Proximal Function Research Articles

THU500 Geospatial Analysis To Quantify Spatial Heterogeneity Of Tumor Microenvironment

Abstract Disclosure: J. Yoo: None. C. Mitra: None. Y. Yue: None. A. Soliman: None. Z. Madak Erdogan: None. Metabolic heterogeneity, a concept describing distinct differences in nutrient metabolism within the cells of a healthy or diseased tissue, is a common challenge in development and cancer research. Current methods, such as histology and Magnetic Resonance Imaging (MRI), cannot visualize nutrient uptake into single cells, making it difficult to understand the heterogeneity that affects cellular growth and metabolism. Visium Spatial Transcriptomics, a method that shows regional gene expression, is emerging as a powerful spatial analysis tool, and we aim to integrate this transcriptomic method with other biologically relevant datasets to highlight the importance of cell-microenvironment interactions. We propose to leverage geostatistical tools to model the multivariate covariance structure of genes expression profiles to allow: 1) understanding of their spatial characteristics and covariance changes under certain conditions (e.g. drug treatment or damage), 2) using these covariance structures to simulate synthetic samples at a scale sufficient to train the state of art neural network architectures, and 3) incorporating spatial awareness directly in the machine learning/deep learning models by enriching the spatial transcriptomics data using distance proximity functions. We will quantify the tumor microenvironment spatial heterogeneity using different approaches. First, we will analyze the degree of spatial auto-correlation to estimate the ranges of spatial heterogeneity within a tumor. We also plan to quantify the degree of anisotropy to identify if the tumor heterogeneity is happening along specific axis. Different local clustering indicators will be also calculated, such as the Getis-Ord (Gi*) statistic and Local Moran's I to identify the prevalence of hot and cold spots in the tumor. These hot and cold spots will be used to segment the tumor area into sub-regions and further quantify the local heterogeneity with a single tumor. We hypothesize that transcriptional heterogeneity reflects phenotypic differences in different regions of healthy or diseased tissue, rendering cells in certain regions to display a differential response to external stimuli (e.g. diet or drugs). Integration of multiple information (e.g. retrospective patient data) with different spatial heterogeneity indicators identified from the geospatial analyses could aid in identification of patients who are resistant to cancer therapies and further advance personalized therapy. Presentation: Thursday, June 15, 2023

Using down-scan capabilities from recreational-grade side-scan sonar systems to sample paddlefish and evaluate depth use in a reservoir

Recreational-grade side-scan sonar (SSS) has only recently been applied to estimate abundance of Paddlefish Polyodon spathula, a large pelagic planktivore, in reservoirs. Current recreational-grade SSS units also have a dedicated down-scan channel, which may be useful for detecting Paddlefish in reservoirs because the range of depths they inhabit. We investigated the utility of down-scan images using SSS data from a previously published study of Paddlefish in Keystone Lake, Oklahoma. Two readers counted Paddlefish and estimated the depth of each fish and the water column. We used proximity functions in a geographic information system to find individual Paddlefish that were common between the readers. We further used proximity functions to identify common fish observed from the SSS survey conducted previously as an aid to compare and refine down-scan estimates. Depth of Paddlefish averaged approximately 7 m, but fish were deeper when water was deeper. Density estimates from down-scan were comparable to side-scan, but only after utilizing the side-scan data to adjust for detection-by-distance in a dual-gear approach. Down-scan data thus appear to be useful for not only estimating density of Paddlefish, but also for incorporating depth use, creating a three-dimensional database of locations that can inform managers of optimal depths for sampling gear (e.g., gill nets), improve monitoring efficiency, and facilitate better management of reservoir populations.

