Long-term effects of childhood difficulties on depressive symptoms among older adults: Role of adulthood income and income satisfaction.

AIM: This study examines how childhood difficulties are associated with late-life depression. Using the concept of agency within the structure of the life course perspective, this study investigates how subjective income satisfaction in adulthood plays a role in the relationship between adulthood objective income and late-life depressive symptoms among older adults who have experienced childhood difficulties. METHODS: Using data from two waves (2006, 2021) of the Korean Welfare Panel Study (N = 1822), we identified respondents with and without childhood difficulties, and performed a series of hierarchical zero-inflated Poisson regression models. RESULTS: Childhood difficulties (ß, 0.07; 95% confidence interval [CI], 0.04-0.11), adulthood low income (ß, 0.17; 95% CI, 0.13-0.21), and low income satisfaction (ß, 0.16; 95% CI, 0.12-0.21) are associated with an increased level of depressive symptoms in late life. In the context of the association between objective income level and late-life depressive symptoms, the buffering effect of income satisfaction in adulthood was found among the respondents who had experienced childhood difficulties (ß, 0.22; 95% CI, 0.09-0.34). CONCLUSIONS: Childhood difficulties are a critical risk factor impacting late-life psychological well-being. How an individual subjectively evaluates his or her economic status in adulthood plays a major role in mitigating the negative impact of childhood difficulties on late-life health inequality. Interventions to reduce the risk of childhood difficulties and their negative long-lasting impact may alleviate individuals' exposure to depression in late life. Geriatr Gerontol Int 2024; 24: 246-252.

The mineralocorticoid receptor and extra-synaptic NMDA receptor in the lateral habenula involve in the vulnerability to early life stress in the maternal separation model.

The lateral habenula (LHb) plays a pivotal role in regulating emotional responses during stress reactions, and its hyperactivity has been associated with depression. Recently it has been demonstrated that chronic early-life stress results in individual differences in stress vulnerability among rodents. However, how synaptic function in the LHb varies between susceptibility and resilience to early life stress remains elusive. In this study, we used a maternal separation model to assign animals with different stress vulnerabilities into groups and investigated the synaptic responses in the LHb. Our findings indicate that synaptic long-term depression (LTD) was impaired and extra-synaptic LTD was enhanced in the LHb of the susceptible group. To mimic the synaptic alteration in stress situations, when administered corticosterone, a stress hormone, the intervention appeared to impair synaptic LTD in the LHb of the control group, through the activation of mineralocorticoid receptors (MR). Indeed, there was an up-regulation of MR mRNA observed in the susceptible group. Following there was an up-regulation of both NR2A and NR2B subunits in the LHb. These results indicated that MR and extra-synaptic NMDA receptors in LHb are critically engaged in the susceptibilities to stress. Furthermore, our findings propose potential therapeutic targets for alleviating stress-related symptoms.

The Effects of Charitable Giving on Life Satisfaction of Older Korean Adults: The Moderating Role of Relationship Satisfaction and Social Trust.

OBJECTIVES: This study investigates the effects of charitable giving on the life satisfaction of older Korean adults, examining the moderating role of relationship satisfaction and social trust, as the indicators for social capital. METHODS: Nationally representative sample of individuals aged 65 to100 (N = 8,359) from the 2019 Social Survey was used for the analyses. RESULTS: The results from Coarsened Exact Matching and Structural Equation Modeling show that charitable giving positively affects older Korean adults' life satisfaction. Moreover, the results of moderation analyses suggest that the effects of charitable giving on life satisfaction are stronger for those with lower levels of relationship satisfaction and social trust. DISCUSSION: The results imply that social capital, such as relationship satisfaction or social trust, needs to be taken into consideration when exploring the effects of charitable giving in later life.

Oxytocin-induced anxiogenic behavior in juvenile male rats.

