Resilience of Family Caregivers of People With Dementia in South Korea: A Scoping Review.

BACKGROUND: Due to rapid increases in the number of Korean people with dementia, dementia has become a priority health issue in South Korea. Likewise, the well-being of family caregivers of people with dementia has also become an issue of concern. However, little is known about the resilience of Korean family caregivers because there is a lack of review studies from a Korean cultural perspective about the resilience of family caregivers of people with dementia. OBJECTIVES: The purpose of this scoping review was to investigate quantitative studies related to resilience theories, measurement instruments, correlates and resilience interventions for family caregivers of people with dementia. METHOD: This review was conducted according to the Joanna Briggs Institute based on Arksey and O'Malley. Nine databases were searched to retrieve evidence published in English or Korean between January 2000 and September 2022. Studies with a quantitative research design reporting the resilience of family caregivers of people with dementia based on a resilience theory framework were included. RESULTS: A total of 13 studies were included in this review. All studies used either a modified McCubbin and McCubbin's family stress, adjustment and adaptation model or Walsh's family resilience model. All resilience instruments were used without cross-cultural adaptation. Family adaptation, social support, life satisfaction, family (di)stress and caregiver burden were associated with resilience among family caregivers. A few family resilience-enhancing programmes showed a positive effect on caregiver resilience. CONCLUSION: This review noted that all the resilience measures documented in this study need to test for cultural adaptation in a Korean context. Further research is required to develop and implement family-based, culturally tailored interventions to effectively enhance Korean resilience for family caregivers of people with dementia. IMPLICATIONS FOR PRACTICE: Gerontological nurses should include Korean family caregivers in their nursing care and assess whether family caregivers have depression or suicidal thoughts to promote better health outcomes for caregivers and their family members.

High Thickness Tolerance in All-Polymer-Based Organic Photovoltaics Enables Efficient and Stable In-Door Operation.

Organic photovoltaics (OPVs) have great potential to drive low-power consumption electronic devices under indoor light due to their highly tunable optoelectronic properties. Thick devices (>300 nm photo-active junctions) are desirable to maximize photocurrent and to manufacture large-scale modules via solution-processing. However, thick devices usually suffer from severe charge recombination, deteriorating device performances. Herein, the study demonstrates excellent thickness tolerance of all-polymer-based PVs for efficient and stable indoor applications. Under indoor light, device performance is less dependent on photoactive layer thickness, exhibiting the best maximum power output in thick devices (34.7 µW cm-2 in 320-475 nm devices). Thick devices also exhibit much better photostability compared with thin devices. Such high thickness tolerance of all-polymer-based PV devices under indoor operation is attributed to strongly suppressed space-charge effects, leading to reduced bimolecular recombination losses in thick devices. The unbalanced charge carrier mobilities are identified as the main cause for significant space-charge effects, which is confirmed by drift-diffusion simulations. This work suggests that all-polymer-based PVs, even with unbalanced mobilities, are highly desirable for thick, efficient, and stable devices for indoor applications.

Mesenchymal Stem Cell Therapy in Alopecia Areata: Visual and Molecular Evidence from a Mouse Model.

Recent studies have highlighted the potential of Mesenchymal Stem Cells (MSCs) as an alternative treatment for Alopecia Areata (AA) due to their immunosuppressive properties. While MSCs have shown promise in cell experiments, their effectiveness in vivo remains uncertain. This study aims to validate local administration of MSC therapy's efficacy in AA treatment through animal experiments. AA was induced through Interferon-gamma (IFN-γ) administration in mice, and MSC treatment (MSCT)'s effects were assessed visually and through tissue analysis. The MSC-treated group showed more hair regrowth compared to the control (CTL) group. MSCT notably reduced local inflammatory cytokines (JAK1, JAK2, STAT1, STAT3, IFN-γR, IL-1ß, IL-16, IL-17α, and IL-18) in AA-induced mice's skin, but systemic cytokine levels remained unchanged. Furthermore, MSC treatment normalized the expression of Wnt/ß-catenin signaling pathway genes (LEF1 and ß-catenin) and growth factors (FGF7 and FGF2), which are crucial for hair cycle regulation. This study lays the groundwork for further exploring MSCs as a potential treatment for AA, but more research is needed to fully understand their therapeutic potential.

Glucose-dependent insulinotropic polypeptide (GIP) alleviates ferroptosis in aging-induced brain damage through the Epac/Rap1 signaling pathway.

