Life before Stonehenge: The hunter-gatherer occupation and environment of Blick Mead revealed by sedaDNA, pollen and spores.

The Neolithic and Bronze Age construction and habitation of the Stonehenge Landscape has been extensively explored in previous research. However, little is known about the scale of pre-Neolithic activity and the extent to which the later monumental complex occupied an 'empty' landscape. There has been a long-running debate as to whether the monumental archaeology of Stonehenge was created in an uninhabited forested landscape or whether it was constructed in an already partly open area of pre-existing significance to late Mesolithic hunter-gatherers. This is of significance to a global discussion about the relationship between incoming farmers and indigenous hunter-gatherer societies that is highly relevant to both Old and New World archaeology. Here we present the results of plant sedaDNA, palynological and geoarchaeological analysis at the Late hunter-gatherer site complex of Blick Mead at the junction of the drylands of Salisbury Plain and the floodplain of the River Avon, on the edge of the Stonehenge World Heritage Site. The findings are placed within a chronological framework built on OSL, radiocarbon and relative archaeological dating. We show that Blick Mead existed in a clearing in deciduous woodland, exploited by aurochsen, deer and hunter-gatherers for approximately 4000 years. Given its rich archaeology and longevity this strongly supports the arguments of continuity between the Late Mesolithic hunter-gatherers activity and Neolithic monument builders, and more specifically that this was a partially open environment important to both groups. This study also demonstrates that sediments from low-energy floodplains can provide suitable samples for successful environmental assaying using sedaDNA, provided they are supported by secure dating and complementary environmental proxies.

Chitosan based bioadhesives for biomedical applications: A review.

Due to the promising properties of chitosan for biomedical engineering applications like biodegradability, biocompatibility, and non-toxicity, it is one of the most interesting biopolymers in this field. Therefore, Chitosan and its derivatives have attracted great attention in vast variety of biomedical applications. In the current paper, different types of chitosan-based bioadhesives including passive and active and their different types of external stimuli response structure such as thermo, pH and Light responsive systems are discussed. Different bioadhesives mechanisms with chitosan as an adhesive agent or main polymer component and some examples were also presented. Chitosan based bioadhesives and their potential biomedical applications in drug delivery systems, suture less surgery, wound dressing and hemostatic are also discussed. The results confirmed wound healing, hemostatic and bioadhesion capabilities of the chitosan bioadhesives and its great potential for biomedical applications.

Identifying Causative Microorganisms in Left Ventricular Assist Device Infections as a Guide for Developing Bacteriophage Therapy.

BACKGROUND: As more left ventricular-assist devices (LVADs) are implanted, multidrug-resistant LVAD infections are becoming increasingly common, partly due to bacterial biofilm production. To aid in developing bacteriophage therapy for LVAD infections, we have identified the most common bacterial pathogens that cause LVAD driveline infections (DLIs) in our heart transplant referral center. MATERIALS AND METHODS: We studied a retrospective cohort of patients who received LVADs from November 2003 to August 2017 to identify the common causative organisms of LVAD infection. We also studied a prospective cohort of patients diagnosed with DLIs from October 2018 to May 2019 to collect bacterial strains from DLIs for developing bacteriophages to lyse causative pathogens. LVAD infections were classified as DLI, bacteremia, and pump/device infections in the retrospective cohort. RESULTS: In the retrospective cohort of 582 patients, 186 (32.0%) developed an LVAD infection, with 372 microbial isolates identified. In the prospective cohort, 96 bacterial strains were isolated from 54 DLIs. The microorganisms causing DLIs were similar in the two cohorts; the most common isolate was Staphylococcus aureus. We identified 6 prospective S. aureus strains capable of biofilm formation. We developed 3 bacteriophages that were able to lyse 5 of 6 of the biofilm-forming S. aureus strains. CONCLUSIONS: Similar pathogens caused LVAD DLIs in our retrospective and prospective cohorts, indicating our bacterial strain bank will be representative of future DLIs. Our banked bacterial strains will be useful in developing phage cocktails that can lyse ≥80% of the bacteria causing LVAD infections at our institution.

Extracorporeal membrane oxygenation as a bridge to durable left ventricular assist device implantation in INTERMACS-1 patients.

