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Abstract Background In parallel with population aging, the prevalence of neurological and neurodegenerative diseases has been dramatically increasing over the past few decades. Neurodegenerative diseases reduce the quality of life of patients and impose a high cost on the health system. These slowly progressive diseases can cause functional, perceptual, and behavioral deficits in patients. Therefore, neurodegenerative impairments have always been an interesting subject for scientists and clinicians. One of these diseases is spinal cord injury (SCI). SCI can lead to irreversible damage and is classified into two main subtypes: traumatic and non‐traumatic, each with very different pathophysiological features. Aims This review aims to gather relevant information about the beneficial effects of curcumin (Cur), with specific emphasis on its anti‐inflammatory properties towards spinal cord injury (SCI) patients. Materials & Methods The review collates data from extensive in‐vitro, in‐vivo, and clinical trials documenting the effects of CUR on SCI. It examines the modulation of pathophysiological pathways and regulation of the inflammatory cascades after CUR administration. Results Various pathophysiological processes involving the nuclear factor erythroid 2‐related factor 2 (Nrf2), nuclear factor kappa B (NF‐kB), and transforming growth factor beta (TGF‐β) signaling pathways have been suggested to exacerbate damages resulting from SCI. CUR administration showed to modulate these signaling pathways which lead to attenuation of SCI complications. Discussion Anti‐inflammatory compounds, particularly CUR, can modulate these pathophysiological pathways and regulate the inflammatory cascades. CUR, a well‐known natural product with significant anti‐inflammatory effects, has been extensively documented in experimental and clinical trials. Conclusion Curcumin's potential to alter key steps in the Nrf2, NF‐kB, and TGF‐β signaling pathways suggests that it may play a role in attenuating SCI complications.

Abstract The study was designed to quantify retina function in a spontaneous mutation mouse model of diabetes, in which sustained dyslipidemia was induced chemically. The goal of the study was to identify if dyslipidemia in the presence of hyperglycemia resulted in either a synergistic, or a merely additive, exacerbation of retinal and visual dysfunctions in diabetes. Two cohorts of mice, male C57BL/6 and C57BL/KsJ-db/db mice were divided into two groups each. One group of each strain received the triblock copolymer, poloxamer 407 (P-407), administered by intraperitoneal injection (“WT P-407” and “db/db P-407” groups) with saline as a control in the remaining two groups (“WT” and “db/db” groups). Blood glucose, total cholesterol (TC) and total triglyceride (TG) levels were quantified using enzyme-based colorimetric assays. Retina function was measured using electroretinography (ERG) and visual acuity was determined by behaviorally assessing parameters of the optomotor reflex. TC and TG levels were normal in both saline controls (WT) and db/db mice but were significantly elevated in the WT P-407 group (p

Keypoints Obesity and NAFLD/NASH are commonly accompanied by inflammation. We tested if serum hs-CRP is associated with indices of NAFLD/NASH and liver fibrosis in morbidly obese patients. hs-CRP was significantly associated with any degree of histologically diagnosed liver damage.

