Life Over Limb: Why Not Both? Revisiting Tourniquet Practices Based on Lessons Learned From the War in Ukraine.

The use of tourniquets for life-threatening limb hemorrhage is standard of care in military and civilian medicine. The United States (U.S.) Department of Defense (DoD) Committee on Tactical Combat Casualty Care (CoTCCC) guidelines, as part of the Joint Trauma System, support the application of tourniquets within a structured system reliant on highly trained medics and expeditious evacuation. Current practices by entities such as the DoD and North Atlantic Treaty Organization (NATO) are supported by evidence collected in counter-insurgency operations and other conflicts in which transport times to care rarely went beyond one hour, and casualty rates and tactical situations rarely exceeded capabilities. Tourniquets cause complications when misused or utilized for prolonged durations, and in near-peer or peer-peer conflicts, contested airspace and the impact of high-attrition warfare may increase time to definitive care and limit training resources. We present a series of cases from the war in Ukraine that suggest tourniquet practices are contributing to complications such as limb amputation, overall morbidity and mortality, and increased burden on the medical system. We discuss factors that contribute to this phenomenon and propose interventions for use in current and future similar contexts, with the ultimate goal of reducing morbidity and mortality.

HtrA1 prevents and reverses α-synuclein aggregation, rendering it non-toxic and seeding incompetent.

Parkinson disease (PD) is closely linked to the misfolding and accumulation of α-synuclein (α-syn) into Lewy bodies. HtrA1 is a PDZ serine protease that degrades fibrillar tau, which is associated with Alzheimer disease (AD). Further, inactivating mutations to mitochondrial HtrA2 have been implicated in PD. Here, we establish that HtrA1 inhibits the aggregation of α-syn as well as FUS and TDP-43, which are implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We demonstrate that the protease domain of HtrA1 is necessary and sufficient for inhibition of aggregation, yet this activity is independent of HtrA1 proteolytic activity. Further, we find that HtrA1 also disaggregates preformed α-syn fibrils, which may promote their clearance. Treatment of α-syn fibrils with HtrA1 renders α-syn incapable of seeding the aggregation of endogenous α-syn in mammalian biosensor cells. We find that HtrA1 remodels α-syn by specifically targeting the NAC domain, which is the key domain that catalyzes α-syn oligomerization and fibrillization. Finally, in a primary neuron model of α-syn aggregation, we show that HtrA1 and its proteolytically inactive form both detoxify α-syn and prevent the formation of hyperphosphorylated α-syn accumulations. Our findings suggest that HtrA1 prevents aggregation and promotes disaggregation of multiple disease-associated proteins, and may be a therapeutic target for treating a range of neurodegenerative disorders.

An astrocyte BMAL1-BAG3 axis protects against alpha-synuclein and tau pathology.

The circadian clock protein BMAL1 modulates glial activation and amyloid-beta deposition in mice. However, the effects of BMAL1 on other aspects of neurodegenerative pathology are unknown. Here, we show that global post-natal deletion of Bmal1 in mouse tauopathy or alpha-synucleinopathy models unexpectedly suppresses both tau and alpha-synuclein (αSyn) aggregation and related pathology. Astrocyte-specific Bmal1 deletion is sufficient to prevent both αSyn and tau pathology in vivo and induces astrocyte activation and the expression of Bag3, a chaperone critical for macroautophagy. Astrocyte Bmal1 deletion enhances phagocytosis of αSyn and tau in a Bag3-dependent manner, and astrocyte Bag3 overexpression is sufficient to mitigate αSyn spreading in vivo. In humans, BAG3 is increased in patients with AD and is highly expressed in disease-associated astrocytes (DAAs). Our results suggest that early activation of astrocytes via Bmal1 deletion induces Bag3 to protect against tau and αSyn pathologies, providing new insights into astrocyte-specific therapies for neurodegeneration.

Integrating terrestrial scavenging ecology into contemporary wildlife conservation and management.