Glucose-dependent insulinotropic polypeptide (GIP), a 42-aminoacid hormone, exerts multifaceted effects in physiology, most notably in metabolism, obesity, and inflammation. Its significance extends to neuroprotection, promoting neuronal proliferation, maintaining physiological homeostasis, and inhibiting cell death, all of which play a crucial role in the context of neurodegenerative diseases. Through intricate signaling pathways involving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis and regulates a defense system against ferroptosis, an essential process in aging. Our study, utilizing GIP-overexpressing mice and in vitro cell model, elucidates the pivotal role of GIP in preserving neuronal integrity and combating age-related damage, primarily through the Epac/Rap1 pathway. These findings shed light on the potential of GIP as a therapeutic target for the pathogenesis of ferroptosis in neurodegenerative diseases and aging. [BMB Reports 2024; 57(9): 417-423].

Impact of a game-based interprofessional education program on medical students' perceptions: a text network analysis using essays.

BACKGROUND: The increasing complexity of the healthcare environment and the necessity of multidisciplinary teamwork have highlighted the importance of interprofessional education (IPE). IPE aims to enhance the quality of patient care through collaborative education involving various healthcare professionals, such as doctors, nurses, and pharmacists. This study sought to analyze how game-based IPE activities influence students' perceptions and reflective thinking. It also aimed to identify the shifts in perception and effectiveness caused by this educational approach. METHODS: The study is based on a game-based IPE program conducted at University A, involving medical and nursing students in structured learning and team-based activities. Data were collected using essays written by the students after they had participated in IPE activities. Text network analysis was conducted by extracting key terms, performing centrality analysis, and visualizing topic modeling to identify changes in students' perceptions and reflective thinking. RESULTS: Keywords such as "patient," "thought," "group," "doctor," "nurse," and "communication" played a crucial role in the network, indicating that students prioritized enhancing their communication and problem-solving skills within the educational environment. The topic modeling results identified three main topics, each demonstrating the positive influence of game-based collaborative activities, interprofessional perspectives, and interdisciplinary educational experiences on students. Topic 3 (interdisciplinary educational experience) acted as a significant mediator connecting Topic 1 (game-based collaborative activity experience) and Topic 2 (interprofessional perspectives). CONCLUSION: This study demonstrates that game-based IPE activities are an effective educational approach for enhancing students' team building skills, particularly communication and interprofessional perspectives. Based on these findings, future IPE programs should focus on creating collaborative learning environments, strengthening communication skills, and promoting interdisciplinary education. The findings provide essential insights for educational designers and medical educators to enhance the effectiveness of IPE programs. Future research should assess the long-term impacts of game-based IPE on clinical practice, patient outcomes, and participants' professional development.

Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications.

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a 40% recurrence rate, lacking effective prognostic biomarkers and surveillance methods. This prospective, multicenter, observational study aimed to evaluate circulating tumor DNA (ctDNA) as a biomarker for detecting MCC recurrence. METHODS: Plasma samples, clinical data, and imaging results were collected from 319 patients. A tumor-informed ctDNA assay was used for analysis. Patients were divided into discovery (167 patients) and validation (152 patients) cohorts. Diagnostic performance, including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), was assessed. RESULTS: ctDNA showed high sensitivity, 95% (discovery; 95% CI, 87 to 99) and 94% (validation; 95% CI, 85 to 98), for detecting disease at enrollment, with corresponding specificities of 90% (95% CI, 82 to 95) and 86% (95% CI, 77 to 93). A positive ctDNA during surveillance indicated increased recurrence risk, with hazard ratios (HRs) of 6.8 (discovery; 95% CI, 2.9 to 16) and 20 (validation; 95% CI, 8.3 to 50). The PPV for clinical recurrence at 1 year after a positive ctDNA test was 69% (discovery; 95% CI, 32 to 91) and 94% (validation; 95% CI, 71 to 100), respectively. The NPV at 135 days after a negative ctDNA test was 94% (discovery; 95% CI, 90 to 97) and 93% (validation; 95% CI, 89 to 97), respectively. Patients positive for ctDNA within 4 months after treatment had higher rates of recurrence, with 1-year rates of 74% versus 21% (adjusted HR, 7.4 [95% CI, 2.7 to 20]). CONCLUSION: ctDNA testing exhibited high prognostic accuracy in detecting MCC recurrence, suggesting its potential to reduce frequent surveillance imaging. ctDNA also identifies high-risk patients who need more frequent imaging and may be best suited for adjuvant therapy trials.

