Improving Breast Cancer Treatment Specificity Using Aptamers Obtained by 3D Cell-SELEX

Three-dimensional spheroids of non-malignant MCF10A and malignant SKBR3 breast cells were used for subsequent 3D Cell-SELEX to generate aptamers for specific binding and treatment of breast cancer cells. Using 3D Cell-SELEX combined with Next-Generation Sequencing and bioinformatics, ten abundant aptamer families with specific structures were identified that selectively bind to SKBR3, and not to MCF10A cells. Multivalent aptamer polymers were synthesized by co-polymerization and analyzed for binding performance as well as therapeutic efficacy. Binding performance was determined by confocal fluorescence imaging and revealed specific binding and efficient internalization of aptamer polymers into SKBR3 spheroids. For therapeutic purposes, DNA sequences that intercalate the cytotoxic drug doxorubicin were co-polymerized into the aptamer polymers. Viability tests show that the drug-loaded polymers are specific and effective in killing SKBR3 breast cancer cells. Thus, the 3D-selected aptamers enhanced the specificity of doxorubicin against malignant over non-malignant breast cells. The innovative modular DNA aptamer platform based on 3D Cell SELEX and polymer multivalency holds great promise for diagnostics and treatment of breast cancer

Total Joint Replacement in the Past Does Not Relate to a Deteriorated Functional Level and Health Status in the Oldest Old

Total hip or knee replacement is effective in improving joint function, quality of life, and pain reduction. The oldest old population with joint replacements (TJR) is underrepresented in current literature. We compared health-related and functional characteristics of oldest olds with and without TJR. Participants (aged 85 years) were divided into a group with and without TJR. Comorbidity, physical and joint functioning, daily living activities, quality of life, and mortality were recorded. Thirty-eight of 599 participants (6.3%) received a TJR in the past. Participants with a TJR had slightly less comorbidities, walked slower (P = 0.006), and complained more about hip-pain (P = 0.007). Mortality of those with a TJR was lower during the first 8-year followup (P = 0.04). All other characteristics were comparable between groups. We conclude that subjects with a TJR performed equally well, besides showing a lower gait speed and a higher frequency of hip-pain. Except for the lower gaitspeed, having a TJR is not associated with poorer health

Newer long-acting insulin prescriptions for patients with type 2 diabetes: Prevalence and practice variation in a retrospective cohort study

BACKGROUND: Little is known about prescription patterns of expensive non-recommended newer long-acting insulins (glargine 300 U/mL and degludec) for patients with type 2 diabetes mellitus (T2DM). AIM: To identify practice variation in, and practice- and patient-related characteristics associated with, the prescription of newer long-acting insulins to patients with T2DM in primary care. DESIGN AND SETTING: A retrospective cohort study in Dutch general practices (Nivel Primary Care Database). METHOD: A first prescription for intermediate or long-acting insulins in 2018 was identified in patients aged ≥40 years using other T2DM drugs. Per practice, the median percentage and interquartile range (IQR) of patients with newer insulin prescriptions were calculated. Multilevel logistic regression models were constructed to calculate intraclass correlation coefficients (ICCs) and quantify the association of patient and practice characteristics with prescriptions for newer insulins (odds ratios [ORs] and 95% confidence intervals [CIs]). RESULTS: In total, 7757 patients with prescriptions for intermediate or long-acting insulins from 282 general practices were identified. A median percentage of 21.2% (IQR 12.5–36.4%) of all patients prescribed intermediate or long-acting insulins per practice received a prescription for newer insulins. After multilevel modelling, the ICC decreased from 20% to 19%. Female sex (OR 0.77, 95% CI = 0.69 to 0.87), age ≥86 years compared with 40–55 years (OR 0.22, 95% CI = 0.15 to 0.34), prescriptions for metformin (OR 0.66, 95% CI = 0.53 to 0.82), sulfonylurea (OR 0.58, 95% CI = 0.51 to 0.66), or other newer T2DM drugs (OR 3.10, 95% CI = 2.63 to 3.66), and dispensing practices (OR 1.78, 95% CI = 1.03 to 3.10) were associated with the prescription of newer insulins. CONCLUSION: The inter-practice variation in the prescription of newer insulins is large and could only be partially explained by patient- and practice-related differences. This indicates substantial opportunities for improvement