Abstract Sarcopenia is an age‐related muscle disorder typically associated with a poor quality of life. Its definition has evolved over time, and several underlying causes of sarcopenia in the elderly have been proposed. However, the exact mechanisms involved in sarcopenia, as well as effective treatments for this condition, are not fully understood. The purpose of this article was to conduct a comprehensive review of previous evidence regarding the definition, diagnosis, risk factors, and efficacy of plant‐derived natural products for sarcopenia. The methodological approach for the current narrative review was performed using PubMed, Scopus, and Web of Science databases, as well as Google Scholar (up to March 2021) in order to satisfy our objectives. The substantial beneficial effects along with the safety of some plant‐derived natural products including curcumin, resveratrol, catechin, soy protein, and ginseng on sarcopenia are reported in this review. Based on clinical studies, nutraceuticals and functional foods may have beneficial effects on physical performance, including handgrip and knee‐extension strength, weight‐lifting capacity, time or distance travelled before feeling fatigued, mitochondrial function, muscle fatigue, mean muscle fibre area, and total number of myonuclei. In preclinical studies, supplementation with herbs and natural bioactive compounds resulted in beneficial effects including increased plantaris mass, skeletal muscle mass and strength production, increased expression of anabolic factors myogenin, Myf5 and MyoD, enhanced mitochondrial capacity, and inhibition of muscle atrophy and sarcopenia. We found that several risk factors such as nutritional status, physical inactivity, inflammation, oxidative stress, endocrine system dysfunction, insulin resistance, history of chronic disease, mental health, and genetic factors are linked or associated with sarcopenia. The substantial beneficial effects of some nutraceuticals and functional foods on sarcopenia, including curcumin, resveratrol, catechin, soy protein, and ginseng, without any significant side effects, are reported in this review. Plant‐derived natural products might have a beneficial effect on various components of sarcopenia. Nevertheless, due to limited human trials, the clinical benefits of plant‐derived natural products remain inconclusive. It is suggested that comprehensive longitudinal clinical studies to better understand risk factors over time, as well as identifying a treatment strategy for sarcopenia that is based on its pathophysiology, be undertaken in future investigations.

Abstract The statin family of drugs are safe and effective therapeutic agents for the treatment of arteriosclerotic cardiovascular disease (CVD). Due to a wide range of health benefits in addition to their cholesterol lowering properties, statins have recently attracted significant attention as a new treatment strategy for several conditions, which are not directly related to normalizing a lipid profile and preventing CVD. Statins exert a variety of beneficial effects on different aspects of oral health, which includes their positive effects on bone metabolism, their anti-inflammatory and antioxidant properties, and their potential effects on epithelization and wound healing. Additionally, they possess antimicrobial, antiviral, and fungicidal properties, which makes this class of drugs attractive to the field of periodontal diseases and oral and dental health. However, to the best of our knowledge, there has been no comprehensive study to date, which has investigated the effects of statin drugs on different aspects of dental and oral health. Therefore, the primary objective of this paper was to review the effect of statins on dental and oral health. Results of our extensive review have indicated that statins possess remarkable and promising effects on several aspects of dental and oral health including chronic periodontitis, alveolar bone loss due to either extraction or chronic periodontitis, osseointegration of implants, dental pulp cells, orthodontic tooth movement, and orthodontic relapse, tissue healing (wound/bone healing), salivary gland function, and finally, anti-cancer effects. Hence, statins can be considered as novel, safe, inexpensive, and widely-accessible therapeutic agents to improve different aspects of dental and oral health.

Nonalcoholic fatty liver disease (NAFLD) is initiated by excessive fat buildup in the liver, affecting around 35% of the world population. Various circumstances contribute to the initiation and progression of NAFLD, and it encompasses a wide range of disorders, from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. Although several treatments have been proposed, there is no definitive cure for NAFLD. In recent decades, several medications related to other metabolic disorders have been evaluated in preclinical studies and in clinical trials due to the correlation of NAFLD with other metabolic diseases. Fenofibrate is a fibrate drug approved for dyslipidemia that could be used for modulation of hepatic fat accumulation, targeting peroxisome proliferator-activator receptors, and de novo lipogenesis. This drug offers potential therapeutic efficacy for NAFLD due to its capacity to decrease the accumulation of hepatic lipids, as well as its antioxidant, anti-inflammatory, and antifibrotic properties. To better elucidate the pathophysiological processes underlying NAFLD, as well as to test therapeutic agents/interventions, experimental animal models have been extensively used. In this article, we first reviewed experimental animal models that have been used to evaluate the protective effects of fenofibrate on NAFLD/NASH. Next, we investigated the impact of fenofibrate on the hepatic microcirculation in NAFLD and then summarized the beneficial effects of fenofibrate, as compared to other drugs, for the treatment of NAFLD. Lastly, we discuss possible adverse side effects of fenofibrate on the liver.

