Surgical approach to microwave and radiofrequency liver ablation for hepatocellular carcinoma and colorectal liver metastases less than 5 cm: a systematic review and meta-analysis.

BACKGROUND: Primary hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM) represent the two most common malignant neoplasms of the liver. The objective of this study was to assess outcomes of surgical approaches to liver ablation comparing laparoscopic versus percutaneous microwave ablation (MWA), and MWA versus radiofrequency ablation (RFA) in patients with HCC or CRLM lesions smaller than 5 cm. METHODS: A systematic review was conducted across seven databases, including PubMed, Embase, and Cochrane, to identify all comparative studies between 1937 and 2021. Two independent reviewers screened for eligibility, extracted data for selected studies, and assessed study bias using the modified Newcastle Ottawa Scale. Random effects meta-analyses were subsequently performed on all available comparative data. RESULTS: From 1066 records screened, 11 studies were deemed relevant to the study and warranted inclusion. Eight of the 11 studies were at high or uncertain risk for bias. Our meta-analyses of two studies revealed that laparoscopic MW ablation had significantly higher complication rates compared to a percutaneous approach (risk ratio = 4.66; 95% confidence interval = [1.23, 17.22]), but otherwise similar incomplete ablation rates, local recurrence, and oncologic outcomes. The remaining nine studies demonstrated similar efficacy of MWA and RFA, as measured by incomplete ablation, complication rates, local/regional recurrence, and oncologic outcomes, for both HCC and CRLM lesions less than 5 cm (p > 0.05 for all outcomes). There was no statistical subgroup interaction in the analysis of tumors < 3 cm. CONCLUSION: The available comparative evidence regarding both laparoscopic versus percutaneous MWA and MWA versus RFA is limited, evident by the few studies that suffer from high/uncertain risk of bias. Additional high-quality randomized trials or statistically matched cohort studies with sufficient granularity of patient variables, institutional experience, and physician specialty/training will be useful in informing clinical decision making for the ablative treatment of HCC or CRLM.

MODs vs. NPs: Vying for the Future of Printed Electronics.

This Minireview compares two distinct ink types, namely metal-organic decomposition (MOD) and nanoparticle (NP) formulations, for use in the printing of some of the most conductive elements: silver, copper and aluminium. Printing of highly conductive features has found purpose across a broad array of electronics and as processing times and temperatures reduce, the avenues of application expand to low-cost flexible substrates, materials for wearable devices and beyond. Printing techniques such as screen, aerosol jet and inkjet printing are scalable, solution-based processes that historically have employed NP formulations to achieve low resistivity coatings printed at high resolution. Since the turn of the century, the rise in MOD inks has vastly extended the range of potentially applicable compounds that can be printed, whilst simultaneously addressing shelf life and sintering issues. A brief introduction to the field and requirements of an ink will be presented followed by a detailed discussion of a wide array of synthetic routes to both MOD and NP inks. Unindustrialized materials will be discussed, with the challenges and outlook considered for the market leaders: silver and copper, in comparison with the emerging field of aluminium inks.

Inflammation and depressive phenotypes: evidence from medical records from over 12 000 patients and brain morphology.

BACKGROUND: Preclinical and human studies suggest an association between chronic inflammation and the development of depressive behaviors. This is proposed to occur through downstream effects of inflammatory cytokines on neuroplasticity, neurogenesis and neurotransmitter function, although the neural correlates remain poorly understood in humans. METHODS: In Study 1, structural magnetic resonance imaging and serum inflammatory cytokine data were analyzed from 53 psychiatrically healthy female participants. Correlational analyses were conducted between interleukin-6 (IL-6) and volume in a priori regions implicated in the pathophysiology of major depressive disorder (MDD). In Study 2, medical data [including serum inflammatory acute phase reactants (C-reactive protein)] were analyzed for 12 589 participants. Participants were classified as having (n = 2541) v. not having (n = 10 048) probable lifetime MDD using phenotypes derived using machine-learning approaches. Non-parametric analyses compared inflammation between groups, whereas regression analyses probed whether inflammation predicted probable MDD classification while accounting for other variables. RESULTS: In Study 1, significant negative correlations emerged between IL-6 and hippocampal, caudate, putamen and amygdalar volume. In Study 2, the MDD group showed a higher probability of elevated inflammation than the non-MDD group. Moreover, elevated inflammation was a significant predictor of probable MDD classification. CONCLUSIONS: Findings indicate that inflammation is cross-sectionally related to reduced volume in brain regions implicated in MDD phenotypes among a sample of psychiatrically healthy women, and is associated with the presence of probable MDD in a large clinical dataset. Future investigations may identify specific inflammatory markers predicting first MDD onset.

Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.

The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response (n = 10), moderate-response (n = 21), and mild-response (n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability.SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how individual neuroendocrine stress response patterns are linked to affective responses to stress and structural variability in neuroendocrine regulatory brain regions. By applying latent class linear mixed modeling on individuals' patterns of cortisol responses to a prolonged acute stressor, we identified three distinct trajectories of cortisol response. Relative to the group showing a moderate cortisol response, groups characterized by hyper and mild cortisol response were both associated with more negative affect. Moreover, a continuous measure of cortisol response showed that high and low levels of stress-induced cortisol release correlated with reduced hippocampal gray matter volume. Given that neuroendocrine stress responses are conceptualized as biomarkers of stress susceptibility, these insights may have clinical implications.

Impact of high-fat, low-carbohydrate diet on myocardial substrate oxidation, insulin sensitivity, and cardiac function after ischemia-reperfusion.

High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulin-ketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels.

Potentiated processing of negative feedback in depression is attenuated by anhedonia.

BACKGROUND: Although cognitive theories of depression have postulated enhanced processing of negatively valenced information, previous EEG studies have shown both increased and reduced sensitivity for negative performance feedback in MDD. To reconcile these paradoxical findings, it has been speculated that sensitivity for negative feedback is potentiated in moderate MDD, but reduced in highly anhedonic subjects. The goal of this study was to test this hypothesis by analyzing the feedback-related negativity (FRN), frontomedial theta power (FMT), and source-localized anterior midcingulate cortex (aMCC) activity after negative feedback. METHODS: Fourteen unmedicated participants with Major Depressive Disorder (MDD) and 15 control participants performed a reinforcement learning task while 128-channel Electroencephalogram (EEG) was recorded. FRN, FMT, and LORETA source-localized aMCC activity after negative and positive feedback were compared between groups. RESULTS: The MDD group showed higher FRN amplitudes and aMCC activation to negative feedback than controls. Moreover, aMCC activation to negative feedback was inversely related to self-reported anhedonia. In contrast, self-reported anxiety correlated with feedback-evoked frontomedial theta (FMT) within the depression group. CONCLUSIONS: The present findings suggest that, among depressed and anxious individuals, enhanced processing of negative feedback occurs relatively early in the information processing stream. These results extend prior work and indicate that although moderate depression is associated with elevated sensitivity for negative feedback, high levels of anhedonia may attenuate this effect.

Platinum(II) Phenylpyridyl Schiff Base Complexes as Latent, Photoactivated, Alkene Hydrosilylation Catalysts.

Photoactivated catalysts for the hydrosilylation of alkenes with silanes offer temporal control in manufacturing processes that require silicone curing. We report the development of a range of air-stable Pt(II) (salicylaldimine)(phenylpyridyl), [Pt(sal)(ppy)], complexes as photoinitiated hydrosilylation catalysts. Some of these catalysts show appreciable latency in thermal catalysis and can also be rapidly (10 s) activated by a LED UV-light source (365 nm), to give systems that selectively couple trimethylvinylsilane and hexamethylsiloxymethylsilane to give the linear hydrosilylation product. Although an undetectable (by NMR spectroscopy) amount of precatalyst is converted to the active form under UV-irradiation in the timescale required to initiate hydrosilylation, clean and reliable kinetics can be measured for these systems that allow for a detailed mechanism to be developed for Pt(sal)(ppy)-based photoactivated hydrosilylation. The suggested mechanism is shown to have close parallels with, but also subtle differences from, those previously proposed for thermally-activated Karstedt-type Pt(0) systems.

Neural mobilization in low back and radicular pain: a systematic review.

BACKGROUND: Low back pain can present with radicular pain caused by lumbosacral nerve root pathology. Neural mobilization (NM) is a treatment technique used to treat low back and radicular pain (LBRP). PURPOSE: To evaluate the effectiveness of NM interventions in improving pain, disability, and function in adults with LBRP. DATA SOURCES: CINAHL Plus, MEDLINE (Ovid), Physiotherapy Evidence Database, and Cochrane databases were searched. STUDY SELECTION: Randomized controlled trials assessing the effect of NM on pain, disability, and/or function in adults with LBRP. DATA EXTRACTION: Authors reviewed studies and used the PEDro scale and the revised Cochrane risk-of-bias tool to assess methodological quality and risk of bias. DATA SYNTHESIS: Eight studies were included. Six of the eight studies found the addition of NM to conservative treatment improved all measured outcomes. One study found improvements in some but not all functional measures, and delayed improvements in pain. One study found improvements in measures of neural sensitivity, but not overall pain and disability. CONCLUSIONS: NM may be an effective tool for short-term improvements in pain, function, and disability associated with LBRP. Additional high quality research is needed. STUDY REGISTRATION: : This systematic review protocol was registered with PROSPERO (registration number: CRD42020192338).

