The Surviving, Not Thriving, Photoreceptors in Patients with Stargardt Disease.

Stargardt disease (STGD1), associated with biallelic variants in the gene, is the most common heritable macular dystrophy and is currently untreatable. To identify potential treatment targets, we characterized surviving STGD1 photoreceptors. We used clinical data to identify macular regions with surviving STGD1 photoreceptors.

Mobility of Rare Earth Elements in Coastal Aquifer Materials under Fresh and Brackish Water Conditions.

The indispensable role of rare earth elements (REEs) in manufacturing high-tech products and developing various technologies has resulted in a surge in REE extraction and processing. The latter, in turn, intensifies the release of anthropogenic REEs into the environment, particularly in the groundwater system. REE contamination in coastal aquifer systems, which serve as drinking and domestic water sources for large populations, demands a thorough understanding of the mechanisms that govern REE transport and retention in these environments.

Daily Light Onset and Plasma Membrane Tethers Regulate Mitochondria Redistribution within the Retinal Pigment Epithelium.

The retinal pigment epithelium (RPE) is an essential component of the retina that plays multiple roles required to support visual function. These include light onset- and circadian rhythm-dependent tasks, such as daily phagocytosis of photoreceptor outer segments. Mitochondria provide energy to the highly specialized and energy-dependent RPE.

Biomarker evidence of early vision and rod energy-linked pathophysiology benefits from very low dose DMSO in 5xFAD mice.

Here, we test whether early visual and OCT rod energy-linked biomarkers indicating pathophysiology in nicotinamide nucleotide transhydrogenase (Nnt)-null 5xFAD mice also occur in Nnt-intact 5xFAD mice and whether these biomarkers can be pharmacologically treated. Four-month-old wild-type or 5xFAD C57BL/6 substrains with either a null (B6J) Nnt or intact Nnt gene (B6NTac) and 5xFAD B6J mice treated for one month with either R-carvedilol + vehicle or only vehicle (0.01% DMSO) were studied.

Diffusion in Porous Rock Is Anomalous.

Molecular diffusion of chemical species in subsurface environments─rock formations, soil sediments, marine, river, and lake sediments─plays a critical role in a variety of dynamic processes, many of which affect water chemistry. We investigate and demonstrate the occurrence of anomalous (non-Fickian) diffusion behavior, distinct from classically assumed Fickian diffusion. We measured molecular diffusion through a series of five chalk and dolomite rock samples over a period of about two months.

Acetazolamide Challenge Changes Outer Retina Bioenergy-Linked and Anatomical OCT Biomarkers Depending on Mouse Strain.

Purpose: The purpose of this study was to test the hypothesis that optical coherence tomography (OCT) bioenergy-linked and anatomical biomarkers are responsive to an acetazolamide (ACZ) provocation.

Methods: C57BL/6J mice (B6J, a strain with relatively inefficient mitochondria) and 129S6/ev mice (S6, a strain with relatively efficient mitochondria) were given a single IP injection of ACZ (carbonic anhydrase inhibitor) or vehicle. In each mouse, the Mitochondrial Configuration within Photoreceptors based on the profile shape Aspect Ratio (MCP/AR) index was determined from the hyper-reflective band immediately posterior to the external limiting membrane (ELM).

Do multiple physiological OCT biomarkers indicate age-related decline in rod mitochondrial function in C57BL/6J mice?

Purpose: To test the hypothesis that rod photoreceptor mitochondria function progressively declines over time.

Methods: 2, 12, and 24 month-old dark- and light-adapted C57BL/6J (B6J) mice were examined by OCT. We measured (i) an index of mitochondrial configuration within photoreceptors measured from the profile shape aspect ratio (MCP/AR) of the hyperreflective band posterior to the external limiting membrane (ELM), (ii) a proxy for energy-dependent pH-triggered water removal, the thickness of the ELM-retinal pigment epithelium (ELM-RPE), and its correlate (iii) the hyporeflective band (HB) signal intensity at the photoreceptor tips.

Blockade of IL-6R prevents preterm birth and adverse neonatal outcomes.

Background: Preterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks treatment.

Methods: Proteomic and scRNA-seq human data were analysed to evaluate the role of IL-6 and IL-1α in SIAI. A C57BL/6 murine model of SIAI-induced preterm birth was developed by the ultrasound-guided intra-amniotic injection of IL-1α.

Controls that expedite first-passage times in disordered systems.

First-passage time statistics in disordered systems exhibiting scale invariance are studied widely. In particular, long trapping times in energy or entropic traps are fat-tailed distributed, which slow the overall transport process. We study the statistical properties of the first-passage time of biased processes in different models, and we employ the big-jump principle that shows the dominance of the maximum trapping time on the first-passage time.

Amniotic fluid rubidium concentration association with newborn birthweight: a maternal-neonatal pilot study.

Background: Although most biological systems, including human tissues, contain rubidium, its biogeochemical functions and possible role in neonatal birthweight are largely unknown. An animal study indicated a correlation between rubidium deficiency in the maternal diet and lower newborn birthweight.

Objective: This pilot study measured rubidium concentrations in amniotic fluid during the second trimester of (low-risk) pregnancy and investigated potential correlations between rubidium levels and third-trimester newborn birthweight-small for gestational age, appropriate for gestational age, and large for gestational age-and between preterm birth and term birth in uncomplicated pregnancies.

A decade of faculty development for health professions educators: lessons learned from the Macy Faculty Scholars Program.

