Search

OBJECTIVE: Arabic gum Acacia (AG) is rich in fiber which improves lipid metabolism besides its antioxidant effect. Folium mori (FM) is a widely used herb due to its immunomodulatory, antimicrobial, and antioxidant activity. In the current study, we explore the antidiabetic, anti-inflammatory, as well as antioxidant activities of AG and FM in Streptozotocin (STZ), induced diabetic rats. MATERIALS AND METHODS: STZ diabetic rats were orally administrated with metformin and/or a combination of AG and FM for 4 weeks. Glycemic levels, Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), cholesterol, triglycerides, urea, and creatinine were determined. Malondialdehyde (MDA), glutathione peroxidase (GPx), and Superoxide dismutase (SOD) were also evaluated. Gene expression and profile as well as immunohistopathological were also evaluated. RESULTS: The results elicited no toxicological profile of both AG and FM. Plasma glucose level was decreased starting from 1st week to 4th week; besides, there was an improvement in glycated hemoglobin, insulin, and fructosamine. Liver and kidney damage markers were decreased in both AG and FM-treated rats. A significant increase in the antioxidant defense system and a decrease in oxidative stress markers were also observed. Gene expression analysis in brain tissues revealed a significant decrease in Interleukin beta 1 (IL-ß1), Caspase 3 (Cas-3), and Transforming growth factor beta (TGF-β). CONCLUSIONS: Oral treatment of metformin with AG and FM in STZ-injected rats could ameliorate protective pathways and can be one of the promising oral anti-diabetic herbal agents. [ABSTRACT FROM AUTHOR]

We have previously presented a computational protocol that is based on an embedded cluster model and operates in the framework of TD-DFT in conjunction with the excited state dynamics (ESD) approach. The protocol is able to predict the experimental absorption and emission spectral shapes of Eu 2+ -doped phosphors. In this work, the applicability domain of the above protocol is expanded to Eu 2+ -doped phosphors bearing multiple candidate Eu doping centers. It will be demonstrated that this protocol provides full control of the parameter space that describes the emission process. The stability of Eu doping at various centers is explored through local energy decomposition (LED) analysis of DLPNO-CCSD(T) energies. This enables further development of the understanding of the electronic structure of the targeted phosphors, the diverse interactions between Eu and the local environment, and their impact on Eu doping probability, and control of the emission properties. Hence, it can be employed to systematically improve deficiencies of existing phosphor materials, defined by the presence of various intensity emission bands at undesired frequencies, towards classes of candidate Eu 2+ -doped phosphors with desired narrow band red emission. For this purpose, the chosen study set consists of three UCr 4 C 4 -based narrow-band phosphors, namely the known alkali lithosilicates RbNa[Li 3 SiO 4 ] 2 :Eu 2+ (RNLSO2), RbNa 3 [Li 3 SiO 4 ] 4 :Eu 2+ (RNLSO) and their isotypic nitridolithoaluminate phosphors consisting of CaBa[LiAl 3 N 4 ] 2 :Eu 2+ (CBLA2) and the proposed Ca 3 Ba[LiAl 3 N 4 ] 4 :Eu 2+ (CBLA), respectively. The theoretical analysis presented in this work led us to propose a modification of the CBLA2 phosphor that should have improved and unprecedented narrow band red emission properties. Finally, we believe that the analysis presented here is important for the future rational design of novel Eu 2+ -doped phosphor materials, with a wide range of applications in science and technology.