Tris(ß-ketoiminate) Aluminium(III) Compounds as Aluminium Oxide Precursors.

Precursor design is the crucial step in tailoring the deposition profile towards a multitude of functional materials. Most commercially available aluminium oxide precursors require high processing temperatures (>500 °C). Herein, we report the tuning of the decomposition profile (200-350 °C) of a range of octahedrally coordinated tris(ß-ketoiminate) aluminium complexes of the type [Al(MeCN(R)CHC=OMe)3 ], by varying the R substituents in the ligands. The complexes are derived from the reaction of trimethylamine alane (TMAA) and a series of N-substituted ß-ketoiminate ligands (R-acnacH, R=Me, Et, i Pr, Ph) with varying R-substituents sizes. When the more sterically encumbered ligand (R=Mes) was used, the Al atom became five-coordinate, therefore representing the threshold to octahedral coordination around the metal in these type of compounds, which, consequently, lead to a change of decomposition profile. The resulting compounds have been characterised by NMR spectroscopy, mass spectrometry, elemental analysis and single crystal X-ray diffraction. [Al(MeCN(Me)CHC=OMe)3 ] has been used as a single source precursor for the deposition of Al2 O3 . Thin films were deposited via aerosol assisted chemical vapour deposition (AACVD), with toluene as the solvent, and were analysed using SEM, EDX and XPS.

Unraveling the Steric Link to Copper Precursor Decomposition: A Multi-Faceted Study for the Printing of Flexible Electronics.

The field of printed electronics strives for lower processing temperatures to move toward flexible substrates that have vast potential: from wearable medical devices to animal tagging. Typically, ink formulations are optimized using mass screening and elimination of failures; as such, there are no comprehensive studies on the fundamental chemistry at play. Herein, findings which describe the steric link to decomposition profile: combining density functional theory, crystallography, thermal decomposition, mass spectrometry, and inkjet printing, are reported. Through the reaction of copper(II) formate with excess alkanolamines of varying steric bulk, tris-co-ordinated copper precursor ions: "[CuL3 ]," each with a formate counter-ion (1-3) are isolated and their thermal decomposition mass spectrometry profiles are collected to assess their suitability for use in inks (I1-3 ). Spin coating and inkjet printing of I1,2 provides an easily up-scalable method toward the deposition of highly conductive copper device interconnects (ρ = 4.7-5.3 × 10-7 Ω m; ≈30% bulk) onto paper and polyimide substrates and forms functioning circuits that can power light-emitting diodes. The connection among ligand bulk, coordination number, and improved decomposition profile supports fundamental understanding which will direct future design.

Family therapy training in child and adolescent psychiatry fellowship programs.

OBJECTIVE: This study describes the current state of family therapy training in a sample of child and adolescent psychiatry fellowship programs. METHOD: Child and adolescent psychiatry fellows (N=66) from seven training programs completed a questionnaire assessing demographics, family therapy training experiences, common models of treatment and supervision, attitudes about family therapy, and perspectives on clinical training and clinical skill. RESULTS: Fellows ascribed a high degree of importance to family therapy skills, yet most had not seen more than one outpatient family with family therapy supervision during their training. They identified structural family therapy and family psychoeducation as the primary family treatment orientations in their programs. CONCLUSION: Although child psychiatry fellows believed that strong family therapy skills would benefit their patients, most had limited supervised experiences with families. Child and adolescent psychiatry training programs appear to offer exposure to family therapy without sufficient opportunities to develop proficiency. The author discusses educational implications for child and adolescent psychiatry.

Molecular and cellular immune features of aged patients with severe COVID-19 pneumonia.

