Loss of Esr1 Does Not Affect Hearing and Balance.

Although estrogen affects the structure and function of the nervous system and brain and has a number of effects on cognition, its roles in the auditory and vestibular systems remain unclear. The actions of estrogen are mediated predominately through two classical nuclear estrogen receptors, estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2). In the current study, we investigated the roles of ESR1 in normal auditory function and balance performance using 3-month-old wild-type (WT) and Esr1 knockout (KO) mice on a CBA/CaJ background, a normal-hearing strain. As expected, body weight of Esr1 KO females was lower than that of Esr1 KO males. Body weight of Esr1 KO females was higher than that of WT females, while there was no difference in body weight between WT and Esr1 KO males. Similarly, head diameter was higher in Esr1 KO vs. WT females. Contrary to our expectations, there were no differences in auditory brainstem response (ABR) thresholds, ABR waves I-V amplitudes and ABR waves I-V latencies at 8, 16, 32, and 48 kHz, distortion product otoacoustic emission (DPOAE) thresholds and amplitudes at 8, 16, and 32 kHz, and rotarod balance performance (latency to fall) between WT and Esr1 KO mice. Furthermore, there were no sex differences in ABRs, DPOAEs, and rotarod balance performance in Esr1 KO mice. Taken together, our findings show that Esr1 deficiency does not affect auditory function or balance performance in normal hearing mice, and suggest that loss of Esr1 is likely compensated by ESR2 or other estrogen receptors to maintain the structure and function of the auditory and vestibular systems under normal physiological conditions.

The Effectiveness and Safety of Nurse-Led Auricular Acupressure on Chemotherapy-Induced Peripheral Neuropathy Among Patients With Breast Cancer: A Randomized, Double-Blind, Sham-Controlled Trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a major symptom of distress among chemotherapy-treated cancer survivors. Although various interventions have been attempted, there is no criterion-standard treatment. OBJECTIVE: The aim of this study was to examine the efficacy and safety of auricular acupressure (AA) in improving peripheral neuropathy symptoms in breast cancer patients undergoing taxane-based treatment. METHODS: A total of 51 eligible participants were enrolled and randomly allocated (1:1) to AA or sham control groups. The intervention was performed weekly for 3 weeks using different ear points, depending on the group. The Total Neuropathy Score was used to measure CIPN objectively. The Numerical Rating Scale and the European Organization for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy-20 were used to measure the subjective symptoms of CIPN. Outcomes were compared between groups by time interaction using generalized estimating equations based on the intention-to-treat principle. RESULTS: Only 1 participant dropped out because of nausea and mild fever. The results of generalized estimating equations showed significant improvement in Numerical Rating Scale scores on the hands and feet and total Chemotherapy-Induced Peripheral Neuropathy-20 in the experimental group compared with the sham control group (all Ps < .05). Although the experimental group showed a greater reduction in Total Neuropathy Score scores than the sham control group, no significant differences were found. CONCLUSION: Auricular acupressure is an effective and safe nurse-led intervention for managing CIPN symptoms in breast cancer patients. IMPLICATIONS FOR PRACTICE: The findings help nurses to integrate AA easily and usefully into nursing care, contributing to managing symptoms of CIPN in cancer patients and survivors.

A Phase 3 Randomized Clinical Trial to Compare Efficacy and Safety between Combination Therapy and Monotherapy in Elderly Patients with Advanced Gastric Cancer (KCSG ST13-10).

PURPOSE: This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy. MATERIALS AND METHODS: Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy. RESULTS: After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%. CONCLUSION: Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

Developing a Multimodal Monitoring System for Geriatric Depression: A Feasibility Study.

The Internet of Medical Things is promising for monitoring depression symptoms. Therefore, it is necessary to develop multimodal monitoring systems tailored for elderly individuals with high feasibility and usability for further research and practice. This study comprised two phases: (1) methodological development of the system; and (2) system validation to evaluate its feasibility. We developed a system that includes a smartphone for facial and verbal expressions, a smartwatch for activity and heart rate monitoring, and an ecological momentary assessment application. A sample of 21 older Koreans aged 65 years and more was recruited from a community center. The 4-week data were collected for each participant (n = 19) using self-report questionnaires, wearable devices, and interviews and were analyzed using mixed methods. The depressive group (n = 6) indicated lower user acceptance relative to the nondepressive group (n = 13). Both groups experienced positive emotions, had regular life patterns, increased their self-interest, and stated that a system could disturb their daily activities. However, they were interested in learning new technologies and actively monitored their mental health status. Our multimodal monitoring system shows potential as a feasible and useful measure for acquiring mental health information about geriatric depression.

