Allogeneic stem cell transplant for treatment of mycosis fungoides and Sezary syndrome: a systematic review and meta-analysis.

Allogeneic hematopoietic stem cell transplant (allo-HSCT) has been noted to be a potential curative treatment in cases of advanced-stage mycosis fungoides (MF) or Sezary syndrome (SS). To assess outcomes of allo-HSCT for MF/SS we performed a systematic review and meta-analysis including 15 manuscripts and 557 patients, published from 2010-2023. Meta-analysis revealed 1-year and 3+year overall survival (OS) of 51% (95% CI 39-64%) and 40% (32-49%). Progression-free survival at 1 year and 3+years were 42% (31-53%) and 33% (25-42%). Non-relapse mortality was 18% (13-23%). Relapse occurred in of 47% (40-53%) with a median time to relapse of 7.9 months (range 1.6-24 months). Rates of acute and chronic graft-versus-host disease (GVHD) were 45% (35-55%) and 40% (33-48%). Reduced-intensity conditioning (RIC) was associated with superior OS compared to myeloablative conditioning (MAC) (58% vs. 30%, p < 0.001). Of patients with relapse after allo-HSCT, 46% treated with donor lymphocyte infusion (DLI) achieved complete remission. These data support use of allo-HSCT for treatment of advanced-stage MF/SS and suggest superiority of RIC over MAC. Rates of GVHD were comparable to allo-HSCT in general. The improved OS for RIC and high rate of CR with DLI underscore the importance of the graft-versus-lymphoma effect in allo-HSCT for MF/SS.

Breaking the Link Between Negative Emotion and Unhealthy Eating: the Role of Emotion Regulation.

Stressful experiences frequently lead to increased consumption of unhealthy foods, high in sugar and fat yet low in nutrients. Can emotion regulation help break this link? In a laboratory experiment (N = 200), participants were encouraged to ruminate on a current, distressing personal problem, followed by instruction to use a specific emotion regulation strategy for managing feelings around that problem (challenge appraisal, relaxation/distraction, imagined social support, no-instruction control). Participants then spent 15 min on an anagram task in which 80% of items were unsolvable-a frustrating situation offering a second, implicit opportunity to use the regulation strategy. During the anagram task they had free access to a snack basket containing various options. Analyses revealed significant differences among regulation conditions in consumption of candy versus healthy snack options; challenge appraisal led to the healthiest snack choices, imagined social support to the least healthy snack choices. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00190-5.

Auditory oddball hypoactivation in schizophrenia.

Individuals with schizophrenia (SZ) show aberrant activations, assessed via functional magnetic resonance imaging (fMRI), during auditory oddball tasks. However, associations with cognitive performance and genetic contributions remain unknown. This study compares individuals with SZ to healthy volunteers (HVs) using two cross-sectional data sets from multi-center brain imaging studies. It examines brain activation to auditory oddball targets, and their associations with cognitive domain performance, schizophrenia polygenic risk scores (PRS), and genetic variation (loci). Both sample 1 (137 SZ vs. 147 HV) and sample 2 (91 SZ vs. 98 HV), showed hypoactivation in SZ in the left-frontal pole, and right frontal orbital, frontal pole, paracingulate, intracalcarine, precuneus, supramarginal and hippocampal cortices, and right thalamus. In SZ, precuneus activity was positively related to cognitive performance. Schizophrenia PRS showed a negative correlation with brain activity in the right-supramarginal cortex. GWA analyses revealed significant single-nucleotide polymorphisms associated with right-supramarginal gyrus activity. RPL36 also predicted right-supramarginal gyrus activity. In addition to replicating hypoactivation for oddball targets in SZ, this study identifies novel relationships between regional activity, cognitive performance, and genetic loci that warrant replication, emphasizing the need for continued data sharing and collaborative efforts.

Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil.

