[The Comparative Effectiveness of Using Cold Water Oral Spray and Cold Saline Oral Spray for Thirst Relief in Patients With Endotracheal Intubation in the Intensive Care Unit].

BACKGROUND: Thirst is a common symptom among patients with endotracheal intubation in the intensive care unit (ICU), with an estimated prevalence of 88%. PURPOSE: This study was designed to compare the effectiveness of cold saline spray and cold water spray in alleviating thirst, and to explore the maintenance and sustained effects of both groups in relieving thirst among patients with endotracheal intubation in the ICU. METHODS: Patients with indwelling tracheal tubes in the medical ICU were recruited from one medical center in northern Taiwan and randomly assigned to either the cold saline (n = 18) or cold water (n = 18) group. The cold saline group received three rounds of cold saline spray at a temperature of 2°C - 8°C. Each round consisted of 10 sprays directed toward each of the four surfaces of the oral cavity followed by a 5-minute wait period. This process was repeated three times, with 30-minute intervals between interventions. The cold water group received the same intervention steps using a cold water spray at 2°C - 8°C. Thirst intensity was measured using a numeric rating scale before and after each of the three interventions in both groups. Demographic and relevant physiological data were collected on the participants by reviewing their medical records. RESULTS: Both of the interventions were found to effectively alleviate thirst intensity, with no significant difference between the two groups in terms of thirst intensity reduction after each intervention detected. Only the cold water spray had a maintenance effect, while the two groups had a continuous sustained effect in alleviating thirst intensity. CONCLUSIONS: Both of the interventions effectively alleviated thirst, and the cold water spray had both maintenance and sustained effects in alleviating thirst intensity. Based on the results, the cold water spray method may be considered as the priority treatment for thirst alleviation by healthcare providers in the clinical management of patients with tracheal intubation.

Assessing the clinical utility of abdominal computed tomography in sepsis patients with unknown origin: A retrospective cohort study.

Early identification of the sources of infection in emergency department (ED) patients of sepsis remains challenging. Computed tomography (CT) has the potential to identify sources of infection. This retrospective study aimed to investigate the role of CT in identifying sources of infection in patients with sepsis without obvious infection foci in the ED. A retrospective chart review was conducted on patients with fever and sepsis visiting the ED of Linkou Chang Gung Memorial Hospital between July 1, 2020 and June 30, 2021. Data on patient demographics, vital signs, clinical symptoms, underlying medical conditions, laboratory results, administered interventions, length of hospital stay, and mortality outcomes were collected and analyzed. Of 218 patients included in the study, 139 (63.8%) had positive CT findings. The most common sources of infection detected by CT included liver abscesses, acute pyelonephritis, and cholangitis. Laboratory results showed that patients with positive CT findings had higher white blood cell and absolute neutrophil counts and lower hemoglobin levels. Positive blood culture results were more common in patients with positive CT findings. Additionally, the length of hospital stay was longer in the group with positive CT findings. Multivariate logistic regression analysis revealed that hemoglobin levels and positive blood culture results independently predicted positive CT findings in patients with fever or sepsis without an obvious source of infection. In patients with sepsis with an undetermined infection focus, those presenting with leukocytosis, anemia, and elevated absolute neutrophil counts tended to have positive findings on abdominal CT scans. These patients had high rates of bacteremia and longer lengths of stay. Abdominal CT remains a valuable diagnostic tool for identifying infection sources in carefully selected patients with sepsis of undetermined infection origins.

Development of a thermotaxis and rheotaxis microfluidic device for motile spermatozoa sorting.

Male infertility is a pervasive global reproductive challenge, primarily attributed to a decline in semen quality. Addressing this concern, there has been a growing focus on spermatozoa sorting in assisted reproductive technology. This study introduces a groundbreaking development in the form of a thermotaxis and rheotaxis microfluidic (TRMC) device designed for efficient motile spermatozoa sorting within a short 15-min timeframe. The TRMC device mimics the natural sperm sorting mechanism of the oviduct, selecting spermatozoa with superior motility and DNA integrity. The experimental outcomes demonstrate a remarkable enhancement in the percentage of progressive spermatozoa following sorting, soaring from 3.90% to an impressive 96.11% when subjected to a temperature decrease from 38 °C to 35 °C. Notably, sperm motility exhibited a substantial 69% improvement. The TRMC device exhibited a commendable recovery rate of 60.93%, surpassing current clinical requirements. Furthermore, the sorted spermatozoa displayed a notable reduction in the DNA fragmentation index to 6.94%, signifying a substantial 90% enhancement in DNA integrity. This remarkable advancement positions the TRMC device as highly suitable for applications in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), offering a promising solution to male infertility challenges.

