Lung cancer-specific symptoms and fear of cancer recurrence among recurrence-free non-small cell lung cancer survivors.

PURPOSE: Lung cancer survivors have more psychosocial problems, including depression and anxiety disorder, than other cancer survivors. Lung cancer-specific symptoms, such as cough, dyspnea, or pain in chest, might increase FCR among survivors. We aimed to evaluate the association between lung cancer-specific symptoms and FCR among recurrence-free non-small cell lung cancer (NSCLC) survivors. METHODS: This is a cross-sectional study. Recurrence-free NSCLC survivors were recruited from January to October 2020 at a tertiary hospital in Seoul, Korea. We measured FCR using the Korean version of FCRI-SF and categorized them into three groups: non-clinical FCR (nFCR, < 13), subclinical FCR (sFCR, 13 to 21), and clinical FCR (cFCR, ≥ 22). Lung cancer-specific symptoms were measured using the Korean version of EORTC QLQ-LC13 and EORTC QLQ-C30. RESULTS: A total of 727 survivors were enrolled. One-third (30.8%) of survivors reported sFCR, and 19.7% had cFCR. In a multivariate analysis, survivors with severe pain in chest were 4.7 times (95% CI: 2.4-9.0) more likely to experience cFCR compared to those without it. Mild dyspnea (OR 1.7, 95% CI: 1.1-2.7) and mild dysphagia (OR 2.4, 95% CI: 1.3-4.4) were associated with cFCR. Survivors with sFCR (Coef. - 6.3, 95% CI: - 9.8, - 2.8) and cFCR (Coef. - 11.3, 95% CI: - 15.5, - 7.2) had poorer quality of life compared to survivors with nFCR. CONCLUSION: NSCLC survivors were experiencing lung cancer-specific symptoms even a few years after treatment, which were associated with cFCR, resulting in poor HRQoL. It is necessary to develop a lung cancer-specific symptom checklist and use it during even long-term surveillance.

Strategic combination of bacteriophages with highly susceptible cells for enhanced intestinal settlement and resistant cell killing.

Avian pathogenic Escherichia coli (APEC) causes enormous economic losses and is a primary contributor to the emergence of multidrug resistance (MDR)-related problems in the poultry industry. Bacteriophage (phage) therapy has been successful in controlling MDR, but phage-resistant variants have rapidly emerged through the horizontal transmission of diverse phage defense systems carried on mobile genetic elements. Consequently, while multiple phage cocktails are recommended for phage therapy, there is a growing need to explore simpler and more cost-effective phage treatment alternatives. In this study, we characterized two novel O78-specific APEC phages, φWAO78-1 and φHAO78-1, in terms of their morphology, genome, physicochemical stability and growth kinetics. Additionally, we assessed the susceptibility of thirty-two O78 APEC strains to these phages. We analyzed the roles of highly susceptible cells in intestinal settlement and fecal shedding (susceptible cell-assisted intestinal settlement and shedding, SAIS) of phages in chickens via coinoculation with phages. Furthermore, we evaluated a new strategy, susceptible cell-assisted resistant cell killing (SARK), by comparing phage susceptibility between resistant cells alone and a mixture of resistant and highly susceptible cells in vitro. As expected, high proportions of O78 APEC strains had already acquired multiple phage defense systems, exhibiting considerable resistance to φWAO78-1 and φHAO78-1. Coinoculation of highly susceptible cells with phages prolonged phage shedding in feces, and the coexistence of susceptible cells markedly increased the phage susceptibility of resistant cells. Therefore, the SAIS and SARK strategies were demonstrated to be promising both in vivo and in vitro.

Supporting Life Adjustment in Patients With Lung Cancer Through a Comprehensive Care Program: Protocol for a Controlled Before-and-After Trial.

BACKGROUND: Lung cancer diagnosis affects an individual's quality of life as well as physical and emotional functioning. Information on survivorship care tends to be introduced at the end of treatment, but early intervention may affect posttreatment adjustment. However, to the best of our knowledge, no study has explored the effect of early information intervention on the return to work, family, and societal roles of lung cancer survivors. OBJECTIVE: We report the study protocol of a comprehensive care prehabilitation intervention designed to facilitate lung cancer survivors' psychological adjustment after treatment. METHODS: A comprehensive care program was developed based on a literature review and a qualitative study of patients with lung cancer and health professionals. The Lung Cancer Comprehensive Care Program consists of educational videos and follow-up visits by a family medicine physician. To prevent contamination, the control group received routine education, whereas the intervention group received routine care and intervention. Both groups completed questionnaires before surgery (T0) and at 1-month (T1), 6-month (T2), and 1-year (T3) follow-up visits after surgery. The primary outcome was survivors' psychological adjustment to cancer 6 months after pulmonary resection. RESULTS: The historical control group (n=441) was recruited from September 8, 2021, to April 20, 2022, and the intervention group (n=350) was recruited from April 22, 2022, to October 17, 2022. All statistical analyses will be performed upon completion of the study. CONCLUSIONS: This study examined the effectiveness of an intervention that provided general and tailored informational support to lung cancer survivors, ranging from before to the end of treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05078918; https://clinicaltrials.gov/ct2/show/NCT05078918. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54707.