Psychometric Properties of the Korean Version of the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a multidimensional symptom cluster induced by neurotoxic chemotherapy agents among patients with cancer. A well-developed tool for assessing CIPN can help with the early detection and timely management of patients. This study assessed the reliability and validity of the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool (CIPNAT) in Korean women with breast cancer who were treated with chemotherapy. METHODS: A psychometric analysis of the Korean version of CIPNAT was conducted with 207 patients with breast cancer who were treated with chemotherapy. Patients were assessed using the CIPNAT and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy-20 (CIPN-20). Analyses of internal consistency reliability, concurrent validity, and construct validity (based on structural and discriminant validity testing) were performed to evaluate the psychometric properties. RESULTS: The Korean version of the CIPNAT had good internal consistency (Cronbach's alpha = 0.95; the item-total correlation coefficients ranged 0.34-0.76). The CIPNAT and CIPN-20 were moderately correlated (r = .67). Confirmatory factor analyses showed a four-factor structural model with acceptable model fit indices. Discriminant validity was supported by differences between individuals treated with and without taxane-based chemotherapy (p < .001). IMPLICATIONS FOR PRACTICE: The Korean version of the CIPNAT was a valid and reliable screening tool for identification of CIPN symptoms and functional interference in Korean women who received chemotherapy for breast cancer. The instrument can be useful for the timely and routine assessment of CIPN symptoms and functional limitations of patients with cancer by oncology nurses.

Cognitive impairment in women newly diagnosed with thyroid cancer before treatment.

PURPOSE: The study aims to assess cognitive function in women newly diagnosed with non-metastatic thyroid cancer before any treatment and to identify factors associated with cognitive problems. METHODS: Korean women newly diagnosed with thyroid cancer awaiting initial surgical treatment (n = 130) completed neuropsychological tests and self-report questionnaires on symptom distress and psychological distress. Additionally, information on thyroid function was obtained through a medical chart audit. Descriptive statistics and multivariable regression analyses were performed to describe the incidence of cognitive problems and to identify possible predictors of neuropsychological performance. RESULTS: Approximately 95% of women newly diagnosed with thyroid cancer had impaired neuropsychological test scores on one or more tests of attention and cognitive control. Further analyses found that 78% of women met both the Global Deficit Score and the International Cancer and Cognition Task Force criteria for impairment. Finally, regression analyses found that older age, fewer years of education, greater depressed mood, and having a hypothyroid state but not having a comorbid condition, fatigue, sleep problems, symptom burden, or symptom interference were associated with worse neuropsychological test performance in this sample. Additional explorative regression analysis using mean T-scores corrected for age, education, and gender continued to find that hypothyroid state was associated with worse neuropsychological test performance. CONCLUSIONS: Findings suggest that individuals newly diagnosed with non-metastatic thyroid cancer are vulnerable to cognitive deficits at diagnosis before any treatment. As such, healthcare workers should assess individuals newly diagnosed with thyroid cancer diagnosis awaiting treatment for the disease for cognitive deficits and intervene to reduce symptom distress and optimize function.

Validation and psychometric properties of the multidimensional scale of perceived social support among Korean breast cancer survivors.

Objective: Social support plays a key role in dealing with various challenges accompanying cancer treatment and survivorship. The multidimensional scale of perceived social support (MSPSS) is a valid measurement used globally to assess general support from social interpersonal relations. This study aims to validate the psychometric properties of the Korean version of the MSPSS among Korean women with breast cancer. Methods: Two independent cross-sectional studies collected data from 349 non-metastatic breast cancer survivors. Statistical analyses of confirmatory factor analyses, t-test, and Pearson correlation were performed to test construct validity, including factorial structure, concurrent validity, and known-group comparisons. Internal consistency and test-retest reliability were used to evaluate the reliability. Results: Factor analysis confirmed a three-factor construct (i.e., family, friends, and spouse) with good fit indices. Concurrent validity was verified by correlations with social well-being and interpersonal relationships, which are theoretically relevant concepts. Known-group validity was also confirmed by different MSPSS scores according to depression and symptom distress levels. Reliability was supported by good internal consistency and acceptable test-retest correlation coefficients. Conclusions: The findings demonstrate the MSPSS is a valid and reliable measurement to assess the extent to which women with breast cancer perceive social support from spouses, other family members, and friends in Korea. Further studies should verify the psychometric properties of the MSPSS in patients with other cancers beyond breast cancer. Health professionals could administer the MSPSS to evaluate the diverse resources of social support among cancer survivors.