Taurine Rescues Cancer-induced Atrophy in Human Skeletal Muscle Cells via Ameliorating the Inflammatory Tumor Microenvironment.

BACKGROUND/AIM: Cancer cachexia is a wasting syndrome that has a devastating impact on the prognosis of patients with cancer. It is well-documented that pro-inflammatory cytokines are involved in the progression of this disorder. Therefore, this study was conducted to investigate the protective effect of taurine, an essential nonprotein amino acid with great anti-inflammatory properties, in attenuating muscle atrophy induced by cancer. MATERIALS AND METHODS: Conditioned media (CM) derived from T24 human bladder carcinoma cells with or without 5 mM taurine were incubated with human skeletal muscle cells (HSkMCs) and their differentiation was examined. The intracellular reactive oxygen species (ROS), morphology, and the catabolic pathway were monitored. RESULTS: T24-derived CM with high levels of TNF-α and IL-6 caused aberrant ROS accumulation and formation of atrophic myotubes by HSkMCs. In T24 cancer cells, taurine significantly inhibited the production of TNF-α and IL-6. In HSkMCs, taurine increased ROS clearance during differentiation and preserved the myotube differentiation ability impaired by the inflammatory tumor microenvironment. In addition, taurine ameliorated myotube atrophy by regulating the Akt/FoxO1/MuRF1 and MAFbx signaling pathways. CONCLUSION: Taurine rescues cancer-induced atrophy in human skeletal muscle cells by ameliorating the inflammatory tumor microenvironment. Taurine supplementation may be a promising approach for intervening with the progression of cancer cachexia.

The upregulation of VGF enhances the progression of oral squamous carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent neoplasm worldwide, necessitating a deeper understanding of its pathogenesis. VGF nerve growth factor inducible (VGF), a neuropeptide, plays critical roles in nerve and endocrine cell regulation. METHODS: In this study, the TCGA datasets were initially screened, identifying the upregulation of VGF in various malignancies. We focused on OSCC cell lines, identifying the suppressor mRNA miR-432-5p as a negative regulator of VGF. Additionally, we examined the prognostic value of VGF expression in OSCC tumors and its impact on cellular functions. RESULTS: VGF expression was found to be an independent prognostic predictor in OSCC tumors. Cells expressing VGF exhibited increased oncogenicity, influencing the proliferation and migration of oral mucosal fibroblast. Transcriptome analysis revealed associations between VGF and various pathological processes, including malignancies, exosome release, fibrosis, cell cycle disruption, and tumor immune suppression. Moreover, IL23R expression, a favorable OSCC prognostic factor, was inversely correlated with VGF expression. Exogenous IL23R expression was found to suppress VGF-associated mobility phenotypes. CONCLUSIONS: This study highlights the multifaceted role of VGF in OSCC pathogenesis and introduces the miR-432-5p-VGF-IL23R regulatory axis as a critical mediator. The combined expression of VGF and IL23R emerges as a potent predictor of survival in oral carcinoma cases, suggesting potential implications for future therapeutic strategies.

MoodSensing: A smartphone app for digital phenotyping and assessment of bipolar disorder.

BACKGROUND: Daily life tracking has proven to be of great help in the assessment of patients with bipolar disorder. Although there are many smartphone apps for tracking bipolar disorder, most of them lack academic verification, privacy policy and long-term maintenance. METHODS: Our developed app, MoodSensing, aims to collect users' digital phenotyping for assessment of bipolar disorder. The data collection was approved by the Institutional Review Board. This study collaborated with professional clinicians to ensure that the app meets both clinical needs and user experience requirements. Based on the collected digital phenotyping, deep learning techniques were applied to forecast participants' weekly HAM-D and YMRS scale scores. RESULTS: In experiments, the data collected by our app can effectively predict the scale scores, reaching the mean absolute error of 0.84 and 0.22 on the scales. The statistical data also demonstrate the increase in user engagement. CONCLUSIONS: Our analysis reveals that the developed MoodSensing app can not only provide a good user experience, but also the recorded data have certain discriminability for clinical assessment. Our app also provides relevant policies to protect user privacy, and has been launched in the Apple Store and Google Play Store.

Safety and effectiveness of remdesivir for the treatment of COVID-19 patients with end-stage renal disease: A retrospective cohort study.