Scavenging plays a vital role in maintaining ecosystem health and contributing to ecological functions; however, research in this sub-discipline of ecology is underutilized in developing and implementing wildlife conservation and management strategies. We provide an examination of the literature and recommend priorities for research where improved understanding of scavenging dynamics can facilitate the development and refinement of applied wildlife conservation and management strategies. Due to the application of scavenging research broadly within ecology, scavenging studies should be implemented for informing management decisions. In particular, a more direct link should be established between scavenging dynamics and applied management programs related to informing pharmaceutical delivery and population control through bait uptake for scavenging species, prevention of unintentional poisoning of nontarget scavenging species, the epidemiological role that scavenging species play in disease dynamics, estimating wildlife mortalities, nutrient transfer facilitated by scavenging activity, and conservation of imperiled facultative scavenging species. This commentary is intended to provide information on the paucity of data in scavenging research and present recommendations for further studies that can inform decisions in wildlife conservation and management. Additionally, we provide a framework for decision-making when determining how to apply scavenging ecology research for management practices and policies. Due to the implications that scavenging species have on ecosystem health, and their overall global decline as a result of anthropic activities, it is imperative to advance studies in the field of scavenging ecology that can inform applied conservation and management programs.

VCP suppresses proteopathic seeding in neurons.

BACKGROUND: Neuronal uptake and subsequent spread of proteopathic seeds, such as αS (alpha-synuclein), Tau, and TDP-43, contribute to neurodegeneration. The cellular machinery participating in this process is poorly understood. One proteinopathy called multisystem proteinopathy (MSP) is associated with dominant mutations in Valosin Containing Protein (VCP). MSP patients have muscle and neuronal degeneration characterized by aggregate pathology that can include αS, Tau and TDP-43. METHODS: We performed a fluorescent cell sorting based genome-wide CRISPR-Cas9 screen in αS biosensors. αS and TDP-43 seeding activity under varied conditions was assessed using FRET/Flow biosensor cells or immunofluorescence for phosphorylated αS or TDP-43 in primary cultured neurons. We analyzed in vivo seeding activity by immunostaining for phosphorylated αS following intrastriatal injection of αS seeds in control or VCP disease mutation carrying mice. RESULTS: One hundred fifty-four genes were identified as suppressors of αS seeding. One suppressor, VCP when chemically or genetically inhibited increased αS seeding in cells and neurons. This was not due to an increase in αS uptake or αS protein levels. MSP-VCP mutation expression increased αS seeding in cells and neurons. Intrastriatal injection of αS preformed fibrils (PFF) into VCP-MSP mutation carrying mice increased phospho αS expression as compared to control mice. Cells stably expressing fluorescently tagged TDP-43 C-terminal fragment FRET pairs (TDP-43 biosensors) generate FRET when seeded with TDP-43 PFF but not monomeric TDP-43. VCP inhibition or MSP-VCP mutant expression increases TDP-43 seeding in TDP-43 biosensors. Similarly, treatment of neurons with TDP-43 PFFs generates high molecular weight insoluble phosphorylated TDP-43 after 5 days. This TDP-43 seed dependent increase in phosphorlyated TDP-43 is further augmented in MSP-VCP mutant expressing neurons. CONCLUSION: Using an unbiased screen, we identified the multifunctional AAA ATPase VCP as a suppressor of αS and TDP-43 aggregate seeding in cells and neurons. VCP facilitates the clearance of damaged lysosomes via lysophagy. We propose that VCP's surveillance of permeabilized endosomes may protect against the proteopathic spread of pathogenic protein aggregates. The spread of distinct aggregate species may dictate the pleiotropic phenotypes and pathologies in VCP associated MSP.

The Occurrence of Ophidiomyces ophiodiicola in Northern Georgia Wild and Captive Snake Populations.