Wound Healing-Promoting and Melanogenesis-Inhibiting Activities of Angelica polymorpha Maxim. Flower Absolute In Vitro and Its Chemical Composition.

Angelica polymorpha Maxim. (APM) is used in traditional medicine to treat chronic gastritis, rheumatic pain, and duodenal bulbar ulcers. However, it is not known whether APM has epidermis-associated biological activities. Here, we investigated the effects of APM flower absolute (APMFAb) on responses associated with skin wound healing and whitening using epidermal cells. APMFAb was obtained by solvent extraction and its composition was analyzed by GC/MS. Water-soluble tetrazolium salt, 5-bromo-2'-deoxyuridine incorporation, Boyden chamber, sprouting, and enzyme-linked immunosorbent assays and immunoblotting were used to examine the effects of APMFAb on HaCaT keratinocytes and B16BL6 melanoma cells. APMFAb contained five compounds and induced keratinocyte migration, proliferation, and type IV collagen synthesis. APMFAb also induced the phosphorylations of ERK1/2, JNK, p38 mitogen-activated protein kinase, and AKT in keratinocytes. In addition, APMFAb decreased serum-induced B16BL6 cell proliferation and inhibited tyrosinase expression, melanin contents, and microphthalmia-associated transcription factor expression in α-melanocyte-stimulating hormone-stimulated B16BL6 cells. These findings demonstrate that APMFAb has beneficial effects on skin wound healing by promoting the proliferation, migration, and collagen synthesis of keratinocytes and on skin whitening by inhibiting melanin synthesis in melanoma cells. Therefore, we suggest that APMFAb has potential use as a wound healing and skin whitening agent.

Biodegradation and Removal of PAHs by Bacillus velezensis Isolated from Fermented Food.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment. They are highly toxigenic and carcinogenic. Probiotic bacteria isolated from fermented foods were tested to check their ability to degrade and/or detoxify PAHs. Five probiotic bacteria with distinct morphologies were isolated from a mixture of 26 fermented foods co-cultured with benzo(a)pyrene (BaP) containing Bushnell Haas minimal broth. Among them, B. velezensis (PMC10) significantly reduced the abundance of BaP in the broth. PMC10 completely degraded BaP presented at a lower concentration in broth culture. B. velezensis also showed a clear zone of degradation on a BaP-coated Bushnell Haas agar plate. Gene expression profiling showed significant increases of PAH ringhydroxylating dioxygenases and 4-hydroxybenzoate 3-monooxygenase genes in B. velezensis in response to BaP treatment. In addtion, both live and heat-killed B. velezensis removed BaP and naphthalene (Nap) from phosphate buffer solution. Live B. velezensis did not show any cytotoxicity to macrophage or human dermal fibroblast cells. Live-cell and cell-free supernatant of B. velezensis showed potential anti-inflammatory effects. Cell-free supernatant and extract of B. velezensis also showed free radical scavenging effects. These results highlight the prospective ability of B. velezensis to biodegrade and remove toxic PAHs from the human body and suggest that the biodegradation of BaP might be regulated by ring-hydroxylating dioxygenase-initiated metabolic pathway.

Stromal vascular fraction injection to treat intractable radiation-induced rectovaginal fistula.

Rectovaginal fistula, which can arise after an injury to the vaginal canal or rectum, is a troublesome obstacle for patients' everyday life. In most cases, it can be covered with a local flap, but previous radiation therapy increases the recurrence rate, making it especially difficult to cure. As the application of stromal vascular fraction (SVF) obtained from enzymatically digested autologous adipose tissue has become increasingly common, several reports have advocated its effectiveness for the treatment of refractory wounds. In light of the angiogenic, regenerative characteristics of SVF, it was incorporated as a treatment option in two cases of rectovaginal fistula discussed here. As described in this report, irradiated rectovaginal fistulas in rectal cancer patients were successfully treated with SVF injection, and we suggest SVF as a feasible treatment option for cases of rectovaginal fistula that would otherwise be very difficult to cure.

Comparison of Sinusoidal Obstruction Syndrome in Gastric Cancer Patients Receiving S-1/oxaliplatin Versus Capecitabine/oxaliplatin.

