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The Topical Collection “Accrual of Climate Change Risk in Six Vulnerable Countries” provides a harmonised assessment of risks to human and natural systems due to global warming of 1.5–4 °C in six countries (China, Brazil, Egypt, Ethiopia, Ghana, and India) using a consistent set of climate change and socioeconomic scenarios. It compares risks in 2100 if warming has reached 3 °C, broadly corresponding to current global greenhouse gas emission reduction policies, including countries’ National Determined Contributions, rather than the Paris Agreement goal of limiting warming to ‘well below’ 2 °C and ‘pursuing efforts’ to limit to 1.5 °C. Global population is assumed either constant at year 2000 levels or to increase to 9.2 billion by 2100. In either case, greater warming is projected to lead, in all six countries, to greater exposure of land and people to drought and fluvial flood hazard, greater declines in biodiversity, and greater reductions in the yield of maize and wheat. Limiting global warming to 1.5 °C, compared with ~ 3 °C, is projected to deliver large benefits for all six countries, including reduced economic damages due to fluvial flooding. The greatest projected benefits are the avoidance of a large increase in exposure of agricultural land to severe drought, which is 61%, 43%, 18%, and 21% lower in Ethiopia, China, Ghana, and India at 1.5 °C than at 3 °C, whilst avoided increases in human exposure to severe drought are 20–80% lower at 1.5 °C than 3 °C across the six countries. Climate refugia for plants are largely preserved at 1.5 °C warming in Ghana, China, and Ethiopia, but refugia shrink in areal extent by a factor of 2, 3, 3, 4, and 10 in Ghana, China, India, Ethiopia, and Brazil, respectively, if warming reaches 3 °C. Economic damages associated with sea-level rise are projected to increase in coastal nations, but more slowly if warming were limited to 1.5 °C. Actual benefits on the ground will also depend on national and local contexts and the extent of future investment in adaptation. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease, whereas the underlying molecular trails involved in its pathogenesis are not fully elucidated. Hence, the current study aimed to investigate the role of miRNA-373/P2X7/NLRP3/NF-κB trajectory in its pathogenesis as well as the possible anti-inflammatory effects of probenecid and l-carnitine in ameliorating osteoarthritis via modulating this pathway. In the current study, male Sprague Dawley rats were used and monoiodoacetate (MIA)-induced knee osteoarthritis model was adopted. Probenecid and/or L-carnitine treatments for 14 days succeeded in reducing OA knee size and reestablishing motor coordination and joint mobility assessed by rotarod testing. Moreover, different treatments suppressed the elevated serum levels of IL-1β, IL-18, IL-6, and TNF-α via tackling the miRNA-373/P2X7/NLRP3/NF-κB, witnessed as reductions in protein expressions of P2X7, NLRP3, cleaved caspase-1 and NF-κB. These were accompanied by increases in procaspase-1 and IκB protein expression and in miRNA-373 gene expression OA knee to various extents. In addition, different regimens reversed the abnormalities observed in the H and E as well as Safranin O-Fast green OA knees stained sections. Probenecid or l-carnitine solely showed comparable results on the aforementioned parameters, whereas the combination therapy had the most prominent effect on ameliorating the aforementioned parameters. In conclusion, l-carnitine augmented the probenecid's anti-inflammatory effect to attenuate MIA-induced osteoarthritis in rats by provoking the miRNA-373 level and inhibiting the P2X7/NLRP3/NF-κB milieu, leading to the suppression of serum inflammatory cytokines: IL-1β, IL-18, IL-6, and TNF-α. These findings suggest the possibility of using probenecid and l-carnitine as a useful therapeutic option for treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the accuracy and inter-observer agreement of a quantitative pulmonary surface irregularity (PSI) score on high-resolution chest CT (HRCT) for predicting transplant-free survival in patients with IPF. For this IRB-approved HIPAA-compliant retrospective single-center study, adult patients with IPF and HRCT imaging (N = 50) and an age- and gender-matched negative control group with normal HRCT imaging (N = 50) were identified. Four independent readers measured the PSI score in the midlungs on HRCT images using dedicated software while blinded to clinical data. A t-test was used to compare the PSI scores between negative control and IPF cohorts. In the IPF cohort, multivariate cox regression analysis was used to associate PSI score and clinical parameters with transplant-free survival. Inter-observer agreement for the PSI score was assessed by intraclass correlation coefficient (ICC). The technical failure rate of the midlung PSI score was 0% (0/100). The mean PSI score of 5.38 in the IPF cohort was significantly higher than 3.14 in the negative control cohort (p <.001). In the IPF cohort, patients with a high PSI score (≥ median) were 8 times more likely to die than patients with a low PSI score (HR: 8.36; 95%CI: 2.91–24.03; p <.001). In a multivariate model including age, gender, FVC, DLCO, and PSI score, only the PSI score was associated with transplant-free survival (HR:2.11 per unit increase; 95%CI: 0.26–3.51; p =.004). Inter-observer agreement for the PSI score among 4 readers was good (ICC: 0.88; 95%CI: 0.84–0.91). The PSI score had high accuracy and good inter-observer agreement on HRCT for predicting transplant-free survival in patients with IPF. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the ability of parasternal intercostal thickening fraction (PIC TF) to predict the need for mechanical ventilation, and survival in subjects with severe Coronavirus disease-2019 (COVID-19). This prospective observational study included adult subjects with severe COVID-19. The following data were collected within 12 h of admission: PIC TF, respiratory rate oxygenation index, P aO 2 / F iO 2 ratio, chest CT, and acute physiology and chronic health evaluation II score. The ability of PIC TF to predict the need for ventilatory support (primary outcome) and a composite of invasive mechanical ventilation and/or 30-days mortality were performed using the area under the receiver operating characteristic (AUC) analysis. Multivariate analysis was done to identify the independent predictors for the outcomes. Fifty subjects were available for the final evaluation. The AUC (95% confidence interval [CI]) for the right and left PIC TF ability to predict the need for ventilator support was 0.94 (0.83–0.99), 0.94 (0.84–0.99), respectively, with a cut off value of > 8.3% and positive predictive value of 90–100%. The AUC for the right and left PIC TF to predict invasive mechanical ventilation and/or 30 days mortality was 0.95 (0.85–0.99) and 0.90 (0.78–0.97), respectively. In the multivariate analysis, only the PIC TF was found to independently predict invasive mechanical ventilation and/or 30-days mortality. In subjects with severe COVID-19, PIC TF of 8.3% can predict the need to ventilatory support with a positive predictive value of 90–100%. PIC TF is an independent risk factor for the need for invasive mechanical ventilation and/or 30-days mortality. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that Trimetazidine (TMZ) improves vascular endothelial function and reduces the inflammatory process progression. However, limited data have been available regarding its effects on myocardial fibrosis following ischemia and causing left ventricular dysfunction. Purpose: To investigate the impact of TMZ adjuvant therapy for ischemic cardiomyopathy (ICM) on cardiac fibrosis, vascular endothelial function, inflammation, and myocardial functions. Methods: This randomized, double-blind controlled clinical trial included 48 patients (aged 59.4 ± 9 years) with ICM who were randomly assigned to two groups: TMZ 35 mg twice daily and placebo in addition to conventional ICM medications. All patients received the tablets for 3 months. Both groups were then compared in terms of connective tissue growth factor (CTGF), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-α), and some echocardiographic indices, weekly angina attacks and nitrate consumption before and after treatment. Results: No significant differences between CTGF, ET-1, and TNF-α levels, in addition to some echocardiographic indices, were observed between both groups before treatment. After treatment, the TMZ group had significantly lower ET-1 than the placebo group, with both groups exhibiting a substantial decrease in TNF-α and CTGF. The TMZ group had lower mean ± SD levels for TNF-α and CTGF and showed significant improvement in echocardiographic indices and weekly angina attacks after treatment. Conclusion: Adjunctive TMZ therapy for ICM effectively improved vascular endothelial function and reduced inflammation. Furthermore, our exploratory findings may be used to provide new information on the potential effects of TMZ on myocardial fibrosis by downregulating CTGF. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate Eustachian tube (ET) function tests and their impact on outcomes of tympanoplasty in patients with inactive chronic suppurative otitis media. Materials and methods: A prospective study was conducted involving patients diagnosed with chronic suppurative otitis media (CSOM) and having a central dry perforation. Assessment of the ET function was done for all included cases by three tests; pressure swallow equalization test, saccharine test and methylene blue test. The primary outcome is the graft success rate defined as intact graft without any residual perforation at 6 months postoperatively. Secondary outcomes include hearing assessment and possible associated complications. Results: 64 patients were included in the study with an average age of 36.59 ± 11.96 years. All patients underwent assessment of the ET function by saccharine test, methylene blue test and pressure equalization test (PET) followed by microscopic post-auricular tympanoplasty. Successful tympanoplasty is achieved in 93.75% of cases with residual perforation in four patients. Mean air–bone gap is significantly improved from 23.73 ± 2.80 preoperatively to 10.93 ± 5.46 postoperatively. Results of Methylene blue test has no statistical impact on graft take rate (p value = 0.379), while saccharine test and pressure equalization test results have statistically significant correlation with graft success (p value ≤ 0.001). Conclusions: Saccharine and Pressure equalization tests have a good positive correlation with the graft healing in tympanoplasty, while methylene blue test was found to have no correlation with the success rate. [ABSTRACT FROM AUTHOR]

