Low efficiency of leucocyte plugging-based drug delivery to cancer in mice.

Cells of the immune system were proposed for use as Trojan horse for tumour-specific drug delivery. The efficacy of such cell-based drug delivery depends on the site-specific cell homing. This present study was aimed to investigate the potential of leucocytes for intratumoural site-specific enrichment using a locoregional application route in experimental liver tumours.

Distributed Global Debris Thickness Estimates Reveal Debris Significantly Impacts Glacier Mass Balance.

Supraglacial debris affects glacier mass balance as a thin layer enhances surface melting, while a thick layer reduces it. While many glaciers are debris-covered, global glacier models do not account for debris because its thickness is unknown. We provide the first globally distributed debris thickness estimates using a novel approach combining sub-debris melt and surface temperature inversion methods.

Low Energy Electron Irradiation Is a Potent Alternative to Gamma Irradiation for the Inactivation of (CAR-)NK-92 Cells in ATMP Manufacturing.

Background: With increasing clinical use of NK-92 cells and their CAR-modified derivatives in cancer immunotherapy, there is a growing demand for efficient production processes of these "off-the-shelf" therapeutics. In order to ensure safety and prevent the occurrence of secondary tumors, (CAR-)NK-92 cell proliferation has to be inactivated before transfusion. This is commonly achieved by gamma irradiation.

Pathologic femur fractures following surgery and radiotherapy for soft tissue sarcomas: A case series.

Introduction: Combined limb-sparing surgery and radiation therapy are considered the standard of care for higher grade soft tissue sarcomas (STS) of the extremities. The risk of post-radiation fracture after this treatment modality is well known, but still underestimated, and can end in serious long-term secondary problems years later.

Presentation Of Case: We reviewed the records of three patients with pathological femur fractures years after wide local excision of an STS of the proximal lower extremity.

Repurposing CPAP machines as stripped-down ventilators.

The worldwide shortage of medical-grade ventilators is a well-known issue, that has become one of the central topics during the COVID-19 pandemic. Given that these machines are expensive and have long lead times, one approach is to vacate them for patients in critical conditions while patients with mild to moderate symptoms are treated with stripped-down ventilators. We propose a mass-producible solution that can create such ventilators with minimum effort.

European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision.

To revise the 2010 consensus guideline on chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Seventeen disease experts, a patient representative, and two Cochrane methodologists constructed 12 Population/Intervention/Comparison/Outcome (PICO) questions regarding diagnosis and treatment to guide the literature search. Data were extracted and summarized in GRADE summary of findings (for treatment PICOs) or evidence tables (for diagnostic PICOs).

Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development.

De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). In mouse, constitutive Cul3 haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window.

From the low-density lipoprotein receptor-related protein 1 to neuropathic pain: a potentially novel target.

This review describes the roles of the low-density lipoprotein receptor-related protein 1 (LRP-1) in inflammatory pathways, nerve nerve degeneration and -regeneration and in neuropathic pain. Induction of LRP-1 is able to reduce the activation of the proinflammatory NFκB-mediated pathway and the mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase and p38 signaling pathways, in turn decreasing the production of inflammatory mediators. Low-density lipoprotein receptor-related protein 1 activation also decreases reactive astrogliosis and polarizes microglial cells and macrophages from a proinflammatory phenotype (M1) to an anti-inflammatory phenotype (M2), attenuating the neuroinflammatory environment.

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.

C2orf69 mutations disrupt mitochondrial function and cause a multisystem human disorder with recurring autoinflammation.

BACKGROUNDDeciphering the function of the many genes previously classified as uncharacterized open reading frame (ORF) would complete our understanding of a cell's function and its pathophysiology.METHODSWhole-exome sequencing, yeast 2-hybrid and transcriptome analyses, and molecular characterization were performed in this study to uncover the function of the C2orf69 gene.RESULTSWe identified loss-of-function mutations in the uncharacterized C2orf69 gene in 8 individuals with brain abnormalities involving hypomyelination and microcephaly, liver dysfunction, and recurrent autoinflammation.

Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects.

Aircraft noise induces vascular and cerebral inflammation and oxidative stress causing hypertension and cardiovascular/cerebral dysfunction. With the present studies, we sought to determine the role of myeloid cells in the vascular vs. cerebral consequences of exposure to aircraft noise.

Percutaneous Irreversible Electroporation for Treatment of Small Hepatocellular Carcinoma Invisible on Unenhanced CT: A Novel Combined Strategy with Prior Transarterial Tumor Marking.

Introduction: To explore the feasibility, safety, and efficiency of ethiodized oil tumor marking combined with irreversible electroporation (IRE) for small hepatocellular carcinomas (HCCs) that were invisible on unenhanced computed tomography (CT).