BACKGROUND/AIM: Oxaliplatin-based chemotherapy is associated with hepatic sinusoidal obstruction syndrome (SOS). PATIENTS AND METHODS: We analyzed patients from two prospective trials, in which capecitabine/oxaliplatin (XELOX, 8 cycles; n=51) and S-1/oxaliplatin [SOX, continuous (SOX-C, n=50), or intermittent (discontinuation after cycle 6 and restart on progression, SOX-I, n=50)] were administered. We compared severity (splenomegaly, thrombocytopenia, liver enzyme levels, and hepatic parenchymal heterogeneity), clinical significance (delay or dose-reduction of chemotherapy), and reversibility of SOS (splenomegaly and thrombocytopenia after stopping chemotherapy) between SOX and XELOX in gastric cancer patients. RESULTS: SOX was more likely to be associated with splenomegaly, thrombocytopenia, hyperbilirubinemia, and hepatic parenchymal heterogeneity than XELOX. Splenomegaly was partially reversible after stopping chemotherapy in both regimens, but recovery rate was lower in SOX. Proportion of delayed or dose-reduced chemotherapy cycles due to thrombocytopenia was significantly higher in SOX-C than in XELOX. CONCLUSION: S-1 combination is more likely to worsen oxaliplatin-induced hepatic sinusoidal injuries than capecitabine in gastric cancer patients.

Efficacy and safety of auricular acupressure for chemotherapy-induced peripheral neuropathy among patients with breast cancer: a study protocol for a randomized controlled trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a frequently-reported distress symptom in breast carcinoma patients under chemotherapy. Although previous studies emphasized lack of ideal neuroprotective or therapeutic agents for CIPN, there are no strongly recommended treatments. Nevertheless, auricular acupressure (AA) is a novel remedy for controlling symptoms in many healthcare settings. However, therapeutic effects of AA among patients with CIPN have not yet been elucidated fully. Therefore, we designed a trial to examine the effectiveness and safety of AA in breast cancer patients. METHODS: This randomized, double-blind, sham-controlled trial will assess 120 breast cancer survivors. After enrollment, the participants will be stratified depending on administration of medications prescribed for CIPN treatment, and then assigned randomly to the experimental or control groups in an allocation ratio of 1:1. For experimental groups, AA will be applied on four points, namely, shemen, liver, spleen, and finger/toe, while for the control groups, sham AA will be exerted on other four points that are remote from the treatment points and unrelated to neuropathic symptoms. All participants will undergo the same acupressure procedure, for two minutes each time, thrice daily for 3 weeks, and CIPN symptoms and health-related quality of life will be assessed by a blinded research assistant and a physician before, during, immediately after, and 4 weeks after AA. Occurrence, type, and severity of safety issues will be routinely monitored to confirm the non-toxic nature of AA. Repeated measures analysis of variance will be used to examine the changing pattern of CIPN symptoms and based on sensitivity analysis. DISCUSSION: It is expected that the rationale and design of this protocol will offer knowledge regarding a standardized process to guide current and future studies and accumulates clinical experiences in applying non-pharmacological intervention. The present trial is the first to examine the therapeutic effects of AA in breast cancer patients with CIPN. The findings of the study may provide convincing evidence regarding the effectiveness of CIPN symptoms. TRIAL REGISTRAION: Clinical Research Information Service, Republic of Korea, ID: KCT0004930. Registered retrospectively on April 14, 2020.

Effects of Chemotherapy-Induced Peripheral Neuropathy in Women With Breast Cancer: A Structural Equation Approach With the Theory of Unpleasant Symptoms.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurotoxic effect. Chemotherapy-induced peripheral neuropathy symptoms have multidimensional characteristics that are associated with various physiologic, psychological, and situational factors and affect individual's abilities to effectively function in performing daily tasks. The theory of unpleasant symptoms mediates the relationships among CIPN symptom experience, reduced performance in daily tasks, and causative factors. OBJECTIVES: The aim of this study was to examine how influencing factors (physiologic, psychological, and situational) affect CIPN symptoms and the impact of symptom experience on functional interference in daily activities of chemotherapy-treated breast cancer survivors. METHODS: A cross-sectional survey about causative factors, CIPN symptoms, and functional interference was completed by 190 women treated with adjuvant chemotherapy for nonmetastatic breast cancer. The hypothetical model was tested using structural equation modeling analysis. RESULTS: The proposed model provided a good fit to the data. Physiologic and psychological factors accounted for 25.5% of the variance in CIPN symptom experience and explained 37.1% of the variance interfering with functional performance through CIPN symptom experience. CONCLUSION: Disease- and treatment-related physiologic factors and coexisting psychological distress play crucial roles in explaining CIPN symptom experience and daily function in breast cancer survivors. IMPLICATIONS FOR PRACTICE: The findings help healthcare professionals to improve long-term care for breast cancer survivors in terms of education for self-monitoring, coping, and establishing supportive environment that can contribute to reducing the unmet needs and interference associated with persistent CIPN.

