Correlation Between Tacrolimus Levels in Blood Samples Obtained from Central Catheter and Peripheral Venipuncture in Lung Transplant Patients (Ven-Cat Study).

BACKGROUND: Following lung transplantation (LT), receiving immunosuppressive therapy is crucial. Tacrolimus is considered a drug with a narrow therapeutic range and its use requires constant monitoring. This study aimed to evaluate the correlation between tacrolimus levels obtained from central venous catheter and direct venipuncture in adult patients undergoing LT. METHODS: This prospective study included LT patients hospitalized in conventional ward carrying a central catheter through which no intravenous tacrolimus was administered. Trough samples were obtained through direct puncture and from the central catheter. Pearson correlation coefficient was calculated to quantify the mean difference between the 2 measures. RESULTS: A total of 54 sample pairs from 16 LT patients were obtained, mostly male (81.3%) and bilateral transplant recipients (93.8%); the transplant procedure was the primary reason for admission (81.3%). The difference in tacrolimus levels between both samples was 0.3 (0.1-0.6) mcg/L, with the measurement for the samples obtained through venipuncture being mostly higher than that for those obtained from the catheter. A strong correlation was observed between the tacrolimus levels in the samples obtained from the catheter and through venipuncture (Pearson correlation coefficient, 0.991; P < 0.001; R2 = 0.982). CONCLUSIONS: There is an excellent correlation between tacrolimus levels obtained from venipuncture and those obtained from central venous catheter in LT patients undergoing oral tacrolimus therapy.

Natural allelic variation confers diversity in the regulation of flag leaf traits in wheat.

Flag leaf (FL) dimension has been reported as a key ecophysiological aspect for boosting grain yield in wheat. A worldwide winter wheat panel consisting of 261 accessions was tested to examine the phenotypical variation and identify quantitative trait nucleotides (QTNs) with candidate genes influencing FL morphology. To this end, four FL traits were evaluated during the early milk stage under two growing seasons at the Leibniz Institute of Plant Genetics and Crop Plant Research. The results showed that all leaf traits (Flag leaf length, width, area, and length/width ratio) were significantly influenced by the environments, genotypes, and environments × genotypes interactions. Then, a genome-wide association analysis was performed using 17,093 SNPs that showed 10 novel QTNs that potentially play a role in modulating FL morphology in at least two environments. Further analysis revealed 8 high-confidence candidate genes likely involved in these traits and showing high expression values from flag leaf expansion until its senescence and also during grain development. An important QTN (wsnp_RFL_Contig2177_1500201) was associated with FL width and located inside TraesCS3B02G047300 at chromosome 3B. This gene encodes a major facilitator, sugar transporter-like, and showed the highest expression values among the candidate genes reported, suggesting their positive role in controlling flag leaf and potentially being involved in photosynthetic assimilation. Our study suggests that the detection of novel marker-trait associations and the subsequent elucidation of the genetic mechanism influencing FL morphology would be of interest for improving plant architecture, light capture, and photosynthetic efficiency during grain development.

Multi-organ clinical ultrasound as a complement to the diagnostic process in an internal medicine consultation.

INTRODUCTION: Evaluating outpatient cases in internal medicine consultations presents a significant diagnostic challenge. Ultrasound can be a highly useful tool in assessment and decision-making. PATIENTS AND METHODS: A prospective observational study was conducted on a cohort of patients attending an internal medicine rapid assessment clinic. Eighty patients were prospectively recruited. A medical consultation was conducted as per usual clinical practice, followed by a POCUS evaluation; collecting pulmonary, cardiac, and abdominal data. All findings were analyzed and recorded, particularly those that were significant or altered the initial diagnosis, subsequent tests, or treatment. RESULTS: Significant ultrasound findings were found in 37.5% of the patients. Of all ultrasound scans, the most clinically relevant were in the heart region (31.9%), followed by the abdomen (26%). These findings led to a change in overall management in 27.5% of patients. Using logistic regression, a model was developed to estimate the presence of clinically relevant findings with an area under the curve (AUC) of 0.78 (95% CI 0.66-0.89; p < 0.001) with 80% Sensitivity and 66% Specificity. CONCLUSION: The systematic and standardized incorporation of clinical ultrasound in internal medicine consultations contributes to decision-making, can provide significant findings that allow for modifications in clinical suspicion and therapeutic management.