In this retrospective study , we present the findings in 250 homicides by asphyxia in Denmark in a 25-year period, with a particular focus on the autopsy findings in strangulation. Our intention is for the results to be used in future death investigations, where difficulties in interpretation of findings in potential asphyxial deaths arise. Asphyxia homicides showed a strong bias with respect to sex, age, and homicide type. The frequent female victim was typically an adult, whereas the rarer male victim was most often a child. Female offenders most often killed their children, and male offenders most often killed their female partner. Generally, most asphyxia homicides took place in a domestic setting. Manual strangulation and ligature strangulation were the most common mechanisms of asphyxia homicides (81.6%). A lack of petechial hemorrhages, especially in the conjunctiva, was rare in homicidal strangulation, but there were exceptions, especially when there was postmortem decomposition, making it impossible to verify them. Most victims of strangulation had skin lesions in the face (including the jawline) or on the neck, with accompanying hemorrhages in muscle and connective tissue, but the findings could be subtle or compounded by decomposition. Fractures of the laryngo-hyoid complex were common in strangulation, particularly in manual strangulation (chi-sq = 4.0993, df = 1, P < 0.05) and were clearly related to the age of the victim (chi-sq = 82.193, df = 4, P < 0.001). In children and young adults dying from homicidal strangulation, a lack of fractures is to be expected, while a lack of fractures is unusual, but not entirely unexpected, for adults and aged people. [ABSTRACT FROM AUTHOR]

Background and Objective: Paclitaxel and doxorubicin are associated with neurotoxicity and cardiotoxicity respectively. This study aimed at investigating the role of alpha-lipoic acid (ALA) in counteracting paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer.Patients and Methods: This randomized double-blind placebo-controlled prospective study included 64 patients with breast cancer who were randomized into control group (n = 32) which received 4 cycles of doxorubicin plus cyclophosphamide (every 21 days) followed by weekly doses of paclitaxel for 12 weeks plus placebo tablets once daily and ALA group (n = 32) which received the same chemotherapeutic regimen plus ALA 600 once daily for 6 months. Patients were assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) for grading of neuropathy and by 12-item neurotoxicity questionnaire (Ntx-12). The assessment included also echocardiography and evaluation of serum levels of brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and neurotensin (NT). Data were analyzed by paired and unpaired t-test, Mann-Whitney U test, and chi-square test.Results: As compared to placebo, ALA provoked significant improvement in NCI-CTCAE neuropathy grading and Ntx-12 score after the end of 9th and 12th weeks of paclitaxel intake (p = 0.039, p = 0.039, p = 0.03, p = 0.004, respectively). At the end of the chemotherapy cycles, ALA resulted in significant decline in serum levels of BNP, TNF-α, MDA, and neurotensin (p < 0.05) as compared to baseline data and placebo.Conclusion: Alpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer.Trial Registration: ClinicalTrials.gov: NCT03908528. [ABSTRACT FROM AUTHOR]

