A 2-step synthesis of Combretastatin A-4 and derivatives as potent tubulin assembly inhibitors

A series of combretastatin derivatives were designed and synthesised by a two-step stereoselective synthesis by use of Wittig olefination followed by Suzuki cross-coupling. Interestingly, all new compounds (2a-2i) showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, 2a, 2b and 2e were the most active across three cancer cell lines. In addition, these compounds inhibited the polymerisation of tubulin in vitro more efficiently than CA-4. They caused cell cycle arrest in G2/M phase further confirming their ability to inhibit tubulin polymerisation

The burden of road traffic accidents in a French Departement: the description of the injuries and recent changes

International audienceBACKGROUND: A significant reduction in road traffic accidents has been observed since prevention measures were introduced by the French public authorities in 2002. The goals of this study are to describe the burden of road traffic accidents in a French Departement, and to identify changes if any between the periods 1997-2001 and 2002-2006 on the basis of the disability adjusted life years (DALY). METHODS: Years of lost life (YLL) and years lived with disability (YLD) were calculated for two periods using the mortality and incidence data in the Rhone Departement Registry of Road Traffic Accident Casualties. RESULTS: YLD and YLL that are related to road traffic accidents are at their maximum value between 15 and 24 years of age. For men, intracranial fractures and intracranial injuries dominate, and for women it is spinal cord injuries that account for highest rates of YLD. A reduction in the rates of YLL and YLD has been observed for both genders and all age groups between 1997-2001 and 2002-2006. CONCLUSION: The reduction in DALY between the two periods is explained both by the reduction in the number of fatalities and injuries but also by an increase in the age at which they occur

The injury epidemiology of cyclists based on a road trauma registry

<p>Abstract</p> <p>Background</p> <p>Bicycle use has increased in some of France's major cities, mainly as a means of transport. Bicycle crashes need to be studied, preferably by type of cycling. Here we conduct a descriptive analysis.</p> <p>Method</p> <p>A road trauma registry has been in use in France since 1996, in a large county around Lyon (the Rhône, population 1.6 million). It covers outpatients, inpatients and fatalities. All injuries are coded using the Abbreviated Injury Scale (AIS). Proxies were used to identify three types of cycling: learning = children (0-10 years old); sports cycling = teenagers and adults injured outside towns; cycling as means of transport = teenagers and adults injured in towns. The study is based on 13,684 cyclist casualties (1996-2008).</p> <p>Results</p> <p>The percentage of cyclists injured in a collision with a motor vehicle was 8% among children, 17% among teenagers and adults injured outside towns, and 31% among those injured in towns. The percentage of serious casualties (MAIS 3+) was 4.5% among children, 10.9% among adults injured outside towns and 7.2% among those injured in towns. Collisions with motor-vehicles lead to more internal injuries than bicycle-only crashes.</p> <p>Conclusion</p> <p>The description indicates that cyclist type is associated with different crash and injury patterns. In particular, cyclists injured in towns (where cycling is increasing) are generally less severely injured than those injured outside towns for both types of crash (bicycle-only crashes and collisions with a motor vehicle). This is probably due to lower speeds in towns, for both cyclists and motor vehicles.</p

Protective and risk factors in amateur equestrians and description of injury patterns: A retrospective data analysis and a case - control survey

Background In Switzerland there are about 150,000 equestrians. Horse related injuries, including head and spinal injuries, are frequently treated at our level I trauma centre. Objectives To analyse injury patterns, protective factors, and risk factors related to horse riding, and to define groups of safer riders and those at greater risk Methods We present a retrospective and a case-control survey at conducted a tertiary trauma centre in Bern, Switzerland. Injured equestrians from July 2000 - June 2006 were retrospectively classified by injury pattern and neurological symptoms. Injured equestrians from July-December 2008 were prospectively collected using a questionnaire with 17 variables. The same questionnaire was applied in non-injured controls. Multiple logistic regression was performed, and combined risk factors were calculated using inference trees. Results Retrospective survey A total of 528 injuries occured in 365 patients. The injury pattern revealed as follows: extremities (32%: upper 17%, lower 15%), head (24%), spine (14%), thorax (9%), face (9%), pelvis (7%) and abdomen (2%). Two injuries were fatal. One case resulted in quadriplegia, one in paraplegia. Case-control survey 61 patients and 102 controls (patients: 72% female, 28% male; controls: 63% female, 37% male) were included. Falls were most frequent (65%), followed by horse kicks (19%) and horse bites (2%). Variables statistically significant for the controls were: Older age (p = 0.015), male gender (p = 0.04) and holding a diploma in horse riding (p = 0.004). Inference trees revealed typical groups less and more likely to suffer injury. Conclusions Experience with riding and having passed a diploma in horse riding seem to be protective factors. Educational levels and injury risk should be graded within an educational level-injury risk index

