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Diabetic foot ulcers (DFU) are a major sequela of uncontrolled diabetes with a high risk of adverse outcomes. Poor DFU outcomes disproportionately impact patients living in rural and economically distressed communities with lack of access to consistent, quality care. This study aimed to analyze the risk of geographic and economic disparities, including rural status and county economic distress, on the disease burden of DFU at presentation utilizing the SVS WIfI classification system. We conducted a retrospective review of 454 patients diagnosed with a DFU from 2011 to 2020 at a single institution's inpatient and outpatient wound care service. Patients >18 years old, with type II diabetes mellitus, and diabetic foot ulcer were included. ANCOVA analyses showed rural patients had significantly higher WIfI composite scores (F(1,451) = 9.61, p = .002), grades of wound (F(1,439) = 11.03, p = .001), and ischemia (F(1,380) = 12.574, p = .001) compared to the urban patients. Patients that resided in at-risk economic counties had significantly higher overall WIfI composite scores (F(2,448) = 3.31, p = .037) than patients who lived in transitional economic counties, and higher foot infection grading (F(2,440) = 3.02, p = .05) compared to patients who lived in distressed economic counties. DFU patients who resided in distressed economic counties presented with higher individual grades of ischemia (F(2, 377) = 3.14, p = .04) than patients in transitional economic counties. Chi-Square analyses demonstrated patients who resided in urban counties were significantly more likely to present with grade 1 wounds (χ2(3) = 9.86, p = .02) and grade 0 ischemia (χ2(3) = 16.18, p = .001) compared to patients in rural areas. Economically distressed patients presented with significantly less grade 0 ischemia compared to patients in transitional economic counties (χ2(6) = 17.48, p = .008). Our findings are the first to demonstrate the impact of geographic and economic disparities on the disease burden of DFU at presentation utilizing the SVS WIfI classification system. This may indicate need for improved multidisciplinary primary care prevention strategies with vascular specialists in these communities to mitigate worsening DFU and promote early intervention. •Diabetic Foot Ulcer patients in rural areas are significantly more likely to present with higher grades of wound and ischemia of foot ulcer.•Diabetic Foot Ulcer patients in economically distressed counties are significantly more likely to present with higher grades of ischemia of foot ulcer.•Rural-residing Diabetic Foot Ulcer patients had greater overall disease burden of foot ulcer compared to urban-residing patients.

High-energy open fractures of the tibia are frequently associated with tissue loss, wound contamination, and compromised vascularity that often result in amputation. The management of these severe injuries remains a challenge for orthopedic reconstructive surgeons. Studies have compared the timing of soft tissue coverage of Gustilo type IIIB open tibia fractures with associated outcomes such as rate of deep infection, primary union, length of hospitalization, flap failure, and eventual secondary amputation. These studies often highlight better outcomes with specific time domains that are not always attainable at a large tertiary hospital with multi-system trauma patients. Many studies do not account for delayed patient transfers after initial open fracture management elsewhere. This retrospective analysis of the limb salvage outcomes included 140 consecutive patients with Gustilo type IIIB open tibia fractures who presented to the authors' level I trauma center between 2001 and 2014. The authors included patients who required delayed coverage or who were transferred from outside institutions. The majority (77%) were male, and the mean age was 39.4 years. Motor vehicle accidents were the most common cause of injury, and 83% of patients obtained full weight-bearing status with successful limb salvage. Twenty patients had a secondary amputation, with the cause being refractory osteomyelitis in 52%. This study provides guidance on treating a heterogeneous patient population with severe open tibia fractures typically seen in a large tertiary hospital orthopedic trauma service. [ Orthopedics . 2019; 42(5):260–266.]

