Patterns of major trauma admissions to a level 1 trauma centre: A five year database analysis.

INTRODUCTION: It is only in recent years that major trauma systems and networks have been operating in the UK. High-quality data is available from the Trauma Audit and Research Network (TARN) database, enabling regional analysis. Our aim was to analyse Trauma Team Activations within the Cheshire and Merseyside major trauma network and discuss the implications of these data on resource allocation, training and trauma prevention. METHODS: A retrospective analysis was performed for all patients requiring Trauma Team Activation (TTA) at a category one adult Major Trauma Centre (MTC) who were submitted to the TARN database from the 1st January 2015 to the 1st January 2020. Data collected included the date and time of arrival, location of injury and Injury Severity Score (ISS) in addition to routine demographic data. Dates of major sporting events and school holidays were obtained. RESULTS: 4811 patients were identified. The median age was 57 years; 65.8 % were male. The mean frequency of TTAs was 18.5 per week. Patterns identified include annual peaks during the summer months, October and December, weekly peaks on Thursdays and Sundays and daily peaks between 16:00 and 23:59 with 45.0 % of TTAs occurring between these hours. There were 5.9 additional TTAs per week during the Isle of Man TT races. The median ISS increased from 14 to 23 for TT race TTAs and from 14 to 36 for Manx Grand Prix TTAs. Those injured during the TT races were twice as likely to require surgery and those injured during the MGP required five additional days in intensive care. School holidays did not independently affect major trauma volumes. CONCLUSIONS: Major trauma in Cheshire and Merseyside did follow distinct patterns according to calendar month, day and time. Major motorsport increased trauma volumes and severity; school holidays did not. Such analysis could enable Major Trauma Centres to tailor the supply of trauma services to meet a predictable local demand for the benefit of our staff and patients.

Sternal fractures and thoracic injury: an analysis of 288 sternal fractures attending a major trauma centre.

INTRODUCTION: Sternal fractures (SF) are uncommon injuries usually associated with a significant mechanism of injury. Concomitant injury is likely, and a risk of mortality is substantial. AIM: Our aim in this study was to identify the risk factors for mortality in patients who had sustained sternal fractures. METHODS: We conducted a single centre retrospective review of the trust's Trauma Audit and Research Network Database, from May 2014 to July 2021. Our inclusion criteria were any patients who had sustained a sternal fracture. The regions of injury were defined using the Abbreviated Injury Score. Pearson Chi-Squared, Fisher Exact tests and multivariate regression analyses were performed using IBM SPSS. RESULTS: A total of 249 patients were identified to have sustained a SF. There were 19 patients (7.63%) who had died. The most common concomitant injuries with SF were Rib fractures (56%), Lung Contusions (31.15%) and Haemothorax (21.88%). There was a significant increase in age (59.93 vs 70.06, p = .037) and admission troponin (36.34 vs. 100.50, p = .003) in those who died. There was a significantly lower GCS in those who died (10.05 vs. 14.01, p < .001). On multi regression analysis, bilateral rib injury (p = 0.037, OR 1.104) was the only nominal variable which showed significance in mortality. CONCLUSION: Sternal Fractures are uncommon but serious injuries. Our review has identified that bilateral rib injuries, increase in age, low GCS, and high admission troponin in the context of SF, were associated with mortality.

Prediction of distal tibial articular extension in tibial shaft fractures: both posterior malleolar fracture and non posterior malleolar fracture intra-articular extension.