Microdosimetric analysis of monoenergetic electrons and beta-emitting radionuclides based on mesh-type cell models and RBE prediction

AimsMicrodosimetric indicators are commonly used to describe the energy deposition characteristics of ionizing radiation at the subcellular and DNA levels to predict radiation-induced biological effects. Monoenergetic electrons and beta-emitting radionuclides (β nuclides) have a certain range in low-density media, and their microdosimetric indicators in the cell nucleus are of great significance for understanding the characteristics of different types of β nuclides and the evaluation of relative biological effectiveness (RBE). MethodsMicrodosimetry in the nucleus is greatly affected by cell morphology, so in this paper, based on laser confocal tomography images of BEAS-2B and L-O2 cell lines, two types of mesh-type cell models were constructed to restore the morphological features of real cells. The Geant4-DNA toolkit was used to simulate the lineal energy and dose distribution of monoenergetic electrons (0.1 keV-1 MeV) and 5 types of beta nuclides (Cs-137, Cs-134, C-14, I-131, and H-3) in the cell nucleus with different initial energies. The effects of factors such as initial energy, sensitive site (radius = 2 nm, 10 nm, 30 nm, 300 nm), and cell type on microdosimetric quantities in the nucleus and their predictions of nuclide RBE were analysed. ResultsThe results show that for the same type of nuclide, there are different RBE values between BEAS-2B and L-O2 cells, with Cs-134 having a difference of 17.75% and H-3 having a difference of 10.58%. In addition, the mean lineal energy in the nucleus fluctuates with changes in the initial energy and sampling site radius of monoenergetic electrons, especially for low and medium energies where the sampling site radius has a significant effect. Moreover, the proximity functions of monoenergetic electrons with an initial energy below 1 keV are greatly affected by the cell shape, and those above 20 keV are greatly affected by the model volume. ConclusionsThe study confirms the necessity of using mesh cell models for microdosimetric analysis in the cell nucleus and predicting its biological effects by combining mesh models of real human cells to simulate microdosimetric indicators of monoenergetic electrons and beta-emitting nuclides. The estimation of the RBE of β nuclides achieved in this study has reference value for predicting radiobiological damage in different cell types.

Access to Certified Burn Centers in the United States: The Geospatial and Transport Cost of Transfer.

Specialized burn centers are critical to minimizing burn-associated morbidity and mortality. However, American Burn Association-verified burn centers are unequally distributed across the United States, and fewer centers are available for pediatric patients relative to adults. The economic burden of transporting patients to these centers contributes significantly to the high cost of burn care. This study quantifies inequitable burn care access in the contiguous United States due to age group and location as a function of physical proximity to a verified burn center and transportation cost. County-level distances to the nearest verified adult or pediatric burn center were determined and mapped. Distance calculations for each population were combined with transport cost data (2022 CMS Ambulance Fee Schedules) to estimate transportation costs for each population (adult vs pediatric, urban vs rural). Pediatric patients reside 30.5 miles further than adults from the nearest center, significantly increasing transportation costs. Ground and air transport costs also increased for rural versus urban patients. Notably, rural patients face almost double the cost of air transport. While physical proximity to burn care appears to differ only modestly across age and region, this marginal increase in distance is associated with significant economic impact. This study highlights physical and economic barriers to burn care access faced by rural and pediatric patients and underscores the critical need to improve equity in burn care access. Future studies should expand on this report's findings to more fully characterize the additional costs associated with inequitable burn care access.

Empowering Foot Health: Harnessing the Adaptive Weighted Sub-Gradient Convolutional Neural Network for Diabetic Foot Ulcer Classification.

In recent times, DFU (diabetic foot ulcer) has become a universal health problem that affects many diabetes patients severely. DFU requires immediate proper treatment to avert amputation. Clinical examination of DFU is a tedious process and complex in nature. Concurrently, DL (deep learning) methodologies can show prominent outcomes in the classification of DFU because of their efficient learning capacity. Though traditional systems have tried using DL-based models to procure better performance, there is room for enhancement in accuracy. Therefore, the present study uses the AWSg-CNN (Adaptive Weighted Sub-gradient Convolutional Neural Network) method to classify DFU. A DFUC dataset is considered, and several processes are involved in the present study. Initially, the proposed method starts with pre-processing, excluding inconsistent and missing data, to enhance dataset quality and accuracy. Further, for classification, the proposed method utilizes the process of RIW (random initialization of weights) and log softmax with the ASGO (Adaptive Sub-gradient Optimizer) for effective performance. In this process, RIW efficiently learns the shift of feature space between the convolutional layers. To evade the underflow of gradients, the log softmax function is used. When logging softmax with the ASGO is used for the activation function, the gradient steps are controlled. An adaptive modification of the proximal function simplifies the learning rate significantly, and optimal proximal functions are produced. Due to such merits, the proposed method can perform better classification. The predicted results are displayed on the webpage through the HTML, CSS, and Flask frameworks. The effectiveness of the proposed system is evaluated with accuracy, recall, F1-score, and precision to confirm its effectual performance.