Lack of Clinically Significant Relationships of Age or Body Mass Index with Merkel Cell Carcinoma Immunotherapy Outcomes.

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a high risk of metastasis. The development of anti-PD-1/PD-L1 immunotherapy has improved outcomes for advanced MCC, yet about 50% of such patients do not achieve durable responses. This study analyzed the effects of age and body mass index (BMI) on immunotherapy response in 183 advanced MCC patients from a single-center longitudinal database. Using Fine-Gray or Cox regression models, treatment response, progression-free survival (PFS), MCC-specific survival, and overall survival (OS) were evaluated. Age showed a significant non-linear relationship with treatment response (p = 0.04), with patients much older or younger than 70 years less likely to respond. However, age was not significantly associated with PFS (p = 0.21), MCC-specific survival (p = 0.72), or OS (p = 0.36). Similarly, BMI was not significantly correlated with treatment response (p = 0.41), PFS (p = 0.52), MCC-specific survival (p = 0.78), or OS (p = 0.71). Unlike previous studies suggesting that obesity and advanced age improve outcomes in other cancers, these associations were not observed in MCC. These findings suggest that age and BMI should not influence eligibility for immunotherapy in MCC patients, emphasizing the importance of unbiased patient selection for this treatment.

Contributing Factors to Endothelial Dysfunction in Individuals with Spinal Cord Injuries.

Background: Patients with spinal cord injuries (SCIs) are at a greater risk for the development of cardiovascular diseases (CVDs) than able-bodied individuals due to the high risk of endothelial dysfunction. Summary: For instance, patients with SCIs lose autonomic control of the heart and vasculature, which results in severe fluctuations in blood pressure. These oscillations between hypotension and hypertension have been shown to damage blood vessel endothelial cells and may contribute to the development of atherosclerosis. Furthermore, the loss of skeletal muscle control results in skeletal muscle atrophy and inward remodeling of the conduit arteries. It has been shown that blood vessels in the legs are chronically exposed to high shear, while the aorta experiences chronically low shear. These alterations to shear forces may adversely impact endothelial vasodilatory capacity and promote inflammatory signaling and leukocyte adherence. Additionally, microvascular endothelial vasodilatory capacity is impaired in patients with an SCI, and this may precede changes in conduit artery endothelial function. Finally, due to immobility and a loss of skeletal muscle mass, patients with SCIs have a higher risk of metabolic disorders, inflammation, and oxidative stress. Key Messages: Collectively, these factors may impair endothelium-dependent vasodilatory capacity, promote leukocyte adhesion and infiltration, promote the peroxidation of lipids, and ultimately support the development of atherosclerosis. Therefore, future interventions to prevent CVDs in patients with SCIs should focus on the management of endothelial health to prevent endothelial dysfunction and atherosclerosis.

The EAT-Lancet Diet Index Is Associated with Lower Obesity and Incidence of Type 2 Diabetes in the Multiethnic Cohort.

BACKGROUND: The EAT-Lancet Commission has developed dietary recommendations, named the EAT-Lancet diet, to promote healthy nutrition and sustainable food production worldwide. OBJECTIVES: We developed an adapted score for the EAT-Lancet diet for participants of the Multiethnic Cohort (MEC) Study and its relation with incidence of obesity and type 2 diabetes (T2D). METHODS: The MEC includes 5 ethnic groups followed since 1993-1996. Anthropometric characteristics and dietary intake were assessed by questionnaire at cohort entry (Qx1) and 10 y later (Qx3). To create the EAT-Lancet index (range: 0-48 points), a 3-point scoring system for 16 food groups standardized to 2500 kcal/d was applied. T2D cases were identified through repeated self-reports and administrative data. In a prospective design, obesity at Qx3 and T2D incidence were evaluated using Cox regression to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) while adjusting for relevant covariates. RESULTS: Among 193,379 MEC participants, the overall mean of the EAT-Lancet index score was 25 ± 4 points and 46,140 new T2D cases were identified. Higher adjusted means were observed in females than males, in participants of Japanese American and Native Hawaiian ancestry, and in those with healthy weight than overweight or obese. Obesity was lower in cohort members with higher EAT-Lancet scores (HR: 0.76; 95% CI: 0.73, 0.79 for tertile 3 compared with 1). Although T2D incidence was 10% lower among participants in the highest (27-42 points) compared with the lowest (9-23 points) EAT-Lancet index tertile (HR: 0.90; 95% CI: 0.88, 0.92), the association was attenuated after BMI adjustment (HR: 0.97; 95% CI: 0.94, 0.99). This inverse association with T2D was restricted to African American and European American participants. CONCLUSIONS: These findings support the hypothesis that adherence to the EAT-Lancet diet is related to a lower risk of obesity, which may be partially responsible for the small reduction in T2D incidence.