Left ventricular assist devices (LVADs) are increasingly used as destination therapy or as a bridge to future cardiac transplant in patients with end-stage heart failure. Extracorporeal membrane oxygenation (ECMO) can be used to bridge patients in cardiogenic shock or with decompensated heart failure to durable mechanical circulatory support. We assessed outcomes in patients in critical cardiogenic shock (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS] profile 1) who underwent implantation of a continuous-flow (CF)-LVAD, with or without preoperative ECMO bridging. For this retrospective study, we selected INTERMACS profile 1 patients who underwent CF-LVAD implantation at our institution between Sep 1, 2004 and Nov 30, 2018. Of 768 patients identified, 133 (17.3%) were INTERMACS profile 1; 26 (19.5%) received preoperative ECMO support, and 107 (80.5%) did not. Postimplantation outcomes were compared between the ECMO and no-ECMO groups. No significant differences were found in 30-day mortality (15.4 vs. 15.9%, P = 0.95) or survival at 1 year (53.8 vs. 60.9%, P = 0.51). Three patients who received ECMO before CF-LVAD implantation subsequently underwent cardiac transplant. In the ECMO group, the lactate level 1 day after ECMO initiation was lower in survivors than nonsurvivors (2.7 ± 2.2 vs. 7.4 ± 4.2 mmol/L, P = 0.02; area under the curve = 0.85, P = 0.01) after CF-LVAD implantation. Bridging with ECMO to CF-LVAD implantation in carefully selected INTERMACS profile 1 patients (those who are at the highest risk for critical cardiogenic shock and for whom palliation may be the only other option) produced acceptable postoperative outcomes.Field of research: Artificial lung/ECMO.

Depyrogenation using Plasmas: A Novel Approach for Endotoxin Deactivation Using a Dielectric Barrier Discharge at Atmospheric Pressure.

Developing a low-cost depyrogenation process is vital in extending medical applicability of polymers that can be used in medicine. We present an overview of the plasma-based depyrogenation literature and address the need to develop a non-thermal plasma-based depyrogenation process for delicate materials such as chitosan. We present a low-cost plasma apparatus to treat chitosan powder in hermetically sealed bags. We decouple the experiments into two; depyrogenation experiments for dried standard endotoxin on glass slides, and chitosan modifications analysis through FTIR spectroscopy. We demonstrate depyrogenation efficacy with up to a 4-log reduction in endotoxin levels and discuss minor changes observed in plasma-treated chitosan.

Multi-layer dressing made of laminated electrospun nanowebs and cellulose-based adhesive for comprehensive wound care.

In this work, multi-layer wound dressing was made of laminated layers of electrospun fibers supported by adhesive sheet. Graft copolymerization of methyl methacrylate (MMA) and 2-Ethyl-1-hexyl acrylate (EHA) onto carboxymethyl cellulose (CMC) was conducted to obtain an adhesive sheet with 1.52 (N/cm2) loop tack, 1.7 (N/cm) peel strength and 25 s shear strength. Diclofenac sodium, anti-inflammatory drug, was loaded to the adhesive sheet with encapsulation efficiency 73%. The contact layer to wound was made of synthesized anti-bleeding agents, chitosan iodoacetamide (CI) loaded into electrospun polyvinyl alcohol (PVA) fibers. It was fabricated from fiber diameter 300 nm by electrospinning of 5% wt/v of CI (D.S. 18.7%) mixed with 10% wt/v PVA, at 20 kV and 17 cm airgap. The second, pain-relief layer was fabricated by encapsulating up to 50% wt/wt of capsaicin into gelatin nanofibers (197 nm) crosslinked by glyoxal. The third, antimicrobial layer was fabricated from PVA electrospun fibers loaded with 2% wt/wt gentamicin. Biocompatibility test showed insignificant adverse effects of the fabricated layers on fibroblast cells. Animal test on rat showed accelerated wound healing from 21 to 7 days for the multi-layer dressing. Histopathological findings corroborated the intactness of the epidermis layer of the treated samples.

Synthesis of chitosan iodoacetamides via carbodiimide coupling reaction: Effect of degree of substitution on the hemostatic properties.

