Efficacy and safety of biosimilar trastuzumab (CT-P6) in routine clinical practice in the Republic of Korea: a real-world post-marketing surveillance study.

BACKGROUND: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers. RESEARCH DESIGN AND METHODS: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness. RESULTS: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response. CONCLUSIONS: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.

Effects of Korean Versus Western Diets on Reproductive Function in Young Korean Men: A 12-Week Randomized Parallel Clinical Trial.

Background: Studies report that diet may have contributed to a 50-60% decrease in human sperm quality over the past few decades. Unhealthy lifestyles affect the structure of spermatozoa, affecting the male reproductive potential. This study aimed to compare the effects of Korean and Western diets on reproductive function in young male Koreans. Methods: Study participants were provided either the Korean Diet (KD group) or the Western Diet (WD group) for 12 weeks. Semen quality parameters such as volume, motility, cell count, and sex hormone levels were evaluated. Sexual function was assessed using the International Index of Erectile Function and the Male Sexual Health Questionnaire. Efficacy and safety evaluations were conducted at baseline, 8 weeks, and 12 weeks. Results: The KD group demonstrated a significantly increased sperm motility after 8 weeks relative to baseline but decreased after 12 weeks. In contrast, sperm motility in the WD group significantly decreased after 8 weeks compared with baseline and remained constant after 12 weeks. Statistically, a near-significant difference was observed between groups (p = 0.057). Similarly, free testosterone levels in the KD group increased after 12 weeks compared with baseline, whereas that in the WD group decreased. The free testosterone levels in the KD group were significantly higher than those in the WD group (p = 0.020). There were no statistically significant differences in other sex hormone and sexual function questionnaires between the groups. None of the participants reported any severe side effects, and no significant alterations in clinical diagnostic test values were detected. Conclusion: The results of the study strongly reveal that KD positively affects sperm motility and male hormone levels in young men, indicating potential benefits for reproductive function.

Supplementation of Heat-Treated Lactiplantibacillus plantarum nF1 Changes the Production of Short-Chain Fatty Acids in Healthy Infants.

Background: Imbalance of the gut microbiome and decrease in the number of short-chain fatty acid (SCFA)-producing bacteria often affect human health by altering intestinal and immune homeostasis. The use of probiotics has been shown to be an attractive method to modulate gut microbiota to prevent or treat intestinal dysbiosis. Likewise, this study aimed to determine whether the oral consumption of heat-treated Lactiplantibacillus plantarum nF1 (HLp-nF1) induces changes in the gut environment in healthy infants by measuring changes in fecal SCFAs. Methods: The study enrolled 43 infants aged under 2 months, with 30 infants in the HLp-nF1 group receiving HLp-nF1 orally (2.5 × 1010 cells/g/pack, daily dose of two packs) for 8 weeks. The fecal samples were collected and the questionnaires were administered at weeks 0 and 8. Results: The concentrations of the total SCFAs, acetate, propionate, and butyrate significantly increased following HLp-nF1 supplementation (P < 0.0001, P < 0.0001, P < 0.0001, and P=0.028, respectively). Conclusions: Supplementation of HLp-nF1 has a positive effect on SCFA production and could be a potentially useful and straightforward method to manipulate SCFA formation.

Ambulatory electrocardiographic longitudinal monitoring in a canine model for Duchenne muscular dystrophy identifies decreased very low frequency power as a hallmark of impaired heart rate variability.