Randomized phase II study of platinum-based chemotherapy plus controlled diet with or without metformin in patients with advanced non-small cell lung cancer.

OBJECTIVES: Accumulating evidence indicates anti-diabetic drug metformin has anti-cancer effect by controlling cancer metabolism. We evaluated whether addition of metformin to chemotherapy improved survival of lung cancer patients. MATERIALS AND METHODS: This randomized phase II study enrolled 164 patients with chemo-native, EGFR-ALK wild-type, stage IIIB/IV non-small-cell lung cancer (NSCLC). Patients were randomized to receive chemotherapy either with metformin (1000 mg twice daily) or alone every 3 weeks for six cycles. The patients received gemcitabine (1000 mg/m2) on days 1 and 8 and carboplatin (5 area under the curve) on day 1. Exploratory studies included serum metabolic panels, positron-emission tomography (PET) imaging, and genetic mutation tests for metabolism-related genes. RESULTS: Metformin group showed no significant difference in the risk of progression and death compared to control group (progression: hazard ratio [HR] = 1.01 [95% confidence interval (CI) = 0.72 - 1.42], P = 0.935; death: HR = 0.95 [95% CI = 0.67-1.34], P = 0.757). Squamous cell carcinoma (SqCC) had significantly higher fluorodeoxyglucose (FDG) uptake on baseline PET image than non-SqCC NSCLC (P = 0.004). In the SqCC with high FDG uptake, the addition of metformin significantly decreased the risk of progression and death (progression: HR = 0.31 [95% CI = 0.12-0.78], P = 0.013; death: HR = 0.42 [95% CI = 0.18-0.94], P = 0.035). The HDL-cholesterol level was significantly increased after the treatment in metformin group compared to control group (P = 0.011). The metformin group showed no survival benefit in the patients with hyperinsulinemia or patients whose insulin level was decreased after treatment. CONCLUSIONS: Addition of metformin to chemotherapy provided no survival benefit in unselected NSCLC patients. However, it significantly improved the survival of the selected patients with SqCC showing high FDG uptake. It suggests metformin shows the synergistic anti-tumor effect in the tumor which are highly dependent on glucose metabolism.

Cochlear detoxification: Role of alpha class glutathione transferases in protection against oxidative lipid damage, ototoxicity, and cochlear aging.

Age-related hearing loss (AHL) is the most common form of hearing impairment. AHL is thought to be a multifactorial condition resulting from the interaction of numerous causes including aging, genetics, exposure to noise, and exposure to endogenous and exogenous toxins. Cells possess many detoxification enzymes capable of removing thousands of cytotoxic xenobiotics and endogenous toxins such as 4-hydroxynonenal (4-HNE), one of the most abundant cytotoxic end products of lipid peroxidation. The cellular detoxification system involves three phases of enzymatic detoxification. Of these, the glutathione transferase (GST) detoxification system converts a toxic compound into a less toxic form by conjugating the toxic compound to reduced glutathione by GST enzymes. In this review, we describe the current understanding of the cochlear detoxification system and examine the growing link between GST detoxification, oxidative lipid damage, ototoxicity, and cochlear aging with a particular focus on the alpha-class GSTs (GSTAs). We also describe how exposure to ototoxic drugs, exposure to noise, or aging results in increased 4-HNE levels, how 4-HNE damages various cell components under stress conditions, and how GSTAs detoxify 4-HNE in the auditory system.

Impact of changes in perceived attentional function on postsurgical health-related quality of life in breast cancer patients awaiting adjuvant treatment.