Crash characteristics and patterns of injury among hospitalized motorised two-wheeled vehicle users in urban India

<p>Abstract</p> <p>Background</p> <p>Traffic crashes and consequent injuries represent a growing public health concern in India, particularly in light of increasing motorization. Motorised two-wheeled vehicles (MTV) constitute a large portion of the vehicle fleet in India. We report the crash characteristics and injury patterns among a cohort of MTV riders and pillions presenting to hospital post-crash.</p> <p>Methods</p> <p>Consecutive MTV riders and pillions, whether alive or dead, injured in a road traffic crash presenting to the emergency departments of two government hospitals and three branches of a private hospital in urban Hyderabad, India, were recruited to this study.</p> <p>Results</p> <p>378 MTV users were enrolled to the study of whom 333 (88.1%) were male, 252 (66.7%) were riders and median age was 31.3 years. A total of 223 (59%) MTV users were injured in multi-vehicle crashes while one-third had a frontal impact. The majority (77%) were assessed as having a Glasgow coma score (GCS) of 13–15, 12% a GCS of 9–12 and 11% a GCS of 3–8. No difference was seen in the severity distribution of injuries based on GCS among riders and pillions. Open wounds and superficial injuries to the head (69.3%) and upper extremity (27%) and lower extremity (24%) were the most common injuries. 43 (11%) sustained an intracranial injury, including 12 (28%) with associated fracture of the bones of the head. There were few differences in types of injuries sustained by riders and pillions though riders had a significantly lower risk of crush injuries of the lower extremity than pillions (relative risk, RR 0.25, 95% CI 0.08–0.81) and female pillions were at a significantly lower risk of sustaining fractures of the lower extremity than male pillions (RR 0.30, 95% CI 0.09 – 0.94). Overall, 42 (11%) MTV users died, of which 42.8% died before reaching the hospital. Only 74 (19.6%) MTV users had worn a helmet correctly and failure to wear a helmet was associated with a five times greater risk of intracranial injury (RR 4.99, 95% CI 1.23–20.1). Of the 19 pre-hospital deaths, 16 (84%) had not worn a helmet.</p> <p>Conclusion</p> <p>Head injuries accounted for the major proportion of injuries sustained in MTV users. Non-helmet use was associated with increased risk of serious head injuries. The data presented on the nature and severity of injuries sustained by MTV users can assist with planning to deal with these consequences as well as prevention of these injuries given the high use of MTV in India.</p

PP2A inactivation is a crucial step in triggering apoptin-induced tumor-selective cell killing

Apoptin (apoptosis-inducing protein) harbors tumor-selective characteristics making it a potential safe and effective anticancer agent. Apoptin becomes phosphorylated and induces apoptosis in a large panel of human tumor but not normal cells. Here, we used an in vitro oncogenic transformation assay to explore minimal cellular factors required for the activation of apoptin. Flag-apoptin was introduced into normal fibroblasts together with the transforming SV40 large T antigen (SV40 LT) and SV40 small t antigen (SV40 ST) antigens. We found that nuclear expression of SV40 ST in normal cells was sufficient to induce phosphorylation of apoptin. Mutational analysis showed that mutations disrupting the binding of ST to protein phosphatase 2A (PP2A) counteracted this effect. Knockdown of the ST-interacting PP2A–B56γ subunit in normal fibroblasts mimicked the effect of nuclear ST expression, resulting in induction of apoptin phosphorylation. The same effect was observed upon downregulation of the PP2A–B56δ subunit, which is targeted by protein kinase A (PKA). Apoptin interacts with the PKA-associating protein BCA3/AKIP1, and inhibition of PKA in tumor cells by treatment with H89 increased the phosphorylation of apoptin, whereas the PKA activator cAMP partially reduced it. We infer that inactivation of PP2A, in particular, of the B56γ and B56δ subunits is a crucial step in triggering apoptin-induced tumor-selective cell death