Who is at risk for weight gain after weight-gain associated treatment with antipsychotics, antidepressants, and mood stabilizers: A machine learning approach.

BACKGROUND: Weight gain is a common side effect in psychopharmacology; however, targeted therapeutic interventions and prevention strategies are currently absent in day-to-day clinical practice. To promote the development of such strategies, the identification of factors indicative of patients at risk is essential. METHODS: In this study, we developed a transdiagnostic model using and comparing decision tree classifiers, logistic regression, XGboost, and a support vector machine to predict weight gain of ≥5% of body weight during the first 4 weeks of treatment with psychotropic drugs associated with weight gain in 103 psychiatric inpatients. We included established variables from the literature as well as an extended set with additional clinical variables and questionnaires. RESULTS: Baseline BMI, premorbid BMI, and age are known risk factors and were confirmed by our models. Additionally, waist circumference has emerged as a new and significant risk factor. Eating behavior next to blood glucose were found as additional potential predictor that may underlie therapeutic interventions and could be used for preventive strategies in a cohort at risk for psychotropics induced weight gain (PIWG). CONCLUSION: Our models validate existing findings and further uncover previously unknown modifiable factors, such as eating behavior and blood glucose, which can be used as targets for preventive strategies. These findings underscore the imperative for continued research in this domain to establish effective preventive measures for individuals undergoing psychotropic drug treatments.

Deep learning the cis-regulatory code for gene expression in selected model plants.

Elucidating the relationship between non-coding regulatory element sequences and gene expression is crucial for understanding gene regulation and genetic variation. We explored this link with the training of interpretable deep learning models predicting gene expression profiles from gene flanking regions of the plant species Arabidopsis thaliana, Solanum lycopersicum, Sorghum bicolor, and Zea mays. With over 80% accuracy, our models enabled predictive feature selection, highlighting e.g. the significant role of UTR regions in determining gene expression levels. The models demonstrated remarkable cross-species performance, effectively identifying both conserved and species-specific regulatory sequence features and their predictive power for gene expression. We illustrated the application of our approach by revealing causal links between genetic variation and gene expression changes across fourteen tomato genomes. Lastly, our models efficiently predicted genotype-specific expression of key functional gene groups, exemplified by underscoring known phenotypic and metabolic differences between Solanum lycopersicum and its wild, drought-resistant relative, Solanum pennellii.

Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Higher T central and lower effector memory cells in bipolar disorder: A differentiation abnormality?

The aim of this study was to elucidate the nature of T cell abnormalities in bipolar disorder (BD). With the use of multicolor flow cytometry, we first quantified the composition of the different memory and pro-inflammatory immune subpopulations in samples of 58 patients with BD and compared them to 113 healthy controls. Second, to assess if cytomegalovirus infection was related to the resulted immune subpopulation compositions in the two groups, we measured cytomegalovirus-specific antibodies in serum. Thirdly, we assessed differences between the two groups in the serum levels of the immune cell differentiation factor interleukin-7. Compared to healthy controls, patients showed significantly higher T helper-17, T regulatory and T central memory cells (CD4+ and CD8+). Besides, patients showed significantly lower CD4+ T effector memory and CD4+ T effector memory re-expressing RA cells. Cytomegalovirus infection was not related to the observed abnormalities, with the exception of T helper-17 cells. This immune subpopulation was significantly higher only in patients seropositive to cytomegalovirus infection. Finally, interleukin-7 levels were significantly lower in BD compared to healthy controls. In conclusion, the aberrant levels of T memory cell populations in BD may suggest a T cell differentiation abnormality. The role of interleukin-7 in this putative abnormality should be further investigated.

Green Revolution dwarfing Rht genes negatively affected wheat floral traits related to cross-pollination efficiency.

