NR2F2 Reactivation in Early-life Adipocyte Stem-like Cells Rescues Adipocyte Mitochondrial Oxidation.

In humans, perinatal exposure to an elevated omega-6 (n6) relative to omega-3 (n3) Fatty Acid (FA) ratio is associated with the likelihood of childhood obesity. In mice, we show perinatal exposure to excessive n6-FA programs neonatal Adipocyte Stem-like cells (ASCs) to differentiate into adipocytes with lower mitochondrial nutrient oxidation and a propensity for nutrient storage. Omega-6 FA exposure reduced fatty acid oxidation (FAO) capacity, coinciding with impaired induction of beige adipocyte regulatory factors PPARγ, PGC1α, PRDM16, and UCP1.

Key questions and gaps in understanding adipose tissue macrophages and early-life metabolic programming.

The global obesity epidemic, with its associated comorbidities and increased risk of early mortality, underscores the urgent need for enhancing our understanding of the origins of this complex disease. It is increasingly clear that metabolism is programmed early in life and that metabolic programming can have life-long health consequences. As a critical metabolic organ sensitive to early-life stimuli, proper development of adipose tissue (AT) is crucial for life-long energy homeostasis.

Adipocyte Mitochondria: Deciphering Energetic Functions across Fat Depots in Obesity and Type 2 Diabetes.

Adipose tissue, a central player in energy balance, exhibits significant metabolic flexibility that is often compromised in obesity and type 2 diabetes (T2D). Mitochondrial dysfunction within adipocytes leads to inefficient lipid handling and increased oxidative stress, which together promote systemic metabolic disruptions central to obesity and its complications. This review explores the pivotal role that mitochondria play in altering the metabolic functions of the primary adipocyte types, white, brown, and beige, within the context of obesity and T2D.

Radiochemistry and In Vivo Imaging of [Ti]Ti-THP-PSMA.

Titanium-45 (Ti) is a radionuclide with excellent physical characteristics for use in positron emission tomography (PET) imaging, including a moderate half-life (3.08 h), decay by positron emission (85%), and a low mean positron energy of 0.439 MeV.

How I Do It: ERAS protocol featuring erector spinae plane block for percutaneous nephrolithotomy.

Percutaneous nephrolithotomy (PCNL) is the gold-standard treatment for large and complex renal stones. Though associated with higher stone-free rates compared to other minimally invasive stone procedures, this comes at the expense of increased morbidity including postoperative pain and discomfort. We describe our enhanced recovery after surgery (ERAS) protocol for PCNL with emphasis on the use of erector spinae plane blocks to improve patient satisfaction and reduce postoperative opioid use and bother.

Prospective Randomized Trial of Antibiotic Prophylaxis Duration for Percutaneous Nephrolithotomy in Low-Risk Patients.

Postoperative infection and sepsis account for the most common complications following percutaneous nephrolithotomy (PCNL), as high as 14% in low-risk patients. Although the American Urological Association (AUA) recommends perioperative antibiotics for 24 hours or less for PCNL, practice patterns vary regarding duration of antibiotic therapy. We aimed to compare the efficacy of 24-hour antibiotic coverage short-course protocol of antibiotic prophylaxis for PCNL.

An indium-111-labelled membrane-targeted peptide for cell tracking with radionuclide imaging.

Cell labelling agents that enable longitudinal tracking of administered cells will support the clinical development of cell-based therapies. Radionuclide imaging with gamma and positron-emitting radioisotopes can provide quantitative and longitudinal mapping of cells . To make this widely accessible and adaptable to a range of cell types, new, versatile and simple methods for directly radiolabelling cells are required.

Neonatal intake of Omega-3 fatty acids enhances lipid oxidation in adipocyte precursors.

Establishing metabolic programming begins during fetal and postnatal development, and early-life lipid exposures play a critical role during neonatal adipogenesis. We define how neonatal consumption of a low omega-6 to -3 fatty acid ratio (n6/n3 FA ratio) establishes FA oxidation in adipocyte precursor cells (APCs) before they become adipocytes. , APCs isolated from mouse pups exposed to the low n6/n3 FA ratio had superior FA oxidation capacity, elevated beige adipocyte mRNAs Ppargc1α, Ucp2, and Runx1, and increased nuclear receptor NR2F2 protein.

Correlation of hypoxia PET tracer uptake with hypoxic radioresistance in cancer cells: PET biomarkers of resistance to stereotactic radiation therapy?

Purpose: The pO threshold of an ideal PET hypoxia tracer for radiotherapy planning in cancer would match those observed in clinically and biologically relevant processes such as radioresistance and HIF1α expression. To identify such tracers, we directly compared uptake in vitro of hypoxia PET tracers ([F]FMISO, [Cu]CuATSM, and analogues [Cu]CuATS, [Cu]CuATSE, [Cu]CuCTS, [Cu]CuDTS, [Cu]CuDTSE, [Cu]CuDTSM) with levels of radioresistance and HIF1α expression in cultured cancer cells under identical hypoxic conditions ranging from extreme hypoxia to normoxia. Pimonidazole uptake was also compared as a marker of hypoxia.

