The joint effect of attachment orientations and empathy on compassion fatigue and compassion satisfaction among oncologists.

OBJECTIVE: Compassion fatigue, which consists of burnout and secondary traumatic stress, and compassion satisfaction are conceptualized as the negative and positive emotional reactions of working in the helping professions. In this study we examined the joint effect of oncologists' attachment orientations and empathy on their compassion fatigue and satisfaction. METHODS: Seventy-three oncologists completed a demographic questionnaire, the shortened version of the Experiences in Close Relationships scale, the Interpersonal Reactivity Index, and the Professional Quality of Life questionnaire. RESULTS: A cluster analysis based on empathy and attachment orientations yielded three meaningful clusters that seem to reflect the three attachment orientations: secure, anxious and avoidant. The oncologists in the three clusters differed in their compassion fatigue levels (i.e. both burnout and secondary traumatic stress) and in their compassion satisfaction levels. Secure attachment (i.e. low scores on both anxious attachment and avoidant attachment) along with high levels of the cognitive component of empathy (perspective-taking) resulted in lower levels of compassion fatigue and higher levels of compassion satisfaction than did insecure attachment. CONCLUSIONS: The study emphasizes the importance of oncologists' attachment orientations and appropriate distance/closeness to their patients in protecting them from compassion fatigue and helping them experience compassion satisfaction.

The association between communication behavior and psychological distress among couples coping with cancer: Actor-partner effects of disclosure and concealment.

OBJECTIVE: This study applies the Actor-Partner Interdependence Model (APIM) to explore the associations between disclosure and concealment with depression and anxiety among patients with cancer and their partners. METHOD: 90 patient-spouse dyads completed the Self-Disclosure Index (SDI), the Self-Concealment Scale (SCS), the Couples Illness Self-Concealment (CISC) questionnaire, and anxiety and depression via the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Significant actor effects were found for most variables, showing disclosure is negatively and concealment is positively associated with depression and anxiety (ß between |0.29| to |0.65|, p ≤ .029). Partner's effect showed a negative association between patients' self-disclosure and their spouses' depression (ß = -0.35, p = .043). Patients' anxiety was negatively associated with similarity in all communication variables (ß between -0.21 to -0.22, p = .042). CONCLUSIONS: Dyadic communication is an important correlate of distress among couples coping with cancer. Specifically, concealment behaviors have a positive association with distress, whereas disclosure is related to lower levels of anxiety and depression among both partners. In addition, whereas patients are affected more strongly than their spouses by the dyadic similarity, spouses seem to be more attuned to their partners' behaviors and therefore potentially more related to patients' propensity for sharing.

Comparing end-of-life care of hematologic malignancy versus solid tumor patients in a tertiary care center.

OBJECTIVES: To compare end-of-life (EOL) care for solid tumor and hematologic malignancy (HM) patients. METHODS: We collected data on the last 100 consecutive deceased HM and 100 consecutive deceased solid tumor patients who died prior to June 1st 2020, treated at a single center. We compared demographic parameters, cause of death as ascertained by review of medical records by two independent investigators, and EOL quality indicators including: place of death, use of chemotherapy or targeted/biologic treatment, emergency department visits as well as hospital, inpatient hospice and Intensive Care Unit admissions and the time spent as inpatient over the last 30 days of life; mechanical ventilation and use of blood products during the last 14 days of life. RESULTS: In comparison with solid tumor patients, HM patients more commonly died from treatment complications (13% vs. 1%) and unrelated causes (16% vs. 2%, p < .001 for all comparisons). HM patients died more frequently than solid tumor patients in the intensive care unit (14% vs. 7%) and the emergency department (9% vs. 0%) and less frequently in hospice (9% vs. 15%, p = .005 for all comparisons). In the 2 weeks prior to death HM patients were more likely than solid tumor patients to undergo mechanical ventilation (14% vs. 4%, p = .013), receive blood (47% vs. 27%, p = .003) and platelet transfusions (32% vs. 7%, p < .001); however, no statistical difference was found in use of either of chemotherapy (18% vs. 13%, p = .28) or targeted treatment (10% vs. 5%, p = .16). CONCLUSIONS: HM patients were more likely than solid tumor patients to undergo aggressive measures at EOL. Rarity of HM deaths, frequently caused by complications of treatment and unrelated causes, may affect treatment choices at EOL.

Patient-oncologist working alliance and its relation to locus of control.