Duchenne muscular dystrophy (DMD) patients exhibit a late left ventricular systolic dysfunction preceded by an occult phase, during which myocardial fibrosis progresses and some early functional impairments can be detected. These latter include electrocardiographic (ECG) and heart rate variability (HRV) abnormalities. This longitudinal study aimed at describing the sequence of ECG and HRV abnormalities, using Holter ECG in the GRMD (Golden retriever muscular dystrophy) dog model, known to develop a DMD-like disease, including cardiomyopathy. Most of the known ECG abnormalities described in DMD patients were also found in GRMD dogs, including increased heart rate, prolonged QT and shortened PR intervals, ventricular arrhythmias, and several of them could be detected months before the decrease of fractional shortening. The HRV was impaired like in DMD patients, one of the earliest evidenced abnormalities being a decrease in the very low frequency (VLF) component of the power spectrum. This decrease was correlated with the further reduction of fractional shortening. Such decreased VLF probably reflects impaired autonomic function and abnormal vasomotor tone. This study provides new insights into the knowledge of the GRMD dog model and DMD cardiomyopathy and emphasizes the interest to monitor the VLF power in DMD patients, still unexplored in this disease, whilst it is highly predictive of deleterious clinical events in many other pathological conditions.

Mutational analysis of 23 autosomal short tandem repeats based on trio paternity testing in the Korean population.

This study aimed to estimate A-STR mutation rates in 2,317 Korean parent-child trios by examining 20 Combined DNA Index System (CODIS) core loci (D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, CSF1PO, FGA, TH01, TPOX, vWA, D1S1656, D2S441, D2S1338, D10S1248, D12S391, D19S433, and D22S1045) and three non-CODIS loci (Penta E, Penta D, and SE33). Locus-specific mutation rate estimates varied from 0.00 to 8.63 × 10-3 per generation, with an average mutation rate of 1.62 × 10-3 (95 % CI, 1.39-1.88 × 10-3). We also combined data from previous studies to obtain comprehensive genetic values for the Korean population, and the average mutation rate was 1.59 × 10-3 (95 % CI, 1.38-1.82 × 10-3). Single-step mutations (95.69 %) and double-step mutations (3.35 %) were observed in the mutation pattern analysis, and cases expected to have multi-step mutations (0.96 %) were also observed. Large-sized alleles exhibited more loss mutations than gain mutations, and paternal mutations (62.68 %) were more frequently observed than maternal mutations (19.62 %). The calculated values and features of the 23 A-STRs explored in this study are expected to play a crucial role in establishing criteria for forensic genetic interpretation.

Data-Independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Salivary Biomarkers of Primary Sjögren's Syndrome.

Objective As primary Sj?gren's syndrome (pSS) primarily affects the salivary glands, saliva can serve as an indicator of the glands' pathophysiology and the disease's status. This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis.Methods The discovery set contained 49 samples (24 from pSS and 25 from age- and gender-matched healthy controls [HCs]) and the validation set included 25 samples (12 from pSS and 13 from HCs). Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio. Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition (DIA) strategy on a 2D LC?HRMS/MS platform to reveal differential proteins. The crucial proteins were verified using DIA analysis and annotated using gene ontology (GO) and International Pharmaceutical Abstracts (IPA) analysis. A prediction model for SS was established using random forests.Results A total of 1,963 proteins were discovered, and 136 proteins exhibited differential representation in pSS patients. The bioinformatic research indicated that these proteins were primarily linked to immunological functions, metabolism, and inflammation. A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm, and was validated as the predictive biomarkers exhibiting good performance with area under the curve (AUC) of 0.817 for discovery set and 0.882 for validation set.Conclusions The candidate protein panel discovered may aid in pSS diagnosis. Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients. DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

