University of Chieti-Pescara
UniversityChieti, Italy
Research output, citation impact, and the most-cited recent papers from University of Chieti-Pescara (Italy). Aggregated across the NobleBlocks index of 300M+ scholarly works.
Top-cited papers from University of Chieti-Pescara
BACKGROUND: Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide. METHODS: We assessed cardiovascular outcomes of once-daily oral semaglutide in an event-driven, randomized, double-blind, placebo-controlled trial involving patients at high cardiovascular risk (age of ≥50 years with established cardiovascular or chronic kidney disease, or age of ≥60 years with cardiovascular risk factors only). The primary outcome in a time-to-event analysis was the first occurrence of a major adverse cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The trial was designed to rule out 80% excess cardiovascular risk as compared with placebo (noninferiority margin of 1.8 for the upper boundary of the 95% confidence interval for the hazard ratio for the primary outcome). RESULTS: A total of 3183 patients were randomly assigned to receive oral semaglutide or placebo. The mean age of the patients was 66 years; 2695 patients (84.7%) were 50 years of age or older and had cardiovascular or chronic kidney disease. The median time in the trial was 15.9 months. Major adverse cardiovascular events occurred in 61 of 1591 patients (3.8%) in the oral semaglutide group and 76 of 1592 (4.8%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.57 to 1.11; P<0.001 for noninferiority). Results for components of the primary outcome were as follows: death from cardiovascular causes, 15 of 1591 patients (0.9%) in the oral semaglutide group and 30 of 1592 (1.9%) in the placebo group (hazard ratio, 0.49; 95% CI, 0.27 to 0.92); nonfatal myocardial infarction, 37 of 1591 patients (2.3%) and 31 of 1592 (1.9%), respectively (hazard ratio, 1.18; 95% CI, 0.73 to 1.90); and nonfatal stroke, 12 of 1591 patients (0.8%) and 16 of 1592 (1.0%), respectively (hazard ratio, 0.74; 95% CI, 0.35 to 1.57). Death from any cause occurred in 23 of 1591 patients (1.4%) in the oral semaglutide group and 45 of 1592 (2.8%) in the placebo group (hazard ratio, 0.51; 95% CI, 0.31 to 0.84). Gastrointestinal adverse events leading to discontinuation of oral semaglutide or placebo were more common with oral semaglutide. CONCLUSIONS: In this trial involving patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo. (Funded by Novo Nordisk; PIONEER 6 ClinicalTrials.gov number, NCT02692716.).
AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425, \nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981, \nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826, \nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376, \nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294, \nChris Albanese363, Diego Albani561, Matthew L Albert517, Jesus Aldudo128, Hana Alg€ul1164, Mehrdad Alirezaei1198, \nIraide Alloza642,888, Alexandru Almasan206, Maylin Almonte-Beceril524, Emad S Alnemri1212, Covadonga Alonso544, \nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107, \nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756, \nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6, \nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58, \nShailendra Anoopkumar-Dukie388, Manuela Antonioli832,858, Hiroshi Aoki1791, Nadezda Apostolova2007, \nSaveria Aquila1500, Katia Aquilano1876, Koichi Araki292, Eli Arama2098, Agustin Aranda456, Jun Araya591, \nAlexandre Arcaro1472, Esperanza Arias26, Hirokazu Arimoto1225, Aileen R Ariosa1749, Jane L Armstrong1930, \nThierry Arnould1773, Ivica Arsov2120, Katsuhiko Asanuma675, Valerie Askanas1924, Eric Asselin1867, Ryuichiro Atarashi794, \nSally S Atherton369, Julie D Atkin713, Laura D Attardi1131, Patrick Auberger1787, Georg Auburger379, Laure Aurelian1727, \nRiccardo Autelli1992, Laura Avagliano1029,1755, Maria Laura Avantaggiati364, Limor Avrahami1166, Suresh Awale1986, \nNeelam Azad404, Tiziana Bachetti568, Jonathan M Backer28, Dong-Hun Bae1933, Jae-sung Bae677, Ok-Nam Bae409, \nSoo Han Bae2117, Eric H Baehrecke1729, Seung-Hoon Baek17, Stephen Baghdiguian1368, \nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884, \nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239, \nG abor B anhegyi1052, Haijun Bao2109, Benoit Barbeau1363, Maria D Barrachina2007, Esther Barreiro467, Bonnie Bartel997, \nAlberto Bartolom e222, Diane C Bassham550, Maria Teresa Bassi1046, Robert C Bast Jr1273, Alakananda Basu1798, \nMaria Teresa Batista1578, Henri Batoko1336, Maurizio Battino970, Kyle Bauckman2085, Bradley L Baumgarner1909, \nK Ulrich Bayer1594, Rupert Beale1553, Jean-Fran¸cois Beaulieu1360, George R. Beck Jr48,294, Christoph Becker336, \nJ David Beckham1595, Pierre-Andr e B edard749, Patrick J Bednarski301, Thomas J Begley1135, Christian Behl1419, \nChristian Behrends757, Georg MN Behrens406, Kevin E Behrns1627, Eloy Bejarano26, Amine Belaid490, \nFrancesca Belleudi1041, Giovanni B enard497, Guy Berchem706, Daniele Bergamaschi983, Matteo Bergami1401, \nBen Berkhout1441, Laura Berliocchi714, Am elie Bernard1749, Monique Bernard1354, Francesca Bernassola1880, \nAnne Bertolotti791, Amanda S Bess272, S ebastien Besteiro1351, Saverio Bettuzzi1828, Savita Bhalla913, \nShalmoli Bhattacharyya973, Sujit K Bhutia838, Caroline Biagosch1159, Michele Wolfe Bianchi520,1378,1381, \nMartine Biard-Piechaczyk210, Viktor Billes298, Claudia Bincoletto1314, Baris Bingol350, Sara W Bird1128, Marc Bitoun1112, \nIvana Bjedov1258, Craig Blackstone843, Lionel Blanc1183, Guillermo A Blanco1496, Heidi Kiil Blomhoff1812, \nEmilio Boada-Romero1297, Stefan B€ockler1464, Marianne Boes1423, Kathleen Boesze-Battaglia1835, Lawrence H Boise286,287, \nAlessandra Bolino2063, Andrea Boman693, Paolo Bonaldo1823, Matteo Bordi897, J€urgen Bosch608, Luis M Botana1308, \nJoelle Botti1375, German