In this work, we present a computational study that is able to predict the optical absorption and photoluminescent properties of the chiral Re(I) family of complexes [fac-ReX(CO)3L], where X is either Cl or I and L is N-heterocyclic carbene extended with π-conjugated [5]-helicenic unit. The computational strategy is based on carefully calibrated time dependent density functional theory calculations and operates in conjunction with an excited state dynamics approach to treat in addition to absorption (ABS) and photoluminescence (PL), electronic circular dichroism (ECD), and circularly polarized luminescence (CPL) spectroscopies, respectively. The employed computational approach provides, an addition, access to the computation of phosphorescence rates in terms of radiative and non-radiative relaxation processes. The chosen molecules consist of representative examples of non-helicenic (NHC) and helicenic diastereomers. The agreement between theoretical and experimental spectra, including absorption (ABS, ECD) and emission (PL, CPL), is excellent, validating a quantitative interpretation of the spectral features on the basis of natural transition orbitals and TheoDore analyses. It is demonstrated that across the set of studied Re(I) diastereomers, the emission process in the case of NHC diastereomers is metal to ligand charge transfer in nature and is dominated by the easy-axis anisotropy of the emissive excited multiplet. On the contrary, in the cases of the helicenic diastereomers, the emission process is intra ligand charge transfer in nature and is dominated by the respective easy-plane anisotropy of the emissive excited multiplet. This affects remarkably the photoluminescent properties of the molecules in terms of PL and CPL spectral band shapes, spin-vibronic coupling, relaxation times, and the respective quantum yields. Spin-vibronic coupling effects are investigated at the level of the state-average complete active space self-consistent field in conjunction with quasi-degenerate second order perturbation theory. It is in fact demonstrated that a spin-vibronic coupling mechanism controls the observed photophysics of this class of Re(I) complexes., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

In this work, we present a computational protocol that is able to predict the experimental absorption and emission spectral shapes of Eu 2+ -doped phosphors. The protocol is based on time-dependent density functional theory and operates in conjunction with an excited-state dynamics approach. It is demonstrated that across the study set consisting of representative examples of nitride, oxo-nitride, and oxide Eu 2+ -doped phosphors, the energy distribution and the band shape of the emission spectrum are related to the nature of the 4f-5d transitions that are probed in the absorption process. Since the 4f orbitals are very nearly nonbonding, the decisive quantity is the covalency of the 5d acceptor orbitals that become populated in the electronically excited state that leads to emission. The stronger the (anti) bonding interaction between the lanthanide and the ligands is in the excited state, the larger will be the excited state distortion. Consequently, the corresponding emission will get broader due to the vibronic progression that is induced by the structural distortion. In addition, the energy separation of the absorption bands that are dominated by states with valence 4f-5d and a metal to ligand charge transfer character defines a measure for the thermal quenching of the studied Eu 2+ -doped phosphors. Based on this analysis, simple descriptors are identified that show a strong correlation with the energy position and bandwidth of the experimental emission bands without the need for elaborate calculations. Overall, we believe that this study serves as an important reference for designing new Eu 2+ -doped phosphors with desired photoluminescence properties.