Synaptotagmin-4 induces anhedonic responses to chronic stress via BDNF signaling in the medial prefrontal cortex.

Stressful circumstances are significant contributors to mental illnesses such as major depressive disorder. Anhedonia, defined as loss of the ability to enjoy pleasure in pleasurable situations, including rewarding activities or social contexts, is considered a key symptom of depression. Although stress-induced depression is associated with anhedonia in humans and animals, the underlying molecular mechanisms of anhedonic responses remain poorly understood. In this study, we demonstrated that synaptotagmin-4 (SYT4), which is involved in the release of neurotransmitters and neurotrophic factors, is implicated in chronic stress-induced anhedonia. Employing chronic unpredictable stress (CUS), we evaluated two subpopulations of mice, susceptible (SUS, anhedonic) and resilient (RES, nonanhedonic), based on sucrose preference, which was strongly correlated with social reward. The FosTRAP (targeted recombination in active populations) system and optogenetic approach revealed that neural activity in the medial prefrontal cortex (mPFC) was significantly associated with CUS-induced anhedonic behavioral phenotypes. By conducting weighted gene coexpression network analysis of RNA sequencing data from the mPFC of SUS and RES mice, we identified Syt4 as a hub gene in a gene network that was unique to anhedonia. We also confirmed that Syt4 overexpression in the mPFC was pro-susceptible, while Syt4 knockdown was pro-resilient; the pro-susceptible effects of SYT4 were mediated through a reduction in brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) signaling in the mPFC. These findings suggest that SYT4-BDNF interactions in the mPFC represent a crucial regulatory mechanism of anhedonic susceptibility to chronic stress.

A Case of Eccrine Syringofibroadenoma Related to Senile Gluteal Dermatosis.

Eccrine syringofibroadenoma (ESFA) is a tumor of eccrine ductal differentiation. ESFA is a rare disease, with only approximately 80 cases reported worldwide. ESFA can be classified into five subtypes. Senile gluteal dermatosis (SGD) was first reported in Japan in 1979. It is a relatively common geriatric dermatosis in East Asia, and characterized by hyperkeratotic lichenified skin lesions in the gluteal region. An 86-year-old woman presented with a solitary recurrent dark brown plaque in the sacral area. There was a hyperkeratotic lichenified brownish patch around the plaque, which was clinically considered SGD. Histopathological examination of biopsy specimen revealed thin anastomosing reticulated strands of basaloid cuboidal cells. The tumor extends from the basal layer of the epidermis to the dermis. These findings are consistent with those of ESFA. The patient was treated with total excision of the skin lesion. Reactive ESFA is related to tissue regeneration and remodeling after damage, such as trauma and burns. There is no literature reporting ESFA related to SGD so far, but there have been few reports of cases occurring in soles or buttocks, which are constantly under pressure. This is the first report on reactive ESFA related to SGD, and further research is needed to reveal the pathogenic mechanism.

Identification of Novel Biomarkers for Early Diagnosis of Atherosclerosis Using High-Resolution Metabolomics.

Atherosclerosis (AS) is a metabolic disorder and the pre-stage of several cardiovascular diseases, including myocardial infarction, stroke, and angina pectoris. Early detection of AS can provide the opportunity for effective management and better clinical results, along with the prevention of further progression of the disease. In the current study, an untargeted and targeted metabolomic approach was used to identify possible metabolic signatures that have altered levels in AS patients. A total of 200 serum samples from individuals with AS and normal were analyzed via liquid chromatography-high-resolution mass spectrometry. Univariate and multivariate analysis approaches were used to identify differential metabolites. A group of metabolites associated with bile acids, amino acids, steroid hormones, and purine metabolism were identified that are capable of distinguishing AS-risk sera from normal. Further, the targeted metabolomics approach confirmed that six metabolites, namely taurocholic acid, cholic acid, cortisol, hypoxanthine, trimethylamine N-oxide (TMAO), and isoleucine, were found to be significantly upregulated, while the concentrations of glycoursodeoxycholic acid, glycocholic acid, testosterone, leucine, methionine, phenylalanine, tyrosine, and valine were found to be significantly downregulated in the AS-risk sera. The receiver operating characteristic curves of three metabolites, including cortisol, hypoxanthine, and isoleucine, showed high sensitivity and specificity. Taken together, these findings suggest cortisol, hypoxanthine, and isoleucine as novel biomarkers for the early and non-invasive detection of AS. Thus, this study provides new insights for further investigations into the prevention and management of AS.