Bou1405, Marina Bouch e1038, Marion Bouchecareilh1331, Marie-Jos ee Boucher1901, \nMichael E Boulton481, Sebastien G Bouret1926, Patricia Boya133, Micha€el Boyer-Guittaut1345, Peter V Bozhkov1141, \nNathan Brady374, Vania MM Braga469, Claudio Brancolini1997, Gerhard H Braus353, Jos e M Bravo-San Pedro299,393,508,1374, \nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822, \nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480, \nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171, \nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789, \nScott J Bultman1792, Geert Bultynck665, Vladimir Bumbasirevic1470, Yan Burelle1356, Robert E Burke216,217, \nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24, \nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700, \nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983, \nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002, \nSven R Carlsson1267, Didac Carmona-Gutierrez1643, Leticia AM Carneiro312, Oliana Carnevali971, Serena Carra1318, \nAlice Carrier120, Bernadette Carroll900, Caty Casas1324, Josefina Casas1116, Giuliana Cassinelli324, Perrine Castets1462, \nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884, \nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996, \nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628, \nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003, \nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434, \nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783, \nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514, \nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172, \nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113, \nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135, \nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702, \nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703, \nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308, \nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290, \nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105, \nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563, \nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936, \nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657, \nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254, \nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694, \nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781, \nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533, \nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829, \nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395, \nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566, \nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767, \nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301, \nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919, \nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576, \nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572, \nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940, \nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340, \nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254, \nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604, \nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182, \nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775, \nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,
MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Their aberrant expression may be involved in human diseases, including cancer. Indeed, miRNA aberrant expression has been previously found in human chronic lymphocytic leukemias, where miRNA signatures were associated with specific clinicobiological features. Here, we show that, compared with normal breast tissue, miRNAs are also aberrantly expressed in human breast cancer. The overall miRNA expression could clearly separate normal versus cancer tissues, with the most significantly deregulated miRNAs being mir-125b, mir-145, mir-21, and mir-155. Results were confirmed by microarray and Northern blot analyses. We could identify miRNAs whose expression was correlated with specific breast cancer biopathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion, or proliferation index.
Chronic pain is a major source of suffering. It interferes with daily functioning and often is accompanied by distress. Yet, in the International Classification of Diseases, chronic pain diagnoses are not represented systematically. The lack of appropriate codes renders accurate epidemiological investigations difficult and impedes health policy decisions regarding chronic pain such as adequate financing of access to multimodal pain management. In cooperation with the WHO, an IASP Working Group has developed a classification system that is applicable in a wide range of contexts, including pain medicine, primary care, and low-resource environments. Chronic pain is defined as pain that persists or recurs for more than 3 months. In chronic pain syndromes, pain can be the sole or a leading complaint and requires special treatment and care. In conditions such as fibromyalgia or nonspecific low-back pain, chronic pain may be conceived as a disease in its own right; in our proposal, we call this subgroup "chronic primary pain." In 6 other subgroups, pain is secondary to an underlying disease: chronic cancer-related pain, chronic neuropathic pain, chronic secondary visceral pain, chronic posttraumatic and postsurgical pain, chronic secondary headache and orofacial pain, and chronic secondary musculoskeletal pain. These conditions are summarized as "chronic secondary pain" where pain may at least initially be conceived as a symptom. Implementation of these codes in the upcoming 11th edition of International Classification of Diseases will lead to improved classification and diagnostic coding, thereby advancing the recognition of chronic pain as a health condition in its own right.