Aging is a major risk factor for developing severe COVID-19, but few detailed data are available concerning immunological changes after infection in aged individuals. Here we describe main immune characteristics in 31 patients with severe SARS-CoV-2 infection who were >70 years old, compared to 33 subjects <60 years of age. Differences in plasma levels of 62 cytokines, landscape of peripheral blood mononuclear cells, T cell repertoire, transcriptome of central memory CD4+ T cells, specific antibodies are reported along with features of lung macrophages. Elderly subjects have higher levels of pro-inflammatory cytokines, more circulating plasmablasts, reduced plasmatic level of anti-S and anti-RBD IgG3 antibodies, lower proportions of central memory CD4+ T cells, more immature monocytes and CD56+ pro-inflammatory monocytes, lower percentages of circulating follicular helper T cells (cTfh), antigen-specific cTfh cells with a less activated transcriptomic profile, lung resident activated macrophages that promote collagen deposition and fibrosis. Our study underlines the importance of inflammation in the response to SARS-CoV-2 and suggests that inflammaging, coupled with the inability to mount a proper anti-viral response, could exacerbate disease severity and the worst clinical outcome in old patients.

Endogenous control of inflammation characterizes pregnant women with asymptomatic or paucisymptomatic SARS-CoV-2 infection.

SARS-CoV-2 infection can affect all human beings, including pregnant women. Thus, understanding the immunological changes induced by the virus during pregnancy is nowadays of pivotal importance. Here, using peripheral blood from 14 pregnant women with asymptomatic or mild SARS-CoV-2 infection, we investigate cell proliferation and cytokine production, measure plasma levels of 62 cytokines, and perform a 38-parameter mass cytometry analysis. Our results show an increase in low density neutrophils but no lymphopenia or gross alterations of white blood cells, which display normal levels of differentiation, activation or exhaustion markers and show well preserved functionality. Meanwhile, the plasma levels of anti-inflammatory cytokines such as interleukin (IL)-1RA, IL-10 and IL-19 are increased, those of IL-17, PD-L1 and D-dimer are decreased, but IL-6 and other inflammatory molecules remain unchanged. Our profiling of antiviral immune responses may thus help develop therapeutic strategies to avoid virus-induced damages during pregnancy.

Low-Temperature Deposition of Highly Conductive Aluminum Metal Films on Flexible Substrates Using Liquid Alane MOD Precursors.

Metal-organic decomposition (MOD) precursor inks are emerging as the new route to low-temperature deposition of highly conductive metals, owing to the tunability of their decomposition. New methods of printing are being investigated to help negate the progressive issues of the electronics industry, not least the movement toward low-cost polymers and paper substrates. Informed precursor design is crucial if achieving materials capable of this is possible. In this work, the liquid MOD precursors, dimethylethylamine alane (DMEAA) and trimethylamine alane (TEAA), have been used to deposit a highly conductive aluminum (Al) metal with resistivities in the range of 4.10 × 10-5 to 5.32 × 10-7 Ω m (mean electrical resistivity of 8 × 10-6 Ω m, approximately 300 times more resistive than bulk Al metal), without the need for an additional solvent, at low temperatures (100 and 120 °C), on a range of substrates including glass, polyimide, polyethylene terephthalate, and paper. Conductive coatings have been analyzed using X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy and resistivity measurements; as a proof of concept, Al deposited on paper has been used in an electrical circuit. Results indicate that DMEAA is a better precursor, producing more conductive films, which is explained by its lower decomposition temperature and higher Al weight loading, indicating potential for significant industrial application.

A rugged, self-sterilizing antimicrobial copper coating on ultra-high molecular weight polyethylene: a preliminary study on the feasibility of an antimicrobial prosthetic joint material.

We report here for the first time how the combination of a precursor solution and low temperature (170 °C) aerosol assisted chemical vapour deposition were used to bond a copper coating to ultra-high molecular weight polyethylene (UHMWPE) and promote robustness. This metallic thin film remained intact on the UHMWPE substrate after the Scotch tape test and showed notable wear-resistance after 10 cycles of sand paper-abrasion. Antimicrobial assays against both Escherichia coli and Staphylococcus aureus revealed potent dark bactericidal activity with 99.999% reduction in bacterial number within 15 minutes. These results suggest that the modified UHMWPE could be a potential candidate for antimicrobial plastics and in the long term may find application in prosthetic joint applications.

Depression genetic risk score is associated with anhedonia-related markers across units of analysis.