Graft-versus-host disease (GVHD) is the major toxicity of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that a GVHD prophylaxis regimen of post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) would be associated with incidences of acute and chronic GVHD in patients receiving a matched or single antigen mismatched HCT. This Phase II study was conducted at the University of Minnesota using a myeloablative regimen of either total body irradiation (TBI) at a total dose of 1320 cGy, administered in 165-cGy fractions, twice daily from day -4 to day -1, or busulfan (Bu) 3.2 mg/kg daily (cumulative area under the curve, 19,000 to 21,000 µmol/min/L) plus fludarabine (Flu) 40 mg/m2 once daily on days -5 to -2, followed by a GVHD prophylaxis regimen of PTCy 50 mg/kg on days +3 and +4, Tac, and MMF beginning on day +5. The primary endpoint was the cumulative incidence of chronic GVHD necessitating systemic immunosuppression (IST) at 1 year post-transplantation. Between March 2018 and May 2022, we enrolled 125 pediatric and adult patients, with a median follow-up of 813 days. The incidence of chronic GVHD necessitating systemic IST at 1 year was 5.5%. The rate of grade II-IV acute GVHD was 17.1%, and that of grade III-IV acute GVHD was 5.5%. Two-year overall survival was 73.7%, and 2-year graft-versus-host disease-free, relapse-free survival was 52.2%. The 2-year cumulative incidence of nonrelapse mortality was 10.2%, and the rate of relapse was 39.1%. There was no statistically significant difference in survival outcomes between recipients of matched donor transplants versus recipients of 7/8 matched donor transplants. Our data show that myeloablative HCT with PTCy/Tac/MMF results in an extremely low incidence of severe acute and chronic GVHD in well-matched allogeneic HCT.

Recreational Marijuana Use, Adolescent Cognitive Development, and Schizophrenia Susceptibility.

Background: We investigated how low marijuana (MJ) use levels, the typical use pattern in most adolescent users, affect cognitive maturation and schizophrenia risk. Methods: In two complementary adolescent samples where the majority reported minimal MJ use, we compared cognitive performances before and after MJ use initiation. The Iowa sample (40 first-degree relatives and 54 second-degree relatives of patients with schizophrenia and 117 control subjects with no schizophrenia family history) underwent a battery of standardized neuropsychological tests at 0, 18, and 36 months. Based on self-administered Timeline Followback interviews, 26.5% of adolescents had emergent MJ use (eMJ) during follow-up. The second sample (n = 3463), derived from a birth cohort, received substance use and sustained attention assessments between ages 10 and 15 years. Mixed linear models and regression analyses tested the effects of eMJ on longitudinal changes in cognitive performance. Results: In the Iowa sample, longitudinal changes in 5 of 8 cognitive domains were significantly associated with eMJ. On sustained attention, visuospatial working memory, and executive sequencing, adolescents with eMJ showed less age-expected improved performance. In addition, first-degree relatives with eMJ were less improved on processing speed and executive reasoning than first-degree relatives without eMJ. In the birth cohort, greater intraindividual variability in reaction times (indicative of poorer sustained attention) was significantly associated with more frequent MJ use and with recreational use levels. Conclusions: Nonheavy MJ use disrupts normal adolescent maturation and compounds aberrant adolescent maturation associated with familial schizophrenia risk. These findings underscore the importance of reducing adolescent MJ access in the context of increased availability to high-potency MJ.

Phase II Study of Myeloablative 8/8- or 7/8-Matched Allotransplantation with Post-Transplant Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil: Marked Reduction in GVHD Risk Without Increased Relapse Risk Compared to Historical Cyclosporine/Methotrexate.

Introduction: Graft-versus host disease (GVHD) is a major limitation to the success of allogeneic hematopoietic cell transplant (HCT). We hypothesized that the GVHD prophylaxis regimen of post-transplant cyclophosphamide (PTCy), tacrolimus (Tac) and mycophenolate mofetil (MMF) would reduce the incidence of GVHD in patients receiving a matched or single antigen mismatched HCT without an increase in risk of malignant relapse. Methods: This is a phase II study conducted at the University of Minnesota using a myeloablative regimen of either: (A) total body irradiation (TBI, total dose 1320 cGy, administered in 165 cGy fractions, twice a day from days -4 to -1) or (B) Busulfan 3.2mg/kg daily (cumulative AUC 19,000 - 21,000 µmol/min/L) plus fludarabine 160mg/m2 days -5 to -2, followed by a GVHD prophylaxis regimen of PTCy (50mg/kg days +3 and +4), Tac and MMF (beginning day +5). The primary endpoint is cumulative incidence of chronic GVHD requiring systemic immunosuppression at 1-year post-transplant. We compared results to our previous myeloablative protocol for matched donors utilizing cyclosporine/methotrexate (CSA/MTX) GVHD prophylaxis. Results: From March 2018 - June 2022, we enrolled and treated 125 pediatric and adult patients with a median follow up of 472 days. Grade II-IV acute GVHD occurred in 16% (95% confidence interval (CI): 9-23%); Grade III-IV acute GVHD was 4% (CI: 0-8%). No patients experienced grade IV GVHD, and there were no deaths due to GVHD before day 100. Only 3 developed chronic GVHD requiring immune suppression, (4%, CI: 0-8%). Two-year overall survival (OS) was 80% (CI: 69-87%), and (graft-versus-host disease-free, relapse-free survival) GRFS 57% (CI: 45-67%), both higher than historical CSA/MTX. The incidence of grade II-IV aGVHD, cGVHD, and NRM were all lower with PTCy/Tac/MMF compared to historical CSA/MTX. One-quarter (25%) experienced relapse (CI: 15-36%) similar to historical CSA/MTX. There was no statistically significant difference in survival outcomes between recipients of matched versus 7/8 donors. Conclusion: Myeloablative HCT with PTCy/Tac/MMF results in extremely low incidence of severe acute or chronic GVHD, the primary endpoint of this clinical trial. Relapse risk is not increased compared to our historical CSA/MTX cohort.