OBJECTIVES: In this study, we assessed the patient-oncologist relationship, conceptualized as the working alliance from a dyadic perspective, and its relation to locus of control. METHODS: One hundred and three oncologist-patient dyads were recruited. Measures included a sociodemographic and medical questionnaire; the "internal, powerful others, and chance" locus of control scale; and the working alliance inventory. RESULTS: Application of the actor-partner interdependence model yielded 2 actor effects: a positive association between oncologist "internal" locus of control and oncologist working alliance, and a negative association between oncologist "chance" locus of control and oncologist working alliance. It also yielded one partner effect: a positive association between oncologist "internal" locus of control and patient working alliance. SIGNIFICANCE OF RESULTS: The actor-partner effect suggests that oncologists' locus of control has a role in the establishment of the patient-oncologist working alliance; oncologists' internal locus of control is a dominant factor affecting not only their own perceived alliance but patients' perceived alliance as well.

Beyond "being open about it": A systematic review on cancer related communication within couples.

Extensive literature addresses the correlates of communication behaviors within couples in the specific stressful context of oncology. This literature focused mainly on the concepts of disclosure, concealment, holding back and protective buffering to gain more insight into the potential benefits of open communication on the psychological and relational wellbeing of the patient, the spouse and the dyad. The current systematic review aims to present this literature, summarize research findings and suggest empirical, theoretical and clinical implications. Methods: The search method applied in this review was in line with the PRISMA guidelines. Key words related to couples' communication and oncology were used to identify relevant studies according to title and abstract fields from 1.1.2000 until 31.1.22. Results: Out of 3277 papers, a total of 55 articles were identified as relevant for this review. These quantitative studies used cross-sectional and longitudinal designs. Overall, integrating findings from different studies showed that while avoiding communication is negatively associated with psychological and relational wellbeing, the benefits of disclosure seems to be dependent on different factors including the partner's responsiveness, contextual factors and personal characteristics. The existing literature is limited in providing data regarding the nature of adequate or helpful partner responses, the best timing, and the specific topics that are recommended to be disclosed such as specific fears. Most importantly, it is limited in heterogeneity of constructs of communication that were studied, scales that were used and diverse mediators and moderators that were examined. Accordingly, an effort to reach consensus of definition and assessment of communicative behavior is recommended for future studies, and addressing responsiveness to communicative initiations seems to be important for clinical practice.

The paradox: guilt as an antidote to helplessness among oncologists.

PURPOSE: Oncologists are exposed to suffering, loss, and death, and as a result may experience guilt. The study examined two competing hypotheses regarding the relation between locus of control (LOC) and guilt among oncologists and the mediating role of helplessness. METHOD: Eighty-three oncologists answered a demographic questionnaire; the Levenson's "Internal, Powerful Others, and Chance" scale; the Guilt Inventory; and the Learned Helplessness Scale. RESULTS: Oncologists reported moderate levels of guilt, high levels of internal LOC, and low levels of external LOC and helplessness. The results indicate a significant negative relationship between internal LOC and guilt and a significant positive relationship between external LOC (powerful others) and guilt, both mediated by helplessness. It seems that oncologists with external LOC feel helplessness and this metamorphoses into guilt, due to its potentially protective role against feelings of helplessness. CONCLUSIONS: Oncologists are at risk for guilt. Whereas an internal LOC plays an important role as a resilience factor in terms of helplessness, an external LOC is a risk factor for helplessness and guilt. A paradoxical association between guilt and helplessness was found. The implication of which is that guilt may be produced to avoid helplessness; in other words, guilt, however painful, might be preferable to feeling helpless. Interventions focusing on oncologists' coping with uncontrolled situations in their daily work, decreasing their sense of helplessness and guilt, should be implanted.

Oncologists' Locus of Control, Compassion Fatigue, Compassion Satisfaction, and the Mediating Role of Helplessness.