1. Introduction Chronic pain has been recognized as pain that persists past normal healing time5 and hence lacks the acute warning function of physiological nociception.35 Usually pain is regarded as chronic when it lasts or recurs for more than 3 to 6 months.29 Chronic pain is a frequent condition, affecting an estimated 20% of people worldwide6,13,14,18 and accounting for 15% to 20% of physician visits.25,28 Chronic pain should receive greater attention as a global health priority because adequate pain treatment is a human right, and it is the duty of any health care system to provide it.4,13 The current version of the International Classification of Diseases (ICD) of the World Health Organization (WHO) includes some diagnostic codes for chronic pain conditions, but these diagnoses do not reflect the actual epidemiology of chronic pain, nor are they categorized in a systematic manner. The ICD is the preeminent tool for coding diagnoses and documenting investigations or therapeutic measures within the health care systems of many countries. In addition, ICD codes are commonly used to report target diseases and comorbidities of participants in clinical research. Consequently, the current lack of adequate coding in the ICD makes the acquisition of accurate epidemiological data related to chronic pain difficult, prevents adequate billing for health care expenses related to pain treatment, and hinders the development and implementation of new therapies.10,11,16,23,27,31,37 Responding to these shortcomings, the International Association for the Study of Pain (IASP) contacted the WHO and established a Task Force for the Classification of Chronic Pain. The IASP Task Force, which comprises pain experts from across the globe,19 has developed a new and pragmatic classification of chronic pain for the upcoming 11th revision of the ICD. The goal is to create a classification system that is applicable in primary care and in clinical settings for specialized pain management. A major challenge in this process was finding a rational principle of classification that suits the different types of chronic pain and fits into the general ICD-11 framework. Pain categories are variably defined based on the perceived location (headache), etiology (cancer pain), or the primarily affected anatomical system (neuropathic pain). Some diagnoses of pain defy these classification principles (fibromyalgia). This problem is not unique to the classification of pain, but exists throughout the ICD. The IASP Task Force decided to give first priority to pain etiology, followed by underlying pathophysiological mechanisms, and finally the body site. Developing this multilayered classification was greatly facilitated by a novel principle of assigning diagnostic codes in ICD-11, termed “multiple parenting.” Multiple parenting allows the same diagnosis to be subsumed under more than 1 category (for a glossary of ICD terms refer to Table 1). Each diagnosis retains 1 category as primary parent, but is cross-referenced to other categories that function as secondary parents.Table 1: Glossary of ICD-11 terms.The new ICD category for “Chronic Pain” comprises the most common clinically relevant disorders. These disorders were divided into 7 groups (Fig. 1): (1) chronic primary pain, (2) chronic cancer pain, (3) chronic posttraumatic and postsurgical pain, (4) chronic neuropathic pain, (5) chronic headache and orofacial pain, (6) chronic visceral pain, and (7) chronic musculoskeletal pain. Experts assigned to each group are responsible for the definition of diagnostic criteria and the selection of the diagnoses to be included under these subcategories of chronic pain. Thanks to Bedirhan Üstün and Robert Jakob of the WHO, these pain diagnoses are now integrated in the beta version of ICD-11 (http://id.who.int/icd/entity/1581976053). The Task Force is generating content models for single entities to describe their clinical characteristics. After peer review overseen by the WHO Steering Committee,39 the classification of chronic pain will be voted into action by the World Health Assembly in 2017.Figure 1: Organizational chart of Task Force, IASP, and WHO interactions. The IASP Task Force was created by the IASP council and its scope defined in direct consultation of the chairs (R.D.T. and W.R.) with WHO representatives in 2012. The Task Force reports to the IASP Council on an annual basis.2. Classification of chronic pain Chronic pain was defined as persistent or recurrent pain lasting longer than 3 months. This definition according to pain duration has the advantage that it is clear and operationalized. Optional specifiers for each diagnosis record evidence of psychosocial factors and the severity of the pain. Pain severity can be graded based on pain intensity, pain-related distress, and functional impairment. 2.1. Chronic primary pain Chronic primary pain is pain in 1 or more anatomic regions that persists or recurs for longer than 3 months and is associated with significant emotional distress or significant functional disability (interference with activities of daily life and participation in social roles) and that cannot be better explained by another chronic pain condition. This is a new phenomenological definition, created because the etiology is unknown for many forms of chronic pain. Common conditions such as, eg, back pain that is neither identified as musculoskeletal or neuropathic pain, chronic widespread pain, fibromyalgia, and irritable bowel syndrome will be found in this section and biological findings contributing to the pain problem may or may not be present. The term “primary pain” was chosen in close liaison with the ICD-11 revision committee, who felt this was the most widely acceptable term, in particular, from a nonspecialist perspective. 