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Sexual violence can have a destructive impact on the lives of people. It is more common in unstable conditions such as during displacement or migration of people. On the Greek island of Lesvos, Médecins Sans Frontières provided medical care to survivors of sexual violence among the population of asylum seekers. This study describes the patterns of sexual violence reported by migrants and asylum seekers and the clinical care provided to them. This is a descriptive study, using routine program data. The study population consisted of migrants and asylum seekers treated for conditions related to sexual violence at the Médecins Sans Frontières clinic on Lesvos Island (September 2017-January 2018). There were 215 survivors of sexual violence who presented for care, of whom 60 (28%) were male. The majority of incidents reported (94%) were cases of rape; 174 (81%) of survivors were from Africa and 185 (86%) of the incidents occurred over a month before presentation. Half the incidents (118) occurred in transit, mainly in Turkey, and 76 (35%) in the country of origin; 10 cases (5%) occurred on Lesvos. The perpetrator was known to the survivor in 23% of the cases. The need for mental health care exceeded the capacity of available mental care services. Even though the majority of cases delayed seeking medical care after the incident, it is crucial that access to mental health services is guaranteed for those in need. Such access and security measures for people in transit need to be put in place along migration routes, including in countries nominally considered safe, and secure routes need to be developed.

Background Thousands of children migrate to Europe each year in search of safety and the promise of a better life. Many of them transited through Serbia in 2018. Children journey alone or along with their family members or caregivers. Accompanied migrant children (AMC) and particularly unaccompanied migrant children (UMC) have specific needs and experience difficulties in accessing services. Uncertainty about the journey and daily stressors affect their physical and mental health, making them one of the most vulnerable migrant sub-populations. The aim of the study is to describe the demographic, health profile of UMC and AMC and the social services they accessed to better understand the health and social needs of this vulnerable population. Methods We conducted a retrospective, descriptive study using routinely collected program data of UMC and AMC receiving medical, mental and social care at the Médecins sans Frontières clinic, in Belgrade, Serbia from January 2018 through January 2019. Results There were 3869 children who received medical care (1718 UMC, 2151 AMC). UMC were slightly older, mostly males (99%) from Afghanistan (82%). Skin conditions were the most prevalent among UMC (62%) and AMC (51%). Among the 66 mental health consultations (45 UMC, 21 AMC), most patients were from Afghanistan, with 98% of UMC and 67% of AMC being male. UMC as well as AMC were most likely to present with symptoms of anxiety (22 and 24%). There were 24 UMC (96% males and 88% from Afghanistan) that received social services. They had complex and differing case types. 83% of UMC required assistance with accommodation and 75% with accessing essential needs, food and non-food items. Several required administrative assistance (12.5%) and nearly a third (29%) legal assistance. 38% of beneficiaries needed medical care. Most frequently provided service was referral to a state Centre for social welfare. Conclusion Our study shows that unaccompanied and accompanied migrant children have a lot of physical, mental health and social needs. These needs are complex and meeting them in the context of migration is difficult. Services need to better adapt by improving access, flexibility, increasing accommodation capacity and training a qualified workforce.

Background Social support is a core determinant of health and plays a key role in the healing process of people with mental health problems and those who have been exposed to torture or other traumatic events. At the same time, social support is particularly challenging to build in such populations, as self-isolation and social withdrawal are common consequences of traumatic incidents. Defining social support is also challenging as there is no globally adequate definition. Our aim was to explore how social support was understood by Médecins Sans Frontières (MSF) beneficiaries, and how they perceived their needs on Lesvos Island, Greece to be met. Methods This was a qualitative study, based on exploratory free-listing interviews that explored how MSF beneficiaries on Lesvos understood and defined social support, followed by a series of in-depth interviews through which participants explained how they perceived their needs to be met. The study was conducted over a period of two weeks in August 2018, with 32 migrants and asylum seekers (22 male, 10 female) enrolled in the mental health services of MSF on Lesvos Island. The majority of interviewees were single men of African origin who had resided in Moria camp between 2 months and 2.5 years. Countries of origin include Syria, Afghanistan, Cameroon, Democratic Republic of Congo (DRC), Iraq, Iran, Nigeria, Senegal and other West African countries. Results Participants defined social support as the practical, informational and emotional support that people receive from organisations, friends and family members. Results revealed a lack of community links, isolation, tensions and conflict, insufficient amenities and limited orientation to services that lead to and amplify isolation, discrimination and tension. Most of the participants received little or no support both formally from organisations and informally from other migrants and asylum seekers in the camp. Conclusions Functional support networks are urgently required to overcome the consequences of restrictive policies which force people into containment and remove their support systems. Actors who are involved in providing social support, including MSF, are strongly encouraged to engage in activities that work towards building and strengthening peer support networks and creating a sense of community.

[This corrects the article DOI: 10.1371/journal.pone.0239187.].