Abstract The oral route of drug administration is the most common and convenient route for dosing statin drugs, and, in fact, most medications, because of ease of drug delivery, patient compliance, and cost-effectiveness. However, the oral administration of statin drugs has disadvantages such as hepatic first-pass metabolism and degradation within the gastrointestinal tract that limit their overall bioavailability. This review introduces several diverse non-oral delivery methods for the administration of statins. These alternative delivery systems and routes of administration are varied and are capable of improving the bioavailability and therapeutic efficacy of statin drugs.

Introduction: Oxidative stress (OS) during uncontrolled hyperglycemia has a pivotal role in pancreatic dysfunction. Our study aimed to demonstrate that crocin can potentiate anti-oxidant defense systems of pancreatic cells to improve oxidative stress. Methods: Male Wistar rats were divided randomly into four groups: a normal group, a normal-treated group, a diabetic group and a diabetic-treated group (n = 6 rats per group). Diabetes was induced by a single dose of streptozotocin (45 mg/kg/IV). The treated groups received crocin daily for 8 weeks (40 mg/kg/IP). At the end of the experiment, rats were sacrificed and pancreas tissue was obtained. Subsequently, the concentrations of malondialdehyde (MDA), nitrate and glutathione as well as the enzymatic activities of catalase and superoxide dismutase (SOD) were determined in all animals. Data were analyzed by two-way ANOVA with appropriate post hoc testing and a probability value of P < 0.05 was considered to represent a statistically significant difference in mean values. Results: Uncontrolled hyperglycemia weakened the anti-oxidant system by decreasing SOD and catalase enzyme activity in pancreatic tissues and induced OS by increasing the MDA content in diabetic non-treated animals. Crocin potentiated the anti-oxidant defense system by increasing the activity of both SOD and catalase, and improved OS by diminishing MDA production in pancreatic cells of rats contained in the diabetic-treated group. Conclusion: Based on our results, it is concluded that uncontrolled hyperglycemia can weaken the anti-oxidant defense system and cause the development of OS. Also, crocin can improve OS in pancreatic cells by potentiating the anti-oxidant defense system.

Abstract. Traditional methods of inducing hyperlipidemia in animal models are either costly (genetic manipulation) or it is difficult to control for the effects of other variables. For example, during high-fat feeding, the amount of high-fat diet intake per animal cannot be precisely controlled. The aim of this study was to develop an experimental model of fatty organ degeneration induced by poloxamer 407 (P-407). The study was conducted in 2-month-old, male Sprague-Dawley rats that were administered intraperitoneally with either 10% (w/w) P-407 (1 g/kg) or saline (10 mL/kg) for 4 months. Their lipid profile, organ degeneration due to fat deposition, and body mass were assessed. Intraperitoneal administration of P-407 resulted in significant increases in plasma triglycerides (P ≤ 0.001), total cholesterol (P

Diabetic retinopathy (DR) is a significant cause of vision loss and a research subject that is constantly being explored for new mechanisms of damage and potential therapeutic options. There are many mechanisms and pathways that provide numerous options for therapeutic interventions to halt disease progression. The purpose of the present literature review is to explore both basic science research and clinical research for proposed mechanisms of damage in diabetic retinopathy to understand the role of triglyceride and cholesterol dysmetabolism in DR progression. This review delineates mechanisms of damage secondary to triglyceride and cholesterol dysmetabolism vs. mechanisms secondary to diabetes to add clarity to the pathogenesis behind each proposed mechanism. We then analyze mechanisms utilized by both triglyceride and cholesterol dysmetabolism and diabetes to elucidate the synergistic, additive, and common mechanisms of damage in diabetic retinopathy. Gathering this research adds clarity to the role dyslipidemia has in DR and an evaluation of the current peer-reviewed basic science and clinical evidence provides a basis to discern new potential therapeutic targets.