The present study was designed to evaluate the possible protective effects of melatonin (MEL) and/or l-carnitine (L-CAR) against methotrexate (MTX)-induced toxicity in isolated rat hepatocytes. Hepatocytes were prepared using collagenase techniques of perfusion and digestion of rat liver. Trypan blue uptake, as well as, glutathione (GSH), lipid peroxidation (LPO), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-α) levels were measured. Caspase-3 activity was also assessed. Pre-incubation of hepatocytes with MEL (1 mM) and/or l-CAR (10 mM) 30 min prior to intoxication with MTX, significantly protected hepatocytes against toxicity. In addition, LPO, NO, TNF-α levels, and caspase-3 activity were decreased in comparison to the MTX-intoxicated group. Furthermore, the two drugs increased the MTX-depleted GSH level. MEL and L-CAR prevented MTX-induced hepatocytotoxicity, at least partly, by their antioxidative, antiinflammatory, and antiapoptotic effects. Further studies are recommended on the clinical pharmacologic and toxicologic effects of MEL and L-CAR in patients receiving MTX. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) and rheumatoid arthritis (RA) are serious and painful diseases. Protease-activated receptor 2 (PAR2) is involved in the pathology of both OA and RA including roles in synovial hyperplasia, cartilage destruction, osteophyogenesis and pain. PAR2 is activated via cleavage of its N-terminus by serine proteases. In this study a competitive ELISA assay was developed targeting the 36-amino acid peptide that is cleaved and released after PAR2 activation (PRO-PAR2). Technical assay parameters including antibody specificity, intra- and inter-assay variation (CV%), linearity, accuracy, analyte stability and interference were evaluated. PRO-PAR2 release was confirmed after in vitro cleavage of PAR2 recombinant protein and treatment of human synovial explants with matriptase. Serum levels of 22 healthy individuals, 23 OA patients and 15 RA patients as well as a subset of RA patients treated with tocilizumab were evaluated. The PRO-PAR2 antibody was specific for the neo-epitope and intra-inter assay CV% were 6.4% and 5.8% respectively. In vitro cleavage and matriptase treated explants showed increased PRO-PAR2 levels compared to controls. In serum, PRO-PAR2 levels were increased in RA patients and decreased in RA patients treated with tocilizumab. In conclusion, PRO-PAR2 may be a potential biomarker for monitoring RA disease and pharmacodynamics of treatment. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a highly fatal form of liver cancer. Recently, the interest in using amino acids as therapeutic agents has noticeably grown. The present work aimed to evaluate the possible antiproliferative effects of selected amino acids supplementation or deprivation in human HCC cell lines and to investigate their effects on critical signaling molecules in HCC pathogenesis and the outcomes of their combination with the histone deacetylase inhibitor vorinostat. HepG2 and Huh7 cells were treated with different concentrations of l-leucine, l-glutamine, or l-methionine and cell viability was determined using MTT assay. Insulin-like growth factor 1 (IGF1), phosphorylated ribosomal protein S6 kinase (p70 S6K), p53, and cyclin D1 (CD1) protein levels were assayed using ELISA. Caspase-3 activity was assessed colorimetrically. l-leucine supplementation (0.8–102.4 mM) and l-glutamine supplementation (4–128 mM) showed dose-dependent antiproliferative effects in both cell lines but l-methionine supplementation (0.2–25.6 mM) only affected the viability of HepG2 cells. Glutamine or methionine deprivation suppressed the proliferation of HepG2 cells whereas leucine deprivation had no effect on cell viability in both cell lines. The combination between the effective antiproliferative changes in l-leucine, l-glutamine, and l-methionine concentrations greatly suppressed cell viability and increased the sensitivity to vorinostat in both cell lines. The growth inhibitory effects were paralleled with significant decreases in IGF-1, phospho p70 S6k, and CD1 levels and significant elevations in p53 and caspase-3 activity. Changes in amino acids concentrations could profoundly affect growth in HCC cell lines and their response to epigenetic therapy. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to primarily assess the clinical and functional outcomes of arthroscopic treatment of the symptomatic iliopectineal cyst at a minimum 5-year follow-up. Our secondary objective was to document the technical nuances of our arthroscopic technique. Methods: A retrospective review of chart data was performed for 30 patients who underwent arthroscopic treatment of a symptomatic iliopectineal cyst in the period between 1999 and 2015. The mean age of our patients was 57 (33–78) years. All patients completed a minimum follow-up period of 5 years. Our clinical outcomes were assessed by 100 mm VAS for pain, recurrence rate and complications. Functional outcome was evaluated by the modified Harris hip score (mHHS). Patients were asked their level of satisfaction with surgery on a scale of 0–10. Results: In all patients, the valve mechanism of the iliopectineal cyst could be released arthroscopically and the cyst could be completely evacuated. The preoperative symptoms disappeared within 3–6 weeks after the arthroscopic intervention. Patients showed significant improvement in VAS and mHHS 6 months postoperatively and at final follow-up. The average patient satisfaction was 9.2 at 6 months postoperative and 7.9 at final follow-up. None of our patients experienced any complications. At the final follow-up, there was neither clinical nor radiological evidence of cyst recurrence. Conclusions: Arthroscopic treatment of the iliopectineal cyst is a feasible and safe alternative to open surgery resulting in significant improvement of clinical and functional outcomes. [ABSTRACT FROM AUTHOR]

The majority of homicides in the world are caused by firearms and a good understanding of gunshot wounds is important for the forensic pathologist. We have analyzed all 315 homicides by gunshots in Denmark during 1992–2016 with focus on information relevant to forensic pathologists. Of the 1417 homicides in Denmark in 1992–2016, 315 (22.2%) had gunshot trauma as the primary homicide method. During 1992–2016, there has been a significant decrease in the number of gunshot homicides overall, of homicides committed with hunting weapons, and of domestic gunshot homicides. Most victims (70.5%) and offenders (93.7% of homicides with known offenders) were males. Male victims were significantly younger than female victims. Most victims were killed with handguns (43.8%) or shotguns (41.0%). Compared to all other weapons, the victims killed with shotguns had fewer entry wounds, a higher New Injury Severity Score (NISS), and a higher proportion of contact/close-range entry wounds. The head (58.1%) and thorax (46.7%) were often injured, with injuries to the head being more common in contact/close-range entry wounds. The results show that gunshot injuries in homicides are different from suicides and accidents and clearly are affected by the homicide type, the sex of the victim, and the weapon used and that these entities are intertwined. Our findings provide an evidence-based foundation for use in death investigations and for policy development in the area of interpersonal violence. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively validate a method to accurately and rapidly differentiate normal from abnormal spinal bone mineral density (BMD) using colored abdominal CT images. Methods: For this prospective observational study, 196 asymptomatic women ≥ 50 years of age presenting for screening mammograms underwent routine nonenhanced CT imaging of the abdomen. The CT images were processed with software designed to generate sagittal colored images with green vertebral trabecular bone indicating normal BMD and red indicating abnormal BMD (low BMD or osteoporosis). Four radiologists evaluated L1/L2 BMD on sagittal images using visual assessment of grayscale images, quantitative measurements of mean vertebral attenuation, and visual assessment of colored images. Mean BMD values at L1/L2 using quantitative CT with a phantom served as the reference standard. The average accuracy and time of interpretation were calculated. Inter-observer agreement was assessed using intraclass correlation coefficient (ICC). Results: Mean attenuation at L1/L2 was highly correlated with mean BMD (r = 0.96/0.91, p < 0.001 for both). The average accuracy and mean time to assess BMD among four readers for differentiating normal from abnormal BMD was 66% and 6.0 s using visual assessment of grayscale images, 88% and 15.2 s using quantitative measurements of mean vertebral attenuation, and 92% and 2.1 s using visual assessment of colored images (p < 0.001 and p < 0.001, respectively). Inter-observer agreement was poor using visual assessment of grayscale images (ICC:0.31), good using quantitative measurements of mean vertebral attenuation (ICC:0.73), and excellent using visual assessment of colored images (ICC:0.90). Conclusion: Detection of abnormal BMD using colored abdominal CT images was highly accurate, rapid, and had excellent inter-observer agreement. [ABSTRACT FROM AUTHOR]

