Pediatric tuberculosis in Italian children: Epidemiological and clinical data from the Italian register of pediatric tuberculosis

Tuberculosis (TB) is one of the leading causes of death worldwide. Over the last decades, TB has also emerged in the pediatric population. Epidemiologic data of childhood TB are still limited and there is an urgent need of more data on very large cohorts. A multicenter study was conducted in 27 pediatric hospitals, pediatric wards, and public health centers in Italy using a standardized form, covering the period of time between 1 January 2010 and 31 December 2012. Children with active TB, latent TB, and those recently exposed to TB or recently adopted/immigrated from a high TB incidence country were enrolled. Overall, 4234 children were included; 554 (13.1%) children had active TB, 594 (14.0%) latent TB and 3086 (72.9%) were uninfected. Among children with active TB, 481 (86.8%) patients had pulmonary TB. The treatment of active TB cases was known for 96.4% (n = 534) of the cases. Overall, 210 (39.3%) out of these 534 children were treated with three and 216 (40.4%) with four first-line drugs. Second-line drugs where used in 87 (16.3%) children with active TB. Drug-resistant strains of Mycobacterium tuberculosis were reported in 39 (7%) children. Improving the surveillance of childhood TB is important for public health care workers and pediatricians. A non-negligible proportion of children had drug-resistant TB and was treated with second-line drugs, most of which are off-label in the pediatric age. Future efforts should concentrate on improving active surveillance, diagnostic tools, and the availability of antitubercular pediatric formulations, also in low-endemic countries

Anthropometric and glucometabolic changes in an aged mouse model of lipocalin-2 overexpression

Background:: Lipocalin-2 (LCN2) is widely expressed in the organism with pleiotropic roles. In particular, its overexpression correlates with tissue stress conditions including inflammation, metabolic disorders, chronic diseases and cancer. Objectives:: To assess the effects of systemic LCN2 overexpression on adipose tissue and glucose metabolism. Subjects:: Eighteen-month-old transgenic mice with systemic LCN2 overexpression (LCN2-Tg) and age/sex-matched wild-type mice. Methods:: Metabolic cages; histology and real-time PCR analysis; glucose and insulin tolerance tests; ELISA; flow cytometry; microPET and serum analysis. Results:: LCN2-Tg mice were smaller compared to controls but they ate (P = 0.0156) and drank (P = 0.0057) more and displayed a higher amount of visceral adipose tissue. Furthermore, LCN2-Tg mice with body weight 6520 g showed adipocytes with a higher cell area (P < 0.0001) and altered expression of genes involved in adipocyte differentiation and inflammation. In particular, mRNA levels of adipocyte-derived Pparg (P 64 0.0001), Srebf1 (P < 0.0001), Fabp4 (P = 0.056), Tnfa (P = 0.0391), Il6 (P = 0.0198), and Lep (P = 0.0003) were all increased. Furthermore, LCN2-Tg mice displayed a decreased amount of basal serum insulin (P = 0.0122) and a statistically significant impaired glucose tolerance and insulin sensitivity consistent with Slc2a2 mRNA (P 64 0.0001) downregulated expression. On the other hand, Insr mRNA (P 64 0.0001) was upregulated and correlated with microPET analysis that demonstrated a trend in reduced whole-body glucose consumption and MRGlu in the muscles and a significantly reduced MRGlu in brown adipose tissue (P = 0.0247). Nevertheless, an almost nine-fold acceleration of hexokinase activity was observed in the LCN2-Tg mice liver compared to controls (P = 0.0027). Moreover, AST and ALT were increased (P = 0.0421 and P = 0.0403, respectively), which indicated liver involvement also demonstrated by histological staining. Conclusions:: We show that LCN2 profoundly impacts adipose tissue size and function and glucose metabolism, suggesting that LCN2 should be considered as a risk factor in ageing for metabolic disorders leading to obesity

Editorial: Short-Term Versus Long-Term Challenges in Functional Biomaterials Interfacing Living Systems: Two Sides of the Coin

International audienc

Editorial: Short-Term Versus Long-Term Challenges in Functional Biomaterials Interfacing Living Systems: Two Sides of the Coin

International audienc

Zwitterionic Polymer Coated and Aptamer Functionalized Flexible Micro-Electrode Arrays for In Vivo Cocaine Sensing and Electrophysiology

The number of people aged 12 years and older using illicit drugs reached 59.3 million in 2020, among which 5.2 million are cocaine users based on the national data. In order to fully understand cocaine addiction and develop effective therapies, a tool is needed to reliably measure real-time cocaine concentration and neural activity in different regions of the brain with high spatial and temporal resolution. Integrated biochemical sensing devices based upon flexible microelectrode arrays (MEA) have emerged as a powerful tool for such purposes; however, MEAs suffer from undesired biofouling and inflammatory reactions, while those with immobilized biologic sensing elements experience additional failures due to biomolecule degradation. Aptasensors are powerful tools for building highly selective sensors for analytes that have been difficult to detect. In this work, DNA aptamer-based electrochemical cocaine sensors were integrated on flexible MEAs and protected with an antifouling zwitterionic poly (sulfobetaine methacrylate) (PSB) coating, in order to prevent sensors from biofouling and degradation by the host tissue. In vitro experiments showed that without the PSB coating, both adsorption of plasma protein albumin and exposure to DNase-1 enzyme have detrimental effects on sensor performance, decreasing signal amplitude and the sensitivity of the sensors. Albumin adsorption caused a 44.4% sensitivity loss, and DNase-1 exposure for 24 hr resulted in a 57.2% sensitivity reduction. The PSB coating successfully protected sensors from albumin fouling and DNase-1 enzyme digestion. In vivo tests showed that the PSB coated MEA aptasensors can detect repeated cocaine infusions in the brain for 3 hrs after implantation without sensitivity degradation. Additionally, the same MEAs can record electrophysiological signals at different tissue depths simultaneously. This novel flexible MEA with integrated cocaine sensors can serve as a valuable tool for understanding the mechanisms of cocaine addiction, while the PSB coating technology can be generalized to improve all implantable devices suffering from biofouling and inflammatory host responses