The oncology setting may give rise to significant feelings of helplessness among oncologists via patients' inevitable deaths or suffering. The current study examines whether and how oncologists' sense of control (locus of control; LOC) influences their compassion fatigue and satisfaction. Methods: Seventy-three oncologists completed the following questionnaires: the Professional Quality of Life scale; Levenson's Internal, Powerful Others, and Chance scale; the Guilt Inventory, State Guilt subscale; and the Learned Helplessness scale. Results: Oncologists reported high levels of secondary traumatic stress and burnout and moderate levels of compassion satisfaction. A positive association between oncologists' external LOC and compassion fatigue, and a negative association between oncologists' internal LOC and compassion fatigue, were found. Helplessness, but not guilt, had a mediating role in these associations. Internal LOC was also positively associated with compassion satisfaction. Conclusions: The current study highlights oncologists as a population at risk of experiencing compassion fatigue and emphasizes oncologists' locus of control as a predisposition that plays a role in the development of this phenomenon. Additionally, the cognitive as well as the emotional aspects of control were found to be important factors associated with compassion fatigue.

The mediating effect of pleasure and menopausal symptoms on sexual activity among young breast cancer survivors.

PURPOSE: Young breast cancer survivors often go through a rapid change in menopause status due to cancer treatment and suffer from abrupt symptoms. This transition compels them to deal with unique medical and psychological side effects on their quality of life. One of the most affected quality of life domains is sexual functioning. This study explored the differences in frequency of sexual activity between young breast cancer survivors and young healthy women. It also examined whether this difference in sexual activity frequency was mediated by discomfort and/or pleasure during intercourse, both of which are affected by symptoms of premature menopause. METHODS: A total of 97 young breast cancer survivors and 75 young healthy women completed a sociodemographic questionnaire: the Fallowfield's Sexual Activity Questionnaire (FSAQ) and the Menopausal Rating Scale (MRS). Additionally, the breast cancer participants completed a medical data questionnaire. RESULTS: Findings revealed a significant direct effect between group and menopausal symptoms, menopausal symptoms and pleasure, and pleasure and frequency of sexual activity. Structural equation modeling explained the differences between the groups in frequency of sexual activity as mediated by menopausal symptoms and both pleasure and discomfort. CONCLUSIONS AND IMPLICATIONS: These results highlight the impact of pleasure on the frequency of young breast cancer survivors' sexual activity, and its relation to menopausal symptoms. These young women should be provided with appropriate information and interventions that will help them experience increased pleasure during sexual activity despite their early and induced menopausal symptoms.

Temperature and salt controlled tuning of protein clusters.

The formation of molecular assemblies in protein solutions is of strong interest both from a fundamental viewpoint and for biomedical applications. While ordered and desired protein assemblies are indispensable for some biological functions, undesired protein condensation can induce serious diseases. As a common cofactor, the presence of salt ions is essential for some biological processes involving proteins, and in aqueous suspensions of proteins can also give rise to complex phase diagrams including homogeneous solutions, large aggregates, and dissolution regimes. Here, we systematically study the cluster formation approaching the phase separation in aqueous solutions of the globular protein BSA as a function of temperature (T), the protein concentration (cp) and the concentrations of the trivalent salts YCl3 and LaCl3 (cs). As an important complement to structural, i.e. time-averaged, techniques we employ a dynamical technique that can detect clusters even when they are transient on the order of a few nanoseconds. By employing incoherent neutron spectroscopy, we unambiguously determine the short-time self-diffusion of the protein clusters depending on cp, cs and T. We determine the cluster size in terms of effective hydrodynamic radii as manifested by the cluster center-of-mass diffusion coefficients D. For both salts, we find a simple functional form D(cp, cs, T) in the parameter range explored. The calculated inter-particle attraction strength, determined from the microscopic and short-time diffusive properties of the samples, increases with salt concentration and temperature in the regime investigated and can be linked to the macroscopic behavior of the samples.

Attitudes toward death and death acceptance among hemato-oncologists: An Israeli sample.

OBJECTIVE: Hemato-oncologists are highly exposed to patients' death and suffering during their daily work. The current exploratory and cross-sectional study examined death acceptance attitudes, in order to explore whether death acceptance attitudes are associated with fear of death. METHOD: A convenience sample of 50 Israeli hemato-oncologists currently working in a clinical setting participated in the study. They completed the Death Attitudes Profile revised questionnaire (DAP-R), which examines levels of fear of death, death avoidance, approach acceptance, neutral acceptance, and escape acceptance. In addition, the hemato-oncologists reported on levels of exposure to patients' death and suffering. RESULTS: A repeated measures MANOVA revealed significantly lower levels of neutral acceptance, compared with approach and escape acceptance. Path analysis for predicting fear of death by the other study variables revealed that death avoidance fully mediated the relationship between approach acceptance and fear of death as well as revealing a negative correlation between neutral acceptance and fear of death (higher neutral acceptance was related to lower fear of death). No associations were found between exposure to death and suffering and attitudes toward death. SIGNIFICANCE OF RESULTS: In contrast to previous conceptualizations, the ability to adaptively cope with fear of death differed in accordance with death acceptance attitudes. Whereas neutral acceptance adaptively defended from fear of death, approach acceptance was associated with increased fear of death through death avoidance. As hemato-oncologists are highly exposed to patients' death and suffering, and are required to make critical medical decisions on daily basis, these findings may have substantial implications for end-of-life care and the process of medical decision-making regarding the choice of treatment goals: cure, quality of life, and life prolongment. Further research is needed to investigate the role of death acceptance attitudes among hemato-oncologists.