Robotic Single-Port Donor Nephrectomy with the da Vinci SP® Surgical System.

Objectives: The da Vinci SP® Surgical System received U.S. Food and Drug Administration approval for urological procedures in 2018.

Allele-specific suppression in Caenorhabditis elegans reveals details of EMS mutagenesis and a possible moonlighting interaction between the vesicular acetylcholine transporter and ERD2 receptors.

A missense mutant, unc-17(e245), which affects the Caenorhabditis elegans vesicular acetylcholine transporter UNC-17, has a severe uncoordinated phenotype, allowing efficient selection of dominant suppressors that revert this phenotype to wild-type. Such selections permitted isolation of numerous suppressors after EMS (ethyl methanesulfonate) mutagenesis, leading to demonstration of delays in mutation fixation after initial EMS treatment, as has been shown in T4 bacteriophage but not previously in eukaryotes. Three strong dominant extragenic suppressor loci have been defined, all of which act specifically on allele e245, which causes a G347R mutation in UNC-17.

Efficacy and Safety of Mirabegron in Men with Overactive Bladder Symptoms and Benign Prostatic Hyperplasia.

Purpose Of Review: To review the efficacy and safety of mirabegron in men with overactive bladder (OAB) and benign prostatic hyperplasia (BPH).

Recent Findings: Numerous studies have shown mirabegron to be efficacious and safe in treating symptoms of OAB. More recent studies evaluating the use of mirabegron in men with OAB and BPH have also shown the medication to be effective with few adverse side effects when used as monotherapy or in combination therapy.

Optimal His-Tag Design for Efficient [Tc(CO)] and [Re(CO)] Labeling of Proteins for Molecular Imaging and Radionuclide Therapy by Analysis of Peptide Arrays.

Hexahistidine tags (His-tags), incorporated into recombinant proteins to facilitate purification using metal-affinity chromatography, are useful binding sites for radiolabeling with [Tc(CO)] and [Re(CO)] for molecular imaging and radionuclide therapy. Labeling efficiencies vary unpredictably, and the method is therefore not universally useful. To overcome this, we have made quantitative comparisons of radiolabeling of a bespoke Celluspots array library of 382 His-tag-containing peptide sequences with [Tc(CO)] and [Re(CO)] to identify key features that enhance labeling.

Simple Solution to a Difficult Problem: Removal of Large Bladder Calculi Using a Laparoscopic Entrapment Sac.

Percutaneous management of large bladder calculi with the use of a laparoscopic entrapment sac is a minimally invasive procedure that may have advantages over open cystolithotomy and transurethral cystolithotripsy, as well as standard percutaneous cystolithotomy. We first performed this procedure in 2008, and refined it after our initial publication in 2013 by changing the position from lithotomy to supine by using a urethral catheter postoperatively instead of a suprapubic (SP) catheter, by using ultrasound guidance for access, and by changing the procedure from being inpatient to outpatient. Our objective is to assess the continued feasibility of percutaneous entrapment sac cystolithotomy (PESC) and describe modifications that simplify the technique (mPESC), comparing outcomes and complications.

Systematic phenomics analysis of autism-associated genes reveals parallel networks underlying reversible impairments in habituation.

A major challenge facing the genetics of autism spectrum disorders (ASDs) is the large and growing number of candidate risk genes and gene variants of unknown functional significance. Here, we used to systematically functionally characterize ASD-associated genes in vivo. Using our custom machine vision system, we quantified 26 phenotypes spanning morphology, locomotion, tactile sensitivity, and habituation learning in 135 strains each carrying a mutation in an ortholog of an ASD-associated gene.

The effects of fractional microablative CO laser therapy on sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy.

Purpose: To examine the outcomes of sexual function in postmenopausal women and women with a history of breast cancer treated with endocrine therapy who were experiencing the symptoms of GSM for which they were treated with fractional microablative CO laser.

Materials And Methods: From July 2015 to October 2016, a retrospective chart review of women who underwent fractional microablative CO laser therapy (MonaLisa Touch, DEKA) for GSM was conducted. Several validated questionnaires were used to assess changes in symptoms and sexual function including the Female Sexual Function Index (FSFI), the Wong-Baker Faces Scale (WBFS), and the Female Sexual Distress Scale-Revised (FSDSR).

Author Correction: Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury.