BACKGROUND: Remdesivir has been used to treat severe coronavirus 2019 (COVID-19); however, its safety and effectiveness in patients remain unclear. This study aimed to investigate the safety and effectiveness of remdesivir in patients with COVID-19 with end-stage renal disease (ESRD). METHODS: This retrospective study used the Chang Gung Research Database (CGRD) and extracted data from 21,621 adult patients with COVID-19 diagnosed between April 2021 and September 2022. The patients were divided into groups based on their remdesivir use and the presence of ESRD. The adverse effects of remdesivir and their outcomes were analyzed after propensity score matching. RESULTS: To compare the adverse effects of remdesivir, propensity scores were used for one-to-one matching between patients with and without ESRD treated with remdesivir (N = 110). There were no statistically significant differences in heart rates, blood glucose levels, variations in hemoglobin levels before and after remdesivir use, or liver function between the two groups after remdesivir use. A comparison was made between patients with ESRD using remdesivir and those not using remdesivir after propensity score matching (N = 44). Although a shorter length of stay (LOS), lower intensive care unit (ICU) admission rate, and lower intubation rate were noted in the ESRD group treated with remdesivir, the difference was not statistically significant. CONCLUSION: Remdesivir is safe for use in patients with COVID-19 and ESRD; no increased adverse effects were noted compared with patients without ESRD. However, the effectiveness of remdesivir use in patients with COVID-19 and ESRD remains uncertain.

Cold Atmospheric Plasma Jet Irradiation Decreases the Survival and the Expression of Oncogenic miRNAs of Oral Carcinoma Cells.

Despite recent advancements, therapies against advanced oral squamous cell carcinoma (OSCC) remain ineffective, resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Although the effects of CAP in abrogating OSCC have been explored, the exact mechanisms driving CAP-induced cancer cell death and the changes in microRNA (miRNA) expression are not fully understood. We fabricated and calibrated an argon-CAP device to explore the effects of CAP irradiation on the growth and expression of oncogenic miRNAs in OSCC. The analysis revealed that, in OSCC cell lines following CAP irradiation, there was a significant reduction in viability; a downregulation of miR-21, miR-31, miR-134, miR-146a, and miR-211 expression; and an inactivation of the v-akt murine thymoma viral oncogene homolog (AKT) and extracellular signal-regulated kinase (ERK) signals. Pretreatment with blockers of apoptosis, autophagy, and ferroptosis synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways via CAP. Combined treatments using death inhibitors and miRNA mimics, alongside the activation of AKT and ERK following the exogenous expression, counteracted the cell mortality associated with CAP. The CAP-induced downregulation of miR-21, miR-31, miR-187, and miR-211 expression was rescued through survival signaling. Additionally, CAP irradiation notably inhibited the growth of SAS OSCC cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study provides new lines of evidence demonstrating that CAP irradiation diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

SARS-CoV-2 rapid antigen testing positive rate in community testing stations as an indicator for COVID-19 epidemic trend, Taipei, Taiwan, May to August 2021.

BACKGROUND: Real-time surveillance of COVID-19 in large-scale community outbreaks presents challenges. Simple counts of the daily confirmed cases can be misleading due to constraints from bottlenecks in access to care or laboratory testing. This study aimed to investigate the role of the SARS-CoV-2 antigen rapid diagnostic test (Ag-RDT) in addressing these challenges for real-time COVID-19 surveillance. METHODS: This study included the results of 86,994 SARS-CoV-2 Ag-RDT and real-time reverse transcription polymerase chain reaction (RT-PCR) tests. These were conducted at four community testing stations within the Taipei metropolitan area during a community COVID-19 outbreak spanning from May 17, 2021, to August 9, 2021. We examined the correlation between the positive rates of Ag-RDT tests and the epidemic curve of laboratory-confirmed COVID-19 cases by onset date to examine its role in real-time surveillance. RESULTS: During the 85-day study period, the trend of Ag-RDT test positive rates paralleled that of the epidemic curve. The correlation between the Ag-RDT positive rate and the number of cases (Pearson correlation coefficient: 0.968) is comparable to that of the RT-PCR positive rate (Pearson correlation coefficient: 0.964). The Ag-RDT positive rate exhibited a more advanced leading trend, with Ag-RDT leading by 3 days in comparison to the 2-day lead for RT-PCR. CONCLUSION: The positive rate of SARS-CoV-2 Ag-RDT tests at community testing stations serves as a good surrogate for assessing virus activity within the community and a useful tool for real-time COVID-19 surveillance. It is a robust indicator of the outbreak trend and near-term numbers of cases. This finding may facilitate the management of subsequent outbreaks of emerging infectious diseases.

Systematic designs of single metal compounds synthesized using ammonia fluoride-based complex as structure directing agents for energy storage.