Packing and dynamics of a protein solution approaching the jammed state.

The packing of proteins and their collective behavior in crowded media is crucial for the understanding of biological processes. Here we study the structural and dynamical evolution of solutions of the globular protein bovine serum albumin with increasing concentration via drying using small angle X-ray scattering and dynamic light scattering. We probe an evolving correlation peak on the scattering profile, corresponding to the inter-protein distance, ξ, which decreases following a power law of the protein volume fraction, φ. The rate of decrease in ξ becomes faster above a protein concentration of ∼200 mg ml-1 (φ = 0.15). The power law exponent changes from 0.33, which is typical of colloidal or protein solutions, to 0.41. During the entire drying process, we observe the development and the growth of two-step relaxation dynamics with increasing φ as revealed by dynamic light scattering. We find three different regimes of the dependence of ξ as a function of φ. In the dilute regime (φ < 0.22), protein molecules are far apart from each other compared to their size. In this case, the dynamics mainly corresponds to Brownian motion. At an intermediate concentration (0.22 < φ < 0.47), inter-protein distances become comparable to the size of protein molecules, leading to a preferential orientation of the ellipsoidal protein molecules along with a possible deformation. In this regime, the dynamics shows two distinct relaxation times. At a very high concentration (φ > 0.47), the system reaches a jammed state. Subsequently, the secondary relaxation time in this state becomes extremely slow. In this state, the protein molecules have approximately one hydration layer. This study contributes to the understanding of protein molecular packing in crowded environments and the phenomenon of density-driven jamming for soft matter systems.

Interplay between Glass Formation and Liquid-Liquid Phase Separation Revealed by the Scattering Invariant.

The interplay of the glass transition with liquid-liquid phase separation (LLPS) is a subject of intense debate. We use the scattering invariant Q to probe how approaching the glass transition affects the shape of LLPS boundaries in the temperature/volume fraction plane. Two protein systems featuring kinetic arrest with a lower and an upper critical solution temperature phase behavior, respectively, are studied varying the quench depth. Using Q we noninvasively identify system-dependent differences for the effect of glass formation on the LLPS boundary. The glassy dense phase appears to enter the coexistence region for the albumin-YCl3 system, whereas it follows the equilibrium binodal for the γ-globulin-PEG system.

Compassion fatigue among oncologists: the role of grief, sense of failure, and exposure to suffering and death.

PURPOSE: Oncologists cope with unique work characteristics that increase their risk of developing compassion fatigue-that is, burnout and secondary traumatic stress-and can result in reduced capacity and interest in being empathetic to the suffering of others (Stamm B. The concise ProQOL manual, 2010). At the same time, oncologists can experience compassion satisfaction-that is, the positive aspects of caring. This study explored the associations of compassion fatigue and compassion satisfaction with oncologists' grief and sense of failure beyond their reported exposure to suffering and death. METHODS: Seventy-four oncologists completed self-administered questionnaires examining compassion fatigue, compassion satisfaction, grief, exposure to suffering and death, and sense of failure. RESULTS: The oncologists reported that they face the loss of approximately 50% of their patients, and that their patients suffer from profound emotional and physical pain. High levels of compassion fatigue and grief, and moderate levels of sense of failure, were reported. Findings showed a lack of association between exposure to suffering and death and compassion fatigue and satisfaction. However, grief and sense of failure were found to predict both aspects of compassion fatigue: secondary traumatic stress (p < 0.001, p < 0.003, respectively) and burnout (p < 0.002, p < 0.025, respectively). CONCLUSIONS: These results highlight the importance of the oncologists' subjective experiences of grief and sense of failure, beyond their reports of exposure to suffering and death, in terms of their levels of compassion fatigue. Implications of these findings include the need to develop interventions for oncologists that will allow them to acknowledge, process, and overcome negative experiences of failure and grief.

