Kayamatthiesen4565
Primary barrier design for linac shielding depends very sensitively on tenth value layer (TVL) data. Inaccuracies can lead to large discrepancies between measured and calculated values of the barrier transmission. Values of the TVL for concrete quoted in several widely used standard references are substantially different than those calculated more recently. The older standard TVL data predict significantly lower radiation levels outside primary barriers than the more recently calculated values under some circumstances. The difference increases with increasing barrier thickness and energy, and it can be as large as a factor of 4 for 18 MV and concrete thickness of 200 cm. This may be due to significant differences in the beam spectra between the earlier and the more recent calculations. Measured instantaneous air kerma rates sometimes show large variations for the same energy and thickness. This may be due to confounding factors such as extra material on, or inside the barrier, variable field size at the barrier, density of concrete, and distal distance from the barrier surface. In some cases, the older TVL data significantly underestimate measured instantaneous air kerma rates, by up to a factor of 3, even when confounding factors are taken into account. This could lead to the necessity for expensive remediation. The more recent TVL values tend to overestimate the measured instantaneous dose rates. Reference TVL data should be computed in a manner that is mathematically consistent with their use in the calculation of air kerma rate outside barriers directly from the linac "dose" rate in MU/min.Some enzymes annotated as squalene synthase catalyze the prenylation of carbazole-3,4-quinone-containing substrates in bacterial secondary metabolism. Their reaction mechanisms remain unclear because of their low sequence similarity to well-characterized aromatic substrate prenyltransferases (PTs). We determined the crystal structures of the carbazole PTs, and these revealed that the overall structure is well superposed on those of squalene synthases. In contrast, the stacking interaction between the prenyl donor and acceptor substrates resembles those observed in aromatic substrate PTs. Structural and mutational analyses suggest that the Ile and Asp residues are essential for the hydrophobic and hydrophilic interactions with the carbazole-3,4-quinone moiety of the prenyl acceptor, respectively, and a deprotonation mechanism of an intermediary σ-complex involving a catalytic triad is proposed. Our results provide a structural basis for a new subclass of aromatic substrate PTs.Biological self-assemblies self- and cross-regulate each other via chemical reaction networks (CRNs) and feedback. Although artificial transient self-assemblies have been realized via activation/deactivation CRNs, the transient structures themselves do mostly not engage in the CRN. We introduce a rational design approach for chemo-structural feedback, and present a transient colloidal co-assembly system, where the formed co-assemblies accelerate their destruction autonomously. We achieve this by immobilizing enzymes of a deactivating acid-producing enzymatic cascade on pH-switchable microgels that can form co-assemblies at high pH. Since the enzyme partners are immobilized on individual microgels, the co-assembled state brings them close enough for enhanced acid generation. The amplified deactivator production (acid) leads to an almost two-fold reduction in the lifetime of the transiently formed pH-state. Our study thus introduces versatile mechanisms for chemo-structural feedback.Quality of life (QoL) assessment is important to evaluate the effect of the intervention for patients treated with home parenteral and enteral nutrition (HPEN). The purpose of this scoping review is to describe, evaluate, and recommend QoL instruments used in adult patients receiving HPEN. We used the Arksey and O'Malley framework and performed literature searches in five databases (PubMed, CINAHL, EMBASE, Web of Science, and Cochrane Library) to identify possibly relevant articles that focused on QoL of adult patients receiving HPEN. Of the studies that qualify for full-text screening, two independent researchers extracted data. Twenty-seven QoL instruments were identified, consisting of seven generic instruments, 12 disease-specific instruments, and eight therapy-specific instruments. The Short Form-36 was the most widely used generic instrument and the European Organization for Research and Treatment of Cancer QLQ-C30 was the most commonly employed disease-specific instrument. The recently developed therapy-specific tools, NutriQoL and HPN-QoL, were increasingly employed in studies either alone or in combination with other types of instruments. Important aspects of each instrument were summarized to aid clinicians and researchers in selecting an appropriate instrument when measuring the QoL of adult HPEN patients. Findings could also help to identify the necessity to develop new tools or to modify pre-existing ones to measure QoL of HPEN patients.Cellular reprogramming through targeting microRNAs (miRNAs) holds promise for regenerative therapy due to their profound regulatory effects in proliferation, differentiation, and function. We hypothesized that transdifferentiation of vascular smooth muscle cells (SMCs) into endothelial cells (ECs) using a miRNA cassette may provide a novel approach for use in vascular disease states associated with endothelial injury or dysfunction. miRNA profiling of SMCs and ECs and iterative combinatorial miRNA transfections of human coronary SMCs revealed a 4-miRNA cassette consisting of miR-143-3p and miR-145-5p inhibitors and miR-146a-5p and miR-181b-5p mimics that efficiently produced induced endothelial cells (iECs). Transcriptome profiling, protein expression, and functional studies demonstrated that iECs exhibit high similarity to ECs. Injected iECs restored blood flow recovery even faster than conventional ECs in a murine hindlimb ischemia model. This study demonstrates that a 4-miRNA cassette is sufficient to reprogram SMCs into ECs and shows promise as a novel regenerative strategy for endothelial repair.