CD47 is a receptor belonging to the immunoglobulin (Ig) superfamily and broadly expressed on cell membranes. Through interactions with ligands such as SIRPα, TSP-1, integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), CD47 regulates numerous functions like cell adhesion, proliferation, apoptosis, migration, homeostasis, and the immune system. In this aspect, previous research has shown that CD47 modulates phagocytosis via macrophages, the transmigration of neutrophils, and the activation of T-cells, dendritic cells, and B-cells. Moreover, several studies have reported the increased expression of the CD47 receptor in a variety of diseases, including acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), bladder cancer, acute myeloid leukemia (AML), Gaucher disease, Multiple Sclerosis and stroke among others. The ubiquitous expression of the CD47 cell receptor on most resident cells of the CNS has previously been established through different methodologies. However, there is little information concerning its precise functions in the development of different neurodegenerative pathologies in the CNS. Consequently, further research pertaining to the specific functions and roles of CD47 and SIRP is required prior to its exploitation as a druggable approach for the targeting of various neurodegenerative diseases that affect the human population. The present review attempts to summarize the role of both CD47 and SIRP and their therapeutic potential in neurodegenerative disorders.

The concept of lysosomotropic agents significantly changed numerous aspects of cellular biochemistry, biochemical pharmacology, and clinical medicine. In the present review, we focused on numerous low-molecular and high-molecular lipophilic basic compounds and on the role of lipophagy and autophagy in experimental and clinical medicine. Attention was primarily focused on the most promising agents acting as autophagy inducers, which offer a new window for treatment and/or prophylaxis of various diseases, including type 2 diabetes mellitus, Parkinson’s disease, and atherosclerosis. The present review summarizes current knowledge on the lysosomotropic features of medical drugs, as well as autophagy inducers, and their role in pathological processes.

Recent evidence suggests that lipoproteins serve as circulating reservoirs of peroxisomal proliferator activated receptor (PPAR) ligands that are accessible through lipolysis. The present study was conducted to determine the biochemical basis of PPAR-α activation by lipolysis products and their contribution to PPAR-α function in vivo. PPAR-α activation was measured in bovine aortic endothelial cells following treatment with human plasma, VLDL lipolysis products, or oleic acid. While plasma failed to activate PPAR-α, oleic acid performed similarly to VLDL lipolysis products. Therefore, fatty acids are likely to be the PPAR-α ligands generated by VLDL lipolysis. Indeed, unbound fatty acid concentration determined PPAR-α activation regardless of fatty acid source, with PPAR-α activation occurring only at unbound fatty acid concentrations that are unachievable under physiological conditions without lipase action. In mice, a synthetic lipase inhibitor (poloxamer-407) attenuated fasting-induced changes in expression of PPAR-α target genes. Apolipoprotein CIII (apoCIII), an endogenous inhibitor of lipoprotein and hepatic lipase, regulated access to the lipoprotein pool of PPAR-α ligands, because addition of exogenous apoCIII inhibited, and removal of endogenous apoCIII potentiated, lipolytic PPAR-α activation. These data suggest that the PPAR-α response is generated by unbound fatty acids released locally by lipase activity and not by circulating plasma fatty acids.

STUDIES were carried out to evaluate the impact of a high-fat dietary regimen on aortic wall thickness, peripheral blood leukocyte profile, and plasma cholesterol and triglyceride levels in the mast cell-deficient Sl/Sld mouse. The results demonstrated that the mean aortic wall thickness of Sl/Sld mice was significantly higher than their normal littermates, and were increased in both genotypes after a 17-day high-fat regimen. In comparison with normal littermates, Sl/Sld genotypes had elevated levels of plasma triglycerides with normal levels of plasma cholesterol, and the high-fat diet markedly lowered the triglyceride levels. Total peripheral blood leukocytes, the monocyte and granulocyte counts, and hemoglobin levels were significantly lower in Sl/Sld mice, although the number of lymphocytes, eosinophils and basophils were the same in both genotypes. Interestingly, the high-fat diet regimen elevated leukocyte counts and the number of monocytes and granulocytes in Sl/Sld mice.