Merkel cell carcinoma refractory to anti-PD(L)1: utility of adding ipilimumab for salvage therapy.

Merkel cell carcinoma (MCC) incidence has risen to approximately 3,000 cases annually in the USA. Although anti-programmed cell death (ligand) 1 (PD-(L)1) agents are now the first-line treatment for advanced MCC, approximately 50% of such patients do not persistently benefit. In PD-(L)1-refractory cases, ipilimumab (anti-cytotoxic T lymphocyte antigen-4) is often added; however, the extent of the clinical benefit of this combination is controversial. We identified one prospective study, three retrospective studies, and three case reports regarding this combination in refractory MCC. The aggregate response rate from retrospective studies was 32% (13 of 41 patients) with 4 complete responses (CR) and 9 partial responses (PR). In the prospective study, the response rate was very similar at 31% (8 of 26 patients; 4 CR, 4 PR). Response durability was highly variable (range 2 to >43 months), with patients achieving CR having greater durability. Immune-related adverse events (irAEs) were ≥grade III in 29% (retrospective cohort, N=41) and 36% (prospective cohort, N=50). While these aggregate data indicate adding ipilimumab should be considered in this setting, many patients with refractory MCC are ineligible due to comorbidities/irAEs, and approximately 70% will not benefit from this regimen. There is thus a significant unmet need in PD-(L)1-refractory MCC and clinical trials in this setting should be encouraged.

Diet Quality and Risk of Bladder Cancer in the Multiethnic Cohort Study.

This study analyzed the overall quality of the diet using predefined indices, including the Healthy Eating Index-2015 (HEI-2015), the Alternative Healthy Eating Index-2010 (AHEI-2010), the alternate Mediterranean Diet (aMED) score, the Dietary Approaches to Stop Hypertension (DASH) score, and the Dietary Inflammatory Index (DII®), to explore their association with the risk of bladder cancer in the Multiethnic Cohort Study. Data were taken from 186,979 African American, Japanese American, Latino, Native Hawaiian, and non-Hispanic White participants aged 45-75 years, with 1152 incident cases of invasive bladder cancer during a mean follow-up period of 19.2 ± 6.6 years. Cox models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) with comprehensive adjustment for smoking. Comparing the highest vs. lowest diet quality score quintile, HRs (95% CIs) in men was 1.08 (0.86-1.36) for HEI-2015, 1.05 (0.84-1.30) for AHEI-2010, 1.01 (0.80-1.27) for aMED, 1.13 (0.90-1.41) for DASH, and 0.96 (0.76-1.21) for DII®, whereas the corresponding HRs for women were 0.75 (0.53-1.07), 0.64 (0.45-0.92), 0.60 (0.40-0.88), 0.66 (0.46-0.95), and 0.63 (0.43-0.90) with all p values for trend <0.05. The inverse association found in women did not vary by smoking status or race and ethnicity. Our findings suggest that adopting high-quality diets may reduce the risk of invasive bladder cancer among women in a multiethnic population.

Electrical Pulse Stimulation Protects C2C12 Myotubes against Hydrogen Peroxide-Induced Cytotoxicity via Nrf2/Antioxidant Pathway.

Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical pulse stimulation (EPS)-induced antioxidant adaptation in C2C12 myotubes. We found that EPS significantly upregulated Nrf2 and a broad array of downstream antioxidant enzymes involved in multiple antioxidant systems. These effects were completely abolished by pretreatment with a ROS scavenger, N-acetylcysteine. MitoSOX-Red, CM-H2DCFDA, and EPR spectroscopy revealed a significantly higher ROS level in mitochondria and cytosol in EPS cells compared to non-stimulated cells. Seahorse and Oroboros revealed that EPS significantly increased the maximal mitochondrial oxygen consumption rate, along with an upregulated protein expression of mitochondrial complexes I/V, mitofusin-1, and mitochondrial fission factor. A post-stimulation time-course experiment demonstrated that upregulated NQO1 and GSTA2 last at least 24 h following the cessation of EPS, whereas elevated ROS declines immediately. These findings suggest an antioxidant preconditioning effect in the EPS cells. A cell viability study suggested that the EPS cells displayed 11- and 36-fold higher survival rates compared to the control cells in response to 2 and 4 mM H2O2 treatment, respectively. In summary, we found that EPS upregulated a large group of antioxidant enzymes in C2C12 myotubes via a contraction-mitochondrial-ROS-Nrf2 pathway. This antioxidant adaptation protects cells against oxidative stress-associated cytotoxicity.

