European cancer mortality predictions for the year 2016 with focus on leukemias.

BACKGROUND: Current cancer mortality statistics are important for public health decision making and resource allocation. Age standardized rates and numbers of deaths are predicted for 2016 in the European Union. PATIENTS AND METHODS: Population and death certification data for stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukemia and total cancers were obtained from the World Health Organisation database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected numbers of deaths by age group were obtained for 2016 by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: Projected total cancer mortality trends for 2016 in the EU are favourable in both sexes with rates of 133.5/100,000 men and 85.2/100,000 women (8% and 3% falls since 2011, due to population ageing) corresponding to 753,600 and 605,900 deaths in men and women for a total number of 1,359,500 projected cancer deaths (+3% compared to 2011). In men lung, colorectal and prostate cancer fell 11%, 5% and 8% since 2011. Breast and colorectal cancer trends in women are favourable (8% and 7% falls, respectively), but lung and Pancreatic cancer rates rose 5% and 4% since 2011 reaching rates of 14.4 and 5.6/100,000 women. Leukemia shows favourable projected mortality for both sexes and all age groups with stronger falls in the younger age groups, rates are 4.0/100,000 men and 2.5/100,000 women, with respectively falls of 14% and 12%. CONCLUSION: The 2016 predictions for EU cancer mortality confirm the favourable trends in rates particularly for men. Lung cancer is likely to remain the leading site for female cancer rates. Continuing falls in mortality, larger in children and young adults, are predicted in leukemia, essentially due to advancements in management and therapy, and their subsequent adoption across Europe.

Therapeutic and recreational methadone cardiotoxicity.

Several classes of drugs have been associated with an increased risk of cardiovascular disease and occurrence of arrhythmias potentially involved in sudden deaths in chronic users even at therapeutic doses. The study presented herein focuses on pathological changes involving the heart possibly due to methadone use. 60 cases were included in the study in total and were divided into three groups (therapeutic methadone users: 20 cases, recreational methadone users: 20 cases, and sudden death group in subjects who had never taken methadone: 20 cases). Autopsies, histology, biochemistry and toxicology were performed in all cases. Macroscopic and microscopic investigation results in therapeutic methadone users were similar to those observed in sudden, unexpected deaths in non-methadone users. In recreational methadone consumers, macroscopic and microscopic examination of the heart failed to provide results consistent with acute or chronic myocardial or coronary damage, thereby corroborating the hypothesis of death most likely following respiratory depression.

Transabdominal-pelvic-perineal (TAPP) anterolateral thigh flap: A new reconstructive technique for complex defects following extended abdominoperineal resection.

BACKGROUND: Abdominoperineal resection (APR) following radiotherapy is associated with a high rate of perineal wound complications. The anterolateral thigh (ALT) flap, combined with the vastus lateralis (VL) muscle, can cover complex perineal and pelvic anteroposterior defects. This is used for the first time transabdominally through the pelvis and the perineum (TAPP) in the infero-posterior directions; this technique has been described and illustrated in this study. METHODS: Among over 90 patients who underwent perineal reconstruction between May 2004 and June 2011, six patients presented high-grade tumours invading perineum, pelvis and sacrum, thereby resulting in a continuous anteroposterior defect. ALT + VL TAPP reconstructions were performed after extended APR and, subsequently, sacrectomy. Patients were examined retrospectively to determine demographics, operative time, complications (general and flap-related), time to complete healing and length of hospital stay. Long-term flap coverage, flap volume stability and functional and aesthetic outcomes were assessed. RESULTS: Mean operating time of the reconstruction was 290 min. No deaths occurred. One patient presented partial flap necrosis. Another patient presented a novel wound dehiscence after flap healing, due to secondary skin dissemination of the primary tumour. Following volumetric flap analysis on serial post-operative CT scans, no significant flap atrophy was observed. All flaps fully covered the defects. No late complications such as fistulas or perineal hernias occurred. Donor-site recovery was uneventful with no functional deficits. CONCLUSIONS: The use of the ALT + VL flap transabdominally is an innovative method to reconstruct exceptionally complex perineal and pelvic defects extending up to the lower back. This flap guarantees superior bulk, obliterating all pelvic dead space, with the fascia lata (FL) supporting the pelvic floor.