Coronary heart disease secondary to atherosclerosis is still the leading cause of death in the US. Animal models used for elucidating the pathogenesis of this disease primarily involve rabbits and pigs. Previous studies from this laboratory have demonstrated intraperitoneal injections of poloxamer 407 (P-407) in both male and female mice will lead to hyperlipidemia and atherosclerosis, suggesting the use of this polymer to develop a mouse model of atherosclerosis. In order to understand the mechanism of P-407-induced hyperlipidemia and vascular lesion formation, we evaluated the direct effects of P-407 on endothelial cell and macrophage functions in vitro, and its in vivo effects on the oxidation of circulating lipids following long-term (4 month) administration. Our results demonstrated that incubation of P-407 with human umbilical vein endothelial cells in culture did not influence either cell proliferation or interleukin-6 and interleukin-8 production over a concentration range of 0-40 μM. In addition, nitric oxide production by macrophages was not affected by P-407 over a concentration range of 0-20 μM. Finally, we demonstrated that while P-407 could not induce the oxidation of LDL-C in vitro, long-term (4 month) administration of P-407 in mice resulted in elevated levels of oxidized lipids in the plasma. Thus, it is suggested that the formation of atherosclerotic lesions in this mouse model of atherosclerosis does not result from either direct stimulation of endothelial cells or macrophage activation by P-407. Instead, these data would support the premise that oxidation of lipids (perhaps low-density lipoprotein cholesterol) by an indirect mechanism following injection of P-407 may represent one of the mechanisms responsible for atheroma formation.

The article presents a study that determines how the plasma levels of cell adhesion molecules (CAMs) can be modulated in mice with dyslipidemia that is induced by polaxemer 407. The study is undertaken through the administration of polaxemer 407 and plasma concentrations of lipid fractions in a mouse model. The results of the study show that the atherogenic profile of the mouse model is related to the plasma model.

The copolymer surfactant poloxamer 407 (P-407) has been used to induce a dose-controlled dyslipidaemia in both mice and rats. Human macrophages cultured with P-407 exhibit a concentration-dependent reduction in cholesterol efflux to apolipoprotein A1 (apoA1) due to down-regulation of the ATP-binding cassette transporter A1 (ABCA1). Peroxisome proliferator-activated receptor alpha (PPARα) can increase expression of liver X receptor alpha (LXRα) in macrophages and thereby promote the expression of ABCA1, which, in turn, mediates cholesterol efflux to apoA1. This study investigated point(s) along this signalling pathway at which P-407 might act to inhibit cholesterol efflux from macrophages. A transactivation assay was used to evaluate whether P-407 could either activate PPARα or block the activation of PPARα by an established PPARα agonist. P-407 was also evaluated for its potential to alter plasma lipid concentrations following its administration to both normal C57BL/6 and PPARα-deficient mice. P-407 was unable to modulate PPARα activity, as determined in cell-based transactivation assays. Moreover, P-407-induced dyslipidaemia occurred at the same rate and to the same extent in PPARα-deficient mice as was observed in C57BL/6 mice, suggesting no role for PPARα in P-407-mediated dyslipidaemia. Although PPARs are known to mediate the transcriptional regulation of the two major apolipoproteins associated with HDL (apoA1 and apoA2), P-407 treatment resulted in a similar decrease (∼30%) in the plasma concentration of apoA1 in both control and PPARα-deficient mice. Since our previous work demonstrated that P-407 was unable to abrogate the capacity of a known LXRα agonist to increase cholesterol efflux from macrophages, P-407 is likely to exert its effect, either directly or indirectly, on ABCA1, rather than on LXRα. On the basis of these findings it is concluded that PPARα does not mediate the P-407-dependent reduction in apoA1-facilitated cholesterol efflux from macrophages. [ABSTRACT FROM AUTHOR]