TANK-binding kinase 1 (TBK1) mutations are a recently discovered cause of disorders in the frontotemporal dementia (FTD)-amyotrophic lateral sclerosis (ALS) spectrum. We describe a novel L683∗ mutation, predicted to cause a truncated protein and therefore be pathogenic, in a patient presenting with nonfluent variant primary progressive aphasia at the age of 65 years. Her disease progressed over the following years, leading to her being mute and wheelchair bound seven years into her illness. Brain imaging showed asymmetrical left-sided predominant atrophy affecting the frontal, insular, and temporal cortices as well as the striatum in particular. Review of the literature found 60 different nonsense, frameshift, deletion, or splice site mutations, including the newly described mutation, with data on clinical diagnosis available in 110 people: 58% of the cases presented with an ALS syndrome, 16% with an FTD-ALS overlap, 19% with a cognitive presentation (including behavioral variant FTD and primary progressive aphasia) and 4% with atypical parkinsonism. Age at onset (AAO) data were available in 75 people: mean (standard deviation) AAO was 57.5 (10.3) in those with ALS, which was significantly younger than those with a cognitive presentation (AAO = 65.1 (10.5), p = 0.008), or atypical parkinsonism (AAO = 68.3 (8.7), p = 0.021), with a trend compared with the FTD-ALS group (AAO = 61.9 (7.0), p=0.065); there was no significant difference in AAO between the other groups. In conclusion, clinical syndromes across the whole FTD-ALS-atypical parkinsonism spectrum have been reported in conjunction with mutations in TBK1. It is therefore important to include TBK1 on future gene panels for each of these disorders and to suspect such mutations particularly when there are multiple different phenotypes in the same family., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Abnormal behavioural and physiological reactivity to emotional stimuli is a hallmark of frontotemporal dementia (FTD), particularly the behavioural variant (bvFTD). As part of this repertoire, altered phobic responses have been reported in some patients with FTD but are poorly characterised., Methods: We collected data (based on caregiver reports) concerning the prevalence and nature of any behavioural changes related to specific phobias in a cohort of patients representing canonical syndromes of FTD and Alzheimer's disease (AD), relative to healthy older controls. Neuroanatomical correlates of altered phobic reactivity were assessed using voxel-based morphometry., Results: 46 patients with bvFTD, 20 with semantic variant primary progressive aphasia, 25 with non-fluent variant primary progressive aphasia, 29 with AD and 55 healthy age-matched individuals participated. Changes in specific phobia were significantly more prevalent in the combined FTD cohort (15.4% of cases) and in the bvFTD group (17.4%) compared both to healthy controls (3.6%) and patients with AD (3.5%). Attenuation of phobic reactivity was reported for individuals in all participant groups, however new phobias developed only in the FTD cohort. Altered phobic reactivity was significantly associated with relative preservation of grey matter in left posterior middle temporal gyrus, right temporo-occipital junction and right anterior cingulate gyrus, brain regions previously implicated in contextual decoding, salience processing and reward valuation., Conclusion: Altered phobic reactivity is a relatively common issue in patients with FTD, particularly bvFTD. This novel paradigm of strong fear experience has broad implications: clinically, for diagnosis and patient well-being; and neurobiologically, for our understanding of the pathophysiology of aversive sensory signal processing in FTD and the neural mechanisms of fear more generally., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Co-existence of depression and anxiety can be associated with severe detrimental consequences to the physical, mental and social wellbeing of the affected populations. This study was conducted to determine prevalence of depressive and anxiety symptoms among Palestinian medical students and to investigate associations between sociodemographic factors of the students with depressive and anxiety symptoms., Methods: This study was conducted in a cross-sectional observational design using a questionnaire in the period between September 2018 and April 2019 in a major university in the West Bank of Palestine. Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II) and anxiety symptoms were assessed using the Beck Anxiety Inventory (BAI). The questionnaire also collected the sociodemographic characteristics of the students. Reliability of the questionnaire was tested using the test re-test method. A total of 425 medical students were invited to participate in the study., Results: Of those invited, 286 students completed the questionnaire, giving a response rate of 67.3%. More than half (56.6%) of the students had minimal depression, 20.3% had mild depression, 14.0% had moderate depression, 9.1% had severe depression, 23.4% had no anxiety, 29.7% had mild to moderate anxiety, 25.5% had moderate to severe anxiety, and 21.3% had severe anxiety. Multiple linear regression analysis showed that academic stage (p-value < 0.01), Grade Point Average (p-value < 0.01), mental health status (p-value < 0.001), ever attempted suicide (p-value < 0.05), and religious commitment (p-value < 0.01) were predictors of BDI-II scores. Multiple linear regression analysis showed that academic stage (p-value < 0.05) and mental health status (p-value < 0.001) were predictors of BAI scores., Conclusions: Depressive and anxiety symptoms were prevalent among Palestinian medical students in a major university in the West Bank of Palestine. Interventions might be designed to improve self-rated mental health of medical students in their academic years, ameliorate study conditions, and provision of counseling services to improve spirituality might be effective in reducing symptoms of depression and anxiety among medical students in Palestine. Future studies are still needed to investigate if these interventions could be useful in reducing depressive and anxiety symptoms among Palestinian medical students.