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

Background: Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk. Methods: We used data from the PREDIMED study, a 7,447-participant, parallel-group, randomized, multicenter, controlled five-year feeding trial aimed at assessing the effects of the Mediterranean Diet in primary prevention of cardiovascular disease. Polyphenol intake was calculated by matching food consumption data from repeated food frequency questionnaires (FFQ) with the Phenol-Explorer database on the polyphenol content of each reported food. Hazard ratios (HR) and 95% confidence intervals (CI) between polyphenol intake and mortality were estimated using time-dependent Cox proportional hazard models. Results: Over an average of 4.8 years of follow-up, we observed 327 deaths. After multivariate adjustment, we found a 37% relative reduction in all-cause mortality comparing the highest versus the lowest quintiles of total polyphenol intake (hazard ratio (HR) = 0.63; 95% CI 0.41 to 0.97; P for trend = 0.12). Among the polyphenol subclasses, stilbenes and lignans were significantly associated with reduced all-cause mortality (HR =0.48; 95% CI 0.25 to 0.91; P for trend = 0.04 and HR = 0.60; 95% CI 0.37 to 0.97; P for trend = 0.03, respectively), with no significant associations apparent in the rest (flavonoids or phenolic acids). Conclusions: Among high-risk subjects, those who reported a high polyphenol intake, especially of stilbenes and lignans, showed a reduced risk of overall mortality compared to those with lower intakes. These results may be useful to determine optimal polyphenol intake or specific food sources of polyphenols that may reduce the risk of all-cause mortality.

Fármacos no combate à tuberculose: passado, presente e futuro

Approximately every minute, somewhere in the world four people die from tuberculosis (TB), an infection of Mycobacterium tuberculosis with about 3 million deaths per year. In spite of these problems, unfortunaly, it is about 40 years that a novel drug was last introduced on the market. Due to the rapid spread of multi-drug resistant TB strains, resistant against all major anti-tuberculosis drugs, and the recent resurgence of the incidence of tuberculosis in association with the human immunodeficiency virus (HIV) infection and AIDS, we need urgently the development of new drugs to fight tuberculosis. This is covered in the present article.

The burden of disease in Spain: results from the global burden of disease study 2010

BackgroundWe herein evaluate the Spanish population¿s trends in health burden by comparing results of two Global Burden of Diseases, Injuries, and Risk Factors Studies (the GBD studies) performed 20 years apart.MethodsData is part of the GBD study for 1990 and 2010. We present results for mortality, years of life lost (YLLs), years lived with disability, and disability-adjusted life years (DALYs) for the Spanish population. Uncertainty intervals for all measures have been estimated.ResultsNon-communicable diseases accounted for 3,703,400 (95% CI 3,648,270¿3,766,720) (91.3%) of 4,057,400 total deaths, in the Spanish population. Cardiovascular and circulatory diseases were the main cause of mortality among non-communicable diseases (34.7% of total deaths), followed by neoplasms (27.1% of total deaths). Neoplasms, cardiovascular and circulatory diseases, and chronic respiratory diseases were the top three leading causes for YLLs. The most important causes of DALYs in 2010 were neoplasms, cardiovascular and circulatory diseases, musculoskeletal disorders, and mental and behavioral disorders.ConclusionsMortality and disability in Spain have become even more linked to non-communicable diseases over the last years, following the worldwide trends. Cardiovascular and circulatory diseases, neoplasms, mental and behavioral disorders, and neurological disorders are the leading causes of mortality and disability. Specific focus is needed from health care providers and policy makers to develop health promotion and health education programs directed towards non-communicable disorders.

Malária: aspectos históricos e quimioterapia

Malaria is still a very serious worldwide public health problem affecting between 300 and 500 million people and causing from 1.0 to 2.5 million deaths annually. The major problems with this disease are the lack of efficient vaccines and the rapid emergence of chemotherapy resistant P. falciparum strains. In this work we present a synopsis and discussion on malaria to provide the readers with some information on the historical aspects and relevance of this disease as well as the chemotherapy in use today.

Metabólitos secundários de origem vegetal: uma fonte potencial de fármacos antitrombóticos

Cardiovascular diseases are responsible for the largest number of deaths among humans worldwide, including heart attacks, strokes, and thrombosis. The treatment of thrombosis is generally through the administration of anticoagulant and/or antiplatelet drugs, which have some clinical limitations. Plants synthesize a wide variety of bioactive metabolites in response to different stimuli. This review focuses on a number of molecules of vegetal origin belonging to different chemical classes, with significant anticoagulant and antiplatelet effects. Their promising antithrombotic profile confirms the potential of natural products as a source of lead molecules for drug development in the prevention and treatment of thrombosis.