Grief over patients, compassion fatigue, and the role of social acknowledgment among psycho-oncologists.

OBJECTIVE: Compassion fatigue-that is, secondary traumatic stress (STS) and burnout-is a traumatic emotional state experienced by health care providers and expressed in a reduced capacity to be interested in and empathic to the suffering of others. Compassion fatigue may be related to grief over patients' loss. We examined the relation between grief and compassion fatigue among psycho-oncologists while exploring the impact of social acknowledgment on this association. We hypothesized that social acknowledgment would moderate the relation between grief and compassion fatigue. METHODS: Participants were 60 Israeli psycho-oncologists in a cross-sectional study. Measures consisted of a demographic questionnaire, the Texas Revised Inventory of Grief-Present, the Social Acknowledgment questionnaire, and the Professional Quality of Life Questionnaire. RESULTS: The participants reported relatively high levels of grief and high levels of compassion fatigue. Grief and compassion fatigue were significantly positively associated (STS: r = 0.41, p < 0.01; Burnout: r = 0.45, p < 0.01). A k-means cluster analysis based on social acknowledgment and grief yielded three meaningful clusters: High Grief-Low Social Acknowledgment; Medium Grief-High Social Acknowledgment; and Low Grief-Medium Social Acknowledgment. Levels of STS in the first cluster were significantly higher in comparison to levels of STS in each of the other clusters (F = 6.22, p < 0.01). CONCLUSIONS: Psycho-oncologists experience patient loss as part of their daily work. In response, they may develop grief reactions. This grief, when it is not perceived by them as being socially acknowledged, may result in high levels of STS: a phenomenon with undesirable personal and professional implications.

Between empathy and grief: The mediating effect of compassion fatigue among oncologists.

OBJECTIVE: Oncologists are exposed to suffering, loss, and death, which can potentially lead to grief reactions. Although grief over patients may be a natural consequence of the close and longstanding oncologist-patient relationship, the empathy that oncologists feel toward their patients may put them at risk for compassion fatigue (CF). This study examined the mediating role of the two components of CF-secondary traumatic stress (STS) and burnout-in the relation between empathy and grief among oncologists. METHOD: Participants included 71 Israeli oncologists. Measures consisted of a demographic questionnaire, the Texas Revised Inventory of Grief-Present, the Interpersonal Reactivity Index, and the Professional Quality of Life questionnaire. RESULTS: Oncologists reported moderate levels of grief and relatively high levels of both STS and burnout. In addition, they reported high levels of the three components of empathy: perspective taking, empathic concern, and personal distress. The PROCESS SPSS macro revealed support for the mediation model. The mediators (STS and burnout) fully accounted for the relationship between the following two components of empathy-perspective taking and personal distress-and grief. CONCLUSIONS: Oncologists commonly experience grief over patients. We found that oncologists' grief was related to their empathy, and that this association was explained by their levels of CF. The current research may mark a step toward recognizing oncologists' grief as well as understanding the processes associated with it.

Reentrant Phase Behavior in Protein Solutions Induced by Multivalent Salts: Strong Effect of Anions Cl- Versus NO3.

In this work, the effects of the two anions Cl- and NO3- on the phase behavior of bovine serum albumin (BSA) in solution with trivalent salts are compared systematically. In the presence of trivalent metal salts, negatively charged proteins such as BSA in solution undergo a reentrant condensation (RC) phase behavior, which has been established for several proteins with chlorides of trivalent salts. Here, we show that replacing Cl- by NO3- leads to a marked change in the phase behavior. The effect is investigated for the two different cations Y3+ and La3+. The salts are thus YCl3, Y(NO3)3, LaCl3, and La(NO3)3. The experimental phase behavior shows that while the chloride salts induce both liquid-liquid phase separation (LLPS) and RC, the nitrate salts also induce LLPS, but RC becomes partial with La(NO3)3 and disappears with Y(NO3)3. The observed phase behavior is rationalized by effective protein-protein interactions which are characterized using small-angle X-ray scattering. The results based on the reduced second virial coefficients B2/ B2HS and 1/ I( q → 0) demonstrate that the NO3- salts induce a stronger attraction than the Cl- salts. Overall, the effective attraction, the width of the condensed regime in the RC phase diagram, and the nature of LLPS follow the order LaCl3 < YCl3 < La(NO3)3 < Y(NO3)3. Despite the decisive role of cations in RC phase behavior, isothermal titration calorimetry measurements indicate that replacing anions does not significantly influence the cation binding to proteins. The experimental results observed are discussed based on an "enhanced Hofmeister effect" including electrostatic and hydrophobic interactions between protein-cation complexes.

