Medical professionalism is a core aspect of medical education and practice worldwide. Medical professionalism must be reinterpreted to adapt to different social/cultural/historical contexts. We conducted a survey to examine the current understanding and perceived value of medical professionalism among Korean physicians.The survey was distributed to 950 physicians nationwide; 721 (75.89 %) completed surveys were returned between 1 April and 31 July 2011.In their practice, Korean physicians prioritized the values and virtues of medical professionalism in the following (descending) order: veracity, respect for patient autonomy, integrity, responsibility, altruism, and honesty. Approximately two-thirds of physicians responded that medical professionalism is an element of their vocation. When asked to choose the most important sets of attributes or virtues of medical professionalism from a provided list, the top three sets (in descending order of frequency) were: “responsibility and duty,” “veracity, integrity, and honesty,” and “rapport with patients and conversational skill.”Korean physicians value moral duties, such as responsibility and veracity, more than they do moral virtues, such as altruism and honesty with patients. It is presumed that physicians are under pressure due to governmental regulation of the national healthcare system and have difficulty exercising their autonomy.The online version of this article (doi:10.1186/s12910-015-0051-7) contains supplementary material, which is available to authorized users. Medical professionalism is a representative term that embodies the nature, obligations, and identity of medical doctors . The impWe start with the question of Korean physicians’ understanding of medical professionalism. Traditional medicine had been practiced for many centuries in Korea before Western medicine was introduced. Asian medical practitioners have traditionally been expected to be concerned healers who cure sicknesses of body and soul; indeed, they are also respected for these virtues.Doctors in general are recognized as professionals who carry out a socially important role, similar to those of clergy and lawyers . An undeWestern medicine was introduced to Korea during a short period of modernization at the time of Japanese colonization , 18. It According to an old saying, the good doctor treats diseases of the body; the better doctor heals sickness of the soul; and the great doctor cures both of these and societal illness as well. The individual and collective obligations of physicians are to restore the health of the individual and of society . The essPublic concern about medical professionalism and medical ethics has increased due to two dramatic events in Korean medical history . The firThe roles and responsibilities of physicians must be redefined, and medical ethics must be promoted among Korean physicians. Physicians must understand these roles and responsibilities towards patients, their peers, and society if medical professionalism is to be reestablished in Korean society. The purpose of this study was to demonstrate, through physicians’ ratings of importance of the various values or virtues of medical professionalism, that even physicians who are not familiar with the term ‘medical professionalism’ embody the concept through their history of devotion to medical practices that are consistent with these values.This study was based on an anonymous survey  in this finding, with the highest frequency of affirmative responses about professionalism among those in their 60s and the lowest ratings among those in their 20s  order of importance: veracity, respect for patient autonomy, responsibility, integrity, altruism, and honesty , “veracity, integrity, and honesty” , “rapport with patients and conversational skill” , “benevolence, altruism, and compassion” , “trustworthiness” , “public service” , “patient autonomy” 9,120 respondents, 16.71 %), “virtue and good heart” , and “collegial relationships”   incentive and CPD credits; reinforcement of medical ethics activation of regional medical societies; reorganization of medical insurance and adequacy of medical insurance reimbursements; use of role models; emphasis on medical professionalism and self-regulation within medical associations; reinforcement of doctors’ involvement in and relationship with professional societies; public service; and cooperation between Western and Asian medicine (see Table The term “medical professionalism” implies elements of both “medicine” and “professionalism.” Medicine is delivered by doctors who have professed to use their medical knowledge and skill only for the good of the patient. Medicine as a profession is maintained by doctors who develop, comply with, and embody the medical code . TherefoCruess et al.  emphasizWynia et al.  identifiThe Royal Academy of Medicine has stated that a strong motivation to be devoted to others is the primary characteristic required for a medical professional . AccordiAccording to the survey, over two-thirds of the physicians responded that medical professionalism is properly a part of the profession of medicine. Factors highly correlated with this response were physician experience and age. As Aristotle defined virtue as a stable disposition that is formed through habitual acts, physician’s professionalism is formed throughout medical practice over the years. Pelligrino noted that a virtuous physician is not simply born, but is formed through years of deliberate practice. Time and experience are essential factors to nurture, cultivate, and promote medical virtues. As physicians accumulate practice, they are more likely to regard medical professionalism as an element of their vocation .Moral duty and responsibility were the component set that was advocated most highly as indicative of medical professionalism. Part of the survey included cases involving medical moral dilemmas in practice to determine the virtues most valued by Korean physicians. Regardless of whether the respondents endorsed medical professionalism as an element of the vocation, they listed veracity, respect for patient autonomy, integrity, responsibility, altruism, and honesty as important characteristics of medical professionalism. Korean physicians tended to emphasize moral norms, such as veracity and respect for patient autonomy, rather than altruism, as basic virtues or ordering principles of medical professionalism. The survey results reflect the current status of medical professionals in a country with a national health insurance system and a government-led healthcare policy. Korean physicians are overwhelmed with excess documents and are expected to comply with ever-changing policies. Therefore, physicians find it difficult to exercise their discretion and display the virtues of a medical professional; they feel a lack of autonomy as professionals despite their altruistic mindset.The Royal College of Physicians has stated that all doctors must abandon their sense of supremacy, autonomy, and privilege as medical professionals . HoweverIt is presumed that the life-long experience of doctors gives them insight and wisdom, which is consistent with Aristotle’s virtue ethics. According to Aristotle, time and experience are essential to acquire appropriate virtue in practice . It is eIn our study, Korean physicians reported responsibility and obligation as core medical professionalism virtues in their practice, which reflects essential virtues according to the medical code of ethics. However, the physicians also recognized the importance of altruism and empathy as traditional medical professionalism virtues and reported that they realize these virtues in practice whenever the sociocultural conditions facilitate it. In conclusion, physicians tended to have an appropriate attitude toward medical professionalism, yet they felt that the social environment did not enable achievement of their potential as medical professionals. The finding that Korean physicians hold the more normative values like responsibility and veracity in higher esteem than other virtues reflects their lack of autonomy due to excess governmental limitations in the healthcare system. The health insurance review and assessment service evaluates the ‘adequacy’ of treatment provided to the patient . The ‘adThe Korean healthcare system is experiencing a dilemma between extending health care insurance coverage and effectively managing the healthcare insurance budget. The government forces physicians to reduce healthcare service spending rather than raising the level of reimbursement. The degree and quality of healthcare service for a particular patient should left primarily to the physician’s medical expertise and his or her conscience. Government’s reinforcement of regulations and monitoring of physicians’ decisions is not the best way to ensure ethical behaviors in medical practice. To promote ethical culture, it is necessary to allow physician’s autonomy and to encourage a self-policing system within the medical profession . AccordiThe survey results demonstrate the necessity of implementing a CPD program to reinforce the autonomy of the medical profession and to promote medical professionalism in Korea. Physicians’ autonomy requires responsible behaviors by physicians as moral agents. Therefore, the Medical Association should provide physicians with opportunities for continuing education and training to promote ethical behavior. Dissemination of ethical culture among physicians will change societal attitudes toward medical professionals, build trusting and respectful relationships, and contribute to a sound medical culture.The survey results showed that physicians do not recognize the importance of values such as “collegial relationships” or “public service,” and these findings reflect a lack of collective medical professionalism, i.e., an inability and unwillingness to exercise self-governance, to nurture professional attitudes among colleagues, and to establish a moral culture as a professional group. Transformation based on social change is inevitable for Korean physicians and medical societies. As medicine cannot exist apart from society, the social responsibilities of physicians must be emphasized more than has been the case previously.The survey also showed that Korean physicians are aware of the need to strengthen the ethical elements of medical professionalism and proposed CPD as a means of achieving this. Implementing a CPD program for medical professionalism, including vocation, competence, ethical elements, and leadership, will enable doctors to maintain a moral basis for their work. Such a program could lead to establishment of a new and improved medical professionalism in Korea. It is time to initiate a movement for new medical professionalism in Korea. In this way, patient trust and the reliance of society on the medical community can be restored . It is eA solid education program is important to produce good doctors who practice medicine in an exemplary manner. In particular, the program should emphasize the teaching of students and the medical professionalism of young physicians. Nevertheless, just as making a good doctor is similar to making a good person, designing such a program to do either is challenging . The CatKorea has a relatively short history of medical professionalism, which is not yet entrenched in medical education or in the clinical context. The medical community must recognize the importance of appropriate identification and implementation of medical professionalism for Korea in the 21st century. Contemporary medical professionalism should address social concerns including public healthcare and social welfare, as well as the healing relationship between patient and physician. The country has a national health insurance system and a government-oriented health policy. Korean physicians need more opportunities to exercise self-governance and autonomy to be socially responsible for medical education and medical practice. A medical profession equipped with autonomy and independence will contribute to formation of a good medical culture.Medical professionalism is the basis for trust in the patient–doctor relationship, and is a core element of being a good doctor –42. The As mentioned in the Health Foundation’s new definition of medical professionalism, medical practice involves not only doctors but also all other healthcare professionals. doctors and patients has become more of a partnership , 47, 48—