Methods: A retrospective analysis of the institutional database was performed from January 2018 to September 2018. Patients undergoing ethiodized oil tumor marking to improve target-HCC visualization in subsequent CT-guided IRE were retrieved.

Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target.

Objective: We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans.

Design: Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice.

Single-energy versus dual-energy imaging during CT-guided biopsy using dedicated metal artifact reduction algorithm in an in vivo pig model.

Purpose: To evaluate dual-energy CT (DE) and dedicated metal artifact reduction algorithms (iMAR) during CT-guided biopsy in comparison to single-energy CT (SE).

Methods: A trocar was placed in the liver of six pigs. CT acquisitions were performed with SE and dose equivalent DE at four dose levels(1.

Consistent skin α-synuclein positivity in REM sleep behavior disorder - A two center two-to-four-year follow-up study.

Objective/methods: Phosphorylated alpha-synuclein (p-syn) in dermal nerves of patients with isolated REM sleep behavior disorder (iRBD) is detectable by immunofluorescence-labeling. Skin-biopsy-p-syn-positivity was recently postulated to be a prodromal marker of Parkinson's disease (PD) or related synucleinopathies. Here, we provide two-to four-year clinical and skin biopsy follow-up data of 33 iRBD patients, whose skin biopsy findings at baseline were reported in 2017.

Antibodies to the Caspr1/contactin-1 complex in chronic inflammatory demyelinating polyradiculoneuropathy.

Previous studies have described the clinical, serological and pathological features of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and antibodies directed against the paranodal proteins neurofascin-155, contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), or nodal forms of neurofascin. Such antibodies are useful for diagnosis and potentially treatment selection. However, antibodies targeting Caspr1 only or the Caspr1/CNTN1 complex have been reported in few patients with CIDP.

Standardized artificially created stable pertrochanteric femur fractures present more homogenous results compared to osteotomies for orthopaedic implant testing.

Background: With regard to biomechanical testing of orthopaedic implants, there is no consensus on whether artificial creation of standardized bone fractures or their simulation by means of osteotomies result in more realistic outcomes. Therefore, the aim of this study was to artificially create and analyze in an appropriate setting the biomechanical behavior of standardized stable pertrochanteric fractures versus their simulation via osteotomizing.

Methods: Eight pairs of fresh-frozen human cadaveric femora aged 72.

Structural Rationalization for the Nonmutagenic and Mutagenic Bypass of the Tobacco-Derived O4-4-(3-Pyridyl)-4-oxobut-1-yl-thymine Lesion by Human Polymerase η: A Multiscale Computational Study.

Tobacco-derived pyridyloxobutyl (POB) DNA adducts are unique due to the large size and flexibility of the alkyl chain connecting the pyridyl ring to the nucleobase. Recent experimental work suggests that the O4-4-(3-pyridyl)-4-oxobut-1-yl-T (O4-POB-T) lesion can undergo both nonmutagenic (dATP) and mutagenic (dGTP) insertion by the translesion synthesis (TLS) polymerase (pol) η in human cells. Interestingly, the mutagenic rate for O4-POB-T replication is reduced compared to that for the smaller O4-methylthymine (O4-Me-T) lesion, and O4-POB-T yields a different mutagenic profile than the O2-POB-T variant (dTTP insertion).

Radiological management of postoperative lymphorrhea.

Purpose: Postoperative lymphorrhea can occur after different surgical procedures and may prolong the hospital stay due to the need for specific treatment. In this work, the therapeutic significance of the radiological management of postoperative lymphorrhea was assessed and illustrated.

Method: A standardized search of the literature was performed in PubMed applying the Medical Subject Headings (MeSH) term "lymphangiography.

Evaluation of Resection Margin after Image-Guided Dural Tail Resection in Convexity Meningiomas.

Infiltration of adjacent dura with meningioma cells is a common phenomenon. Wide resection of the dural tail (DT) to achieve a gross total resection is a general recommendation. We aimed to investigate a tumor cell infiltration of the DT after image-guided resection of convexity meningiomas.

Association of the A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence.

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian-instrumental interactions.

Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy.

Pathological aggregates of alpha-synuclein in peripheral dermal nerve fibers can be detected in patients with idiopathic Parkinson's disease and multiple system atrophy. This study combines skin biopsy staining for p-alpha-synuclein depositions and radionuclide imaging of the heart with [I]-metaiodobenzylguanidine to explore peripheral denervation in both diseases. To this purpose, 42 patients with a clinical diagnosis of Parkinson's disease or multiple system atrophy were enrolled.