Impact of cell geometry, cellular uptake region, and tumour morphology on Ac and Lu dose distributions in prostate cancer.

Background: Radiopharmaceutical therapy with Ac- and Lu-PSMA has shown promising results for the treatment of prostate cancer. However, the distinct physical properties of alpha and beta radiation elicit varying cellular responses, which could be influenced by factors such as tumour morphology. In this study, we use simulations to examine how cell geometry, region of pharmaceutical uptake within the cell to model different internalization fractions, and the presence of tumour hypoxia and necrosis impact nucleus absorbed doses and dose heterogeneity with Ac and Lu.

A GATE simulation study for dosimetry in cancer cell and micrometastasis from the Ac decay chain.

Background: Radiopharmaceutical therapy (RPT) with alpha-emitting radionuclides has shown great promise in treating metastatic cancers. The successive emission of four alpha particles in the Ac decay chain leads to highly targeted and effective cancer cell death. Quantifying cellular dosimetry for Ac RPT is essential for predicting cell survival and therapeutic success.

Microplastics and their interactions with microbiota.

As a new pollutant, Microplastics (MPs) are globally known for their negative impacts on different ecosystems and living organisms. MPs are easily taken up by the ecosystem in a variety of organisms due to their small size, and cause immunological, neurological, and respiratory diseases in the impacted organism. Moreover, in the impacted environments, MPs can release toxic additives and act as a vector and scaffold for colonization and transportation of specific microbes and lead to imbalances in microbiota and the biogeochemical and nutrients dynamic.

Lu SPECT imaging in the presence ofY: doesY degrade image quantification? a simulation study.

This work aims to investigate the accuracy of quantitative SPECT imaging ofLu in the presence ofY, which occurs in dual-isotope radiopharmaceutical therapy (RPT) involving both isotopes. We used the GATE Monte Carlo simulation toolkit to conduct a phantom study, simulating spheres filled withLu andY placed in a cylindrical water phantom that was also filled with activity of both radionuclides. We simulated multiple phantom configurations and activity combinations by varying the location of the spheres, the concentrations ofLu andY in the spheres, and the amount of background activity.

Arc ubiquitination regulates endoplasmic reticulum-mediated Ca release and CaMKII signaling.

Synaptic plasticity relies on rapid, yet spatially precise signaling to alter synaptic strength. Arc is a brain enriched protein that is rapidly expressed during learning-related behaviors and is essential for regulating metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). We previously showed that disrupting the ubiquitination capacity of Arc enhances mGluR-LTD; however, the consequences of Arc ubiquitination on other mGluR-mediated signaling events is poorly characterized.

B7-H3 Specific CAR T Cells for the Naturally Occurring, Spontaneous Canine Sarcoma Model.

One obstacle for human solid tumor immunotherapy research is the lack of clinically relevant animal models. In this study, we sought to establish a chimeric antigen receptor (CAR) T-cell treatment model for naturally occurring canine sarcomas as a model for human CAR T-cell therapy. Canine CARs specific for B7-H3 were constructed using a single-chain variable fragment derived from the human B7-H3-specific antibody MGA271, which we confirmed to be cross-reactive with canine B7-H3.

Optimized cocktail of 90Y/177Lu for radionuclide therapy of neuroendocrine tumors of various sizes: a simulation study.

Background And Objectives: There is significant interest and potential in the treatment of neuroendocrine tumors via peptide receptor radionuclide therapy (PRRT) using one or both of 90Y and 177Lu-labeled peptides. Given the presence of different tumor sizes in patients and differing radionuclide dose delivery properties, the present study aims to use Monte Carlo simulations to estimate S-values to spherical tumors of various sizes with 90Y and 177Lu separately and in combination. The goal is to determine ratios of 90Y to 177Lu that result in the largest absorbed doses per decay of the radionuclides and the most suitable dose profiles to treat tumors of specific sizes.

Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs.

Theranostics is an emerging paradigm that combines imaging and therapy in order to personalize patient treatment. In nuclear medicine, this is achieved by using radiopharmaceuticals that target identical molecular targets for both imaging (using emitted gamma rays) and radiopharmaceutical therapy (using emitted beta, alpha or Auger-electron particles) for the treatment of various diseases, such as cancer. If the therapeutic radiopharmaceutical cannot be imaged quantitatively, a "theranostic pair" imaging surrogate can be used to predict the absorbed radiation doses from the therapeutic radiopharmaceutical.

