Cone beam CT-based dose accumulation and analysis of delivered dose to the dominant intraprostatic lesion in primary radiotherapy of prostate cancer.

Background: Evaluation of delivered dose to the dominant intraprostatic lesion (DIL) for moderately hypofractionated radiotherapy of prostate cancer by cone beam computed tomography (CBCT)-based dose accumulation and target coverage analysis.

Methods: Twenty-three patients with localized prostate cancer treated with moderately hypofractionated prostate radiotherapy with simultaneous integrated boost (SIB) between December 2016 and February 2020 were retrospectively analyzed. Included patients were required to have an identifiable DIL on bi-parametric planning magnetic resonance imaging (MRI).

The role of Interleukin-18 in recurrent early pregnancy loss.

Background: A successful pregnancy is a unique and complex immunological state. Cytokines seem to be crucial for the implementation of a tolerogenic environment at the feto-maternal interphase towards the semi-allogenic fetus. Importantly, the switch from a Th1- to a Th2 cytokine profile might play a key role.

Weaker protection against tuberculosis in BCG-vaccinated male 129 S2 mice compared to females.

BCG - the only available vaccine against tuberculosis (TB) - was first given to babies 100 years ago in 1921. While it is effective against TB meningitis and disseminated TB, its efficacy against pulmonary TB is variable, notably in adults and adolescents. TB remains one of the world's leading health problems, with a higher prevalence among men.

REDuction of Antibiotic RESistance (REDARES) in urinary tract infections using treatments according to national clinical guidelines: study protocol for a pragmatic randomized controlled trial with a multimodal intervention in primary care.

Background: Urinary tract infections (UTIs) are a common cause of prescribing antibiotics in family medicine. In Germany, about 40% of UTI-related prescriptions are second-line antibiotics, which contributes to emerging resistance rates. To achieve a change in the prescribing behaviour among family physicians (FPs), this trial aims to implement the guideline recommendations in German family medicine.

Quantitative evidence of suppressed TMEM119 microglial immunohistochemistry in fatal morphine intoxications.

The aim of this pilot study was to investigate the diagnostic potential of TMEM119 as a useful microglia-specific marker in combination with immunostainings for phagocytic function and infiltrating capacity of monocytes in cases of lethal monosubstance intoxications by morphine (MOR), methamphetamine (METH), and of ethanol-associated death (ETH) respectively. Human brain tissue samples were obtained from forensic autopsies of cases with single substance abuse (MOR, n = 8; ETH, n = 10; METH, n = 9) and then compared to a cohort of cardiovascular fatalities as controls (n = 9). Brain tissue samples of cortex, white matter, and hippocampus were collected and stained immunohistochemically with antibodies against TMEM119, CD68KiM1P, and CCR2.

High-sensitivity FEES with the professional image enhancement technology "PIET".

Purpose: Flexible endoscopic evaluation of swallowing (FEES) is a standard diagnostic tool in dysphagia. The combination of FEES and narrow band light (narrow band imaging; NBI) provides a more precise and detailed investigation method. So far, this technique could only be performed with the NBI illumination.

Evaluation of Screening Tests in Bavarian Healthcare Facilities during the Second Wave of the SARS-CoV-2 Pandemic.

Due to the lack of data on asymptomatic SARS-CoV-2-positive persons in healthcare institutions, they represent an inestimable risk. Therefore, the aim of the current study was to evaluate the first 1,000,000 reported screening tests of asymptomatic staff, patients, residents, and visitors in hospitals and long-term care (LTC) facilities in the State of Bavaria over a period of seven months. Data were used from the online database BayCoRei (Bavarian Corona Screening Tests), established in July 2020.

Novel CYP11B-ligand [I]IMAZA as promising theranostic tool for adrenocortical tumors: comprehensive preclinical characterization and first clinical experience.

Purpose: Adrenal tumors represent a diagnostic and therapeutic challenge. Promising results have been obtained through targeting the cytochrome P450 enzymes CYP11B1 and CYP11B2 for molecular imaging, and [I]iodometomidate ([I]IMTO) has even been successfully introduced as a theranostic agent. As this radiopharmaceutical shows rapid metabolic inactivation, we aimed at developing new improved tracers.

