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Learning intermolecular causes at liquid-vapor user interfaces.
CONCLUSIONS This large prospective study showed that surgical treatment for spinal metastases significantly improved the HRQOL.The high-resolution X-ray crystal structures of the adducts formed between the "half sandwich"-type Ru(II) coordination compound [RuII(1,4,7-trithiacyclononane)(ethane-1,2-diamine)Cl]+ and two proteins, namely hen egg-white lysozyme and proteinase K, are presented. Apoptosis activator The structures unveil that upon reaction with both enzymes the Ru(II) compound is coordinated by solvent-exposed aspartate residues after releasing the chloride ligand (Asp101 in lysozyme, Asp200 and Asp260 in proteinase K), while retaining the two chelating ligands. The adduct with Asp101 residue at the catalytic cleft of lysozyme is accompanied by residue-specific conformational changes to accommodate the Ru(II) fragment, whereas the complexes bound at the two calcium-binding sites of proteinase K revealed minimal structural perturbation of the enzyme. To the best of our knowledge, proteinase K is used here for the first time as a model system of protein metalation and these are the first X-ray crystal structures of protein adducts of a Ru(II) coordination compound that maintains its coordination sphere almost intact upon binding. Our data demonstrate the role of ligands in stabilizing the protein adducts via hydrophobic/aromatic or hydrogen-bonding interactions, as well as their underlying role in the selection of specific sites on the electrostatic potential surface of the enzymes.We have made a systematic combined quantum mechanical and molecular mechanical (QM/MM) investigation of possible structures of the N2 bound state of nitrogenase. We assume that N2 is immediately protonated to a N2H2 state, thereby avoiding the problem of determining the position of the protons in the cluster. We have systematically studied both end-on and side-on structures, as well as both HNNH and NNH2 states. Our results indicate that the binding of N2H2 is determined more by interactions and steric clashes with the surrounding protein than by the intrinsic preferences of the ligand and the cluster. The best binding mode with both the TPSS and B3LYP density-functional theory methods has trans-HNNH terminally bound to Fe2. It is stabilised by stacking of the substrate with His-195 and Ser-278. However, several other structures come rather close in energy (within 3-35 kJ/mol) at least in some calculations The corresponding cis-HNNH structure terminally bound to Fe2 is second best with B3LYP. A structure with HNNH2 terminally bound to Fe6 is second most stable with TPSS (where the third proton is transferred to the substrate from the homocitrate ligand). Structures with trans-HNNH, bound to Fe4 or Fe6, or cis-HNNH bound to Fe6 are also rather stable. Finally, with the TPSS functional, a structure with cis-HNNH side-on binding to the Fe3-Fe4-Fe5-Fe7 face of the cluster is also rather low in energy, but all side-on structures are strongly disfavoured by the B3LYP method.PURPOSE Progress in radiation therapy of head and neck squamous cell carcinomas (HNSCCs) is logically linked to the development of molecular predictors that would help to enhance individually tailored treatment. MicroRNA (miRNA) expression profiles in tumors have repeatedly been tested to optimize the molecular diagnostics of HNSCC. In addition to tumor tissues, miRNAs are stably present in body fluids, including saliva, and can thus be collected non-invasively. The aim of our current study was to evaluate whether salivary miRNAs have potential as response predictors in HNSCC patients treated with intensity modulated radiation therapy (IMRT). METHODS In total 48 HNSCC patients treated by definitive IMRT were enrolled in our prospective study. To identify predictive salivary miRNAs, we used small RNA sequencing in 14 saliva samples of HNSCC patients and qRT-PCR validation of selected miRNA candidates in an independent set of 34 patients. RESULTS We found that salivary miR-15a-5p and miR-15b-5p exhibited differential levels between patients with and without complete remission (p = 0.025 and p = 0.028, respectively). Subsequent Kaplan-Meier analysis confirmed that patients with higher levels of miR-15a-5p reached a significantly longer locoregional progression-free survival (LPFS) than those with low levels (p = 0.024). Finally, multivariate Cox regression analysis revealed that miR-15a-5p may serve as an independent predictive biomarker of LPFS in HNSCC patients treated with IMRT (HR 0.104; 95% CI 0.004-0.911; p = 0.04). CONCLUSIONS We conclude that salivary miR-15a-5p may represent a potential biomarker for individualized treatment decision-making in HNSCC patients.Background Concurrent opioid and benzodiazepine use ("double-threat") and opioid, benzodiazepine, and muscle relaxant use ("triple-threat") are linked to increased adverse events compared to opioid use alone. Objectives To assess prevalence of double-threat and triple-threat in the US and to measure association between double- and triple-threat and emergency department visits. Setting Nationally representative, 2-year health database of the United States. Method A retrospective cohort study was conducted using the national medical expenditure panel survey. Two-year prevalence of combination use was measured. Association between 2013-2014 double- and triple-threat exposure and emergency department visit compared to non-users, opioid-users, and all other exposure combinations assessed using logistic regression. Main outcome measures Survey-weighted prevalence of triple-threat and double-threat in 2013 and 2014 was measured. The outcome variable of at least one emergency department visit in a study year was utilse increased probability of emergency department visit. Amplified efforts in surveillance, prescribing, and default follow-up for concurrent opioid, benzodiazepine, muscle relaxant use are needed to reduce this public health concern.Background