Oxytocin (OT) is considered beneficial to mental health owing to its anxiolytic, prosocial, and anti-stress effects; however, the adverse effects of OT have been controversial, such as its potentially anxiogenic actions. Although OT influences drug abuse and reciprocally affects vulnerability to drug use, the relationship between OT's anxiogenic working and nicotine preference intake has not been clearly defined. To clarify this issue, the effect of acute peripheral administration of OT on anxiety and nicotine preference was investigated in juvenile male rats. Anxiogenic behaviors were noticeably increased in OT-administrated rats, with an increase in serum corticosterone levels. Moreover, increased anxiety-like behaviors and corticosterone levels were observed in the OT analog carbetocin-injected rats. In the nicotine preference test, the rats' aversive responses to initial nicotine choice and preference were not significantly different between saline-injected and OT-injected rats. However, when administered with OT, there was a significant negative correlation between anxiety-like behavior and low-dose nicotine consumption. Collectively, these results provide evidence that acute OT exposure could induce anxiogenic behavior with corticosterone augmentation, contributing to the attenuation of nicotine preference. This suggests that both aspects of OT, as well as their benefits and drawbacks, should be considered.

NMDA receptor-dependent long-term depression in the lateral habenula: implications in physiology and depression.

Abnormally increased neuronal activity in the lateral habenula (LHb) is closely associated with depressive-like behavior. Despite the emphasis on the pathological importance of NMDA receptor (NMDAR)-dependent long-term depression (LTD) and the involvement of calcium permeable AMPA receptor (CP-AMPAR) as major Ca2+ source, the functions of NMDAR and CP-AMPAR on LTD modulation in the LHb still have not been fully investigated. Here, we found that NMDAR-dependent LTD by low frequency stimulation was induced in both synaptic and extrasynaptic regions in the LHb. In addition, CP-AMPAR was necessary for the activation of NMDAR in the induction phase of NMDAR-dependent LTD. The acute stress, which induced depressive behavior, had a blocked effect on synaptic NMDAR-dependent LTD but left extrasynaptic NMDAR-dependent LTD intact. These findings show that NMDAR-dependent LTD in LHb plays an important role in regulating neuronal activity, which is probable to be excessively increased by repeated stress, via maintaining homeostasis in both synaptic and extrasynaptic regions of the LHb. Moreover, NMDAR and CP-AMPAR may serve as a depression-related modulator and be regarded as a promising therapeutic target for treatment of psychopathology such as depression.

Causes and prevention of revision surgery for preauricular sinus: A histopathological analysis.

OBJECTIVE: Recurrence rates following preauricular sinus (PAS) surgery vary. Few studies have investigated recurrence after primary PAS surgery in histopathological terms. We performed a histopathological analysis of the causes of revision surgery for PAS, with a view to reducing the recurrence rate after primary surgery. METHODS: We reviewed the medical records of patients who underwent revision surgery after primary excision of a PAS between 2002 and 2017. A pathologist reviewed the histopathology slides. RESULTS: In total, 24 patients underwent revision surgery; of those, histopathology slides were available for 18 patients (19 revisions). The mean interval between primary and revision surgery was 50.4 months. We detected lumen with stratified squamous epithelium in 14 of the 19 (73.7%) revisions. Cartilage tissue was attached to the epithelial lining of the lumen in 14 of the 17 (82.4%) slides containing lumen. Inflammatory changes were found in all slides, and granulation tissue was detected in 10 of 19 revision surgery slides. CONCLUSIONS: To prevent PAS recurrence after primary surgery, we recommend a wide local excision including the inflammatory soft tissue, with concomitant partial removal of the cartilage of the ascending helix adjacent to the PAS.

Therapeutic activity of the histone deacetylase inhibitor SB939 on renal fibrosis.