To identify factors that may affect the therapeutic serum magnesium levels after intravenous administration for seizure prophylaxis in pre-eclamptic patients.
One hundred and two women with PE with severe features were identified categorized into two groups subtherapeutic and therapeutic group. Multivariate logistic regression analysis and receiver operation characteristic curve analysis were conducted for the risk factors influencing the serum magnesium concentration.
Among 102 eligible patients, 63 (62%) patients did not attain ideal therapeutic serum magnesium levels. Those patients had elevated albumin levels (p<0.05), higher creatinine clearance (Ccr) (p<0.001), and higher body mass index (BMI) (p<0.001). Logistic regression analysis identified BMI and Ccr as independent risk factors for subtherapeutic serum magnesium concentration (p<0.05). MI-503 Receiver operating characteristic (ROC) curve analysis revealed a greater area under the curve for BMI than for Ccr in predicting subtherapeutic serum magnesium levels (0.787 vs. 0.774).
Maternal body weight and renal function were independent risk factors for subtherapeutic serum magnesium concentration in the early stage after administration.
Maternal body weight and renal function were independent risk factors for subtherapeutic serum magnesium concentration in the early stage after administration.Tumor associated macrophages (TAMs) suppress the cancer immune response and are a key target for immunotherapy. The effects of ruthenium and rhodium complexes on TAMs have not been well characterized. To address this gap in the field, a panel of 22 dirhodium and ruthenium complexes were screened against three subtypes of macrophages, triple-negative breast cancer and normal breast tissue cells. Experiments were carried out in 2D and biomimetic 3D co-culture experiments with and without irradiation with blue light. Leads were identified with cell-type-specific toxicity toward macrophage subtypes, cancer cells, or both. Experiments with 3D spheroids revealed complexes that sensitized the tumor models to the chemotherapeutic doxorubicin. Cell surface exposure of calreticulin, a known facilitator of immunogenic cell death (ICD), was increased upon treatment, along with a concomitant reduction in the M2-subtype classifier arginase. Our findings lay a strong foundation for the future development of ruthenium- and rhodium-based chemotherapies targeting TAMs.With survival outcomes ever improving for patients with a wide range of lymphoma histologies, the focus on reducing long-term complications of therapy has increased. Recently published, complimentary population and retrospective series have highlighted the importance of considering bone health in patients treated for lymphoma. Fracture-related events or the requirement for secondary bone prophylaxis, likely linked to glucocorticoid-induced osteoporosis (GIO) are substantial and clinically meaningful in a significant minority of patients following routinely employed steroid-containing immunochemotherapy. In this review, we describe the pathophysiology of GIO, the risk of GIO in observational front-line lymphoma studies and efficacy of prophylactic measures from several prospective clinical trials are summarized. Finally, areas of importance for future research are discussed and recommendations for GIO risk assessment and management in lymphoma are provided based on the current available literature.
Attaining active glenohumeral external rotation (aGHER), whether via primary reconstruction or spontaneous recovery, is infrequent in patients with neonatal brachial plexus palsy (NBPI). We evaluated the effectiveness of triceps-to-teres minor motor branch transfers to restore this function, both performed primarily (i.e., in conjunction with microsurgical plexus reconstruction) or secondarily (after primary surgery has failed to restore aGHER).
This was a retrospective study of 12 children with NBPI undergoing triceps-to-teres minor motor branch transfer via an axillary approach, six undergoing primary surgery and six secondary. The primary outcome was post-operative restoration of aGHER in abduction. The primary-surgery group consisted of six children of mean age 8 months (range 5-11) with partial injuries ranging from C5-C6 to C5-C8. The secondary-surgery group included six patients with C5-C6 injuries of mean age 43 months (range 23-120), undergoing re-operation a mean 40 months (range 18-116) after their primary surgery.
No complications occurred after surgery. At a mean follow-up of 22 months (range 14-30), aGHER in abduction only was restored in one patient in the primary group while in the secondary group, aGHER in abduction was restored in all patients to a mean 73° (range 70-80) after a mean follow-up of 16 months (range 6-26).
Triceps-to-teres minor motor branch transfer is not indicated as primary surgery for NBPI. However, they can be effective in children in whom primary surgery has failed to restore aGHER, even if the spinal accessory nerve is unavailable for transfer to the infraspinatus motor branch.
Triceps-to-teres minor motor branch transfer is not indicated as primary surgery for NBPI. However, they can be effective in children in whom primary surgery has failed to restore aGHER, even if the spinal accessory nerve is unavailable for transfer to the infraspinatus motor branch.