Tailoring morphology and composition of metal organic frameworks (MOF) can improve energy storage by establishing high surface area, large porosity and multiple redox states. Structure directing agents (SDA) is functional of designing surface properties of electroactive materials. Ammonium fluoride has functional abilities for designing MOF derivatives with excellent energy storage abilities. Systematic design of MOF derivatives using ammonia fluoride-based complex as SDA can essentially create efficient electroactive materials. Metal species can also play significant roles on redox reactions, which are the main energy storage mechanism for battery-type electrodes. In this work, 2-methylimidazole, two novel SDAs of NH4BF4 and NH4HF2, and six metal species of Al, Mn, Co, Ni, Cu and Zn are coupled to synthesize MOF derivatives for energy storage. Metal species-dependent compositions including hydroxides, oxides, and hydroxide nitrates are observed. The nickel-based derivative (Ni-HBF) shows the highest specific capacitance (CF) of 698.0F/g at 20 mV/s, due to multiple redox states and advanced flower-like surface properties. The diffusion and capacitive-control contributions of MOF derivatives are also analyzed. The battery supercapacitor hybrid with Ni-HBF electrode shows a maximum energy density of 27.9 Wh/kg at 325 W/kg. The CF retention of 170.9% and Coulombic efficiency of 93.2% are achieved after 10,000 cycles.

Design of a gradient-rheotaxis microfluidic chip for sorting of high-quality Sperm with progressive motility.

Assisted reproductive technology (ART) is an important invention for the treatment of human infertility, and the isolation of high-quality sperm with progressive motility is one of the most critical steps that eventually affect the fertilization rate. Conventional sperm separation approaches include the swim-up method and density gradient centrifugation. However, the quality of isolated sperm obtained from both approaches can still be improved by improving sorted sperm motility, minimizing the DNA fragmentation rate, and removing abnormal phenotypes. Here, we report a Progressive Sperm Sorting Chip (PSSC) for high-quality sperm isolation. Based on the rheotaxis behavior of sperm, a gradient flow field is created in the chip for progressive sperm sorting. Clinical experiment results for 10 volunteers showed that greater than 90% of isolated sperm exhibit high motility (> 25 µm/s), high linearity (0.8), and a very low DNA fragmentation rate (< 5%). In addition, the whole process is label and chemical free. These features aid in gentle sperm sorting to obtain healthy sperm. This device uniquely enables the selection of high-quality sperm with progressive motility and might be clinically applied for infertility treatment in the near future.

The Distribution Trend and Antimicrobial Susceptibility of Uropathogens in Taiwan: Retrospective Analysis of a 10-Year Study.

Background: The prevalence and antimicrobial susceptibility of uropathogens can vary with time and geographical location. Empirical antibiotic treatment is frequently started before the urine culture reports are received; thus, the correct selection of antibiotics is imperative, as inappropriate use could increase resistance rates. This study evaluates the distribution trends and antimicrobial susceptibility of common uropathogens in Taiwan to help predict causative pathogens, prevent overly broad antibiotic use, and guide the optimal prescription of empirical antibiotic therapy to improve prognosis. Methods: This retrospective study extracted 5,672,246 urine culture sample data, including outpatient, emergency, and inpatient departments, during 2007-2017 from the Chang Gung Research Database. We examined the trend and susceptibility of uropathogens. Results: The three leading microorganisms were Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Pseudomonas aeruginosa (P. aeruginosa). E. coli. was more common among females (42.7%) than males (24.7%), while P. aeruginosa was more common among males (10.2%) than females (4.42%). E. coli and K. pneumoniae were highly susceptible to carbapenems, followed by aminoglycosides. Nevertheless, an increased antimicrobial resistance trend was observed in cephalosporins and quinolones. Conclusions: This study establishes E. coli and K. pneumoniae as the predominant uropathogens. Age and gender of patients result in distribution variations of uropathogens, but geographical location does not. In addition, P. aeruginosa occurs more in the sample of elderly and that too among males. Overall, this study could help clinicians choose appropriate antibiotics to treat urinary tract infections per the prevalent uropathogens and local antimicrobial susceptibility patterns.

Emergency residents' self-perceived readiness for practice: the association of milestones, entrustable professional activities, and professional identities-a multi-institutional survey.