Purpose: To objectively compare structured and freeform abdominopelvic CT reports based on the number and types of errors as well as report length. Methods: 90 structured and 89 freeform reports from abdominopelvic CT scans with IV contrast obtained for the indication of abdominal pain were randomly selected for review. Each report was reviewed for errors, which were counted and categorized based on the type of error. The total number of words in each report was tallied. Results: 105 total errors were found in the structured reports, compared to 157 total errors in freeform reports. There were 1.16 errors per structured report and 1.76 errors per freeform report (p < 0.001). 48% of structured reports contained at least one error, while 71% of freeform reports contained at least one error (p = 0.002). When a difference existed between the styles with regard to error categories, more errors were observed in freeform reports, with the exception of the duplicated period error where structured reports had more errors. No difference on the basis of average words per report existed, with 219.2 words per report for each reporting style. Conclusion: The use of structured reporting for abdominopelvic CT results in less errors in the report when compared to freeform reporting, potentially reducing clinically significant adverse outcomes in patient care. The report length on the basis of number of words per report is not different between the two reporting styles. [ABSTRACT FROM AUTHOR]

Since the 1990s, there has been a reduction in the homicide rate in Denmark and other Western countries. Our hypothesis is that part of the decrease in the sharp force homicide rate can be explained by better and faster medical treatment over time, and we explore this via stab wound homicides, the largest group of homicides in Denmark. To investigate our hypothesis we undertook an epidemiological study of 428 stab wound homicides in Denmark 1992–2016 based on autopsy reports with registration of stab wounds, quantification of injury severity, treatment intensity and survival time. During 1992–2016, there was a significant reduction in the annual number of victims with a single stab wound, but no reduction in victims with multiple stab wounds. Victims with single stab wounds reached the hospital more often, survived longer and had less severe injuries (New Injury Severity Score (NISS)) than victims with multiple stab wounds. Higher NISS correlated with shorter survival time for all the stab wound victims and for the subgroup that underwent medical treatment. During the 25-year study period, the proportion of victims who underwent surgery before dying increased threefold. The victims in the first half of the study period had shorter survival times than the victims in the last half. We concluded that better and faster medical treatment could partly be responsible for the observed decrease in the number of single stab wound homicides and thereby possibly also in the total number of stab wound homicides. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. Methods: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. Results: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. Conclusion: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries. [ABSTRACT FROM AUTHOR]

An irreversible extrapyramidal syndrome occurs in man after intravenous abuse of "homemade" methcathinone (ephedrone, Mcat) that is contaminated with manganese (Mn) and is accompanied by altered basal ganglia function. Both Mcat and Mn can cause alterations in nigrostriatal function but it remains unknown whether the effects of the 'homemade' drug seen in man are due to Mcat or to Mn or to a combination of both. To determine how toxicity occurs, we have investigated the effects of 4-week intraperitoneal administration of Mn (30 mg/kg t.i.d) and Mcat (100 mg/kg t.i.d.) given alone, on the nigrostriatal function in male C57BL6 mice. The effects were compared to those of the 'homemade' mixture which contained about 7 mg/kg of Mn and 100 mg/kg of Mcat. Motor function, nigral dopaminergic cell number and markers of pre- and postsynaptic dopaminergic neuronal integrity including SPECT analysis were assessed. All three treatments had similar effects on motor behavior and neuronal markers. All decreased motor activity and induced tyrosine hydroxylase positive cell loss in the substantia nigra. All reduced 123I-epidepride binding to D2 receptors in the striatum. Vesicular monoamine transporter 2 (VMAT2) binding was not altered by any drug treatment. However, Mcat treatment alone decreased levels of the dopamine transporter (DAT) and Mn alone reduced GAD immunoreactivity in the striatum. These data suggest that both Mcat and Mn alone could contribute to the neuronal damage caused by the 'homemade' mixture but that both produce additional changes that contribute to the extrapyramidal syndrome seen in man. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn's disease (CD) and colorectal cancer (CRC). Measuring COL6α3 in serum may therefore have potential as a biomarker for gastrointestinal disorders. The aims of this study were to develop and validate a competitive ELISA targeting a specific neo-epitope of COL6α3 and evaluate its associations with the gastrointestinal disorders UC, CD and CRC, in comparison to healthy controls. A monoclonal antibody was raised against a matrix metalloproteinase-2 and -9 specific cleavage site of COL6α3 (C6Mα3) and employed in a competitive enzyme-linked immunosorbent assay (ELISA). The assay was developed and technically validated. Levels of C6Mα3 were measured in serum from patients with UC (n = 58), CD (n = 44) and CRC (n = 39) and compared to healthy controls (n = 32). The levels of C6Mα3 were elevated in patients with UC, CD and CRC patients compared to healthy controls (all p < 0.0001). The area under the receiver operating characteristics (AUROC) curve for separation of patients with UC from healthy controls was 0.972 (95% CI: 0.925–1.020, p < 0.0001), with CD from healthy controls was 0.947 (95% CI: 0.885–1.009, p < 0.0001) and with CRC from healthy controls was 0.890 (95% CI: 0.809–0.972, p < 0.0001). We developed a technically robust assay targeting a fragment of COL6, which was elevated in serum from patients with UC, CD and CRC. [ABSTRACT FROM AUTHOR]