BACKGROUND: Multiple authors have highlighted the increased incidence of occult posterior malleolar fractures (PMFs) with spiral tibial shaft fractures, although other reported associated risks of intra-articular extension have been limited. The aim of our study is to investigate both PMFs and non-PMFs intra-articular extensions associated with tibial diaphyseal fractures to try to determine any predictive factors. METHODS: We undertook a retrospective review of a prospectively collected database. The inclusion criteria for this study were any patient who had sustained a diaphyseal tibial fracture, who had undergone surgery during the study period and who had also undergone a CT scan in addition to plain radiographs. The study time period for this study was between 01/01/2013 and 9/11/2021. RESULTS: Out of 764 diaphyseal fractures identified, 442 met the inclusion criteria. A total of 107 patients had PMF extensions (24.21%), and a further 128 patients (28.96%) had intra-articular extensions that were not PMF's. On multivariate analysis, spiral tibial fracture subtypes of the AO/OTA classification (OR 4.18, p < 0.001) and medial direction of tibial spiral from proximal to distal (OR 4.38, p < 0.001) were both significantly associated with PMF. Regarding intra-articular fractures, multivariate analysis showed significant associations with non-spiral (OR 4.83, p < 0.001) and distal (OR 15.32, p < 0.001) tibial fractures and fibular fractures that were oblique (OR 2.01, p = 0.019) and at the same level as tibia fracture (OR 1.83, p = 0.045) or no fracture of the fibular (OR 7.02, p < 0.001). CONCLUSION: In our study, distal tibial articular extension occurs in almost half of tibial shaft fractures. There are very few fracture patterns that are not associated with some type of intra-articular extension, and therefore, a low threshold for preoperative CT should be maintained.

Microplastic adulteration in homogenized fish and seafood - a mid-infrared and machine learning proof of concept.

The objective of this study was to assess the ability of utilizing attenuated total reflection mid-infrared (ATR-MIR) spectroscopy in combination with machine learning techniques to classify the presence of different types of microplastics in artificially adulterated fish and seafood samples. Different polymers namely poly-vinyl chloride (PVC), polycarbonate (PC), polystyrene (PS), polypropylene (PP) and low (LDPE) and high-density polyethylene (HDPE) were mixed with homogenized fish and seafood samples. Homogenized samples were analyzed using MIR spectroscopy and classification models developed using machine learning algorithms such as partial least squares discriminant analysis (PLS-DA). The results of this study revealed that it was possible to identify between adulterated and non-adulterated samples as well as the different microplastic types added to the homogenized samples using ATR-MIR spectroscopy. This study confirmed the ability of combining machine learning methods with ATR-MIR spectroscopy to directly analyze microplastic adulteration in fleshy foods such as fish and seafood. This proof-of-concept study can be utilized and extended to monitor the presence of plastics either in a wide range of fleshy foods or along the entire food value chain.

Impact of heat stress and a feed supplement on hormonal and inflammatory responses of dairy cows.

The aim of this trial was to evaluate the effects of an immunomodulatory supplement (OmniGen AF, OG; Phibro Animal Health Corp.) and heat stress on hormonal, inflammatory, and immunological responses of lactating dairy cows. Sixty multiparous Holstein cows were randomly assigned to 4 treatments in a 2 × 2 factorial arrangement using 2 environments: cooled using fans and misters, or noncooled, and 2 top-dressed feed supplements (56 g/d): OG or a placebo (CTL). Temperature-humidity index averaged 78 during the 8-wk trial. Blood was drawn to analyze cortisol, prolactin, and circulating tumor necrosis factor (TNF)-α and IL-10. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated with hydrocortisone, prolactin, or lipopolysaccharide (LPS), individually or in several combinations, to assess induced proliferation and cytokine production. At d 52, 6 cows per treatment were injected i.v. with an LPS bolus (ivLPS) to assess hormone and cytokine responses. For cooled cows, feeding OG increased plasma cortisol concentration relative to CTL. Noncooled cows fed CTL had lower circulating TNF-α concentrations than noncooled-OG and cooled-CTL cows, with cooled-OG intermediate. Hydrocortisone+LPS-stimulated PBMC from OG cows tended to proliferate more than CTL. Relative to cooled cows, PBMC from noncooled cows produced more TNF-α and IL-10 when stimulated with LPS. Following ivLPS, cooled-OG cows had a greater cortisol response than the other treatments. In conclusion, OG supplementation enhanced cortisol release under basal condition and induced inflammation with cooling compared with CTL. This suggests that heat stress inhibits OG-mediated cortisol release. Heat stress seemed to enhance the inflammatory responses of PBMC from lactating cows. However, OG supplementation promoted PBMC proliferation under stress, or in the presence of hydrocortisone.

3D Printable Electrically Conductive Hydrogel Scaffolds for Biomedical Applications: A Review.