Uncontrolled hemorrhage continues to be the leading cause of death from traumatic injuries both in the battlefield and in the civilian life. Chitosan is among the very few materials that have made the short list of military recommended field-deployable hemostatic dressings. However, the detailed mechanism of its action is still not fully understood. Moreover, in the cases when patients developed coagulopathy, the efficacy of the dressings rely solely on those mechanisms that work outside of the regular blood coagulation cascade. In addition to the well-known erythrocyte agglutination, we proposed to use the reactive N-iodoacetyl group on a new chitosan derivative to accelerate hemostasis. In this paper, we describe the synthesis of chitosan iodoacetamide (CI) with considerations of the stoichiometry among the reagents, the choice of solvent, the pH of the reaction medium, and the reaction time. The reaction was confirmed by FT-IR, 1H and 13C NMR, elemental analysis, iodine content analysis, and SEM-EDS. Water contact angle measurements and Erythrocyte Sedimentation Rate (ESR) method were used to evaluate the hemostatic potential of the newly synthesized CI as a function of their degree of substitution (DS). The range of DS was 5.9% to 27.8% for CI. The mid-range of DS gave the best results for the ESR. CIs exhibit favorable cytocompatibilities up to DS 18.7 compared to the generic unmodified chitosan. In general, the biocompatibility of chitosan iodoacetamide slightly declined with increasing the iodide content up to DS 21.5 owing to its affinity to SH groups of cells.

Chitosan nanoparticles: Polyphosphates cross-linking and protein delivery properties.

Nanoparticles from chitosan, in general, can be prepared through ionotropic gelation, physical crosslinking, with anionic polyphosphates. Tripolyphosphate (TPP) is widely used for such purpose especially in drug delivery applications. TPP is a small ion with a triple negative charge throughout the physiologically acceptable pH range. However, the stability of size and surface charge of the particles still challenging. In the current work, the utilization of Hexametaphosphate (HMP) instead of Tripolyphosphate (TPP) as a cross-linking agent is being investigated. HMP is hexavalent molecule in the neutral and slightly basic medium which offers more binding sites readily available for interaction with chitosan. It is thought that increasing the availability of the binding sites in the HMP molecule would result in stronger ionic complexation with chitosan cationic charges. Consequently, such stronger binding improves particles' stability and lead to average size reduction. A comparative study between chitosan/TPP and chitosan/HMP nanoparticles under different complexation conditions was conducted to investigate the effect of HMP on nanoparticles formation. Bovine Serum Albumin (BSA) was applied as a protein model drug to explore the drug loading efficiency, 96.3%, is higher than its TPP, 91.87%, counterparts. However, TPP cross-linked particles showed superior stability upon storage.

Rapid Identification of Novel Psychoactive and Other Controlled Substances Using Low-Field 1H NMR Spectroscopy.

An automated approach to the collection of 1H NMR (nuclear magnetic resonance) spectra using a benchtop NMR spectrometer and the subsequent analysis, processing, and elucidation of components present in seized drug samples are reported. An algorithm is developed to compare spectral data to a reference library of over 300 1H NMR spectra, ranking matches by a correlation-based score. A threshold for identification was set at 0.838, below which identification of the component present was deemed unreliable. Using this system, 432 samples were surveyed and validated against contemporaneously acquired GC-MS (gas chromatography-mass spectrometry) data. Following removal of samples which possessed no peaks in the GC-MS trace or in both the 1H NMR spectrum and GC-MS trace, the remaining 416 samples matched in 93% of cases. Thirteen of these samples were binary mixtures. A partial match (one component not identified) was obtained for 6% of samples surveyed whilst only 1% of samples did not match at all.

Evaluation of a Chitosan Hemostat in a Porcine Laparoscopic Partial Nephrectomy Model: A Pilot Study.