Financial constraint and perceptions of COVID-19.

In early March 2020, two crises emerged: the COVID-19 public health crisis and a corresponding economic crisis resulting from business closures and skyrocketing job losses. While the link between socioeconomic status and infectious disease is well-documented, the psychological relationships among economic considerations, such as financial constraint and economic anxiety, and health considerations, such as perceptions of disease spread and preventative actions, is not well understood. Despite past research illustrating the strong link between financial fragility and a wide range of behaviors, surprisingly little research has examined the psychological relationship between the economic crisis and beliefs and behaviors related to the co-occurring health crisis. We show that financial constraint predicts people's beliefs about both their personal risk of infection and the national spread of the virus as well as their social distancing behavior. In addition, we compare the predictive utility of financial constraint to two other commonly studied factors: political partisanship and local disease severity. We also show that negative affect partially mediates the relationship between financial constraint and COVID-19 beliefs and social distancing behaviors. These results suggest the economic crisis created by COVID-19 spilled over into people's beliefs about the health crisis and their behaviors.

Five negative symptom domains are differentially associated with resting state amplitude of low frequency fluctuations in Schizophrenia.

This study examined associations between resting-state amplitude of low frequency fluctuations (ALFF) and negative symptoms represented by total scores, second-order dimension (motivation and pleasure, expressivity), and first-order domain (anhedonia, avolition, asociality, alogia, blunted affect) factor scores in schizophrenia (n = 57). Total negative symptom scores showed positive associations with ALFF in temporal and frontal brain regions. Negative symptom domain scores showed predominantly stronger associations with regional ALFF compared to total scores, suggesting domain scores may better map to neural signatures than total scores. Improving our understanding of the neuropathology underlying negative symptoms may aid in addressing this unmet therapeutic need in schizophrenia.

A Practical Review of the Presentation, Diagnosis, and Management of Cutaneous B-Cell Lymphomas.

This review of cutaneous B-cell lymphoma (CBCL) is focused on the clinical presentation, treatment, and workup of each type of lymphoma. Part 1 is an overview of each of the CBCLs, including clinical presentation, recent advances in the pathobiology, and evidence regarding treatment strategies. Part 2 is a detailed guide to the steps in diagnosis and workup of a newly diagnosed CBCL according to the International Society for Cutaneous Lymphoma/European Organization for Research and Treatment of Cancer and NCCN guidelines.

Differences among perpetrators of intimate partner violence utilizing proactive versus reactive aggression

This research aimed to categorize perpetrator’s aggression as reactive or proactive regarding intimate partner violence and explore the relationship with relevant variables. Victim statements in police reports of 60 predominantly Hispanic male adult perpetrators on probation in South Texas were rated, categorizing statements as reactive or proactive. It was hypothesized that more men would display reactive aggression and it would be associated with severe violence, emotion regulation difficulties, state anger, and impulsivity. The study further suggested that emotion regulation, state anger, and impulsivity would moderate the relationship between severity of violence and reactive/proactive classification, and impulsivity would mediate the relationship between state anger and reactive/proactive classification. Results showed 79% of perpetrators using reactive aggression and 21% using proactive aggression. Men with reactive aggression exhibited more severe violence, emotion regulation difficulties, impulsivity, and state anger. There were no moderation effects of study variables on severity of violence and reactive/proactive classification. Impulsivity fully mediated the relationship between state anger and reactive/proactive classification. Our results support approaches that emphasize reactive aggression in intimate partner violenceperpetration due to its frequency and potential recidivism effects. (AU)

