When physician supply does not meet patient demand: A looming epidemic in vascular and renal care for a community with the highest incidence of end-stage renal disease in the United States.

BACKGROUND: South Texas and the Rio Grande Valley (RGV) are medically underserved-communities near the Texas-Mexico border with the highest incidence of end-stage renal disease (ESRD) in the nation, and a shortage of available full-time equivalent (FTE) specialty-physicians. METHODS: Data on the incidence/prevalence of ESRD and workforce projections on vascular-surgeons and nephrologists were collected from the United States Renal Data System and Texas Department of State Health Services. We then merged data from both datasets to identify population-specific healthcare-trends. RESULTS: Texas had the highest rates of ESRD from 2016 to 2020, with its border regions leading the state. By 2032, vascular-surgery and nephrology are projected to have the 1st and 4th worst physician-shortages in the state respectively, with the percentage of these FTE specialty-physicians available to meet the need of the RGV ranging from 42.3 to 58.4 â€‹%. CONCLUSIONS: The RGV is experiencing increased rates of ESRD, while having a paradoxical-decline in specialty-physicians available to provide adequate care.

CILOSTAZOL AFTER ENDOVASCULAR THERAPY FOR FEMOROPOPLITEAL PERIPHERAL ARTERIAL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Endovascular therapy (ET) outcomes for femoropopliteal peripheral arterial disease (FP-PAD) remain suboptimal. Cilostazol therapy may improve patency rates and decrease major adverse limb events after ET for FP-PAD. Our goal is to analyze published studies evaluating the use of cilostazol after ET for FP-PAD. METHODS: We searched MEDLINE, EMBASE, and CENTRAL for randomized and observational studies evaluating cilostazol therapy after ET for FP-PAD. We only included observational studies adjusting for confounding variables. We analyzed observational and randomized studies separately and explored heterogeneity by estimating an I2 statistic. A fixed-effects model was chosen if the I2 statistic was low. If the two-sided probability of observing the difference between groups under a true null hypothesis was less than 5%, we considered this difference statistically significant. RESULTS: We screened 2,171 studies and included 26 papers in our analysis (5 randomized and 21 observational studies). All randomized studies were open label. In randomized studies, the odds of restenosis were lower in patients treated with cilostazol (pooled odds ratio (pOR) = 0.28, 95% confidence interval (CI) 0.18 to 0.43, p < 0.01, I2 = 0%). The odds of target lesion revascularization (TLR) were also lower in patients treated with cilostazol (pOR = 0.35, 95% CI 0.22 to 0.65, p < 0.01, I2 = 0%). In observational studies, we also identified associations between peri-interventional treatment with cilostazol and lower rates of restenosis (pooled hazard ratio (pHR) = 0.57, 95% CI 0.51 to 0.65, p <0.01, I2 = 34%), TLR (pHR = 0.53, 95% CI 0.36 to 0.79, p <0.01, I2 = 0%), and amputation (pHR = 0.54, 95% CI 0.32 to 0.90, p = 0.02, I2 = 30%). CONCLUSIONS: In randomized open label studies, peri-interventional treatment with cilostazol after ET for FP-PAD lowered the odds of restenosis and TLR (Level 1A). Similarly, in observational studies that adjusted for confounding, peri-interventional cilostazol therapy was associated with lower rates of restenosis, TLR, and amputation (Level 2A).

Injectable long-acting ivacaftor-loaded poly (lactide-co-glycolide) microparticle formulations for the treatment of cystic fibrosis: In vitro characterization and in vivo pharmacokinetics in mice.

Optimizing a sustained-release drug delivery system for the treatment of cystic fibrosis (CF) is crucial for decreasing the dosing frequency and improving patients' compliance with the treatment regimen. In the current work, we developed an injectable poly(D,L-lactide-co-glycolide) (PLGA) microparticle formulation loaded with ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that increases the open probability of the CFTR anion channel, using a single emulsion solvent evaporation technique. We aimed to study the effect of different parameters on the characteristics of the prepared formulations to select an optimized microparticle formulation to be used in an in vivo pharmacokinetic study in mice. First, a suite of ivacaftor-loaded microparticles were prepared using different formulation parameters in order to study the effect of varying these parameters on microparticle size, morphology, drug loading, encapsulation efficiency, and in vitro release profiles. Prepared microparticles were spherical with diameters ranging from 1.91-6.93 µm, percent drug loading (% DL) of 3.91-10.3%, percent encapsulation efficiencies (% EE) of 26.6-100%, and an overall slow cumulative release profile. We selected the formulation that demonstrated optimal combined % DL and % EE values (8.25 and 90.7%, respectively) for further studies. These microparticles had an average particle size of 6.83 µm and a slow tri-phasic in vitro release profile (up to 6 weeks). In vivo pharmacokinetic studies in mice showed that the subcutaneously injected microparticles resulted in steady plasma levels of ivacaftor over a period of 28 days, and a 6-fold increase in AUC 0 - t (71.6 µg/mL*h) compared to the intravenously injected soluble ivacaftor (12.3 µg/mL*h). Our results suggest that this novel ivacaftor-loaded microparticle formulation could potentially eliminate the need for the frequent daily administration of ivacaftor to people with CF thus improving their compliance and ensuring successful treatment outcomes.