Hybrid breeding is a promising strategy to quickly improve wheat yield and stability. Due to the usefulness of the Rht 'Green Revolution' dwarfing alleles, it is important to gain a better understanding of their impact on traits related to hybrid development. Traits associated with cross-pollination efficiency were studied using Near Isogenic Lines carrying the different sets of alleles in Rht genes: Rht1 (semi-dwarf), Rht2 (semi-dwarf), Rht1 + 2 (dwarf), Rht3 (extreme dwarf), Rht2 + 3 (extreme dwarf), and rht (tall) during four growing seasons. Results showed that the extreme dwarfing alleles Rht2 + 3, Rht3, and Rht1 + 2 presented the greatest effects in all the traits analyzed. Plant height showed reductions up to 64% (Rht2 + 3) compared to rht. Decreases up to 20.2% in anther length and 33% in filament length (Rht2 + 3) were observed. Anthers extrusion decreased from 40% (rht) to 20% (Rht1 and Rht2), 11% (Rht3), 8.3% (Rht1 + 2), and 6.5% (Rht2 + 3). Positive correlations were detected between plant height and anther extrusion, anther, and anther filament lengths, suggesting the negative effect of dwarfing alleles. Moreover, the magnitude of these negative impacts depends on the combination of the alleles: Rht2 + 3 > Rht3/Rht1 + 2 > Rht2/Rht1 > rht (tall). Reductions were consistent across genotypes and environments with interactions due to magnitude effects. Our results indicate that Rht alleles are involved in multiple traits of interest for hybrid wheat production and the need to select alternative sources for reduced height/lodging resistance for hybrid breeding programs.

Humanization, Adaptation to Change, and Mental Health in Teachers in Three European Countries / Humanización, adaptación al cambio y salud mental en docentes de tres países europeos

Background: The aim of this study was to explore the relationships between humanization, adaptability to change, and mental health in European teachers (Spanish, Portuguese, and Italian teachers), as well as the relationship between humanization and mental health in teachers through the analysis of the mediating role of adaptability to change. Method: A cross-sectional descriptive study was conducted with teachers from three European countries (Spain, n = 263; Portugal, n = 344; and Italy, n = 287). The Healthcare Professional Humanization Scale (HUMAS), General Health Questionnaire (GHQ-28), and the Adaptation to Change Questionnaire (ADAPTA-10) were administered. Results: In all three countries, negative associations were observed between humanization and the presence of problematic symptoms. With respect to the adaptability to change factors, humanization showed negative associations with the emotional factor and positive associations with the cognitive-behavioral factor. Comparative mean analysis revealed differences in humanization, the emotional factor of adaptability to change, and the presence of problematic symptoms. Finally, the mediation models showed the absence of a direct effect in the relationship between humanization and the presence of GHQ-28 symptomatology when it was mediated by the emotional factor (Spanish and Portuguese sample). In the Italian sample, the direct effect of humanization-GHQ-28 symptomatology was significant, with a smaller proportion of the indirect effect of the emotional factor acting as a mediator. On the other hand, when considering the cognitive-behavioral factor as a mediator, the same result was obtained for all three countries: a negative direct effect between humanization and GHQ-28 symptomatology, with no mediation by the cognitive-behavioral factor. Conclusions: The need to improve training in humanization competencies lies in the potential protective function that these competencies can have ... (AU)