hMAGEA2 Accelerates the Progression of Prostate Cancer via the EFNA3-Erk1/2 Signaling Pathway.

BACKGROUND/AIM: Human melanoma-associated antigen A2 (hMAGEA2) family members play several roles in many types of cancer and have been explored as potential prognostic markers. In this study, we investigated the molecular mechanism underlying hMAGEA2-mediated tumorigenesis of prostate cancer. MATERIALS AND METHODS: Immunohistochemistry and western blot were used to assess protein expression whereas microarray and quantitative reverse transcription-PCR determined mRNA expression. CCK-8 assay was used to determine cell proliferation. Colony formation assay was used to examine tumorigenesis. Migration and invasion were examined using a transwell assay. Propidium iodide (PI)/Annexin V double staining was performed to measure apoptosis. Transcriptional activity was measured using Dual-luciferase reporter assay. RESULTS: hMAGEA2 was highly over-expressed in human prostate cancer tissues compared to benign prostatic hyperplasia tissues. To elucidate its biological function in prostate cancer, we established two stable hMAGEA2-knockdown prostate cancer cell lines, PC3M and 22RV1, and found that they presented significantly decreased proliferation, anchorage-independent colony formation, migration, and invasion. As hMAGEA2 knockdown suppressed prostate cancer cell growth, we examined its potential influence on tumor apoptosis. hMAGEA2-knockdown cell lines displayed early apoptosis. Moreover, knockdown of hMAGEA2 resulted in the down-regulation of EFNA3 expression. Luciferase assay showed that hMAGEA2 bound to the EFNA promoter region and regulated its transcription. Down-regulation of EFNA3 expression led to decreased Ras/Braf/MEK/Erk1/2 phosphorylation and, consequently, inhibited prostate cancer progression. CONCLUSION: hMAGEA2 promotes prostate cancer growth, metastasis, and tumorigenesis by regulating the EFNA3-Erk1/2 signaling pathway, indicating its potential as a therapeutic marker for prostate cancer.

Octupole moment driven free charge generation in partially chlorinated subphthalocyanine for planar heterojunction organic photodetectors.

In this study, high-performance organic photodetectors are presented which utilize a pristine chlorinated subphthalocyanine photoactive layer. Optical and optoelectronic analyses indicate that the device photocurrent is primarily generated through direct charge generation within the chlorinated subphthalocyanine layer, rather than exciton separation at layer interfaces. Molecular modelling suggests that this direct charge generation is facilitated by chlorinated subphthalocyanine high octupole moment (-80 DÅ2), which generates a 200 meV shift in molecular energetics. Increasing the thickness of chlorinated subphthalocyanine leads to faster response time, correlated with a decrease in trap density. Notably, photodetectors with a 50 nm thick chlorinated subphthalocyanine photoactive layer exhibit detectivities approaching 1013 Jones, with a dark current below 10-7 A cm-2 up to -5 V. Based on these findings, we conclude that high octupole moment molecular semiconductors are promising materials for high-performance organic photodetectors employing single-component photoactive layer.

Oxidative stress and vascular dysfunction: Potential therapeutic targets and therapies in peripheral artery disease.