Ophidiomycosis, or snake fungal disease, is an emerging wildlife disease caused by the Ophidiomyces ophiodiicola fungus. The fungus can result in high mortality rates among infected snakes and has been documented across much of the eastern US, including southern Georgia. However, little is known about ophidiomycosis in northern Georgia. We surveyed wild snake populations in five counties of northern Georgia between March 2019 and March 2020 and swabbed captured snakes (n=27) for the presence of O. ophiodiicola DNA. We followed similar sampling protocols with a group of captive snakes (n=6) at the Elachee Nature Center in Hall County, Georgia. Quantitative PCR confirmed the presence of O. ophiodiicola DNA in 33% (11/33) of snakes. Eight of the confirmed positive samples were collected from wild snakes (30%, 8/27) across our sample region, while three were from our captive group (50%, 3/6). Our results indicated that O. ophiodiicola is present in wild snake populations in northern Georgia, and the pathogen is present in seemingly healthy captive snakes. This knowledge is critical for conservation and management efforts, but more research is needed to fully understand ophidiomycosis and its effect on snake populations in the region.

PLASMA SEPARATOR TUBES DO NOT HAVE ANY OVERT EFFECTS ON ROUTINE PLASMA CHEMISTRY DATA OF GREEN SEA TURTLES (CHELONIA MYDAS).

Plasma separator tubes (PSTs) are a variant of lithium heparin blood tube containing a polymer gel, which, when centrifuged, creates a physical barrier between plasma and blood cells. Their use is common in laboratory procedures of reptilian species. This study aimed to determine whether the use of plasma separator tubes impacts plasma biochemistry data in green sea turtles (Chelonia mydas) at time of collection and after 24 hr of contact time with the separator gel after centrifugation at refrigerator temperature. A single blood sample was collected from 42 rehabilitating green sea turtles at the Sea Turtle Healing Center, Brevard Zoo, Melbourne, Florida, USA and divided into one lithium heparin tube [LHT (0 hr)] and two PSTs. After immediate centrifugation of all three tubes, plasma was transferred from the LHT (0 hr) and one PST (0 hr) into tubes without additive. The plasma was left in contact with the separator gel in the second PST (24 hr). After 24 hr of refrigeration, all three plasma aliquots were analyzed for the following 23 analytes: sodium, potassium, chloride, carbon dioxide, calcium, phosphorus, magnesium, iron, total protein, albumin, globulin (calculated), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, creatine kinase, glucose, urea nitrogen, creatinine, uric acid, triglyceride, and cholesterol. No statistically significant differences were found for any biochemical analytes between LHT (0 hr), PST (0 hr), and PST (24 hr). The use of PST does not appear to impact routine plasma biochemical analytes in green sea turtles and analytes appear stable in refrigerated plasma for up to 24 hr after centrifugation when using PSTs.

Integrating Trissolcus japonicus (Ashmead, 1904) (Hymenoptera: Scelionidae) into Management Programs for Halyomorpha halys (Stål, 1855) (Hemiptera: Pentatomidae) in Apple Orchards: Impact of Insecticide Applications and Spray Patterns.

Halyomorpha halys (Stål, 1855) (Hemiptera: Pentatomidae) is an invasive species in the United States, where it has caused significant damage to specialty crops, including apples. While integrated pest management techniques have been developed for H. halys in apple, including spray application techniques, it is unknown how these techniques affect foraging, adventive Trissolcus japonicus (Ashmead, 1904) (Hymenoptera: Scelionidae), and its offspring. In this study, egg masses (unparasitized and 2 and 7 day parasitized pre-treatment) were placed in apple orchards in treated and untreated locations that received full block insecticide applications or reduced application techniques, including border row or alternate row middle applications. Bifenthrin, thiamethoxam + λ-cyhalothrin, clothianidin, and methomyl were evaluated. Egg masses were retrieved 24 h after spray applications. For 2 and 7 day parasitized pre-treatment, adult T. japonicus emergence was recorded from each egg mass. For unparasitized egg masses, T. japonicus females were given 24 h to forage and oviposit on post-treatment egg masses with female survivorship, and adult emergence from egg masses was recorded. Female survivorship was significantly lower on post-treatment egg masses retrieved from areas receiving bifenthrin applications. Emergence from post-treatment egg masses was affected by thiamethoxam + λ-cyhalothrin, bifenthrin, and methomyl in some treated areas, whereas less impact was observed on 2 and 7 day pre-treatment parasitized egg masses in general. These data provide further insights into H. halys management and the potential impact of T. japonicus in sprayed orchard agroecosystems.