Low-cost synthesis of peptide libraries and their use for binding studies via temperature-related intensity change.

Protein-peptide interactions are involved in many fundamental cellular functions and constitute promising drug targets. Here, we provide a detailed protocol for the cost-effective preparation of a cellulose-based solid support for synthesis of nanoscale to micromolar-scale peptide libraries. Their subsequent use for high-throughput protein interaction screening as well as affinity determination in solution provides binding data for thousands of unique peptides with a turnover of 1 to 2 weeks, thereby facilitating assessment and development of high-affinity binders.

Clinical performance evaluation of SARS-CoV-2 rapid antigen testing in point of care usage in comparison to RT-qPCR.

Background: Antigen rapid diagnostic tests (RDT) for SARS-CoV-2 are fast, broadly available, and inexpensive. Despite this, reliable clinical performance data from large field studies is sparse.

Methods: In a prospective performance evaluation study, RDT from three manufacturers (NADAL®, Panbio™, MEDsan®, conducted on different samples) were compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) in 5 068 oropharyngeal swabs for detection of SARS-CoV-2 in a hospital setting.

Locked fracture dislocations of the proximal humerus: postoperative results and a proposed modification of the classification.

Background: Locked dislocations of the glenohumeral joint are disabling and often painful conditions and the treatment is challenging. This study evaluates the functional outcome and the different prosthetic treatment options for chronic locked dislocations of the glenohumeral joint and a subclassification is proposed.

Methods: In this single-center retrospective case series, all patients with a chronic locked dislocation treated surgically during a four-year period were analyzed.

Artemisinins and their impact on inhibitory neurotransmission.

Artemisinin, a major extract of the annual mugwort Artemisia annua, and its semisynthetic derivatives represent state-of-the-art antimalarial drugs. These compounds also target, via poorly understood mechanisms, various mammalian pathways, thereby exhibiting anticancer and immunomodulatory properties. Recently, crystal structures of artemisinins with two mammalian targets were determined, namely, gephyrin, the prime scaffolding protein at inhibitory postsynapses, and pyridoxal kinase, a central metabolic enzyme synthesizing vitamin B6.

Autoantibodies to cortactin and agrin in sera of patients with myasthenia gravis.

Autoantibodies against agrin and cortactin have been described in patients with myasthenia gravis. To further validate and characterize these autoantibodies, sera and/or plasma exchange material of 135 patients with myasthenia gravis were screened for anti-agrin or anti-cortactin autoantibodies. Autoantibodies against cortactin were detected in three patients and two controls and could be confirmed by cell-based assays using cortactin-transfected human embryonic kidney cells in both controls and one patient, but were not detectable in follow-up sera of the three patients.

Myelin basic protein and neurofilament H in postmortem cerebrospinal fluid as surrogate markers of fatal traumatic brain injury.

The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.

Anterior deltoid muscle tension quantified with shear wave ultrasound elastography correlates with pain level after reverse shoulder arthroplasty.

Introduction: Reverse shoulder arthroplasty (RSA) leads to medialization and distalization of the centre of rotation of the shoulder joint resulting in lengthening of the deltoid muscle. Shear wave ultrasound elastography (SWE) is a reliable method for quantifying tissue stiffness. The purpose of this study was to analyse if deltoid muscle tension after RSA correlates with the patients' pain level.

Posttraumatic learning deficits correlate with initial trauma severity and chronic cellular reactions after closed head injury in male mice.

Traumatic brain injury (TBI) is often associated with sustained attention and memory deficits. As persisting neuroinflammation and neurodegeneration may contribute to posttraumatic psychomotor dysfunction, we studied the relationship of brain cellular reactions three months after a weight-drop closed head injury in male mice with posttraumatic learning and memory using automated home-cage monitoring of socially housed mice in IntelliCages as well as tests for locomotor activity, anxiety and forepaw fine motor skills. One month after TBI, deficits in place learning and cognitive flexibility in reverse learning were clearly detectable in IntelliCages and these memory deficits correlated with the initial trauma severity on the functional neuroscore.

A large retroperitoneal lipoblastoma as an incidental finding: a case report.

