Depressed 660-km discontinuity caused by akimotoite–bridgmanite transition

The 660-kilometre seismic discontinuity is the boundary between the Earth’s lower mantle and transition zone and is commonly interpreted as being due to the dissociation of ringwoodite to bridgmanite plus ferropericlase (post-spinel transition)1–3. A distinct feature of the 660-kilometre discontinuity is its depression to 750 kilometres beneath subduction zones4–10. However, in situ X-ray diffraction studies using multi-anvil techniques have demonstrated negative but gentle Clapeyron slopes (that is, the ratio between pressure and temperature changes) of the post-spinel transition that do not allow a significant depression11–13. On the other hand, conventional high-pressure experiments face difficulties in accurate phase identification due to inevitable pressure changes during heating and the persistent presence of metastable phases1,3. Here we determine the post-spinel and akimotoite–bridgmanite transition boundaries by multi-anvil experiments using in situ X-ray diffraction, with the boundaries strictly based on the definition of phase equilibrium. The post-spinel boundary has almost no temperature dependence, whereas the akimotoite–bridgmanite transition has a very steep negative boundary slope at temperatures lower than ambient mantle geotherms. The large depressions of the 660-kilometre discontinuity in cold subduction zones are thus interpreted as the akimotoite–bridgmanite transition. The steep negative boundary of the akimotoite–bridgmanite transition will cause slab stagnation (a stalling of the slab’s descent) due to significant upward buoyancy14,15.

Quality of Life, Psychological Distress, and Prognostic Awareness in Caregivers of Patients with Multiple Myeloma

Background: Multiple myeloma (MM) is an incurable hematologic malignancy requiring long-term, continuous therapy. Although caregivers of MM patients play a critical role in supporting their loved ones throughout the illness course, studies examining caregiver quality of life (QOL), psychological distress, and prognostic awareness are lacking. Methods: We conducted a cross-sectional, multisite study of patients undergoing treatment with MM (excluding maintenance therapy) and their caregivers between 6/2020-3/2021. Eligible caregivers were identified by the patient as the primary caregiver and enrolled to 1 of 3 cohorts based on lines of therapy: 1) newly diagnosed receiving first-line therapy; 2) 2-3 lines; 3) ≥4 lines of therapy. Caregivers completed validated questionnaires to assess their QOL, psychological distress, and perceptions of prognosis. Patients also completed validated questions to assess their perception of prognosis. We used descriptive statistics to describe caregiver QOL, psychological distress, and perception of prognosis. We then descriptively compared psychological distress and perception of prognosis between patient and caregiver dyads. Results: We enrolled 127 caregivers of MM patients (newly diagnosed (n=43), 2-3 (n=40), and ≥ 4 lines of therapy (n=44)). Median caregiver age was 61.8 years (range 24.0-81.9); 71.7% (91/127) were female; and 68.5% (87/127) were taking care of their spouse/partner. Caregiver QOL and psychological distress did not differ by lines of therapy. The rate of clinically significant depression, anxiety, and post-traumatic stress disorder (PTSD) symptoms were 15.8% (20/127), 44.1% (56/127), and 24.4% (31/127), respectively. When examining dyads, caregivers reported higher rates of clinically significant anxiety symptoms (44.4% vs. 22.5%) compared to MM patients. Caregivers reported less clinically significant depression symptoms (15.3% vs. 24.2%) and similar rates of clinically significant PTSD symptoms (24.2% vs 25.0%). Overall, 89.6% (112/125) of caregivers reported that it is 'extremely' or 'very' important to know about the patient's prognosis and 55.6% (70/126) stated that they had received adequate information regarding the patient's prognosis. Caregivers reported that prognostic information was 'extremely' or 'very' helpful in making decisions about treatment (94.0%, 109/116), preparing for the future (88.6%, 101/114), and coping with the disease (85.2%, 98/115). Most caregivers (84.2%, 101/120), reported that the oncologist had told them the patient's cancer was incurable. In contrast, only 53.6% (59/110) of caregivers reported that they thought the patient's cancer was incurable and 37.9% (58/114) acknowledged that the patient is terminally ill. Caregiver demographics, line of therapy, QOL, and psychological distress were not associated with their perceptions of the patient's prognosis. When examined in dyads, caregivers were more likely to report that the patient is terminally ill (50.1% vs. 30.1%). There was no difference in caregivers' and patients' report that the oncologist said MM is incurable (83.3% vs. 84.2%). Conclusions: Caregivers of patients undergoing treatment for MM experience substantial psychological distress across the disease continuum, particularly anxiety. Supportive care interventions are needed to improve caregivers' QOL and to reduce their psychological distress. Although the majority of caregivers of MM patients report that knowing the patient's prognosis is extremely important and report that the oncologist told them that the patient was incurable, a significant portion of caregivers report that the patient is curable. Interventions are needed to promote effective coping and to enhance caregiver's perception of the patient's prognosis to facilitate informed-decision making. Disclosures O'Donnell: Janssen: Consultancy; Takeda: Consultancy; Oncopeptide: Consultancy; Adaptive: Consultancy; Karyopharm: Consultancy; Bristol Myer Squibb: Consultancy. Nadeem: Takeda: Consultancy; Bristol Myer Squibb: Consultancy; GSK: Consultancy; Karyopharm: Consultancy; Adaptive: Consultancy. Yee: Karyopharm: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy; GSK: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Adaptive: Consultancy; Bristol Myers Squibb: Consultancy; Amgen: Consultancy. Branagan: Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive: Consultancy; CSL Behring: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Anderson: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees; Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Mo: Janssen: Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy; Eli Lilly: Consultancy. Munshi: Celgene: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Abbvie: Consultancy; Legend: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy; Adaptive Biotechnology: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy. Ghobrial: AbbVie, Adaptive, Aptitude Health, BMS, Cellectar, Curio Science, Genetch, Janssen, Janssen Central American and Caribbean, Karyopharm, Medscape, Oncopeptides, Sanofi, Takeda, The Binding Site, GNS, GSK: Consultancy. Sperling: Adaptive: Consultancy. Richardson: AstraZeneca: Consultancy; Protocol Intelligence: Consultancy; GlaxoSmithKline: Consultancy; Karyopharm: Consultancy, Research Funding; Secura Bio: Consultancy; Sanofi: Consultancy; Regeneron: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy; Celgene/BMS: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Raje: Caribou: Other; Janssen: Other; bluebird bio: Other; Amgen: Other; Celgene: Other; BMS: Other.