Structural Mechanism of Cooperative Regulation of Calcium-Sensing Receptor-Mediated Cellular Signaling.

Calcaium sensing receptors (CaSRs) play a central role in regulating extracellular calcium (Ca) homeostasis and many (patho)physiological processes. This regulation is primarily orchestrated in response to extracellular stimuli via the extracellular domain (ECD). This paper first reviews the modeled structure of the CaSR ECD and the prediction and investigation of the Ca and amino acid binding sites.

Rapid subcellular calcium responses and dynamics by calcium sensor G-CatchER.

The precise spatiotemporal characteristics of subcellular calcium (Ca) transients are critical for the physiological processes. Here we report a green Ca sensor called "G-CatchER" using a protein design to report rapid local ER Ca dynamics with significantly improved folding properties. G-CatchER exhibits a superior Ca on rate to G-CEPIA1er and has a Ca-induced fluorescence lifetimes increase.

An investigation of genetic polymorphisms in heparan sulfate proteoglycan core proteins and key modification enzymes in an Australian Caucasian multiple sclerosis population.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system in young adults. Heparan sulfate proteoglycans (HSPGs) are ubiquitous to the cell surface and the extracellular matrix. HSPG biosynthesis is a complex process involving enzymatic attachment of heparan sulfate (HS) chains to a core protein.

Race-Specific Patterns of Treatment Intensification Among Hypertensive Patients Using Home Blood Pressure Monitoring: Analysis Using Defined Daily Doses in the Heart Healthy Lenoir Study.

Background: Racial disparities in blood pressure (BP) control persist, but whether differences by race in antihypertensive medication intensification (AMI) contribute is unknown.

Objective: To compare AMI by race for patients with elevated home BP readings.

Methods: This prospective cohort study followed adult patients from 6 rural primary care practices who used home BP monitoring (HBPM) and recorded/reported values.

Applicability of Precision Medicine Approaches to Managing Hypertension in Rural Populations.

As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: (i) to determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large studies, are applicable to blood pressure control in subjects from a rural population; (ii) to measure the association of these SNPs with subjects' responsiveness to the hypertension intervention; and (iii) to identify other SNPs that may help understand patient-specific responses to an intervention. We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) and Caucasian Americans (CAU).

Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER.

Intracellular calcium (Ca) transients evoked by extracellular stimuli initiate a multitude of biological processes in living organisms. At the center of intracellular calcium release are the major intracellular calcium storage organelles, the endoplasmic reticulum (ER) and the more specialized sarcoplasmic reticulum (SR) in muscle cells. The dynamic release of calcium from these organelles is mediated by the ryanodine receptor (RyR) and the inositol 1,4,5-triphosphate receptor (IP3R) with refilling occurring through the sarco/endoplasmic reticulum calcium ATPase (SERCA) pump.

Calcium Dynamics Mediated by the Endoplasmic/Sarcoplasmic Reticulum and Related Diseases.

The flow of intracellular calcium (Ca) is critical for the activation and regulation of important biological events that are required in living organisms. As the major Ca repositories inside the cell, the endoplasmic reticulum (ER) and the sarcoplasmic reticulum (SR) of muscle cells are central in maintaining and amplifying the intracellular Ca signal. The morphology of these organelles, along with the distribution of key calcium-binding proteins (CaBPs), regulatory proteins, pumps, and receptors fundamentally impact the local and global differences in Ca release kinetics.

A multicomponent quality improvement intervention to improve blood pressure and reduce racial disparities in rural primary care practices.

The Southeastern United States has the highest prevalence of hypertension and African Americans have disproportionately worse blood pressure control. The authors sought to evaluate the effect of a multicomponent practice-based quality improvement intervention on lowering mean systolic blood pressure (SBP) at 12 and 24 months compared with baseline among 525 patients, and to assess for a differential effect of the intervention by race (African Americans vs white). At 12 months, both African Americans (-5.

The association of health literacy and blood pressure reduction in a cohort of patients with hypertension: The heart healthy lenoir trial.

Objective: Lower health literacy is associated with poorer health outcomes. Few interventions poised to mitigate the impact of health literacy in hypertensive patients have been published. We tested if a multi-level quality improvement intervention could differentially improve Systolic Blood Pressure (SBP) more so in patients with low vs.

Molecular Basis of the Extracellular Ligands Mediated Signaling by the Calcium Sensing Receptor.