Background: Lipoblastoma is a rare benign mesenchymal neoplasm of infancy that most commonly occurs on the extremities and trunk but can arise at variable sites of the body. Retroperitoneal lipoblastomas are particularly rare but can grow to enormous size, and preoperative diagnosis is difficult with diverse, mostly malignant differential diagnoses that would lead to aggressive therapy. Since lipoblastoma is a benign tumor that has an excellent prognosis after resection, correct diagnosis is crucial.

Validity and Efficacy of Methods to Define Blood Brain Barrier Integrity in Experimental Ischemic Strokes: A Comparison of Albumin Western Blot, IgG Western Blot and Albumin Immunofluorescence.

The clinical and preclinical research of ischemic strokes (IS) is becoming increasingly comprehensive, especially with the emerging evidence of complex thrombotic and inflammatory interactions. Within these, the blood brain barrier (BBB) plays an important role in regulating the cellular interactions at the vascular interface and is therefore the object of many IS-related questions. Consequently, valid, economic and responsible methods to define BBB integrity are necessary.

Expanding GABAR pharmacology via receptor-associated proteins.

Drugs directly targeting γ-aminobutyric acid type A receptors (GABARs), the major mediators of fast synaptic inhibition, contribute significantly to today's neuropharmacology. Emerging evidence establishes intracellularly GABAR-associated proteins as the central players in determining cellular and subcellular GABAergic input sites, thereby providing pharmacological opportunities to affect distinct receptor populations and address discrete neuronal dysfunctions. Here, we report on recently studied GABAR-associated proteins and highlight challenges and newly available methods for their functional and physical mapping.

Mass-Encoded Reporters Reporting Proteolytic Activity from within the Extracellular Matrix.

Reporting matrix metalloproteinase (MMP) activity directly from the extracellular matrix (ECM) may provide critical insights to better characterize 2D and 3D cell culture model systems of inflammatory diseases and potentially leverage in vivo diagnosis. In this proof-of-concept study, we designed MMP-sensors, which were covalently linked onto the ECM by co-administration of the activated transglutaminase factor XIIIa (FXIIIa). Elements of the featured MMP-sensors are the D-domain of insulin-like growth factor I (IGF-I) through which co-administered FXIIIa covalently links the sensor to the ECM followed by an MMP sensitive peptide sequence and locally reporting on MMP activity, an isotopically labeled mass tag encoding for protease activity, and an affinity tag facilitating purification from fluids.

Button batteries and typical swallowed foreign bodies can be differentiated in high-resolution X-Rays.

Background: Button battery ingestions have emerged as an increasing medical issue in recent years, especially for children. The frequent use of these energy sources in small appliances and toys is responsible for their ubiquitous occurrence in households. In addition to other possible foreign bodies, button batteries are particularly dangerous as they can cause severe complications in the aerodigestive tract.

Telepathological evaluation of paediatric histological specimens in support of a hospital in Tanzania.

Background/objective: In a project of telepathology (TP) between German pathologists and a hospital in Tanzania, trained technical assistants have uploaded digital histological images onto the internet-based platform ipath. The diagnoses from 486 paediatric specimens were analysed.

Methods: The investigation included diagnoses, either primarily done via TP or secondarily after a further workup of the paraffin-embedded tissue, which was sent to Germany for cases which could not be solved via TP.

Hydroxamic acid-modified peptide microarrays for profiling isozyme-selective interactions and inhibition of histone deacetylases.

Histones control gene expression by regulating chromatin structure and function. The posttranslational modifications (PTMs) on the side chains of histones form the epigenetic landscape, which is tightly controlled by epigenetic modulator enzymes and further recognized by so-called reader domains. Histone microarrays have been widely applied to investigate histone-reader interactions, but not the transient interactions of Zn-dependent histone deacetylase (HDAC) eraser enzymes.

Pregnancy Zone Protein (PZP) is significantly upregulated in the decidua of recurrent and spontaneous miscarriage and negatively correlated to Glycodelin A (GdA).

Background: Pregnancy Zone Protein (PZP) is an immunosuppressive protein that is expressed by the placenta and has also been identified in immune cells. When PZP and Glycodelin A (GdA) are combined, they act synergistically to inhibit Th-1 immune response. Little is known about its combined expression and role in normal and disturbed first trimester pregnancy.