MAPT mutations were the first discovered genetic cause of frontotemporal dementia (FTD) in 1998. Since that time, over 60 MAPT mutations have been identified, usually causing behavioral variant FTD and/or parkinsonism clinically. We describe 2 novel MAPT mutations, D252V and G389&#95;I392del, each presenting in a patient with behavioral variant FTD and associated language and cognitive deficits. Neuroimaging revealed asymmetrical left greater than right temporal lobe atrophy in the first case, and bifrontal atrophy in the second case. Disease duration was 8 years and 5 years, respectively. Postmortem examination in both patients revealed a 3-repeat predominant tauopathy, similar in appearance to Pick's disease. These 2 mutations add to the literature on genetic FTD, both presenting with similar clinical and imaging features to previously described cases, and pathologically showing a primary tauopathy similar to a number of other MAPT mutations., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, a known pathological process of FTD, but has yet to be explored as potential biomarker., Methods: Plasma GFAP and neurofilament light chain (NfL) concentration were measured in 469 individuals enrolled in the Genetic FTD Initiative: 114 C9orf72 expansion carriers (74 presymptomatic, 40 symptomatic), 119 GRN mutation carriers (88 presymptomatic, 31 symptomatic), 53 MAPT mutation carriers (34 presymptomatic, 19 symptomatic) and 183 non-carrier controls. Biomarker measures were compared between groups using linear regression models adjusted for age and sex with family membership included as random effect. Participants underwent standardised clinical assessments including the Mini-Mental State Examination (MMSE), Frontotemporal Lobar Degeneration-Clinical Dementia Rating scale and MRI. Spearman's correlation coefficient was used to investigate the relationship of plasma GFAP to clinical and imaging measures., Results: Plasma GFAP concentration was significantly increased in symptomatic GRN mutation carriers (adjusted mean difference from controls 192.3 pg/mL, 95% CI 126.5 to 445.6), but not in those with C9orf72 expansions (9.0, -61.3 to 54.6), MAPT mutations (12.7, -33.3 to 90.4) or the presymptomatic groups. GFAP concentration was significantly positively correlated with age in both controls and the majority of the disease groups, as well as with NfL concentration. In the presymptomatic period, higher GFAP concentrations were correlated with a lower cognitive score (MMSE) and lower brain volume, while in the symptomatic period, higher concentrations were associated with faster rates of atrophy in the temporal lobe., Conclusions: Raised GFAP concentrations appear to be unique to GRN -related FTD, with levels potentially increasing just prior to symptom onset, suggesting that GFAP may be an important marker of proximity to onset, and helpful for forthcoming therapeutic prevention trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders with both sporadic and genetic forms. Mutations in the progranulin gene (GRN) are a common cause of genetic FTD, causing either a behavioural presentation or, less commonly, language impairment. Presence on T2-weighted images of white matter hyperintensities (WMH) has been previously shown to be more commonly associated with GRN mutations rather than other forms of FTD. The aim of the current study was to investigate the longitudinal change in WMH and the associations of WMH burden with grey matter (GM) loss, markers of neurodegeneration and cognitive function in GRN mutation carriers. 336 participants in the Genetic FTD Initiative (GENFI) study were included in the analysis: 101 presymptomatic and 32 symptomatic GRN mutation carriers, as well as 203 mutation-negative controls. 39 presymptomatic and 12 symptomatic carriers, and 73 controls also had longitudinal data available. Participants underwent MR imaging acquisition including isotropic 1 mm T1-weighted and T2-weighted sequences. WMH were automatically segmented and locally subdivided to enable a more detailed representation of the pathology distribution. Log-transformed WMH volumes were investigated in terms of their global and regional associations with imaging measures (grey matter volumes), biomarker concentrations (plasma neurofilament light chain, NfL, and glial fibrillary acidic protein, GFAP), genetic status (TMEM106B risk genotype) and cognition (tests of executive function). Analyses revealed that WMH load was higher in both symptomatic and presymptomatic groups compared with controls and this load increased over time. In particular, lesions were seen periventricularly in frontal and occipital lobes, progressing to medial layers over time. However, there was variability in the WMH load across GRN mutation carriers - in the symptomatic group 25.0% had none/mild load, 37.5% had medium and 37.5% had a severe load - a difference not fully explained by disease duration. GM atrophy was strongly associated with WMH load both globally and in separate lobes, and increased WMH burden in the frontal, periventricular and medial regions was associated with worse executive function. Furthermore, plasma NfL and to a lesser extent GFAP concentrations were seen to be associated with increased lesion burden. Lastly, the presence of the homozygous TMEM106B rs1990622 TT risk genotypic status was associated with an increased accrual of WMH per year. In summary, WMH occur in GRN mutation carriers and accumulate over time, but are variable in their severity. They are associated with increased GM atrophy and executive dysfunction. Furthermore, their presence is associated with markers of WM damage (NfL) and astrocytosis (GFAP), whilst their accrual is modified by TMEM106B genetic status. WMH load may represent a target marker for trials of disease modifying therapies in individual patients but the variability across the GRN population would prevent use of such markers as a global outcome measure across all participants in a trial., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Varicella zoster virus (VZV) infection has been implicated in multiple sclerosis (MS), but direct causal involvement has been disputed. Nevertheless, knowledge of VZV exposure is important, given the risk of serious complications of first exposure while undergoing immunosuppressive treatment, in particular with fingolimod. We distributed questionnaires to MS clinic patients, requesting information about history of chickenpox, sibling/household/occupational exposure, history of zoster (shingles), and disease-modifying treatment. A random, proportionally representative sample of 51 patients that included patients with positive, negative, and unknown chickenpox history were selected for determination of VZV IgG by ELISA. Of 1206 distributed questionnaires, 605 were returned (50% response rate). Of these, 86% reported history of chickenpox, 5.6% gave negative history, and 8.5% did not know. Of 594 who answered the zoster question, 78% gave a negative response, 4% did not know, and 104 (17%) answered yes. Of these, 83 reported 1 episode; 12 had 2; 5 had 3; and 1 each reported 5, 6, and 15 episodes. Of 51 patients tested for VZV IgG (44 "yes," 4 "no," and 3 "I don't know" answers to the question of whether they had chickenpox), 48 were seropositive; the 3 seronegative all had reported having had chickenpox. The high rate of MS patients reporting prior chickenpox infection is comparable with previous reports. A substantial proportion of MS patients, estimated to be higher than an age-matched general population, report single or multiple episodes of zoster. These data are useful for consideration of immunosuppressive treatments and/or VZV and zoster vaccination.