Infertility-related distress and clinical targets for psychotherapy: a qualitative study

ObjectivesAn estimated 30%–40% of women attending infertility tertiary care facilities experience clinically significant depression and anxiety. However, current psychological interventions for infertility are only modestly effective in this population. In this study, we aimed to identify the specific psychological components of infertility-related distress to assist in the development of a more targeted and effective therapeutic intervention. To our knowledge, this study is the first of its kind to include the views and opinions of mental health professionals who specialise in the field of infertility and the first to explore therapies currently used by mental health professionals.DesignA qualitative approach using semistructured individual interviews and focus group interviews with women who have experience with infertility and also mental health professionals specialising in the field of infertility. Thematic analysis was used to identify patterns and themes emerging from the data.ParticipantsTwenty-one women (aged 25–41 years) struggling to conceive for ≥12 months and 14 mental health professionals participated in semistructured interviews about the psychological challenges related to infertility.ResultsFive themes, each divided into subthemes, emerged from the data and these were developed into a model of infertility-related distress. These five themes are: (1) anxiety, (2) mood disturbance, (3) threat to self-esteem, identity and purpose, (4) deterioration of the couple and (5) weakened support network. In addition, therapeutic techniques used by mental health professionals were identified.ConclusionsThe results of this study suggest specific clinical targets that future interventions treating infertility-related distress should address.

Physiological and metabolic alterations induced by commercial neonicotinoid formulations in Daphnia magna

Neonicotinoid insecticides are widely used agents in agriculture to control a broad range of insect pests. Although use of neonicotinoid pesticides has resulted in the widespread contamination of surface waters, sublethal toxicity data of these products in relation to non-target aquatic biota are still poor. Therefore, the objective of this study was to assess the effects of two neonicotinoid pesticides with widespread use on the basic physiological functions: the thoracic limb activity and heart rate of Daphnia magna, and to screen for their potential to affect the cytochrome P450 monooxygenase system of daphnids. The considered pesticides were the acetamiprid- and thiacloprid based products Mospilan 20 SG and Calypso 480 SC. The dose-dependent variation in the three biological endpoints considered were assessed following 24h exposures. The two neonicotinoid formulations elicited significant depression on the thoracic limb activity and heart rate of daphnids at doses close to the 48h-EC50 of the products, a response mainly attributable to the overall drop in the general health status of the organisms. The dose related variation in the ECOD activity of daphnids exposed to the selected neonicotinoid formulations followed a biphasic pattern, with starting effective doses for Mospilan 20 SG of 6.3 mg L-1 (= 1/20 of 48h-EC50 for Daphnia neonates), and for Calypso 480 SC of 0.034 mg L-1 (= 1/4000 of 48h-EC50). Maximal ECOD activity (2.2 fold increase vs. controls) was induced by Mospilan 20 SG in daphnids exposed to 114 mg L-1 product (= 48h-EC20), and by Calypso 480 SC (1.8 fold increase) at 5.2 mg L-1 dose (= 1/20 of 48h-EC50). The results outlined significant alterations in the physiological traits considered at concentrations below the immobility thresholds (48h-EC50) of the products used as benchmarks to rate their toxicity risks to aquatic biota. Therefore, we think our findings might deserve consideration in the environmental risk evaluation of these products.