Peripheral artery disease (PAD) is the manifestation of atherosclerosis characterized by the accumulation of plaques in the arteries of the lower limbs. Interestingly, growing evidence suggests that the pathology of PAD is multifaceted and encompasses both vascular and skeletal muscle dysfunctions, which contributes to blunted physical capabilities and diminished quality of life. Importantly, it has been suggested that many of these pathological impairments may stem from blunted reduction-oxidation (redox) handling. Of note, in those with PAD, excessive production of reactive oxygen species (ROS) outweighs antioxidant capabilities resulting in oxidative damage, which may have systemic consequences. It has been suggested that antioxidant supplementation may be able to assist in handling ROS. However, the activation of various ROS production sites makes it difficult to determine the efficacy of these antioxidant supplements. Therefore, this review focuses on the common cellular mechanisms that facilitate ROS production and discusses how excessive ROS may impair vascular and skeletal muscle function in PAD. Furthermore, we provide insight for current and potential antioxidant therapies, specifically highlighting activation of the Kelch-like ECH-associated protein 1 (Keap1) - Nuclear Factor Erythroid 2-related factor 2 (Nrf2) pathway as a potential pharmacological therapy to combat ROS accumulation and aid in vascular function, and physical performance in patients with PAD. Altogether, this review provides a better understanding of excessive ROS in the pathophysiology of PAD and enhances our perception of potential therapeutic targets that may improve vascular function, skeletal muscle function, walking capacity, and quality of life in patients with PAD.

Impact of intravenous accessibility and prehospital epinephrine use on survival outcomes of adult nontraumatic out-of-hospital cardiac arrest patients.

BACKGROUND: This study compared out-of-hospital cardiac arrest (OHCA) patient outcomes based on intravenous (IV) access and prehospital epinephrine use. METHODS: A retrospective study in Ulsan, South Korea, from January 2017 to December 2022, analyzed adult nontraumatic OHCA cases. Patients were grouped: Group 1 (no IV attempts), Group 2 (failed IV access), Group 3 (successful IV access without epinephrine), and Group 4 (successful IV access with epinephrine), with comparisons using logistic regression analysis. RESULTS: Among 2,656 patients, Group 4 had significantly lower survival to hospital discharge (adjusted OR 0.520, 95% CI 0.346-0.782, p = 0.002) and favorable neurological outcomes (adjusted OR 0.292, 95% CI 0.140-0.611, p = 0.001) than Group 1. Groups 2 and 3 showed insignificant survival to hospital discharge (adjusted OR 0.814, 95% CI 0.566-1.171, p = 0.268) and (adjusted OR 1.069, 95% CI 0.810-1.412, p = 0.636) and favorable neurological outcomes (adjusted OR 0.585, 95% CI 0.299-1.144, p = 0.117) and (adjusted OR 1.075, 95% CI 0.689-1.677, p = 0.751). In the shockable rhythm group, Group 3 had better survival to hospital discharge (adjusted OR 1.700, 95% CI 1.044-2.770, p = 0.033). CONCLUSIONS: Successful IV access with epinephrine showed worse outcomes in both rhythm groups than no IV attempts. Outcomes for failed IV and successful IV access without epinephrine were inconclusive. Importantly, successful IV access without epinephrine showed favorable survival to hospital discharge in the shockable rhythm group, warranting further research into IV access for fluid resuscitation in shockable rhythm OHCA patients.

Unmasking hidden Merkel cell carcinoma recurrences: Three illustrative cases of patients with rising viral oncoprotein antibody levels and challenge of requiring multi-modal imaging to detect clinical disease.

Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer with a high risk of recurrence and metastasis. Regular surveillance through physical exams and imaging studies is crucial for the timely detection of recurrences. MCC patients who produce antibodies to the Merkel cell polyomavirus oncoprotein may benefit from antibody testing in addition to routine imaging surveillance for the early detection of disease recurrence. The clinically available Anti MERKel cell panel (AMERK) is a sensitive tumor marker for Merkel cell polyomavirus positive MCC. Although AMERK is highly sensitive, imaging remains necessary to confirm the location of disease recurrence. MCC exhibits characteristic imaging features, making appropriate imaging modalities, and interpretation important for detection. We present 3 representative patient cases that highlight effective utilization of the AMERK test in addition to imaging for the early detection of MCC recurrence. The rise in the AMERK titer may occur before the disease reaches detectable size on computed tomography scans. Positron emission tomography (PET)-CT can serve as an alternative modality for the early detection of disease. Even subtle abnormalities in 18F-FDG uptake may be significant if accompanied by an increased AMERK titer. Alternative imaging modalities, such as 68Ga-DOTATATE PET-CT and magnetic resonance imaging, can be useful in revealing clinically occult disease in MCC patients. In summary, the AMERK antibody test, alongside imaging, enhances sensitivity in detecting recurrence. By combining these strategies of blood test and imaging, healthcare professionals can identify early signs of MCC recurrence, leading to prompt interventions and improved patient outcomes.

TASL mediates keratinocyte differentiation by regulating intracellular calcium levels and lysosomal function.