Saxicola spp), which all breed during a short breeding season, but differ in migratory behavior, seasonal territory-acquisition and pace of life.Testosterone facilitates physiological, morphological, and behavioral changes required for breeding in male vertebrates. However, testosterone concentrations and the link between its seasonal changes and those in reproductive behaviors vary greatly among species. To better understand the impact of tropical and temperate environments and life history factors on this variation, we have compared testosterone, territorial behavior and song performance across sequential stages of the breeding season in males of 16 closely related taxa of East African tropical and West European temperate stonechats  contains supplementary material, which is available to authorized users. The sex steroid testosterone coordinates many reproductive traits in male vertebrates (reviewed by ). TestosHowever, quantitative differences in peak testosterone levels and differences in the degree to which testosterone mediates reproductive behaviors have been observed . For exaMore recently, however, several studies have shown that males of tropical species that breed in highly seasonal environments have indeed similar peak testosterone concentrations as temperate seasonal breeders . SuIn birds, song is a major component of territory establishment and mate attraction –55 and dSaxicola spp) have a wide distribution range from tropical to temperate environments, but wherever they occur, they are seasonal breeders ).Zonotrichia that breed in the Neotropics and North America. The life history of neotropical high altitude rufous-collared sparrows (Z. capensis) is very similar to the life history of afrotropical stonechats: both are residents and breed seasonally at high altitudes and in open grassland habitats during a relatively short breeding season of 3–4 months [Previous generalizations of low testosterone concentrations in tropical birds may have been biased by studies of neotropical or Australian species with extended breeding seasons , 101–1074 months . Similar4 months . However4 months , 109 – h(Troglodytes aedon) sang fewer elements at a slower rate than temperate house wrens [The differences in song performance which we report for tropical versus temperate stonechats may well be related to differences in territoriality and migratory behavior. Song characteristics play an important role during male-male interactions  and for se wrens . Neverthse wrens , 111–114se wrens .In seasonally breeding species, regardless of latitude, short peaks of testosterone may help to avoid costs associated with high levels of this hormone, including potential impairment of the immune system, survival and male parental care , 32. Sev(Hylophylax n. naevioides) testosterone concentrations were very low during breeding, but rose transiently during prolonged simulated territorial intrusions [In some species with long breeding seasons, testosterone concentrations increase only during social interactions or periods of social instability . For extrusions . Alternatrusions , exemplitrusions , 118. WhThis is the first study that assessed the role of testosterone, territorial behavior and song concomitantly in several closely related taxa and populations of a songbird breeding at different latitudes from Europe to the Afrotropics. In both European and African male stonechats, a strong territorial response during the fertile period of females coincided with high testosterone concentrations. However, European males sang with a higher song and element rate during the pre-nesting and nest-building phase than African males, despite similar testosterone levels. Thus, in male tropical stonechats seasonal breeding and short breeding seasons may have led to similar peak testosterone concentrations and territorial aggression as in temperate stonechats. However, year-round territories and stable pair-bonds have reduced the pressure of finding a new mate at the beginning of the breeding season in tropical stonechats, which is reflected in a lower song performance in African compared to European male stonechats. Future studies should determine the role of extra-pair paternity in temperate and tropical stonechats as a potential evolutionary driver of high testosterone peaks when females are fertile. Further, as the data collected in this study are correlational, experimental approaches using androgen and estrogen receptor blockers to determine causal relationships between testosterone and behavior are necessary. This kind of information is particularly rare in tropical species, and especially for studies that also investigate song structure. Taken together, our study suggests that breeding in seasonal environments during short breeding seasons is a major selective force for high peak testosterone levels of male birds independent of breeding latitude and variation in pace of life, and that particular behaviors, in our case song performance, can be uncoupled from peak testosterone levels.


This book presents a step-by-step surgical description of vaginal hysterectomy, abdominal hysterectomy, conventional laparoscopic hysterectomy, and robotic-assisted hysterectomy. It brings into balance theoretical background, clinical experience, and scientific findings in a readily comprehensible form with numerous illustrations and tables. The book contains a large proportion of interdisciplinary aspects that make a substantial contribution to meeting the growing requirements of interdisciplinary medical treatment. It offers related disciplines the opportunity to describe areas of common overlap and how these can be treated.Verschiedene chirurgische Verfahren einschließlich vaginaler Hysterektomie, abdominaler Hysterektomie, konservativer laparoskopischer Hysterektomie und roboterassistierter Hysterektomie werden in diesem englischsprachigen Lehrbuch schrittweise beschrieben. In ausgewogener Art und Weise werden theoretische Hintergründe, klinische Erfahrungen und wissenschaftliche Erkenntnisse in leicht verständlicher Form mit zahlreichen Abbildungen und Tabellen dargestellt. Indem es verschiedene interdisziplinäre Aspekte behandelt, wird das Buch den wachsenden Anforderungen der interdisziplinären medizinischen Therapie gerecht. Benachbarte medizinische Fachbereiche kommen zu Wort und haben die Möglichkeit, überlappende Krankheitsbilder und deren Behandlung zu erläutern. This comprehensive surgical approach to hysterectomy rests on the pillars erected by the great masters in gynecology and obstetrics. The first hysterectomy was performed as a vaginal hysterectomy and dates back to ancient times. The procedure was performed in the time of Soranus of Ephesus, 120 years after the birth of Christ. There were many reports of its use in the Middle Ages, nearly always for the extirpation of an inverted uterus, and the patients rarely survived. Hysterectomy became safer with the introduction of anesthesia, antibiotics and antisepsis, blood transfusions, and intravenous therapy. Apart from the transverse abdominal incision introduced by Johannes Pfannenstiel in the 1900s, there was little advance in hysterectomy techniques until the advent of endoscopic surgery and the performance of the first laparoscopic hysterectomy by Kurt Semm in Kiel in 1984, and Harry Reich in Kingston, Pennsylvania in 1988 (In this age of global communication, it seems more than appropriate to publish a specialist surgical book on hysterectomy that features leading surgeons, researchers and teachers from around the globe as contributing authors. With the assistance of over 200 multi-disciplinary authors, the editors have been able to compile a book that meets the requirements of a broad base of readers from beginners to specialists in gynecology. The book at hand also addresses specialists in other surgical fields, such as urologists, visceral surgeons, pathologists, radiologists, anesthesiologists, and conservative gynecologists, dealing with the interdisciplinary challenges associated with hysterectomy.Although there is a flood of literature on this topic, this comprehensive approach to hysterectomy is unique in that it includes the historical background of the leading surgical techniques of the present day and the future perspectives as seen by the leading, contemporary, multi-disciplinary authors.The main part of the book provides a balance of theoretical background, broad clinical experience, and scientific findings in a readily comprehensible and well-described manner, enriched with extensive illustrations and tables. For the beginner, this masterpiece serves as a reliable companion, providing background information and assistance for all procedures associated with hysterectomy. This includes abdominal, vaginal, conventional laparoscopic, and robotic-assisted surgical procedures for benign and malignant indications. Experienced surgeons in particular will be able to broaden their spectrum and learn experimental and innovative surgical approaches because this textbook is unique in offering traditional, up-to-date, and innovative surgical methods for hysterectomy. The associated medical fields, such as general surgery, urology, pathology, anesthesiology, radiology, and general /internal medicine, will benefit from the structured organization of the book and the integration of all interdisciplinary aspects.After beginning with the historical background, there follows a section on topographic anatomy for hysterectomy procedures. This section was written by a renowned clinical anatomist and provides new insights into the female anatomy. The next section comprises five chapters dealing with imaging and diagnostics, followed by a section examining extended, and often controversial, aspects regarding indications and contraindications. Even the often underrepresented aspects of communication and training have a firm place in the book . FurtherThe main aspects of the book deal with the practical performance of hysterectomy with conventional laparoscopic, robotic-assisted, abdominal, and vaginal surgical techniques. In addition to all types of hysterectomies for benign and malignant indications, concomitant procedures such as urogynecologic procedures, lymphadenectomy, and omentectomy are featured in the book.The book has several unique features. The historical chapters were written by world-renowned and respected contemporary witnesses of pioneering surgical developments . The imaThe book examines many interdisciplinary aspects and the editors believe it will make a substantial contribution to meeting the growing requirements of interdisciplinary medical treatment. It offers related disciplines the opportunity to describe the areas of common overlap and how these can be treated.The wide range of contents developed in the course of the conception of the book. Extended hysterectomy procedures cannot be separated from pre- and postsurgical aspects or from procedures on the internal genital organs or those involving the anatomic and functionally-relevant surrounding area. This book gives access to the most advanced treatment concepts of our time. Furthermore, the eBook version meets global demands of unlimited exchange and gives access to the worldwide community interested in this topic. This text book is an important addition to the literature on hysterectomy techniques, accessible to gynecologists worldwide, and thereby contributes towards the global improvement of healthcare for women.