Impact of the early phase of the COVID-19 pandemic on emergency department-to-intensive care unit admissions in Korea: an interrupted time-series analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic resulted in significant disruptions to critical care systems globally. However, research on the impact of the COVID-19 pandemic on intensive care unit (ICU) admissions via the emergency department (ED) is limited. Therefore, this study evaluated the changes in the number of ED-to-ICU admissions and clinical outcomes in the periods before and during the pandemic. METHODS: We identified all adult patients admitted to the ICU through level 1 or 2 EDs in Korea between February 2018 and January 2021. February 2020 was considered the onset point of the COVID-19 pandemic. The monthly changes in the number of ED-to-ICU admissions and the in-hospital mortality rates before and during the COVID-19 pandemic were evaluated using interrupted time-series analysis. RESULTS: Among the 555,793 adult ED-to-ICU admissions, the number of ED-to-ICU admissions during the pandemic decreased compared to that before the pandemic (step change, 0.916; 95% confidence interval [CI] 0.869-0.966], although the trend did not attain statistical significance (slope change, 0.997; 95% CI 0.991-1.003). The proportion of patients who arrived by emergency medical services, those transferred from other hospitals, and those with injuries declined significantly among the number of ED-to-ICU admissions during the pandemic. The proportion of in-hospital deaths significantly increased during the pandemic (step change, 1.054; 95% CI 1.003-1.108); however, the trend did not attain statistical significance (slope change, 1.001; 95% CI 0.996-1.007). Mortality rates in patients with an ED length of stay of ≥ 6 h until admission to the ICU rose abruptly following the onset of the pandemic (step change, 1.169; 95% CI 1.021-1.339). CONCLUSIONS: The COVID-19 pandemic significantly affected ED-to-ICU admission and in-hospital mortality rates in Korea. This study's findings have important implications for healthcare providers and policymakers planning the management of future outbreaks of infectious diseases. Strategies are needed to address the challenges posed by pandemics and improve the outcomes in critically ill patients.

Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

The Relationship Between Interoceptive Awareness, Emotion Regulation and Clinical Symptoms Severity of Depression, Anxiety and Somatization.

OBJECTIVE: The primary objective of this study was to examine the associations among emotion regulation strategies, interoceptive awareness, and psychological distress measures-namely, depression, anxiety, and somatization. Additionally, we aimed to explore the predictive power of various facets of interoceptive awareness in determining the severity of symptoms for each mental disorder. METHODS: A cohort of 130 outpatients diagnosed with depression/anxiety disorder were recruited, and 20 subjects exhibiting incomplete responses were excluded from the dataset, leading to a final sample size of 110 outpatients. The clinical symptoms were measured by Patient Health Questionnaire-9, State-Trait Anxiety Inventory Form Y, and Symptom Checklist-90-Revised, and the usage of emotion-regulation strategies and interoceptive awareness was assessed with Emotion Regulation Questionnaire and Multidimensional Assessment of Interoceptive Awareness (MAIA), respectively. A hierarchical regression analysis was performed to examine whether emotion-regulation strategies and interoceptive awareness explain the statistically significant variance in each of the symptoms. RESULTS: In the depression model, cognitive reappraisal, accept, and attention regulation showed significant associations, while in the anxiety model, cognitive reappraisal, attention regulation, trust, and notice emerged as significant factors. Lastly, cognitive reappraisal and attention regulation were found to be significant contributors to the final model for somatization. CONCLUSION: The inclusion of MAIA subscales improved the predictive ability of the regression model, highlighting the independent association between interoceptive awareness-particularly attention regulation-and clinical symptoms of anxiety and depression. Additionally, the study underscores the relevance of considering the specific pathological context when implementing interventions, as evidenced by the positive associations between the accept subscale and depression and between the notice subscale and anxiety, respectively.

Preoperative prediction of metastatic pheochromocytoma and paraganglioma using clinical, genetic, and biochemical markers: A cohort study.

BACKGROUND: The prevalence of metastatic pheochromocytoma and paraganglioma (PPGL) is approximately 15%-20%. Although there are indicators to assess metastatic risks, none of them predict metastasis reliably. Therefore, we aimed to develop and validate a scoring system using clinical, genetic, and biochemical risk factors to preoperatively predict the metastatic risk of PPGL. METHODS: In the cross-sectional cohort (n = 180), clinical, genetic, and biochemical risk factors for metastasis were identified using multivariate logistic regression analysis, and a novel scoring system was developed. The scoring system was validated and compared with the age, size of tumor, extra-adrenal location, and secretory type (ASES) score in the longitudinal cohort (n = 114). RESULTS: In the cross-sectional cohort, pseudohypoxia group-related gene variants (SDHB, SDHD, or VHL), methoxytyramine >0.16 nmol/L, and tumor size >6.0 cm were independently associated with metastasis after multivariate logistic regression. Using them, the gene variant, methoxytyramine, and size of tumor (GMS) score were developed. In the longitudinal cohort, Harrell's concordance index of the GMS score (0.873, 95% confidence interval [CI]: 0.738-0.941) was higher than that of the ASES score (0.713, 95% CI: 0.567-0.814, p = 0.007). In the longitudinal cohort, a GMS score ≥2 was significantly associated with a higher risk of metastasis (hazard ratio = 25.07, 95% CI: 5.65-111.20). A GMS score ≥2 (p < 0.001), but not ASES score ≥2 (p = 0.090), was associated with shorter progression-free survival. CONCLUSION: The GMS scoring system, which integrates gene variant, methoxytyramine level, and tumor size, provides a valuable preoperative approach to assess metastatic risk in PPGL.