Does hinge sidedness influence laterality of C5 palsy after expansile open-door cervical laminoplasty?

Cervical expansile open-door laminoplasties (EOLPs) have an open side and a hinge side, with the open side being bridged by grafts or miniplates. The authors explored the possibility that the open-door side might have a greater incidence of C5 palsy due to a greater stretch of the ipsilateral C5 nerve root. This study was a retrospective review of prospectively collected data over a period of 25 years specifically assessing surgical complications. Included were patients who underwent EOLP for myelopathy, radiculopathy, or mild central cord injuries (American Spinal Injury Association Impairment Scale [AIS] grade D). Exclusion criteria included preexisting C5 weakness; patients with AIS grade A, B, or C injury; and added instrumentation or additional surgical procedures. Patients were monitored postoperatively for C5 palsy or any other complications. A comparison group included patients who underwent cervical laminectomy and fusion (CLF). A total of 327 laminoplasties were collected, and 31 patients were excluded because of severe spinal cord injury (AIS grades A-C), 3 for preoperative C5 weakness, and 21 for instrumentation or additional surgical procedures. Thus, 272 patients were analyzed with a mean age of 59.9 years (range 22-88 years). Diagnoses at presentation were cervical myelopathy (84.1%), central cord syndrome (7.2%), cervical myeloradiculopathy (3.4%), ossification of the posterior longitudinal ligament (1.9%), and other (3.4%). The most common complications were C5 palsy (n = 7, 2.6%) and wound infection (n = 7, 2.6%). Of the 7 cases of postoperative C5 palsies in this study, 6 occurred on the side of the open door. Of the C5 palsies, 2 were mild, 3 were moderate, and 2 were severe. Two of the 7 C5 palsies had a delayed (> 24 hours) onset. The C5 palsy incidence after CLF was 2.7% with no side preference. C5 palsy after cervical decompression for myelopathy is a known occurrence, with a rate of 2.6% in the current study. The authors found that C5 palsies more commonly occur on the open side of the laminoplasty. This could be due to a greater manipulation of the nerve root on the side of the open door or greater stretch of the C5 root on the open-door side. If clinical symptoms and anatomical stenosis are symmetric, the authors recommend creating the laminoplasty hinge on the patient's dominant side to minimize potential loss of dominant proximal arm function.

A sense of proximity: Cell packing modulates oxygen consumption.

Accurately modeling oxygen transport and consumption is crucial to predict metabolic dynamics in cell cultures and optimize the design of tissue and organ models. We present a methodology to characterize the Michaelis-Menten oxygen consumption parameters in vitro, integrating novel experimental techniques and computational tools. The parameters were derived for hepatic cell cultures with different dimensionality (i.e., 2D and 3D) and with different surface and volumetric densities. To quantify cell packing regardless of the dimensionality of cultures, we devised an image-based metric, referred to as the proximity index. The Michaelis-Menten parameters were related to the proximity index through an uptake coefficient, analogous to a diffusion constant, enabling the quantitative analysis of oxygen dynamics across dimensions. Our results show that Michaelis-Menten parameters are not constant for a given cell type but change with dimensionality and cell density. The maximum consumption rate per cell decreases significantly with cell surface and volumetric density, while the Michaelis-Menten constant tends to increase. In addition, the dependency of the uptake coefficient on the proximity index suggests that the oxygen consumption rate of hepatic cells is superadaptive, as they modulate their oxygen utilization according to its local availability and to the proximity of other cells. We describe, for the first time, how cells consume oxygen as a function of cell proximity, through a quantitative index, which combines cell density and dimensionality. This study enhances our understanding of how cell-cell interaction affects oxygen dynamics and enables better prediction of aerobic metabolism in tissue models, improving their translational value.

The assessment of interhemispheric imbalance using functional near-infrared spectroscopic and transcranial magnetic stimulation for predicting motor outcome after stroke.