Purpose. The current investigation was conducted to examine the effect of secondary structure of model polypeptides on their hindered paracellular diffusion. Methods. Poly-D-glutamic acid (PDGlu) was selected as one of the model polypeptides because of its ability to form two secondary structures; a negatively charged random coil and an α-helix with partial negative charge at pH 7.4 and 4.7, respectively. Poly-d-lysine (PDL) was selected as a positively charged random coil conformation at pH 7.4. Transport experiments were conducted across both a Caco-2 cell monolayer and the intestinal membrane of Sprague-Dawley rats. Additionally, using NMR, an estimation for the diffusion coefficient and the equivalent hydrodynamic radius for each model polypeptide was obtained. Results. PDGlu in the randomly coiled conformation exhibited greater paracellular transport when compared to either the same polypeptide having an α-helix secondary structure or the positively charged, randomly coiled PDL. Conclusions. Randomly coiled PDGlu was able to permeate through the negatively charged tight junctions of both biological membranes to a greater extent than PDGlu having an α-helix structure and suggests that molecular flexibility associated with the random coil conformation may play a more important role than overall charge and hydrodynamic radius on its hindered paracellular diffusion. [ABSTRACT FROM AUTHOR]

When engaging in a task, individuals may prioritize the task’s results (i.e., the outcome), or they may focus on the task in and of itself (i.e., the process). Previous conceptualizations of outcome and process orientations have focused on population- and context-specific motives rather than people’s general proclivity toward these orientations across diverse tasks. Using a context-generalized outcome and process measure, we examined whether older adults (Mage = 72.8) and younger adults (Mage = 18.0) varied in their outcome and process orientations, and explored how these differences were related to temporal focus. The results indicated that, compared to their younger counterparts, older adults were more process oriented, and focused more on the present. Meanwhile, younger adults were more outcome oriented and focused more on the past and the future compared to older adults. Mediation analyses further revealed that older adults were more present focused due to their heightened process orientation, while younger adults were more past and future focused due to their outcome orientation. The implications of these findings in applied settings such as the workplace, health promotion, and business are discussed.

Water resource development can alter the movement and ecology of sturgeons. We studied total (THg) and methylmercury concentrations in whole blood sampled non-lethally from namew (Moose Cree L-dialect, lake sturgeon, Acipenser fulvescens), an endangered and culturally important subsistence fish. Namew were sampled from two tributaries within the Moose Cree Homeland: the Lower Mattagami River (an impacted system with four hydroelectric generating stations) and the North French River (a reference system that is free-flowing system with no development). Results indicated namew from the North French River had higher blood [THg] than those from the Mattagami River. Further modeling showed that trophic position was the primary driver of these differences, with North French namew having the highest nitrogen isotope ratios. Based on further isotope modeling, crayfish were major components of namew diet at all sites, while other prey items differed between sites. Specifically, namew with unobstructed access to the lower watershed had notably more enriched isotope values when compared to the freshwater benthic macroinvertebrates sampled, implying that other prey not captured herein may contribute to their diets and [THg]. Overall, we found differences in namew’s trophic ecology but no elevation in blood mercury levels at a site impacted by hydroelectric operations 60+ years post-impoundment.

Abstract Background Epstein–Barr virus (EBV) infection is ubiquitous and in sub-Saharan Africa, occurs early in life. In a population-based rural African cohort, we leveraged historical samples from the General Population Cohort (GPC) in Uganda to examine the epidemiology of infection with EBV over time, in the era of HIV. Methods We used 9024 serum samples collected from the GPC in 1992, 2000, 2008, from 7576 participants across the age range (0–99 years of age) and tested for anti-EBV immunoglobulin G (IgG) antibodies to EAd, VCA, and EBNA-1 using a multiplex bead-based assay. The related gammaherpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV) seropositivity was also determined by detection of anti-KSHV IgG antibodies to K8.1 or ORF73 measured by recombinant protein enzyme-linked immunosorbent assay. Data on sex, age, and HIV serostatus were also collected. EBV seropositivity was modeled with age (excluding those under one year, who may have had maternal antibodies), sex, HIV serostatus, and KSHV serostatus using generalized linear mixed effects models to produce beta estimates. Results More than 93% of children were EBV seropositive by one year of age. EBV seropositivity was significantly associated with KSHV seropositivity. Anti-EBNA-1 antibody levels decreased with increasing age and were lower on average in people living with HIV. In general, anti-EAd antibody levels increased with age, were higher in males and KSHV seropositive persons, but decreased over calendar time. Anti-VCA antibody levels increased with age and with calendar time and were higher in KSHV seropositive persons but lower in males. Conclusions This is the first study to identify factors associated with EBV antibodies across the entire life-course in rural sub-Saharan Africa. Consistent with other studies, EBV was near ubiquitous in the population by age one year. Patterns of antibodies show changes by age, sex and calendar time, but no association with HIV was evident, suggesting no relationship between EBV sero-epidemiology and the spread of HIV in the population over time in Uganda.