Esta investigación tuvo como objetivo categorizar la agresión del maltratador como reactiva o proactiva en la violencia de pareja y explorar la relación con variables relevantes. Se clasificaron las declaraciones de las víctimas en los informes policiales de 60 hombres adultos agresores predominantemente hispanos en libertad condicional en el sur de Texas, categorizando las declaraciones como reactivas o proactivas. Se hipotetizó que más hombres mostrarían agresión reactiva y que estaría asociada con violencia grave, dificultades en la regulación emocional, ira-estado e impulsividad. El estudio sugirió además que la regulación emocional, la ira-estado y la impulsividad moderarían la relación entre la gravedad de la violencia y la clasificación reactiva/proactiva, y que la impulsividad mediaría la relación entre la ira-estado y la clasificación reactiva/proactiva. Los resultados mostraron que el 79% de los agresores utilizaban la agresión reactiva y el 21% la proactiva. Los hombres con agresión reactiva mostraban una violencia más grave, dificultades en la regulación emocional, impulsividad e ira-estado. No hubo efectos moderadores de las variables estudiadas sobre la gravedad de la violencia y la clasificación reactiva/proactiva. La impulsividad medió totalmente en la relación entre la ira-estado y la clasificación reactiva/proactiva. Nuestros resultados apoyan las perspectivas que enfatizan la agresión reactiva en la violencia en las relaciones de pareja debido a su frecuencia y potenciales efectos de reincidencia. (AU)

Changing patterns of multidisciplinary team treatment, early mortality, and survival in colorectal cancer.

BACKGROUND: This study reports early mortality and survival from colorectal cancer in relation to the pattern of treatments delivered by the multidisciplinary team (MDT) meeting at a high-volume institution in England over 14 years. METHODS: All patients diagnosed with colorectal cancer and discussed during MDT meetings from 2003 to 2016 at a single institution were reviewed. Three time intervals (2003-2007, 2008-2012, and 2013-2016) were compared regarding initial surgical management (resection, local excision, non-resection surgery, and no surgery), initial oncological therapy, 90-day mortality, and crude 2-year survival for the whole cohort. Sub-analyses were performed according to age greater or less than 80 years. RESULTS: The MDT managed 4617 patients over 14 years (1496 in the first interval and 1389 in the last). Over this time, there was a reduction in emergency resections from 15.5 per cent to 9.0 per cent (P < 0.0001); use of oncological therapies increased from 34.6 per cent to 41.6 per cent (P < 0.0001). The 90-day mortality after diagnosis of colorectal cancer dropped from 14.8 per cent to 10.7 per cent (P < 0.001) and 2-year survival improved from 58.6 per cent to 65 per cent (P < 0.001). Among patients aged 80 years or older (425 and 446, in the first and last intervals respectively) there was, in addition, a progressive increase in 'no surgery' rate from 33.6 per cent to 50.2 per cent (P < 0.0001) and a reduction in elective resections from 42.4 per cent to 33.9 per cent (P = 0.010). The 90-day mortality after elective resection fell from 10.0 per cent (18 of 180) to 3.3 per cent (5 of 151; P = 0.013). CONCLUSIONS: Survival from colorectal cancer improved significantly over 14 years. Among patients aged ≥80 years, major changes in the type of treatment delivered were associated with a decrease in postoperative mortality.

A flow electrochemistry-enabled synthesis of 2-substituted N-(methyl-d)piperidines.

A synthesis of N-monodeuteriomethyl-2-substituted piperidines is described. An efficient and readily scalable anodic methoxylation of N-formylpiperidine in an undivided microfluidic electrolysis cell delivers methoxylated piperidine 3, which is a precursor to a N-formyliminium ion and enables C-nucleophiles to be introduced at the 2-position. The isotopically labelled N-deuteriomethyl group is installed using the Eschweiler-Clarke reaction with formic acid-d2 and unlabelled formaldehyde. Monodeuterated N-methyl groups in these molecular systems possess small isotropic proton chemical shift differences important in the investigation of molecules that are able to support long-lived nuclear spin states in solution nuclear magnetic resonance.

Response to Comment on "Following Molecular Mobility during Chemical Reactions: No Evidence for Active Propulsion" and "Molecular Diffusivity of Click Reaction Components: The Diffusion Enhancement Question".