Background and Objective: The ideal hemostatic agent for laparoscopic partial nephrectomy (LPN) would provide complete hemostasis and sealing of the collecting system at a low cost. Chitosan (CS) is an established topical hemostatic agent, but standard sterilization techniques affect its functional and biologic properties, thereby preventing parenteral uses. This study sought to characterize the safety and efficacy of an implanted CS hemostat sterilized with either a standard technique, electron beam (e-beam) irradiation, or a novel technique, nonthermal nitrogen plasma, in a porcine LPN model. Methods: Laparoscopic partial nephrectomies were performed on six farm pigs and hemostasis achieved using only a CS hemostatic agent (Clo-Sur P.A.D.) that was e-beam (n = 3) or plasma sterilized (PS) (n = 3). Number of pads needed to achieve hemostasis, estimated blood loss, operative time, mass of kidney resection, and warm ischemia time were measured. Animals were monitored for 14 weeks and at harvest, retrograde ureteropyelography and histologic analysis were performed. Results: Complete hemostasis and collection system sealing were achieved in both groups. There was a trend toward less pads required for hemostasis (p = 0.056) and reduced blood loss (p = 0.096) with PS pads, although this did not achieve statistical significance. No complications were observed for 14 weeks and gross examination showed the implanted CS was encapsulated in a fibrous capsule. Histologic analysis revealed a healed nephrectomy site with residual CS and associated chronic inflammation, reactive fibrosis, and foreign body giant cell formation. Importantly, the adjacent renal tissue was intact and viable with no residual parenchymal inflammation or cytologic damage. Conclusion: CS pads alone provided safe and effective hemostasis in a porcine LPN model. PS may enhance hemostatic efficacy and resorption compared with e-beam.

Chitosan based hydrogels and their applications for drug delivery in wound dressings: A review.

Advanced development of chitosan hydrogels has led to new drug delivery systems that can release their active ingredients in response to environmental stimuli. This review considers more recent investigation of chitosan hydrogel preparations and the application of these preparations for drug delivery in wound dressings. Applications and structural characteristics of different types of active ingredients, such as growth factors, nanoparticles, nanostructures, and drug loaded chitosan hydrogels are summarized.

Fabrication and characterization of bactericidal thiol-chitosan and chitosan iodoacetamide nanofibres.

Two chitosan derivatives, namely, thiol-chitosan (TCs) and chitosan iodoacetamide (CsIA) were newly synthesized by reacting Cs with thiglycolic acid (TGA) and iodoacetic acid (IA) respectively. After being crosslinked with glutraldehyde (GA), the two derivatives were submitted to FT-IR and H1 NMR analysis for identification and characterization of their chemical features. As TCs and CsIA are water soluble, their electrospun nanofibres mats from aqueous solutions could be crosslinked and achieved using polyvinyl alcohol/Chitosan blend (PVA/Cs) polymers. Morphological structures of the obtained nanofibres and their webs were studied via those of TCs and CsIA free systems. The data also indicate that the crosslinked PVA/Cs/CsIA is more thermally stable than the crosslinked PVA/Cs/TCs and crosslinked PVA/Cs respectively. It was proved that the electrospun fibers containing TCs or CsIA display a superior antibacterial activity against negative bacteria E. Coli with a minimum inhibitory concentration (MIC) of 400µg/ml. These effects are rather in confirmation with bacterial kinetics essays which were also carried out in current work. Of particular interest is that the antimicrobial properties of fibers containing small concentration of either TCs or CsIA are much superior than those obtained with neat Cs electrospun nanofibres used as reference. By and large the results advocate the fibers webs containing TCs or CsIA as excellent candidates for wound dressing applications.

Formulation and characterization of a plasma sterilized, pharmaceutical grade chitosan powder.

Chitosan has great potential as a pharmaceutical excipient. In this study, chitosan flake was micronized using cryo-ball and cryo-jet milling and subsequently sterilized with nitrogen plasma. Micronized chitosan was characterized by laser diffraction, scanning electron microscopy (SEM), conductometric titration, viscometry, loss on drying, FTIR, and limulus amebocyte lysate (LAL) assays. Cryo-jet milling produced mean particle size of 16.05µm, 44% smaller than cryo-ball milling. Cryomilled chitosan demonstrated increased hygroscopicity, but reduced molecular weight and degree of deacetylation (DD). SEM imaging showed highly irregular shapes. FTIR showed changes consistent with reduced DD and an unexplained shift at 1100cm(-1). Plasma treated chitosan was sterile with <2.5EU/g after low-pressure plasma and <1.3EU/g after atmospheric pressure plasma treatment. Plasma treatment decreased the reduced viscosity of chitosan flake and powder, with a greater effect on powder. In conclusion, pharmaceutical grade, sterile chitosan powder was produced with cryo-jet milling and plasma sterilization.

Effect of Plasma Sterilization on the Hemostatic Efficacy of a Chitosan Hemostatic Agent in a Rat Model.