Fibrosis is the final pathological outcome of many chronic kidney diseases and is quite common. Thus, development of effective anti-fibrotic agents is urgently needed. Although histone deacetylases (HDACs) have been reported to be involved in renal fibrosis, current HDAC inhibitors are unsatisfactory anti-fibrosis drugs. Therefore, more potentially relevant anti-renal fibrosis HDAC inhibitors are needed. We initially found that non-cytotoxic concentrations of SB939 (pracinostat) had strong anti-fibrotic activity, drastically decreasing TGF-ß1-induced alpha smooth muscle actin (α-SMA) expression in the NRK renal fibroblast cell line. Similar anti-fibrotic activity of SB939 on epithelial-to-mesenchymal transition (EMT) was confirmed using the HK-2 human renal proximal tubular epithelial cell line. SB939 inhibited Smad-independent TGF-ß signaling involving the MAPK and PI3K/AKT pathways. To evaluate in vivo anti-fibrotic activity, we administered SB939 in a unilateral ureteric obstruction (UUO) model. SB939 treatment markedly inhibited the accumulation of α-SMA and tissue injury. Inflammatory and pro-fibrotic cytokines in the obstructed kidney were also significantly decreased by SB939 treatment. Our results suggest that SB939 might be a promising therapeutic drug for preventing renal fibrosis.

Repeated nicotine exposure in adolescent rats: Reduction of medial habenular activity and augmentation of nicotine preference.

Adolescence is a critical period for the initiation of tobacco use. Nicotine not only stimulates brain reward circuits to establish and maintain the tobacco smoking habit, but also produces aversive reactions to nicotine after initial exposure, due to its noxious properties. Although new insights into the mechanisms that regulate nicotine avoidance could result in an advantageous treatment strategy for addiction, little is known about the mechanism of nicotine aversion in adolescence. Because growing evidences suggest that the habenula to interpeduncular nucleus circuitry plays a critical role in nicotine aversion, we investigated the effects of repeated nicotine exposure on the electrical activity of medial habenular neurons in adolescent rats, using extracellular recordings. Nicotine strongly increased the frequency of spontaneous spike activity in the medial habenula of naïve rats. In repeated nicotine-injected rats, we found a reduction in nicotine-induced spontaneous spike frequency, such that these neurons displayed a significantly lower basal activity and reduced spontaneous activity upon re-exposure to nicotine. Moreover, nicotine intake preference in repeated nicotine-injected rats is significantly more increased than that in saline-injected rats. These results demonstrate that repeated phases of nicotine exposure induce a functional switch in the activity of medial habenular neurons in adolescent rats and suggest that medial habenular activity is one of mediators for an inhibitory motivational signal that limits nicotine consumption.

Attenuation of IFN-γ-induced B7-H1 expression by 15-deoxy-delta(12,14)-prostaglandin J2 via downregulation of the Jak/STAT/IRF-1 signaling pathway.

AIM: B7-H1, which belongs to the B7 family of costimulatory molecules, is implicated in the ability of tumors to evade the host immune response. The development of evasion mechanisms within the tumor microenvironment may be responsible for poor therapeutic responses. In this manuscript, we report that the 15-deoxy-δ(12,14)-prostaglandin J2 (15d-PGJ2), peroxisome proliferator-activated receptor gamma (PPARγ) activator leads to the downregulation of the cancer-associated expression of B7-H1 in response to interferon-gamma (IFN-γ) and the associated signaling cascades. MAIN METHODS: The expression of B7-H1 from IFN-γ-induced B16F10 melanoma cells was measured with flow cytometric analysis. The regulatory mechanisms of 15d-PGJ2 on cellular signaling pathways were examined using Western blot and electrophoretic mobility shift assays. KEY FINDINGS: The flow cytometric analysis revealed that the B7-H1 costimulatory molecule is significantly upregulated in B16F10 melanoma cells by stimulation with IFN-γ. However, 15d-PGJ2 strongly downregulates B7-H1 expression in IFN-γ-stimulated B16F10 melanoma cells. Furthermore, the significant damping effect of 15d-PGJ2 on B7-H1 expression involves the inhibition of the tyrosine phosphorylation of Janus kinase (Jak) and signal transducer(s) and activator(s) of transcription (STAT) and, thereby, the interferon regulatory factor-1 (IRF-1) trans-activation of STAT. These effects of 15d-PGJ2 were not abrogated by the PPARγ antagonist GW9662, indicating that they occur through a PPARγ-independent mechanism. SIGNIFICANCE: In this study, we demonstrate that 15d-PGJ2 suppresses the IFN-γ-elicited expression of B7-H1 by the inhibition of IRF-1 transcription via the Jak/STAT signaling pathway through a PPARγ-independent mechanism in mouse melanoma cells.