To investigate changes in interhemispheric imbalance of cortical excitability during motor recovery after stroke and to clarify the relationship between motor function recovery and alterations in interhemispheric imbalance, with the aim to establish more effective neuromodulation strategies. Thirty-one patients underwent assessments of resting motor threshold (RMT) using transcranial magnetic stimulation (TMS); the cortical activity of the primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA) using functional near-infrared spectroscopy (fNIRS); as well as motor function using upper extremity Fugl-Meyer (FMA-UE). The laterality index (LI) of RMT and fNIRS were also calculated. All indicators were measured at baseline(T1) and 1 month later(T2). Correlations between motor function outcome and TMS and fNIRS metrics at baseline were analyzed using bivariate correlation. All the motor function (FMA-UE1, FMA-UE2, FMA-d2) and LI-RMT (LI-RMT1 and LI-RMT2) had a moderate negative correlation. The higher the corticospinal excitability of the affected hemisphere, the better the motor outcome of the upper extremity, especially in the distal upper extremity (r = -0.366, p = 0.043; r = -0.393, p = 0.029). The greater the activation of the SMA of the unaffected hemisphere, the better the motor outcome, especially in the distal upper extremity (r = -0.356, p = 0.049; r = -0.367, p = 0.042). There was a significant moderate positive correlation observed between LI-RMT2 and LI-SMA1 (r = 0.422, p = 0.018). The improvement in motor function was most significant when both LI-RMT1 and LI-SMA1 were lower. Besides, in patients dominated by unaffected hemisphere corticospinal excitability during motor recovery, LI-(M1 + SMA + PMC)2 exhibited a significant moderate positive association with the proximal upper extremity function 1 month later (r = 0.642, p = 0.007). The combination of both TMS and fNIRS can infer the prognosis of motor function to some extent. Which can infer the role of both hemispheres in recovery and may contribute to the development of effective individualized neuromodulation strategies.

Background matching through fast and reversible melanin-based pigmentation plasticity in tadpoles comes with morphological and antioxidant changes

Facultative colour change is widespread in the animal kingdom, and has been documented in many distantly related amphibians. However, experimental data testing the extent of facultative colour change, and associated physiological and morphological implications are comparatively scarce. Background matching in the face of spatial and temporal environmental variation is thought to be an important proximate function of colour change in aquatic amphibian larvae. This is particularly relevant for species with long larval periods such as the western spadefoot toad, Pelobates cultripes, whose tadpoles spend up to six months developing in temporary waterbodies with temporally variable vegetation. By rearing tadpoles on different coloured backgrounds, we show that P. cultripes larvae can regulate pigmentation to track fine-grained differences in background brightness, but not hue or saturation. We found that colour change is rapid, reversible, and primarily achieved through changes in the quantity of eumelanin in the skin. We show that this increased eumelanin production and/or maintenance is also correlated with changes in morphology and oxidative stress, with more pigmented tadpoles growing larger tail fins and having an improved redox status.

Expected motor function change following decompressive surgery for spinal metastatic disease

Motor function in patients with spinal metastatic disease (SMD) directly impacts a patient's ability to receive systemic therapy and overall survival. Spine surgeons may be in the challenging position to advise a patient on expected motor function outcomes and determine a patient's suitability as a surgical candidate. We present this study to provide this critical information on anticipated motor function change to spine surgeons. Consecutive patients undergoing spinal surgery for SMD at a National Cancer Institute-designated cancer institute were prospectively enrolled. Patient motor function status before and after surgery was assessed using the standard 0 to 5 five-point muscle strength grading scale. The difference in presurgical and postsurgical motor function (proximal and distal) was used to assess motor function changes following surgery. A total of 171 patients were included. The mean age was 62.7±10.46 years and 40.9% (70) were female. Common primary malignancy types were lung (49), kidney (28), breast (25), and prostate (23). The average proximal and distal motor function difference was 0.38 (standard deviation=1.02, p<.0001) and 0.32 (standard deviation=0.91, p<.0001) respectively showing an improvement following surgery. Patients with proximal presurgical motor function of 2, 3, and 4 had an improved motor function in 73%, 77%, and 73% of the patients. Patients with distal presurgical motor function of 2, 3, and 4 had an improved motor function in 80%, 89%, and 70% of the patients. Most patients undergoing surgery for SMD have a modest improvement in motor function following surgery. The degree of improvement in most instances is less than 1 point on a 0 to 5 motor function scale. This is critical knowledge for a spinal surgeon when evaluating SMD patients with significant preoperative motor function deficits. These results aid spinal surgeons in setting expectations and evaluating the need for rapid spinal decompression.