Smoking is associated with adrenal adenomas and adrenocortical carcinomas: a nationwide multicenter analysis.

MICROABSTRACT: The effect of smoking on adrenal cancer is poorly understood. A clear association of adrenal adenoma and adrenocortical carcinoma with smoking among the United States population is observed. This association points to the possibility of environmental carcinogenic and/or lifestyle factors contributing to adrenal cancer formation. Our results support the association of tobacco use with adrenal adenomas and adrenal cortical carcinoma. BACKGROUND: Smoking has been suggested as a risk factor for adrenal cortical carcinoma (ACC), but this hypothesis has only been inferred from a single study using all types of adrenal cancers including pheochromocytoma, neuroblastoma, as well as ACC. Given the high rate of tobacco use in West Virginia, we hypothesized that smoking might contribute to increased prevalence of ACC. MATERIALS AND METHODS: De-identified institutional review board-exempted records were analyzed in the Surveillance, Epidemiology, and End Results (SEER) Program from 2001-2016 and in patients from the United States nationwide, multicenter TriNetX database of 41,063,707 patients from 2008-2018. In addition, the state-level ratio of smoking to ACC prevalence was computed in all 50 states using data from SEER and the Center for Disease Control. West Virginia Health System data from 2008-2018 was extracted to confirm population-level findings. Melanoma was used as a cancer control in both databases. RESULTS: 6,946 ACC cases were identified. West Virginia had the highest smoking rate and the second highest rate of ACC. A significant association was found between smoking and ACC (Pearson correlation coefficient r = 0.4887, p=.0004). From 2008 to 2018 using TriNetX, 846 ACC and 36,434 AA were extracted. Both adrenal neoplasm cohorts had increased prevalence of tobacco use compared with melanoma controls, where 23.5% were smokers compared to 36.4% and 33.9% in the ACC and AA groups, respectively (p<0.0001 each). CONCLUSION: To our knowledge, this is the first United States population-based study supporting smoking as a risk factor for adrenal carcinogenesis and ACC.

Combined treatment of disfiguring facial angiofibromas in tuberous sclerosis complex with surgical debulking and topical sirolimus.

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder that causes the formation of hamartomatous tumors such as facial angiofibromas (FAs). We present a combination of surgical debulking via shave biopsy, curettage, and electrocautery followed by application of sirolimus ointment 1% to the nose to treat FAs in the setting of TSC. This novel approach achieved an optimal therapeutic response in our patient with minimal recurrence of FAs after 1 year of follow-up.

Three Cases Describing Outcomes of Negative-Pressure Wound Therapy With Instillation for Complex Wound Healing.

BACKGROUND: We describe 3 cases where negative-pressure wound therapy with instillation and dwell time (NPWTi-d) was used as an adjunctive therapy for 3 chronic wounds. CASES: Three patients (2 males and 1 female), ranging in age from 28 to 53 years, presented with complex, infected wounds: (1) a diabetic foot ulcer with underlying infection, (2) a dehisced abdominal wound with enterocutaneous fistula, and (3) a large wound of the upper torso and axillary region resulting from soft tissue necrosis. Negative-pressure wound therapy with instillation and dwell time was initiated by instilling normal saline or an antiseptic solution; the solution was left in place for 3 to 10 minutes. Continuous negative pressure was then applied at -125 or -150 mm Hg; cycles were repeated every 1 or 3 hours. Treatment was applied for 5 to 44 days, and dressings were changed every 2 to 3 days. Granulation tissue developed in all 3 wounds; all closed after subsequent skin grafting. CONCLUSIONS: Outcomes of these cases suggest that NPWTi-d may be used as an adjunctive treatment modality for a variety of chronic wounds.