INTRODUCTION: The United States military has had success with chitosan (CS)-based hemostatic agents to control trauma-induced hemorrhages. Despite the positive reviews, additional physical forms of CS may enhance its hemostatic efficacy. Additionally, standard sterilization techniques may negatively affect the hemostatic efficacy of CS. We studied the effects of a CS-based hemostatic pad, the Clo-Sur P.A.D.™ (Scion Cardio-Vascular, Inc.), on severe femoral vessel bleeding in a rat model. The effects of different sterilization techniques on the bioadhesivity, surface atomic concentrations, and hemostatic efficacy of the P.A.D. were also evaluated. METHODS: Hemostatic efficacy, bioadhesivity, and surface atomic concentrations of the P.A.D. were evaluated in its unsterilized form, after sterilization with standard e-beam treatment, and after sterilization with one of three types of non-thermal nitrogen plasma: nitrogen gas, air, or nitrous oxide plasma. After standardized puncture of the femoral artery or transection of the femoral vessels, rats were treated with either a CS P.A.D. or gauze pad. RESULTS: The Clo-Sur P.A.D., regardless of sterilization technique, stopped arterial and mixed arterial/venous bleeding in all cases in <90 s with the time to hemostasis (TTH) significantly less for all P.A.D. treatment groups (P < 0.001; n = 4-5/group) compared to gauze-treated controls (n = 3). E-beam sterilized P.A.D.s consistently showed non-significant trends toward increased TTH and worse hemostasis scores compared to unsterilized and plasma sterilized P.A.D.s. Treating e-beam sterilized P.A.D.s with N2 plasma reverted the hemostatic efficacy to levels equivalent to native, unsterilized PADs. CONCLUSION: A CS-based hemostatic pad successfully controlled severe bleeding in a rat model with combined e-beam and plasma sterilized P.A.D.s showing the most promising results. Further studies are warranted.

Antimicrobial wound dressing nanofiber mats from multicomponent (chitosan/silver-NPs/polyvinyl alcohol) systems.

Novel hybrid nanomaterials have been developed for antimicrobial applications. Here we introduce a green route to produce antibacterial nanofiber mats loaded with silver nanoparticles (Ag-NPs, 25 nm diameter) enveloped in chitosan after reduction with glucose. The nanofiber mats were obtained from colloidal dispersions of chitosan-based Ag-NPs blended with polyvinyl alcohol. Nanofibers (150 nm average diameter and narrow size distribution) were obtained by electrospinning and cross-linked with glutaraldhyde. The effect of crosslinking on the release of silver was studied by atomic absorption spectroscopy. Antimicrobial activity was studied by the viable cell-counting; mats loaded with silver and control samples (chitosan/PVA) with different degrees of cross-linking were compared for their effectiveness in reducing or halting the growth of aerobic bacteria. The results showed superior properties and synergistic antibacterial effects by combining chitosan with Ag-NPs.

Pattern of Adult Surgical Admissions at the Niger Delta University Teaching Hospital, Okolobiri, Bayelsa State-a 2 Year Review

BACKGROUND: It is important to know the pattern of disease in any environment as this information is useful in planning intervention strategies. There is however a paucity of studies on the pattern of surgical diseases in Nigeria. We therefore aim to document the pattern of surgical diseases in adult surgical in- patients at the Niger delta University Teaching Hospital, Okolobiri, Bayelsa State. METHODS: All adult surgical patients admitted into the wards at the Niger delta University teaching hospital between January, 2010 and December, 2012 were retrospectively studied. RESULTS: A total of597 adult surgical in- patients were studied. There were 438 (73.5%) males and 158 (26.5%) females. The mean age of patients was 42.9± 18.2 years. The commonest diagnostic category was trauma 31.7%. This was followed by gastrointestinal conditions 20.6%, external hernias 16.1%, malignancies 8.2%, genitourinary conditions 7.7%, leg ulcers 6.5%, soft tissue infections 3.0% and others 6.2%. We observed a mortality rate of 7.5% which was highest among patients with malignancies at 24.5%. CONCLUSION: Trauma was the commonest cause of surgical admission while the percentage of deaths was highest in patients with malignancies

Kinetic properties and role of bacterial chitin deacetylase in the bioconversion of chitin to chitosan.