Growth in planted areas of Miscanthus for biomass in Europe has stagnated since 2010 due to technical challenges, economic barriers and environmental concerns. These limitations need to be overcome before biomass production from Miscanthus can expand to several million hectares. In this paper, we consider the economic and environmental effects of introducing seed based hybrids as an alternative to clonal M. x giganteus ( Mxg ). The impact of seed based propagation and novel agronomy was compared with current Mxg cultivation and used in 10 commercially relevant, field scale experiments planted between 2012 and 2014 in the United Kingdom, Germany, and Ukraine. Economic and greenhouse gas (GHG) emissions costs were quantified for the following production chain: propagation, establishment, harvest, transportation, storage, and fuel preparation (excluding soil carbon changes). The production and utilization efficiency of seed and rhizome propagation were compared. Results show that new hybrid seed propagation significantly reduces establishment cost to below £900 ha -1 . Calculated GHG emission costs for the seeds established via plugs, though relatively small, was higher than rhizomes because fossil fuels were assumed to heat glasshouses for raising seedling plugs (5.3 and 1.5 kg CO 2 eq. C Mg [dry matter (DM)] -1 ), respectively. Plastic mulch film reduced establishment time, improving crop economics. The breakeven yield was calculated to be 6 Mg DM ha -1 y -1 , which is about half average United Kingdom yield for Mxg ; with newer seeded hybrids reaching 16 Mg DM ha -1 in second year United Kingdom trials. These combined improvements will significantly increase crop profitability. The trade-offs between costs of production for the preparation of different feedstock formats show that bales are the best option for direct firing with the lowest transport costs (£0.04 Mg -1 km -1 ) and easy on-farm storage. However, if pelleted fuel is required then chip harvesting is more economic. We show how current seed based propagation methods can increase the rate at which Miscanthus can be scaled up; ∼×100 those of current rhizome propagation. These rapid ramp rates for biomass production are required to deliver a scalable and economic Miscanthus biomass fuel whose GHG emissions are ∼1/20th those of natural gas per unit of heat.