Electrically conductive hydrogels (ECHs), an emerging class of biomaterials, have garnered tremendous attention due to their potential for a wide variety of biomedical applications, from tissue-engineered scaffolds to smart bioelectronics. Along with the development of new hydrogel systems, 3D printing of such ECHs is one of the most advanced approaches towards rapid fabrication of future biomedical implants and devices with versatile designs and tuneable functionalities. In this review, an overview of the state-of-the-art 3D printed ECHs comprising conductive polymers (polythiophene, polyaniline and polypyrrole) and/or conductive fillers (graphene, MXenes and liquid metals) is provided, with an insight into mechanisms of electrical conductivity and design considerations for tuneable physiochemical properties and biocompatibility. Recent advances in the formulation of 3D printable bioinks and their practical applications are discussed; current challenges and limitations of 3D printing of ECHs are identified; new 3D printing-based hybrid methods for selective deposition and fabrication of controlled nanostructures are highlighted; and finally, future directions are proposed.

Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction.

Cellular senescence has been shown to contribute to skin ageing. However, the role of melanocytes in the process is understudied. Our data show that melanocytes are the only epidermal cell type to express the senescence marker p16INK4A during human skin ageing. Aged melanocytes also display additional markers of senescence such as reduced HMGB1 and dysfunctional telomeres, without detectable telomere shortening. Additionally, senescent melanocyte SASP induces telomere dysfunction in paracrine manner and limits proliferation of surrounding cells via activation of CXCR3-dependent mitochondrial ROS. Finally, senescent melanocytes impair basal keratinocyte proliferation and contribute to epidermal atrophy in vitro using 3D human epidermal equivalents. Crucially, clearance of senescent melanocytes using the senolytic drug ABT737 or treatment with mitochondria-targeted antioxidant MitoQ suppressed this effect. In conclusion, our study provides proof-of-concept evidence that senescent melanocytes affect keratinocyte function and act as drivers of human skin ageing.

Engaging Primary Care Providers to Reduce Unwanted Clinical Variation and Support ACO Cost and Quality Goals: A Unique Provider-Payer Collaboration.

This project was undertaken to reduce unneeded variation among practicing primary care clinicians participating in an accountable care organization (ACO) and to raise quality and reduce costs. This real-world, quasi-controlled experiment compared ACO target improvements between 3 participating geographic regions and members within the ProHealth ACO against nonparticipating regions and members. The authors used a novel care standardization initiative to engage participating providers. This was a 2-year longitudinal study with 6 rounds of serially measured provider care decisions and customized individual and group improvement feedback. Participating providers cared for online patient simulations as they would actual patients, and their care decisions were scored against evidence-based guidelines. This approach generated significant increases in evidence-based quality scores (+27%) and reductions in unneeded testing (-55%) in the patient simulations. Improvements in the online simulated patients correlated with improvements in patient-level ACO quality measures, which showed gains above and beyond the quasi-control group. Reductions calculated for spending on unneeded tests and specialist referrals exceeded $4.8 million. This study found that supporting practicing physicians in ACOs with evidence-based feedback significantly improved care and cost-efficiency.

Graphene, electrospun membranes and granular activated carbon for eliminating heavy metals, pesticides and bacteria in water and wastewater treatment processes.

Access to safe water has a significant impact on all parts of society, its growth and sustainability, both politically and socioeconomically. Consequently, the preservation of water and wastewater treatment have become a global challenge. A major contributor to water pollution is improperly or untreated industrial emissions; water resources can be contaminated with harmful pollutants, toxins or pathogenic microorganisms. Carbon's unique chemistry and its evolution due to recent advances in carbon-based technologies such as nanomaterials, offer significant potential for a variety of water purification strategies. This work details the application of carbon materials in combination with nanotechnology in the form of graphene, graphene composites, electrospun membranes and improved activated carbon in a myriad of water treatment systems with an emphasis on the removal of heavy metals, pesticides and harmful bacteria.

Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis.

