, Comet assay, analysis of telomere length, neuropsychological examinations, psychological screening, abdominal and thyroid ultrasound examination.

Ankle fractures of the geriatric patient: a narrative review.

The present narrative review provides a summary of current concepts for the treatment of ankle fractures in elderly patients. Despite a high complication rate, open reduction and internal fixation is the gold standard for operative care. However, individual patient-based treatment decision considering the soft-tissue status, the fracture pattern, as well as the patient's mobility and comorbidities is mandatory to achieve sufficient patient outcomes.

Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling.

Introduction: SARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants.

Methods: We combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8 T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19.

Environmental release of non-Aroclor polychlorinated biphenyls by a silicone rubber production site did not lead to elevated plasma levels in the nearby population.

In 2019, high concentrations of the non-Aroclor PCB congeners 47, 51, and 68 were released by a silicone rubber production site in North-Rhine Westphalia, Germany. Local authorities announced a consumption alert for home-grown fruits and vegetables for the affected area which led to a great level of insecurity among the population regarding potential health effects. The aim of study was to determine the plasma levels of the non-Aroclor congeners and the six ndl-indicator congeners (PCB 28, 52, 101, 138, 153, 180) in children and women with child-bearing potential living close to the production site.

Welding Fume Instillation in Isolated Perfused Mouse Lungs-Effects of Zinc- and Copper-Containing Welding Fumes.

Zinc- and copper-containing welding fumes can cause systemic inflammation after exposure in humans. Recent ex vivo studies have shown that the observed inflammation originates from exposed immune cells. In vitro studies identified the soluble fraction of metal particles as the main effectors.

Decomposition Products of the Initiator Bis(2,4-dichlorobenzoyl)peroxide in the Silicone Industry: Human Biomonitoring in Plasma and Urine of Workers.

Bis(2,4-dichlorobenzoyl)peroxide (2,4-DCBP) is used as an initiator for silicone rubber production. During hot curing, 2,4-DCBP decomposes into 2,4-dichlorobenzoic acid, 1,3-dichlorobenzene, and the polychlorinated biphenyl (PCB) congeners PCB-47, PCB-51, and PCB-68. The extent of occupational exposure to these decomposition products has not been investigated yet.

Posterior shoulder dislocation with associated reverse Hill-Sachs lesion: clinical outcome 10 years after joint-preserving surgery.

Introduction: Posterior shoulder dislocation in association with reverse Hill-Sachs lesion is a rather rare injury. Few studies reporting results after joint-preserving surgery in these cases are available. This current study presents the clinical outcomes 10 years postoperatively.

Negative ion formation and fragmentation upon dissociative electron attachment to the nicotinamide molecule.

Nicotinamide (CHNO) is a biologically relevant molecule. This compound has several important roles related to the anabolic and metabolic processes that take place in living organisms. It is also used as a radiosensitizer in tumor therapy.

Minced Cartilage in Combination with Autologous Bone Grafting for One-Step Osteochondral Defect Reconstruction in an Athlete's Knee.

A 17-year-old student athlete suffering from stress-related knee pain asked for help. MRI revealed an unstable osteochondral lesion. Because of time pressure due to the patient's academic exams and his schedule as a basketball player, an autologous chondrocyte transplantation (ACT) as the standard surgical treatment plan was not accepted by the patient.

CK1BP Reduces α-Synuclein Oligomerization and Aggregation Independent of Serine 129 Phosphorylation.

The pathological accumulation of α-Synuclein (α-Syn) is the hallmark of neurodegenerative α-synucleinopathies, including Parkinsons's disease (PD). In contrast to the mostly non-phosphorylated soluble α-Syn, aggregated α-Syn is usually phosphorylated at serine 129 (S129). Therefore, S129-phosphorylation is suspected to interfere with α-Syn aggregation.

Plasma levels of unintentionally produced non-Aroclor polychlorinated biphenyl (PCB) congeners in workers from the silicone rubber industry.