The clinical high-risk state for psychosis syndrome (CHR) offers substantial potential benefits in terms of early identification and treatment for at-risk youth. Early treatment might lead to decreased symptoms, thus leading to reduced symptom-related stigma. However, stigma of the clinical high-risk state for psychosis designation might also initiate further stigma through the label of risk for psychosis. Identifying the effects of these sources of stigma is critical in order to best minimize stigma associated with CHR identification and to facilitate recovery.Baseline stigma assessments were conducted with 170 clinical high risk state for psychosis individuals in a major, NIH-funded longitudinal study at Columbia University Medical Center, Harvard University Medical Center, and Maine Medical Center from 2012 to 2017. Labeling-related measures of stigma  adapted to the CHR group, and a parallel measure of symptom-related stigma  were administered. These measures were examined in relation to outcomes of: a) self-esteem, b) quality of life, and c) social functioning, adjusting for sociodemographics and core CHR symptoms (e.g. attenuated psychotic symptoms).Results indicated that stigma related to symptoms was more strongly associated with all outcomes when compared with shame related to the risk-label. Stigma related to symptoms remained a significant predictor of self-esteem and quality of life even after accounting for stigma related to the risk-label and the effects of sociodemographics and CHR symptoms. Conversely, stigma related to the risk-label was no longer a significant predictor for outcomes after accounting for stigma related to symptoms.Overall, symptom-related stigma was a more salient correlate and was independently linked with self-esteem and quality of life even after accounting for the effects of stigma related to the risk-label. These results indicate that treating of symptoms through early identification and treatment may provide major benefit for CHR youth by also alleviating symptom-related stigma. These findings also indicate that CHR services should address stigma associated with symptoms immediately at first identification, as these have substantial effects on psychological and functional outcomes. These findings have implications for guiding implementation of specialized CHR services both in the United States and worldwide.


The treatment landscape for multiple myeloma is rapidly changing. At JADPRO Live 2017, presenters brought advanced practitioners up to date on the newest approaches to the management of this disease, as well as what to be aware of when treating common side effects. Multiple myeloma is a complex malignancy for which the treatment landscape is rapidly changing. Risk stratification is important in determining prognosis and tailoring treatment. At JADPRO Live 2017, Tiffany Richards, PhD, ANP, AOCNP®, and Hans Lee, MD, both from The University of Texas MD Anderson Cancer Center in Houston, brought listeners up to date on the newest approaches to management.Multiple myeloma is a malignancy of the plasma cells that can evolve over time. Almost all patients are initially diagnosed with monoclonal gammopathy of unknown significance (MGUS). Approximately 1% of MGUS patients per year will develop "smoldering myeloma," and about 10% per year of these patients will eventually develop symptomatic disease, Dr. Richards said.The International Myeloma Working Group (IMWG) revised the diagnostic criteria for myeloma in 2014, which now incorporates biomarkers along with the standard "CRAB" criteria , and guides the initiation of treatment . In the For MGUS, most patients can be followed , with evaluations every 3 to 6 months for the first year, then annually thereafter. Patients with smoldering multiple myeloma can also be followed closely or enrolled in a clinical trial for smoldering disease. Studies are now evaluating whether aggressive treatment early on can affect outcomes.Once a diagnosis of multiple myeloma has been made, risk stratification is the next step, as discussed by Dr. Lee. "There have been tremendous advancements in the treatment of myeloma over the past 10 to 15 years, mainly due to the approval of new drugs and resulting in a doubling of overall survival," he said. Since 2013, the treatment armamentarium has grown to include carfilzomib, pomalidomide , panobinostat (Farydak), daratumumab , ixazomib (Ninlaro), and elotuzumab (Empliciti).The life expectancy of standard-risk myeloma patients is now 10 to 12 years, but this falls to 3 years for patients with high-risk cytogenetics, despite the use of the newest agents. Risk stratification, therefore, is important for prognosis and for identifying candidates for novel treatments and clinical trials. High risk is defined by disease biology ; by phenotype (presence of plasma cell leukemia or extramedullary disease); by disease burden ; and by response to therapy.A number of chromosomal translocations, deletions, and amplifications have prognostic significance, particularly those involving the IgH heavy chain locus on chromosome number 14 and hyperdiploidy. Abnormalities of note include deletions 17p and 1p and translocations  and . Identification of these abnormalities by FISH is a critical part of risk stratification. The risk stratification approach is staging via the myeloma International Staging System (ISS), which was revised in 2015 to incorporate FISH studies. The IMWG has produced a simple table for risk stratification that is useful to clinicians .With many options available now, how do clinicians select an initial therapy for a newly diagnosed patient? The first question is whether the patient is a candidate for autologous stem cell transplant. The next step is to determine which frontline therapy should be used beforehand, Dr. Richards said. p = .0037), exceeding 34 months. Similarly, in the whole population, overall survival was improved from a median of 64 months with Rd to 75 months with VRd (p = .0250).For upfront treatment, a proteasome inhibitor has proven critical for good long-term outcomes. In SWOG S0777, the triplet of bortezomib (Velcade)/lenalidomide (Revlimid)/dexamethasone (VRd) proved clearly more effective than the lenalidomide/ dexamethasone (Rd) doublet . The oveIn other studies, bortezomib/thalidomide/dexamethasone provided better outcomes than the triplet of bortezomib/cyclophosphamide/dexamethasone (CyBorD), one being the French IFM 2013-04 trial . AnotherCarfilzomib (Kyprolis) is the newer proteasome inhibitor. Two important phase II studies showed that, with carfilzomib combined with Rd, complete or near complete responses were achieved by 52% and 62% of patients, respectively . In one Ongoing trials are comparing these effective triplets, studying VRd in combination with monoclonal antibodies, and asking whether VRd can delay the need for transplant, she added.In patients not eligible for transplant, the use of Rd as maintenance after frontline therapy, given either for 18 months or continuously, proved effective in the FIRST trial . Progres"So, how do we decide what we’re going to treat our patients with? If the patient is transplant eligible we recommend a triplet regimen. The current standard of care is VRd, but you may want to consider carfilzomib/lenalidomide/dexamethasone (CRd) in patients with high-risk disease. You definitely do not want to give melphalan, which can impact your collection of stem cells," Dr. Richards advised. "For those who are transplant ineligible, based on the patient’s frailty and comorbidities you could use a doublet, such as Rd, or you could consider triplet therapy, such as VRd, with maintenance given after initial therapy. You would also want to consider lower doses."p < .001). Overall survival at 4 years, however, did not differ significantly, "suggesting that patients who deferred on their initial stem cell transplant could be salvaged by stem cell transplant later on in their disease course," he said.After completion of frontline therapy, is stem cell transplant still needed? With the emergence of many effective novel therapies, myeloma specialists have begun to debate this concept, according to Dr. Lee. The most recent and best study addressing this question is the Dana Farber Cancer Institute/IFM 2009 trial, in which patients received three cycles of VRd with stem cell collection, with or without transplant, plus maintenance lenalidomide . ResultsWhether transplant should be performed upfront or can be delayed is still an "evolving question," he continued. Relevant issues are the role of indefinite maintenance with lenalidomide and its effect on long-term outcomes  and the role of minimal residual disease negativity as a clinically relevant endpoint in deciding upon upfront vs. delayed transplant.Lenalidomide maintenance has become an accepted component of care, based on CALGB 100104 in which maintenance improved progression-free survival by 19 months and improved 3-year overall survival as well . LikewisWhile maintenance with lenalidomide alone is probably sufficient for standard-risk patients, there is a trend toward combining an immunomodulatory drug (IMiD) and proteasome inhibitor for maintenance in high-risk patients. In a phase II study from Emory University, the VRd triplet as maintenance after transplant showed promise for patients with high-risk cytogenetics ."For relapsed/refractory myeloma, there are many different options now. It’s good news, but it can also be quite overwhelming to patients," Dr. Richards commented.In selecting a treatment option, clinicians need to determine the goal of treatment, and then look at the patient’s previous treatment and response to it, duration of remission, previous toxicities, other disease-related factors, and comorbidities. If an appropriate clinical trial is available, this should also be considered.If it is an asymptomatic biochemical relapse in a standard-risk patient, treatment options are more flexible. Patients may do well on observation only, or on a doublet or an all-oral regimen; patients with high-risk disease, on the other hand, warrant prompt intervention. "When those patients start to relapse, they take off very quickly," she noted. For patients displaying an aggressive clinical relapse, a daratumumab- or a carfilzomib-based regimen can be considered. Treatment should always be tailored in a way that balances efficacy with quality of life and adheres to the patient’s goals, Dr. Richards emphasized.p = .0001; p = .01; The National Comprehensive Cancer Network has listed a number of triplets as its preferred regimens for relapsed disease, and one doublet, carfilzomib/dexamethasone. In the ENDEAVOR trial, carfilzomib/dexamethasone was superior to bortezomib/dexamethasone, including in high-risk patients, who achieved a 15.5% complete response rate vs. 4.4% with bortezomib/dexamethasone . But wheCarfilzomib/pomalidomide/dexamethasone has also been shown to improve outcomes in high-risk patients. In one study , MM-003,p < .001; For relapsed/refractory multiple myeloma, the monoclonal antibodies—daratumumab and elotuzumab—represent a significant advancement in treatment, Dr. Lee indicated. Elotuzumab was FDA-approved in combination with lenalidomide and dexamethasone based on the ELOQUENT-2 trial, in which response rates were 79% for patients in the elotuzumab arm, vs. 66% with Rd alone, and median progression-free survival was 19.4 vs. 14.9 months . Steps can be taken to greatly mitigate this risk . PremediSince daratumumab can also interfere with red blood cell (RBC) compatibility testing, local blood banks should be alerted to any patients initiated on this drug, and patients should have RBC phenotyping or genotyping prior to starting the drug. Patients should be closely monitored for reactions when receiving an RBC transfusion. There are other special considerations with lab tests  in patients receiving these two monoclonal antibodies, Dr. Lee indicated.These effective agents can be well tolerated, although there are some common side effects, as described by Dr. Richards .Peripheral neuropathy occurs in approximately 75% percent of previously treated patients. Advanced practitioners should be proactive about this toxicity and monitor for it at each visit. Better than using "descriptors," she said, is telling patients " ’Take note of what your hands and feet feel like right now and if that changes, then call so that I can assess you and determine if this is something that we need to be concerned about.’ But don’t just take the patient’s word for it; we know they hide their symptoms. Do your physical exam and look at how they’re walking, test their muscle strength, and make sure they have fine motor movement," she advised.The development of neuropathy signals the need for immediate dose adjustment. "We tend to think about grade 1 as not a big deal, but it’s actually like having your leg asleep all the time. If we dose adjust early, then we can prevent that from worsening," she pointed out. Neuropathy risk is less with subcutaneous bortezomib, carfilzomib, and ixazomib, than with intravenous bortezomib.Patients with neuropathy should be assessed for vitamin B12, B6, and folate deficiency (which can cause it). Gabapentin, pregabalin, duloxetine, acupuncture, physical therapy, and aquatherapy may be helpful, and there is some evidence that glutamine is preventive, she added.Also seen with proteasome inhibitors is an increased risk of herpes zoster. Prophylaxis with valacyclovir or acyclovir is critical, and patients must be instructed to stay on these antivirals. Patients with renal insufficiency should be given intravenous fluids prior to dosing with carfilzomib, but watch for fluid overload; the recommended amount is 250 mL. When creatinine clearance is < 30 mL/min, ixazomib should be dose-reduced. Renal function should also be monitored in patients taking carfilzomib, she said.With IMiDs, fatigue, gastrointestinal problems, thrombocytopenia, neutropenia, peripheral neuropathy, renal dysfunction, peripheral neuropathy, and rash can be issues. Rash, which occurs in up to 20% of patients on IMiDs, can be mitigated with the combination of cetirizine, ranitidine, and L-lysine, after stopping the lenalidomide. When rash resolves, many patients can be restarted on the same initial dose, without recurrence.Risk for thromboembolic events is high in all cancer patients; clinicians should look for other risk factors and anticoagulate with a daily aspirin, full-dose warfarin, or low-molecular-weight heparin. Since risk factors for thromboembolism can change over time, reassessment is important. Patients should know the symptoms and be encouraged to be mobile.For a number of reasons, myeloma patients have a 7-fold increased risk for bacterial infections and a 10-fold risk for viral infections. "Be aware of this risk," Dr. Richards emphasized. In patients with frequent infections, risk can sometimes be reduced by monthly intravenous immunoglobulin treatment and by antibiotic prophylaxis. Patients receiving a proteasome inhibitor or a monoclonal antibody should also be on antiviral prophylaxis. Patients should receive appropriate vaccines (including flu vaccine and pneumonia vaccines), but not live vaccines.Patients should understand the importance of proper handwashing and should avoid people who are ill . Patients traveling outside of the country should be immunized appropriately.Patients must understand the importance of staying on their medications, and of recognizing and reporting adverse events so that doses can be modified. "You want to reinforce the rationale for the ongoing treatment plan. It’s important that patients understand that if we can keep them on therapy, even at a reduced dose, that’s better than them not taking their medication or skipping doses," Dr. Richards said.Medication calendars, especially for patients on all-oral regimens, can be very helpful to patients and caregivers. She also told listeners to watch for treatment fatigue in their patients, and be willing to discuss treatment breaks when the disease is stable. Practitioners should also be aware that financial issues can be barriers to adherence, as can depression.With multiple drugs available, treatment can to some degree be tailored to the patient, Dr. Richards continued. For example, for a patient with preexisting neuropathy, a carfilzomib-based regimen may be preferred over bortezomib. For a patient with cardiomyopathy, a bortezomib-based regimen may be safer than carfilzomib. For a patient with renal failure, one might consider CyBorD to induce a rapid response. For patients with diabetes, the engagement of the primary care provider or endocrinologist is important, since steroids can cause diabetes. Patients with a history of bleeding should probably avoid an IMiD plus dexamethasone in favor of a proteasome inhibitor plus alkylating agent, which will avoid the need for thromboprophylaxis.


Zea mays L.) varieties could be facilitated by a greater understanding of the natural variation underlying kernel color, including as it relates to carotenoid biosynthesis and retention in maize grain. Greater abundance of carotenoids in maize kernels is generally accompanied by deeper orange color, useful for distinguishing provitamin A-dense varieties to consumers. While kernel color can be scored and selected with high-throughput, low-cost phenotypic methods within breeding selection programs, it remains to be well established as to what would be the logical genetic loci to target for selection for kernel color. We conducted a genome-wide association study of maize kernel color, as determined by colorimetry, in 1,651 yellow and orange inbreds from the Ames maize inbred panel. Associations were found with y1, encoding the first committed step in carotenoid biosynthesis, and with dxs2, which encodes the enzyme responsible for the first committed step in the biosynthesis of the isoprenoid precursors of carotenoids. These genes logically could contribute to overall carotenoid abundance and thus kernel color. The lcyE and zep1 genes, which can affect carotenoid composition, were also found to be associated with colorimeter values. A pathway-level analysis, focused on genes with a priori evidence of involvement in carotenoid biosynthesis and retention, revealed associations for dxs3 and dmes1, involved in isoprenoid biosynthesis; ps1 and vp5, within the core carotenoid pathway; and vp14, involved in cleavage of carotenoids. Collectively, these identified genes appear relevant to the accumulation of kernel color.Rapid development and adoption of biofortified, provitamin A-dense orange maize ( Malnutrition, or hidden hunger, remains a serious issue, even as increased agricultural productivity has helped to provide more energy and calories on a global scale . As muchFor biofortification to be effective, micronutrient densities must reach levels that impact human health, and the varieties and final food products must be acceptable to growers and consumers. Through decades of technical and broader contextual work, the international breeding organizations of CIMMYT, IITA and HarvestPlus, and partners have achieved the successful development of provitamin A-dense maize varieties, nearing target nutrient levels, which also have local and regional adaptation and relevance (cis-epoxycarotenoid dioxygenases (NCEDs), including strigolactones, abscisic acid (ABA), and various aromatic volatile compounds  is formed by deoxy-xylulose 5-phosphate synthase (DXS) in the first step of the non-mevalonate  pathway for isoprenoid biosynthesis in plastids. Seven more reactions are needed for the formation of the immediate carotenoid precursor, geranylgeranyl pyrophosphate (GGPP) from isopentenyl pyrophosphate (IPP)  Hirschb Hirschb. A numbea priori candidates for the genetic control of kernel color, given that their gene action could feasibly impact the hue and/or intensity of maize endosperm coloration.Many carotenoid compounds have yellow-to-red coloration dependent on functional groups and the length of their conjugated double bond systems , though Carotenoid composition, or relative abundance of individual carotenoid compounds, is typically quantified using high-performance liquid chromatography (HPLC). However, HPLC is cost- and labor-intensive and may not be amenable to the high-throughput measurements called for in certain stages of a breeding program . For exaGradation in orange kernel color was previously visually scored on an ordinal scale, on bulks of kernels sampled from maize ears of 10 recombinant inbred line (RIL) families of the U.S. maize nested association mapping (NAM) population (L*a*b*) system is based on color-opponent theory, or color being perceived by the following pairs of opposites  to facilitate pollination, harvesting and phenotyping efforts. Each set was arranged in a 20 × 24 incomplete block design. Each block within each set was augmented with an experiment-wide check line (B73) plot in a random position, and six other check lines of varying maturities based on flowering time  were included twice per block in random positions. An experimental unit consisted of a one-row plot, 3.81 m in length containing approximately 15 plants. Plots had a spacing between rows of 0.762 m. Efforts were made to hand-pollinate up to six plants per plot. Self-pollinated ears were hand-harvested and dried for 72 h with forced hot air. After drying, ears were stored away from light in burlap sacks at ambient winter temperatures in West Lafayette, IN, for up to four months until measurements could be taken.We grew a 2,448 experimental inbred line subset of a population consisting of 2,815 maize inbred lines maintained by the National Plant Germplasm System . We will use the term colorimeter and colorimetry henceforth. The color values L*, a*, b*, and hue (h) were measured. Chroma (C*) values were not provided by the colorimeter, thus this value was calculated according to the formula Chroma = (a*2 + b*2)1/2 1/2 . These mijklmnY is an individual phenotypic observation; μ represents the grand mean; checki is the effect of check i; genotypej is the effect of experimental genotype (non-check line) j; yeark is the effect of the year k; genotype × yearjk is the effect of the interaction between genotype j and year k; set(year)kl is the effect of set l within year k; row(year)lm is the effect of row m within year l; block(set × year)kln is the effect of block n within set l within year k; and εijklmn is the residual (or random error term) for individual phenotypic observation n. The residuals were assumed to be independent and identically distributed, normal random variables with mean zero and variance σε2; that is, ∼iid N. The Kenward-Roger approximation was applied to calculate degrees of freedom . Studentized deleted residuals  between the BLUP values for each pair of colorimeter traits was calculated to assess the degree of their association (at α = 0.05), using the ‘cor’ function in R version 3.5.1  was obtained for a*, b*, and C*.Prior to conducting the GWAS, the Box-Cox power transformation  was usedhttp://datacommons.cyverse.org/browse/iplant/home/shared/panzea/genotypes/GBS/v27). Additional quality filters were imposed to retain SNPs with a call rate greater than 70%, minor allele frequency (MAF) greater than 2%, and inbreeding coefficient greater than 80%, resulting in a final dataset of 268,006 high-quality SNPs. In addition, inbred lines with a call rate lower than 40% were excluded, given that missing genotype scores were still present in the SNP data set after partial imputation.A GWAS was conducted for each of the five traits using the single-nucleotide polymorphism (SNP) data set developed using the genotyping-by-sequencing (GBS) platform for the Ames panel (2R statistic (2RLR)   was usedArabidopsis thaliana, and was previously used for a pathway-level analysis of carotenoid HPLC measurements in a small (n = 201) maize association panel (z-iso) and homogentisate solanesyl transferase (w3), are referred to as pathway genes or a priori candidate genes in this study. Pathway-level analysis was used to reduce the number of association tests conducted, thus using a priori knowledge of the pathway to reduce the magnitude of the correction used to control the FDR at 5% . The SNP marker data are available on CyVerse as previously specified, and accession names are listed in Tables S1 and S2. Supplemental material available at FigShare: L* (r = 0.75) and negatively correlated with a* (r = -0.94). Chroma and b* values were strongly positively correlated (r = 0.99) , given the larger magnitude of b* relative to a* and the equal weighting of these two traits in the calculation of Chroma, whereas a* values corresponded more to hue (perceived color) in this data set.All of the colorimeter traits were highly heritable, with line-mean heritabilities ranging from 0.75 to 0.89 . Hue val = 0.99) . This coP-value of 5% (Table S3). Manhattan plots for each trait are presented in Figure S1. Associations were detected for two genes involved in the provision of substrate for carotenoid biosynthesis. A single SNP was detected within  a gene encoding 1-deoxy-D-xylulose 5-phosphate synthase (dxs2), the first and committed step in the MEP pathway, with significant associations for a* and hue (a* were detected within a gene encoding phytoene synthase (y1), the first and committed step in the biosynthesis of carotenoids.A total of 27 unique SNPs were identified in GWAS for the five kernel colorimeter traits at an FDR-adjusted  and hue . Two SNPlcyE), which affects the partitioning of substrate into the α- and β- branches of the carotenoid pathway. A significant SNP associated with a* was located near the gene encoding zeaxanthin epoxidase (zep1), approximately 25 kb downstream of the gene. Zeaxanthin epoxidase converts zeaxanthin to antheraxanthin and subsequently violaxanthin, all within the β-branch of the pathway.Two genes in the core carotenoid pathway were also identified. Two significant SNP associations were detected for hue within the gene encoding lycopene ε-cyclase . The product of this gene model was found to have 96% identity at the protein level with cytochrome P450 14 . Three other significant SNPs for a* were proximal to a gene that encodes isopentenyl transferase  and is expressed in the endosperm of B73 , the penultimate enzyme in glycolysis. This gene was highly expressed in endosperm of B73 . Two SNPs were significant for hue in the vicinity of 4-diphosphocytidyl-2C-methyl-D-erythritol synthase , another gene in the MEP pathway. Within the core carotenoid pathway, two additional genes were identified for a*: lycopene β-cyclase  and phytoene desaturase . Finally, a gene related to carotenoid cleavage, encoding 9-cis-epoxycarotenoid dioxygenase (NCED) , was identified for L*.Additional associations were identified through pathway analysis in regions proximal to a number of genes not identified in GWAS. An association was found for Chroma in the vicinity of another gene that encodes DXS , a gene that controls the first committed step in carotenoid biosynthesis  is separate vs. coordinated.Although joint linkage analysis of visual color score data detected a QTL in the vicinity of lcyE and zep1—genes affecting flux within and through the core carotenoid pathway—were identified both in this study of kernel color and in the prior study of carotenoid HPLC values in the Goodman-Buckler panel  have 11 conjugated double bonds and correspondingly have lower a* values and higher b* values than α-carotene and lutein, which have 10 conjugated double bonds  as well as lutein, zeaxanthin, total α-xanthophylls, and total β-xanthophylls. An allele of lcyE with reduced expression was found to result in the formation of fewer ε-rings and a reduction in α-branch compounds relative to β-branch compounds  in the present study suggests that kernel color can be utilized to select for greater carotenoid abundance in general. However, the simultaneous identification of lcyE and zep1 (genes involved in carotenoid composition) suggests that the relative abundance of individual carotenoid compounds is likely to also be affected when selecting on kernel color. Therefore, the levels of individual carotenoid compounds will need to be monitored when colorimetry is applied as an early selection tool for lines having favorable orange color, to ensure that the favorable genetic variants needed for the maintenance or improvement of provitamin A levels are also retained. For example, the concentrations of the more abundant provitamin A carotenoids in maize grain, β-carotene and β-cryptoxanthin, might be increased simultaneously with orange kernel color if substrate were to be modulated via lcyE to flow preferentially through the β-branch of the pathway. Alternatively or in addition, favorable alleles of the gene encoding β-carotene hydroxylase (crtRB1), which converts β-carotene to β-cryptoxanthin to zeaxanthin, could be selected that favor accumulation and retention of these provitamin A compounds while also producing sufficient zeaxanthin to obtain the vivid orange color.Taken together, the identification of vs. starchy endosperm layers —has many potential metabolic routes. Nevertheless, the action of enolase resides only two steps prior to that of DXS (which takes pyruvate as one of its substrates), and PEP is an important precursor for isoprenoid biosynthesis. An engineering strategy in E. coli that increased PEP concentrations was found to elevate levels of lycopene, the carotenoid compound that sits at the pathway branch point , its activity has been found in maize to affect the distribution of aleurone m layers . Certainm layers . The findxs3 suggests that this gene, in addition to dxs2, may play a role in the accumulation of carotenoids in the maize kernel. An association was found with dmes2, which encodes 4-diphosphocytidyl-2C-methyl-D-erythritol synthase, the third step in the MEP pathway. The gene encoding this enzyme in A. thaliana, present in a single copy and termed MCT, has been found along with certain other MEP pathway genes to have very low seed expression levels in certain developmental stages, in a manner that may be limiting to carotenoid biosynthesis  locus in maize  was not contained in the QTL support interval identified on chromosome 9 , the macrotransposon insertion that created Wc was subsequently characterized in Wc was only significant in two of the 10 NAM families analyzed . This dispersion could present particular difficulties for the detection of genetic signal in the presence of low SNP coverage and/or rare variation. Finally, given that only lines with yellow to orange endosperm were analyzed in this study, it could be that the variation in ccd1 copy number was too constrained , which corresponds to pure red, with the +b* axis (at 90°) corresponding to pure yellow. The hue angles observed in this study ranged from 61.78 to 93.08° (Notably, o 93.08° . Given ty1 and dxs2, in conjunction with the previously established alleles of lcyE and crtRB1, provide a logical and promising strategy for the rapid development of provitamin A-dense maize lines that also produce a recognizable and desirable orange kernel color.Further studies are needed to determine whether natural variation at the loci identified in these analyses corresponds to differences in transcription levels, post-translational regulation, and/or enzyme activity. A GWAS using kernel color phenotypes and HPLC-based carotenoid values for the same set of materials may enable the identification of alleles that are favorable for kernel color as well as carotenoid composition and concentration. An increasing knowledge of the genetic mechanisms affecting kernel color, and the potential relationships between color values and carotenoid values, will be useful in coordinating breeding efforts to improve both sets of phenotypes. Establishing optimal ranges for each colorimeter trait for use in a selection index could provide a useful and inexpensive breeding tool, particularly to screen for kernel color and total carotenoid levels in the early stages of breeding. Some of the evaluation, selection, and elimination could potentially be done while the ears are still on the plants, or in a harvest pile at the end of a nursery row. This would save labor and reduce handling of non-selected ears. Selection of favorable alleles of the loci detected in this study, particularly