Kaposi sarcoma in a patient with chronic renal failure undergoing dialysis.

Kaposi sarcoma (KS) is a multicentric proliferative vascular tumor involving the skin and other organs. Human herpesvirus 8 (HHV-8) has been detected in KS lesions and is considered the putative causative agent of KS. The relationship between chronic renal failure, HHV-8, and KS is not clear. KS appears to develop in association with renal transplantation, but is unlikely with dialysis, and there have been few reports on this. Here, we report the case of a 51-year-old man, who underwent peritoneal dialysis to treat chronic renal failure, and presented with multiple brownish plaques on his soles. On histopathological examination, abnormally proliferated vessels, vascular slits, and spindle-shaped cells were seen in the dermis. Immunohistochemical staining for HHV-8 was positive. This case is another example in which factors other than immunosuppression contributed to the development of KS, due to activation of HHV-8.

Squamoid eccrine ductal carcinoma of the scalp.

Squamoid eccrine ductal carcinoma (SEDC) is an exceedingly rare tumor that shows both squamous and adnexal ductal differentiation. We report a case of this unusual tumor occurring on the occiput of a 53-year-old man. A histopathological examination revealed a nodular lesion infiltrating the dermis and subcutaneous tissue with numerous duct-like structure and squamoid differentiation foci. Five months later, the patient presented with a palpable mass at the site of the previous excision and the right side of the neck. Sono-guided fine needle aspiration of the right neck mass was performed and was diagnosed as a metastastasis of a lymph node. A right neck node dissection and re-excision of the occiput was performed. The histopathological findings were similar, but squamoid differentiation was more prominent than that in the previous lesion. Because of the rarity of SEDC, little is known about its biological behavior and optimal treatment.

Protective role of V-set and immunoglobulin domain-containing 4 expressed on kupffer cells during immune-mediated liver injury by inducing tolerance of liver T- and natural killer T-cells.

UNLABELLED: V-set and Ig domain-containing 4 (VSIG4, CRIg, or Z39Ig), a newly identified B7-related cosignaling molecule, is a complement receptor and a coinhibitory ligand that negatively regulates T-cell immunity. Despite its exclusive expression on liver Kupffer cells (KCs) that play key roles in liver tolerance, the physiological role of VSIG4 in liver tolerance remains undefined. Mice lacking VSIG4 had poor survival rates and severe liver pathology in a concanavalin A (ConA)-induced hepatitis (CIH) model, which could be prevented by adoptive transfer of VSIG4(+) KCs. The absence of VSIG4 rendered endogenous liver T- and natural killer T (NKT)-cells more responsive to antigen-specific stimulation and impaired tolerance induction in those cells against their cognate antigens. T-cell costimulation with VSIG4.Ig suppressed Th1-, Th2-, and Th17-type cytokine production and arrested the cell cycle at the G(0) /G(1) phase but did not induce apoptosis in vitro. VSIG4-mediated tolerance induction and cell-cycle arrest were further supported by down-regulation of G(1) phase-specific Cdk2, Cdk4, and Cdk6, and up-regulation of tolerance-inducing p27(KIP-1) in VSIG4.Ig-stimulated T-cells. Administration of soluble VSIG4.Ig to wildtype mice prevented CIH development and prolonged the survival of mice with established CIH. CONCLUSION: Collectively, our results suggest that VSIG4(+) KCs play a critical role in the induction and maintenance of liver T- and NKT-cell tolerance, and that modulation of the VSIG4 pathway using a VSIG4.Ig fusion protein may provide useful immunological therapies against immune-mediated liver injury including autoimmune hepatitis.

