Objective: This study retrospectively examined the practice of chlorpromazine (CPZ) administration for sleep disturbance in a palliative care unit, with particular attention to concomitant use of midazolam (MDZ). Methods: A total of 126 patients were reviewed. Among them, 98 patients who continued CPZ for three days or longer were evaluated for changes in nighttime sleep status using a sleep score and for daytime consciousness level. Results: MDZ was used concomitantly in 99 patients (78.5%). Adverse events related to CPZ were observed in 12 patients (9.5%), mainly oversedation and extrapyramidal symptoms, while no severe circulatory or respiratory suppression was noted. Among the 98 patients who received CPZ continuously for three days or longer, sleep scores showed an improving trend; however, some patients experienced decreased daytime alertness, and the possibility that adverse events were underestimated cannot be excluded. Conclusion: This study was a retrospective, single-center analysis based on medical records and therefore has limitations related to the subjectivity of assessment tools and clinical judgment. Further prospective studies using standardized evaluation scales are required to establish the efficacy and safety of CPZ for sleep disturbance.

Primary hyperparathyroidism (PHPT) with concomitant thyroid cancer is rare and is usually caused by a parathyroid adenoma rather than parathyroid carcinoma. Although an association between PHPT and well-differentiated thyroid carcinoma has been reported, it is often considered coincidental. We report a case of a 50-year-old female presenting with tingling, shoulder pain, muscle weakness, and elevated serum calcium and parathyroid hormone levels. Neck ultrasonography revealed a hypoechoic nodule in the left inferior region to the thyroid gland and thyroid nodules in both lobes. A Tc99m-MIBI parathyroid scan showed a focal hot nodule, and fine-needle aspiration confirmed papillary thyroid carcinoma, later verified by histopathology. The patient underwent surgery and was diagnosed with PHPT and papillary thyroid carcinoma. This case highlights the importance of evaluation for concomitant thyroid malignancy in PHPT patients with suspicious thyroid nodules.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Microorganisms inhabiting soils contaminated with heavy metals produce melanin, a dark brown pigment, as a survival strategy. In this study, a melanin-producing bacterium, Acinetobacter sp. ME1, with heavy metal tolerance and plant growth-promoting traits, was isolated from abandoned mine soil. Strain ME1 exhibited growth at concentrations of Zn up to 250 mg/L, Cd and Pb up to 100 mg/L, and Cr up to 50 mg/L. It had the ability to produce the plant hormone indole-3-acetic acid and siderophores along with 1-aminocyclopropane-1-carboxylic acid deaminase and protease activities. Additionally, it showed antioxidant activity, including catalase and 2,2-diphenyl-1-picryhydrazyl (DPPH) scavenging activities. The optimal conditions for melanin production by ME1 were a pH of 7 and a temperature of 35 ℃. At 1000 mg/L, ME1-extracted melanin exhibited DPPH radical scavenging activity of (25.040±0.007)%, a sun protection factor of 15.200±0.260, and 19.6% antibacterial activity against the plant pathogen Xanthomonas campestris. Furthermore, its adsorption capacity was (0.235±0.073) mg/g melanin for Zn and (0.277±0.008) mg/g melanin for Ni. In plants of Brassica chinensis grown under conditions of hydroponic cultivation with single heavy metal contamination of Cd, Zn, Pb, or Cr, the removal efficiency of each heavy metal was improved by 0.1‒1.8 times after 3 d following inoculation with the strain ME1 compared to the plants grown under the same conditions without inoculation. In addition, ME1 inoculation improved the removal efficiency of each heavy metal by 0.1‒1.0 times under multiple heavy metal contamination conditions. These findings suggest that Acinetobacter sp. ME1 could be used to enhance phytoremediation efficiency in heavy metal-contaminated soils. Moreover, the melanin it produces also holds promise in cosmetics, household products, and medical applications due to its photoprotective, antioxidant, and antimicrobial properties.
Acinetobacter/metabolism* ; Biodegradation, Environmental ; Metals, Heavy/metabolism* ; Melanins/metabolism* ; Soil Microbiology ; Antioxidants/metabolism* ; Plant Development ; Soil Pollutants/metabolism* ; Indoleacetic Acids/metabolism*

Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.