Faculty development (FD) programs are critical for providing the knowledge and skills necessary to drive positive change in health professions education, but they take many forms to attain the program goals. The Macy Faculty Scholars Program (MFSP), created by the Josiah Macy Jr. Foundation (JMJF) in 2010, intends to develop participants as leaders, scholars, teachers, and mentors.

Multiple Bioenergy-Linked OCT Biomarkers Suggest Greater-Than-Normal Rod Mitochondria Activity Early in Experimental Alzheimer's Disease.

Purpose: In Alzheimer's disease, central brain neurons show evidence for early hyperactivity. It is unclear if this occurs in the retina, another disease target. Here, we tested for imaging biomarker manifestation of prodromal hyperactivity in rod mitochondria in vivo in experimental Alzheimer's disease.

Transducin-Deficient Rod Photoreceptors Evaluated With Optical Coherence Tomography and Oxygen Consumption Rate Energy Biomarkers.

Purpose: To test the hypothesis that rod energy biomarkers in light and dark are similar in mice without functional rod transducin (Gnat1rd17).

Methods: Gnat1rd17 and wildtype (WT) mice were studied in canonically low energy demand (light) and high energy demand (dark) conditions. We measured rod inner segment ellipsoid zone (ISez) profile shape, external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness, and magnitude of a hyporeflective band (HB) intensity dip located between photoreceptor tips and apical RPE; antioxidants were given in a subset of mice.

Fast and slow light-induced changes in murine outer retina optical coherence tomography: complementary high spatial resolution functional biomarkers.

Fast (seconds) and slow (minutes to hours) optical coherence tomography (OCT) responses to light stimulation have been developed to probe outer retinal function with higher spatial resolution than the classical full-field electroretinogram (ERG). However, the relationships between functional information revealed by OCT and ERG are largely unexplored. In this study, we directly compared the fast and slow OCT responses with the ERG.

The Impact of Radiographic, Metabolic and Demographic Characteristics on Kidney Stone Recurrence.

Urolithiasis is a frequent disease with cited rates of recurrence after initial diagnosis that vary widely and range between 35% and 50%. We assessed the radiographic recurrence rate in patients with urinary stones and its risk factors. We retrospectively identified patients who were diagnosed with urinary stones on non-contrast computed tomography from 2010 to 2011, and underwent another imaging examination at least six months afterwards.

Potential Markers to Reduce Non-Contrast Computed Tomography Use for Symptomatic Patients with Suspected Ureterolithiasis.

Most patients with ureterolithiasis are managed successfully with conservative treatment. In this context, delineation of clinical risk factors that identify patients with low risk for surgical intervention may reduce use of Non-Contrast Computed Tomography (NCCT). Here, emergency department patient files from a 14-month period were reviewed retrospectively, to identify patients who underwent NCCT and showed a ureteral stone.

Functional Changes Within the Rod Inner Segment Ellipsoid in Wildtype Mice: An Optical Coherence Tomography and Electron Microscopy Study.

Purpose: To test the hypothesis that changing energy needs alter mitochondria distribution within the rod inner segment ellipsoid.

Methods: In mice with relatively smaller (C57BL/6J [B6J]) or greater (129S6/ev [S6]) retina mitochondria maximum reserve capacity, the profile shape of the rod inner segment ellipsoid zone (ISez) was measured with optical coherence tomography (OCT) under higher (dark) or lower (light) energy demand conditions. ISez profile shape was characterized using an unbiased ellipse descriptor (minor/major aspect ratio).

Design of a fully intraureteral stent and proof-of-concept evaluation.

Background: Ureteral stents are employed regularly to facilitate urine drainage and ureteral healing in a wide variety of endourological procedures, associated mainly with ureteral stone obstruction. However, stent use frequently impairs patient quality of life, which is generally attributed to the presence of anchoring stent curls in the bladder and/or kidney. The purpose of this study was to examine the potential effectiveness and safety of a newly designed, fully intraureteral stent, in an initial proof-of-concept evaluation.

Drainage of infected kidneys with ureteral stents: does size matter?

Purpose: The purpose of our study was to evaluate the ability of ureteral stents with different diameters to drain pus that accumulates in an obstructed kidney using an in vitro model.

Methods: We developed an in vitro model of an obstructed kidney filled with pus. The model included a silicon kidney unit based on computed tomography (CT) data, a 3D printed ureteral stone based on a real extracted ureteral stone, a latex ureter model, a bladder vessel, and a fluid with qualities resembling pus.

Mobility and Retention of Rare Earth Elements in Porous Media.

There is growing concern that rare earth elements (REEs) will become emerging soil-water contaminants because of their increased use in new technologies and products, which may lead to unavoidable release to the environment. To better understand the environmental behavior of REEs, a comprehensive set of adsorption and column transport experiments was conducted in quartz sand media. The retention and mobility of three representative REEs (La, Gd, and Er) were studied in the presence and absence of humic acid (HA; 5, 20, and 50 mg L) and under a range of pH conditions (5-8).

Magnetic resonance imaging of in vitro urine flow in single and tandem stented ureters subject to extrinsic ureteral obstruction.

Objective: To quantify the relative volumetric flows in stent and ureter lumina, as a function of stent size and configuration, in both unobstructed and externally obstructed stented ureters.

Methods: Magnetic resonance imaging was used to measure flow in stented ureters using a phantom kidney model. Volumetric flow in the stent and ureter lumina were determined along the stented ureters, for each of four single stent sizes (4.

When should we give up on expectant management for patients with proximal ureteral stones?

Background: Proximal ureteral stones (PUS) have relatively low rates of spontaneous expulsion. However, some patients do well on expectant management. Our aim was to compare risk factors for surgical intervention in patients with PUS who underwent primary intervention to those subjected to expectant management.