Hyaluronic Acid Based Adipose Tissue-Derived Extracellular Matrix Scaffold in Wound Healing: Histological and Immunohistochemical Study.

BACKGROUND: In this study, we explored the potential of human adipose tissue-derived extracellular matrix (adECM) sheets augmented with crosslinked hyaluronic acid (HA) as advanced wound dressings. We aimed to enhance healing efficacy while optimizing cost efficiency. METHODS: The adECM was processed from healthy donor tissue and combined with crosslinked HA to form ECM-HA sheets (Scaffiller, Medikan, Korea). In vitro experiments involved seeding adipose-derived stem cells (ASCs) onto these sheets and assessing cell survival and cytokine production. In vivo testing utilized a rat wound model, comparing ECM-HA sheet with HA-based dressing and polyurethane foam dressing. Re-epithelialization and collagen deposition were examined through histopathological examinations, whereas immunohistochemistry was used to assess CD31, alpha smooth muscle actin (α-SMA), and Tenascin C expression as contributing factors to wound healing. RESULTS: Results indicated that ECM-HA sheets were produced efficiently, with enhanced growth factor production and ASC survival observed in vitro. In vivo, ECM-HA sheets demonstrated accelerated wound healing, evidenced by improved epithelialization, thicker dermis, increased collagen deposition, and enhanced vascularity. Notably, they exhibited reduced myofibroblast activity and increased expression of Tenascin C, suggesting a favorable healing environment. CONCLUSION: ECM-HA sheets offer a promising approach for wound management, combining the benefits of adECM and HA. They present improved stability and cost-effectiveness while promoting essential aspects of wound healing such as angiogenesis and collagen formation. This study underscores the therapeutic potential of ECM-HA sheets in clinical applications aimed at facilitating wound repair.

Phase-change memory via a phase-changeable self-confined nano-filament.

Phase-change memory (PCM) has been considered a promising candidate for solving von Neumann bottlenecks owing to its low latency, non-volatile memory property and high integration density1,2. However, PCMs usually require a large current for the reset process by melting the phase-change material into an amorphous phase, which deteriorates the energy efficiency2-5. Various studies have been conducted to reduce the operation current by minimizing the device dimensions, but this increases the fabrication cost while the reduction of the reset current is limited6,7. Here we show a device for reducing the reset current of a PCM by forming a phase-changeable SiTex nano-filament. Without sacrificing the fabrication cost, the developed nano-filament PCM achieves an ultra-low reset current (approximately 10 µA), which is about one to two orders of magnitude smaller than that of highly scaled conventional PCMs. The device maintains favourable memory characteristics such as a large on/off ratio, fast speed, small variations and multilevel memory properties. Our finding is an important step towards developing novel computing paradigms for neuromorphic computing systems, edge processors, in-memory computing systems and even for conventional memory applications.

FPR3 reprograms glycolytic metabolism and stemness in gastric cancer via calcium-NFATc1 pathway.

