The globus pallidus internus (GPi) has been the primary target for deep brain stimulation (DBS) to treat severe medication-refractory dystonia. Some patients with primary cervical or segmental ...dystonia develop subtle bradykinesia occurring in previously nondystonic body regions during GPi DBS. Subthalamic nucleus (STN) DBS may provide an alternative target choice for treating dystonia, but has only been described in a few short reports, without blinded rating scales, statistical analysis, or detailed neuropsychological studies.
In this prospective pilot study, we analyzed the effect of bilateral STN DBS on safety, efficacy, quality of life, and neuropsychological functioning in 9 patients with medically refractory primary cervical dystonia. Severity of dystonia was scored by a blinded rater (unaware of the patient's preoperative or postoperative status) using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) preoperatively and 3, 6, and 12 months postsurgery. Lead location, medications, and adverse events were also measured.
STN DBS was well-tolerated with no serious adverse effects. The TWSTRS total score improved (p < 0.001) from a mean (±SEM) of 53.1 (±2.57), to 19.6 (±5.48) at 12 months. Quality of life measures were also improved. STN DBS induced no consistent neuropsychological deficits. Several patients reported depression in the study and 3 had marked weight gain. No patients developed bradykinetic side effects from stimulation, but all patients developed transient dyskinetic movements during stimulation.
This prospective study showed that bilateral STN DBS resulted in improvement in dystonia and suggests that STN DBS may be an alternative to GPi DBS for treating primary cervical dystonia.
This study provides Class III evidence that bilateral subthalamic nucleus deep brain stimulation results in significant improvement in cervical dystonia without bradykinetic side effects.
Ten borylated bipyridines (BOBIPYs) have been synthesized and selected structural modifications have been made that allow useful structure–optical property relationships to be gathered. These systems ...have been further investigated using DFT calculations and spectroscopic measurements, showing blue to green fluorescence with quantum yields up to 41 %. They allow full mapping of the structure to determine where selected functionalities can be implemented, to tune the optical properties or to incorporate linking groups. The best derivative was thus functionalised with an alkyne linker, which would enable further applications through click chemistry and in this optic, the stability of the fluorophores has been evaluated.
Lighting the way: A family of borylated bipyridines (BOBIPYs) fluorophores offers tunable optical properties and linker possibilities via a designed strategy of synthesis. The photophysical properties of these compounds have been measured, and the results interrogated by DFT calculations, enabling the mapping of the structure for further implementations.
Bone tissue is highly vascularized. The crosstalk of vascular and osteogenic cells is not only responsible for the formation of the strongly divergent tissue types but also for their physiological ...maintenance and repair. Extrusion-based bioprinting presents a promising fabrication method for bone replacement. It allows for the production of large-volume constructs, which can be tailored to individual tissue defect geometries. In this study, we used the all-gelatin-based toolbox of methacryl-modified gelatin (GM), non-modified gelatin (G) and acetylated GM (GMA) to tailor both the properties of the bioink towards improved printability, and the properties of the crosslinked hydrogel towards enhanced support of vascular network formation by simple blending. The vasculogenic behavior of human dermal microvascular endothelial cells (HDMECs) and human adipose-derived stem cells (ASCs) was evaluated in the different hydrogel formulations for 14 days. Co-culture constructs including a vascular component and an osteogenic component (i.e. a bone bioink based on GM, hydroxyapatite and ASCs) were fabricated via extrusion-based bioprinting. Bioprinted co-culture constructs exhibited functional tissue-specific cells whose interplay positively affected the formation and maintenance of vascular-like structures. The setup further enabled the deposition of bone matrix associated proteins like collagen type I, fibronectin and alkaline phosphatase within the 30-day culture.
Introduction:
Ecological momentary assessment (EMA) has shown that smoking behavior is linked to transient variables in the smoker’s immediate context. Such research suggests that daily hassles ...(e.g., losing one’s keys) may be more likely to lead to cigarette craving and eventual lapse than infrequent, large-scale stressors (e.g., death of a loved one) among individuals attempting to quit smoking. However, individual differences in distress tolerance (DT) may moderate the relationship between daily hassles and daily cigarette craving during a quit attempt.
Methods:
A sample of 56 veterans and community members drawn from a larger smoking-cessation study completed structured interviews and paper-and-pencil questionnaires during an initial laboratory visit and, directly following a quit attempt, were monitored via EMA. Multilevel modeling was used to examine the relationship between daily hassles and daily cigarette craving and to determine whether DT moderated this relationship.
Results:
Daily hassles were positively associated with daily cigarette craving, and this association was moderated by individual differences in DT, such that the lower one’s DT, the stronger the relationship between daily hassles and daily cigarette craving. This model explained 13% of the intraindividual variability and 8% of the interindividual variability in daily cigarette craving.
Conclusions:
Smoking-cessation interventions may be strengthened by targeting smokers’ individual responses to contextual factors, such as by helping smokers develop skills to cope more effectively with distress prior to and during the quit phase.
Deep brain stimulation (DBS) of the globus pallidus internus (GPI) is a promising new procedure for the treatment of dystonia. The authors describe their technical approach for placing electrodes ...into the GPI in awake patients with dystonia, including methodology for electrophysiological mapping of the GPI in the dystonic state, clinical outcomes and complications, and the location of electrodes associated with optimal benefit.