Spatial distribution of selenium and other potentially toxic elements surrounding mountaintop coal mines in the Elk Valley, British Columbia, Canada

Despite the extensive use of mountaintop coal mining in the Elk Valley, British Columbia, Canada's largest metallurgical coal-producing region, little is known about the transport and deposition of fugitive dust emissions within its mountain landscape. This study aimed to assess the extent and spatial distribution of selenium and other potentially toxic elements (PTEs) near the town of Sparwood originating from fugitive dust emitted from two mountaintop coal mines. To achieve these objectives concentrations of 47 elements within moss tissues of Hylocomium splendens, Pleurozium schreberi, and Ptilium crista-castrensis were analyzed from 19 locations between May 29 to June 1, 2022. Contamination factors were then calculated to identify areas of contamination, along with generalized additive models to assess the relationship between selenium and the mines. Finally, Pearson correlation coefficients were calculated between selenium and other PTEs to determine which exhibited similar behaviour. This study found that selenium concentrations are a function of proximity to mountaintop mines, and the region's topographic features and prevailing wind patterns play a role in the transport and deposition of fugitive dust. Contamination is highest immediately surrounding mines and decreases at increasing distances, with the region's steep mountain ridges shielding the deposition of some fugitive dust when acting as a geographic barrier between adjacent valleys. Furthermore, silver, germanium, nickel, uranium, vanadium, and zirconium were identified as other PTEs of concern. The implications of this study are significant as it demonstrated the extent and spatial distribution of contaminants originating from fugitive dust emissions surrounding mountaintop mines and some of the controls to its distribution in mountain regions. As Canada and other mining jurisdictions look to expand critical mineral development, it will be important for proper risk assessment and mitigation in mountain regions to limit community and environmental exposure to contaminants within fugitive dust.

31-LB: The Relationship between Improvements in Glycemic Control following a Digital Health Intervention and the Food Environment in a Medicare Advantage Population

Diabetes is a complex disease that is influenced by social determinants of health (SDOH). An inadequate food environment, as a function of socioeconomic status and proximity to food retailers, has been associated with both increased prevalence of diabetes and barriers to diabetes self-management. This work examined the relationship between improvements in glycemic control as a result of a digital health intervention and the food environment in Medicare Advantage members at risk for diabetes-related complications (hemoglobin A1c [A1c] ≥ 8%). Participants enrolled in the Vida Health Diabetes Management program as part of their medical insurance benefit and utilized remote sessions with Registered Dietitians and Certified Diabetes Care and Education Specialists as well as content related to goal-setting to account for SDOH factors. The 2010 USDA Food Access Research Atlas was used to identify areas of low income and the absence of a food retailer within 0.5 or 1 urban and 10 rural miles (LILA). Participants were included if they had a laboratory A1c between -365 to -1 and 60 to 365-days of enrollment. Participants with baseline A1c ≥ 8.0 (n=430, 229 F, 68.9 y) demonstrated a decrease of -0.90 points (SD 1.71, p&amp;lt;0.001). Thirty-five percent resided in LILA areas at the 0.5, and twenty percent at 1 mile distance. Participants who resided in LILA areas had higher baseline A1c (0.5 difference: 0.37 (p=0.02), 1 difference: 0.51 (p=0.005)). Those with baseline A1c ≥ 9.0 (n=216, 120 F, 67.8 y) demonstrated a decrease of -1.38 points (SD 1.96, p&amp;lt;0.001). Thirty-nine percent resided in LILA areas at the 0.5, and twenty-three percent at 1 mile distance. Baseline A1c differences were not observed. Differences in improvements in A1c based on LILA were not observed (p’s &amp;gt; 0.05). Irrespective of LILA residence, the Vida Health program demonstrated significant improvements in glycemic control within 1 year in a high-risk Medicare Advantage population. Disclosure C. Edwards: Employee; Vida Health. L. Voelker: Employee; Vida Health. G. Zimmermann: Employee; Vida Health. K. Rawlings: Employee; Vida Health. A. Venkatesan: Employee; Vida Health. Funding Vida Health

Contagious Transmission in a Swedish National Sample of Alcohol Use Disorders as a Function of Geographical Proximity Among Siblings and Propinquity-of-Rearing Defined Acquaintances.