Injury in China: a systematic review of injury surveillance studies conducted in Chinese hospital emergency departments

<p>Abstract</p> <p>Background</p> <p>Injuries represent a significant and growing public health concern in China. This <it>Review </it>was conducted to document the characteristics of injured patients presenting to the emergency department of Chinese hospitals and to assess of the nature of information collected and reported in published surveillance studies.</p> <p>Methods</p> <p>A systematic search of MEDLINE and China Academic Journals supplemented with a hand search of journals was performed. Studies published in the period 1997 to 2007 were included and research published in Chinese was the focus. Search terms included emergency, injury, medical care.</p> <p>Results</p> <p>Of the 268 studies identified, 13 were injury surveillance studies set in the emergency department. Nine were collaborative studies of which eight were prospective studies. Of the five single centre studies only one was of a prospective design. Transport, falls and industrial injuries were common mechanisms of injury. Study strengths were large patient sample sizes and for the collaborative studies a large number of participating hospitals. There was however limited use of internationally recognised injury classification and severity coding indices.</p> <p>Conclusion</p> <p>Despite the limited number of studies identified, the scope of each highlights the willingness and the capacity to conduct surveillance studies in the emergency department. This <it>Review </it>highlights the need for the adoption of standardized injury coding indices in the collection and reporting of patient health data. While high level injury surveillance systems focus on population-based priority setting, this <it>Review </it>demonstrates the need to establish an internationally comparable trauma registry that would permit monitoring of the trauma system and would by extension facilitate the optimal care of the injured patient through the development of informed quality assurance programs and the implementation of evidence-based health policy.</p

Pengaruh pembelajaran berbasis Inkuiri terhadap kemampuan berpikir kritis anak kelas B4 RA Sunan Ampel Arjosari Pasuruan di Masa Pandemi

Penelitian ini bertujuan untuk mengetahui pengaruh pembelajaran berbasis inkuiri terhadap kemampuan berpikir kritis anak kelas B4 RA Sunan Ampel Arjosari Pasuruan di masa pandemi. Penelitian ini didasari oleh hasil pengamatan peneliti terhadap proses belajar mengajar di kelas B4 RA Sunan Ampel Arjosari Pasuruan di masa pandemi. Peneliti menemukan pendekatan yang digunakan saat proses belajar mengajar belum cukup saintifik. Unsur-unsur pembelajaran saintifik yang mengedepankan keaktifan anak untuk berpikir dan membuat pertanyaan kritis belum terindikasi dari kegiatan yang dilaksanakan dalam proses pembelajaran. Sampel penelitian ini yaitu siswa kelas B4 RA Sunan Ampel Arjosari Pasuruan berjumlah 14 anak. Data penelitian didapat melalui tes dan observasi. Analisis data penelitian menggunakan uji perbandingan non parametrik Wilcoxon dan uji korelasi non parametrik Spearman. Hasil penelitian menunjukkan bahwa pengaruh pembelajaran berbasis inkuiri terhadap kemampuan berpikir kritis anak kelas B4 RA Sunan Ampel Arjosari Pasuruan sangat kuat dan berbanding lurus. Dibuktiikan dengan uji korelasi Spearman yang menunjukkan koefisien korelasi 0,76 dan nilai Sig. 0,002<0,05 (hubungan positif dan sangat kuat, berhubungan signifikan). Selain itu, kemampuan berpikir kritis anak kelas B4 RA Sunan Ampel Arjosari Pasuruan sesudah diterapakan pembelajaran berbasis inkuiri di masa pandemi meningkat. Hal ini ditunjukkan oleh rerata nilai tes kemampuan berpikir kritis yaitu 91.0207 (meningkat sebanyak 14,04%). Penurunan kemampuan berpikir kritis hanya terjadi pada 2 dari 14 anak (menurun sebanyak 0,27% dan 2,36%) sedangkan peningkatan kemampuan berpikir kritis pada sebagian besar anak kelas B4 yaitu 12 dari 14 anak (meningkat sebanyak 1,52% hingga 73%)