Aerobic glycolysis accelerates tumor proliferation and progression, and inhibitors or drugs targeting abnormal cancer metabolism have been developing. Cancer stem-like cells (CSCs) significantly contribute to tumor initiation, metastasis, therapy resistance, and recurrence. Formyl peptide receptor 3 (FPR3), a member of FPR family, involves in inflammation, tissue repair, and angiogenesis. However, studies in exploring the regulatory mechanisms of aerobic glycolysis and CSCs by FPR3 in gastric cancer (GC) remain unknown. Here, we demonstrated that overexpressed FPR3 suppressed glycolytic capacity and stemness of tumor cells, then inhibited GC cells proliferation. Mechanistically, FPR3 impeded cytoplasmic calcium ion flux and hindered nuclear factor of activated T cells 1 (NFATc1) nuclear translocation, leading to the transcriptional inactivation of NFATc1-binding neurogenic locus notch homolog protein 3 (NOTCH3) promoter, subsequently obstructing NOTCH3 expression and the AKT/mTORC1 signaling pathway, and ultimately downregulating glycolysis. Additionally, NFATc1 directly binds to the sex determining region Y-box 2 (SOX2) promoter and modifies stemness in GC. In conclusion, our work illustrated that FPR3 played a negative role in GC progression by modulating NFATc1-mediated glycolysis and stemness in a calcium-dependent manner, providing potential insights into cancer therapy.

Visceral adipose tissue reduction measured by deep neural network architecture improved reflux esophagitis endoscopic grade.

BACKGROUND AND AIMS: Visceral obesity is a risk factor for reflux esophagitis (RE). We investigated the risk of RE according to visceral adipose tissue (VAT) measured by deep neural network architecture using computed tomography and evaluated the longitudinal association between abdominal adipose tissue changes and the disease course of RE. METHODS: Individuals receiving health checkups who underwent esophagogastroduodenoscopy (EGD) and abdominal computed tomography (CT) at Seoul National University Healthcare System Gangnam Center between 2015 and 2016 were included. Visceral and subcutaneous adipose tissue areas and volumes were measured using a deep neural network architecture and CT. The association between the abdominal adipose tissue area and volume and the risk of RE was evaluated. Participants who underwent follow-up EGD and abdominal CT were selected; the effects of changes in abdominal adipose tissue area and volume on RE endoscopic grade were investigated using Cox proportional hazards regression. RESULTS: We enrolled 6570 patients who underwent EGD and abdomen CT on the same day. RE was associated with male sex, hypertension, diabetes, excessive alcohol intake, current smoking status, and levels of physical activity. The VAT area and volume increased the risk of RE dose-dependently. A decreasing VAT volume was significantly associated with improvement in RE endoscopic grade (HR:3.22, 95%CI:1.82-5.71). Changes in subcutaneous adipose tissue volume and the disease course of RE were not significantly correlated. CONCLUSIONS: Visceral obesity is strongly associated with RE. VAT volume reduction was prospectively associated with improvement in RE endoscopic grade dose-dependently. Visceral obesity is a potential target for RE treatment.

The experience of shared decision-making for people with asthma: A systematic review and metasynthesis of qualitative studies.

OBJECTIVES: To identify, describe and synthesise the views and experiences of adults living with asthma regarding shared decision-making (SDM) in the existing qualitative literature METHODS: We conducted a comprehensive search of 10 databases (list databases) from inception until September 2023. Screening was performed according to inclusion criteria. Tools from the Joanna Briggs lnstitute were utilised for the purposes of data extraction and synthesis in this study. The data extraction process in this study employed the Capability, Opportunity and Motivation Model of Behaviour (COM-B model) as a framework, and a pragmatic meta-aggregative approach was employed to synthesise the collected results. RESULTS: Nineteen studies were included in the metasynthesis. Three synthesised themes were identified: the capability of people living with asthma, the opportunities of people living with asthma in SDM, and the motivation of the people living with asthma in SDM. CONCLUSIONS: We have identified specific factors influencing people living with asthma engaging in SDM. The findings of this study can serve as a basis for the implementation of SDM in people living with asthma and provide insights for the development of their SDM training programs. The ConQual score for the synthesised findings was rated as low. To enhance confidence, future studies should address dependability and credibility factors. PRACTICE IMPLICATIONS: This review contemplates the implementation of SDM from the perspective of people living with asthma, with the aim of providing patient-centred services for them. The results of this review can benefit the implementation of SDM and facilitate information sharing. It offers guidance for SDM skills training among adults living with asthma, fosters a better doctor-patient relationship and facilitates consensus in treatment decisions, thereby enabling personalised and tailored medical care. PATIENT OR PUBLIC CONTRIBUTION: Three nursing graduate students participated in the data extraction and integration process, with two students having extensive clinical experience that provided valuable insights for the integration.