Effect of Regular Physical Exercise on Gut Microbiota and Depressive Behaviors in Rats

Objective. The gut microbiota, as the critical mediator of the gut-brain axis, can produce and transport neuroactive substances, thus playing a significant role in the pathogenesis of depression. Although regular physical exercise is an important nondrug antidepressant, its specific effector mechanism is still unclear. Methods. Rats were randomly divided into four different groups (n = 10 for each group) as follows: normal group (G1), depression group (G2), fluoxetine treatment group (G3), and regular exercise treatment group (G4). All rats underwent forced swimming tests, tail suspension tests, open field tests, and elevated plus-maze tests to detect behavioristics. Then, corticosterone levels were detected by ELISA. Additionally, taxonomic analysis of the gut microbiota in all rats was performed after they were exercised regularly for 60 days. Results. Compared with the G1 group, the rats in the G2 group showed significant depression-like behaviors, with increased serum corticosterone levels. The proportions of Bacteroides, Actinomycetes, Proteobacteria, Saccharomyces, and Cyanobacteria in rats of the G2 group were lower than those in the G1 group, while the proportions of Firmicutes, Tenicotte, Deferrobacteria, and Fusobacteria were increased. Furthermore, after regular exercise treatment, the gut microbiota of rats was effectively improved, almost returning to the level of the G1 group, and depressive behavior and corticosterone levels were also restored, which was almost the same as the effect of fluoxetine treatment. Conclusion. Regular physical exercise could alleviate depressive-like behaviors by modulating the species and function of the gut microbiota.

Correlation of psychosocial support concerns and depression in Deaf adults at Nairobi and Kajiado Counties, Kenya

The Deaf are considered persons with disabilities owing to societal stigma resulting in inequality and discrimination. The sequential mixed methodology utilized a cross-sectional approach, with interviews translated and administered in Kenyan Sign Language. The MMSE screened for mental status, while PHQ-9 assessed for depression and WSAS for Psychosocial Support Concerns (PSS) concerns. Researcher-designed in-depth interviews explored qualitative themes. In addition, Focus Group Discussions, ethnographic observation checklist, and mental health providers’ key informant interviews corroborated data. Deaf adults (N=100, 83% response rate) reported inadequate counseling access (62%) while 55% reported no depression. However, 45% depicted clinically significant depression levels, with a notable 28% of Deaf adults also indicating suicidality. Content analyses revealed family, socioeconomic welfare and stigma as the topmost PSS concerns. The study found a significant positive correlation between depression and overall PSS concerns at 0.225 (p=0.024), and home management PSS concern with depression at 0.253 (p=0.011). ANOVA analyses revealed statistically significant differences between the depression categories’ effects on PSS concerns, F = 3.22, p =.026. T-tests analyses indicated that means for None and Mild Depression (M=8.93, SD=8.80) were significantly lower than for Severe depression, t (13) = -3.16, p = .007, 95% CI [-15.15, -2.85]; and Moderately Severe (M=12.64, SD=7.40) were significantly lower than for Severe depression, t (13) -2.67, p = .019, 95% CI [-9.57, -1.00]. The study implications are to design Deaf-friendly assessments. The study recommends Deaf-centric interventions and for further study, national census on Deaf mental health and development of instruments normed for Kenyan Deaf populations.

Deep Eutectic Solvents and Pharmaceuticals

Deep eutectic solvents (DES) are eutectic mixtures that present a deviation from the ideal thermodynamic solid–liquid phase behavior, where a significant depression in the melting temperature occurs. If properly designed and chosen, DES may be liquid at room and the human body’s temperatures and display a biocompatible character, thus representing relevant options in the pharmaceutical field. Accordingly, DES have been studied as alternative solvents or in formulations of pharmaceuticals to improve their solubility and stability. Depending on the DES components, these mixtures might exhibit interesting biological activities compatible with several applications. The use of DES as functional agents or as novel liquid forms of active pharmaceutical ingredients (API-DES) with the goal of improving bioavailability, permeability and therapeutic efficacy of a given API stands as alternative strategies in the pharmaceutical field for drug delivery purposes.