Extracellular matrix in solid tumors has emerged as a specific, stable, and abundant target for affinity-guided delivery of anticancer drugs. Here we describe the homing peptide that interacts with the C-isoform of Tenascin-C (TNC-C) upregulated in malignant tissues. TNC-C binding PL3 peptide (amino acid sequence: AGRGRLVR) was identified by in vitro biopanning on recombinant TNC-C. Besides TNC-C, PL3 interacts via its C-end Rule (CendR) motif with cell-and tissue penetration receptor neuropilin-1 (NRP-1). Functionalization of iron oxide nanoworms (NWs) and metallic silver nanoparticles (AgNPs) with PL3 peptide increased tropism of systemic nanoparticles towards glioblastoma (GBM) and prostate carcinoma xenograft lesions in nude mice (eight and five-fold respectively). Treatment of glioma-bearing mice with proapoptotic PL3-guided NWs improved the survival of the mice, whereas treatment with untargeted particles had no effect. PL3-coated nanoparticles were found to accumulate in TNC-C and NRP-1-positive areas in clinical tumor samples, suggesting a translational relevance. The systemic tumor-targeting properties and binding of PL3-NPs to the clinical tumor sections, suggest that the PL3 peptide may have applications as a targeting moiety for the selective delivery of imaging and therapeutic agents to solid tumors. [ABSTRACT FROM AUTHOR]

One of the most lethal malignancies worldwide is colorectal cancer (CRC). Alterations in various signalling pathways, including PI3K-mTOR and NF-κB, have been reported in CRC with subsequent dysregulation of proliferation, apoptosis, angiogenesis and, questionably, autophagy processes. BEZ-235 (dactolisib) is a dual PI3K-mTOR inhibitor with potent anti-tumour activity. However, the observed toxicity of BEZ-235 necessitated the termination of its clinical trials. Hence, we aimed to evaluate the potential long-lasting anti-carcinogenic effects of adding diosmin (DIO, a natural NF-κB inhibitor) to BEZ-235 in HCT-116 CRC cells. The median inhibitory concentrations (IC50s) of BEZ-235 and/or DIO were evaluated in the HCT-116 CRC cell line. Caspase-3 activity was assessed colorimetrically, and p-Akt, NF-κB, CD1, VEGF and LC3B levels were assessed by ELISA. Additionally, LC3-II and P62 gene expression were assessed using qRT-PCR. The observed CIs (combination indices) and DRIs (dose reduction indices) confirmed the synergistic effect of DIO and BEZ-235. Co-administration of both drugs either in combination-1 (1 μM for BEZ-235, 250 μM for DIO) or in combination-2 (0.51 μM for BEZ-235 + 101.99 μM for DIO) inhibited the PI3K/Akt/mTOR/NF-κB axis, leading to the induction of apoptosis (via active caspase-3), and the inhibition of proliferation marker (CD1), angiogenesis marker (VEGF), autophagy protein (LC3B) and altered effects on LC3-IIandP62 gene expression. Our results reveal the synergistic chemotherapeutic effects of DIO combined with BEZ-235 in the HCT-116 CRC cell line and encourage future preclinical and clinical studies of this combination with reduced BEZ-235 concentrations to avoid its reported toxicity. [ABSTRACT FROM AUTHOR]

To summarize the published forensic pathology evidence base in deaths concluded to be the result of suicidal ligature strangulation, an uncommon entity. Four electronic bibliographic databases Medline Ovid, Embase, Scopus, HEINonline were screened for relevant literature. No date restrictions were applied. All English language case reports or case series were included. Articles were evaluated and key data extracted according to predefined criteria. A total of 1554 references eventually yielded 24 papers with 31 eligible case reports. The location of the deaths and background circumstances and history mirror broadly those of suicide generally. The range of ligature types was diverse. 19/31 cases reported one or more knots present. In the remaining 12 cases, the ligatures did not lend themselves to knots. In only one case were laryngeal fractures reported, but the available material does not justify confidence in that report given the significance of the finding. This systematic review has identified and synthesized the evidence from 31 case reports of suicidal ligature strangulation. A forensic pathologist faced with a possible case can locate it within the spectrum of reported cases and therefore identify its common and distinguishing features. Inherent difficulties for research in forensic pathology mean that case reports are an important source of learning and evidence for the discipline. Opportunities for improvement exist especially in harmonizing terminology and standardizing techniques generally, and in reports of suicidal ligature strangulation in particular. [ABSTRACT FROM AUTHOR]

Quality of life (QoL) disturbances are common after aneurysmal subarachnoid hemorrhage (aSAH) both in physical and mental health domains and their causes are not clearly understood. Corticotropin-releasing hormone receptor 1 (CRHR1) is involved in stress reactivity and development of mental health disturbances after negative life-events. We performed a retrospective cohort study of long-term QoL outcomes among 125 surgically treated aSAH patients (2001–2013). QoL was assessed with Short Form Health Survey (SF-36) and compared to an age and gender matched general population. Genotyping of CRHR1 single nucleotide polymorphisms was performed (Rs7209436, Rs110402, Rs242924) and their effect on QoL scores was explored. aSAH patients experienced a reduced quality of life in all domains. CRHR1 minor genotype was associated with higher SF-36 mental health (OR = 1.31–1.6, p < 0.05), role-emotional (OR = 1.57, p = 0.04) and vitality scores (OR = 1.31–1.38, p < 0.05). Association of all studied SNP's with vitality and Rs242924 with mental health scores remained statistically significant after Bonferroni correction. Mental quality of life scores were associated with physical state of patients, antidepressant history and CRHR1 genotype. Predisposition to mental health disturbances after stressful life-events might be associated with reduced mental QoL after aSAH and selected patients could be provided advanced counselling in the recovery phase. [ABSTRACT FROM AUTHOR]