Clinical and laboratory factors associated with the presence of dysmorphic oocytes in intracytoplasmic sperm injection cycles.

OBJECTIVE: This study investigated the clinical and laboratory factors associated with the presence of dysmorphic oocytes in intracytoplasmic sperm injection (ICSI) cycles. METHODS: The study involved 200 ICSI cycles, performed from 2020 to 2021, that yielded at least one mature oocyte. Clinical characteristics and ovarian stimulation methods were compared between 68 cycles with at least one dysmorphic oocyte (the dysmorphic group) and 132 cycles with normal-form oocytes only (the non-dysmorphic group). Dysmorphic oocytes were characterized by dark cytoplasm, cytoplasmic granularity, cytoplasmic vacuoles, refractile bodies in the cytoplasm, smooth endoplasmic reticulum in the cytoplasm, an oval shape, an abnormal zona pellucida, a large perivitelline space, debris in the perivitelline space, or an abnormal polar body. RESULTS: The ages of the women, indications for in vitro fertilization, serum anti-Müllerian hormone levels, and rates of current ovarian endometrioma were similar between the dysmorphic and non-dysmorphic groups. In both groups, the three ovarian stimulation regimens, two types of pituitary suppression, and total gonadotropin dose were employed similarly. However, the dual-trigger method was used more frequently in the dysmorphic group (67.6% vs. 50%, p=0.024). The dysmorphic group contained significantly more immature oocytes and exhibited significantly lower oocyte maturity (50% vs. 66.7%, p=0.001) than the non-dysmorphic cycles. Within the dysmorphic group, significantly lower oocyte maturity was found in the cycles using a dual-trigger, but not in those with a human chorionic gonadotropin trigger. CONCLUSION: ICSI cycles with dysmorphic oocytes are closely associated with reduced oocyte maturity. This association was observed exclusively in dual-trigger cycles.

Lactobacillus reuteri ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System.

Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD). Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.

Merkel Cell Carcinoma of the Trunk: Two Case Reports and Imaging Review.

Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumor primarily located in the head and neck. We report the imaging features of pathologically confirmed MCC in the trunk. On US, MCC showed heterogeneous echogenicity with perpendicular hypoechoic linear bands that resembled "columns of smoke" in the skin and subcutaneous layers as well as prominent vascularity. On MRI, the tumor showed hypointensity on T1-weighted images and hyperintensity on proton density and T2-weighted images with linear low-signal bands in the skin and subcutaneous layers as well as intense enhancement on T1-enhanced images. Although MCC has nonspecific imaging features, these characteristics may be helpful for the early diagnosis of this disease.

Continuous On-Chip Cell Washing Using Viscoelastic Microfluidics.

Medium exchange of particles/cells to a clean buffer with a low background is essential for biological, chemical, and clinical research, which has been conventionally conducted using centrifugation. However, owing to critical limitations, such as possible cell loss and physical stimulation of cells, microfluidic techniques have been adopted for medium exchange. This study demonstrates a continuous on-chip washing process in a co-flow system using viscoelastic and Newtonian fluids. The co-flow system was constructed by adding a small amount of biocompatible polymer (xanthan gum, XG) to a sample containing particles or cells and introducing Newtonian fluids as sheath flows. Polymer concentration-dependent and particle size-dependent lateral migration of particles in the co-flow system were examined, and then the optimal concentration and the critical particle size for medium exchange were determined at the fixed total flow rate of 100 µL/min. For clinical applications, the continuous on-chip washing of white blood cells (WBCs) in lysed blood samples was demonstrated, and the washing performance was evaluated using a scanning spectrophotometer.

Recent Studies in Photodynamic Therapy for Cancer Treatment: From Basic Research to Clinical Trials.