Antecedentes: El objetivo del trabajo fue explorar la relación entre humanización, capacidad de adaptación al cambio y salud mental en docentes europeos (españoles, portugueses e italianos) y la relación entre humanización y salud mental en docentes mediante el análisis del rol mediador de la capacidad de adaptación al cambio. Método: Se realizó un estudio descriptivo transversal con docentes de tres países europeos (España, n = 263, Portugal, n = 344 e Italia, n = 287). Se administró la Healthcare Professional Humanization Scale (HUMAS), el General Health Questionnaire (GHQ-28) y el Cuestionario de Adaptación al Cambio (ADAPTA-10). Resultados: En los tres países se obervó una asociación negativa entre humanización y la presencia de sintomatología problemática. Con los factores de adaptación al cambio la humanización presentó una asociación negativa con el factor emocional y positiva con el cognitivo-conductual. Del análisis comparativo de medias se obtuvieron diferencias en humanización, el factor emocional de adaptación al cambio y la presencia de sintomatología problemática. Finalmente, los modelos de mediación mostraron la ausencia de un efecto directo en la relación entre humanización y la presencia de sintomatología GHQ-28 cuando esta se encontraba mediada por el factor emocional (muestra española y portuguesa). En la muestra italiana fue significativo el efecto directo de la humanización-sintomatología GHQ-28, con menor proporción del efecto indirecto del factor emocional actuando este como mediador. Por otro lado, tomando como mediador el factor cognitivo-conductual, se obtuvo el mismo resultado para los tres países: un efecto directo negativo entre la humanización y la sintomatología GHQ-28, no estando este mediado por el factor cognitivo-conductual. Conclusiones: La necesidad de mejorar la formación en competencias de humanización reside en la potencial función protectora que pueden ejercer sobre la salud mental de los docentes. (AU)

Ozone Improved Bone Dynamic of Female Rats Using Zoledronate.

The aim of this study was to analyze the effect of ozone (OZN) therapy on the dynamics of bone tissue in ovariectomized rats treated with zoledronic acid (ZOL). Female Wistar rats aged 6 months (n = 110) were subjected to bilateral ovariectomy (OVX). At month 3 post-OVX, 10 animals were euthanized to characterize the bone tissue architecture using microtomography (micro-CT). The remaining animals were divided into two groups: ZOL group, administered with ZOL (100 µg/kg body weight); saline (SAL) group (0.45 mL of SAL solution), both for 28 days. At month 3 post-treatment, 10 animals from each group were euthanized to characterize the bone architecture using micro-CT. The remaining animals were divided into the following groups: ZOL (n = 20), ZOL + OZN (n = 20); SAL (n = 20), and SAL + OZN (n = 20). The animals in ZOL + OZN and SAL + OZN groups were intraperitoneally administered with OZN (0.7 mg/kg body weight) once every 2 days. On days 30 and 60, six animals from each group were euthanized for analysis and structural characterization of bones in the femoral head and spine. Some samples of the femoral neck were subjected to biomechanical tests, while some samples were analyzed under a laser confocal microscope. The other samples collected from the femoral neck and spine were analyzed for area of neoformed bone and used for performing inflammatory cell and osteocyte counts. Data were submitted to statistical analysis considering a significance level of p < 0.05. Bone volume percentage and osteocyte and inflammatory cell counts were upregulated in the femoral head region of the ZOL + OZN group. Biomechanical analysis of the femoral neck revealed that the modulus of elasticity was similar between the ZOL and ZOL + OZN groups but differed significantly between the SAL and SAL + OZN groups. The positive areas for calcein and alizarin in the ZOL and ZOL + OZN groups were higher than those in the SAL and SAL + OZN groups. This suggested a positive synergistic effect of OZN and ZOL on the maintenance of bone mass and restoration of bone tissue vitality in ovariectomized rats.

Association of clinical parameters and polygenic risk scores for body mass index, schizophrenia, and diabetes with antipsychotic-induced weight gain.