In their Comment (DOI: 10.1021/jacs.2c02965) on two related publications by our groups (J. Am. Chem. Soc. 2021, 143, 20884-20890; DOI: 10.1021/jacs.1c09455) and another (J. Am. Chem. Soc. 2022, 144, 1380-1388; DOI: 10.1021/jacs.1c11754), Huang and Granick discuss the diffusion NMR measurements of molecules during a copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. Here we respond to these comments and maintain that no diffusion enhancement was observed for any species during the reaction. We show that the relaxation agent does not interfere with the CuAAC reaction kinetics nor the diffusion of the molecules involved. Similarly, the gradient pulse length and diffusion time do not affect the diffusion coefficients. Peak overlap was completely removed in our study with the use of hydrazine as the reducing agent. The steady-state assumption does not hold for these diffusion measurements that take several minutes, which is the reason monotonic gradient orders are not suitable. Finally, we discuss the other reactions where similar changes in diffusion have been claimed. Our conclusions are fully supported by the results represented in our original JACS Article and the corresponding Supporting Information.

Text Analysis of Evolving Emotions and Sentiments in COVID-19 Twitter Communication.

Scientists and regular citizens alike search for ways to manage the widespread effects of the COVID-19 pandemic. While scientists are busy in their labs, other citizens often turn to online sources to report their experiences and concerns and to seek and share knowledge of the virus. The text generated by those users in online social media platforms can provide valuable insights about evolving users' opinions and attitudes. The objective of this research is to analyze text of such user disclosures to study human communication during a pandemic in four primary ways. First, we analyze Twitter tweet information, generated throughout the pandemic, to understand users' communications concerning COVID-19 and how those communications have evolved during the pandemic. Second, we analyze linguistic sentiment concepts (analytic, authentic, clout, and tone concepts) in different Twitter settings (sentiment in tweets with pictures or no pictures and tweets versus retweets). Third, we investigate the relationship between Twitter tweets with additional forms of internet activity, namely, Google searches and Wikipedia page views. Finally, we create and use a dictionary of specific COVID-19-related concepts (e.g., symptom of lost taste) to assess how the use of those concepts in tweets are related to the spread of information and the resulting influence of Twitter users. The analysis showed a surprisingly lack of emotion in the initial phases of the pandemic as people were information seeking. As time progressed, there were more expressions of sentiment, including anger. Further, tweets with and without pictures and/or video had statistically significant differences in text sentiment characteristics. Similarly, there were differences between the sentiment in tweets and retweets and tweets. We also found that Google and Wikipedia searches were predictive of sentiment in the tweets. Finally, a variable representing a dictionary of COVID-related concepts was statistically significant when related to users' Twitter influence score and number of retweets, illustrating the general impact of COVID-19 on Twitter and human communication. Overall, the results provide insights into human communication as well as models of human internet and social media use. These findings could be useful for the management of global challenges beyond, or different from, a pandemic.

Nonlinear functional network connectivity in resting functional magnetic resonance imaging data.

In this work, we focus on explicitly nonlinear relationships in functional networks. We introduce a technique using normalized mutual information (NMI) that calculates the nonlinear relationship between different brain regions. We demonstrate our proposed approach using simulated data and then apply it to a dataset previously studied by Damaraju et al. This resting-state fMRI data included 151 schizophrenia patients and 163 age- and gender-matched healthy controls. We first decomposed these data using group independent component analysis (ICA) and yielded 47 functionally relevant intrinsic connectivity networks. Our analysis showed a modularized nonlinear relationship among brain functional networks that was particularly noticeable in the sensory and visual cortex. Interestingly, the modularity appears both meaningful and distinct from that revealed by the linear approach. Group analysis identified significant differences in explicitly nonlinear functional network connectivity (FNC) between schizophrenia patients and healthy controls, particularly in the visual cortex, with controls showing more nonlinearity (i.e., higher normalized mutual information between time courses with linear relationships removed) in most cases. Certain domains, including subcortical and auditory, showed relatively less nonlinear FNC (i.e., lower normalized mutual information), whereas links between the visual and other domains showed evidence of substantial nonlinear and modular properties. Overall, these results suggest that quantifying nonlinear dependencies of functional connectivity may provide a complementary and potentially important tool for studying brain function by exposing relevant variation that is typically ignored. Beyond this, we propose a method that captures both linear and nonlinear effects in a "boosted" approach. This method increases the sensitivity to group differences compared to the standard linear approach, at the cost of being unable to separate linear and nonlinear effects.

