The distribution of boron in biological samples coming from BNCT protocols can be determined by the analysis of autoradiographic images formed by nuclear tracks on polymeric detectors. The tissue ...section is first explored to delimit regions of interest (ROIs), and then it is removed in order to reveal nuclear tracks through an etching process. A quantitative autoradiographic technique was developed to measure the boron concentration in the sample by counting the nuclear tracks on the detector. However, under certain circumstances, rapid measurements of boron distribution are required. For that purpose, a methodology was developed, allowing a rapid and easy determination of boron concentration and distribution in a tissue section by measuring grey levels in the corresponding high fluence autoradiographic image (HFA). The grey levels are then converted to optical density values which are then correlated with boron concentration values. In order to validate the technique, consecutive sections of several tissue samples were analyzed by the conventional counting method and by HFA. The image analysis and boron concentration estimation can be carried out in under 15 min, and relative differences between zones can be easily determined.
Alcohol use disorder (AUD) is a brain disorder associated with high rates of mortality and morbidity worldwide. Baclofen, a selective gamma-aminobutyric acid-B (GABA-B) receptor agonist, has emerged ...as a promising drug for AUD. The use of this drug remains controversial, in part due to uncertainty regarding dosing and efficacy, alongside concerns about safety. To date there have been 15 randomized controlled trials (RCTs) investigating the use of baclofen in AUD; three using doses over 100 mg/day. Two additional RCTs have been completed but have not yet been published. Most trials used fixed dosing of 30-80 mg/day. The other approach involved titration until the desired clinical effect was achieved, or unwanted effects emerged. The maintenance dose varies widely from 30 to more than 300 mg/day. Baclofen may be particularly advantageous in those with liver disease, due to its limited hepatic metabolism and safe profile in this population. Patients should be informed that the use of baclofen for AUD is as an "off-label" prescription, that no optimal fixed dose has been established, and that existing clinical evidence on efficacy is inconsistent. Baclofen therapy requires careful medical monitoring due to safety considerations, particularly at higher doses and in those with comorbid physical and/or psychiatric conditions. Baclofen is mostly used in some European countries and Australia, and in particular, for patients who have not benefitted from the currently used and approved medications for AUD.
Abstract Background The importance of quality-of-life (QoL) research has been recognised over the past two decades in patients with head and neck (H&N) cancer. The aims of this systematic review are ...to evaluate the QoL status of H&N cancer survivors one year after treatment and to identify the determinants affecting their QoL. Methods Pubmed, Medline, Scopus, Sciencedirect and CINAHL (2000–2011) were searched for relevant studies, and two of the present authors assessed their methodological quality. The characteristics and main findings of the studies were extracted and reported. Results Thirty-seven studies met the inclusion criteria, and the methodological quality of the majority was moderate to high. While patients of the group in question recover their global QoL by 12 months after treatment, a number of outstanding issues persist – deterioration in physical functioning, fatigue, xerostomia and sticky saliva. Age, cancer site, stage of disease, social support, smoking, feeding tube placement and alcohol consumption are the significant determinants of QoL at 12 months, while gender has little or no influence. Conclusions Regular assessments should be carried out to monitor physical functioning, degree of fatigue, xerostomia and sticky saliva. Further research is required to develop appropriate and effective interventions to deal with these issues, and thus to promote the patients’ QoL.
Calcium phosphate (CaPO4) tubes with features comparable to mineralized biological microstructures, such as Haversian canals, were grown from a calcium gel/phosphate solution chemical garden system. ...A significant difference in gel mass in response to high and low solute phosphate equivalent environments existed within 30 min of solution layering upon gel (p = 0.0067), suggesting that the nature of advective movement between gel and solution is dependent on the solution concentration. The transport of calcium cations (Ca2+) and phosphate anions (PO4 3–) was quantified and changes in pH were monitored to explain the preferential formation of tubes within a PO4 3– concentration range of 0.5–1.25 M. Ingress from the anionic solution phase into the gel followed by the liberation of Ca2+ ions from the gel was found to be essential for acquiring self-assembled tubular CaPO4 structures. Tube analysis by scanning electron microscopy (SEM), X-ray diffraction (XRD), and micro X-ray florescence (μ-XRF) revealed hydroxyapatite (HA, Ca10(PO4)6(OH)2) and dicalcium phosphate dihydrate (DCPD, CaHPO4·2H2O) phases organized in a hierarchical manner. Notably, the tubule diameters ranged from 100 to 150 μm, an ideal size for the permeation of vasculature in biological hard tissue.
In recent years, there has been a major paradigm shift in the management of non-small cell lung cancer (NSCLC). NSCLC should now be further sub-classified by histology and driver mutation if one is ...known or present. Translational research advances now allow such mutations to be inhibited by either receptor monoclonal antibodies (mAb) or small molecule tyrosine kinase inhibitors (TKI). Whilst empirical chemotherapy with a platinum-doublet remains the gold standard for advanced NSCLC without a known driver mutation, targeted therapy is pushing the boundary to significantly improve patient outcomes and quality of life. In this review, we will examine the major subtypes of oncogenic drivers behind NSCLC as well as the development of targeted agents available to treat them both now and in the foreseeable future.
The potassium-chloride co-transporter KCC2, encoded by SLC12A5, plays a fundamental role in fast synaptic inhibition by maintaining a hyperpolarizing gradient for chloride ions. KCC2 dysfunction has ...been implicated in human epilepsy, but to date, no monogenic KCC2-related epilepsy disorders have been described. Here we show recessive loss-of-function SLC12A5 mutations in patients with a severe infantile-onset pharmacoresistant epilepsy syndrome, epilepsy of infancy with migrating focal seizures (EIMFS). Decreased KCC2 surface expression, reduced protein glycosylation and impaired chloride extrusion contribute to loss of KCC2 activity, thereby impairing normal synaptic inhibition and promoting neuronal excitability in this early-onset epileptic encephalopathy.
Background. An inability to perform tasks involving reaching is a common problem following stroke. Evidence supports the use of robotic therapy and functional electrical stimulation (FES) to reduce ...upper limb impairments, but current systems may not encourage maximal voluntary contribution from the participant because assistance is not responsive to performance. Objective. This study aimed to investigate whether iterative learning control (ILC) mediated by FES is a feasible intervention in upper limb stroke rehabilitation. Methods. Five hemiparetic participants with reduced upper limb function who were at least 6 months poststroke were recruited from the community. No participants withdrew. Intervention. Participants undertook supported tracking tasks using 27 different trajectories augmented by responsive FES to their triceps brachii muscle, with their hand movement constrained in a 2-dimensional plane by a robot. Eighteen 1-hour treatment sessions were used with 2 participants receiving an additional 7 treatment sessions. Outcome measures. The primary functional outcome measure was the Action Research Arm Test (ARAT). Impairment measures included the upper limb Fugl— Meyer Assessment (FMA), tests of motor control (tracking accuracy), and isometric force. Results. Compliance was excellent and there were no adverse events. Statistically significant improvements were measured (P ≤ .05) in FMA motor score, unassisted tracking for 3 out of 4 trajectories, and in isometric force over 5 out of 6 directions. Changes in ARAT were not statistically significant. Conclusion. This study has demonstrated the feasibility of using ILC mediated by FES for upper limb stroke rehabilitation.
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