Chitin is an extremely insoluble material with very limited industrial use; however it can be deacetylated to soluble chitosan which has a wide range of applications. The enzymatic deacetylation of various chitin samples was investigated using the bacterial chitin deacetylase (CDA), which was partially purified from Alcaligenes sp. ATCC 55938 growth medium and the kinetic parameters of the enzyme were determined. Also, the efficiency of biocatalyst recycling by immobilization technique was examined. CDA activity reached its maximum (0.419 U/ml) after 18 h of bacterial cultivation. When glycol chitin was used as a substrate, the optimum pH of the enzyme was estimated to be 6 after checking a pH range between 3 and 9, while the optimum temperature was found to be 35°C. Addition of acetate (100 mM) in the assay mixture resulted in 50% loss of enzyme activity. The Km value of the enzyme is 1.6 × 10(-4) µM and Vmax is 24.7 µM/min. The average activity of CDA was 0.38 U/ml for both of immobilized and freely suspended cells after 18 h of bacterial growth. Some related patents are also discussed here.

Mechanically robust, rapidly actuating, and biologically functionalized macroporous poly(N-isopropylacrylamide)/silk hybrid hydrogels.

A route toward mechanically robust, rapidly actuating, and biologically functionalized polymeric actuators using macroporous soft materials is described. The materials were prepared by combining silk protein and a synthetic polymer (poly(N-isopropylacrylamide) (PNIAPPm)) to form interpenetrating network materials and macroporous structures by freeze-drying, with hundreds of micrometer diameter pores and exploiting the features of both polymers related to dynamic materials and structures. The chemically cross-linked PNIPAAm networks provided stimuli-responsive features, while the silk interpenetrating network formed by inducing protein ß-sheet crystallinity in situ for physical cross-links provided material robustness, improved expansion force, and enzymatic degradability. The macroporous hybrid hydrogels showed enhanced thermal-responsive properties in comparison to pure PNIPAAm hydrogels, nonporous silk/PNIPAAm hybrid hydrogels, and previously reported macroporous PNIPAAm hydrogels. These new systems reach near equilibrium sizes in shrunken/swollen states in less than 1 min, with the structural features providing improved actuation rates and stable oscillatory properties due to the macroporous transport and the mechanically robust silk network. Confocal images of the hydrated hydrogels around the lower critical solution temperature (LCST) revealed macropores that could be used to track changes in the real time morphology upon thermal stimulus. The material system transformed from a macroporous to a nonporous structure upon enzymatic degradation. To extend the utility of the system, an affinity platform for a switchable or tunable system was developed by immobilizing biotin and avidin on the macropore surfaces.

Chitosan-coated poly(vinyl alcohol) nanofibers for wound dressings.

A PVA nanofibrous matrix was prepared by electrospinning an aqueous 10 wt % PVA solution. The mean diameter of the PVA nanofibers electrospun from the PVA aqueous solution was 240 nm. The water resistance of the as-spun PVA nanofibrous matrix was improved by physically crosslinking the PVA nanofibers by heat treatment at 150 degrees C for 10 min, which were found to be the optimal heat treatment conditions determined from chemical and morphological considerations. In addition, the heat-treated PVA (H-PVA) nanofibrous matrix was coated with a chitosan solution to construct biomimetic nanofibrous wound dressings. The chitosan-coated PVA (C-PVA) nanofibrous matrix showed less hydrophilic and better tensile properties than the H-PVA nanofibrous matrix. The effect of the chitosan coating on open wound healing in a mouse was examined. The C-PVA and H-PVA nanofibrous matrices showed faster wound healing than the control. The histological examination and mechanical stability revealed the C-PVA nanofibrous matrix to be more effective as a wound-healing accelerator in the early stages of wound healing than the H-PVA nanofibrous matrix.

Biochemical informatics methods for diagnosis and disease management.

New technological advances are beginning to have a direct impact on many aspects of healthcare, including screening, diagnosis, treatment, and disease management. A multidisciplinary approach permits the development of sophisticated patient-centered models that rely on bioinformatics, molecular biology, analytical and biochemistry, and healthcare informatics. In the work described here, a decision support model based on neural networks is used to combine results from laboratory tests with clinical parameters to produce a prognostic model for metastatic carcinoma. In addition, techniques for drug design and development are presented that can lead to medications that target specific cancer cells.