Total gonads carotenoid varied seasonally, with the highest level being observed in males during spawning season. Echinenone was the main pigment present in gonads, showing highest concentrations in males during spawning and gonad recovering. During the growing and early maturation period gonads were more reddish, yellowish and brighter, as well as more firm, irrespectively of the sex. Based on all seasonal changes affecting gonad yield and quality, the period between November and February seems the most suitable to harvest high quality gonads in the Atlantic coast of Portugal.Sea urchin population harvest in the North Atlantic coast of Portugal was characterized in terms of gonad yield, nutritional composition and important market-related traits, over one reproductive cycle (March 2016 to March 2017). Most of the quality attributes showed a seasonal variation strongly dependent on sea urchin sex. Maximum gonad yield (18%) was observed in March 2017. A single spawning event occurred between May and July. Gonads are rich sources of protein (12–18% WW) with low fat content (≤6% WW), that increase during the gametogenic stages of recovery and growing (November-December). Polyunsaturated fatty acids were the dominant class in both sexes (4.2–14.7 mg.g The global volume of sea urchin captures in 2016 reached 28575 tonnes, whilst farming has further contributed with 10057 tonnes2. Japan is an important driver of sea urchin market and represents 75% of total imports (11116 tonnes) of major sea urchin product forms  estimated in 14739 tonnes in 20162. Urchin roe can reach a high commercial value as demand often exceeds the market supply. Recently, excessive exploitation and destructive harvesting methods have caused the depletion of wild stocks3.Sea urchin gonads (roe) are a prized and gourmet seafood delicacy, due to its unique flavourParacentrotus lividus has being intensively harvested in most of its geographical range, throughout the Mediterranean Sea and the North eastern Atlantic, from Scotland (northern) to Canary Islands (southern)4. In Europe, the natural stocks found in France, Italy and Spain are considered overexploited, even so intensive harvesting is still occurring: in the North regions of Spain landings reached 520 tonnes in 20145. In Portugal, P. lividus is the dominant echinoid species in the rocky shores6 and landings are mainly concentrated in the North Atlantic coast (Viana do Castelo) where harvests reached 28 tonnes in 20157. Commercial harvesting has increased over the last decade, which might reflect the demand to supply markets of nearby regions, such as North Spain8.The sea urchin 9. A premium gonad is characterized by its size combined with specific sensory traits sought by the consumers . Desirable gonads present a bright yellowish-orange colour10, umami taste11, firm texture and high freshness12. However, gonads size and sensory traits largely depend on several factors, namely: (i) sea urchin species, (ii) gonads maturation stage (reproductive cycle), (iii) environmental cues  and (iv) animal nutritional status .The main market for sea urchin gonads is Japan where the price for fresh gonads is considerable higher than for frozen or dried/salted; fresh roe can reach 40–100€/kgP. lividus reproduction follows a predictable seasonal pattern characterized by six gametogenic stages13. The annual reproductive cycle of this species can present one or two spawning seasons, depending on the habitat, latitudinal location and environmental conditions to which populations are subjected to4. Some studies have investigated the role of exogenous factors, such as temperature, photoperiod and primary production in sea urchin gametogenesis and spawning. However, it has been suggested that the environmental cues that trigger spawning may differ from those that stimulate gonadal growth and development14. Byrne13 observed that temperatures lower than 13 °C may inhibit spawning of P. lividus populations in Ireland. Shpigel, et al.15 reported that short days and increasing temperatures (18–22 °C) enhanced gonad development and gametogenesis, while Spirlet, et al.16, Spirlet, et al.17 suggested that the spawning event may be triggered by shorter day-length. Latitudinal patterns can also be found in echinoids reproductive cycles, the gonad index of P. lividus showed a clear geographical trend with the Atlantic populations reaching higher GSI than the Mediterranean populations18.14. Gonads are preferentially consumed before the beginning of gametogenesis, when their nutritive phagocytes are in maximum volume and rich in nutrients, attributes that contribute to a sweeter flavour and firmer texture. Once gametogenesis begins, the taste and texture of gonads deteriorates, mainly due to the utilization of yolk protein into synthesis of new compounds19.During the reproductive cycle, gonads from both females and males increase in size (yield) over two distinct periods: before gametogenesis, when nutrient reserves are stored in the nutritive phagocytes, and during gametogenesis, when increased number and size of gametes is observed10. Gonad echinenone content is limited by the availability, uptake and bioconversion of β-carotene from dietary sources, in particular from algae21. The consumption of different algae with different carotenoid profiles influences the concentration of pigments present in sea urchins22. Also, diet type  can drastically influence not only the biochemical composition of gonads but also their organoleptic properties, such as flavour and texture23.Gonad colour is a pivotal factor determining its quality and marketability. The desirable yellow-orange colour is determined by carotenoids deposited in the gonads, mainly the accumulation of echinenone that is its dominant pigment24, ecological25 and conservational8 issues of Portuguese populations of P. lividus, little is known about important market-related traits of this high valued species and its potential to commercialization. This study aims to characterize the seasonal variations of P. lividus gonads in terms of maximum yield, nutritional value, colour and texture over one reproductive cycle. The possible relationship between sex, season and gametogenic cycle and selected market-related traits was discussed, for the first time in a wild population, and the best period to harvest high quality gonads in the North Atlantic coast of Portugal was determined.To date, apart from a few studies focusing environmental26Detailed data on sea water temperature was obtained through daily records of an oceanic buoy located close to our study area. The annual variation of water temperature was minor and ranged between 11.8–16.4 °C Fig. . TemperaP ≥ 0.05). This evidences a size-class consistency in the evaluated sea urchin groups, allowing a direct comparison of gonadal quality traits over the 13-month period. Gonad weight decreased to almost half of its value from March-16 to June , then slowly increased until March-17 (15 ± 3.3 g), consequently affecting GSI values over the year. The annual reproductive cycle of P. lividus population from Praia Norte is presented in Fig. P < 0.05), but was similar between sexes  and test diameter (6.4 ± 0.4 cm) of all sampled animals were not significantly different over time . Lipid content of gonads . Again, gonad energy was at minimum levels during spawning (3–4 kJ/g WW), and achieved maximum content (7 kJ/g WW) in November, during growing. Both sexes showed similar moisture content, ranging from 66 to 81% over the year  and peaked in June during spawning , followed by saturated fatty acids (SFA) (2.3–11.0 mg.g−1 WW) and monounsaturated fatty acids (MUFA) (2.2–7.7 mg.g−1 WW). The most represented PUFA was 20:5n-3 (EPA), varying between 1.5–4.8 mg.g−1 WW followed by 20:4n-6 , 18:4n-3 (0.1–2.5 mg.g−1 WW) and 18:3n-3 . Reduced amounts of 22:6n-3  were found in gonads of both sexes. Females had significantly higher levels of PUFA than males, particularly from the n-3 family (P < 0.05), however both DHA and ARA levels were similar between sexes (P ≥ 0.05). As a reference for the consumption of seafood as part of a healthy diet, the levels of EPA + DHA in fresh gonads varied between 1.5–4.9 mg/g, being highest in November for both sexes. Most PUFA showed a seasonal variation in their content, being generally higher in November during gonad growth (stage II). Among SFA, the main compounds were 16:0 (1.3–6.2 mg.g−1 WW), 14:0 (0.5–3.3 mg.g−1 WW) and 18:0 (0.3–0.7 mg.g−1 WW). Total SFA were significantly higher in females than males, and in November compared to the other months (P < 0.05). MUFA were mainly represented by 20:1n-9 (0.6–1.8 mg.g−1 WW), 20:1n-11 (0.5–1.5 mg.g−1 WW) and 18:1n-7 (0.3–1.2 mg.g−1 WW), which were in higher amount in female gonads and preferentially concentrated in November (growing stage of gonads) (P < 0.05). A positive correlation was found between total lipids and EPA and DHA levels . EPA and ARA were negatively correlated to L* (r = −0.58 and −0.48) and positively correlated to β-carotene  composition of female and male gonads of P. lividus gonads is presented in Fig. P < 0.05, Supplementary Table P < 0.05, Fig. The seasonal variation of colour parameters lightness (L*), redness (a*) and yellowness (b*) in P. lividus is presented in Fig. −1 WW) during the spawning period when compared to February-March 2017 (61 to 72 µg.g−1 WW), months prior to spawning characterized by high GSI values. By contrast, levels of total carotenoids did not vary significantly in females (61 to 103 µg.g−1 WW) over the 13-month period. A negative correlation  compared to females. β-cryptoxanthin was the second highest pigment in gonads; it had similar levels in both sexes (P ≥ 0.05) and evidenced a seasonal variation  levels of β-carotene decreased to 10.88 µg.g−1 WW, while in September (after spawning) levels peaked up to 26.58 µg.g−1 WW. The less abundant pigment in gonads was α-carotene (0.3–2.2 µg.g−1 WW), levels were significantly higher in male than in female gonads and peaked in June (during spawning). Females showed significantly higher amount of lutein pigment (0.5–8.7 µg.g−1 WW) compared to males (0.9–4.0 µg.g−1 WW), and the interaction between sex and month was found significant (P < 0.05). Lutein levels in females were higher from April to September, before and after spawning occurred.Five carotenoid pigments were identified and quantified in the gonads of both sexes: α-, β-carotene, echinenone, lutein and β-cryptoxanthin. Levels of individual pigments are shown in Table P = 0.56). β-carotene levels were positively correlated with both total carotenoid and α-carotene content in gonads (r = 0.71 and 0.44). Also, α- carotene was negatively correlated to GSI , coinciding with the rise of seawater temperatures up to its maximum value (16.4 °C). Spirlet, et al.16 pointed that populations of echinoids from temperate waters exhibit similar reproductive patterns: nutrient storage during Fall and Winter followed by a long spawning season during late Spring and Summer. A single annual spawning season was also described in populations from the Atlantic cost of France, Ireland and Spain27 and in the Mediterranean Sea28. However, the occurrence of two spawning events during an annual cycle has been described for P. lividus in the Mediterranean Sea29 and in the central West coast of Portugal6, where seawater temperatures are usually higher than those reported in presently studied area.Different aspects of the reproductive cycle of 6. The differences found in the two Portuguese populations might be explained by local environmental conditions, habitat and seasonality factors. According to Ouréns, et al.18, the GSI values of P. lividus show a geographical trend, where the Atlantic populations reach higher values than the Mediterranean ones. Also, a latitudinal pattern in the Atlantic populations was described, with higher GSI values at higher latitudes. Environmental cues such as food availability and quality, sea water temperature or/and photoperiod have been