2.2. Chronic cancer pain Pain is a frequent and debilitating accompaniment of cancer8 that as yet has not been represented in the ICD. The Task Force decided to list it as a separate entity because there are specific treatment guidelines.7,38 Chronic cancer pain includes pain caused by the cancer itself (the primary tumor or metastases) and pain that is caused by the cancer treatment (surgical, chemotherapy, radiotherapy, and others). Cancer-related pain will be subdivided based on location into visceral, bony (or musculoskeletal), and somatosensory (neuropathic). It will be described as either continuous (background pain) or intermittent (episodic pain) if associated with physical movement or clinical procedures. The treatment-related pain will be cross-referenced from the chapters on postsurgical pain and neuropathic pain. 2.3. Chronic postsurgical and posttraumatic pain Because pain that persists beyond normal healing is frequent after surgery and some types of injuries, the entity of postsurgical and posttraumatic pain was created. This is defined as pain that develops after a surgical procedure or a tissue injury (involving any trauma, including burns) and persists at least 3 months after surgery or tissue trauma26; this is a definition of exclusion, as all other causes of pain (infection, recurring malignancy) as well as pain from a pre-existing pain problem need to be excluded. In view of the different causality, as well as from a medicolegal point of view, a separation between postsurgical pain and pain after all other trauma is regarded as useful. Depending on the type of surgery, chronic postsurgical pain is often neuropathic pain (on average 30% of cases with a range from 6% to 54% and more).15 Pain including such a neuropathic component is usually more severe than nociceptive pain and often affects the quality of life more adversely.21 2.4. Chronic neuropathic pain Chronic neuropathic pain is caused by a lesion or disease of the somatosensory nervous system.20,22 The somatosensory nervous system provides information about the body including skin, musculoskeletal, and visceral organs. Neuropathic pain may be spontaneous or evoked, as an increased response to a painful stimulus (hyperalgesia) or a painful response to a normally nonpainful stimulus (allodynia). The diagnosis of neuropathic pain requires a history of nervous system injury, for example, by a stroke, nerve trauma, or diabetic neuropathy, and a neuroanatomically plausible distribution of the pain.22 For the identification of definite neuropathic pain, it is necessary to demonstrate the lesion or disease involving the nervous system, for example, by imaging, biopsy, neurophysiological, or laboratory tests. In addition, negative or positive sensory signs compatible with the innervation territory of the lesioned nervous structure must be present.36 Diagnostic entities within this category will be divided into conditions of peripheral or central neuropathic pain. 2.5. Chronic headache and orofacial pain The International Headache Society (IHS) has created a headache classification17 that is implemented in full in the chapter on neurology. This classification differentiates between primary (idiopathic), secondary (symptomatic) headache, and orofacial pain including cranial neuralgias. In the section on chronic pain, only chronic headache and chronic orofacial pain will be included. Chronic headache and chronic orofacial pain is defined as headaches or orofacial pains that occur on at least 50% of the days during at least 3 months. For most purposes, patients receive a diagnosis according to the headache phenotypes or orofacial pains that they currently present. The section will list the most frequent chronic headache conditions. The most common chronic orofacial pains are temporomandibular disorders,32 which have been included in this subchapter of chronic pain. Chronic orofacial pain can be a localized presentation of a primary headache.2 This is common in the trigeminal autonomic cephalalgias, less common in migraines, and rare in tension-type headache. Several chronic orofacial pains such as post-traumatic trigeminal neuropathic pain,3 persistent idiopathic orofacial pain, and burning mouth syndrome are cross-referenced to, eg, primary chronic pain and neuropathic pain. The temporal definition of “chronic” has been extrapolated from that of chronic headaches.1 2.6. Chronic visceral pain Chronic visceral pain is persistent or recurrent pain that originates from the internal organs of the head and neck region and the thoracic, abdominal, and pelvic cavities.24,33,34 The pain is usually perceived in the somatic tissues of the body wall (skin, subcutis, muscle) in areas that receive the same sensory innervation as the internal organ at the origin of the symptom (referred visceral pain).12 In these areas, secondary hyperalgesia (increased sensitivity to painful stimuli in areas other than the primary site of the nociceptive input) often occurs30; the intensity of the symptom may bear no relationship with the extent of the internal damage or noxious visceral stimulation.9 The section on visceral pain will be subdivided according to the major underlying mechanisms, ie, persistent inflammation, vascular mechanisms (ischemia, thrombosis), obstruction and distension, traction and compression, combined mechanisms (eg, obstruction and inflammation concurrently), and referral from other locations. Pain due to cancer will be cross-referenced to the chapter chronic cancer pain and pain due to functional or unexplained mechanisms to chronic primary pain. 2.7. Chronic musculoskeletal pain Chronic musculoskeletal pain is defined as persistent or recurrent pain that arises as part of a disease process directly affecting bone(s), joint(s), muscle(s), or related soft tissue(s). According to the constraints of the approach as described in the Introduction, this category is therefore limited to nociceptive pain and does not include pain that may be perceived in musculoskeletal tissues but does not arise therefrom, such as the pain of compression neuropathy or somatic referred pain. The entities subsumed in this approach include those characterized by persistent inflammation of infectious, autoimmune or metabolic etiology, such as rheumatoid arthritis, and by structural changes affecting bones, joints, tendons, or muscles, such as symptomatic osteoarthrosis. Musculoskeletal pain of neuropathic origin will be cross-referenced to neuropathic pain. Well-described apparent musculoskeletal conditions for which the causes are incompletely understood, such as nonspecific back pain or