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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., (© 2023 John Wiley & Sons Ltd.)

Background: Health and social care services are under strain providing care in the community particularly at hospital discharge. Patient and carer experiences can inform and shape services., Objective: To develop service user-led recommendations enabling smooth transition for people living with memory loss from acute hospital to community., Design: Lead and co-researchers conducted semi-structured interviews with 15 pairs of carers and patients with memory loss at discharge, 6 and 12 weeks post-discharge and one semi-structured interview with health and social care professionals and Admiral Nurses. Framework analysis was guided by co-researchers. Two focus groups of study participants, facilitated by co-researchers, met to shape and finalize recommendations., Setting and Participants: Recruitment took place in acute hospitals in two National Health Service (NHS) Trusts in England. Patients were aged 65 and over, with memory loss, an in-patient for at least 1 week returning to the community, who had a carer consenting to be in the study., Results: Poor delivery of services caused considerable stress to some study families living with memory loss. Three key recommendations included a need for a written, mutually agreed discharge plan, a named coordinator of services, and improved domiciliary care services., Discussion and Conclusions: Vulnerable patients with memory loss find coming out of hospital after an extended period a stressful experience. The SHARED study contributes to understanding the hospital discharge process through the eyes of the patient and carer living with memory loss and has the potential to contribute to more efficient use of resources and to improving health outcomes in communities., (© 2016 The Authors. Health Expectations Published by John Wiley & Sons Ltd.)

The intracellular bacterial pathogen Coxiella burnetii is a category B select agent that causes human Q fever. In vivo, C. burnetii targets alveolar macrophages wherein the pathogen replicates in a lysosome-like parasitophorous vacuole (PV). In vitro, C. burnetii infects a variety of cultured cell lines that have collectively been used to model the pathogen's infectious cycle. However, differences in the cellular response to infection have been observed, and virulent C. burnetii isolate infection of host cells has not been well defined. Because alveolar macrophages are routinely implicated in disease, we established primary human alveolar macrophages (hAMs) as an in vitro model of C. burnetii-host cell interactions. C. burnetii pathotypes, including acute disease and endocarditis isolates, replicated in hAMs, albeit with unique PV properties. Each isolate replicated in large, typical PV and small, non-fused vacuoles, and lipid droplets were present in avirulent C. burnetii PV. Interestingly, a subset of small vacuoles harboured single organisms undergoing degradation. Prototypical PV formation and bacterial growth in hAMs required a functional type IV secretion system, indicating C. burnetii secretes effector proteins that control macrophage functions. Avirulent C. burnetii promoted sustained activation of Akt and Erk1/2 pro-survival kinases and short-termphosphorylation of stress-related p38. Avirulent organisms also triggered a robust, early pro-inflammatory response characterized by increased secretion of TNF-α and IL-6, while virulent isolates elicited substantially reduced secretion of these cytokines. A corresponding increase in pro- and mature IL-1β occurred in hAMs infected with avirulent C. burnetii, while little accumulation was observed following infection with virulent isolates. Finally, treatment of hAMs with IFN-γ controlled intracellular replication, supporting a role for this antibacterial insult in the host response to C. burnetii. Collectively, the current results demonstrate the hAM model is a human disease-relevant platform for defining novel innate immune responses to C. burnetii., (© 2012 John Wiley & Sons Ltd.)

The association of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status of breast cancer patients with total choline (tCho) concentration and tumor volume was investigated using in vivo proton magnetic resonance spectroscopy and MRI at 1.5 T. Values for tCho concentration were determined in 120 locally advanced breast cancer patients (stages IIB, IIIA, IIIB, and IIIC), 31 early breast cancer patients (stage IIA), 38 patients with benign lesions, and 37 controls. Significantly higher tCho concentration and lower tumor volume were observed in early breast cancer patients compared to locally advanced breast cancer patients (P<0.05). tCho concentration and tumor volume did not correlate with age and menstruation. tCho cutoff values were obtained for the differentiation of malignant from benign breast tissues (2.54 mmol/kg); malignant versus normal (1.45 mmol/kg) and benign versus normal tissues (0.82 mmol/kg). Estrogen receptor negative patients showed significantly larger tumor volumes, indicating higher angiogenesis with aggressive tumor behavior. Nontriple negative and triple positive patients had a significantly higher tCho concentration compared to triple negative patients (P<0.05), indicating complex molecular mechanism of cell proliferation and the molecular heterogeneity of breast lesions. The results indicate the potential use of integration of breast 1H magnetic resonance spectroscopy in diagnostic workup., (Copyright © 2011 Wiley Periodicals, Inc.)