Background MUTYH‐associated polyposis is a rare disorder resulting from mutations involved in DNA mismatch repair. This results in an increased susceptibility to colonic adenomatosis and other cancers. Studies have examined the resulting frequency of extracolonic manifestations; however, these typically occur alone, concurrently, or temporally separate from an already diagnosed colorectal cancer in individuals with a biallelic mutation. Case Reported here is a case of five distinct primary neoplasms presenting simultaneously in a patient monoallelic for an MYH mutation. These neoplasms included squamous cell carcinoma of the vulva, rectal adenocarcinoma, synchronous anal adenocarcinoma, papillary thyroid carcinoma, and ovarian serous psammocarcinoma. Throughout her course, she underwent multiple surgical procedures, neoadjuvant chemoradiation, with further adjuvant therapy, and treatment ongoing. Due to her unique presentation, she underwent genetic testing that demonstrated she was monoallelic for an MYH mutation. Conclusion The patient had a positive response to her treatment and surgical procedures with ongoing adjuvant therapy. She will continue to undergo further genetic testing, and testing for her children is being considered. This case demonstrates a unique presentation associated with a monoallelic MYH mutation that is not described in the current literature and warrants further investigation.

BackgroundPrior studies have associated nighttime transfer of patients from the intensive care unit (ICU) with increased morbidity. This study sought to examine this relationship in traumatically injured patients, as this has not been previously performed.MethodsA retrospective review of traumatically injured patients admitted to a Level I Trauma Center’s ICU from January 2021 to September 2022 was performed. “Day shift” (DS) was defined as 07:00 to 19:00 and “night shift” (NS) as 19:01 to 06:59. The time of transfer completion was based on the time of the patient arrival at the destination unit. The univariate analysis compared patients with completed transfers during DS and NS. Multivariate logistic regression was performed to predict readmission to the ICU.ResultsA total of 1,800 patients were included in the analysis, with 608 patients that had completed transfers during NS, and 1,192 during DS. Both groups were similar, with no significant differences in age, sex, Injury Severity Score (ISS), mechanism of injury, or median total comorbidities. The NS group had a longer median time to transfer completion (10.1 (IQR 5.5–13.6) hours vs 5.1 (IQR 2.9–8.4) hours; p<0.001). A significantly higher proportion of the NS group had a readmission to the ICU (60 (10.0%) vs 86 (7.0%); p=0.03) or a major complication (72 (11.9%) vs 107 (9.0%); p=0.048). When controlling for age, comorbidities, ISS, time to bed assignment and to transfer completed, and ICU length of stay, transfer completion during NS was associated with 1.56 times higher odds of having an ICU readmission (OR 1.56 (95% CI 1.05, 2.33); p=0.03).ConclusionsTrauma patients transferred from the ICU during NS experienced longer delays, readmission to the ICU, and major complications significantly more often. With increasing hospital bed shortages, patient transfers must be analyzed to minimize worsened outcomes, especially in traumatically injured patients.Level of evidenceLevel III, therapeutic/care management.

The bZIP gene superfamily is a family of transcription factors that have gone through multiple duplication events within bilaterians, specifically in vertebrates. This has led to multiple paralogs in each bZIP family while early diverging phyla have a single ortholog. These duplication events have motivated questions if the paralogs evolved to have new functions (neofunctionalization) or evolved to split the functions of the ancestor ortholog (subfunctionalization). The transcription factor, Nuclear Factor Erythroid 2 (NFE2) duplicated within vertebrates into at least four paralogs of Nrf1, Nrf2, Nrf3, and Nf-e2. Of these paralogs Nrf2 is well studied and has been characterized to upregulate antioxidant genes to alleviate stress from oxidizing molecules such as reactive oxygen species in the cell. The other three paralogs are involved proteasomal activity, redox homeostasis, and developmental processes. Knowing these paralogs have differing roles in vertebrates, NFE2 needs to be studied in an organism that has a single ortholog to decipher between neofunctionalization vs. subfunctionalization. Cnidarians are an insightful group to study NFE2 due to being sister group to bilaterians and possess a single ortholog. Using the sea anemone Nematostella vectensis as a model my research was focused to provide information on the ancestral function of NFE2 to compare with vertebrate paralogs and orthologs present in other invertebrates. In this study, database, phylogenetic, and molecular approaches were used to identify domains within and establish an interactome to begin characterization of function of Nematostella NFE2. Domain comparisons in NFE2 throughout animals showed that cnidarians have core domains important for DNA binding but lack some that elicit protein-protein interactions. In studying what proteins interact with Nematostella NFE2 I characterized an antibody specific to NFE2 to perform proteomic analysis. Of the resulting hundreds of characterized interactors, few were commonly characterized in vertebrates. From this proteomic analysis, cnidarian NFE2 may have a protein interactome unique in comparison to vertebrates, regulation mechanisms. Future research to characterize these proteins have been summarized to better understand the mechanisms of NFE2 regulation in animal evolution.