Understanding the burden of traumatic injuries at the United States-Mexico border: A scoping review of the literature.

ABSTRACT: The US-Mexico border is the busiest land crossing in the world and faces continuously increasing numbers of undocumented border crossers. Significant barriers to crossing are present in many regions of the border, including walls, bridges, rivers, canals, and the desert, each with unique features that can cause traumatic injury. The number of patients injured attempting to cross the border is also increasing, but significant knowledge gaps regarding these injuries and their impacts remain. The purpose of this scoping literature review is to describe the current state of trauma related to the US-Mexico border to draw attention to the problem, identify knowledge gaps in the existing literature, and introduce the creation of a consortium made up of representatives from border trauma centers in the Southwestern United States, the Border Region Doing Research on Trauma Consortium. Consortium members will collaborate to produce multicenter up-to-date data on the medical impact of the US-Mexico border, helping to elucidate the true magnitude of the problem and shed light on the impact cross-border trauma has on migrants, their families, and the US health care system. Only once the problem is fully described can meaningful solutions be provided.

Toward Brain-on-a-Chip: Human Induced Pluripotent Stem Cell-Derived Guided Neuronal Networks in Tailor-Made 3D Nanoprinted Microscaffolds.

Brain-on-a-chip (BoC) concepts should consider three-dimensional (3D) scaffolds to mimic the 3D nature of the human brain not accessible by conventional planar cell culturing. Furthermore, the essential key to adequately address drug development for human pathophysiological diseases of the nervous system, such as Parkinson's or Alzheimer's, is to employ human induced pluripotent stem cell (iPSC)-derived neurons instead of neurons from animal models. To address both issues, we present electrophysiologically mature human iPSC-derived neurons cultured in BoC applicable microscaffolds prepared by direct laser writing. 3D nanoprinted tailor-made elevated cavities interconnected by freestanding microchannels were used to create defined neuronal networks-as a proof of concept-with two-dimensional topology. The neuronal outgrowth in these nonplanar structures was investigated, among others, in terms of neurite length, size of continuous networks, and branching behavior using z-stacks prepared by confocal microscopy and cross-sectional scanning electron microscopy images prepared by focused ion beam milling. Functionality of the human iPSC-derived neurons was demonstrated with patch clamp measurements in both current- and voltage-clamp mode. Action potentials and spontaneous excitatory postsynaptic currents-fundamental prerequisites for proper network signaling-prove full integrity of these artificial neuronal networks. Considering the network formation occurring within only a few days and the versatile nature of direct laser writing to create even more complex scaffolds for 3D network topologies, we believe that our study offers additional approaches in human disease research to mimic the complex interconnectivity of the human brain in BoC studies.

Structure-Activity Relationship of RGD-Containing Cyclic Octapeptide and αvß3 Integrin Allows for Rapid Identification of a New Peptide Antagonist.

The αvß3 integrin, a receptor for many extracellular matrix proteins with RGD-sequence motif, is involved in multiple physiological processes and highly expressed in tumor cells, therefore making it a target for cancer therapy and tumor imaging. Several RGD-containing cyclic octapeptide (named LXW analogs) were screened as αvß3 antagonists with dramatically different binding affinity, and their structure-activity relationship (SAR) remains elusive. We performed systematic SAR studies and optimized LXW analogs to improve antagonistic potency. The NMR structure of LXW64 was determined and docked to the integrin. Structural comparison and docking studies suggested that the hydrophobicity and aromaticity of the X7 amino acid are highly important for LXW analogs binding to the integrin, a potential hydrophobic pocket on the integrin surface was proposed to play a role in stabilizing the peptide binding. To develop a cost-efficient and fast screening method, computational docking was performed on LXW analogs and compared with in vitro screening. A consistency within the results of both methods was found, leading to the continuous optimization and testing of LXW mutants via in silico screening. Several new LXW analogs were predicted as the integrin antagonists, one of which-LXZ2-was validated by in vitro examination. Our study provides new insight into the RGD recognition specificity and valuable clues for rational design of novel αvß3 antagonists.

(1)H, (13)C and (15)N resonance assignments and secondary structure analysis of translation initiation factor 1 from Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen and a primary cause of infection in humans. P. aeruginosa can acquire resistance against multiple groups of antimicrobial agents, including ß-lactams, aminoglycosides and fluoroquinolones, and multidrug resistance is increasing in this organism which makes treatment of the infections difficult and expensive. This has led to the unmet need for discovery of new compounds distinctly different from present antimicrobials. Protein synthesis is an essential metabolic process and a validated target for the development of new antibiotics. Translation initiation factor 1 from P. aeruginosa (Pa-IF1) is the smallest of the three initiation factors that acts to establish the 30S initiation complex to initiate translation during protein biosynthesis, and its structure is unknown. Here we report the (1)H, (13)C and (15)N chemical shift assignments of Pa-IF1 as the basis for NMR structure determination and interaction studies. Secondary structure analyses deduced from the NMR chemical shift data have identified five ß-strands with an unusually extended ß-strand at the C-terminal end of the protein and one short α-helix arranged in the sequential order ß1-ß2-ß3-α1-ß4-ß5. This is further supported by (15)N-{(1)H} hetero NOEs. These secondary structure elements suggest the Pa-IF1 adopts the typical ß-barrel structure and is composed of an oligomer-binding motif.