Expression of galectin-9 by IFN-γ stimulated human nasal polyp fibroblasts through MAPK, PI3K, and JAK/STAT signaling pathways.

Galectin-9 exhibited potent and selective eosinophil chemoattractant activity and attracted eosinophils in vitro and in vivo. Nasal polyposis is a chronic inflammatory disease of the upper airway characterized by the marked presence of inflammatory cells, particularly eosinophils. Thus, galectin-9 may be implicated in the pathogenesis of nasal polyposis. The study was designed to investigate whether interferon-gamma (IFN-γ) can induce the augmentation of galectin-9 expression and induce the expression of galectin-9 in nasal polyps. We examined the correlation between galectin-9 expression and eosinophil infiltration in nasal polyps. In addition, we identified the signaling pathways involved in the elevation of galectin-9 expression in response to IFN-γ. Our data demonstrate that the involvement of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3 phosphate kinase (PI3K), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) may play important roles in the selective recruitment of eosinophils in nasal polyp tissues through the production of galectin-9. These findings suggest that galectin-9 expression is associated with eosinophil infiltration in polyps of patients with nasal polyposis.

Current trends in the epidemiological and pathological characteristics of gastrointestinal stromal tumors in Korea, 2003-2004.

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.

Evaluation of anti-allergic properties of caffeic acid phenethyl ester in a murine model of systemic anaphylaxis.

Caffeic acid phenethyl ester (CAPE) is an active component of honeybee propolis extracts. It has several positive effects, including anti-inflammatory, anti-oxidation, anti-cancer, anti-bacterial, anti-viral, anti-fungal, and immunomodulatory effects. In particular, the suppressive effect of NF-kappaB may disrupt a component of allergic induction. The principal objective of this experimental study was to evaluate the effects of CAPE on the active systemic anaphylaxis induced by ovalbumin (OVA) challenge in mice. Mice were intraperitoneally sensitized and intravenously challenged with OVA. Histopathological analysis, nuclear factor (NF)-kappaB activation, and the plasma levels of histamine and total IgE after allergen challenge were evaluated. After challenges, all of the sham-treated mice developed anaphylactic symptoms, increased plasma levels of histamine and OVA-specific IgE, marked vascular leakage, NF-kappaB activation, platelet-activating factor (PAF) production, and histological changes including pulmonary edema and hemorrhage in the renal medullae within 20 min. By way of contrast, a reduction in the plasma levels of histamine and OVA-specific IgE and an inhibition of NF-kappaB activation and PAF release were observed in the CAPE-treated mice. In addition, a significant prevention of hemoconcentration and OVA-induced pathological changes were noted. These results indicate that CAPE demonstrates an anti-allergic effect, which may be the result of its protective effects against IgE-mediated allergy.

Mixed tumor of the vagina: a case report.

We report a case of mixed tumor arising in the lower vaginal wall. The patient was a 20-yr-old nullipararous woman. The tumor was relatively well-defined with expansile margin, and showed solid sheets or fascicles of stromal-type spindle cells and ovoid epithelial cells with sparsely scattered nests of mature squamous epithelium and glands lined by mucinous epithelium. Cellular atypia was not conspicuous, however, mitosis was counted upto 6 per 10 high power fields. We examined this tumor immunohistochemically and ultrastructurally and reviewed the articles to identify the histogenesis. Positive reaction for vimenin and cytokeratin of stromaltype spindle cells and presence of desmosome-like structures and tonofilaments on electron microscopic examination suggested the epithelial origin of the stromaltype spindle cells.