Xanthogranulomatous Pyelonephritis: A Complicated Febrile Urinary Tract Infection Detected by Point-of-Care Ultrasound in the Emergency Department.

BACKGROUND: Febrile urinary tract infections (UTIs) include a spectrum of pathologies from uncomplicated pyelonephritis to urosepsis, including xanthogranulomatous pyelonephritis (XGP). Most febrile UTIs are treated with antibiotics alone, but studies indicate nearly 12% of cases of presumed simple pyelonephritis require emergent urologic intervention. How to identify these individuals, while limiting unnecessary advanced imaging and delays in diagnosis, challenges all emergency providers. We review the diagnosis and management of XGP, as well as the evidence regarding the role of renal ultrasound in the identification of complicated presentations of febrile UTIs. CASE REPORT: We present a case of XGP, a complicated febrile UTI requiring immediate urologic intervention, diagnosed by point-of-care ultrasound. A 40-year-old female presented in severe sepsis and complaining of flank pain. Prompt bedside ultrasound demonstrated hydronephrosis, expediting definitive urologic treatment via percutaneous nephrostomy tube placement. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: With a mortality rate exceeding 40%, obstructed pyonephrosis requires prompt decompression. Given its exceptional sensitivity for identifying hydronephrosis and ability to detect abscesses and emphysematous changes, we advocate a point-of-care ultrasound-first approach to screen for cases of complicated febrile UTIs in order to expedite treatment and limit radiation in uncomplicated presentations.

Dengue, Zika and Chikungunya: Emerging Arboviruses in the New World.

The arboviruses that cause dengue, chikungunya, and Zika illnesses have rapidly expanded across the globe in recent years, with large-scale outbreaks occurring in Western Hemisphere territories in close proximity to the United States (U.S.). In March 2016, the Centers for Disease Control and Protection (CDC) expanded its vector surveillance maps for A. aegypti and A. albopictus, the mosquito vectors for these arboviruses. They have now been shown to inhabit a larger portion of the U.S., including the heavily populated northeast corridor. Emergency physicians need to further familiarize themselves with these diseases, which have classically been considered only in returning travelers but may soon be encountered in the U.S. even in the absence of travel. In this paper, we discuss the presentation and treatment of dengue, Zika, and chikungunya, as well as special challenges presented to the emergency physician in evaluating a patient with a suspected arbovirus infection.

Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated insulin secretion.

It is well known that mitochondrial metabolism of pyruvate is critical for insulin secretion; however, we know little about how pyruvate is transported into mitochondria in ß-cells. Part of the reason for this lack of knowledge is that the carrier gene was only discovered in 2012. In the current study, we assess the role of the recently identified carrier in the regulation of insulin secretion. Our studies show that ß-cells express both mitochondrial pyruvate carriers (Mpc1 and Mpc2). Using both pharmacological inhibitors and siRNA-mediated knockdown of the MPCs we show that this carrier plays a key role in regulating insulin secretion in clonal 832/13 ß-cells as well as rat and human islets. We also show that the MPC is an essential regulator of both the ATP-regulated potassium (KATP) channel-dependent and -independent pathways of insulin secretion. Inhibition of the MPC blocks the glucose-stimulated increase in two key signaling molecules involved in regulating insulin secretion, the ATP/ADP ratio and NADPH/NADP(+) ratio. The MPC also plays a role in in vivo glucose homeostasis as inhibition of MPC by the pharmacological inhibitor α-cyano-ß-(1-phenylindol-3-yl)-acrylate (UK5099) resulted in impaired glucose tolerance. These studies clearly show that the newly identified mitochondrial pyruvate carrier sits at an important branching point in nutrient metabolism and that it is an essential regulator of insulin secretion.