chronic widespread pain, will be included in the section on chronic primary pain. 3. Outlook Irrespective of its etiology, chronic pain is a major source of suffering and requires special treatment and care. Our proposal may not represent a perfect solution for the classification of all manifestations of chronic pain. However, it does represent the first systematic approach to implementing a classification of chronic pain in the ICD. It is based on international expertise and agreement, and consistent with the requirements of the ICD regarding the structure and format of content models. The 7 major categories of chronic pain were identified after considerable research and discussion. They represent a compromise between comprehensiveness and practical applicability of the classification system. Several clinically important conditions that were neglected in former ICD revisions will now be mentioned, eg, chronic cancer pain or chronic neuropathic pain. Etiological factors, pain intensity, and disability related to pain will be reflected. With the introduction of chronic primary pain as a new diagnostic entity, the classification recognizes conditions that affect a broad group of patients with pain and would be neglected in etiologically defined categories. We hope that this classification strengthens the representation of chronic pain conditions in clinical practice and research and welcome comments to improve it further. Conflict of interest statement Q. Aziz has attended advisory board meetings for Almirall pharmaceuticals and Grunenthal. He has also received funding for clinical trials from Ono Pharmaceutical and Protexin. M.I. Bennett has received consultancy or speaker fees from Pfizer, Bayer, Astellas, and Grunenthal in the last 5 years. M. Cohen has received honoraria for contributions to educational programs from Mundipharma Pty Limited and Pfizer. S. Evers received honoraria (as speaker and/or member of advisory boards) and research grants within the past 5 years by AGA Medical (now St Jude), Allergan, Almirall, Astra Zeneca, Berlin-Chemie, CoLucid, Desitin, Eisai, GlaxoSmithKline, Ipsen Pharma, Menarini, MSD, Novartis, Pfizer, Reckitt-Benckiser, UCB. N.B. Finnerup has received speaker's honoraria from Pfizer, Grunenthal, and Norpharma, research grant from Grünenthal, and consultancy fee from Astellas and is member of the IMI “Europain” collaboration where industry members of this are: Astra Zeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal, Eli Lilly, Boehringer Ingelheim, Astellas, Abbott, and Lundbeck. M.B. First on the faculty of the Lundbeck International Neuroscience Foundation. In the past 2 years, M.A. Giamberardino received research funding or honoraria (participation in Advisory Board) from Bayer Healthcare, Helsinn, and Epitech Group. S. Kaasa declares no conflict of interest related to this work. In the past year he received honoraria from Helsinn related to participation in Advisory Board. E. Kosek has received consultancy and speaker fees in the past 24 months from Eli Lilly and Company and Orion and has ongoing research collaborations with Eli Lilly and Company and Abbott and Pierre Fabre. M. Nicholas received honoraria for contributing to educational sessions for Mundipharma and Pfizer in the last 5 years. S. Perrot received honoraria as a speaker and/or member of the advisory board in the past 5 years from Pfizer, BMS, Grunenthal, Elli Lilly, Sanofi, Daichi-Sankyo, Astellas, and Mundipharma. He has received grant support from BMS. W. Rief received honoraria (as speaker and/or member of advisory boards on topics such as adherence, placebo mechanisms) within the past 5 years from Berlin Chemie, Astra Zeneca, Bayer, Heel (research grant). J. Scholz has received speaker fees from Convergence, GlaxoSmithKline, Pfizer, St Jude Medical, and Zalicus. He has served on advisory boards or consulted for Convergence, Pfizer, Sanofi Aventis, and Zalicus Pharmaceuticals. He has received grant support from GlaxoSmithKline and Pfizer. In the last 5 years, the Anaesthesiology Unit of the University of Western Australia, but not S. Schug personally, has received research and travel funding and speaking and consulting honoraria from bioCSL, Bionomics, Eli Lilly, Grunenthal, Janssen, Mundipharma, Pfizer, Phosphagenics and iX Biopharma within the last 2 years. B.H. Smith has received lecture and consultancy fees, on behalf of his institution, from Pfizer, Grunenthal, Eli Lilly, and Napp. He has received unconditional educational grants from Pfizer Ltd; and he has received travel and accommodation support from Napp. P. Svensson served as a paid consultant for Sunstar Suisse SA. R.-D. Treede has received speaker's honoraria, research grants or consultancy fees from AbbVie, Acron, Astellas, Bauerfeind, Boehringer Ingelheim, Grünenthal, Hydra, Mundipharma, and Pfizer and is a member of the IMI “Europain” collaboration where industry members of this are: Astra Zeneca, Pfizer, Esteve, UCB-Pharma, Sanofi Aventis, Grünenthal, Eli Lilly, Boehringer Ingelheim, Astellas, Abbott, and Lundbeck. J.W.S. Vlaeyen is a member of the PHILIPS advisory board on pain management and declares no conflicts of interest with regard to this work. S.-J. Wang has served on the advisory boards of Allergan and Eli Lilly, Taiwan. He has received speaking honoraria from local companies (Taiwan branches) of Pfizer, Elli Lilly, and GSK. He has received research grants from the Novartis Taiwan, Taiwan Ministry of Science and Technology, Taipei-Veterans General Hospital and Taiwan Headache Society. The other authors have no conflicts of interest to declare. Acknowledgements The authors are members of the Classification of Pain Diseases Task Force of the International Association for the Study of Pain (IASP), which gave logistical and financial support to perform this work. We acknowledge the contributions of the following IASP Special Interest Groups (SIGs): Abdominal & Pelvic Pain SIG, Acute Pain SIG, Cancer Pain SIG, Neuropathic Pain SIG and the Orofacial Pain SIG, and the Classification Committee of the International Headache Society (IHS). Author contributions: R.-D. Treede, W. Rief, and A. Barke contributed equally to this topical review.
autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
The details of all steps involved in the quantification of biofilm formation in microtiter plates are described. The presented protocol incorporates information on assessment of biofilm production by staphylococci, gained both by direct experience as well as by analysis of methods for assaying biofilm production. The obtained results should simplify quantification of biofilm formation in microtiter plates, and make it more reliable and comparable among different laboratories.
This review of the role of platelets in atherothrombosis illuminates the surprisingly numerous activities of these tiny, anucleate cells and stresses their participation in the inflammatory component of atherothrombosis. The information is presented in the context of the prevention of atherothrombosis by antiplatelet agents now in clinical use.
The uncontrolled spread of the coronavirus disease 2019 (COVID-19) has called for unprecedented measures, to the extent that the Italian government has imposed a quarantine on the entire country. Quarantine has a huge impact and can cause considerable psychological strain. The present study aims to establish the prevalence of psychiatric symptoms and identify risk and protective factors for psychological distress in the general population. An online survey was administered from 18-22 March 2020 to 2766 participants. Multivariate ordinal logistic regression models were constructed to examine the associations between sociodemographic variables; personality traits; depression, anxiety, and stress. Female gender, negative affect, and detachment were associated with higher levels of depression, anxiety, and stress. Having an acquaintance infected was associated with increased levels of both depression and stress, whereas a history of stressful situations and medical problems was associated with higher levels of depression and anxiety. Finally, those with a family member infected and young person who had to work outside their domicile presented higher levels of anxiety and stress, respectively. This epidemiological picture is an important benchmark for identifying persons at greater risk of suffering from psychological distress and the results are useful for tailoring psychological interventions targeting the post-traumatic nature of the distress.
Functional neuroimaging and electrophysiological studies have documented a dynamic baseline of intrinsic (not stimulus- or task-evoked) brain activity during resting wakefulness. This baseline is characterized by slow (<0.1 Hz) fluctuations of functional imaging signals that are topographically organized in discrete brain networks, and by much faster (1-80 Hz) electrical oscillations. To investigate the relationship between hemodynamic and electrical oscillations, we have adopted a completely data-driven approach that combines information from simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Using independent component analysis on the fMRI data, we identified six widely distributed resting state networks. The blood oxygenation level-dependent signal fluctuations associated with each network were correlated with the EEG power variations of delta, theta, alpha, beta, and gamma rhythms. Each functional network was characterized by a specific electrophysiological signature that involved the combination of different brain rhythms. Moreover, the joint EEG/fMRI analysis afforded a finer physiological fractionation of brain networks in the resting human brain. This result supports for the first time in humans the coalescence of several brain rhythms within large-scale brain networks as suggested by biophysical studies.
Apoptosis is a form of programmed cell death that results in the orderly and efficient removal of damaged cells, such as those resulting from DNA damage or during development. Apoptosis can be triggered by signals from within the cell, such as genotoxic stress, or by extrinsic signals, such as the binding of ligands to cell surface death receptors. Deregulation in apoptotic cell death machinery is an hallmark of cancer. Apoptosis alteration is responsible not only for tumor development and progression but also for tumor resistance to therapies. Most anticancer drugs currently used in clinical oncology exploit the intact apoptotic signaling pathways to trigger cancer cell death. Thus, defects in the death pathways may result in drug resistance so limiting the efficacy of therapies. Therefore, a better understanding of the apoptotic cell death signaling pathways may improve the efficacy of cancer therapy and bypass resistance. This review will highlight the role of the fundamental regulators of apoptosis and how their deregulation, including activation of anti-apoptotic factors (i.e., Bcl-2, Bcl-xL, etc) or inactivation of pro-apoptotic factors (i.e., p53 pathway) ends up in cancer cell resistance to therapies. In addition, therapeutic strategies aimed at modulating apoptotic activity are briefly discussed.