The purpose of this study was to determine whether alcohol use disorder (AUD) can be transmitted contagiously in siblings and likely acquaintances growing up close to one another (Propinquity-of-Rearing Defined Acquaintances [PRDAs]). PRDAs were pairs of same-age subjects growing up within 1 km of each other and sharing the same school class, where one of whom (PRDA1) was first registered for AUD at age 15 or older. Using adult residential location, we predicted proximity-dependent risk for an AUD first registration in a second PRDA within 3 years of PRDA1's registration. In 150,195 informative siblings, cohabitation status (hazard ratio [HR] = 1.22, 95% confidence interval [CI] [1.08, 1.37]), but not proximity, predicted risk for AUD onset. In 114,375 informative PRDA pairs, a log model fit best, predicting lower risk the greater the distance (HR = 0.88, 95% CI [0.84, 0.92]) with risks for AUD at 10, 50, and 100 km from affected PRDA1 cases equaling, respectively: 0.73 [0.66, 0.82], 0.60 [0.51, 0.72], and 0.55 [0.45, 0.68]. Within PRDA acquaintanceships, results resembled those found among PRDA pairs. The proximity-dependent contagious risk for AUD among PRDA pairs was attenuated by increasing age, lower genetic risk, and higher educational attainment. Cohabitation but not distance predicted transmission of AUD between siblings. However, contagious transmission of AUD among acquaintances growing up and attending school together was present and attenuated by increasing distance in adulthood. The impact of adult proximity on transmission was moderated by age, educational attainment, and genetic risk for AUD. Our results provide support for the validity of contagion models for AUD.

39 Certified Burn Center Access in the United States: The Geospatial and Transport Cost of Transfer

Abstract Introduction Specialized burn centers are critical in minimizing burn-associated morbidity and mortality. However, American Burn Association (ABA)-verified burn centers are unequally distributed across the US, and fewer verified centers are available for pediatric patients relative to adults. The economic burden of transport to verified centers represents a significant proportion of the already high cost of burn-associated care. The present study aims to quantify inequitable burn care access in the contiguous US due to age group and locality as a function of physical proximity and transportation cost. Methods County-level distances (n=3,106) to the nearest ABA-verified adult or pediatric burn center were determined and mapped. Distances were then analyzed separately for rural (n = 1440) and urban (n = 1666) counties for both adult and pediatric burn centers. Distance calculations for each population were combined with transport cost data (2022 CMS Ambulance fee Schedules) to determine the average cost of transport for each patient population (adult vs. pediatric, urban vs. rural). Results 59 Adult and 43 Pediatric ABA-verified centers were identified from the ABA burn center directory. Pediatric patients reside 30.57 miles (p &amp;lt; 0.001) further than adults from the nearest center, accounting for a 10.5% - 15.9% transport cost increase. Transport costs increased dramatically between urban and rural counties, with rural patients facing a cost increase of 32.7% and 80.88% for ground and air transportation, respectively. Conclusions Physical proximity to burn care may appear to differ only modestly across age and region. However, the seemingly marginal increase in distance significantly impacts the cost of patient transport. The present study highlights both physical and economic barriers to burn care access faced by rural and pediatric patients. Increasing ABA burn center certification in targeted areas across the US may decrease the disparities in access to burn care faced by these groups. Applicability of Research to Practice Identify areas that may benefit from expansion of certified burn-care access and additional provider education.