Antipsychotic-induced weight gain (AIWG) is a common adverse event in schizophrenia. Genome-wide association studies (GWAS) and polygenic risk scores (PRS) for other diseases or traits are recent approaches to disentangling the genetic architecture of AIWG. 200 patients with schizophrenia treated monotherapeutically with antipsychotics were included in this study. A multiple linear regression analysis with ten-fold crossvalidation was performed to predict the percentage weight change after five weeks of treatment. Independent variables were sex, age, body mass index (BMI) at baseline, medication-associated risk, and PRSs (BMI, schizophrenia, diabetes, and metabolic syndrome). An explorative GWAS analysis was performed on the same subjects and traits. PRSs for BMI (ß = 3.78; p = 0.0041), schizophrenia (ß = 5.38; p = 0.021) and diabetes type 2 (ß = 13.4; p = 0.046) were significantly associated with AIWG. Other significant factors were sex, baseline BMI and medication. Compared to the model without genetic factors, the addition of PRSs for BMI, schizophrenia, and diabetes type 2 increased the goodness of fit by 6.5 %. The GWAS identified the association of three variants (rs10668573, rs10249381 and rs1988834) with AIWG at a genome-wide level of p < 1 · 10-6. Using PRS for schizophrenia, BMI, and diabetes type 2 increased the explained variation of predicted weight gain, compared to a model without PRSs. For more precise results, PRSs derived from other traits (ideally AIWG) should be investigated. Potential risk variants identified in our GWAS need to be further investigated and replicated in independent samples.

Deconstructing depression by machine learning: the POKAL-PSY study.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621).

Psychometric properties of the Hungarian childhood trauma questionnaire short form and its validity in patients with adult attention-deficit hyperactivity disorder or borderline personality disorder.

BACKGROUND: Compelling evidence supports the role of childhood traumatization in the etiology of psychiatric disorders, including adult attention-deficit hyperactivity disorder (aADHD) and borderline personality disorder (BPD). The aim of this study was to examine the psychometric properties of the Hungarian version of the Childhood Trauma Questionnaire Short Form (H-CTQ-SF) and to investigate the differences between patients diagnosed with aADHD and BPD in terms of early traumatization. METHODS: Altogether 765 (mean age = 32.8 years, 67.7% women) patients and control subjects were enrolled from different areas of Hungary. Principal component analysis and confirmatory factor analysis were carried out to explore the factor structure of H-CTQ-SF and test the validity of the five-factor structure. Discriminative validity was assessed by comparing clinical and non-clinical samples. Subsequently, aADHD and BPD subgroups were compared with healthy controls to test for the role of early trauma in aADHD without comorbid BPD. Convergent validity was explored by measuring correlations with subscales of the Personality Inventory for DSM-5 (PID-5). RESULTS: The five scales of the H-CTQ-SF demonstrated adequate internal consistency and reliability values. The five-factor model fitted the Hungarian version well after exclusion of one item from the physical neglect scale because of its cross-loading onto the emotional neglect subscale. The H-CTQ-SF effectively differentiated between the clinical and non-clinical samples. The BPD, but not the aADHD group showed significant differences in each CTQ domain compared with the healthy control group. All CTQ domains, except for physical abuse, demonstrated medium to high correlations with PID-5 emotional lability, anxiousness, separation insecurity, withdrawal, intimacy avoidance, anhedonia, depressivity, suspiciousness, and hostility subscales. CONCLUSIONS: Our study confirmed the psychometric properties of the H-CTQ-SF, an easy-to-administer, non-invasive, ethically sound questionnaire. In aADHD patients without comorbid BPD, low levels of traumatization in every CTQ domain were comparable to those of healthy control individuals. Thus, the increased level of traumatization found in previous studies of aADHD might be associated with the presence of comorbid BPD. Our findings also support the role of emotional neglect, emotional abuse and sexual abuse in the development of BPD.

Feasible low bone density condition for assessing bioactivity in ex-in vivo and in vivo studies.

OBJECTIVE: To choose a critical animal model for assessments of bone repair with implant installation by comparing senile rats (SENIL) to young ovariectomized rats (OXV). METHODOLOGY: For the ex-in vivo study, the femurs were precursors for bone marrow mesenchymal stem cells. Cellular responses were performed, including cell viability, gene expression of osteoblastic markers, bone sialoprotein immunolocalization, alkaline phosphatase activity, and mineralized matrix formation. For the in vivo study, the animals received implants in the region of the bilateral tibial metaphysis for histometric, microtomography, reverse torque, and confocal microscopy. RESULTS: Cell viability showed that the SENIL group had lower growth than OVX. Gene expression showed more critical responses for the SENIL group (p<0.05). The alkaline phosphatase activity obtained a lower expression in the SENIL group, as for the mineralization nodules (p<0.05). The in vivo histological parameters and biomechanical analysis showed lower data for the SENIL group. The confocal microscopy indicated the presence of a fragile bone in the SENIL group. The microtomography was similar between the groups. The histometry of the SENIL group showed the lowest values (p<0.05). CONCLUSION: In experimental studies with assessments of bone repair using implant installation, the senile model promotes the most critical bone condition, allowing a better investigation of the properties of biomaterials and topographic changes.