Can the PROPER intervention reduce psychotropic drug prescription in nursing home residents with dementia?:Results of a cluster-randomized controlled trial

Objectives:To evaluate the effect of the PROPER intervention in nursing home residents with dementia on the prevalence of psychotropic drug use and neuropsychiatric symptoms.Design:A cluster-randomized controlled design with two parallel groups (intervention versus usual care) and assessments at 0, 6, 12, and 18 months.Setting:Thirty-one dementia special care units within 13 long-term care organizations in the Netherlands.Participants:Three hundred eighty nursing home residents with dementiaIntervention:The PROPER intervention consisted of a structured and repeated multidisciplinary medication review, supported by education and continuous evaluation.Measurements:Prescriptions of antipsychotics, antidepressants, anxiolytics, and hypnotics, and occurrence of neuropsychiatric symptoms.Results:The prescription of any type of psychotropic drugs increased in the intervention group, and decreased in the control group, with an estimated difference of 3.9 percentage points per 6 months (p = 0.01). Effects for the individual drug groups were minor (differences of 1.6 percentage points and below per 6 months) and not statistically significant. The occurrence of neuropsychiatric symptoms remained stable in both the intervention and control groups during the follow-up of 18 months.Conclusions:The PROPER intervention failed to demonstrate effectiveness in reducing the prevalence of psychotropic drugs. It may be interesting to enrich the intervention with components that address personal attitudes and communication between nursing home professionals, not only with respect to the prescription of psychotropic drugs, but also to neuropsychiatric symptoms

Low-temperature structural model of hcp solid C70_{70}

We report intermolecular potential-energy calculations for solid C_${70}$ and determine the optimum static orientations of the molecules at low temperature; we find them to be consistent with the monoclinic structural model proposed by us in an earlier report [Solid State Commun. {\bf 105), 247 (1998)]. This model indicates that the C_5 axis of the molecule is tilted by an angle $\approx$18^o from the monoclinic b axis in contrast with the molecular orientation proposed by Verheijen {\it et al.} [J. Chem. Phys. {\bf 166}, 287 (1992)] where the C_5 axis is parallel to the monoclinic b axis. In this calculation we have incorporated the effective bond charge Coulomb potential together with the Lennard-Jones potential between the molecule at the origin of the monoclinic unit cell and its six nearest neighbours, three above and three below. The minimum energy configuration for the molecular orientations turns out to be at $\theta$=18^o, $\phi$=8^o, and $\psi$=5^o, where $\theta$, $\phi$, and $\psi$ define the molecular orientations.Comment: ReVTeX (4 pages) + 2 PostScript figure

Improving psychotropic drug prescription in nursing home patients with dementia:design of a cluster randomized controlled trial

Background: Neuropsychiatric symptoms are highly prevalent in nursing home patients with dementia. Despite modest effectiveness and considerable side effects, psychotropic drugs are frequently prescribed for these neuropsychiatric symptoms. This raises questions whether psychotropic drugs are appropriately prescribed. The aim of the PROPER (PRescription Optimization of Psychotropic drugs in Elderly nuRsing home patients with dementia) II study is to investigate the efficacy of an intervention for improving the appropriateness of psychotropic drug prescription in nursing home patients with dementia.Methods/design: The PROPER II study is a multi-center cluster randomized controlled, pragmatic trial using parallel groups. It has a duration of eighteen months and four six-monthly assessments. Six nursing homes will participate in the intervention and six will continue care as usual. The nursing homes will be located throughout the Netherlands, each participating with two dementia special care units with an average of fifteen patients per unit, resulting in 360 patients. The intervention consists of a structured and repeated multidisciplinary medication review supported by education and continuous evaluation. It is conducted by pharmacists, physicians, and nurses and consists of three components: 1) preparation and education, 2) conduct, and 3) evaluation/guidance. The primary outcome is the proportion of patients with appropriate psychotropic drug use. Secondary outcomes are the overall frequency of psychotropic drug use, neuropsychiatric symptoms, quality of life, activities of daily living, psychotropic drug side effects and adverse events (including cognition, comorbidity, and mortality). Besides, a process analysis on the intervention will be carried out.Discussion: This study is expected to improve the appropriateness of psychotropic drug prescription for neuropsychiatric symptoms in nursing home patients with dementia by introducing a structured and repeated multidisciplinary medication review supported by education and continuous evaluation.</p