D98. Access to Certified Burn Centers in The United States: The Geospatial and Transport Cost of Transfer

PURPOSE: Although ABA-verified burn centers are critical in minimizing burn-associated morbidity and mortality, disparities in burn care access remain – particularly for rural and pediatric patients. The present study quantifies inequitable burn care access as a function of physical proximity and assesses its impact on burn-associated transport costs. METHODS: County-level distances (n=3,106) to the nearest ABA-verified adult (n=59) or pediatric (n=43) burn center were determined and mapped. Average per mile transport cost for each population (urban vs. rural) was estimated from CMS ambulance fee schedules. Total transport cost was determined based on county-level distance calculations, and cost burden was compared between cohorts. RESULTS: Pediatric patients reside 30.57 miles (p < 0.001) further than adults from the nearest center, accounting for a 10.5% - 15.9% transport cost increase. Transport costs increased dramatically between urban and rural counties, with rural patients facing a cost increase of 32.7% and 80.88% for ground and air transportation, respectively. CONCLUSION: Physical proximity to burn care may appear to differ only modestly across age and region. However, the seemingly marginal increase in distance significantly impacts the cost of patient transport. The present study highlights both physical and economic barriers to access faced by rural and pediatric burn patients. Increasing ABA burn center certification in targeted areas across the US may decrease the disparities in access to burn care faced by these groups.

Reflections on TRP and TP/GFR in the definition of renal phosphate loss: conceptual review.

Fractional tubular reabsorption of phosphate (TRP) has been used for over 60years to establish the existence of renal phosphate loss. It is a parameter of corrected volume per decilitre of glomerular filtration rate (GFR). Later, a mass parameter per dl GFR called TP/GFR (tubular PO4 reabsorption per dl GFR) was devised which some authors have sought to substitute for TRP. The aim of the present work is to attempt to demonstrate that TRP and TP/GFR are similar parameters and, in certain aspects, TRP is more effective for diagnosis. Data were gathered on the metabolism of phosphate corresponding to a group of healthy children without hypophosphatemia (n = 47), a group of patients with idiopathic hypercalciuria (n = 27), and ten patients diagnosed with X-linked hypophosphatemia (XLH). The TRP, the TP/GFR, and the percent tubular reabsorption of phosphate were calculated. All the patients with XLH presented TRP values lower than 95ml/dl GFR and of TP/GFR equal to or lower than 2.8mg/dl GFR. In the total sample, a direct correlation was observed between TRP and TP/GFR (r = 0.65; p = 0.01). The TRP and the percent tubular reabsorption of phosphate values were the same in the three groups (r = 1; p = 0.01). TRP and TP/GFR are similar parameters. TRP is more effective than TP/GFR given that in renal hypophosphatemia it is always below 95% and above 95% in reduced phosphatemia and normal kidney proximal tubular function. There is no solid reason for using TP/GFR rather than TRP. A higher resolution version of the Graphical abstract is available as Supplementary information.

Can DPP-4 Enhibitors and SGLT-2 Inhibitors Pleotropic Effects be Extended to Treat Diabetic Nephropathy?

Impaired insulin secretion and resistance remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. Diabetic nephropathy is one of the most common microvascular complications and a major cause of end-stage renal disease. Despite many treatment options available, diabetic kidney disease continues to affect a large population with diabetes. The kidneys have the highest DPP-4 expression level in mammalians. DPP- 4 is expressed in several segments of the nephron and the tubule interstitium, placing it at the nexus of inflammation, immune system activation, glomerular and proximal tubular function, salt regulation, and kidney fibrosis. Moreover, DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. DPP-4 inhibition is associated with mitigation of diabetic and hypertensive renal injury and protection of renal function. Renal glucose reabsorption by SGLT proteins is a critical component of glycemic regulation. SGLT2 protein expression is increased in human diabetic nephropathy even with advanced kidney disease indicating that SGLT2 can be an effective target in treatment of diabetic nephropathy. This review article discusses roles played by DPP-4 inhibitors and SGLT-2 inhibitors alone and in combination in diabetic nephropathy supported by clinical evidences. MEDLINE and EMBASE were searched through September 2022. Randomized controlled trials published in English that evaluated SGLT2 inhibitors and/or DPP4 inhibitors in patients with T2DM were selected. J MEDICINE 2023; 24: 43-49

Neural bases characterizing chronic and severe upper-limb motor deficits after brain lesion.