Category: Midfoot/Forefoot; Trauma Introduction/Purpose: Navicular fractures are uncommon foot fractures and there is scarce literature exploring the complications and radiologic outcomes of these fractures. The aim of this study is to examine fracture patterns and surgical data to see the effect they have on complications and radiographic outcomes after open reduction internal fixation of the navicular. Methods: A retrospective study was performed to identify patients who underwent operative treatment of a navicular fracture over a nine-year period (2013-2022). Patients were screened by review of CPT codes that included tarsal fractures and imaging review was used to identify those with navicular fractures. Minimum follow-up for inclusion was 6 months. Patient demographics were recorded and radiographs were reviewed and fractures were classified per the Sangeorzan and Schmid classification systems. Surgical data including approach(es), implants, and supplemental fixation was recorded. Postoperative radiographs were assessed for the presence of union, avascular necrosis, foot collapse, and arthritis. Complications defined as infection, unanticipated reoperation, and amputation were recorded. Results: 38 patients met inclusion criteria. 8 patients had a postoperative complication (21.1%). There was 1 superficial infection (2.6%) and 7 patients needed unanticipated reoperations: 2 (5.3%) for wound dehiscence, two (5.3%) for secondary arthritis, and 3 for symptomatic hardware removal (7.9%). Radiologic outcomes consisted of 7 cases of TNJ arthritis (18.4%), 6 cases of avascular necrosis (15.8%), and 7 cases of foot collapse (18.4%). There were significantly increased rates of TNJ arthritis in Schmid type III navicular fractures compared to type I and II (7 vs 0 vs 0, respectively; p=0.021), with 35% of Schmid type IIIs going on to develop TNJ arthritis. The need for reoperation of the navicular was increased if patients required a TNJ spanning construct [2 (50%) vs 2 (5.9%), p=0.007]. Conclusion: Navicular fractures that require ORIF have a high complication rate and a likelihood of developing suboptimal radiographic outcomes. We found that patients who dislocate their TNJ (Schmid Type-III), had an increased rate of TNJ arthritis which likely stems from the more severe nature of the injury, the keystone role of the navicular and the instability present across Chopart’s joint. For patients requiring a TNJ spanning construct there was an increased risk for unanticipated reoperation likely due to the size and nature of the spanning construct hardware. Patient education on these risk factors will guide treatment options and set proper expectations.

In most countries around the world, the population is rapidly aging. A by-product of these demographic shifts is that older adults will likely occupy more positions of power and influence in our societies than ever before. Further, cultural differences might shape how these transitions unfold around the globe. Across two studies, we investigated whether business and political leaders differed in age across various cultures. Study 1 (N = 1,034) showed that business leaders were significantly older in Eastern (e.g., China, India, and Japan) cultures than Western (e.g., United States, Sweden, and United Kingdom) cultures, even while controlling for population structure (e.g., percentage of elderly in the society), gross domestic product (GDP), and wealth distribution across the population (GINI). Study 2 (N = 1,268) conceptually replicated these findings by showing that political leaders were once again older in Eastern vs. Western cultures. Furthermore, cultural tightness mediated the relationship between culture and older leadership. These findings highlight how cultural differences impact not only our preferences, but also important outcomes in consequential domains such as business and politics. Potential explanations for why cultural tightness may be related to differences in leader age across cultures are discussed. To build on these findings, future research should assess the potential causal mechanisms underlying the cultural effect on leader age, and explore the various practical implications of this effect.