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Nagpal, A.

Publications and source records attributed to Nagpal, A..

4 recordsLinked to original sources

Neuroimaging signature associated with symptom exacerbation in early-stage psychosis

Recent reports have indicated that the occurrence of symptom exacerbation in early-stage psychosis could result in brain changes. Such a symptom exacerbation is frequently called relapse, which underlies a poorer disease outcome. Thus, it is important to identify neuroimaging alterations that are specifically seen in patients who experience relapse in early-stage psychosis. We hypothesized that this specific patient group may be more homogenous in disease-associated signatures likely to be linked to relapse, compared with the overall patient group. Such sub-stratified patient group and neuroimaging signatures would be useful for the biological understanding of relapse. To address this goal, we conducted a cross-sectional study (85 patients with early-stage psychosis and 94 healthy controls) with the use of medical records in a retrospective manner. To define the specific sub-group with the past experience of relapse, we used hospitalization due to psychotic symptom exacerbation, according to many publications that used this factor as a proxy for relapse. By examining resting-state functional connectivity (FC) for the study subjects, we validated our hypothesis and defined 131 FCs possibly associated with relapse. Through these studies, 3 brain regions (the thalamus, precentral gyrus, and dorsal anterior cingulate cortex) were underscored.

neuroscience↗

A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy, from a first episode psychosis cohort that includes 138 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a significant reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a significant reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC GSH, HP and SFG volumes, and age at onset could potentially be trait biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.

neuroscience↗

Resonance Raman spectra for the in-situ identification of bacteria strains and their inactivation

The resonance Raman spectra of bacterial carotenoids have been employed to identify bacterial strains and their intensity changes as a function of ultraviolet(UV) radiation dose have been used to differentiate between live and dead bacteria. The enhanced resonance Raman spectra of color-pigmented bacteria were recorded after excitation with visible light diode lasers. In addition, the resonance enhanced Raman spectra enabled us to detect bacteria in water at much lower concentrations (~108 cells/mL) than normally detected spectroscopically. A handheld spectrometer capable of recording resonance Raman spectra in-situ was designed, constructed and was used to record the spectra. In addition to bacteria, the method presented in this paper may also be used to identify fungi, viruses and plants, in-situ, and detect infections within a very short period of time.

biophysics↗

An engineered monomer binding-protein for α-synucleinefficiently inhibits the proliferation of amyloid fibrils

Removing or preventing the formation of -synuclein aggregates is a plausible strategy against Parkinsons disease. To this end we have engineered the {beta}-wrapin AS69 to bind monomeric -synuclein with high affinity. In cultured cells, AS69 reduced the occurrence of -synuclein oligomers and of visible -synuclein aggregates. In flies, AS69 reduced -synuclein aggregates and the locomotor deficit resulting from -synuclein expression in neuronal cells. In a mouse model based on the intracerebral injection of pre-formed -synuclein seed fibrills (PFFs), AS69 co-injection reduced the density of dystrophic neurites observed three months later. In biophysical experiments in vitro, AS69 highly sub-stoichiometrically inhibited auto-catalytic secondary nucleation processes, even in the presence of a large excess of monomer. We present evidence that the AS69--synuclein complex, rather than the free AS69, is the inhibitory species responsible for sub-stoichiometric inhibition. These results represent a new paradigm that high affinity monomer binders can be strongly sub-stoichiometric inhibitors of nucleation processes.

bioengineering↗