Maintaining epidermal homeostasis relies on a tightly organized process of proliferation and differentiation of keratinocytes. While past studies have primarily focused on calcium regulation in keratinocyte differentiation, recent research has shed light on the crucial role of lysosome dysfunction in this process. TLR adaptor interacting with SLC15A4 on the lysosome (TASL) plays a role in regulating pH within the endo-lysosome. However, the specific role of TASL in keratinocyte differentiation and its potential impact on proliferation remains elusive. In our study, we discovered that TASL deficiency hinders the proliferation and migration of keratinocytes by inducing G1/S cell cycle arrest. Also, TASL deficiency disrupts proper differentiation process in TASL knockout human keratinocyte cell line (HaCaT) by affecting lysosomal function. Additionally, our research into calcium-induced differentiation showed that TASL deficiency affects calcium modulation, which is essential for keratinocyte regulation. These findings unveil a novel role of TASL in the proliferation and differentiation of keratinocytes, providing new insights into the intricate regulatory mechanisms of keratinocyte biology.

Intake of Sugar and Food Sources of Sugar and Colorectal Cancer Risk in the Multiethnic Cohort Study.

BACKGROUND: The influence of sugar intake on the risk of colorectal cancer (CRC) remains controversial, and there is a need to investigate the heterogeneity of effects among racial and ethnic groups. OBJECTIVES: To examine the association of intake of simple sugars and their food sources with CRC risk according to race/ethnicity in a multiethnic cohort study. METHODS: We analyzed data from 192,651 participants who participated in the Multiethnic Cohort Study comprising African American, Japanese American, Latino, Native Hawaiian, and White older adults living in Hawaii and California with an average follow-up of 19 y. Intakes of total and specific types of sugars and sugary foods were estimated from a quantitative food frequency questionnaire completed by the participants in 1993-1996. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC risk according to quintiles (Q) of sugar and food intakes using Cox models adjusted for potential confounders. RESULTS: As of December 2017, 4403 incident CRC cases were identified. Among all participants, multivariable-adjusted CRC HRs for Q2, Q3, Q4, and Q5 compared with Q1 for total sugars were 1.03 (95% CI: 0.94, 1.13), 1.05 (95% CI: 0.96, 1.16), 1.12 (95% CI: 1.01, 1.24), and 1.13 (95% CI: 1.01, 1.27), respectively. A similar positive association was observed for total fructose, glucose, fructose, and maltose but not for added sugars and sugary foods. The increased risk appeared to be limited to colon cancer and to be strongest among younger participants (i.e., 45-54 y at baseline); an association with CRC was observed for sugar-sweetened beverages in the latter group. Among racial and ethnic groups, increased risk of CRC was most apparent in Latinos. CONCLUSIONS: In this diverse cohort, intakes of total sugar, total fructose, glucose, fructose, and maltose were associated with an increased risk of CRC, and the association was strongest for colon cancer, younger participants, and Latinos.

Reproductive Factors and Thyroid Cancer Risk: The Multiethnic Cohort Study.

Background: Women are three times more likely to be diagnosed with thyroid cancer than men, with incidence rates per 100,000 in the United States of 20.2 for women and 7.4 for men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and menopausal hormone therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods: Risk factors for thyroid cancer were evaluated among female participants (n = 118,344) of the Multiethnic Cohort Study. The cohort was linked to Surveillance, Epidemiology, and End Results cancer incidence and statewide death certificate files in Hawaii and California, with 373 incident papillary thyroid cancer cases identified. Exposures investigated include age at menarche, parity, first pregnancy outcome, birth control use, and menopausal status and type. Multivariable Cox proportional hazards models were used to obtain relative risk (RR) of papillary thyroid cancer and their 95% confidence intervals (CI). Covariates included age, race and ethnicity, reproductive history, body size, smoking, and alcohol consumption. Results: We observed a statistically significant increased risk of papillary thyroid cancer for oophorectomy (adjusted RR 1.58, 95% CI: 1.26, 1.99), hysterectomy (adjusted RR 1.65, 95% CI: 1.33, 2.04), and surgical menopause (adjusted RR 1.55, 95% CI: 1.22, 1.97), and decreased risk for first live birth at ≤20 years of age versus nulliparity (adjusted RR 0.66, 95% CI: 0.46, 0.93). These associations did not vary by race and ethnicity (p het > 0.44). Conclusion: The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in all racial and ethnic groups in our multiethnic population, which validates uniform obstetric and gynecological practice.