5 research outputs found
Post-traumatic stress disorder: A biopsychosocial case-control study investigating peripheral blood protein biomarkers
Experiencing traumatic events is unfortunately commonplace and, in some cases, may lead to the onset of debilitating mental health disorders, such as post-traumatic stress disorder (PTSD). Current diagnostic criteria for PTSD results in high depression and anxiety comorbidity. Better understanding of biological mechanisms and pathways underlying PTSD could aid in more accurate case identification and stratification of treatments. Recent meta-analysis has identified chronic PTSD to be associated with increased expression of pro-inflammatory cytokines and alterations in neuronal structures which contribute to an overall reduction in brain volume. Despite this, there are currently no biological markers in clinical use to identify PTSD or monitor treatment. This case-control study (n = 40) aimed to identify differences in peripheral blood biomarkers, and biomarker combinations, able to distinguish PTSD participants from controls, and examine in a biopsychosocial framework. The levels of 5/37 biomarkers investigated were significantly altered in the serum of PTSD participants: HDL and LDL cholesterol, tPA, IL-8 and EGF. Biomarkers could be used in combination with psychological criteria, in a biopsychosocial model, to support clinical management decisions and ensure appropriate individual treatment pathways
Somatotypes trajectories during adulthood and their association with COPD phenotypes
Rationale: Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all
characterised by airflow limitation.
Objectives: We hypothesised that somatotype changes – as a surrogate of adiposity – from early adulthood
follow different trajectories to reach distinct phenotypes.
Methods: Using the validated Stunkard’s Pictogram, 356 COPD patients chose the somatotype that best
reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based
trajectory modelling was used to determine somatotype trajectories. We then compared the current
COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory.
Measurements and main results: At 18 years of age, 88% of the participants described having a lean or
medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m−2
) while the other 12% a
heavier somatotype (estimated BMI between 25 and 27 kg·m−2
). From age 18 onwards, five distinct
trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout
adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age
40. Patients with this trajectory were primarily females with low BMI and DLCO (diffusing capacity of the
lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had
significantly lower forced expiratory volume in 1 s (FEV1), DLCO, more emphysema and a worse BODE
(BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss
of tissue (MOLT) phenotype.
Conclusions: COPD patients have distinct somatotype trajectories throughout adulthood. Those with the
MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in
early adulthood deserve particular attention as they seem to develop more severe COPD
Bimodal expression of potential drug target CLL-1 (CLEC12A) on CD34+ blasts of AML patients
Objectives: This study aims to retrospectively assess C-lectin-like molecule 1 (CLL-1) bimodal expression on CD34+ blasts in acute myeloid leukemia (AML) patients (total N = 306) and explore potential CLL-1 bimodal associations with leukemia and patient-specific characteristics.
Methods: Flow cytometry assays were performed to assess the deeper immunophenotyping of CLL-1 bimodality. Cytogenetic analysis was performed to characterize the gene mutation on CLL-1-negative subpopulation of CLL-1 bimodal AML samples.
Results: The frequency of a bimodal pattern of CLL-1 expression of CD34+ blasts ranged from 8% to 65% in the different cohorts. Bimodal CLL-1 expression was most prevalent in patients with MDS-related AML (P = .011), ELN adverse risk (P = .002), NPM1 wild type (WT, P = .049), FLT3 WT (P = .035), and relatively low percentages of leukemia-associated immunophenotypes (P = .006). Additional immunophenotyping analysis revealed the CLL-1- subpopulation may consist of pre-B cells, immature myeloblasts, and hematopoietic stem cells. Furthermore, (pre)-leukemic mutations were detected in both CLL-1+ and CLL-1- subfractions of bimodal samples (N = 3).
Conclusions: C-lectin-like molecule 1 bimodality occurs in about 25% of AML patients and the CLL-1- cell population still contains malignant cells, hence it may potentially limit the effectiveness of CLL-1-targeted therapies and warrant further investigation.
Keywords: CD34+ blasts; CLL-1; acute myeloid leukemia; bimodality; bone marrow aspirates; flow cytometry
Somatotypes trajectories during adulthood and their association with COPD phenotypes
Rationale: Chronic obstructive pulmonary disease (COPD) comprises distinct phenotypes, all
characterised by airflow limitation.
Objectives: We hypothesised that somatotype changes – as a surrogate of adiposity – from early adulthood
follow different trajectories to reach distinct phenotypes.
Methods: Using the validated Stunkard’s Pictogram, 356 COPD patients chose the somatotype that best
reflects their current body build and those at ages 18, 30, 40 and 50 years. An unbiased group-based
trajectory modelling was used to determine somatotype trajectories. We then compared the current
COPD-related clinical and phenotypic characteristics of subjects belonging to each trajectory.
Measurements and main results: At 18 years of age, 88% of the participants described having a lean or
medium somatotype (estimated body mass index (BMI) between 19 and 23 kg·m−2
) while the other 12% a
heavier somatotype (estimated BMI between 25 and 27 kg·m−2
). From age 18 onwards, five distinct
trajectories were observed. Four of them demonstrating a continuous increase in adiposity throughout
adulthood with the exception of one, where the initial increase was followed by loss of adiposity after age
40. Patients with this trajectory were primarily females with low BMI and DLCO (diffusing capacity of the
lung for carbon monoxide). A persistently lean trajectory was seen in 14% of the cohort. This group had
significantly lower forced expiratory volume in 1 s (FEV1), DLCO, more emphysema and a worse BODE
(BMI, airflow obstruction, dyspnoea and exercise capacity) score thus resembling the multiple organ loss
of tissue (MOLT) phenotype.
Conclusions: COPD patients have distinct somatotype trajectories throughout adulthood. Those with the
MOLT phenotype maintain a lean trajectory throughout life. Smoking subjects with this lean phenotype in
early adulthood deserve particular attention as they seem to develop more severe COPD