Chronic treatment with the AMP-kinase activator AICAR increases glycogen storage and fatty acid oxidation in skeletal muscles but does not reduce hyperglucagonemia and hyperglycemia in insulin deficient rats.

This study tested whether the glycogen-accumulating effect of chronic in vivo pharmacological 5'AMP-activated protein kinase (AMPK) activation could improve glycemic control under conditions of insulin deficiency. Male Wistar rats were rendered diabetic through the administration of streptozotocin (STZ) and then treated for 7 consecutive days with the AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR). Subsequently, glycogen content and synthesis, glucose oxidation, and fatty acid oxidation (FAO) were determined in oxidative and glycolytic skeletal muscles. Glycemia, insulinemia, glucagonemia, and circulating triglycerides (TG) and non-esterified fatty acids (NEFAs) were measured after AICAR treatment. Insulin was almost undetectable in STZ rats and these animals were severely hyperglycemic. Glycogen content was markedly low mainly in glycolytic muscles of STZ rats and AICAR treatment restored it to control values. No differences were found among all muscles studied with regards to the content and phosphorylation of Akt/protein kinase B and glycogen synthase kinase 3. Even though glycogen synthase content was reduced in all muscles from STZ rats, insulin-induced dephosphorylation/activation of this enzyme was preserved and unaffected by AICAR treatment. Glucagon and NEFAS were 2- and 7.4-fold fold higher in STZ rats than controls, respectively. AICAR did not affect hyperglycemia and hyperglucagonemia in STZ rats; however, it normalized circulating NEFAs and significantly increased FAO in glycolytic muscles. In conclusion, even though AICAR-induced AMPK activation enhanced glycogen accumulation in glycolytic muscles and normalized circulating NEFAs and TG levels, the hyperglycemic effects of glucagon likely offset the potentially glucose-lowering effects of AICAR, resulting in no improvement of glycemic control in insulin-deficient rats.

Frequent food insecurity among injection drug users: correlates and concerns.

BACKGROUND: Food insecurity and nutrition are two topics that are under-researched among injection drug users (IDUs). Our study examined the extent and correlates of food insecurity among a sample of IDUs and explored whether there is an association between food insecurity and injection-related HIV risk. METHODS: A cross-sectional survey was conducted using interviewer-administered questionnaires. Data were collected at a needle exchange program in London, Ontario, Canada between September 2006 and January 2007. Participants included 144 English-speaking IDUs who had injected drugs in the past 30 days. Participants were asked about their socio-demographic characteristics, HIV risk behaviours, food insecurity, and health/social service use. RESULTS: In the past 6 months, 54.5% of participants reported that on a daily/weekly basis they did not have enough to eat because of a lack of money, while 22.1% reported this type of food insecurity on a monthly basis. Moreover, 60.4% and 24.3% reported that they did not eat the quality or quantity of food they wanted on a daily/weekly or a monthly basis, respectively. Participants reported re-using someone else's injection equipment: 21% re-used a needle, 19% re-used water, and 37.3% re-used a cooker. The odds of sharing injection equipment were increased for food insecure individuals. CONCLUSIONS: Findings show that IDUs have frequent and variable experiences of food insecurity and these experiences are strongly correlated with sharing of injection-related equipment. Such behaviours may increase the likelihood of HIV and HCV transmission in this population. Addressing food-related needs among IDUs is urgently needed.

Biphasic peptide amphiphile nanomatrix embedded with hydroxyapatite nanoparticles for stimulated osteoinductive response.