MRI and in vivo MRS have rapidly evolved as sensitive tools for diagnosis and therapeutic monitoring in cancer research. In vivo MRS provides information on tumor metabolism, which is clinically valuable in the diagnosis and assessment of tumor response to therapy for the management of women with breast diseases. Several centers complement breast MRI studies with (1)H MRS to improve the specificity of diagnosis. Malignant breast tissues show elevated water-to-fat ratio and choline-containing compounds (total choline, tCho), and any effect of therapy on tissue viability or metabolism will be manifested as changes in these levels. Sequential (1)H MRS studies have shown significantly reduced tCho levels during the course of therapy in patients who were responders. However, there are challenges in using in vivo MRS because of the relatively low sensitivity in detecting the tCho resonance with decreased lesion size or significant reduction in the tumor volume during therapy. MRS is also technically challenging because of the low signal-to-noise ratio and heterogeneous distribution of fat and glandular tissues in the breast. MRS is best utilized for the diagnosis of focal masses, most commonly seen in patients with ductal-type neoplasms; however, it has limitations in detecting nonfocal masses, such as the linear pattern of tumors seen in invasive lobular carcinoma. Further work is required to assess the clinical utility of quantitative MRS, with the goal of automation, which will reduce the subjectivity currently inherent in both qualitative and semi-quantitative MRS., (Copyright © 2011 John Wiley & Sons, Ltd.)

A new class of redox-switched anthraquinone derived lariat ethers 1-(1-anthraquinonyloxy) 3, 6, 9 trioxaundecane 11-ol (M(1)), 1-(1-anthraquinonyloxy) 3, 6 dioxaoctane 9-ol (M(2)), 1-(1-anthraquinonyloxy) 3 oxapentane 5-ol (M(3)), 1-(1-anthraquinonyloxy) 3 oxapentane 5-butane (M(4)), 1-(1-anthraquinonyloxy) 3, 6 dioxaoctane 9-methane (M(5)) and 1-(1-anthraquinonyloxy) 3 oxapentane 5-methane (M(6)) have been synthesized and characterized by spectral analysis. These ionophores were used in liquid membrane carrier facilitated transport of main group metal cations across supported liquid membrane (SLM). Cellulose nitrate membrane was used as membrane support. Effect of various parameters such as variation in concentration of metal as well as ionophore, effect of chain length and end group of ionophore have been studied. The sequence of metal ions transported by ionophore M(1) is Na(+) > Li(+) > K(+) > Ca(2+) > Mg(2+) and the order of metal ions transported by ionophores (M(2)-M(6)) is Li(+) > Na(+) > K(+) > Ca(2+) > Mg(2+). Ionophore M(1) is selective for Na(+), Li(+), and K(+) and ionophores (M(2)-M(6)) are selective for Li(+) and Na(+).

The metabolic differences between the muscle biopsies of patients with limb girdle muscular dystrophy (LGMD) and normal controls were characterized using high-resolution 1H and 13C NMR spectroscopy. In all, 44 metabolites were unambiguously assigned in the perchloric acid extracts of skeletal muscle tissue, using 2D double quantum filtered (DQF COSY), total correlation (TOCSY), and 1H/13C heteronuclear multiple quantum coherence (HMQC) spectroscopy. The concentrations of glycolytic substrate, glucose (p=0.03), gluconeogenic amino acids, glutamine (p=0.02) and alanine (p=0.009) together with glycolytic product, lactate (p=0.04), were found to be significantly lowered in LGMD patients as compared with controls. The reduction in the concentration of glucose may be attributed to the decrease in the concentration of gluconeogenic amino acids in the degenerated muscle. Reduction in the rate of anaerobic glycolysis and lowered substrate concentration appear to be the possible reasons for the decrease in the concentration of lactate. A significant reduction in the concentration of choline in LGMD patients was also observed compared with controls. Lower concentration of choline may be the result of decreased rate of membrane turnover in LGMD patients. The data presented here provide an insight into the potentials of in-vitro NMR spectroscopy in the study of muscle metabolism., (Copyright 2003 John Wiley & Sons, Ltd.)