During apoptosis, pro-apoptotic BAX and BAK are activated, causing mitochondrial outer membrane permeabilisation (MOMP), caspase activation and cell death. However, even in the absence of caspase activity, cells usually die following MOMP Such caspase-independent cell death is accompanied by inflammation that requires mitochondrial DNA (mtDNA) activation of cGAS-STING signalling. Because the mitochondrial inner membrane is thought to remain intact during apoptosis, we sought to address how matrix mtDNA could activate the cytosolic cGAS-STING signalling pathway. Using super-resolution imaging, we show that mtDNA is efficiently released from mitochondria following MOMP In a temporal manner, we find that following MOMP, BAX/BAK-mediated mitochondrial outer membrane pores gradually widen. This allows extrusion of the mitochondrial inner membrane into the cytosol whereupon it permeablises allowing mtDNA release. Our data demonstrate that mitochondrial inner membrane permeabilisation (MIMP) can occur during cell death following BAX/BAK-dependent MOMP Importantly, by enabling the cytosolic release of mtDNA, inner membrane permeabilisation underpins the immunogenic effects of caspase-independent cell death.

Biomolecular study of human thymidylate synthase conformer-selective inhibitors: New chemotherapeutic approach.

Thymidylate synthase (TS) is a well-validated target for the therapy of adult cancers. Propane-1,3-diphosphonic acid (PDPA) has significant inhibitory properties against human thymidylate synthase (hTS) relative to mouse TS which is not predicted to adopt an inactive conformer. The current research aims to identify novel, lead inhibitors of hTS and examine the prediction that they bind selectively to hTS enzymes existing in different conformational equilibria. Conformer-selectivity was evaluated through performing activity inhibition studies, as well as intrinsic fluorescence (IF) studies in comparison to the known orthosteric inhibitor raltitrexed (RTX). Human TS was isolated from recombinant bacteria expressing either native hTS, capable of conformational switching, or an actively stabilized mutant (R163K-hTS). The examined test compounds were rationally or virtually predicted to have inhibitory activity against hTS. Among these compounds, glutarate, N-(4-carboxyphenyl) succinamic acid, and diglycolic anhydride showed higher selectivity towards native hTS as compared to R163K-hTS. The active site inhibitor RTX showed significantly higher inhibition of R163K-hTS relative to hTS. Targeting hTS via conformational selectivity represents a future approach for overcoming reported resistance towards active-state TS analogs.

Novel pre-treatment of zeolite materials for the removal of sodium ions: potential materials for coal seam gas co-produced wastewater.

Coal seam gas (CSG) is the extraction of methane gas that is desorbed from the coal seam and brought to the surface using a dewatering and depressurisation process within the saturated coalbed. The extracted water is often referred to as co-produced CSG water. In this study, co-produced water from the coal seam of the Bowen Basin (QLD, Australia) was characterised by high concentration levels of Na(+) (1156 mg/L), low concentrations of Ca(2+) (28.3 mg/L) and Mg(2+) (5.6 mg/L), high levels of salinity, which are expected to cause various environmental problems if released to land or waters. The potential treatment of co-produced water using locally sourced natural ion exchange (zeolite) material was assessed. The zeolite material was characterized for elemental composition and crystal structure. Natural, untreated zeolite demonstrated a capacity to adsorb Na(+) ions of 16.16 mEq/100 g, while a treated zeolite using NH4 (+) using a 1.0 M ammonium acetate (NH4C2H3O2) solution demonstrated an improved 136 % Na(+) capacity value of 38.28 mEq/100 g after 720 min of adsorption time. The theoretical exchange capacity of the natural zeolite was found to be 154 mEq/100 g. Reaction kinetics and diffusion models were used to determine the kinetic and diffusion parameters. Treated zeolite using a NH4 (+) pre-treatment represents an effective treatment to reduce Na(+) concentration in coal seam gas co-produced waters, supported by the measured and modelled kinetic rates and capacity.

The nicotine metabolite, cotinine, attenuates glutamate (NMDA) antagonist-related effects on the performance of the five choice serial reaction time task (5C-SRTT) in rats.

