Biomarkers

Plasma-based diagnostics are ideal for detecting a variety of diseases because they offer a method of detection that is minimally invasive, readily available, and easy to use for monitoring patients as they progress through a disease or respond to treatment. The only serum marker for PDAC is CA19-9 which lacks specificity, has limited sensitivity, and is unreliable for early detection. It is therefore of great importance to develop a diagnostic that is viable for screening and early detection. Exosomal miRNA were determined via bioinformatics analyses and then examined in PDAC cell lines to identify markers with greatest potential. These markers were then examined in plasma from PDAC patients and control groups. Four markers, miR-93-5p, miR-339-3p, miR-425-5p, and miR-425-3p, emerged as the most viable biomarker panel with the ability to detect PDAC in 100% of the early stages (N=5) compared to CA19-9 which showed increased levels in only one patient with early stage PDAC. Additionally, the diagnostic has a specificity of 80% and a sensitivity of 94.7%, making it comparable to CA19-9, and may even be beneficial for use in conjunction with CA19-9.
A plasma-based diagnostic was also developed for multi-strain HIV-1 detection utilizing the loop-mediated isothermal amplification (LAMP) method. LAMP primers were developed against the integrase and vpr regions of the HIV-1 genome. They were tested first in cultured HIV samples and then examined for their ability to amplify HIV-1 subtypes A-G. The integrase primer set provided a reliable means of diagnosing all 55 strains and isolates in under 30 minutes, whereas vpr was inconsistent and exhibited high variability in detecting the HIV subtypes. Our limit of detection for B-subtype with integrase was 30 viral copies/reaction. This could provide the basis for a novel, point-of-care diagnostic for use in underdeveloped regions.

Objective: Our main objectives were to identify cognitive markers of progression to a more severe cognitive diagnosis, explore possible differences between ethnic groups and to correlate cognitive markers of progression with biomarkers of AD (hippocampal and entorhinal volumes) and frontal volumes (lateral orbitofrontal, medial orbitofrontal, superior frontal, and rostral middle frontal volumes). Method: 207 participants (Mage = 71.79, SD = 7.48, 123 Hispanic Americans [HA]) were followed for an average of 23 months. Participants were classified into 3 diagnostic groups (Cognitively normal [CN], mild cognitive impairment [MCI], or dementia) based on the CDR global score and the neuropsychological baseline data was used as predictors of progression status. For the CN group, the Benson Figure delayed recall was a predictor of cognitive decline, and within the MCI group, the Benson delayed recall, the HVLT immediate recall, the TMTB, category fluency, and three measures of the LASSI-L (A1 cued recall, A2 cued recall, and delayed recall) were significant predictors of progression to dementia and are suggested as cognitive markers of progression for MCI individuals. Memory cognitive markers and category fluency correlated with medial temporal lobe volumes, and the TMT-B correlated with superior frontal volume. We did not observe significant differences in cognitive markers across ethnic groups. Conclusion: we identified cognitive markers of progression for CN and for MCI diagnoses which were not different across ethnic groups. These findings contribute to literature on the early identification of individuals at risk of progression to a more severe cognitive status even within asymptomatic individuals which can facilitate a more time- and cost-effective practice that is essential to the provision of the appropriate treatment to those at higher risk of progression.

This study examined the acute and chronic responses of brain-derived neurotrophic factor (BDNF), cathepsin B (CatB), insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) and if changes in these biomarkers were correlated during resistance training. Fourteen resistance trained men performed resistance training 3 days per week for 6 weeks in two groups. The only difference between groups was the proximity to failure of each set (4-6 repetitions in reserve or 1-3 repetitions in reserve). Serum was collected immediately before and after training on day 1 of weeks 1 and 6.
There were no significant group interactions for any of the biomarkers assessed, there were no main effects for time (p>0.05), and no significant correlations were observed between any of the biomarkers. However, a significant main effect for exercise for BDNF (p=0.03) and IL-6 (p=0.003) was observed. For CatB, a significant exercise × time (p=0.002) interaction was observed, indicating differences in the acute change of CatB in week 6 (+15.78%; g=0.25) vs. week 1 (-7.46%; g=0.13). In summary, these results suggest that multi-joint resistance exercise far from failure can confer a BDNF response. This investigation is the first to demonstrate the potential for acute resistance exercise to elicit a transient increase in CatB.

This study examined if multi-joint resistance exercises could elicit expression of biomarkers associated with neuroprotection. Thirteen well-trained males performed 4 sets to failure at 80% of a one-repetition maximum (1RM) on the back squat, bench press, and deadlift. The biomarkers measured immediately pre- and post-exercise were brain derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), cathepsin B (CatB), and interleukin 6 (IL-6). There was a main time effect (p<0.01) for BDNF with significant increases in the deadlift (p=0.01) and bench press (p=0.01) conditions, but not the squat (p=0.21). There was a main time effect (p<0.01) for IL-6 with a significant increase in the squat (p<0.01). There was no significant increase in CatB or IGF-1 (p>0.05). Additionally, there was no significant relationship between BDNF and IL-6 response.