The human oocyte is surrounded by the zona pellucida—an elastic, transparent extracellular matrix consisting of specific glycoproteins. The zona pellucida is preserved after fertilization and surrounds the developing human embryo for a few days. The embryo needs to get out of the zona pellucida before implantation to establish cell contacts between the trophectoderm and endometrial epithelium. The release of the embryo from the zona pellucida is carried out at the stage of the blastocyst and called zona hatching. During zona hatching the blastocyst breaks the zona pellucida and performs active movements to escape through a gap formed in the zona. While microscopic description of zone hatching is well known, biochemical and cytological basis of zone hatching remains poorly understood. The break of the zona pellucida occurs under the influence of two forces: mechanical pressure of the growing blastocyst on the zone and chemical dissolution of the zone material with secreted lytic enzymes. There is only one paper (Sathananthan et al., 2003), which describes the specialized cells in the trophectoderm that locally dissolve the zona pellucida, promoting the emergence of the hole for blastocyst release. Taking into account the singleness of the paper and the absence of further development of this subject by the authors in the following decade, the existence of specialized cells for zone hatching should be assumed with great care. Lytic enzymes, secreted by cells of the trophectoderm for dissolving the zona pellucida, are different. Depending on the species of the mammal, different classes of proteases participate in the zone hatching process: serine proteases, cysteine proteases, metalloproteinases. Proteases, secreted by human trophectoderm, are not described. The mechanisms of the active movement during blastocyst hatching are investigated to a lesser degree. Only the involvement of the cytoskeleton of trophectoderm cells in the mechanism of blastocyst compression was shown, and the participation of desmosomes in the coordinated change in the form of trophectoderm cells during compression is suggested. This review summarizes literature data on the possible mechanisms of zone hatching in the development of human embryos, obtained in experiments in vitro, as well as in animal models.

Terbinafine is a commonly prescribed antifungal agent used in the treatment of trichophytic onychomycosis and chronic cutaneous mycosis that are resistant to other treatments. This case report highlights a rarely documented but important adverse hepatic reaction that was caused by the use of oral terbinafine. A woman in her thirties presented with a 3-week history of jaundice, malaise, itching, nausea, decreased appetite, weight loss, dark orange urine and intermittent non-radiating epigastric pain. She had recently finished a 3-week course of oral terbinafine for a fungal nail infection. Liver biopsy findings were consistent with chronic active hepatitis secondary to a drug reaction. A few days after initial presentation, the patient developed erythema nodosum. Delayed development of erythema nodosum secondary to terbinafine could not be excluded., (2014 BMJ Publishing Group Ltd.)

Training in procedures has been identified as the top priority for core medical trainees (GMC trainee survey 2011). Current practice relies on each trainee being lucky enough to encounter each procedure during clinical rotations and during on-calls. Where trainees are not lucky enough, they are entering their registrar years without the skills to efficiently lead the medical 'on-take'.(1) This can lead to delays in patient diagnosis or treatment. Because a single delay can easily burgeon into a lengthy series of multiple delays, this can lead to an associated prolongation of patient stay.(3) Both confidence and competence in practical procedures can be increased with a procedure bleep system. A dedicated procedure bleep, carried on a rotational basis alerts the bleep holder when a medical procedure is planned. The bleep holder then attends to observe, assist, perform, or teach the relevant procedure. This scheme shares the opportunities for procedure exposure amongst all trainees and ensures that a good breadth of experience has been gained independent of current placement. Formal evaluation revealed that 95% (19/20) of junior trainees felt more confident and competent as a result of participation. Furthermore, consultants felt this initiative reduced the burden on the medical registrars on-call. By ensuring our diagnostic and therapeutic interventions are conducted efficiently, we are actively reducing length of hospital stay and improving the standard of healthcare provided.