Chronic and severe upper-limb motor deficits can result from damage to the corticospinal tract. However, it remains unclear what their characteristics are and whether only corticospinal tract damage determines their characteristics. This study aimed to investigate the clinical characteristics and neural bases of chronic and severe upper-limb motor deficits. Motor deficits, including spasticity, of 45 patients with brain lesions were assessed using clinical scales. Regarding their scores, we conducted a principal component analysis that statistically extracted the clinical characteristics as two principal components. Using these principal components, we investigated the neural bases underlying their characteristics through lesion analyses of lesion volume, lesion sites, corticospinal tract, or other regional white-matter integrity. Principal component analysis showed that the clinical characteristics of chronic and severe upper-limb motor deficits could be described as a comprehensive severity and a trade-off relationship between proximal motor functions and wrist/finger spasticity. Lesion analyses revealed that the comprehensive severity was correlated with corticospinal tract integrity, and the trade-off relationship was associated with the integrity of other regional white matter located anterior to the posterior internal capsule, such as the anterior internal capsule. This study indicates that the severity of chronic and severe upper-limb motor deficits can be determined according to the corticospinal tract integrity, and such motor deficits may be further characterized by the integrity of other white matter, where the corticoreticular pathway can pass through, by forming a trade-off relationship where patients have higher proximal motor functions but more severe wrist/finger spasticity, and vice versa.

Effect of anti-retroviral regimen on proximal tubular function in Zambian adolescents and young adults living with HIV: A cross sectional study

Background: Tenofovir regimens remain the preferred formulations in the HIV guidelines for adolescents and young adults in Zambia and globally. However, some adolescents and young adults are maintained on abacavir by clinicians because of anxiety about possible proximal tubular dysfunction from tenofovir. We assessed the effect of two regimens on proximal tubular function in adolescents and young adults living with HIV. Methods: This was a cross-sectional study involving 180 participants with HIV receiving either tenofovir or abacavir for ≥12 months at the largest tertiary teaching hospital. Two first-morning urine and blood specimens were collected and analyzed for proximal tubular markers, glomerular function, electrolytes, and routine monitoring tests. Proximal tubular function was determined by measuring the fractional excretion of phosphate (FePO4). Proximal tubular dysfunction was defined by FePO4 ≥20% regardless of serum phosphate and FePO4 ≥10-20% when serum phosphate was below 0.81mmol/L. Results: The prevalence of proximal tubular dysfunction was 6% and was higher in the tenofovir group than the abacavir (10% vs. 2%, p&lt;0.058). However, after adjusting for potential confounders, tenofovir was not associated with worse proximal tubular function. Age, urine b2-microglobulin: creatinine ratio, C-reactive protein, and urine protein: creatinine ratio was all associated with worsening proximal tubular dysfunction. Reduced estimated glomelurar filtration rate (eGFR) was found in four (2.2%) participants; three of which were on tenofovir. Conclusions: Proximal tubular dysfunction defined by FePO4 was more prevalent in the tenofovir group than the abacavir group, but not after adjusting for age. Our findings should be interpreted with caution as age differences between the two groups confounded the results.

Discussion on the form of construction function in the peridynamic differential operator based on relative function

The peridynamic differential operator (PDDO) adopts nonlocal idea, realizes the solution of any order derivative of a function through the integration of a constructed PD function, and expands the motion equation based on function derivative into the nonlocal peridynamic integral equation. Even at the discontinuity, the peridynamic integral equation still has a definition and the form remains unchanged. When calculating any order derivative of a function f(x), two PDDO formulas can be used, one is the PDDO formula based on proximal function f(x + ξ) and the other is PDDO formula based on relative function f(x + ξ) − f(x). The key to using these two formulas is to construct the PD function. This paper discusses the construction method of the PD function in PDDO formula based on relative function. It is found that it can be constructed by supplementing an equation as well as by reducing a construction term of PD polynomial. After derivation, it is found that it is necessary to reduce a construction term that is even power to all variables, and it is invalid to reduce a construction term with an odd power to a certain variable. Numerical examples show that the two construction methods can lead to high-precision calculation results.