Twenty-three adult and pediatric patients with various forms of dystonia were included in this study. Baseline neurological status and DBS-related improvement in motor function were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The implantation of DBS leads was performed using magnetic resonance (MR) imaging-based stereotaxy, single-cell microelectrode recording, and intraoperative test stimulation to determine thresholds for stimulation-induced adverse effects. Electrode locations were measured on computationally reformatted postoperative MR images according to a prospective protocol.
Physiologically guided implantation of DBS electrodes in patients with dystonia was technically feasible in the awake state in most patients, and the morbidity rate was low. Spontaneous discharge rates of GPI neurons in dystonia were similar to those of globus pallidus externus neurons, such that the two nuclei must be distinguished by neuronal discharge patterns rather than rates. Active electrode locations associated with robust improvement (> 70% decrease in BFMDRS score) were located near the intercommissural plane, at a mean distance from the pallidocapsular border of 3.6 mm.
Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment — e.g., with letrozole. ...Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment.
The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor–positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points.
Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use.
CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.
•Pain levels of myalgia/limb pain and arthralgia increase under letrozole intake.•Within one year pain levels increase in both, CAM users as well as non-CAM users.•In CAM users pain levels were higher at all time points than in non-CAM users.•The greatest increase of pain levels was noted in the first six treatment months.•CAM does not prevent or improve the development of myalgia/limb pain and arthralgia.
Nucleation of particles with sulfuric acid, water, and nitrogeneous bases was studied in a flow reactor. Sulfuric acid and water levels were set by flows over sulfuric acid and water reservoirs, ...respectively, and the base concentrations were determined from measured permeation rates and flow dilution ratios. Particle number distributions were measured with a nano‐differential‐mobility‐analyzer system. Results indicate that the nucleation capability of NH3, methylamine, dimethylamine, and trimethylamine with sulfuric acid increases from NH3 as the weakest, methylamine next, and dimethylamine and trimethylamine the strongest. Three other bases were studied, and experiments with triethylamine showed that it is less effective than methylamine, and experiments with urea and acetamide showed that their capabilities are much lower than the amines with acetamide having basically no effect. When both NH3 and an amine were present, nucleation was more strongly enhanced than with just the amine present. Comparisons of nucleation rates to predictions and previous experimental work are discussed, and the sulfuric acid‐base nucleation rates measured here are extrapolated to atmospheric conditions. The measurements suggest that atmospheric nucleation rates are significantly affected by synergistic interactions between ammonia and amines.
Key Points
Sulfuric acid nucleation with bases strongly depend on the type of base
When both an amine and ammonia are present, nucleation is enhanced
Only weak effects were observed with amides
Firemaster 550 (FM550) is an additive flame retardant formulation of brominated and aryl phosphate ester (APE) components introduced as a major replacement product for the commercial polybrominated ...diphenyl ether mixture (known as PentaBDE) used primarily in polyurethane foam. However, little is known about the potential effects of FM550-based ingredients during early vertebrate development. Therefore, we first screened the developmental toxicity of each FM550 component using zebrafish as an animal model. Based on these initial screening assays, we found that exposure to the brominated components as high as 10µM resulted in no significant effects on embryonic survival or development, whereas exposure to triphenyl phosphate (TPP) or mono-substituted isopropylated triaryl phosphate (mono-ITP)-two APEs comprising almost 50% of FM550-resulted in targeted effects on cardiac looping and function during embryogenesis. As these cardiac abnormalities resembled aryl hydrocarbon receptor (AHR) agonist-induced phenotypes, we then exposed developing embryos to TPP or mono-ITP in the presence or absence of an AHR antagonist (CH223191) or AHR2-specific morpholino. Based on these studies, we found that CH223191 blocked heart malformations following exposure to mono-ITP but not TPP, whereas AHR2 knockdown failed to block the cardiotoxic effects of both components. Finally, using a cell-based human AHR reporter assay, we found that mono-ITP (but not TPP) exposure resulted in a significant increase in human AHR-driven luciferase activity at similar nominal concentrations as a potent reference AHR agonist (β-naphthoflavone). Overall, our findings suggest that two major APE components of FM550 induce severe cardiac abnormalities during early vertebrate development.
Anthocyanin accumulation is coordinated in plants by a number of conserved transcription factors. In apple (Malus × domestica), an R2R3 MYB transcription factor has been shown to control fruit flesh ...and foliage anthocyanin pigmentation (MYB10) and fruit skin color (MYB1). However, the pattern of expression and allelic variation at these loci does not explain all anthocyanin-related apple phenotypes. One such example is an open-pollinated seedling of cv Sangrado that has green foliage and develops red flesh in the fruit cortex late in maturity. We used methods that combine plant breeding, molecular biology, and genomics to identify duplicated MYB transcription factors that could control this phenotype. We then demonstrated that the red-flesh cortex phenotype is associated with enhanced expression of MYBllOa, a paralog of MYB10. Functional characterization of MYB110a showed that it was able to up-regulate anthocyanin biosynthesis in tobacco (Nicotiana tabacum). The chromosomal location of MYB110a is consistent with a whole-genome duplication event that occurred during the evolution of apple within the Maloideae family. Both MYB10 and MYB110a have conserved function in some cultivars, but they differ in their expression pattern and response to fruit maturity.
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