suggested to modulate P. lividus reproductive potential4. Interestingly, in this study, the mean GSI value observed at March-16 (9%) varied considerably from that observed in march-17 (17%). Since sea water temperature (mean of 12.5 °C) and day-length (mean of 12 h light) followed a quite similar variation pattern in these particular months, it is possible that changes in food availability or food type could have affected the development and maturation of gonads and thus partially explain the marked variation on GSI values.In this study, the highest GSI value (18%) observed in March 2017 was almost 2.5 times greater than the highest value registered in a southern population (8%) of PortugalP. lividus populations from Portugal6, Ireland13 and Mediterranean Sea30. Sellem and Guillou31 highlighted the importance of using histological analysis to interpret GSI variation; these authors related punctual decreases of GSI values with changes in gonad reserves rather to gamete release. However, changes in the GSI observed over the study period, namely gonad size and weight, followed the gonad maturation pattern described by histological analysis: an increase of size was observed during the growing (II) stage due to nutrient storage in the non-germinal cells, continued until reaching the maximum yield at maturation (IV) stage then, with spawning, gonads became smaller and empty in content (stages V and VI).GSI showed a seasonal variation, but did not differ between sexes. Similar results were observed in other P. lividus gonads showed a clear seasonal variation also varying with sex. Protein was the major component of gonads, ranging between 12–18% WW while total lipid content was considered low (≤6% WW). All biochemical parameters were within the range of values previously reported for P. lividus32. Moreover, the seasonal variation of nutrient content in gonads reflected the reproductive cycle. Previous reports showed that the best period to harvest gonads with high nutritional quality and commercial value is during the growing period, generally prior to the onset of gametogenesis, when the nutritive phagocytes are full33 and accumulate higher levels of protein, lipid and carbohydrates34. In the present study we observed that gonads reached their highest content of protein, lipid and energy in November  and maintained this high nutritional value until January-February , before full maturation of gametes, suggesting this period as desirable for harvesting nutrient-rich gonads. Afterwards, when gonads were mature and peaked their GSI (March-17), their nutritive content started decreasing, in terms of lipids and energy, reinforcing that gonad quality deteriorates with gametes development. Changes in the biochemical content of gonads can impair their flavour, leading to a loss of economic value. Murata, et al.35 described that mature ovaries of Hemicentrotus pulcherrimus had a bitter taste, which was strongly correlated with the presence of a novel sulfur-containing amino acid, pulcherrimine. Furthermore, it was shown that the yolk protein stored in nutritive phagocytes is used during gametogenesis to synthesize new proteins and other nitrogen substances19, which might contribute to changes in gonad flavour. Despite these observations, no correlation could be found between the biochemical components of gonad and the GSI (which reflected gametogenic stages), confirming previous observations by Montero-Torreiro and Garcia-Martinez27. Likewise in many other species, the nutritional composition of edible tissues (gonads) seems to be highly dependent on sea urchin diet36. Changes on feed type and abundance throughout the year may affect the assimilation of nutrients and modify gonad composition. Moreover, recent studies have evaluated the effect of natural  and formulated diets on P. lividus gonad biochemical composition38 in order to promote the production of high valued gonads.The biochemical composition of P. lividus gonads was in general agreement with data reported in the literature40. But only a few of these studies discern sex as factor, mostly focusing on the effects of season or diet. Martínez-Pita, et al.39 found differences in the FA profile of ovary and testis of P. lividus: females showed higher levels of 14:0, LA and ALA whereas males exhibited higher levels of 18:0 and ARA; in terms of FA classes, only SFA differed between sexes, being higher in females. These authors also observed differences in the FA profile of two distinct populations, which suggested that environmental factors, such as food source, may influence the gonad FA profile of individuals of the same sex. The source and availably of food, as well as other site-associated factors, should be taken into consideration when results are being compared with the literature, since it may mask the effects of sex or season. In our work, females showed much higher concentrations of PUFA, MUFA and SFA compared to males, and although concentrations were within the expected values for sea urchins, the variation between sexes was more pronounced compared to other studies of P. lividus39 and Psammechinus miliaris41.The FA profile of P. lividus male and female gonads, has been presented for a wild population. The seasonal effect on FA composition of gonads was clear; females and males had preferentially higher concentrations of the sum of PUFA, MUFA and SFA classes in November, which was coincident with the period of gonad growth (stage II), when the gonads were richer in nutrients. It was possible to relate the season factor with the gametogenic cycle, yet no correlation was found between GSI and any FA in gonads. Carboni, et al.37 showed that the FA profile of P. lividus (without sex distinction) changed during gametogenesis, however differences were related to dietary lipid intake and not to seasonality. As previously discussed, diet has an important role in determining the nutritional composition of gonads36. Sea urchins are generalist grazers, but they often prefer feeding on large kelp (Laminaria ps.) species. The selective ingestion of certain macro algae and their respective nutritional value, have certainly contributed to modulate the FA content of sea urchin gonads once macro algae are rich in PUFA, particularly in EPA42. A recent study conducted in the North coast of Portugal with Laminaria ochroleuca, an algae consumed by P. lividus4, showed a seasonal pattern of growth and reproduction for this algae43. Interestingly, L. ochroleuca accumulated more nutrients during its growth period (winter)43, which was coincident with the increase of nutrient content of gonads, namely FA.To our knowledge, this is the first time that effects of sex/season/gametogenic cycle on FA composition of 41. In contrast, ARA and DHA levels only suffered a seasonal variation, being more concentrated in November, in both males and females. The recommended daily consumption of EPA + DHA to decrease the risk of cardiovascular diseases in humans is between 0.25-0.5 g44. If sea urchins are consumed during the period of highest concentration of PUFA in gonads (the growing stage in November) an intake of 50 g of P. lividus (around 5 adults) can provide near 0.245 g of EPA + DHA, which covers the daily recommended dose to promote human health, reinforcing the nutritional importance of sea urchin.Regarding the most relevant PUFA, EPA was preferentially accumulated in the ovary and levels decreased with increasing maturity stage, from September-November to February 2017. Previous studies have reported a trend of EPA accumulation in the gonads of sea urchins46. The results obtained by the CIE L*a*b* system were within the range of values reported for wild P. lividus fed on macroalgae. Seasonal changes in gonad colour were also reported for Strongylocentrotus franciscanus12 and S. droebachiensis1, which may be related to changes in gonad yield and possibly maturation stage (gametogenesis). In the present study, a positive correlation between L*, b* values and the GSI was observed, suggesting that the increase of gonad yield, from the growing to the full maturation stage, led to increased brightness and yellowish colour. Moreover, previous findings in P. lividus showed that gonads during the spawning season had an unacceptable coloration (dark red/brown) whilst during the growing period exhibited an excellent/good coloration (bright orange or yellow)45. In terms of colour, Cook and Kelly47 classified as acceptable to excellent coloration  gonads presenting (mean) values of 42 for L*, 20 for a* and 35 for b*. Our results showed that L* a* and b* values observed, in both sexes, between November (growing stage) and February (pre-mature stage) were similar or higher than those proposed by Cook and Kelly47, suggesting that gonads presented a desirable coloration for market. Additionally, it was also in this period that gonads become nutritionally richer and increased in size, as previously discussed. By combining all these positive features, one can propose the period between November and February as the most suitable to harvest premium gonads. Moreover, colour values decreased at spawning (June), showing some loss of colour quality, as previously observed with the nutrient content.Few studies have evaluated the seasonal variation of gonad colour from wild populations of sea urchins, despite the relevance of this trait for market valorisation. In most cases gonad colour was evaluated visually or instrumentally and without sex differentiationP. lividus45, P. miliaris48 and S. droebachiensis49. Carotenoids are pigments deposited in the gonads however, and according to Symonds, et al.45, acceptability of gonad colour is not directly linked neither with the levels of individual carotenoids nor their ratios found in the gonad. In fact total carotenoids picked after spawning, when gonads are known to be unacceptable for consumers45.Total carotenoids in gonads did not differ between sexes but showed some seasonality. Total carotenoid content varied with gonad maturation stages and followed a similar pattern in several sea urchin species, increasing during spawning (June) probably due to gonad loss of biomass, and decreasing afterwards. This is consistent with previous observations in 45. Moreover, echinenone levels were highest in males after spawning and onset of recovery period (September-November) whereas females showed more steady levels over time. Although no detailed evaluation of carotenoids deposition in gametes (eggs and semen) was performed, the white colour of semen contrasts with the orange coloration of eggs, suggesting that males might have kept most of the carotenoids in their gonads during spawning, that could partly explain their highest concentration after spawning, when gonad volume is strongly reduced. Moreover, males showed a considerable variation of echinenone concentration after spawning, which was also observed by Symonds, et al.45. This is probably related with the high variability in gametogenic stages of males observed post-spawning, that were found at recovery, partly spawned and spent stages. Also, no correlation could be