Objectives: The performance of an adequate and complete series of cervical radiographs in the trauma patient is essential in order to ensure safe trauma management. Eastern Association for the Surgery of Trauma (EAST) has produced widely recognised guidelines with which trauma units should comply. The aim of the study is to ascertain the adequacy of cervical spine imaging of trauma patients in a specialist trauma unit (head injury) using EAST guidelines as gold standard. An additional assessment of institutional reporting accuracy is conducted., Methods: Data were examined from 81 consecutive trauma patients requiring cervical spine radiography. EAST guidelines were applied retrospectively to this cohort in order to define guideline compliance. An additional cohort assessment was conducted addressing the accuracy and adequacy of the formal institutional reports associated with these radiographs., Results: 99% of patients undergoing a full cervical trauma series had at least one inadequate initial image. Of these, 85% had at least one inadequate lateral or peg view (of which 26% did not have repeat radiographs performed). Over one-third of all trauma patients left the emergency department with inadequate cervical spine imaging (incomplete cervical spine series or inadequate films). From the institutional reporting perspective, only 27% of all inadequate initial and repeat lateral or peg views were subsequently explicitly reported as being inadequate., Discussion: These findings call into question current practice. Clearly, multiple confounders exist in the context of process variability in a heterogeneous population such as that attending an emergency department. This study offer solutions to address this problem.

Restoration of disturbed functions of the organs and tissues is the main task of contemporary genetic and cellular biotechnology, including genetic and cellular therapy. Duchenne dystrophy, one of the most widespread human genetic diseases, is at the same time the most extensively studied from the viewpoint of both genetic and histological changes leading to muscle fiber degeneration. Although many studies carried out on models, recognized analogous to Duchenne dystrophy, gave hopeful results, clinical tests with the use of developed methods gave no expected success and the rate of mortality from this disease amounts to 100%. Based on the world experience and analysis of the authors' data, possible influence of the intensity of regeneration on success of genetic and cellular therapy has been considered.

"Gene-gun" ballistic transfection (BT) was used to deliver genetic constructs pMLVDy and pHSADy containing full-length cDNA of the dystrophin gene to musculus quadriceps remoris and musculus gluteus of mdx mice, which represent a natural model of Duchenne muscular dystrophy. Clusters of dystrophin-positive muscular fibers (DPMF) were immunocytochemically detected in sites exposed to BT. The average number of DPMF was 2% by the 17th day and 3% by the 60th day after BT with pMLVDy, whereas the number of revertant DPMF was 0.2% in control mice (without BT). When pHSADy was used, the average number of DPMF was 3% 20 days after BT. In this case, dystrophin was uniformly spread though the myoplasm in 3% of cells and produced a slight signal in separate regions under the sarcolemma in 10% of muscle fibers. The number of revertant DPMF increased to 0.6% after BT with naked particles and to 2.8% after BT with the marker lacZ gene, in both bombarded and contralateral legs. The number of DPMF in the corresponding muscles of the contralateral leg significantly increased and reached 2.8% by the 60th day after BT with pMLVDy and 6.7% by the 20th day after BT with pHSADy. Human dystrophin gene cDNA was detected in all skeletal muscles, heart, intestine, tongue, and brain by polymerase chain reaction (PCR) three weeks after BT. Immunoblot analysis showed that normal 427-kDa human dystrophin was synthesized in muscles of mdx mice. The results suggest applicability of BT for delivery of dystrophin constructs into muscles.