Identification of a novel splice variant in SEC23B gene in a patient with concomitant presence of congenital dyserythropoietic anemia II and Gilbert's syndrome.

BACKGROUND: Congenital dyserythropoietic anemia Ⅱ (CDA Ⅱ) is a rare inherited disorder of defective erythropoiesis caused by SEC23B gene mutation. CDA Ⅱ is often misdiagnosed as a more common type of clinically related anemia, or it remains undiagnosed due to phenotypic variability caused by the coexistence of inherited liver diseases, including Gilbert's syndrome (GS) and hereditary hemochromatosis. METHODS: We describe the case of a boy with genetically undetermined severe hemolytic anemia, hepatosplenomegaly, and gallstones whose diagnosis was achieved by targeted next generation sequencing. RESULTS: Molecular analysis revealed a maternally inherited novel intronic variant and a paternally inherited missense variant, c.[994-3C > T];[1831C > T] in the SEC23B gene, confirming diagnosis of CDA Ⅱ. cDNA analysis verified that the splice acceptor site variant results in two mutant transcripts, one with an exon 9 skip and one in which exons 9 and 10 are deleted. SEC23B mRNA levels in the patient were lower than those in healthy controls. The patient was also homozygous for the UGT1A1*6 allele, consistent with GS. CONCLUSION: Identification of the novel splice variant in this study further expands the spectrum of known SEC23B gene mutations. Molecular genetic approaches can lead to accurate diagnosis and management of CDA Ⅱ patients, particularly for those with GS coexisting.

Prevalence and Associated Factors of Depression and Anxiety Among Healthcare Workers During the Coronavirus Disease 2019 Pandemic: A Nationwide Study in Korea.

BACKGROUND: A healthcare system's collapse due to a pandemic, such as the coronavirus disease 2019 (COVID-19), can expose healthcare workers (HCWs) to various mental health problems. This study aimed to investigate the impact of the COVID-19 pandemic on the depression and anxiety of HCWs. METHODS: A nationwide questionnaire-based survey was conducted on HCWs who worked in healthcare facilities and public health centers in Korea in December 2020. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety. To investigate factors associated with depression and anxiety, stepwise multiple logistic regression analysis was performed. RESULTS: A total of 1,425 participating HCWs were included. The mean depression score (PHQ-9) of HCWs before and after COVID-19 increased from 2.37 to 5.39, and the mean anxiety score (GAD-7) increased from 1.41 to 3.41. The proportion of HCWs with moderate to severe depression (PHQ-9 ≥ 10) increased from 3.8% before COVID-19 to 19.5% after COVID-19, whereas that of HCWs with moderate to severe anxiety (GAD-7 ≥ 10) increased from 2.0% to 10.1%. In our study, insomnia, chronic fatigue symptoms and physical symptoms after COVID-19, anxiety score (GAD-7) after COVID-19, living alone, and exhaustion were positively correlated with depression. Furthermore, post-traumatic stress symptoms, stress score (Global Assessment of Recent Stress), depression score (PHQ-9) after COVID-19, and exhaustion were positively correlated with anxiety. CONCLUSION: In Korea, during the COVID-19 pandemic, HCWs commonly suffered from mental health problems, including depression and anxiety. Regularly checking the physical and mental health problems of HCWs during the COVID-19 pandemic is crucial, and social support and strategy are needed to reduce the heavy workload and psychological distress of HCWs.