Formation of the native bone extracellular matrix (ECM) provides an attractive template for bone tissue engineering. The structural support and biological complexity of bone ECM are provided within a composite microenvironment that consists of an organic fibrous network reinforced by inorganic hydroxyapatite (HA) nanoparticles. Recreating this biphasic assembly, a bone ECM analogous scaffold comprising self-assembling peptide amphiphile (PA) nanofibers and interspersed HA nanoparticles was investigated. PAs were endowed with biomolecular ligand signaling using a synthetically inscribed peptide sequence (i.e., RGDS) and integrated with HA nanoparticles to form a biphasic nanomatrix hydrogel. It was hypothesized the biphasic hydrogel would induce osteogenic differentiation of human mesenchymal stem cells (hMSCs) and improve bone healing as mediated by RGDS ligand signaling within PA nanofibers and embedded HA mineralization source. Viscoelastic stability of the biphasic PA hydrogels was evaluated with different weight concentrations of HA for improved gelation. After demonstrating initial viability, long-term cellularity and osteoinduction of encapsulated hMSCs in different PA hydrogels were studied in vitro. Temporal progression of osteogenic maturation was assessed by gene expression of key markers. A preliminary animal study demonstrated bone healing capacity of the biphasic PA nanomatrix under physiological conditions using a critical size femoral defect rat model. The combination of RGDS ligand signaling and HA nanoparticles within the biphasic PA nanomatrix hydrogel demonstrated the most effective osteoinduction and comparative bone healing response. Therefore, the biphasic PA nanomatrix establishes a well-organized scaffold with increased similarity to natural bone ECM with the prospect for improved bone tissue regeneration.

Osteogenic differentiation of human mesenchymal stem cells synergistically enhanced by biomimetic peptide amphiphiles combined with conditioned medium.

An attractive strategy for bone tissue engineering is the use of extracellular matrix (ECM) analogous biomaterials capable of governing biological response based on synthetic cell-ECM interactions. In this study, peptide amphiphiles (PAs) were investigated as an ECM-mimicking biomaterial to provide an instructive microenvironment for human mesenchymal stem cells (hMSCs) in an effort to guide osteogenic differentiation. PAs were biologically functionalized with ECM isolated ligand sequences (i.e. RGDS, DGEA), and the osteoinductive potential was studied with or without conditioned medium, containing the supplemental factors of dexamethasone, ß-glycerol phosphate and ascorbic acid. It was hypothesized that the ligand-functionalized PAs would synergistically enhance osteogenic differentiation in combination with conditioned medium. Concurrently, comparative evaluations independent of osteogenic supplements investigated the differentiating potential of the functionalized PA scaffolds as promoted exclusively by the inscribed ligand signals, thus offering the potential for therapeutic effectiveness under physiological conditions. Osteoinductivity was assessed by histochemical staining for alkaline phosphatase (ALP) and quantitative real-time polymerase chain reaction analysis of key osteogenic markers. Both of the ligand-functionalized PAs were found to synergistically enhance the level of visualized ALP activity and osteogenic gene expression compared to the control surfaces lacking biofunctionality. Guided osteoinduction was also observed without supplemental aid on the PA scaffolds, but at a delayed response and not to the same phenotypic levels. Thus, the biomimetic PAs foster a symbiotic enhancement of osteogenic differentiation, demonstrating the potential of ligand-functionalized biomaterials for future bone tissue repair.

Operator error and system deficiencies: analysis of 508 mining incidents and accidents from Queensland, Australia using HFACS.

Historically, mining has been viewed as an inherently high-risk industry. Nevertheless, the introduction of new technology and a heightened concern for safety has yielded marked reductions in accident and injury rates over the last several decades. In an effort to further reduce these rates, the human factors associated with incidents/accidents needs to be addressed. A modified version of the Human Factors Analysis and Classification System was used to analyze incident and accident cases from across the state of Queensland to identify human factor trends and system deficiencies within mining. An analysis of the data revealed that skill-based errors were the most common unsafe act and showed no significant differences across mine types. However, decision errors did vary across mine types. Findings for unsafe acts were consistent across the time period examined. By illuminating human causal factors in a systematic fashion, this study has provided mine safety professionals the information necessary to reduce mine incidents/accidents further.