Investigations of pathophysiological mechanisms implicated in vulnerability to depression have been negatively impacted by the significant heterogeneity characteristic of psychiatric syndromes. Such challenges are also reflected in numerous null findings emerging from genome-wide association studies (GWAS) of depression. Bolstered by increasing sample sizes, recent GWAS studies have identified genetics variants linked to MDD. Among them, Okbay and colleagues (Nat. Genet. 2016 Jun;48(6):624-33) identified genetic variants associated with three well-validated depression-related phenotypes: subjective well-being, depressive symptoms, and neuroticism. Despite this progress, little is known about psychopathological and neurobiological mechanisms underlying such risk. To fill this gap, a genetic risk score (GRS) was computed from the Okbay's study for a sample of 88 psychiatrically healthy females. Across two sessions, participants underwent two well-validated psychosocial stressors, and performed two separate tasks probing reward learning both before and after stress. Analyses tested whether GRS scores predicted anhedonia-related phenotypes across three units of analyses: self-report (Snaith Hamilton Pleasure Scale), behavior (stress-induced changes in reward learning), and circuits (stress-induced changes in striatal reward prediction error; striatal volume). GRS scores were negatively associated with anhedonia-related phenotypes across all units of analyses but only circuit-level variables were significant. In addition, the amount of explained variance was systematically larger as variables were putatively closer to the effects of genes (self-report < behavior < neural circuitry). Collectively, findings implicate anhedonia-related phenotypes and neurobiological mechanisms in increased depression vulnerability, and highlight the value of focusing on fundamental dimensions of functioning across different units of analyses.

Precursors for Atmospheric Plasma-Enhanced Sintering: Low-Temperature Inkjet Printing of Conductive Copper.

Bidentate diamine and amino-alcohol ligands have been used to form solid, water-soluble, and air-stable monomeric copper complexes of the type [Cu(NH2CH2CH(R)Y)2(NO3)2] (1, R=H, Y=NH2; 2, R=H, Y=OH; 3, R=Me, Y=OH). The complexes were characterized by elemental analysis, mass spectrometry, infrared spectroscopy, thermal gravimetric analysis, and single-crystal X-ray diffraction. Irrespective of their decomposition temperature, precursors 1-3 yield highly conductive copper features [1.5×10-6â€…Ω m (±5×10-7â€…Ω m)] upon atmospheric-pressure plasma-enhanced sintering.

Association Between Interleukin-6 and Striatal Prediction-Error Signals Following Acute Stress in Healthy Female Participants.

BACKGROUND: Stress is widely known to alter behavioral responses to rewards and punishments. It is believed that stress may precipitate these changes through modulation of corticostriatal circuitry involved in reinforcement learning and motivation, although the intervening mechanisms remain unclear. One candidate is inflammation, which can rapidly increase following stress and can disrupt dopamine-dependent reward pathways. METHODS: Here, in a sample of 88 healthy female participants, we first assessed the effect of an acute laboratory stress paradigm on levels of plasma interleukin-6 (IL-6), a cytokine known to be both responsive to stress and elevated in depression. In a second laboratory session, we examined the effects of a second laboratory stress paradigm on reward prediction error (RPE) signaling in the ventral striatum. RESULTS: We show that individual differences in stress-induced increases in IL-6 (session 1) were associated with decreased ventral striatal RPE signaling during reinforcement learning (session 2), though there was no main effect of stress on RPE. Furthermore, changes in IL-6 following stress predicted intraindividual variability in perceived stress during a 4-month follow-up period. CONCLUSIONS: Taken together, these data identify a novel link between IL-6 and striatal RPEs during reinforcement learning in the context of acute psychological stress, as well as future appraisal of stressful life events.

Reward Responsiveness Varies by Smoking Status in Women with a History of Major Depressive Disorder.

Major depressive disorder (MDD) and nicotine dependence are highly comorbid, with studies showing that ~50% of individuals with MDD smoke. The link between these disorders persists even after the clinical symptoms of depression subside, as indicated by high levels of nicotine dependence among individuals with remitted depression (rMDD). Recent evidence indicates that individuals with rMDD show blunted responses to reward as measured by a probabilistic reward task (PRT), which assesses the ability to modify behavior as a function of reward history. Given nicotine's ability to enhance reward responsiveness, individuals with rMDD might smoke to address this persistent reward deficit. However, it is unclear whether smokers with rMDD show enhanced reward responsiveness relative to rMDD individuals who do not smoke. To test this hypothesis, we evaluated reward responsiveness on the PRT in four groups (N=198): individuals with and without rMDD who were or were not nicotine dependent. As hypothesized, rMDD nonsmokers had lower reward responsiveness relative to both control nonsmokers and rMDD smokers; conversely, smokers with rMDD showed behavioral patterns comparable to those without a history of depression. Given nicotine's ability to enhance reward sensitivity, it is possible that nicotine normalizes the otherwise blunted reward responsiveness in individuals with rMDD. Therapies aimed at enhancing this reward-based deficit may be beneficial in the treatment of both nicotine dependence and MDD.