Increased activity of leucine-rich repeat kinase 2 (LRRK2) is an important risk factor for Parkinson's disease. LRRK2 localizes to lysosomal membranes, and changes in lysosome physiology are emerging as key regulators of its activation, yet the mechanisms by which distinct perturbations engage this kinase remain unclear. Analysis of osmotic and membrane-integrity challenges revealed that LRRK2 integrates multiple upstream cues through parallel interactions with Rab GTPases and GABARAP. Manipulations that caused lysosome enlargement, including inhibition of PIKfyve, showed that osmotic swelling leads to the accumulation of multiple Rabs on lysosomes and Rab-dependent LRRK2 activation independently of GABARAP. In contrast, under conditions of lysosome deacidification, CASM-dependent lipidation of GABARAP creates a platform that cooperates with Rabs in LRRK2 activation. These findings demonstrate how LRRK2 interprets perturbations of lysosome function through a combination of Rab- and GABARAP-dependent mechanisms, providing a framework for understanding both normal physiological regulation and pathological dysregulation in Parkinson's disease.

Background A genome-wide assessment of nucleotide diversity in a polyploid species must minimize the inclusion of homoeologous sequences into diversity estimates and reliably allocate individual haplotypes into their respective genomes. The same requirements complicate the development and deployment of single nucleotide polymorphism (SNP) markers in polyploid species. We report here a strategy that satisfies these requirements and deploy it in the sequencing of genes in cultivated hexaploid wheat ( Triticum aestivum , genomes AABBDD) and wild tetraploid wheat ( Triticum turgidum ssp. dicoccoides , genomes AABB) from the putative site of wheat domestication in Turkey. Data are used to assess the distribution of diversity among and within wheat genomes and to develop a panel of SNP markers for polyploid wheat. Results Nucleotide diversity was estimated in 2114 wheat genes and was similar between the A and B genomes and reduced in the D genome. Within a genome, diversity was diminished on some chromosomes. Low diversity was always accompanied by an excess of rare alleles. A total of 5,471 SNPs was discovered in 1791 wheat genes. Totals of 1,271, 1,218, and 2,203 SNPs were discovered in 488, 463, and 641 genes of wheat putative diploid ancestors, T. urartu , Aegilops speltoides , and Ae. tauschii , respectively. A public database containing genome-specific primers, SNPs, and other information was constructed. A total of 987 genes with nucleotide diversity estimated in one or more of the wheat genomes was placed on an Ae. tauschii genetic map, and the map was superimposed on wheat deletion-bin maps. The agreement between the maps was assessed. Conclusions In a young polyploid, exemplified by T. aestivum , ancestral species are the primary source of genetic diversity. Low effective recombination due to self-pollination and a genetic mechanism precluding homoeologous chromosome pairing during polyploid meiosis can lead to the loss of diversity from large chromosomal regions. The net effect of these factors in T. aestivum is large variation in diversity among genomes and chromosomes, which impacts the development of SNP markers and their practical utility. Accumulation of new mutations in older polyploid species, such as wild emmer, results in increased diversity and its more uniform distribution across the genome.