Assessing and satisfying patient expectation are essential in successful patient-centered communication. Recognizing the gap between patient expectation and perception during pharmacist-patient communication can help to identify communication problems and suggest ways to improve communication. link2 Objective To evaluate the gap between patient expectation and perception of sharing information and communications skills during pharmacist-patient communication. Setting Community pharmacies in South Korea. Method A questionnaire was developed to collect expectation and perception of sharing information and communication skills. Items for sharing information included drug effect, dosage/route of administration, adverse drug reactions, storage, drug-drug interactions, drug-food interactions, managing a missed dose or overdose, co-medication, and past drug allergies. Communication skills included friendliness, expertise, easy language, emphasis on main content, confirmation of understanding, enough time, calm ug interaction, and past drug allergies (all, median 2). Gap scores were negatively associated with age 50-59 years, ≥ 60 years, and presence of ≥ 1 chronic illness. Patient perception of communication skills, especially regarding private space, were poor. Conclusions The information shared with pharmacists was significantly less than that expected by participants, and most pharmacist communication skills were evaluated as poor. Understanding the expectation of each patient and communicating accordingly with appropriate communication skills are necessary to improve patient-centered communication in community pharmacies.PURPOSE The complexity and severity of rare genetic conditions pose substantial burden to families. While the importance of spillovers on carers' health in resource allocation decisions is increasingly recognised, there is significant lack of empirical evidence in the context of rare diseases. The objective of this study was to estimate the health spillovers of paediatric rare genetic conditions on parents. METHODS Health-related quality-of-life (HRQoL) data from children with rare genetic conditions (genetic kidney diseases, mitochondrial diseases, epileptic encephalopathies, brain malformations) and their parents were collected using the CHU9D and SF-12 measures, respectively. We used two approaches to estimate parental health spillovers. To quantify the 'absolute health spillover', we matched our parent cohort to the Australian general population. To quantify the 'relative health spillover', regression models were applied using the cohort data. RESULTS Parents of affected children had significantly lower HRQoL compared to matched parents in the general public (- 0.06; 95% CIs - 0.08, - 0.04). link3 Multivariable regression demonstrated a positive association between parental and child health. The mean magnitude of HRQoL loss in parents was estimated to be 33% of the HRQoL loss observed in children (95% CIs 21%, 46%). CONCLUSION Paediatric rare genetic conditions appear to be associated with substantial parental health spillovers. This highlights the importance of including health effects on family members and caregivers into economic evaluation of genomic technologies and personalised medicine. Overlooking spillover effects may undervalue the benefits of diagnosis and management in this context. This study also expands the knowledge of family spillover to the rare disease spectrum.BACKGROUND Atrial fibrillation (AF) affects millions of people worldwide and can remain undiagnosed for years. It is a major cause of cerebrovascular stroke (CVS); hence, early detection is extremely important in order to decrease the risk of CVS. We conducted a retrospective observational study looking into the prevalence of silent AF in 3299 patients admitted from January 2014 to December 2017 in a tertiary care stroke specialized center. Ischemic CVS was confirmed either by using multislice computed tomography (MSCT) or magnetic resonance imaging (MRI) of the brain. AF was diagnosed by electrocardiography (ECG) at the time of admission or during the hospital stay. Patients with a history of AF were excluded from the study. RESULTS Of the 3299 patients admitted by acute ischemic CVS, 707 (21.43%) had a history of AF and thus were excluded from the study. Of the remaining 2592 patients eligible for the study, 1666 (64.27%) were males with a mean age of 56.06 years (± 16.01). A total of 2313 (89.24%) patients remained in sinus rhythm throughout the hospital stay, 211 (8.14%) patients were in AF on admission, and 68 (2.62 %) patients developed AF during their hospital stay. The total number of newly diagnosed patients with AF was 279 (10.76%). CONCLUSION The prevalence of de novo atrial fibrillation in patients presented with acute cerebrovascular stroke is high. The implementation of good screening programs can significantly reduce the risk of disabilities and morbidities.Hydrocephalus (HC) can be associated with vestibular schwannoma (VS) at presentation. Although spontaneous resolution of HC after VS removal is reported, first-line treatment is varied including preoperative ventriculoperitoneal (VP) shunt, external ventricular drainage (EVD), or lumbar drainage (LD). We performed a systematic review to clarify optimal management of HC associated with VS at presentation, as well as characteristics of patients with initial and persistent HC after VS removal, and prevalence of HC associated with VS. Fourteen studies were included. Patients were grouped according to the timing of HC treatment. The overall rate of VP shunts was 19.4%. Among patients who received VS removal as first-line treatment, 6.9% underwent permanent shunts. In a subgroup of 132 patients (studies with no-aggregate data), t test analysis for mean tumor size (P = 0.02) and mean CSF protein level (P  less then  0.001) demonstrated statistically significant differences between patients with resolved HC (3.48 cm and 201 mg/dL) and patients with persistent HC (2.
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