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The strong association between lipoprotein (a) [Lp(a)] and atherosclerotic cardiovascular disease has led to considerations of Lp(a) being a potential target for mitigating residual cardiovascular risk. While approximately 20 % of the population has an Lp(a) level greater than 50 mg/dL, there are no currently available pharmacological lipid-lowering therapies that have demonstrated substantial reduction in Lp(a). Novel therapies to lower Lp(a) include antisense oligonucleotides and small-interfering ribonucleic acid molecules and have shown promising results in phase 2 trials. Phase 3 trials are currently underway and will test the causal relationship between Lp(a) and ASCVD and whether lowering Lp(a) reduces cardiovascular outcomes. In this review, we summarize emerging insights related to Lp(a)'s role as a risk-enhancing factor for ASCVD, association with calcific aortic stenosis, effects of existing therapies on Lp(a) levels, and variations amongst patient populations. The evolving therapeutic landscape of emerging therapeutics is further discussed., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RB reports consulting/advisory fees from Amgen, and Novartis. MG reports consulting fees from BMS, Aepha, Horizon Therapeutics, Kiniksa Pharmaceuticals Corp. BW reports advisory/consulting from Novo Nordisk, BMS, Aepha, Horizon Therapeutics, and Kiniksa Pharmaceuticals., (© 2024 The Authors. Published by Elsevier B.V.)

The aim of the study was to investigate how the fine particle content of lactose carriers prepared with different types of lactose fines regulates dry powder inhaler (DPI) formulation performance of a cohesive batch of micronised budesonide. Budesonide formulations (0.8 wt%) were prepared with three different lactose carriers (Lactohale (LH) LH100, 20 wt% LH210 in LH100 and 20 wt% LH300 in LH100). Fine particle fraction of emitted dose (FPFED) and mean mass aerodynamic diameter (MMAD) of budesonide was assessed with a Next Generation Impactor (NGI) using a Cyclohaler at 90 l/min. Morphological and chemical characteristics of particles deposited on Stage 2 were determined using a Malvern Morphologi G3-ID. The results indicate that increasing concentration of lactose fines (<4.5 μm) not only increased the FPFED but also the MMAD of budesonide, suggesting drug deposition in agglomerates. Presence of agglomerates on Stage 2 was confirmed by morphological analysis of particles. Raman analysis of material collected on Stage 2 indicated that the more fine lactose particles were available the more agglomerates of budesonide and lactose were delivered to Stage 2. These results suggest drug-fines agglomerate formation is an important mechanism for how lactose fines improve and regulate DPI formulation performance., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objectives: Laboratory tests are usually requested for monitoring during outpatient parenteral antimicrobial therapy (OPAT), but these recommendations are not always followed. The purpose of this study was to determine whether rehospitalization during the OPAT course is associated with the availability of these test results to the treating physician., Methods: Electronic health records (EHRs) from all patients in the Cleveland Clinic OPAT registry with start dates from 1 January to 28 February 2011 were reviewed in a retrospective cohort study. Comprehensive data on patient and OPAT characteristics were obtained for the first OPAT course per patient. Availability of laboratory test results was defined as documentation of results of at least one recommended test in the health system's EHR. Proportions of patients rehospitalized were compared for OPAT courses with test results available and non-available. Adjustments were made for patient age, hospital length of stay, anticipated OPAT duration, OPAT site and Charlson comorbidity index score., Results: Four hundred patients received OPAT during the study period; 60% at home, 36% in skilled nursing facilities or long-term acute care facilities and 4% in other settings. Recommended monitoring laboratory test results were available to infectious disease physicians in 291 (73%) OPAT episodes. There were 82 patient readmissions (21%) while on OPAT. In a multivariable logistic regression model, non-availability of recommended test results was independently associated with readmissions while on OPAT (adjusted OR 2.53; 95% CI 1.36-4.73)., Conclusions: Non-availability of recommended test results to treating physicians for patients on OPAT is associated with increased readmissions during OPAT.

How myosin 10, an unconventional myosin, walks processively along actin is still controversial. Here, we used single molecule fluorescence techniques, TIRF and FIONA, to study the motility and the stepping mechanism of dimerized myosin 10 heavy-meromyosin-like fragment on both single actin filaments and two-dimensional F-actin rafts cross-linked by fascin or α-actinin. As a control, we also tracked and analyzed the stepping behavior of the well characterized processive motor myosin 5a. We have shown that myosin 10 moves processively along both single actin filaments and F-actin rafts with a step size of 31 nm. Moreover, myosin 10 moves more processively on fascin-F-actin rafts than on α-actinin-F-actin rafts, whereas myosin 5a shows no such selectivity. Finally, on fascin-F-actin rafts, myosin 10 has more frequent side steps to adjacent actin filaments than myosin 5a in the F-actin rafts. Together, these results reveal further single molecule features of myosin 10 on various actin structures, which may help to understand its cellular functions.

Fifty elderly Catholic nuns from the Midwest were interviewed in a descriptive study to obtain information regarding affectivity and mental health. Lawton's Philadelphia Geriatric Center affectivity instrument was used to determine frequency of positive versus negative emotions and 10 dimensions of affectivity. Overall, these subjects reported positive emotional experiences to be more common than negative ones. The nuns were shown to be strongest in the affectivity dimensions of duration of feelings, affective dissimulation, and emotional adaptation. They scored lowest on sensation seeking, variability of feelings, and emotional maturity. The mean scores of these subjects demonstrated statistically stronger emotional experiences than did Lawton's subjects. In response to an open-ended question on definition of health, evidence of a multidimensional perception of health was present among these elderly nuns. This research provides the foundation for further work designing and implementing interventions aimed at promoting optimal mental health among members of cultural minority groups.

A description of a 26-year-old patient who had hearing difficulties, progressive nephropathy, and conus of the lens in both eyes is given. The ERG was below normal and the EOG remained normal. About the same time the nephropathy affliction occurred, a ringed abscess appeared in the left eye. Afterwards it healed with a scar, but half a year later the same affliction appeared in the right eye.