Novel Players in the Integrin Signaling Orchestra: TCPTP and MDGI

Metastases are the major cause of cancer deaths. Tumor cell dissemination from the primary tumor utilizes dysregulated cellular adhesion and upregulated proteolytic degradation of the extracellular matrix for progeny formation in distant organs. Integrins are transmembrane adhesive receptors mediating cellcell and cellmatrix interactions that are crucial for regulating cell migration, invasion, proliferation, and survival. Consequently, increased integrin activity is associated with augmented migration and invasion capacity in several cancer types. Heterodimeric integrins consist of an alpha - and beta-subunit that are held together in a bent conformation when the receptor is inactive, but extension and separation of subdomains is observed during receptor activation. Either inside-out or outside-in activation of receptors is possible through the intracellular molecule binding to an integrin cytoplasmic domain or extracellular ligand association with an integrin ectodomain, respectively. Several regulatory binding partners have been characterized for integrin cytoplasmic beta-domains, but the regulators interacting with the cytoplasmic alpha-domains have remained elusive. In this study, we performed yeast two-hybrid screens to identify novel binding partners for the cytoplasmic integrin alpha-domains. Further examination of two plausible candidates revealed a significant coregulatory role of an integrin alpha-subunit for cellular signaling processes. T-cell protein tyrosine phosphatase (TCPTP) showed a specific interaction with the cytoplasmic tail of integrin alpha1. This association stimulated TCPTP phosphatase activity, leading to negative regulation of epidermal growth factor receptor (EGFR) signaling and diminished anchorage-independent growth. Another candidate, mammary-derived growth inhibitor (MDGI), exhibited binding to several different integrin cytoplasmic alpha-tails through a conserved GFFKR sequence. MDGI overexpression in breast cancer cells altered EGFR trafficking and caused a remarkable accumulation of EGFR in the cytoplasm. We further demonstrated in vivo that MDGI expression induced a novel form of anti-EGFR therapy resistance. Moreover, MDGI binding to α-tails retained integrin in an inactive conformation attenuating integrin-mediated adhesion, migration, and invasion. In agreement with these results, sustained MDGI expression in breast cancer patients correlated with an increased 10-year distant disease-free survival. Taken together, the integrin signaling network is far from a complete view and future work will doubtless broaden our understanding further.

EFFECTS OF HARVESTING ON LEAF PRODUCTION AND REPRODUCTIVE PERFORMANCE OF Copernicia prunifera (Mill.) H.E. Moore1

ABSTRACT This work aimed to evaluate the consequences of the monthly extraction of immature leaves in survival, leaf production and reproductive performance ofCopernicia prunifera H. E. Moore palm, popularly known as carnaúba. One hundred sixty reproductive adult palms were monitored for 17 months in four extractive communities located at the coast of the state of Piauí. As a result, it was observed that leaves, flowers, fruits and seeds production were reduced in the palm submitted to 50% or 75% monthly extraction. Higher levels of extraction were followed by smaller levels in seed germination. No deaths were observed even in the group subjected to 75% monthly leaves exploration. In order not to produce damage to palm trees development it is suggested that leaf extraction rate should not exceed 25% monthly as well as pausing of extractive activity preferentially during fruit maturation.

Ferimento transfixante de útero em gestante

In de past 50 years, maternal mortality rates have declined, in contrast, the number of deaths due to injury during pregnancy is on the rise. The authors report a case of 24° week pregnant woman victim of penetrating abdominal trauma by gunshot who sustained a grade I11 transfixing injury of the uterine fundus. Treatment was conservative regarding the fetus. Hysteroraphia of the injuries was executed with closure of both penetrating orifices. Obstetrical-gynecological evaluation and echogram documented letal viability in the post-operative period. Post-operative follow-up was performed with periodical echograms up to delivery on the ninth month. Clinical findings, treatment and follow-up will be discussed.