The unintentional release of non-Aroclor-PCBs 47, PCB 68 and PCB 51 by a silicone manufacturing company in North Rhine-Westphalia, Germany, due to the use of bis-(2,4-dichlorobenzoyl)peroxide (2,4-DCBP) as an initiator has raised serious concerns about the possible uptake of these congeners by workers in silicone rubber production. We have conducted a pilot study in Germany to quantify these congeners in plasma samples of employees working in and handling silicone rubber during production and electrical cable manufacturing. A total of 117 plasma samples were collected from workers in 7 companies and 84 plasma samples from control subjects not working in silicone industry.

Modelling past human internal exposure to lower chlorinated indicator PCBs using proxies - A calculation based on multiple longitudinal PCB analyses.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants with former applications in electric transformers, capacitors, hydraulic fluids or joint sealants. While current internal exposure to PCBs can be readily assessed by human biomonitoring, the evaluation of longgone past exposures, in particular the estimation of past exposure to lower chlorinated non-dioxin-like PCB 28, 52 or 101 is limited due to the relatively short biological half-life of these PCB-congeners. This study was aimed to find a proxy that would allow an estimation of the former plasma level for these congeners even several years after exposure cessation.

Radiographic parameter(s) influencing functional outcomes following angular stable plate fixation of proximal humeral fractures.

Purpose: Radiographic parameters which correlate with poor clinical outcome after proximal humeral fractures could be helpful indicators to answer the question which patients should be followed up closer. Moreover, during surgery, radiographic parameters correlating with unfavourable outcome should be avoided. The primary aim of the study was to compare radiographic measurements between the injured and the contralateral, uninjured shoulder.

Longitudinal changes in telomere length in PCB-exposed individuals: interaction with CMV infection.

We recently demonstrated a significant shortening of age-adapted telomere length (TL) in lymphocytes of polychlorinated biphenyls (PCB)-exposed individuals. Here, we analyzed TL in individuals of the same PCB-exposed cohort during a 6-year follow-up period, investigating the change in TL between the first and second measurement as a function of time, concentration of PCBs and cytomegalovirus (CMV) infection. The age-adjusted TL of lymphocytes within the cohort of PCB-exposed individuals recovered from a first assessment in 2011 to a second assessment in 2017.

Estimating plasma half-lives of dioxin like and non-dioxin like polychlorinated biphenyls after occupational exposure in the German HELPcB cohort.

Polychlorinated biphenyls (PCBs) are carcinogenic persistent organic pollutants that have been used as mixtures in transformers, electrical capacitors or hydraulic oils in underground mining until their ban in the late 1980s in Germany. The widespread use of PCBs has led to an age-dependent body burden in the general population. In order to determine the human half-lives of different PCB-congeners, we have used data collected between 2010 and 2017 from the prospective investigation of the German HELPcB-cohort with high initial occupational exposure to PCBs from a transformer recycling company.

Fractures of the Humeral Ulnar Condyle in Children - a Rare but Complicated Injury.

Background: Ulnar humeral condyle fractures are rare paediatric elbow fractures, classified as Salter-Harris IV paediatric elbow injuries. Due to constant radiological changes in the elbow with varying manifestation of ossification centres as well as late ossification of the trochlea, diagnosis of these injuries is challenging. To avoid long-term complications, the treating surgeon should be familiar with the rare injury picture, diagnostics and adequate therapeutic measures.

Comparability of Patient-reported Outcome Measures and Clinical Assessment Tools for Shoulder Function in Patients with Proximal Humeral Fracture.

Background: Patient-reported outcome measures (PROMs) are gaining increasing importance in the context of quality management. Different PROMs and scoring tools are available to assess shoulder function after proximal humeral fracture (PHFx). In Europe, these include the Constant-Murley Score (CS), Neer Score (NS), Oxford Shoulder Score (OSS), University of California at Los Angeles Score (UCLA) and Disabilities of the Arm, Shoulder and Hands Score (DASH).

Reactions in Tirapazamine Induced by the Attachment of Low-Energy Electrons: Dissociation Versus Roaming of OH.

Tirapazamine (TPZ) has been tested in clinical trials on radio-chemotherapy due to its potential highly selective toxicity towards hypoxic tumor cells. It was suggested that either the hydroxyl radical or benzotriazinyl radical may form as bioactive radical after the initial reduction of TPZ in solution. In the present work, we studied low-energy electron attachment to TPZ in the gas phase and investigated the decomposition of the formed TPZ anion by mass spectrometry.