Photodynamic therapy (PDT) is an emerging and less invasive treatment modality for various types of cancer. This review provides an overview of recent trends in PDT research, ranging from basic research to ongoing clinical trials, focusing on different cancer types. Lung cancer, head and neck cancer, non-melanoma skin cancer, prostate cancer, and breast cancer are discussed in this context. In lung cancer, porfimer sodium, chlorin e6, and verteporfin have shown promising results in preclinical studies and clinical trials. For head and neck cancer, PDT has demonstrated effectiveness as an adjuvant treatment after surgery. PDT with temoporfin, redaporfin, photochlor, and IR700 shows potential in early stage larynx cancer and recurrent head and neck carcinoma. Non-melanoma skin cancer has been effectively treated with PDT using methyl aminolevulinate and 5-aminolevulinic acid. In prostate cancer and breast cancer, PDT research is focused on developing targeted photosensitizers to improve tumor-specific uptake and treatment response. In conclusion, PDT continues to evolve as a promising cancer treatment strategy, with ongoing research spanning from fundamental investigations to clinical trials, exploring various photosensitizers and treatment combinations. This review sheds light on the recent advancements in PDT for cancer therapy and highlights its potential for personalized and targeted treatments.

CT Findings of May-Thurner Syndrome in Diffuse Idiopathic Skeletal Hyperostosis: A Case Report.

May-Thurner syndrome (MTS) is a rare cause of deep vein thrombosis. Several cases of MTS because of various causes have been reported. However, MTS due to osteophytes in patients with underlying diffuse idiopathic skeletal hyperostosis (DISH) has not been reported in English literature, to the best of our knowledge. Here, we present the CT findings of MTS in patient with DISH.

Exploring the relationships among art therapy students' burnout, practicum stress, and teacher support.

Introduction: This study examines how teacher support and practicum stress affect art therapy graduate students' burnout. Methods: A total of 125 master's and doctoral students from art therapy graduate schools in Korea participated in the study. We conducted a correlation analysis and multiple regression analysis to explore the relationship between the variables. Results: The correlation analysis results showed that burnout, practicum stress, and social support are significantly interrelated. The regression analysis results indicated that practicum stress increases burnout while social support decreases it. When we used the sub-factors of social support as independent variables, we found that professor support rather than the support of colleagues or family significantly reduced burnout. When we divided the perceived teacher support into emotional support and academic support, our analysis identified that academic support was more important than emotional support to reduce students' burnout. Conclusion: Art therapy students' practicum stress can cause psychological burnout, while teacher support-especially academic support-can lower the possibility of experiencing such burnout.

The Role of Glutamate Underlying Treatment-resistant Depression.

The monoamine hypothesis has significantly improved our understanding of mood disorders and their treatment by linking monoaminergic abnormalities to the pathophysiology of mood disorders. Even 50 years after the monoamine hypothesis was established, some patients do not respond to treatments for depression, including selective serotonin reuptake drugs. Accumulating evidence shows that patients with treatment-resistant depression (TRD) have severe abnormalities in the neuroplasticity and neurotrophic factor pathways, indicating that different treatment approaches may be necessary. Therefore, the glutamate hypothesis is gaining attention as a novel hypothesis that can overcome monoamine restrictions. Glutamate has been linked to structural and maladaptive morphological alterations in several brain areas associated with mood disorders. Recently, ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has shown efficacy in TRD treatment and has received the U.S. Food and Drug Administration approval, revitalizing psychiatry research. However, the mechanism by which ketamine improves TRD remains unclear. In this review, we re-examined the glutamate hypothesis, bringing the glutamate system onboard to join the modulation of the monoamine systems, emphasizing the most prominent ketamine antidepressant mechanisms, such as NMDAR inhibition and NMDAR disinhibition in GABAergic interneurons. Furthermore, we discuss the animal models used in preclinical studies and the sex differences in the effects of ketamine.

Analysis of facial vascular pattern characteristics in the Korean population.

BACKGROUND: Facial erythema is a common problem among patients visiting dermatologists. However, data on the clinical characteristics of facial erythema in healthy people are lacking. We aimed to compare and analyze the severity and pattern of facial vascularity in healthy subjects based on their age and gender. MATERIALS AND METHODS: This study included 198 Korean volunteers (126 females and 72 males) with Fitzpatrick skin types II, III, or IV. Fourteen different anatomical areas on the face were divided into facial erythema units. Each unit was scored from one (least erythematous) to five (most erythematous) according to the observed level of erythema on the red images implemented as hemoglobin content. We also evaluated the presence of facial telangiectatic macules. RESULTS: On average, the perinasal, nasal, and cheek units were the most hypervascular regions. In contrast, the degree of facial erythema was lowest in the labial (perioral), neck, and temporal regions. The average value of erythema was higher in males than in females. Additionally, the severity of erythema tended to increase with age. In both males and females, the number of telangiectatic macules increased with age. CONCLUSIONS: We analyzed the clinical characteristics of erythema in healthy subjects with Fitzpatrick skin types II, III, or IV in the Korean population. This study is expected to be used to identify the neurovascular pathogenesis of the most common regions of facial dermatosis in the future.

