Nucleoporin 153 deficiency in adult neural stem cells defines a pathological protein-network signature and defective neurogenesis in a mouse model of AD.

Background: Reduction of adult hippocampal neurogenesis is an early critical event in Alzheimer's disease (AD), contributing to progressive memory loss and cognitive decline. Reduced levels of the nucleoporin 153 (Nup153), a key epigenetic regulator of NSC stemness, characterize the neural stem cells isolated from a mouse model of AD (3×Tg) (AD-NSCs) and determine their altered plasticity and gene expression.

Methods: Nup153-regulated mechanisms contributing to NSC function were investigated: (1) in cultured NSCs isolated from AD and wild type (WT) mice by proteomics; (2) in vivo by lentiviral-mediated delivery of Nup153 or GFP in the hippocampus of AD and control mice analyzing neurogenesis and cognitive function; (3) in human iPSC-derived brain organoids obtained from AD patients and control subjects as a model of neurodevelopment.

Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens.

It has been recently established that GPR158, a class C orphan G protein-coupled receptor, serves as a metabotropic glycine receptor. GPR158 is highly expressed in the nucleus accumbens (NAc), a major input structure of the basal ganglia that integrates information from cortical and subcortical structures to mediate goal-directed behaviors. However, whether glycine modulates neuronal activity in the NAc through GPR158 activation has not been investigated yet.

Structure-specific rigid dose accumulation dosimetric analysis of ablative stereotactic MRI-guided adaptive radiation therapy in ultracentral lung lesions.

Background: Definitive local therapy with stereotactic ablative radiation therapy (SABR) for ultracentral lung lesions is associated with a high risk of toxicity, including treatment related death. Stereotactic MR-guided adaptive radiation therapy (SMART) can overcome many of the challenges associated with SABR treatment of ultracentral lesions.

Methods: We retrospectively identified 14 consecutive patients who received SMART to ultracentral lung lesions from 10/2019 to 01/2021.

Magnetic Resonance-Guided Stereotactic Body Radiation Therapy/Hypofractionated Radiation therapy for Metastatic and Primary Central and Ultracentral Lung Lesions.

Introduction: The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or hypofractionated radiation therapy (MRgHRT) enables the safe delivery of high-dose radiation to central and UC lung lesions.

Methods: Patients with UC or central lesions were treated with MRgSBRT/MRgHRT with real-time gating or adaptation.

Acute restraint stress impairs histamine type 2 receptor ability to increase the excitability of medium spiny neurons in the nucleus accumbens.

Histamine, a monoamine implicated in stress-related arousal states, is synthesized in neurons exclusively located in the hypothalamic tuberomammillary nucleus (TMN) from where they diffusely innervate striatal and mesolimbic networks including the nucleus accumbens (NAc), a vital node in the limbic loop. Since histamine-containing TMN neuron output increases during stress, we hypothesized that exposure of mice to acute restrain stress (ARS) recruits endogenous histamine type 2 receptor (H2R) signaling in the NAc, whose activation increases medium spiny neurons (MSNs) intrinsic excitability via downregulation of A-type K currents. We employed an ARS paradigm in which mice were restrained for 120 min, followed by a 20-min recovery period, after which brain slices were prepared for ex vivo electrophysiology.

Activation of histamine type 2 receptors enhances intrinsic excitability of medium spiny neurons in the nucleus accumbens.

Histaminergic neurons are exclusively located in the hypothalamic tuberomammillary nucleus, from where they project to many brain areas including the nucleus accumbens (NAc), a brain area that integrates diverse monoaminergic inputs to coordinate motivated behaviours. While the NAc expresses various histamine receptor subtypes, the mechanisms by which histamine modulates NAc activity are still poorly understood. Using whole-cell patch-clamp recordings, we found that pharmacological activation of histamine 2 (H2) receptors elevates the excitability of NAc medium spiny neurons (MSNs), while activation of H1 receptors failed to significantly affect MSN excitability.

Triggered kV Imaging During Spine SBRT for Intrafraction Motion Management.

To monitor intrafraction motion during spine stereotactic body radiotherapy(SBRT) treatment delivery with readily available technology, we implemented triggered kV imaging using the on-board imager(OBI) of a modern medical linear accelerator with an advanced imaging package. Triggered kV imaging for intrafraction motion management was tested with an anthropomorphic phantom and simulated spine SBRT treatments to the thoracic and lumbar spine. The vertebral bodies and spinous processes were contoured as the image guided radiotherapy(IGRT) structures specific to this technique.

Wee1 Rather Than Plk1 Is Inhibited by AZD1775 at Therapeutically Relevant Concentrations.

Wee1 kinase is an inhibitor of cyclin-dependent kinase (cdk)s, crucial cell cycle progression drivers. By phosphorylating cdk1 at tyrosine 15, Wee1 inhibits activation of cyclin B-cdk1 (Cdk1), preventing cells from entering mitosis with incompletely replicated or damaged DNA. Thus, inhibiting Wee1, alone or in combination with DNA damaging agents, can kill cancer cells by mitotic catastrophe, a tumor suppressive response that follows mitosis onset in the presence of under-replicated or damaged DNA.

[Immediate reocclusion of the infrapopliteal segment after thrombolysis in acute ischemia of the lower limb of the thrombotic nature].

Early reocclusion of below knee segment after fibrinolytic therapy is mainly due to thrombo-embolism, coagulopathy or to the arterial wall condition. 42 patients facing acute lower limb ischaemia because of iliofemoral thrombosis (prosthesis 19, native artery 23) underwent locoregional thrombolysis. UK was given in 33 cases while the others received rt-PA.

[Composite bypass using endarterectomized autologous superficial femoral artery. A valid concept in the extension of lower limb salvage surgery].

Saphenous vein is nowadays the material of choice performing on femoro-distal revascularisation; when this is not available, it is important to use a material which gives the closest approximation of an ideal conduit and for same time an easy handling during the execution of the anastomosis. Although vein's degenerative alterations are very rare, it has now been shown that there is widespread destruction of the endothelium among infrainguinal vein grafting, producing a relatively thrombogenic surface. These factors may contribute to the initial failure rate of these bypasses.

Aneurysm of the abdominal aorta in a young woman. Atherosclerotic or inflammatory in origin?

The case is described of a 27 year old woman with aneurysms of the abdominal aorta. In the absence of any signs of atherosclerotic disease, an inflammatory aetiology was suspected, a view that was supported by the macroscopic intraoperative findings and preoperative autoimmune assays. The literature on this rare pathology is examined.