Background: Chronic intestinal inflammation results in tissue damage partly caused by an increase in matrix metalloproteinases (MMP) activity causing degradation of extracellular matrix (ECM) proteins. We studied intestinal tissue remodeling by quantifying ECM protein fragments in serum in dextran sulfate sodium (DSS)-induced colitis, to investigate ECM protein fragments as serological biomarkers of intestinal tissue remodeling and disease activity.Methods: Male Sprague-Dawley rats received 5% DSS in drinking water for 5 days followed by 11 days with regular water. Disease activity index (DAI) was scored daily. Serum was collected on day 0, 6, 7, and 16. ELISAs were used to quantify MMP-derived remodeling fragments of basement membrane type IV collagen (C4M and PRO-C4) and interstitial matrix type III collagen (C3M and rPRO-C3).Results: In DSS rats, serum levels relative to baseline of C4M, PRO-C4, and C3M were elevated (P < 0.01; P < 0.001; P < 0.001) at day 7, which declined at day 16. Levels of rPRO-C3 were lower in DSS rats at day 7 and increased to normal levels at day 16. The ratio between C3M and rPRO-C3 showed an overall degradation (P < 0.0001) of collagen type III in DSS rats at day 7, which correlated to the DAI (r2 = 0.5588, P < 0.0001).Conclusion: Our data suggest that remodeling of the basement membrane (C4M and PRO-C4) and the interstitial matrix (C3M and rPRO-C3) increased during DSS-induced colitis and declined with reversal of the disease. Thus, serological biochemical biomarkers of the ECM reflect tissue remodeling and could be studied as markers of disease activity in IBD. [ABSTRACT FROM AUTHOR]

Purpose: Both sliding hip screws (SHS) and cancellous screws are used in the surgical management of intracapsular femoral neck fracture. However, there is paucity of information as to which is the superior treatment modality. We performed this systematic review and meta-analysis study to compare the clinical outcomes of SHS and cancellous screws for the treatment of femoral neck fractures in adult patients. Methods: We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL, up to December 2017. Randomized controlled trials (RCTs) directly comparing the clinical outcomes of SHS and cancellous screws for femoral neck fractures were retrieved with no language or publication year restrictions. Data retrieved included operative details, nonunion rate, avascular necrosis, reoperation, infection and mortality, hip pain, functional hip scores, and medical complications. These were pooled as risk ratio or mean difference (MD) with their corresponding 95% confidence interval (CI). Heterogeneity was assessed by Chi-square test. Results: Ten RCTs involving 1934 patients were included in the final analysis. The pooled estimate showed that the SHS group was associated with more intraoperative blood loss (MD = 110.01 ml, 95% CI [52.42, 167.60], p = 0.00002) than the cancellous screws. There was no significant difference in terms of operative time, postoperative hip function, nonunion, avascular necrosis, reoperation rate, infection, fracture healing, hip pain, medical complications, and mortality rate. Conclusion: Based on our study, the cancellous screws group was associated with less intraoperative blood loss in comparison with the SHS group. No other significant differences were found between the two interventions. [ABSTRACT FROM AUTHOR]

Purpose: Elastin is a signature protein of lungs. Increased elastin turnover driven by altered proteolytic activity is an important part of lung tumorigenesis. Elastin-derived fragments have been shown to be pro-tumorigenic, however, little is known regarding the biomarker potential of such elastin fragments. Here, we present an elastin turnover profile by non-invasively quantifying five specific elastin degradation fragments generated by different proteases.Methods: Elastin fragments were assessed in serum from patients with stage I-IV non-small cell lung cancer (NSCLC) (n = 40) and healthy controls (n = 30) using competitive ELISAs targeting different protease-generated fragments of elastin: ELM12 (generated by matrix metalloproteinase MMP-9 and -12), ELM7 (MMP-7), EL-NE (neutrophil elastase), EL-CG (cathepsin G) and ELP-3 (proteinase 3).Results: ELM12, ELM7, EL-NE and EL-CG were all significantly elevated in NSCLC patients (n = 40) when compared to healthy controls (n = 30) (ELM12, p = 0.0191; ELM7, p < 0.0001; EL-NE, p < 0.0001; EL-CG, p < 0.0001). ELP-3 showed no significant difference between patients and controls (p = 0.8735). All fragments correlated positively (Spearman, r: 0.69-0.81) when compared pairwise, except ELM12 (Spearman, r: 0.042-0.097). In general, all fragments were detectable across all stages of the disease.Conclusions: Elastin fragments generated by different proteases are elevated in lung cancer patients compared to healthy controls but differ in their presence. This demonstrates non-invasive biomarker potential of elastin fragments in serum from lung cancer patients and suggests that different pathological mechanisms may be responsible for the elastin turnover, warranting further validation in clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate precision of a software-based liver surface nodularity (LSN) score derived from CT images.Methods: An anthropomorphic CT phantom was constructed with simulated liver containing smooth and nodular segments at the surface and simulated visceral and subcutaneous fat components. The phantom was scanned multiple times on a single CT scanner with adjustment of image acquisition and reconstruction parameters (N = 34) and on 22 different CT scanners from 4 manufacturers at 12 imaging centers. LSN scores were obtained using a software-based method. Repeatability and reproducibility were evaluated by intraclass correlation (ICC) and coefficient of variation. Using abdominal CT images from 68 patients with various stages of chronic liver disease, inter-observer agreement and test-retest repeatability among 12 readers assessing LSN by software- vs. visual-based scoring methods were evaluated by ICC.Results: There was excellent repeatability of LSN scores (ICC:0.79-0.99) using the CT phantom and routine image acquisition and reconstruction parameters (kVp 100-140, mA 200-400, and auto-mA, section thickness 1.25-5.0 mm, field of view 35-50 cm, and smooth or standard kernels). There was excellent reproducibility (smooth ICC: 0.97; 95% CI 0.95, 0.99; CV: 7%; nodular ICC: 0.94; 95% CI 0.89, 0.97; CV: 8%) for LSN scores derived from CT images from 22 different scanners. Inter-observer agreement for the software-based LSN scoring method was excellent (ICC: 0.84; 95% CI 0.79, 0.88; CV: 28%) vs. good for the visual-based method (ICC: 0.61; 95% CI 0.51, 0.69; CV: 43%). Test-retest repeatability for the software-based LSN scoring method was excellent (ICC: 0.82; 95% CI 0.79, 0.84; CV: 12%).Conclusion: The software-based LSN score is a quantitative CT imaging biomarker with excellent repeatability, reproducibility, inter-observer agreement, and test-retest repeatability. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is still a leading cancer killer in the community. Molecular targeted therapy with celecoxib (CXB) has shown promising antitumor effects; however, its use may be limited due to serious side effects. Curcumin (CUR) has also shown beneficial effects against HCC. Then, it was aimed to investigate the effects of adding CUR to CXB on HCC HepG2 cells. HepG2 cells were treated with CXB and/or CUR at increasing concentrations to investigate synergistic drug interactions, as calculated combination index (CI). Combination treatment effects on cell viability and caspase-3 activation were assessed. The levels of Akt, nuclear factor-kappa B (NF-κB), prostaglandin E2 (PGE2), malondialdehyde (MDA), cyclin D1 (CD1), and vascular endothelial growth factor (VEGF) were also evaluated. CXB (3.13-100 μM) and/or CUR (1.25-40 μM) reduced HepG2 cell viability dose-dependently. Nevertheless, lower combined concentrations showed higher synergism (CI < 1) and higher CXB dose reduction index (DRI > 1). Also, the addition of CUR to CXB resulted in increased cytotoxicity and caspase-3 activation, as compared to CXB alone. In addition, the selected combination significantly reduced the levels of Akt, NF-κB, PGE2, MDA, CD1, and VEGF, as compared to either agent alone. In conclusion, CUR augmented the CXB-mediated antitumor effects in HepG2 cells through, at least in part, antiproliferative, antioxidant, and pro-apoptotic mechanisms. This may allow the further use of CXB at lower concentrations, combined with CUR, as a promising safer targeted strategy for HCC management. [ABSTRACT FROM AUTHOR]