Benefits of dapagliflozin in the whole spectrum of heart failure in clinical practice: the RICA registry.

Aims: To determine the projected benefits of dapagliflozin after an acute heart failure (HF) event in Spain. Methods: A multicenter and prospective study that included subjects aged 50 years or older consecutively admitted with HF to internal medicine departments in Spain. The projected clinical benefits of dapagliflozin were calculated via pooled analysis of the DAPA-HF and DELIVER trials. Results: A total of 5644 subjects were analyzed, of whom 79.2% were eligible for dapagliflozin, according to criteria of the DAPA-HF and DELIVER trials. Full implementation of dapagliflozin would imply a 1-year absolute risk reduction of 2.3% for death (number needed to treat = 43) and 5.7% (number needed to treat = 17) for HF rehospitalization. Conclusion: Treatment with dapagliflozin could significantly reduce HF burden in clinical practice.

Heart failure is a severe condition that is associated with a high risk of complications. This means that it is important to start using new therapies that have demonstrated a clinical benefit. Clinical trials have shown that dapagliflozin reduces the risk of developing these complications in patients with heart failure. However, it is important to find out whether the results of clinical trials are also seen in real-life populations. We estimated the potential benefits of dapagliflozin in people admitted to hospital more than once with heart failure. The study took place in Spain. Our data suggest that treatment with dapagliflozin could reduce the complications associated with heart failure in real-life patients.

Premature T cell aging in major depression: A double hit by the state of disease and cytomegalovirus infection.

Introduction: Previous research indicates that premature T cell senescence is a characteristic of major depressive disorder (MDD). However, known senescence inducing factors like cytomegalovirus (CMV) infection or, probably, childhood adversity (CA) have not been taken into consideration so far. Objective: Differentiation and senescent characteristics of T cells of MDD patients were investigated in relation to healthy controls (HC), taking the CMV seropositivity and CA into account. Methods: 127 MDD and 113 HC of the EU-MOODSTRATIFICATION cohort were analyzed. Fluorescence activated cell sorting (FACS) analysis was performed to determine B, NK, and T cell frequencies. In a second FACS analysis, naïve, effector memory (Tem), central memory (Tcm), effector memory cells re-expressing RA (TEMRA), as well as CD28+ and CD27+ memory populations, were determined of the CD4+ and CD8+ T cell populations in a subsample (N = 35 MDD and N = 36 HC). CMV-antibody state was measured by IgG ELISA and CA by the Childhood Trauma Questionnaire. Results: We detected a CMV-antibody positivity in 40% of MDD patients (35% HC, n. s.) with seropositive MDD cases showing a higher total childhood trauma score. Second, a higher inflation of memory CD4+ T helper cells in CMV seronegative patients as compared to seronegative HC and reduced numbers of naïve CD4+ T helper cells in CMV seropositive patients (not in CMV seropositive HC) were found. Third, a higher inflation of memory CD8+ T cytotoxic cells in CMV seropositive cases as compared to CMV seropositive HC, particularly of the TEMRA cells, became apparent. Higher percentages of CD4+ TEMRA and late stage CD27-CD28- TEMRA cells were similar in both HC and MDD with CMV seropositivity. Overall, apportioning of T cell subpopulations did not differ between CA positive vs negative cases. Conclusions: MDD patients show several signs of a CMV independent "MDD specific" premature T cell aging, such as a CMV independent increase in CD4+ T memory cells and a latent naïve CD4 T-cell reduction and a latent CD8+ T-cell increase. However, these two latent T cell senescence abnormalities only become evident with CMV infection (double hit).