Changes in morphological dimensions of MDX mouse myofibres in M. rectus femoris were recorded after ballistic transfection (BT) with pHSADys and pVMMDys plasmids containing cDNA of the full-length human dystrophin gene. The dystrophin expression was observed by an immunomorphological procedure with P6 antibody and PAP method. Dystrophin positive (dyst+) myofibres were divided into two types, with a typical dystrophin expression under sarcoplasma membrane and an atypical expression through the whole sarcoplasm, respectively. The share of atypical dyst+ myofibres was seen to rise during the experiment from 27%, at 2-3 weeks after BT, up 84% by 2 months after BT. The atypical dyst+ myofibres usually underwent destruction. At the same time, the share of entire dyst+ myofibres decreased from 17 to 2-5% by 2 months. Morphological dimensions of the myofibres (square in mkm2, perimeter, smallest and largest diameters) were calculated with the help of computer analyser. The middle square of both types of dyst+ myofibres was larger than that of dyst- myofibres, both in BT target M. rectus femoris and in the same contralateral muscle, but never exceeded the value of middle square of C57B1 mouse myofibres in the same muscle. The form of dyst+ myofibres was not modified by the dystrophin expression. The nuclei of dyst+ myofibres remained in the central region of sarcoplasm. A conclusion is made that BT of human dystrophin gene inside MDX mouse myofibres allows dystrophin gene expression and enlargement of the dyst+ myofibres. Dystrophin expression is not able to induce a complete and stable differentiation of striated muscle of adult MDX mice.

Ballistic transfection, based on cell and tissue bombardment by the tungsten and gold microparticles covered with the gene DNA, was used for the delivery of a bacterial beta-galactosidase and a full-length cDNA copy of the human dystrophin genes into mouse skeletal muscles. CMV-lacZ, SV40-lacZ, LTR-lacZneo and full-length cDNA dystrophin (pDMD-1, approximately 16 kb) in eukaryotic expression vector pJ OMEGA driven by mouse leukaemia virus promotor (pMLVDy) were used throughout the studies. Musculus glutaeus superficialis of C57BL/6J and quadriceps femoris of mdx male mice were opened surgically under anesthesia and bombarded by means of the gene-gun technique originally developed by us. Different mixtures of gold and tungsten particles at ratios of 4:1, 1:1, 1:4 were applied. X-gal assay revealed marked beta-gal activity, both in total muscles and whole muscle fibers on histological sections, up to three months after transfection. The most intensive staining was observed after SV40-lacZ delivery. No staining was detected with LTR-lacZneo DNA as well as in untreated muscles. The higher tungsten particle concentration in the bombardment mixture correlated with more intense X-gal staining. At the gold/tungsten ratio of 1:4 the microparticles penetrated the musculus glutaeus superficialis and transfected the underlying musculus glutaeus medius as well. Immuno-cytochemical assay for human dystrophin revealed dystrophin positive myofibers (DPM) in the bombarded area up to two months after transfection. The proportion of DMP varied from 2.5% on day 17 up two 5% on day 60 after bombardment compared to only 0.5% in the control mdx mice. These results suggest the applicability of particle bombardment for gene delivery into muscle fibers.

A simple new method for preparing plasmid DNA and preformed zwitterionic liposome complexes is proposed. The ability of these metallonucleoliposome complexes to serve as a vehicle for gene delivery to mammalian cells in vivo was studied. A high level of expression of the reporter gene introduced was observed in mouse skeletal muscles in vivo.

The method of ballistic transfection initially proposed for genetic transformation of plants was used for animal cells in vitro and in situ. The method consists in bombarding the transfected cells with microparticles of heavy metals carrying foreign DNA. Having penetrated in the cell nucleus, the microparticles transport the introduced gene. Successful genetic transformation of the cultured mouse cells and fish embryos was realized and this allowed to study mammalian cells in situ. The studies performed allowed us to demonstrate expression of the reporter genes of chloramphenicol acetyltransferase, galactosidase and neomycin phosphotransferase in the mouse liver, mammary gland and kidney explants, in the liver and cross-striated muscle of mouse and rat in situ and in developing mouse embryos at the stages of two-cell embryo, morula and blastocyst. All these genes were introduced by ballistic transfection. In the liver and cross-striated muscle the transgene activity was found within two-three months after transfection. Thus, the ballistic introduction of the foreign genes in the cells in situ was demonstrated and this opens possibilities for the use of this method in gene therapy. Methodical aspects of the bombarding and transfection are considered in detail and the published data on transfection and genetic transformation of mammalian cells are discussed.