Performing a knee arthroscopy among patients with degenerative knee disease:one-third is potentially low value care

PURPOSE: The purpose of this study was to assess in which proportion of patients with degenerative knee disease aged 50+ in whom a knee arthroscopy is performed, no valid surgical indication is reported in medical records, and to explore possible explanatory factors. METHODS: A retrospective study was conducted using administrative data from January to December 2016 in 13 orthopedic centers in the Netherlands. Medical records were selected from a random sample of 538 patients aged 50+ with degenerative knee disease in whom arthroscopy was performed, and reviewed on reported indications for the performed knee arthroscopy. Valid surgical indications were predefined based on clinical national guidelines and expert opinion (e.g., truly locked knee). A knee arthroscopy without a reported valid indication was considered potentially low value care. Multivariate logistic regression analysis was performed to assess whether age, diagnosis ("Arthrosis" versus "Meniscal lesion"), and type of care trajectory (initial or follow-up) were associated with performing a potentially low value knee arthroscopy. RESULTS: Of 26,991 patients with degenerative knee disease, 2556 (9.5%) underwent an arthroscopy in one of the participating orthopedic centers. Of 538 patients in whom an arthroscopy was performed, 65.1% had a valid indication reported in the medical record and 34.9% without a reported valid indication. From the patients without a valid indication, a joint patient-provider decision or patient request was reported as the main reason. Neither age [OR 1.013 (95% CI 0.984-1.043)], diagnosis [OR 0.998 (95% CI 0.886-1.124)] or type of care trajectory [OR 0.989 (95% CI 0.948-1.032)] were significantly associated with performing a potentially low value knee arthroscopy. CONCLUSIONS: In a random sample of knee arthroscopies performed in 13 orthopedic centers in 2016, 65% had valid indications reported in the medical records but 35% were performed without a reported valid indication and, therefore, potentially low value care. Patient and/or surgeons preference may play a large role in the decision to perform an arthroscopy without a valid indication. Therefore, interventions should be developed to increase adherence to clinical guidelines by surgeons that target invalid indications for a knee arthroscopy to improve care. LEVEL OF EVIDENCE: IV

1H and 13C resonance assignments of a guanine sensing riboswitch’s terminator hairpin

Here we report the nearly complete base assignments and partial sugar assignments of the 35-residue terminator hairpin of the Bacillus subtilisxpt-pbuX-mRNA guanine sensing riboswitch

Polyethylene thickness is a risk factor for wear necessitating insert exchange

PURPOSE: The aim of this observational study was to investigate the optimal minimal polyethylene (PE) thickness in total knee arthroplasty (TKA) and identify other risk factors associated with revision of the insert due to wear. METHODS: A total of 84 TKA were followed for 11-16 years. All patients received the same prosthesis design (Interax; Howmedica/ Stryker) with halfbearings: separate PE-inserts medially and laterally. Statistical analysis comprised Cox-regression to correct for confounding. RESULTS: Eight knees (9.5%) had been revised due to thinning inserts and an additional patient is scheduled for revision. PE thickness, diagnosis, BMI and weight are risk factors for insert exchange. For each millimetre decrease in PE thickness, the risk of insert exchange increases 3.0 times, which remains after correction for age, gender, weight, diagnosis and femoral-tibial angle. Insert exchange was 4.73 times more likely in OA-patients compared to RA-patients. For every unit increase in BMI and weight the risk for insert exchange increases 1.40 times and 1.14 times, respectively. CONCLUSIONS: In conclusion we therefore advise against the use of thin PE inserts in modular TKA and recommend PE inserts with a minimal 8-mm thickness.Optimising joint reconstruction management in arthritis and bone tumour patient

Environmental consciousness in the Netherlands

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