found between echinenone in gonads and L* a* b* parameters, confirming previous observations in P. lividus45 and P. miliaris48. Gonads present a high content of pigments but its biochemical nature failed to be correlated with data obtained by instrumental or sensorial analysis, suggesting that the visual perception of colour may be influenced by other factors, besides carotenoid pigments. In P. lividus, unacceptable gonad coloration was observed with both very low and high levels of echinenone and total carotenoids in gonads45. These results suggest that carotenoids clearly made a contribution towards the red-orange pigmentation of the sea urchin gonad, but other factors may induce the sensorial evaluation of colour. The second major group of pigments present in P. lividus gonads were β-carotene and β-cryptoxantin, which only differ seasonally and not between sex. These findings may reinforce the hypothesis that, in P. lividus, echinenone is likely to be formed by bio-conversion of β-carotene via β-isocryptoxanthin10 and its metabolism may occur mainly in gonads21. Symonds, et al.45 also identified β-carotene as the second major group of pigments in P. lividus gonads, but in a different study, Shpigel, et al.20 reported the absence of β-carotene in gonads of urchins fed with a natural algal diet.Echinenone was the dominant carotenoid in the gonad of both males and females, confirming previous reports for this specieset al.12. These authors demonstrated that S. franciscanus gonads had higher moisture content and softer texture during maturation whereas the opposite was observed during the recovering and growing period, suggesting that gonads firmness was increased by lower moisture content. Few studies determined gonad texture, and were mostly focused on subjective evaluations50 rather than in instrumental analysis using a texture analyser12. The effect of sex in gonad texture was never reported before. Resilience is considered an useful texture measure for market valorisation, since a strong relation between high resilience values and high-quality rated gonads was reported by McBride, et al.12. In the present study, gonads resilience was not affected over time nor differed between sexes, being always higher than 75%. This may suggest that resilience remains acceptable throughout the year cycle.Firmer gonads were observed in November, during the growing period (stage II), whereas in both sexes, lower gonad firmness was observed in September (after spawning), when gonads appear as spent. Firmness was negatively correlated with gonad moisture content (r = −0.63), being in agreement with McBride, In conclusion, this study clearly demonstrated that most of the evaluated quality attributes were mainly dependent on sea urchin sex, but also showed a seasonal variation. According to the present observations, it is suggested that the best period for commercial harvesting sea urchins in the North Atlantic coast of Portugal is between November and February. During this period, gonads are mainly at the growing and premature stages of gametogenesis, holding a good nutrient storage in their nutritive phagocytes, as demonstrated by the highest levels of protein, lipid, n-3 and n-6 PUFA and energy content, in both males and females. In addition, gonads showed lower moisture content and simultaneously higher firmness, that is a valuable attribute. Also during this period, gonads were found more reddish, yellowish and brighter, irrespectively of the sex, being the values within those considered acceptable and desirable in the European market, were a bright and yellowish-orange gonad is rated premium. Moreover, as it was evidenced that most commercially important traits change seasonally compromising the gonad value, sea urchin production under controlled conditions (echinoculture) can be a sustainable alternative to assure a regular supply of high quality gonads. The present data can be further used to help tailoring new formulated feeds able to produce sea urchins with the desired gonad attributes for international markets.P. lividus were collected at Praia Norte , Portugal, after authorization from the national maritime authority (Captaincy of the Port of Viana do Castelo) and the Portuguese Institute for Nature Conservation and Forests (ICNF). Moreover, the sampling site did not involve protected areas nor endangered/protected species in the Atlantic region, and followed the Portuguese law Portaria n.⍛ 82/2011 on “minimum size for captures and harvesting”, implying that only commercial sized sea urchins (test diameter ≥5 cm) were collected.All animal procedures respecting capture of wild specimens and tissue sampling were previously approved by the CIIMAR ethical committee, in compliance with the European Union Directive 2010/63/EU and the Portuguese law Decreto-Lei n⍛ 113/2013 on “protection of animals used for scientific purposes”. Wild sea urchins P. lividus were collected between March 2016 and March 2017, by snorkeling in subtidal rocky reefs of Praia Norte, Portugal. Sea temperature records from A Guarda (Spain) oceanic buoy  were obtained from CMEMS (http://marine.copernicus.eu-SST_GLO_SST_L4_NRT_OBSERVATIONS) through AquaSafe by Hidromod (http://www.hidromod.com). Day length data were obtained for Porto city (near our sampling site) and assessed from the Observatório Astronónico de Lisboa, University of Lisbon26.Adult 13: recovery (stage I), with primary gametes and nutritive phagocytes; growing (stage II) with clusters of primary gametes and packed nutritive phagocytes, premature (stage III) with gametes at all stages of development and reduced amount of nutritive phagocytes; mature (stage IV) with mature gametes and few nutritive phagocytes; partly spawned (stage V) with loosely packed gametes and depletion of nutritive phagocytes and spent (stage VI) with gonads empty of gametes.Eighteen (N = 18) sea urchins were collected monthly and transported to CIIMAR facilities in seawater. Individual records of test diameter and total wet weight were performed in laboratory; animals were then placed in an ice bath for 30 min before dissection Fig. . The fivP. lividus, likewise other sea urchin species, yet both male and female individuals were collected monthly over the 13-month period, without needing any further sampling during the same month. Sex ratio in samplings varied over time: a minimum of seven and maximum of eleven individuals from the same sex were collected , but a ratio of 9:9 female:male (N = 18) was found in the majority of the sampled months ; crude protein (N x 6.25) by a flash combustion technique followed by a gas chromatographic separation and thermal conductivity detection  and gross energy in an adiabatic bomb calorimeter . Total lipids were determined following the method described by Folch, et al.53 with dichloromethane-methanol (2:1) and gravimetric determination.Chemical analyses were run in duplicate, following the AOAC54, as described by Campos, et al.55. To each sample was added 1 mL of internal standard solution . FAME were analysed in duplicate, using a Shimadzu GC-2010 Plus gas chromatograph , equipped with a flame-ionization detector and an Omegawax 250 capillary column . FAME were identified by comparing their retention times with known standards and quantified as mg.g−1 of dry biomass, using the internal standard C23:0.The fatty acid methyl esters (FAME) contained in total lipid extracts were transesterified by acidic methylation65. Readings were calibrated against a white tile and three replicate measurements were taken for each gonad and averaged to determine colour parameters.Gonad colour was evaluated instrumentally and by determination of the carotenoid content and profile. Colour was measured by the CIE 1976  method using a CR-400 colorimeter (Konica Minolta) at standard illuminant Det al.45 with some modifications. Briefly, carotenoids from frozen gonad tissue (0.4–0.5 g) were extracted, in duplicate, in acetone . After centrifugation at 3500 × g for 10 min, at 8 °C, the supernatant was collected and the extraction procedure was repeated twice to obtain a colourless supernatant. Supernatants were evaporated to dryness under a constant stream of nitrogen, re-suspended in n-hexane and filtered with a 0.2 μL syringe filter for further analysis. Total carotenoid content was determined in a spectrophotometer , using the absorption maximum in hexane and the extinction coefficient (E1%1cm) of 250056, based in the equation describe by Pocock, et al.57:1%1cm = the extinction coefficient of a 1% (w/v) solution in a 1 cm cuvette at a defined wavelength. G = sample weight (g).Total carotenoid extraction was performed according to Symonds, −1 of gonad biomass.The qualitative and quantitative profile of carotenoids was performed by high-performance liquid chromatography analysis , and was restricted to five sampled months: April, June, September, November 2016 and February 2017, selected to cover the gametogenic stages identified in this study. Each carotenoid extract was suspended in n-hexane and 20 μL were injected in a reverse phase Acclaim™ C30 LC column  with a mixture of acetonitrile, methanol, dichloromethane, hexane and ammonium acetate  under isocratic conditions . Detection was achieved by a diode array detector  at 454 nm. Retention times and spectra of compounds were analysed by comparison with pure standards and quantification performed by the calibration curves of α- carotene, β-carotene, echinenone, , lutein and β-cryptoxanthin . Data were analysed using the Waters Empower™ 2 software and expressed as mg.gAn instrumental evaluation of firmness and resilience properties was performed in gonads using a TA.XT.plus analyser, fitted with a 5 kg load cell and controlled by Exponent v6 software . Firmness was defined as the force (g) required to compress a sample at 25% of its original height (at a 1.7 mm/s) using a 35 mm cylinder probe. Resilience was defined as the capacity of a sample to recover its original height after a compression with the same probe, being determined as: Resilience (%) =  × 100. Briefly, after firmness determination the gonad was compressed up to 60% of its original height and held that position for 2 s. The post-test height was recorded after 15 s. Tests were performed individually in fresh gonads samples in three months of the studied period – September, November and February – which represented the recovery (I), growing (II) and premature (III) stages of gametogenesis, respectively. These stages of gametogenesis were selected based on their relevance to gonad quality, since market acceptability is higher before gametes development and spawning.P < 0.05.Data are presented as means and standard deviation. Tests for normality and homogeneity of variances were performed by Kolmogorov-Smirnov and Levene’s tests, respectively. A two-way ANOVA followed by HSD Tukey test, using sex  and month as independent variables, was performed with STATISTICS 6.4 package . Pearson’s correlation was used to relate all parameters, independently of the sex factor. In all cases significant differences were considered when Dataset 1