Cotinine, the most predominant metabolite of nicotine in mammalian species, has a pharmacological half-life that greatly exceeds its precursor. However, until recently, relatively few studies had been conducted to systematically characterize the behavioral pharmacology of cotinine. Our previous work indicated that cotinine improves prepulse inhibition of the auditory startle response in rats in pharmacological impairment models and that it improves working memory in non-human primates. Here we tested the hypothesis that cotinine improves sustained attention in rats and attenuates behavioral alterations induced by the glutamate (NMDA) antagonist MK-801. The effects of acute subcutaneous (dose range 0.03-10.0 mg/kg) and chronic oral administration (2.0 mg/kg/day in drinking water) of cotinine were evaluated in fixed and variable stimulus duration (VSD) as well as variable intertrial interval (VITI) versions of a five choice serial reaction time task (5C-SRTT). The results indicated only subtle effects of acute cotinine (administered alone) on performance of the 5C-SRTT (e.g., decreases in timeout responses). However, depending on dose, acute treatment with cotinine attenuated MK-801-related impairments in accuracy and elevations in timeout responses, and it increased the number of completed trials. Moreover, chronic cotinine attenuated MK-801-related impairments in accuracy and it reduced premature and timeout responses when the demands of the task were increased (i.e., by presenting VSDs or VITIs in addition to administering MK-801). These data suggest that cotinine may represent a prototype for compounds that have therapeutic potential for neuropsychiatric disorders (i.e., by improving sustained attention and decreasing impulsive and compulsive behaviors), especially those characterized by glutamate receptor alterations.

Total synthesis and stereochemical assignment of cis-uvariamicin I and cis-reticulatacin.

Diastereoisomeric mixtures of cis-uvariamicin I (15R,16R,19S,20S,36S and 15S,16S,19R,20R,36S) and cis-reticulatacin (17R,18R,21S,22S,36S and 17S,18S,21R,22R,36S) were synthesized to determine the stereochemistry of the natural products isolated from Annona muricata. It was not possible to resolve a mixture of the four synthetic isomers using chiral HPLC, but the mixed isomers could be distinguished using chiral HPLC EIMS with extracted fragment ion analysis. Comparison of synthetic standards with the natural isolate revealed that cis-uvariamicin I and cis-reticulatacin are present in nature as mixtures of threo-cis-threo diastereoisomers. It is suggested that the nomenclature for the natural products is amended as follows: (15R,16R,19S,20S,36S)-cis-uvariamicin I (cis-uvariamicin IA); (15S,16S,19R,20R,36S)-cis-uvariamicin I (cis-uvariamicin IB); (17R,18R,21S,22S,36S)-cis-reticulatacin (cis-reticulatacin A); (17S,18S,21R,22R,36S)-cis-reticulatacin (cis-reticulatacin B).

Tibial Nailing During Pregnancy: A Safe Option.

We present a case of a distal tibial fracture in a pregnant patient treated with an intermedullary device. The risks associated with operative treatment of fractures in pregnancy are discussed. The patient underwent a successful procedure using a novel tibial nail which reduced both operative time and radiation exposure. Surgical intervention allowed the mother to have a normal delivery. The patient had an excellent outcome with no adverse effects reported by either mother or baby.

Permeation and reservoir formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P) across porcine esophageal tissue in the presence of ethanol and menthol.

Environmental influences may affect carcinogen absorption and residency in the tissues of the aero-digestive tract. We quantified the effect of ethanol and menthol on the rates of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P) absorption using a fully validated in vitro diffusion system, capable of accurately and precisely quantifying tobacco carcinogen permeation and reservoir formation in porcine esophageal mucosa. Confocal microscopy was employed to visualize the location of B[a]P in the exposed membranes. Markedly different extents of permeation and reservoir formation for the tobacco carcinogens were recorded in the presence of ethanol and menthol. The water-soluble NNK permeated the membrane rapidly, while the lipophilic B[a]P did not appreciably diffuse through the tissue. Significantly different extents of reservoir formation were observed for the different carcinogens and in the presence of the different penetration-enhancer solvents. Alcohol (at 5% concentration) did not influence the permeation or reservoir formation of NNK. A mentholated donor solution (0.08%) both decreased the flux of NNK and significantly increased the tissue reservoir formation. The magnitude of the reservoir formed by B[a]P was relatively extensive (even though membrane permeation rates were negligible), being greatest in the presence of both ethanol and menthol. This suggests synergy between the two penetration-enhancer species acting on this carcinogen. Confocal microscopy studies confirmed that there was an appreciable intra-cellular, and specifically nuclear, association of the B[a]P species during the reservoir formation process. The aqueous solubility of the diffusing species and the presence of penetration enhancers appeared to be key factors in the absorption and cellular binding processes. The results presented support the hypothesis that the use of mentholated cigarettes, or the concomitant consumption of alcohol while smoking, may have marked effects on the fate of tobacco chemicals. This finding may help to explain elevated rates of esophageal squamous cell carcinoma in African Americans.