Complement activation is a recognised mediator of myocardial ischaemia-reperfusion-injury (IRI) and cardiomyocytes are a known source of complement proteins including the central component C3, whose activation products can mediate tissue inflammation, cell death and profibrotic signalling. We investigated the potential to detect and quantify the stable covalently bound product C3d by external body imaging, as a marker of complement activation in heart muscle in a murine model of myocardial IRI. We used single-photon-emission-computed-tomography (SPECT) in conjunction with Technecium-labelled recombinant complement receptor 2 (Tc-rCR2), which specifically detects C3d at the site of complement activation.

Simple, mild, one-step labelling of proteins with gallium-68 using a tris(hydroxypyridinone) bifunctional chelator: a Ga-THP-scFv targeting the prostate-specific membrane antigen.

Background: Labelling proteins with gallium-68 using bifunctional chelators is often problematic because of unsuitably harsh labelling conditions such as low pH or high temperature and may entail post-labelling purification. To determine whether tris(hydroxypyridinone) (THP) bifunctional chelators offer a potential solution to this problem, we have evaluated the labelling and biodistribution of a THP conjugate with a new single-chain antibody against the prostate-specific membrane antigen (PSMA), an attractive target for staging prostate cancer (PCa). A single-chain variable fragment (scFv) of J591, a monoclonal antibody that recognises an external epitope of PSMA, was prepared in order to achieve biokinetics matched to the half-life of gallium-68.

Cold Kit for Prostate-Specific Membrane Antigen (PSMA) PET Imaging: Phase 1 Study of Ga-Tris(Hydroxypyridinone)-PSMA PET/CT in Patients with Prostate Cancer.

Ga-labeled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as Ga-labeled ,'-bis(2-hydroxybenzyl)ethylenediamine-,'-diacetic acid (HBED)-PSMA-11, are promising small molecules for targeting prostate cancer. A new radiopharmaceutical, Ga-labeled tris(hydroxypyridinone) (THP)-PSMA, has a simplified design for single-step kit-based radiolabeling. It features the THP ligand, which forms complexes with Ga rapidly at a low concentration, at room temperature, and over a wide pH range, enabling direct elution from a Ge/Ga generator into a lyophilized radiopharmaceutical kit in 1 step without manipulation.

A 99mTc-labelled scFv antibody fragment that binds to prostate-specific membrane antigen.

Introduction: Prostate-specific membrane antigen (PSMA) is an extensively studied antigen for imaging prostate cancer. We prepared a single-chain variable fragment (scFv) of J591, a monoclonal antibody that recognises an external epitope of PSMA, incorporating a His-tag for labelling with Tc tricarbonyl, and evaluated its binding using human PCa cell lines.

Methods: J591(scFv) was expressed in HEK-293T cells and purified by metal ion affinity chromatography, followed by size exclusion chromatography.

HO-Improved O activation on the Pd-Au bimetallic surface.

Improved activation of adsorbed O by co-adsorbed HO on the Pd-Au(111) surface has been observed. When co-adsorbed with HO, O admolecules on the Pd-Au surface are more strongly bound via their interactions with HO. This interaction leads to large enhancements in the dissociation of O as determined via the generation of CO upon exposure to CO.

Opportunities and challenges for metal chemistry in molecular imaging: from gamma camera imaging to PET and multimodality imaging.

The development of medical imaging is a highly multidisciplinary endeavor requiring the close cooperation of clinicians, physicists, engineers, biologists and chemists to identify capabilities, conceive challenges and solutions and apply them in the clinic. The chemistry described in this article illustrates how synergistic advances in these areas drive the technology and its applications forward, with each discipline producing innovations that in turn drive innovations in the others. The main thread running through the article is the shift from single photon radionuclide imaging towards PET, and in turn the emerging shift from PET/CT towards PET/MRI and further, combination of these with optical imaging.

Non-invasive molecular imaging of inflammatory macrophages in allograft rejection.

Background: Macrophages represent a critical cell type in host defense, development and homeostasis. The ability to image non-invasively pro-inflammatory macrophage infiltrate into a transplanted organ may provide an additional tool for the monitoring of the immune response of the recipient against the donor graft. We therefore decided to image in vivo sialoadhesin (Sn, Siglec 1 or CD169) using anti-Sn mAb (SER-4) directly radiolabelled with (99m)Tc pertechnetate.

Effect of annealing in oxygen on alloy structures of Pd-Au bimetallic model catalysts.

It has been reported that Pd-Au bimetallic catalysts display improved catalytic performance after adequate calcination. In this study, a model catalyst study was conducted to investigate the effects of annealing in oxygen on the surface structures of Pd-Au alloys by comparing the physicochemical properties of Pd/Au(111) surfaces that were annealed in ultrahigh vacuum (UHV) versus in an oxygen ambient. Auger electron spectroscopy (AES) and Basin hopping simulations reveal that the presence of oxygen can inhibit the diffusion of surface Pd atoms into the subsurface of the Au(111) sample.