Objectives Sexual violence can have a destructive impact on the lives of people. It is more common in unstable conditions such as during displacement or migration of people. On the Greek island of Lesvos, Médecins Sans Frontières provided medical care to survivors of sexual violence among the population of asylum seekers. This study describes the patterns of sexual violence reported by migrants and asylum seekers and the clinical care provided to them. Methods This is a descriptive study, using routine program data. The study population consisted of migrants and asylum seekers treated for conditions related to sexual violence at the Médecins Sans Frontières clinic on Lesvos Island (September 2017-January 2018). Results There were 215 survivors of sexual violence who presented for care, of whom 60 (28%) were male. The majority of incidents reported (94%) were cases of rape; 174 (81%) of survivors were from Africa and 185 (86%) of the incidents occurred over a month before presentation. Half the incidents (118) occurred in transit, mainly in Turkey, and 76 (35%) in the country of origin; 10 cases (5%) occurred on Lesvos. The perpetrator was known to the survivor in 23% of the cases. The need for mental health care exceeded the capacity of available mental care services. Conclusion Even though the majority of cases delayed seeking medical care after the incident, it is crucial that access to mental health services is guaranteed for those in need. Such access and security measures for people in transit need to be put in place along migration routes, including in countries nominally considered safe, and secure routes need to be developed.

This study investigates the extraction kinetics of luteolin, a bioactive flavonoid with recognized antioxidant and health-promoting properties, from the aerial parts of Reseda luteola (dyer’s weld), with emphasis on its industrial potential. A comparative analysis with peanut shells (Arachis hypogea) identified R. luteola as a superior source, containing 14 ± 3 mg of LUT/g of material, approximately eight times higher than the amount in peanut shells. Luteolin occurred predominantly as luteolin-7-O-glycoside (57%) and the aglycone (35%). Methanolic semi-batch extraction at 25 °C yielded 9.6 mg LUT/g (70%) within 60 min at a solid-to-liquid ratio of 1:9, demonstrating significantly greater solvent efficiency than conventional Soxhlet or maceration techniques. Kinetic modeling, based on Fick’s second law, revealed a biphasic process with a low rate constant ratio (3:1) between the two stages, indicating the need for process optimization. These results establish R. luteola as a cost-effective and sustainable source of luteolin for dietary supplements and functional foods, while indicating the need to explore alternative solvents and advanced extraction methods to further optimize yield and efficiency.

[This corrects the article DOI: 10.1371/journal.pone.0117654.].[This corrects the article DOI: 10.1371/journal.pone.0117654.].

Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR) pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/C30) to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs) from OC patients, sensitive (n = 7) or resistant (n = 4) to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9) were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05). Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03). Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05). We conclude that perturbations of DNA repair pathways as measured in PBMCs from OC patients correlate with the drug sensitivity of these cells and reflect the individualized response to platinum-based chemotherapy.

Arkadia is a positive regulator of the TGFβ-SMAD2/3 pathway, acting through its C-terminal RING-H2 domain and targeting for degradation of its negative regulators. Here we explore the role of regions outside the RING domain (non-RING elements) of Arkadia on the E2-E3 interaction. The contribution of the non-RING elements was addressed using Arkadia RING 68 aa and Arkadia 119 aa polypeptides. The highly conserved NRGA (asparagine-arginine-glycine-alanine) and TIER (threonine-isoleucine-glutamine-arginine) motifs within the 119 aa Arkadia polypeptide, have been shown to be required for pSMAD2/3 substrate recognition and ubiquitination in vivo. However, the role of the NRGA and TIER motifs in the enzymatic activity of Arkadia has not been addressed. Here, nuclear magnetic resonance interaction studies with the E2 enzyme, UBCH5B, C85S UBCH5B-Ub oxyester hydrolysis, and auto-ubiquitination assays were used to address the role of the non-RING elements in E2-E3 interaction and in the enzymatic activity of the RING. The results support that the non-RING elements including the NRGA and TIER motifs are required for E2-E3 recognition and interaction and for efficient auto-ubiquitination. Furthermore, while Arkadia isoform-2 and its close homologue Arkadia 2C are known to interact with free ubiquitin, the results here showed that Arkadia isoform-1 does not interact with free ubiquitin.

Arkadia (RNF111) is a positive regulator of the TGF-β signaling that mediates the proteasome-dependent degradation of negative factors of the pathway. It is classified as an E3 ubiquitin ligase and a SUMO-targeted ubiquitin ligase (STUBL), implicated in various pathological conditions including cancer and fibrosis. The enzymatic (ligase) activity of Arkadia is located at its C-terminus and involves the RING domain. Notably, E3 ligases require E2 enzymes to perform ubiquitylation. However, little is known about the cooperation of Arkadia with various E2 enzymes and the type of ubiquitylation that they mediate. In the present work, we study the interaction of Arkadia with the E2 partners UbcH5B and UbcH13, as well as UbcH7. Through NMR spectroscopy, we found that the E2–Arkadia interaction surface is similar in all pairs examined. Nonetheless, the requirements and factors that determine an enzymatically active E2–Arkadia complex differ in each case. Furthermore, we revealed that the cooperation of Arkadia with different E2s results in either monoubiquitylation or polyubiquitin chain formation via K63, K48, or K11 linkages, which can determine the fate of the substrate and lead to distinct biological outcomes.