Background: The ongoing medical crisis in Korea has severely impacted the operational environment of intensive care units (ICU), posing significant challenges to quality care for critically ill patients. This study aimed to evaluate the effects of the ongoing crisis on ICUs. Methods: A survey was conducted in July 2024 among intensivists in charge of ICUs at institutions accredited by the Korean Society of Critical Care Medicine for critical care. The survey compared data from January 2024 (pre-crisis) and June 2024 (post-crisis) on the number ICU beds, staffing composition, work hours, and the number and roles of nurse practitioners. Results: Among the total of 71 participating ICUs, 22 experienced a reduction in the number of operational beds, with a median decrease of six beds per unit, totaling 127 beds across these ICUs. The numbers of residents and interns decreased from an average of 2.3 to 0.1 per ICU, and the average weekly working hours of intensivists increased from 62.3 to 78.8 hours. Nurse practitioners helped fill staffing gaps, with their numbers rising from 150 to 242 across ICUs, and their scope of practice expanded accordingly. Conclusions The medical crisis has led to major changes in the critical care system, including staffing shortages, increased workloads, and an expanded role for nurse practitioners. This is a critical moment to foster interest and engage in active discussions aimed at creating a sustainable and resilient ICU system.

Background: Latency in transferring patients from intensive care units (ICUs) to general wards impedes the optimal allocation of ICU resources, underscoring the urgency of initiatives to reduce it. This study evaluates the extent of ICU transfer latency and assesses the potential benefits of minimizing it. Methods: Transfer latency was measured as the time between the first transfer request and the actual ICU discharge at a single-center tertiary hospital in 2021. Computer-based simulations and cost analyses were performed to examine how reducing transfer latency could affect average hourly ICU bed occupancy, the proportion of time ICU occupancy exceeds 80%, and hospital costs. The first analysis evaluated all ICU admissions, and the second analysis targeted a subset of ICU admissions with longer transfer latency, those requiring infectious precautions. Results: A total of 7,623 ICU admissions were analyzed, and the median transfer latency was 5.7 hours. Eliminating transfer latency for all ICU admissions would have resulted in a 32.8% point decrease in the proportion of time ICU occupancy exceeded 80%, and a potential annual savings of $6.18 million. Eliminating transfer latency for patients under infectious precautions would have decreased the time ICU occupancy exceeded 80% by 13.5% points, and reduced annual costs by a potential $1.26 million. Conclusions Transfer latency from ICUs to general wards might contribute to high ICU occupancy. Efforts to minimize latency for all admissions, or even for a subset of admissions with particularly long transfer latency, could enable more efficient use of ICU resources.

Background: Residents and nurses who activate rapid response teams (RRTs) are well positioned to offer insights on its effectiveness. Here, we assess such evaluation of RRTs and identify barriers to activation in a 1,400-bed teaching hospital. Methods: We conducted a 24-item Likert-scale survey from January to May 2017 among residents and ward nurses with RRT experience. Factor analysis was used to identify the barriers. Results: This study comprised 305 nurses and 53 residents, most of whom were satisfied with their RRT experiences. Factor analysis showed that lack of awareness of activation criteria was a major barrier, with only 21.4% and 22.2% participants, respectively, confident about their knowledge of activation protocols. Of the survey respondents, 85.7% reported first contacting the doctor before activating the RRT. Despite the protocol, 66.7% first discussed the decision with other staff, and 71.5% called the RRT when the patient’s condition worsened despite management. Conclusions Nurses and residents value RRTs but face barriers in initiation, primarily due to a lack of confidence in applying the activation criteria. Many prefer to consult a doctor or manage the patient before calling the RRT.