Outcomes of bilateral axillo-breast approach robotic parathyroidectomy versus open parathyroidectomy for primary hyperparathyroidism: a single-institution retrospective study.

Purpose: Bilateral axillo-breast approach robotic parathyroidectomy (BABA-RP) aims to remove overactive or enlarged parathyroid glands with no visible neck collar incision. In this study, we compared the safety and surgical outcomes of BABA-RP vs. those of an open surgery group to ascertain whether BABA-RP is a safe and feasible surgical approach for patients with primary hyperparathyroidism (pHPT). Methods: This single-institution retrospective cohort study included 74 patients with primary HPT who underwent open parathyroidectomy (n = 37) or BABA-RP (n = 37) at our institution between November 2014 and March 2023. Patient demographics, biochemical cure rates, operative time, blood loss rates, and complication rates were examined and compared. Results: The patients in the BABA-RP group were younger and had a longer mean operative time. Regarding complication events, 2 patients in the open surgery group and 1 patient in the BABA-RP group had transient hypoparathyroidism. All 74 patients achieved biochemical cure at <6 months, regardless of the approach used. Two patients in the BABA-RP group and 1 patient in the open surgery group had carcinoma on surgical pathology. All 3 patients with parathyroid carcinoma remained recurrence-free at 1-year follow-up. Conclusion: Compared with the open procedure, BABA-RP is a safe and feasible procedure that provides an excellent biochemical cure rate for patients with pHPT and has superior cosmetic benefits with equivalent surgical outcomes.

Effect of dietary heat-killed Lactiplantibacillus plantarum VSG3 on growth, immunity, antioxidant status, and immune-related gene expression in pathogen-aggravated Cyprinus carpio.

Heat-killed probiotics offer an alternative approach to enhance growth and disease resistance in farmed fish. In this study, we isolated Lactiplantibacillus plantarum VSG3 from the gut of Labeo rohita to investigate the effects of heat-killed L. plantarum (HK-LP) on the health and growth performance of Cyprinus carpio fingerlings. Different concentrations of HK-LP (0, 50, 100, 200, 300, and 400 mg/kg) were administered to the fish, followed by a challenge with Aeromonas hydrophila after 8 weeks of feeding. Notably, the LP200 group exhibited significantly improved percentage weight gain and specific growth rate, accompanied by the lowest feed conversion ratio. Post-challenge survival rates were considerably enhanced in the LP200 group, reaching 60.65%. Moreover, serum analysis indicated significantly higher levels of total protein and albumin in the LP200 group than in the control group. Although HK-LP had no substantial impact on certain serum parameters (glucose, total cholesterol, cortisol, and alanine aminotransferase), aspartate aminotransferase levels were considerably low in the LP200 group. Intestinal protease and trypsin activities significantly increased in the LP200 group, while no significant changes were observed in lipase and amylase activities post-pathogen challenge. Serum immunological indices, including lysozyme, alternative complement pathway, and phagocytic activity, improved considerably in the LP200 group. Additionally, serum antioxidant enzyme activities (superoxide dismutase [SOD], glutathione peroxidase [GPx], catalase [CAT], and myeloperoxidase) were significantly elevated in the LP200 group, while malondialdehyde level was reduced. Gene expression analysis in liver tissue indicated strong upregulation of antioxidant-related genes (SOD, CAT, nuclear factor erythroid 2 [NFE2]-related factor 2 [Nrf2], Kelch-like ECH-associated protein 1[Keap1]) in the LP100 and LP200 groups. Pro-inflammatory cytokines (IL-1ß and TNF-α) were considerably downregulated in the kidneys of the LP200 post-challenged fish, although the anti-inflammatory cytokine IL-10 showed an increased expression. Quadratic regression analysis identified the optimal dietary HK-LP level for maximizing growth and immune performance (200.381-270.003 mg/kg). In summary, our findings underscore the potential of HK-LP as a valuable dietary supplement for enhancing carp aquaculture, particularly at the appropriate concentration.