Purpose: Trauma mechanisms and patterns of severe injuries during the Estonian independence have not been evaluated. The aim of the study was to compare the incidence and outcomes of severe injuries between time periods of early independence from the Soviet Union and the present time. Methods: After the ethics review board approval, all adult trauma admissions to major trauma facilities in 1993-1994 and 2013-2014 with Injury Severity Score >15 were identified. Data collection included demographics, injury severity variables, interventions, and in-hospital outcomes. Primary outcome was in-hospital mortality. Secondary outcomes included incidence of penetrating trauma, hospital length of stay (HLOS), and in-hospital complications. Primary outcome difference comparing the two time segments was determined using logistic regression analysis. Results: A total of 1064 patients were included, 593 and 471 from 1993-1994 to 2013-2014, respectively. Incidence of penetrating trauma during 1993-1994 was 11.1 % and in 2013-2014 at 6.4 % ( p = 0.007). Gunshot injuries constituted 62.1 and 23.3 % of all penetrating trauma in 1993-1994 and 2013-2014, respectively ( p < 0.001). The overall mean HLOS was 15.5 ± 19.8 days and did not differ between the periods. The rate of adjusted complications showed a trend for a decreased incidence (adj. p = 0.064). Adjusted mortality rate was 50.3 and 16.4 % during 1993-1994 and 2013-2014, respectively (adj. OR 7.01; 95 % CI 4.69-10.47; p < 0.001). Conclusions: Effective law enforcement, gun control, evolution of trauma system, and reduction of interpersonal violence have all contributed to a significant decrease in penetrating trauma incidence and all-cause adjusted mortality during the 20 years of Estonian independence. [ABSTRACT FROM AUTHOR]

Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We previously showed that osteoclast function can be restored by lentiviral vector-mediated expression of TCIRG1, but the exact threshold for restoration of resorption as well as the cellular response to vector-mediated TCIRG1 expression is unknown. Here we show that expression of TCIRG1 protein from a bicistronic TCIRG1/GFP lentiviral vector was only observed in mature osteoclasts, and not in their precursors or macrophages, in contrast to GFP expression, which was observed under all conditions. Thus, vector-mediated TCIRG1 expression appears to be post-transcriptionally regulated, preventing overexpression and/or ectopic expression and ensuring protein expression similar to that of wild-type osteoclasts. Codon optimization of TCIRG1 led to increased expression of mRNA but lower levels of protein and functional rescue. When assessing the functional rescue threshold in vitro, addition of 30 % CB CD34+ cells to IMO CD34+ patient cells was sufficient to completely normalize resorptive function after osteoclast differentiation. From both an efficacy and a safety perspective, these findings will clearly be of benefit during further development of gene therapy for osteopetrosis. [ABSTRACT FROM AUTHOR]

This work aims to estimate the prevalence of Helicobacter pylori ureA gene and evaluate cagA gene-positive strains in both patients of laryngeal squamous cell carcinoma (LSCC) and those with benign laryngeal polyps. This study included 49 patients confirmed pathologically to have LSCC and 15 patients with benign laryngeal polyps over a period from June 2013 to March 2015. Samples of laryngeal tissue were collected during direct laryngoscope under general anesthesia to be pathologically evaluated followed by analysis for H. pylori detection. Each laryngeal tissue sample was divided into three parts; one for bacteriological examination, the second for pathological examination and the third for PCR to detect both ureA and cagA genes. Out of 49 LSCC samples, 31 (64.6 %) was positive for ureA by PCR. Out of them, 29 samples (93.5 %) were cagA positive. Only three cases (20 %) of the benign laryngeal polyp were ureA positive by PCR and one of them was cagA positive by PCR. By the bacteriological culture, only eight samples (25.8 %) gave growth. All of them were ureA positive and only seven of them were cagA positive. There was a significant association between presence of H. pylori and LSCC as compared to benign laryngeal polyp which may contribute in the pathogenesis of laryngeal carcinoma. These results should be confirmed by further studies over larger number of cases. [ABSTRACT FROM AUTHOR]