Nanosecond Tracer Diffusion as a Probe of the Solution Structure and Molecular Mobility of Protein Assemblies: The Case of Ovalbumin.

Protein diffusion is not only an important process ensuring biological function but can also be used as a probe to obtain information on structural properties of protein assemblies in liquid solutions. Here, we explore the oligomerization state of ovalbumin at high protein concentrations by means of its short-time self-diffusion. We employ high-resolution incoherent quasielastic neutron scattering to access the self-diffusion on nanosecond timescales, on which interparticle contacts are not altered. Our results indicate that ovalbumin in aqueous (D2O) solutions occurs in increasingly large assemblies of its monomeric subunits with rising protein concentration. It changes from nearly monomeric toward dimeric and ultimately larger than tetrameric complexes. Simultaneously, we access information on the internal molecular mobility of ovalbumin on the nanometer length scale and compare it with results obtained for bovine serum albumin, immunoglobulin, and ß-lactoglobulin.

Multivalent-Ion-Activated Protein Adsorption Reflecting Bulk Reentrant Behavior.

Protein adsorption at the solid-liquid interface is an important phenomenon that often can be observed as a first step in biological processes. Despite its inherent importance, still relatively little is known about the underlying microscopic mechanisms. Here, using multivalent ions, we demonstrate the control of the interactions and the corresponding adsorption of net-negatively charged proteins (bovine serum albumin) at a solid-liquid interface. This is demonstrated by ellipsometry and corroborated by neutron reflectivity and quartz-crystal microbalance experiments. We show that the reentrant condensation observed within the rich bulk phase behavior of the system featuring a nonmonotonic dependence of the second virial coefficient on salt concentration c_{s} is reflected in an intriguing way in the protein adsorption d(c_{s}) at the interface. Our findings are successfully described and understood by a model of ion-activated patchy interactions within the framework of the classical density functional theory. In addition to the general challenge of connecting bulk and interface behavior, our work has implications for, inter alia, nucleation at interfaces.

Crowding-Controlled Cluster Size in Concentrated Aqueous Protein Solutions: Structure, Self- and Collective Diffusion.

We investigate the concentration-controlled formation of clusters in ß-lactoglobulin (BLG) protein solutions combining structural and dynamical scattering techniques. The static structure factor from small-angle X-ray scattering as well as de-Gennes narrowing in the nanosecond diffusion function D(q) from neutron spin echo spectroscopy support a picture of cluster formation. Using neutron backscattering spectroscopy, a monotonous increase of the average hydrodynamic cluster radius is monitored over a broad protein concentration range, corresponding to oligomeric structures of BLG ranging from the native dimers up to roughly four dimers. The results suggest that BLG forms compact clusters that are static on the observation time scale of several nanoseconds. The presented analysis provides a general framework to access the structure and dynamics of macromolecular assemblies in solution.

Strong Isotope Effects on Effective Interactions and Phase Behavior in Protein Solutions in the Presence of Multivalent Ions.

In this article, we have studied the influence of the isotopic composition of the solvent (H2O or D2O) on the effective interactions and the phase behavior of the globular protein bovine serum albumin in solution with two trivalent salts (LaCl3 and YCl3). Protein solutions with both salts exhibit a reentrant condensation phase behavior. The condensed regime (regime II) in between two salt concentration boundaries (c* < cs < c**) is significantly broadened by replacing H2O with D2O. Within regime II, liquid-liquid phase separation (LLPS) occurs. The samples that undergo LLPS have a lower critical solution temperature (LCST). The value of LCST decreases significantly with increasing solvent fraction of D2O. The effective protein-protein interactions characterized by small-angle X-ray scattering demonstrate that although changing the solvent has negligible effects below c*, where the interactions are dominated by electrostatic repulsion, an enhanced effective attraction is observed in D2O above c*, consistent with the phase behavior observed. As the LCST-LLPS is an entropy-driven phase transition, the results of this study emphasize the role of entropy in solvent isotope effects.