Langerhans Cell Histiocytosis in the Nasal Bone: A Rare Case.

Nasal bone involvement of Langerhans cell histiocytosis is rarely reported. Here we present a case of a 13-year-old boy with a palpable nasal mass. Ultrasonography revealed a hypoechoic mass on the left side of the nose. Both CT scanning and MRI showed an osteolytic mass. The lesion seen on MRI was well-defined mass with homogeneous enhancement. Histopathological examination of the resected specimen confirmed the diagnosis of LCH.

Determination of vitamin K encapsulated into lipid nanocarriers by dispersive liquid-liquid microextraction combined with liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry.

Dispersive liquid-liquid microextraction was used in conjunction with liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry to quantitate vitamins K1 and K2 in vitamin-fortified emulsions, and vital microextraction parameters were optimized using response surface methodology coupled with Box-Behnken design. Under optimal microextraction conditions, highly linear (R 2 > .999) calibration curves were obtained for both vitamins in a broad concentration range (1-1000 µg/L), and vitamin recoveries exceeded 90%. The detection and quantitation limits equaled 1.89 and 5.72 µg/L for vitamin K1, respectively, and 5.00 and 15.15 µg/L for vitamin K2, respectively. When applied to vitamin-K-loaded nanoemulsions and solid lipid nanoparticles, the developed method achieved excellent results, outperforming the currently employed Korean Food Code method, and therefore holding great promise for the quantitation of vitamin K in vitamin-fortified food products.

Effect of COVID-19 (SARS-CoV-2) Vaccination on Patients with Atopic Dermatitis Treated with Dupilumab: A Multicenter, Observational Study.

BACKGROUND: Atopic dermatitis (AD) patients usually wonder if their condition will worsen after vaccination or if they should continue with the treatment they are receiving. Considering that many patients treated with dupilumab had previously experienced severe AD symptoms and flares, the concerns are more understandable. OBJECTIVE: This study aimed to investigate the safety of the coronavirus disease 2019 (COVID-19) vaccination in patients with AD treated with dupilumab. METHODS: We enrolled 133 patients (101 dupilumab-treated and 32 systemic oral agents-treated as control group) with AD from six hospitals. Patients were asked about worsening pruritus and AD (5-point Likert scale) after vaccination. AD variables (eczema area and severity index [EASI], investigator's global assessment [IGA], itch numerical rating scale [NRS], sleep NRS, and patient-oriented eczema measure [POEM]) were compared pre- and post-vaccination. Adverse reactions to the COVID-19 vaccination were observed. RESULTS: The incidence of adverse reactions to COVID-19 vaccines and worsening AD symptoms in dupilumab-treated patients were not significantly different compared with that in the control group. The itch NRS score increased significantly after vaccination (p<0.001). However, there were no statistically significant differences between the pre-and post-EASI, IGA, and POEM scores. Eight patients (7.9%) had worse EASI scores and required rescue therapy; however, most were easily managed with low-dose steroids or topical agents. None of the patients discontinued dupilumab treatment. CONCLUSION: No serious adverse reactions were observed in patients with AD after COVID-19 vaccination. Exacerbation of pruritus and AD symptoms was observed but was mostly mild and transient.

Prognostic Implication of Exfoliative Airway Pathology in Cancer-Free Coal Workers' Pneumoconiosis.

BACKGROUND: The purpose of this study is to see if exfoliative pulmonary airway pathology in cancer-free coal workers' pneumoconiosis (CWP) can be used as a biomarker for predicting pulmonary morbidity. METHODS: We investigated persistent metaplastic changes in bronchoscopic washing cytology and differential cell counts in bronchoalveolar lavages (BAL) in 97 miners with CWP and 80 miners without CWP as the control. Clinicopathological parameters were examined including pulmonary function tests and the presence of progressive massive fibrosis. RESULTS: When compared to the control group, severe alveolitis, severe goblet cell hyperplasia (GCH), severe hyperplastic epithelial change, and severe squamous metaplasia were the distinguishing biomarkers in CWP. Multivariate analysis revealed that severe alveolitis and severe GCH, along with miner duration and current smoker, were independent predictors of pulmonary mortality. The survival analysis revealed a significantly different survival rate between the three groups: no evidence of severe alveolitis and severe GCH, presence of severe alveolitis or severe GCH but not both, and both severe alveolitis and severe GCH. CONCLUSIONS: The severities of alveolitis and goblet cell hyperplasia in the bronchoscopic study are independent prognostic factors for CWP. A pathologic grading system based on these two parameters could be used in the stratification and clinical management of CWP patients.