Enhancing human security through crisis management : opportunities and challenges for learning

Inhimilliseen turvallisuuteen kriisinhallinnan kautta – oppimisen mahdollisuuksia ja haasteita Kylmän sodan jälkeen aseelliset konfliktit ovat yleensä alkaneet niin sanotuissa hauraissa valtioissa ja köyhissä maissa, ne ovat olleet valtioiden sisäisiä ja niihin on osallistunut ei-valtiollisia aseellisia ryhmittymiä. Usein ne johtavat konfliktikierteeseen, jossa sota ja vakaammat olot vaihtelevat. Koska kuolleisuus konflikteissa voi jäädä alle kansainvälisen määritelmän (1000 kuollutta vuodessa), kutsun tällaisia konflikteja ”uusiksi konflikteiksi”. Kansainvälinen yhteisö on pyrkinyt kehittämään kriisinhallinnan ja rauhanrakentamisen malleja, jotta pysyvä rauhantila saataisiin aikaiseksi. Inhimillinen turvallisuus perustuu näkemykseen, jossa kunnioitetaan jokaisen yksilön ihmisoikeuksia ja jolla on vaikutusta myös kriisinhallinnan ja rauhanrakentamisen toteuttamiseen. Tutkimukseen kuuluu kaksi empiiristä osaa: Delfoi tulevaisuuspaneeliprosessin sekä kriisinhallintahenkilöstön haastattelut. Viisitoista eri alojen kriisinhallinta-asiantuntijaa osallistui paneeliin, joka toteutettiin vuonna 2008. Paneelin tulosten mukaan tulevat konfliktit usein ovat uusien konfliktien kaltaisia. Lisäksi kriisinhallintahenkilöstöltä edellytetään vuorovaikutus- ja kommunikaatiokykyä ja luonnollisesti myös varsinaisia ammatillisia valmiuksia. Tulevaisuuspaneeli korosti vuorovaikutus- ja kommunikaatiotaitoja erityisesti siviilikriisinhallintahenkilöstön kompetensseissa, mutta samat taidot painottuivat sotilaallisen kriisinhallinnan henkilöstön kompetensseissakin. Kriisinhallinnassa tarvitaan myös selvää työnjakoa eri toimijoiden kesken. Kosovossa työskennelleen henkilöstön haastatteluaineisto koostui yhteensä 27 teemahaastattelusta. Haastateltavista 9 oli ammattiupseeria, 10 reservistä rekrytoitua rauhanturvaajaa ja 8 siviilikriisinhallinnassa työskennellyttä henkilöä. Haastattelut toteutettiin helmi- ja kesäkuun välisenä aikana vuonna 2008. Haastattelutuloksissa korostui vuorovaikutus- ja kommunikaatiotaitojen merkitys, sillä monissa käytännön tilanteissa haastateltavat olivat ratkoneet ongelmia yhteistyössä muun kriisinhallintahenkilöstön tai paikallisten asukkaiden kanssa. Kriisinhallinnassa toteutui oppimisprosesseja, jotka usein olivat luonteeltaan myönteisiä ja informaalisia. Tällaisten onnistumisten vaikutus yksilön minäkuvaan oli myönteinen. Tällaisia prosesseja voidaan kuvata ”itseä koskeviksi oivalluksiksi”. Kriisinhallintatehtävissä oppimisella on erityinen merkitys, jos halutaan kehittää toimintoja inhimillisen turvallisuuden edistämiseksi. Siksi on tärkeää, että kriisinhallintakoulutusta ja kriisinhallintatyössä oppimista kehitetään ottamaan huomioon oppimisen eri tasot ja ulottuvuudet sekä niiden merkitys. Informaaliset oppimisen muodot olisi otettava paremmin huomioon kriisinhallintakoulutusta ja kriisinhallintatehtävissä oppimista kehitettäessä. Palautejärjestelmää olisi kehitettävä eri tavoin. Koko kriisinhallintaoperaation on saatava tarvittaessa myös kriittistä palautetta onnistumisista ja epäonnistumisista. Monet kriisinhallinnassa työskennelleet kaipaavat kunnollista palautetta työrupeamastaan. Liian rutiininomaiseksi koettu palaute ei edistä yksilön oppimista. Spontaanisti monet haastatellut pitivät tärkeänä, että kriisinhallinnassa työskennelleillä olisi mahdollisuus debriefing- tyyppiseen kotiinpaluukeskusteluun. Pelkkä tällainen mahdollisuus ilmeisesti voisi olla monelle myönteinen uutinen, vaikka tilaisuutta ei hyödynnettäisikään. Paluu kriisinhallintatehtävistä Suomeen on monelle haasteellisempaa kuin näissä tehtävissä työskentelyn aloittaminen ulkomailla. Tutkimuksen tulokset kannustavat tutkimaan kriisinhallintaa oppimisen näkökulmasta. On myös olennaista, että kriisinhallinnan palautejärjestelmiä kehitetään mahdollisimman hyvin edistämään sekä yksilöllistä että organisatorista oppimista kriisinhallinnassa. Kriisinhallintaoperaatio on oppimisympäristö. Kriisinhallintahenkilöstön kommunikaatio- ja vuorovaikutustaitojen kehittäminen on olennaista tavoiteltaessa kestävää rauhanprosessia, jossa konfliktialueen asukkaatkin ovat mukana.