1H NMR Studies of Intramolecular OH/OH Hydrogen Bonds via Titratable Isotope Shifts.

Methanol titrations of partially deuterated 1,4- and 1,3-diols dissolved in nonpolar solvents such as CD2Cl2 and benzene-d6 have provided 1H NMR measurements of OH/OD isotope shifts, diagnostic for intact intramolecular hydrogen bonds, under conditions of increasing protic solvent concentration. 1,4- and 1,3-diols with conformationally favored intramolecular OH/OH hydrogen bonds can be titrated to constant isotope shift values, albeit with variable sign, in the presence of excess methanol equivalents, providing evidence for intact intramolecular hydrogen bonds under these conditions. Conversely, the isotope shift in a 1,3-diol with a conformationally labile intramolecular hydrogen bond titrated to zero when in the presence of excess equivalents methanol, consistent with intramolecular hydrogen bond rupture under these conditions. Additionally, the titration behavior of hydroxyl chemical shifts in diols and protected derivatives has revealed significant OH/OD isotope shifts in the absence of chemical shift differences (δOHin = δOHout) that are necessary for an equilibrium isotope effect, lending evidence for an intrinsic contribution to the isotope effect. OH/OD isotope shift titration thus provides a means for understanding the origins of these isotope effects and for probing the intact or nonintact nature of intramolecular OH/OH hydrogen bonds in response to intermolecular hydrogen bonds provided by a protic solvent.

Following Molecular Mobility during Chemical Reactions: No Evidence for Active Propulsion.

The reported changes in self-diffusion of small molecules during reactions have been attributed to "boosted mobility". We demonstrate the critical role of changing concentrations of paramagnetic ions on nuclear magnetic resonance (NMR) signal intensities, which led to erroneous measurements of diffusion coefficients. We present simple methods to overcome this problem. The use of shuffled gradient amplitudes allows accurate diffusion NMR measurements, even with time-dependent relaxation rates caused by changing concentrations of paramagnetic ions. The addition of a paramagnetic relaxation agent allows accurate determination of both diffusion coefficients and reaction kinetics during a single experiment. We analyze a copper-catalyzed azide-alkyne cycloaddition "click" reaction, for which boosted mobility has been claimed. With our methods, we accurately measure the diffusive behavior of the solvent, starting materials, and product and find no global increase in diffusion coefficients during the reaction. We overcome NMR signal overlap using an alternative reducing agent to improve the accuracy of the diffusion measurements. The alkyne reactant diffuses slower as the reaction proceeds due to binding to the copper catalyst during the catalytic cycle. The formation of this intermediate was confirmed by complementary NMR techniques and density functional theory calculations. Our work calls into question recent claims that molecules actively propel or swim during reactions and establishes that time-resolved diffusion NMR measurements can provide valuable insight into reaction mechanisms.

Subjective social status and physical health: The role of negative affect and reappraisal.

RATIONALE: Having low subjective social status is associated with an array of negative health outcomes. However, the mechanisms linking subjective social status to health are not yet clear. One candidate mechanism is negative affect. Researchers have proposed that having low subjective social status may be associated with higher levels of negative affect, and these higher levels of negative affect may be associated with poor health. However, research demonstrating that status-related negative affect is prospectively associated with health in humans is limited. OBJECTIVE: We examined whether negative affect prospectively mediates the relationship between subjective social status and physical health. In addition, we tested whether reappraisal - an affect regulation strategy used to downregulate negative affect - moderates the links among subjective social status, negative affect, and physical health. METHOD: We used two-wave longitudinal data from the Midlife in the United States (MIDUS) project to conduct a series of regression, mediation, and moderated mediation analyses to examine the relationships among subjective social status, negative affect, reappraisal, and health (i.e., four outcomes, chronic conditions, somatic symptoms, self-reported health and mortality). RESULTS: Negative affect mediates the relationship between status and change in morbidity (n = 3289; i.e., change in number of chronic conditions, somatic symptoms, self-reported health) and mortality (n = 4953), such that subjective social status is inversely associated with negative affect, and negative affect is positively associated with poor health. Reappraisal moderates each of these relationships, such that individuals who are low on subjective social status and have high scores on a novel measure of reappraisal experience lower levels of negative affect and better health than individuals who are low on subjective social status but who have low scores on this measure. CONCLUSION: These results have important implications for our understanding of subjective social status and how it relates to physical health.