Depression, Anxiety and Quality of Life in Greek Hospital Staff: A Study in the Aftermath of the Debt Crisis Era

Background: Several studies investigated the mental health needs of hospital staff in Greece during the debt crisis era. Yet, no relevant data are available regarding the mental health of hospital staff after this period. The aims of this study are: 1) To investigate the prevalence of clinically significant depression and anxiety in healthcare workers in a general hospital in Athens, Greece; 2) to search for the association of quality of life with anxiety and depression in those workers; 3) to investigate the association of sociodemographic characteristics with those parameters.Methods: The Zung Depression Rating Scale, the Zung Anxiety Rating Scale, the Short-Form Survey-12, assessing quality of life, and sociodemographic assessments were administrated in 110 workers of a public hospital in Athens, Greece. The assessments were completed during January, 2020.Results: Of the study participants, 38.2% had clinically significant anxiety and 6.4% had clinically significant depression. Males had lower scores of depression compared to females (p=0.003). As for the effects of educational level, differences were noted in psychological quality of life between secondary education participants when compared to tertiary education (Mean Difference -3.527, p=0.021), post-graduate (Mean Difference -3.937, p=0.012) and PhD participants (Mean Difference -5.100, p=0.007). Quality of life and its psychological and physical health subscales had strong inverse associations with depression and anxiety (p=0.000).Conclusions: Relevant interventions are necessary to decrease anxiety in hospital staff, which is elevated in the aftermath of the debt crisis period. In addition, health policy makers have to reduce the gender gap in mental health between male and female workers, since the latter had higher levels of depression.

Chew and spit (CHSP) in bariatric patients: a case series

Background Studies into the disordered eating behaviour of chew and spit have alluded to several cohorts more likely to engage in the behaviour, one such group being bariatric surgery candidates and patients. Weight-loss surgery candidates have received little to no attention regarding engaging in chew and spit behaviour. Changes in pre- and post- surgery eating pathology related to chew and spit behaviour has yet to be explored and described in academic literature. Case presentation The current study reports on three cases of individual women, aged 30, 35, and 62 respectively, who indicated engagement in chew and spit. All three cases underwent bariatric surgery (two underwent gastric bypass, one underwent vertical sleeve gastrectomy). Eating pathology—including chew and spit behaviour, anxiety and depression, and adherence to the Norwegian nutritional guidelines were examined pre-operatively and post-operatively (one and two-year follow-up). At baseline (pre-surgery), two participants reported that they engaged in chew and spit, compared to one patient post-surgery. All three cases reported that they, to at least some extent, adhered to dietary guidelines post-surgery. Subjective bingeing frequency appeared to be relatively low for all three cases, further declining in frequency at one-year follow-up. At baseline, one participant reported clinically significant depression and anxiety, with no clinically significant depression or anxiety reported at follow-ups in participants that chew and spit. Conclusions The current study provides a starting point for the exploration of chew and spit as a pathological symptom of disordered eating in bariatric patients. It highlights the need to further explore chew and spit before and after weight-loss surgery.

Crustal structure in the Campanian region (Southern Apennines, Italy) from potential field modelling

We present a 3D model of the main crustal boundaries beneath the Campanian region and the onshore and offshore surrounding areas, based on high-resolution potential field data. Our main objective is the definition of the main structural interfaces in the whole Campanian region from gravity and magnetic data, thanks to their ability to define them on a regional and continuous way. The complex morphology of the Mesozoic carbonate platform, which is fundamental to constrain the top of geothermal reservoir, was reconstructed by inverting the vertical gradient of gravity. We assumed local information from seismic models and boreholes to improve the model. We modeled the deep crustal structures by spectral analysis of Bouguer gravity and magnetic data. The inferred depth estimates indicate a shallow crystalline basement below the Tyrrhenian crust and the Apulian foreland and a significant depression beneath the Bradanic foredeep. The map of the Moho boundary shows a NE-SE verging trough below the Southern Apennine chain and two pronounced uplifts beneath the foreland and the Tyrrhenian crust. We also estimated the depth to the magnetic bottom, showing a thick magnetic crust below the mountain chain and shallow depths where the crustal heat flow is high. The models were compared with seismic sections along selected profiles; a good agreement was observed, despite of some inherent lower resolution for the gravity modelling from spectral methods. The regional covering and the continuity of our estimated crustal interfaces make it a new and valid reference for further geological, geophysical and geothermal studies, especially in areas such as northern and eastern Campania, where there is an incomplete geophysical and geological information.