BACKGROUND: Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear. METHODS: In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration. RESULTS: Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analysis. A primary-outcome event occurred in 67 of the 522 patients (12.8%) in the edoxaban group as compared with 71 of the 524 patients (13.5%) in the dalteparin group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70 to 1.36; P=0.006 for noninferiority; P=0.87 for superiority). Recurrent venous thromboembolism occurred in 41 patients (7.9%) in the edoxaban group and in 59 patients (11.3%) in the dalteparin group (difference in risk, -3.4 percentage points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 36 patients (6.9%) in the edoxaban group and in 21 patients (4.0%) in the dalteparin group (difference in risk, 2.9 percentage points; 95% CI, 0.1 to 5.6). CONCLUSIONS: Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials.gov number, NCT02073682 .).
Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used to treat arthritis, menstrual pain, and headache. Although they are effective, their long-term use is limited by gastrointestinal effects such as dyspepsia and abdominal pain and, less often, gastric or duodenal perforation or bleeding. Development of the coxibs, a new group of antiinflammatory drugs, represents a response to the unsatisfactory therapeutic profile of NSAIDs. Both groups of drugs inhibit prostaglandin G/H synthase, the enzyme that catalyzes the transformation of arachidonic acid to a range of lipid mediators, termed prostaglandins and thromboxanes (Figure 1). However, whereas NSAIDs inhibit the two recognized forms of the . . .
Numerous experimental, epidemiologic, and clinical studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors, have promise as anticancer agents. NSAIDs restore normal apoptosis in human adenomatous colorectal polyps and in various cancer cell lines that have lost adenomatous polyposis coli gene function. NSAIDs also inhibit angiogenesis in cell culture and rodent models of angiogenesis. Many epidemiologic studies have found that long-term use of NSAIDs is associated with a lower risk of colorectal cancer, adenomatous polyps, and, to some extent, other cancers. Two NSAIDs, sulindac and celecoxib, have been found to inhibit the growth of adenomatous polyps and cause regression of existing polyps in randomized trials of patients with familial adenomatous polyposis (FAP). However, unresolved questions about the safety, efficacy, optimal treatment regimen, and mechanism of action of NSAIDs currently limit their clinical application to the prevention of polyposis in FAP patients. Moreover, the development of safe and effective drugs for chemoprevention is complicated by the potential of even rare, serious toxicity to offset the benefit of treatment, particularly when the drug is administered to healthy people who have low annual risk of developing the disease for which treatment is intended. This review considers generic approaches to improve the balance between benefits and risks associated with the use of NSAIDs in chemoprevention. We critically examine the published experimental, clinical, and epidemiologic literature on NSAIDs and cancer, especially that regarding colorectal cancer, and identify strategies to overcome the various logistic and scientific barriers that impede clinical trials of NSAIDs for cancer prevention. Finally, we suggest research opportunities that may help to accelerate the future clinical application of NSAIDs for cancer prevention or treatment.
This article describes a proposal for the new diagnosis of chronic primary pain (CPP) in ICD-11. Chronic primary pain is chosen when pain has persisted for more than 3 months and is associated with significant emotional distress and/or functional disability, and the pain is not better accounted for by another condition. As with all pain, the article assumes a biopsychosocial framework for understanding CPP, which means all subtypes of the diagnosis are considered to be multifactorial in nature, with biological, psychological, and social factors contributing to each. Unlike the perspectives found in DSM-5 and ICD-10, the diagnosis of CPP is considered to be appropriate independently of identified biological or psychological contributors, unless another diagnosis would better account for the presenting symptoms. Such other diagnoses are called "chronic secondary pain" where pain may at least initially be conceived as a symptom secondary to an underlying disease. The goal here is to create a classification that is useful in both primary care and specialized pain management settings for the development of individualized management plans, and to assist both clinicians and researchers by providing a more accurate description of each diagnostic category.