Background: As a successful innovation, competency-based medical education and its assessment tools continue to be a key strategy in training future doctors and tracking their performance trajectories. Linked to professional identity, evidence suggests that clinical competence is related to thinking, acting and feeling like a physician. Thus, incorporating the values and attitudes of healthcare professions as part of their professional identity in the clinical workplace improves professional performance. Methods: Through a cross-sectional study, we examined the association of milestone, entrustable professional activities (EPA) and professional identity using self-reported tools among emergency medicine residents from 12 teaching hospitals across Taiwan. Milestone, EPA and professional identity were assessed using the Emergency Medicine Milestone Scale, Entrustable Professional Activity Scale and Emergency Physician Professional Identity and Value Scale, respectively. Results: The results of a Pearson correlation indicated a significant positive correlation between milestone-based core competencies and EPAs (r = 0.40 ~ 0.74, p < 0.01). The professional identity domain of skills acquisition, capabilities and practical wisdom was positively correlated with milestone-based core competencies of patient care, medical knowledge, practice-based learning and improvement, and system-based practice (r = 0.18 ~ 0.21, p ≤ 0.05), and six items of EPA (r = 0.16 ~ 0.22, p < 0.05). Additionally, the professional identity domain of professional recognition and self-esteem was positively correlated with practice-based learning and improvement, and system-based practice milestone competencies (r = 0.16 ~ 0.19, p < 0.05). Conclusion: This study demonstrates milestone and EPA assessment tools are highly linked and therefore, can be synergistically used by supervisors and clinical educators to evaluate clinical performance during residency training. Emergency physicians' professional identity is partly influenced by the advancement of skills and a resident's ability to learn, effectively perform tasks and make appropriate medical decisions at the system level in their clinical practice. Further research is warranted to understand the importance of residents' competency in relation to their professional identity development trajectory during clinical training.

The Concordant Disruption of B7/CD28 Immune Regulators Predicts the Prognosis of Oral Carcinomas.

Immune modulation is a critical factor in determining the survival of patients with malignancies, including those with oral squamous cell carcinoma (OSCC) and head and neck SCC (HNSCC). Immune escape or stimulation may be driven by the B7/CD28 family and other checkpoint molecules, forming ligand-receptor complexes with immune cells in the tumor microenvironment. Since the members of B7/CD28 can functionally compensate for or counteract each other, the concomitant disruption of multiple members of B7/CD28 in OSCC or HNSCC pathogenesis remains elusive. Transcriptome analysis was performed on 54 OSCC tumors and 28 paired normal oral tissue samples. Upregulation of CD80, CD86, PD-L1, PD-L2, CD276, VTCN1, and CTLA4 and downregulation of L-ICOS in OSCC relative to the control were noted. Concordance in the expression of CD80, CD86, PD-L1, PD-L2, and L-ICOS with CD28 members was observed across tumors. Lower ICOS expression indicated a worse prognosis in late-stage tumors. Moreover, tumors harboring higher PD-L1/ICOS, PD-L2/ICOS, or CD276/ICOS expression ratios had a worse prognosis. The survival of node-positive patients was further worsened in tumors exhibiting higher ratios between PD-L1, PD-L2, or CD276 and ICOS. Alterations in T cell, macrophage, myeloid dendritic cell, and mast cell populations in tumors relative to controls were found. Decreased memory B cells, CD8+ T cells, and Tregs, together with increased resting NK cells and M0 macrophages, occurred in tumors with a worse prognosis. This study confirmed frequent upregulation and eminent co-disruption of B7/CD28 members in OSCC tumors. The ratio between PD-L2 and ICOS is a promising survival predictor in node-positive HNSCC patients.

Long-term DEHP/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations.

Plasticizers are considered as environmental pollution released from medical devices and increased potential oncogenic risks in clinical therapy. Our previous studies have shown that long-term exposure to di-ethylhexyl phthalate (DEHP)/mono-ethylhexyl phthalate (MEHP) promotes chemotherapeutic drug resistance in colorectal cancer. In this study, we investigated the alteration of glycosylation in colorectal cancer following long-term plasticizers exposure. First, we determined the profiles of cell surface N-glycomes by using mass spectrometry and found out the alterations of α2,8-linkages glycans. Next, we analyzed the correlation between serum DEHP/MEHP levels and ST8SIA6 expression from matched tissues in total 110 colorectal cancer patients. Moreover, clinical specimens and TCGA database were used to analyze the expression of ST8SIA6 in advanced stage of cancer. Finally, we showed that ST8SIA6 regulated stemness in vitro and in vivo. Our results revealed long-term DEHP/MEHP exposure significantly caused cancer patients with poorer survival outcome and attenuated the expression of ST8SIA6 in cancer cells and tissue samples. As expected, silencing of ST8SIA6 promoted cancer stemness and tumorigenicity by upregulating stemness-associated proteins. In addition, the cell viability assay showed enhanced drug resistance in ST8SIA6 silencing cells treated with irinotecan. Besides, ST8SIA6 was downregulated in the advanced stage and positively correlated with tumor recurrence in colorectal cancer. Our results imply that ST8SIA6 potentially plays an important role in oncogenic effects with long-term phthalates exposure.