Vitamin E amides, a new class of vitamin E analogues with enhanced proapoptotic activity.

Vitamin E (VE) analogues, epitomized by alpha-tocopheryl succinate (alpha-TOS), are proapoptotic agents with selective antineoplastic activity. The molecule of alpha-TOS comprises several structurally and functionally distinct moieties that can be modified in order to yield analogues with higher activity. In order to find analogues with higher apoptogenic efficacy, we prepared novel compounds where the ester bond was replaced by an amide bond. All of these analogues were significantly more proapoptotic than their ester counterparts, with alpha-tocopheryl maleyl amide being the most effective. Importantly, methylation of the free carboxylic group completely obliterated apoptogenic activity of the compounds. Similarly as shown for the ester analogues, the amides induced apoptosis by mitochondrial destabilization. Superiority of amides over the ester analogues may be due to their higher partitioning into the lipid phase, as suggested by the log p-values that were lower for the amides than the corresponding esters. In conclusion, we present evidence that modification of the ester bond of agents such as alpha-TOS can be used as a basis for generating novel analogues with higher efficacy of killing malignant cells, an activity that suggests anticancer effect of the agents.

Treatment of patch and plaque stage mycosis fungoides with imiquimod 5% cream.

BACKGROUND: Systemic interferon is effective in the treatment of mycosis fungoides (MF). Imiquimod is effective in the treatment of some epidermal neoplasms and induces localized interferon production. OBJECTIVE: To evaluate the safety and efficacy of topical imiquimod 5% cream for the treatment of patch and plaque stage MF. METHODS: Six patients with stage IA to IIB MF were treated with topical imiquimod 5% cream 3 times per week for 12 weeks in this open label pilot study. Index lesions were biopsied pre- and post- treatment, and up to 4 additional treated lesions were monitored for 16 weeks. RESULTS: Three of 6 patients had histologic clearance of disease in index lesions, and also demonstrated significant improvement in the clinical scores for all treated lesions. A fourth patient had 2 of 4 lesions respond clinically. Application site reactions were limited to those patients responding to treatment. CONCLUSION: In this preliminary open label study topical imiquimod 5% cream was well tolerated and associated with a histologic and clinical response rate of 50%.

Identification of ACAT1- and ACAT2-specific inhibitors using a novel, cell-based fluorescence assay: individual ACAT uniqueness.

Acyl CoA:cholesterol acyltransferase 1 (ACAT1) and ACAT2 are enzymes responsible for the formation of cholesteryl esters in tissues. While both ACAT1 and ACAT2 are present in the liver and intestine, the cells containing either enzyme within these tissues are distinct, suggesting that ACAT1 and ACAT2 have separate functions. In this study, NBD-cholesterol was used to screen for specific inhibitors of ACAT1 and ACAT2. Incubation of AC29 cells, which do not contain ACAT activity, with NBD-cholesterol showed weak fluorescence when the compound was localized in the membrane. When AC29 cells stably transfected with either ACAT1 or ACAT2 were incubated with NBD-cholesterol, the fluorescent signal localized to the nonpolar core of cytoplasmic lipid droplets was strongly fluorescent and was correlated with two independent measures of ACAT activity. Several compounds were found to have greater inhibitory activity toward ACAT1 than ACAT2, and one compound was identified that specifically inhibits ACAT2. The demonstration of selective inhibition of ACAT1 and ACAT2 provides evidence for uniqueness in structure and function of these two enzymes. To the extent that ACAT2 is confined to hepatocytes and enterocytes, the only two cell types that secrete lipoproteins, selective inhibition of ACAT2 may prove to be most beneficial in the reduction of plasma lipoprotein cholesterol concentrations.