Coronavirus-19 (COVI-19) involves humans as well as animals and may cause serious damage to the respiratory tract, including the lung: coronavirus disease (COVID-19). This pathogenic virus has been identified in swabs performed on the throat and nose of patients who suffer from or are suspected of the disease. When COVI-19 infect the upper and lower respiratory tract it can cause mild or highly acute respiratory syndrome with consequent release of pro-inflammatory cytokines, including interleukin (IL)-1β and IL-6. The binding of COVI-19 to the Toll Like Receptor (TLR) causes the release of pro-IL-1β which is cleaved by caspase-1, followed by inflammasome activation and production of active mature IL-1β which is a mediator of lung inflammation, fever and fibrosis. Suppression of pro-inflammatory IL-1 family members and IL-6 have been shown to have a therapeutic effect in many inflammatory diseases, including viral infections. Cytokine IL-37 has the ability to suppress innate and acquired immune response and also has the capacity to inhibit inflammation by acting on IL-18Rα receptor. IL-37 performs its immunosuppressive activity by acting on mTOR and increasing the adenosine monophosphate (AMP) kinase. This cytokine inhibits class II histocompatibility complex (MHC) molecules and inflammation in inflammatory diseases by suppressing MyD88 and subsequently IL-1β, IL-6, TNF and CCL2. The suppression of IL-1β by IL-37 in inflammatory state induced by coronavirus-19 can have a new therapeutic effect previously unknown. Another inhibitory cytokine is IL-38, the newest cytokine of the IL-1 family members, produced by several immune cells including B cells and macrophages. IL-38 is also a suppressor cytokine which inhibits IL-1β and other pro-inflammatory IL-family members. IL-38 is a potential therapeutic cytokine which inhibits inflammation in viral infections including that caused by coronavirus-19, providing a new relevant strategy.
The Paleocene-Eocene thermal maximum (PETM) has been attributed to the rapid release of approximately 2000 x 10(9) metric tons of carbon in the form of methane. In theory, oxidation and ocean absorption of this carbon should have lowered deep-sea pH, thereby triggering a rapid (<10,000-year) shoaling of the calcite compensation depth (CCD), followed by gradual recovery. Here we present geochemical data from five new South Atlantic deep-sea sections that constrain the timing and extent of massive sea-floor carbonate dissolution coincident with the PETM. The sections, from between 2.7 and 4.8 kilometers water depth, are marked by a prominent clay layer, the character of which indicates that the CCD shoaled rapidly (<10,000 years) by more than 2 kilometers and recovered gradually (>100,000 years). These findings indicate that a large mass of carbon (>>2000 x 10(9) metric tons of carbon) dissolved in the ocean at the Paleocene-Eocene boundary and that permanent sequestration of this carbon occurred through silicate weathering feedback.
The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.
Objectives. The present study aimed to explore the effect of risk factors associated with the COVID-19 outbreak experience on parents and children well-being. Methods. Parents of 2 to14 years old children completed an on-line survey reporting their home environment condition, the contact they had with the pandemic consequences, the difficulties experienced due to the quarantine, their perception of individual and parent-child dyadic stress, and children emotional and behavioral problems. Results. Results evidenced that the perception of the strain of the quarantine is a crucial factor that undermines both parents and children well-being. Quarantine’s impact on children’s behavioral and emotional problems is mediated by parent’s individual and dyadic stress with a stronger effect of the latter. Parents who reported more difficulties in dealing with quarantine show more stress. This, in turn, increases children problems. Living in a more at-risk area, the quality of home environment, or the contact with the pandemic consequences, do not have effect on families’ well-being. Conclusions. Dealing with quarantine is a particularly stressful experience for parents who must balance personal life, work, and children upbringing, being left alone without other helping sources. This situation puts parents at a higher risk of experiencing distress, potentially impairing their ability to be supportive caregivers. The lack of support these children receive in such a difficult moment may be the reason of their higher psychological symptoms. Policies should take more into consideration the implications of the lockdown for families’ mental health, and supportive intervention for the immediate and the future should be promoted.
The anti-inflammatory, antiangiogenic, anticoagulant, and antiadhesive properties of fucoidans obtained from nine species of brown algae were studied in order to examine the influence of fucoidan origin and composition on their biological activities. All fucoidans inhibited leucocyte recruitment in an inflammation model in rats, and neither the content of fucose and sulfate nor other structural features of their polysaccharide backbones significantly affected the efficacy of fucoidans in this model. In vitro evaluation of P-selectin-mediated neutrophil adhesion to platelets under flow conditions revealed that only polysaccharides from Laminaria saccharina, L. digitata, Fucus evanescens, F. serratus, F. distichus, F. spiralis, and Ascophyllum nodosum could serve as P-selectin inhibitors. All fucoidans, except that from Cladosiphon okamuranus carrying substantial levels of 2-O-alpha-D-glucuronopyranosyl branches in the linear (1-->3)-linked poly-alpha-fucopyranoside chain, exhibited anticoagulant activity as measured by activated partial thromboplastin time whereas only fucoidans from L. saccharina, L. digitata, F. serratus, F. distichus, and F. evanescens displayed strong antithrombin activity in a platelet aggregation test. The last fucoidans potently inhibited human umbilical vein endothelial cell (HUVEC) tubulogenesis in vitro and this property correlated with decreased levels of plasminogen-activator inhibitor-1 in HUVEC supernatants, suggesting a possible mechanism of fucoidan-induced inhibition of tubulogenesis. Finally, fucoidans from L. saccharina, L. digitata, F. serratus, F. distichus, and F. vesiculosus strongly blocked MDA-MB-231 breast carcinoma cell adhesion to platelets, an effect which might have critical implications in tumor metastasis. The data presented herein provide a new rationale for the development of potential drugs for thrombosis, inflammation, and tumor progression.