Turun seudun turvallisen ja kestävän liikkumisen suunnitelma

Turun seudun turvallisen ja kestävän liikkumisen suunnitelma on laadittu seudun kuntien ja Varsinais-Suomen ELY-keskuksen yhteistyönä. Suunnitelmassa on selvitetty liikenneturvallisuuden, liikkumisen, toimintaympäristön ja liikennejärjestelmän nykytilaa sekä kartoitettu liikenneturvallisuusongelmia erilaisten analyysien ja kyselyiden avulla. Nykytila-analyysin pohjalta on asetettu liikenneturvallisuustyön visio ja tavoitteet sekä määritetty toimenpide-ehdotukset. Tavoitteisiin pääsemistä tukevat liikenneympäristön parantamistoimenpiteiden ohjelma, liikkumisen ohjauksen toimintaohjelma sekä hallintokuntien liikenneturvallisuustyön toimenpiteistä kootut toimintasuunnitelmat. Onnettomuusanalyysin perusteella liikenneturvallisuuden tila oli Turun seudulla hieman koko Suomen keskiarvoa heikompi. Seudulla tapahtui vuosina 2001-2010 henkilövahinkoon johtaneita onnettomuuksia keskimäärin 132 / 100 000 asukasta, kun vastaava luku oli 126 koko maan osalta. Kuolemaan johtaneita onnettomuuksia tapahtui seudulla vähemmän, mutta loukkaantumiseen johtaneita onnettomuuksia koko maan keskiarvoa enemmän. Onnettomuuksissa kuoli tai loukkaantui koko maan keskiarvoa enemmän jalankulkijoita ja polkupyöräilijöitä. Lukumäärällisesti eniten onnettomuuksia tapahtui 18–19-vuotiaille, mutta henkilövahinkoon johtaneita onnettomuuksia tapahtui selvästi eniten 15–16-vuotiaille. Seudulla tapahtuneista liikenneonnettomuuksista aiheutui vuosittain keskimäärin 127,2 miljoonan euron kustannukset, josta kuntien osuus oli vuosittain noin 22,3 miljoonaa euroa. Asukkaille suunnatun kyselyn mukaan sekä työmatkat että lyhyet vapaa-ajan matkat tehtiin useimmiten henkilöautolla. Koululaisia pidettiin turvattomimpana tienkäyttäjäryhmänä, ja kävelyä sekä pyöräilyä turvattomimpina kulkutapoina. Välinpitämättömyyttä pidettiin merkittävimpänä syynä erilaisiin liikennerikkomuksiin ja tärkeimmäksi kehittämistarpeeksi nousi liikennekäyttäytyminen. Yhdyskuntarakenteen ja toimintaympäristön analyysin perusteella seudulla on hyvät edellytykset kestävien kulkumuotojen kuten joukkoliikenteen houkuttelevuuden lisäämiselle sekä kävelyn ja pyöräilyn verkoston kehittämiselle. Onnettomuusanalyysin ja valtakunnallisten tavoitteiden pohjalta Turun seudulle asetettiin liikenneturvallisuustyön tavoitteet. Tavoitelaskelman mukaan liikennekuolemien ja loukkaantuneiden määrä tulee puolittaa vuosien 2006-2010 keskiarvosta vuoteen 2020 mennessä. Tavoitteen mukaan liikenteessä kuolee enintään 6 (lähtötaso 12) ja loukkaantuu 236 (lähtötaso 471) vuonna 2020. Vaikutusarvion perusteella voidaan arvioida päästävän tavoitteeseen suunnitelmakauden aikana. Tavoitteiden saavuttaminen on kuitenkin haasteellista ja edellyttää tehokasta yhteistyötä eri tahojen välillä. Tavoitteeseen tulee pyrkiä laajaa keinovalikoimaa käyttäen. Suunnitelmatyön aikana aktivoitiin kuntien turvallisen ja kestävän liikkumisen ryhmät, joiden toiminnan tueksi laadittiin toimintasuunnitelmat sekä vuosikello työn eri vaiheista. Ryhmät vastaavat suunnitelman toteuttamisesta, toteutumisen seurannasta ja tarvittaessa päivittämisestä.