Beta-D-Glucan in Patients with Haematological Malignancies

(1-3)-beta-D-glucan (BDG) is an almost panfungal marker (absent in zygomycetes and most cryptococci), which can be successfully used in screening and diagnostic testing in patients with haematological malignancies if its advantages and limitations are known. The aim of this review is to report the data, particularly from the last 5 years, on the use of BDG in haematological population. Published data report mainly on the performance of the Fungitell™ assay, although several others are currently available, and they vary in method and cut-off of positivity. The sensitivity of BDG for invasive fungal disease (IFD) in haematology patients seems lower than in other populations, possibly because of the type of IFD (lower sensitivity was found in case of aspergillosis compared to candidiasis and pneumocystosis) or the use of prophylaxis. The specificity of the test can be improved by using two consecutive positive assays and avoiding testing in the case of the concomitant presence of factors associated with false positive results. BDG should be used in combination with clinical assessment and other diagnostic tests, both radiological and mycological, to provide maximum information. Good performance of BDG in cerebrospinal fluid (CSF) has been reported. BDG is a useful diagnostic method in haematology patients, particularly for pneumocystosis or initial diagnosis of invasive fungal infections

Superior electrochemical performance of carbon nanotubes directly grown on sharp microelectrodes

We report for the first time how coatings made by directly growing carbon nanotubes (CNTs) on the tip of neural microelectrodes outperform others made by electrodeposited CNT composites. Not only do they reduce microelectrode impedance but they also are able to inject high currents without degradation and are stable in time. These results suggest that they are excellent candidates for chronic applications especially when both neural recording and stimulation have to be performed by the same microelectrode. \ua9 2011 American Chemical Society

PEDOT/CNT Flexible MEAs Reveal New Insights into the Clock Gene's Role in Dopamine Dynamics

Abstract Substantial evidence has shown that the Circadian Locomotor Output Cycles Kaput (Clock) gene is a core transcription factor of circadian rhythms that regulates dopamine (DA) synthesis. To shed light on the mechanism of this interaction, flexible multielectrode arrays (MEAs) are developed that can measure both DA concentrations and electrophysiology chronically. The dual functionality is enabled by conducting polymer PEDOT doped with acid‐functionalized carbon nanotubes (CNT). The PEDOT/CNT microelectrode coating maintained stable electrochemical impedance and DA detection by square wave voltammetry for 4 weeks in vitro. When implanted in wild‐type (WT) and Clock mutation (MU) mice, MEAs measured tonic DA concentration and extracellular neural activity with high spatial and temporal resolution for 4 weeks. A diurnal change of DA concentration in WT is observed, but not in MU, and a higher basal DA concentration and stronger cocaine‐induced DA increase in MU. Meanwhile, striatal neuronal firing rate is found to be positively correlated with DA concentration in both animal groups. These findings offer new insights into DA dynamics in the context of circadian rhythm regulation, and the chronically reliable performance and dual measurement capability of this technology hold great potential for a broad range of neuroscience research

3D Fuzzy Graphene Microelectrode Array for Neurotransmitter Sensing at Sub-cellular Spatial Resolution

Dopamine (DA) is a monoamine neurotransmitter involved in the modulation of various physiological brain functions, including learning, motivation, reward, and motor functions. The development of a high sensitivity real-time sensor for multi-site detection of DA with high spatial resolution has critical implications for both neuroscience and clinical communities to improve understanding and treatments of neurological and neuropsychiatric disorders. Here, we present high-surface area out-of-plane grown three-dimensional (3D) fuzzy graphene (3DFG) microelectrode arrays (MEAs) for highly selective, sensitive, and stable DA electrochemical sensing. 3DFG microelectrodes present a remarkable sensitivity to DA (2.87 ± 0.25 nA/nM, withLOD of 990±15 pM), the highest reported for nanocarbon MEAs using Fast Scan Cyclic Voltammetry (FSCV). The high surface area of 3DFG allows for miniaturization of electrode down to 2 x 2 μm^2, without compromising the electrochemical performance. Moreover, 3DFG MEAs are electrochemically stable under 7.2 million scans of continuous FSCV cycling, present exceptional selectivity over the most common interferents in vitro with minimum fouling by electrochemical byproducts, and can discriminate DA and serotonin (5-HT) in response to the injection of their 50:50 mixture. These results highlight the potential of 3DFG MEAs as a promising platform for FSCV based multi-site detection of DA with high sensitivity, selectivity, and spatial resolution.</div