Factor Analysis of Patients Who Find Tablets or Capsules Difficult to Swallow Due to Their Large Size: Using the Personal Health Record Infrastructure of Electronic Medication Notebooks.

BACKGROUND: Understanding patient preference regarding taking tablet or capsule formulations plays a pivotal role in treatment efficacy and adherence. Therefore, these preferences should be taken into account when designing formulations and prescriptions. OBJECTIVE: This study investigates the factors affecting patient preference in patients who have difficulties swallowing large tablets or capsules and aims to identify appropriate sizes for tablets and capsules. METHODS: A robust data set was developed based on a questionnaire survey conducted from December 1, 2022, to December 7, 2022, using the harmo smartphone app operated by harmo Co, Ltd. The data set included patient input regarding their tablet and capsule preferences, personal health records (including dispensing history), and drug formulation information (available from package inserts). Based on the medication formulation information, 6 indices were set for each of the tablets or capsules that were considered difficult to swallow owing to their large size and concomitant tablets or capsules (used as controls). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of each index. The index demonstrating the highest area under the curve of the ROC was selected as the best index to determine the tablet or capsule size that leads to swallowing difficulties. From the generated ROCs, the point with the highest discriminative performance that maximized the Youden index was identified, and the optimal threshold for each index was calculated. Multivariate logistic regression analysis was performed to identify the risk factors contributing to difficulty in swallowing oversized tablets or capsules. Additionally, decision tree analysis was performed to estimate the combined risk from several factors, using risk factors that were significant in the multivariate logistic regression analysis. RESULTS: This study analyzed 147 large tablets or capsules and 624 control tablets or capsules. The "long diameter + short diameter + thickness" index (with a 21.5 mm threshold) was identified as the best indicator for causing swallowing difficulties in patients. The multivariate logistic regression analysis (including 132 patients with swallowing difficulties and 1283 patients without) results identified the following contributory risk factors: aged <50 years (odds ratio [OR] 1.59, 95% CI 1.03-2.44), female (OR 2.54, 95% CI 1.70-3.78), dysphagia (OR 3.54, 95% CI 2.22-5.65), and taking large tablets or capsules (OR 9.74, 95% CI 5.19-18.29). The decision tree analysis results suggested an elevated risk of swallowing difficulties for patients with taking large tablets or capsules. CONCLUSIONS: This study identified the most appropriate index and threshold for indicating that a given tablet or capsule size will cause swallowing difficulties, as well as the contributory risk factors. Although some sampling biases (eg, only including smartphone users) may exist, our results can guide the design of patient-friendly formulations and prescriptions, promoting better medication adherence.

ERECTA-family receptor kinases regulate stem cell homeostasis via buffering its cytokinin responsiveness in the shoot apical meristem.

Shoot apical meristems (SAMs), which are maintained at the tips of stems, are indeterminate structures and sources of stem cells from which all aerial organs are ultimately derived. Although mechanisms that regulate the homeostasis of the stem cells have been extensively investigated, identification of further unknown regulators should provide better understanding of the regulation. Here, we report that members of the Arabidopsis ERECTA (ER) receptor kinase family redundantly play a significant role in the regulation of stem cell homeostasis. In wild-type seedlings, the expression of WUSCHEL (WUS), a central regulator of the stem cell population, is stimulated by cytokinin. Interestingly, however, the SAM morphology and the expression of CLAVATA3 (CLV3), which is expressed in stem cells and therefore serves as a stem cell marker, are relatively stable against cytokinin treatment regardless of increased WUS expression. These findings indicate the presence of a mechanism to buffer stem cell homeostasis against an increase in cytokinin. Mutant seedlings lacking all ER-family members, which are expressed in the SAM, show an increase in the stem cell population and also the up-regulation of a cytokinin-responsive gene in the SAM. In this mutant, WUS expression is stimulated by cytokinin treatment as efficiently as in wild-type plants. However, in contrast to wild-type plants, SAM morphology and CLV3 expression respond drastically to cytokinin treatment, suggesting that the buffering mechanism to maintain stem cell homeostasis against an increase in cytokinin is severely impaired in this mutant. We suggest that the ER family regulates stem cell homeostasis via buffering its cytokinin responsiveness in the SAM.

Modulation of the balance between stem cell proliferation and consumption by ERECTA-family genes.

Stem cells in the vegetative shoot apical meristem proliferate to produce more stem cells (self-renewal) and are simultaneously consumed to form leaf promordia. Therefore, to keep a stable number of stem cells, regulation of the balance between their proliferation and consumption is important. Recently we reported that stem cell population is increased in mutant plants lacking the entire ERECTA (ER) receptor kinase family. Here we describe that loss of function of the entire ER-family causes a decrease in leaf number in spite of the increase in stem cell population. This suggests that stem cell consumption might be decreased in the mutant, and this could be one of reasons why stem cell population appears to be increased. This situation is in sharp contrast to clv3 mutant, which also shows an increase in stem cell population but does not show a decrease in leaf production. We briefly discuss differences between the er-family mutant and the clv3 mutant.

Effects of exercise intensity on circulating leukocyte subpopulations.

OBJECTIVES: The purpose of this study was to examine the relation between exercise intensity and immune function. METHODS: Ten healthy young males underwent a constant work rate exercise of three levels, 90%, 80% and 70% ventilatory threshold (VT) work rate, for 20 min on a bicycle ergometer. These work rates were calculated for each individual based on his VT work rate obtained by the incremental exercise tests. Blood samples were collected before and after the exercise, and immune function indices were measured. RESULTS: Compared with the obtained[Formula: see text] at[Formula: see text] in the incremental test, the[Formula: see text] with the exercise of 70% VT work rate was at a similar level and the one with the exercise of 90% or 80% VT work rate had a significantly greater value. The numbers of leukocytes and neutrophils significantly increased in the 90% and 70% VT work rate groups. In 80% VT work rate group, the CD4/CD8 ratio was significantly depressed. The CD16(+)CD57(-) (%), natural killer cell populations, had a tendency to increase at 80% VT work rate, and also the CD16(+)CD57(-) (%) had a similar tendency at 90% or 80% VT work rate. CONCLUSIONS: This study shows that moderate exercise reaching or exceeding the VT level acutely affects T cell and NK cell subsets.