Small molecule bio-signature in childhood intra-thoracic tuberculosis identified by metabolomics.

The diagnosis of pediatric tuberculosis (TB) remains a major challenge, hence the evaluation of new tools for improved diagnostics is urgently required. We investigated the serum metabolic profile of children with culture-confirmed intra-thoracic TB (ITTB) (n = 23) and compared it with those of non-TB controls (NTCs) (n = 13) using proton NMR spectroscopy-based targeted and untargeted metabolomics approaches. In targeted metabolic profiling, five metabolites (histidine, glycerophosphocholine, creatine/phosphocreatine, acetate, and choline) differentiated TB children from NTCs. Additionally, seven discriminatory metabolites (N-α-acetyl-lysine, polyunsaturated fatty acids, phenylalanine, lysine, lipids, glutamate + glutamine, and dimethylglycine) were identified in untargeted metabolic profiling. The pathway analysis revealed alterations in six metabolic pathways. The altered metabolites were associated with impaired protein synthesis, hindered anti-inflammatory and cytoprotective mechanisms, abnormalities in energy generation processes and membrane metabolism, and deregulated fatty acid and lipid metabolisms in children with ITTB. The diagnostic significance of the classification models obtained from significantly distinguishing metabolites showed sensitivity, specificity, and area under the curve of 78.2%, 84.6%, and 0.86, respectively, in the targeted profiling and 92.3%, 100%, and 0.99, respectively, in the untargeted profiling. Our findings highlight detectable metabolic changes in childhood ITTB; however, further validation is warranted in a large cohort of the pediatric population.

Evaluation of Memory and Language Network in Children and Adolescents with Visual Impairment: A Combined Functional Connectivity and Voxel-based Morphometry Study.

Functional network changes associated with Braille reading are different in early blind (EB) and late blind (LB) participants. The objectives were to study the functional connectivity (of memory and language areas based on blood oxygen level-dependent [BOLD] mapping) and structural changes in EB and LB children and adolescents. A total of 110 participants (all right-handed) were recruited in two age groups of 6-12 years (children) and 13-19 years (adolescents) consisting of EB (n = 20), LB (n = 20), and sighted controls (SC, n = 15) in each group. Group differences were estimated between children and adolescent groups. Structural changes in visual cortex and medial temporal area, increased BOLD activations and altered functional connectivity in the primary visual cortex, inferior frontal gyrus, middle temporal gyrus, and hippocampus during Braille reading task were observed in adolescents as compared with children blind groups (pFDR corrected <0.05). Functional results were positively correlated with duration of Braille reading and age at onset in EB and LB groups (p ≤ 0.01). Visual, language, and learning memory networks were different in adolescents and children of both EB and LB groups, and also between EB and LB groups suggesting cross-modal plasticity. The functional and structural results revealed education dependent cross-modal plasticity in visually impaired participants. Memory and language network were affected more in the LB group than the EB group, and more in children than adolescents.

Magnetic resonance spectroscopy imaging-directed transrectal ultrasound biopsy increases prostate cancer detection in men with prostate-specific antigen between 4-10 ng/mL and normal digital rectal examination.

OBJECTIVES: To evaluate the ability of magnetic resonance spectroscopic imaging to improve prostate cancer detection rate. METHODS: A retrospective analysis was carried out of 278 men with prostate-specific antigen in the range of 4-10 ng/mL and normal digital rectal examination who underwent transrectal ultrasound-guided prostate biopsy. Outcomes were compared between men who had a standard biopsy versus those who also underwent a prebiopsy magnetic resonance spectroscopic imaging. Men with an abnormal voxel on magnetic resonance spectroscopic imaging had standard transrectal ultrasound biopsies plus biopsies directed to the abnormal voxels. RESULTS: The study group (n = 140) and control group (n = 138) were similar in baseline parameters, such as mean age, prostate size and mean prostate-specific antigen. The overall cancer detection in the magnetic resonance spectroscopic imaging positive group (24.4%) was more than double that of the control group (10.1%). On comparing the magnetic resonance spectroscopic imaging results with the transrectal ultrasound biopsy findings, magnetic resonance spectroscopic imaging had 95.6% sensitivity, 41.9% specificity, a positive predictive value of 24.4%, a negative predictive value of 98% and an accuracy of 51.4%. CONCLUSIONS: Magnetic resonance spectroscopic imaging-directed transrectal ultrasound biopsy increases the cancer detection rate compared with standard transrectal ultrasound biopsy in patients with normal digital rectal examination and elevated prostate-specific antigen in the range of 4-10 ng/mL.

In vivo MR spectroscopy for breast cancer diagnosis.

Breast cancer is a significant health concern in females, worldwide. In vivo proton (1H) MR spectroscopy (MRS) has evolved as a non-invasive tool for diagnosis and for biochemical characterization of breast cancer. Water-to-fat ratio, fat and water fractions and choline containing compounds (tCho) have been identified as diagnostic biomarkers of malignancy. Detection of tCho in normal breast tissue of volunteers and in lactating females limits the use of tCho as a diagnostic marker. Technological developments like high-field scanners, multi channel coils, pulse sequences with water and fat suppression facilitated easy detection of tCho. Also, quantification of tCho and its cut-off for objective assessment of malignancy have been reported. Meta-analysis of in vivo 1H MRS studies have documented the pooled sensitivities and the specificities in the range of 71-74% and 78-88%, respectively. Inclusion of MRS has been shown to enhance the diagnostic specificity of MRI, however, detection of tCho in small sized lesions (≤1 cm) is challenging even at high magnetic fields. Potential of MRS in monitoring the effect of chemotherapy in breast cancer has also been reported. This review briefly presents the potential clinical role of in vivo 1H MRS in the diagnosis of breast cancer, its current status and future developments.