Background and purpose: Non-steroidal anti-inflammatory drugs are associated with several side effects, such as gastrointestinal mucosal damage, renal toxicity, and cardiovascular side effects. Aiming to find a novel analgesic/anti-inflammatory drug with minimal side effects, the present study was designed to screen and evaluate some newly synthesized pyrazole derivatives. Method: Anti-inflammatory activity using carrageenan-induced rat paw edema and cotton-pellet-induced granuloma, COX-1/COX-2 selectivity using thin layer chromatography, and analgesic using hot plate and tail flick tests as well as ulcerogenic and renal side effects of the ten compounds were assessed. Results and discussion: The results of the carrageenan-induced rat paw edema showed that the carboxyphenylhydrazone derivative (N9) was more potent than the chlorophenyl counterpart (N8) with a relative activity compared to celecoxib of 1.08 and −0.13, respectively, after 1 h. Even though this is true, N9 caused significant increase in the ulcer index, creatinine, and Blood Urea Nitrogen levels. The cotton granuloma test showed that the carboxyphenylhydrazone derivative (N7) was also more potent than its chlorophenyl counterpart (N6) with a relative activity compared to celecoxib of 1.13 and 0.86, respectively. Moreover, adding an acetyl not only increased the anti-inflammatory activity from a relative activity compared to celecoxib of 0.57-1.17 for the compounds X4 and N5, respectively, in the granuloma test, but also increased the selectivity toward COX-2 from 0.197 to 47.979. Conclusion: As a conclusion, from the ten compounds analyzed, N5 and N7 showed promising results as anti-inflammatory/analgesic agents with low ulcerogenicity and nephrotoxicity and thus should be further analyzed to determine the ED50 and other side effects. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate epidemiology of severe injuries in Estonia while comparing outcomes at regional trauma facilities. Methods: After the ethics review board approval, all consecutive trauma admissions with Injury Severity Score (ISS) > 15 to North Estonia Medical Center/Tallinn Children's Hospital (NEMC + TCH) and Tartu University Hospital (TUH) were identified between 1/1/2013 and 31/12/2013. Data collection included demographics, admission data, injury severity variables, interventions, and in-hospital outcomes. Primary outcome was in-hospital mortality. Secondary outcomes were complications per Clavien-Dindo and hospital length of stay (HLOS). Logistic regression analysis was used to compare adjusted mortality between the two regional hospitals. Results: A total of 256 patients met inclusion criteria. The mean ISS for the cohort was 23.6 ± 7.8, 13.3 % were hypotensive on admission, and 44.1 % had a Glasgow Coma Scale < 9. Overall rate of complications was 40.2 % that did not differ between the facilities. The mean HLOS at the NEMC + TCH and the TUH were 20.1 ± 25.1 and 10.5 ± 11.2 days ( p < 0.001), respectively. Overall mortality was 20.7 % ( n = 53). Mortality was 25.4 and 14.9 % for the NEMC + TCH and the TUH, respectively ( p = 0.04). Logistic regression analysis resulted in comparable mortality at the regional trauma facilities (adj. OR 1.38; 95 % CI 0.66-2.92; p value 0.39). Conclusions: The annual incidence of injuries with ISS > 15 was 256 cases with overall mortality at 20.7 % in Estonia. We observed comparable adjusted outcomes at the major regional trauma facilities. This study contains benchmarking data on severely injured patients in Estonia providing potential for future trauma care evaluation and regional outcome comparisons. [ABSTRACT FROM AUTHOR]

Purpose: Homicide in Greenland has not often been investigated. The latest published study documented a dramatic rise in the homicide rate from around 1/100,000 inhabitants to more than 23/100,000 inhabitants from 1946 to 1984. The aim of our study was to characterize homicides in Greenland from 1985 to 2010 and to compare trends during this period with those in previous studies and with homicide characteristics in Denmark, northern Europe, and other Arctic regions. Methods: We identified a total of 281 homicides by legal definition and 194 by medical definition, the latter from the years 1990 to 2010. We procured case files for a total of 129 victims (71 male, 58 female) and 117 perpetrators (85 male, 32 female). Results: We identified an overall decrease in the homicide rate during our study period. The decrease in the medical homicide rate was significant ( p = 0.007). The homicide rate ranged from 25/100,000 inhabitants to 13/100,000 inhabitants when results were grouped within 5-year periods. There were significantly more male perpetrators ( p < 0.001) and among female perpetrators there were significantly more male victims ( p < 0.001). Sharp force and gunshot-related killings dominated homicide methods (41 and 29 % respectively), with sharp force deaths increasing throughout the investigation period. Altercations were the main motive (49 %). Alcohol-related homicides decreased in our study period. Conclusions: While the Greenlandic homicide rate has decreased, it is markedly higher compared to that seen in Denmark and northern Europe. However, it resembles the rate seen in the rest of the Arctic. Liberal gun laws do not affect the proportion of gun-related killings. Despite the high homicide rate, women account for almost half the victims. [ABSTRACT FROM AUTHOR]

New tetrahydroquinoline derivatives were synthesized, characterized, and evaluated for their in vitro and in vivo acetylcholinesterase inhibitory activity as well as hepatotoxicity using tacrine as a reference standard. The obtained results revealed that most of the compounds comprising a chloro substituent displayed higher activity when compared with the other analogs. Among the newly synthesized compounds, four analogs displayed in vitro and in vivo acetylcholinesterase inhibitory activity comparable to or slightly higher than tacrine. Among these compounds, the 2-chlorotetrahydroquinoline derivative emerged with hepatotoxicity results comparable to saline. Graphical abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Background: The aim of this investigation is the development of primarily healthy hips in children who have required orthoses/protheses over the long term due to ipsilateral distally located deformities of the leg. These children show ipsilateral in-toeing gait and Duchenne's limping followed by a coxa valga antetorta and facultative hip decentration. A practical question is whether these hips are in danger of decompensation. An additional theoretical question is how the external shape and internal architecture changes if a primarily healthy hip is underused. Methods: Ten children with healthy hips who are unilaterally long-term orthotics/prosthetics-dependent agreed to undergo an instrumental gait analysis. The results were analyzed and correlated with clinical findings, a common activity score and planimetric radiographic data. Results: The intra-individual comparison revealed a number of significant changes in the hip of the deformed leg ( p < 0.05). Clinically, the internal rotation was increased (15° ± 4.2°), while the external rotation was diminished (13° ± 1.3°). Radiologically, the projected caput-collum-diaphyseal angle, the lesser trochanter to articular surface distance and the head-shaft angle were increased by 11.1° ± 15.4°, 5.8 ± 4.2 mm and 11.9° ± 0.6°, respectively. Both the Sharp and acetabular angles were increased, the former by 3.6° ± 0.6° and the latter by 3.2° ± 0.6°. Kinetic gait analysis showed increased stride length (6.8 ± 3.7 cm), shortened stance phase (6.6 ± 1.6 %) and reduced forces transmitted to the ground (92.2 ± 34.3 N). The kinematic analysis showed increased hip abduction (14.0° ± 8.2°), while the pelvic obliquity was not significantly changed (0.01° ± 0.01°). Conclusions: Duchenne's limp and lack of weight-bearing stress are the decisive pathogenic factors of the underused coxa valga and acetabular dysplasia. These changes follow the mechanobiological concept of 'function modifies design', which means function influences external shape and internal architecture of bones and joints. As a practical consequence we recommend that one pelvic radiograph be performed as a precaution at the end of puberty of children with these conditions. Level of evidence: Level II retrospective study. [ABSTRACT FROM AUTHOR]