Ca-sensing receptors (CaSRs) play a central role in regulating extracellular calcium concentration ([Ca]) homeostasis and many (patho)physiological processes in multiple organs. This regulation is orchestrated by a cooperative response to extracellular stimuli such as small changes in Ca, Mg, amino acids, and other ligands. In addition, CaSR is a pleiotropic receptor regulating several intracellular signaling pathways, including calcium mobilization and intracellular calcium oscillation.

A community-based lifestyle and weight loss intervention promoting a Mediterranean-style diet pattern evaluated in the stroke belt of North Carolina: the Heart Healthy Lenoir Project.

Background: Because residents of the southeastern United States experience disproportionally high rates of cardiovascular disease (CVD), it is important to develop effective lifestyle interventions for this population.

Methods: The primary objective was to develop and evaluate a dietary, physical activity (PA) and weight loss intervention for residents of the southeastern US. The intervention, given in eastern North Carolina, was evaluated in a 2 year prospective cohort study with an embedded randomized controlled trial (RCT) of a weight loss maintenance intervention.

Structural basis for regulation of human calcium-sensing receptor by magnesium ions and an unexpected tryptophan derivative co-agonist.

Ca(2+)-sensing receptors (CaSRs) modulate calcium and magnesium homeostasis and many (patho)physiological processes by responding to extracellular stimuli, including divalent cations and amino acids. We report the first crystal structure of the extracellular domain (ECD) of human CaSR bound with Mg(2+) and a tryptophan derivative ligand at 2.1 Å.

Lamellipodin-Deficient Mice: A Model of Rectal Carcinoma.

During a survey of clinical rectal prolapse (RP) cases in the mouse population at MIT animal research facilities, a high incidence of RP in the lamellipodin knock-out strain, C57BL/6-Raph1tm1Fbg (Lpd-/-) was documented. Upon further investigation, the Lpd-/- colony was found to be infected with multiple endemic enterohepatic Helicobacter species (EHS). Lpd-/- mice, a transgenic mouse strain produced at MIT, have not previously shown a distinct immune phenotype and are not highly susceptible to other opportunistic infections.

Lessons Learned From Implementing Health Coaching in The Heart Healthy Lenoir Hypertension Study.

Background: Health coaching is increasingly important in patient-centered medical homes.

Objectives: Describe formative evaluation results and lessons learned from implementing health coaching to improve hypertension self-management in rural primary care.

Methods: A hypertension collaborative was formed consisting of six primary care sites.

Systemic Coronaviral Disease in 5 Ferrets.

The prevalence of reported systemic coronaviral disease in ferrets (Mustela putorius furo), which resembles the dry form of feline infectious peritonitis, has been increasing in the literature since its initial diagnosis and characterization approximately 10 y ago. Here we describe the clinical signs, pathologic findings, and diagnosis by immunohistochemistry using an FIPV3-70 monoclonal antibody of systemic coronaviral disease in 5 ferrets, 2 of which were strictly laboratory-housed; the remaining 3 were referred from veterinary private practices. This case report illustrates the importance of considering FRSCV infection as a differential diagnosis in young, debilitated ferrets with abdominal masses and other supporting clinical signs.

Perceived Social Standing, Medication Nonadherence, and Systolic Blood Pressure in the Rural South.

Purpose: Little is known about how perceived social standing versus traditional socioeconomic characteristics influence medication adherence and blood pressure (BP) among African American and white patients with hypertension in the rural southeastern United States.

Methods: Perceived social standing, socioeconomic characteristics, self-reported antihypertensive medication adherence, and BP were measured at baseline in a cohort of rural African American and white patients (n = 495) with uncontrolled hypertension attending primary care practices. Multivariate models examined the relationship of perceived social standing and socioeconomic indicators with medication adherence and systolic BP.

The calcium sensing receptor: from calcium sensing to signaling.

The Ca(2+)-sensing receptor (the CaSR), a G-protein-coupled receptor, regulates Ca(2+) homeostasis in the body by monitoring extracellular levels of Ca(2+) ([Ca(2+)]o) and responding to a diverse array of stimuli. Mutations in the Ca(2+)-sensing receptor result in hypercalcemic or hypocalcemic disorders, such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and autosomal dominant hypocalcemic hypercalciuria. Compelling evidence suggests that the CaSR plays multiple roles extending well beyond not only regulating the level of extracellular Ca(2+) in the human body, but also controlling a diverse range of biological processes.