PURPOSE: Few studies have assessed pre-surgery cognitive impairment or the impact of pre-surgery cognitive impairment on quality of life. The purpose of this study was to assess changes in perceived cognitive function from pre-surgery to 1 month post-surgery and to determine whether cognitive function predicted health-related quality of life in women who awaited adjuvant treatment for breast cancer. METHODS: This study used a descriptive pre-post design to assess women newly diagnosed with breast cancer prior to any treatment (N = 132). Cognition was assessed using the Attentional Function Index (AFI) and health-related quality of life was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G). Statistical methods included descriptive, comparative and regression analyses. Covariates assessed and controlled for in analyses included depressed mood, fatigue, disturbed sleep, surgery-related symptoms (lymphedema/decreased mobility), and cultural tendency. RESULTS: Perceived attention and memory function decreased from pre-surgery to 1 month post-surgery alongside alterations in arm function and a decrease in depressed mood (p < 0.05). Regression analysis indicated that, after controlling for covariates, poorer perceived attention and memory function, surgery-specific symptoms, and a greater tendency toward collectivism predicted poorer quality of life. CONCLUSION: Perceived function on tasks requiring attention and working memory 1 month post-surgery was poorer compared to pre-surgery suggesting that the mental and physical demands of a new diagnosis of breast cancer and surgery may effect cognitive function. Additionally, changes in perceived cognitive function significantly predicted perceived quality of life in women awaiting adjuvant treatment for breast cancer. Findings suggest that breast cancer patients are at risk for an early decline in cognitive function and that interventions aimed at supporting and optimizing function may improve quality of life early in the disease trajectory.

Age-dependent efficacy of subthalamic nucleus deep brain stimulation in young- and late-onset Parkinson's disease based on a 10 year follow-up.

INTRODUCTION: Long-term efficacy and safety of subthalamic nucleus deep brain stimulation (STN DBS) in patients with young-onset Parkinson's disease (YOPD) and late-onset PD (LOPD) (i.e. motor symptom initial appearance at ages ≤40 and > 40 years, respectively) was compared to identify relationships between PD onset age and the efficacy of DBS. METHODS: Statistical analyses compared specific motor and non-motor features among 13 patients with YOPD and 11 with LOPD. Medication reduction patterns and dyskinesia severity scores at baseline and after 1, 3, 5, and 10 years of follow-up were also analyzed using a repeated measures ANOVA tests. Lastly, a correlation analysis identified relationships between the impact of DBS settings (volume of activated tissue) and levodopa equivalent daily dose (LED), dyskinesia severity scores, Unified Parkinson's Disease Rating Scale (UPDRS) part III, and UPDRS part II (disability) scores. RESULTS: Ten years after DBS surgery, the reduction of LED from baseline (85.9 ± 592.6 mg versus 623.2 ± 464.9 mg; p = .023) and levodopa-induced dyskinesia (LID) scores (Unified Dyskinesia Rating Scale [UDysRS] parts III items 16-22; 1.6 ± 2.8 versus 5.5 ± 4.1; p = .013) were significantly lower in YOPD patients than LOPD patients. There were no significant differences between the two groups regarding UPDRS part III score improvement in response to levodopa, psychosis occurrence, or adverse effects. CONCLUSION: Ten years after STN DBS surgery, LOPD patients showed greater LED reduction, and YOPD patients showed greater LID improvement, although the general long-term outcomes were similar between YOPD and LOPD patients.

Mesenchymal stem cells co-cultured with colorectal cancer cells showed increased invasive and proliferative abilities due to its altered p53/TGF-ß1 levels.

Signaling between cancer cells, their neighboring cells, and mesenchymal stem cells (MSCs) forms the tumor microenvironment. The complex heterogeneity of this microenvironment varies depending on the tumor type and its origins. However, most of the existing cancer-based studies have focused on cancer cells. In this study, we used a direct co-culture system (cross-talk signaling) to induce cross-interaction between cancer cells and mesenchymal stem cells. This induced deformation of MSCs. MSCs showed a diminished ability to maintain homeostasis. In particular, increase in the invasion ability of MSCs by TGF-ß1 and decrease in p53, which plays a key role in cancer development, is an important discovery. It can thus be deduced that blocking these changes can effectively inhibit metastatic colorectal cancer. In conclusion, understanding the interactions and changes in MSCs associated with cancer will help develop novel therapeutic strategies for cancer.

GSTA4 mediates reduction of cisplatin ototoxicity in female mice.

Cisplatin is one of the most widely used chemotherapeutic drugs for the treatment of cancer. Unfortunately, one of its major side effects is permanent hearing loss. Here, we show that glutathione transferase α4 (GSTA4), a member of the Phase II detoxifying enzyme superfamily, mediates reduction of cisplatin ototoxicity by removing 4-hydroxynonenal (4-HNE) in the inner ears of female mice. Under cisplatin treatment, loss of Gsta4 results in more profound hearing loss in female mice compared to male mice. Cisplatin stimulates GSTA4 activity in the inner ear of female wild-type, but not male wild-type mice. In female Gsta4-/- mice, cisplatin treatment results in increased levels of 4-HNE in cochlear neurons compared to male Gsta4-/- mice. In CBA/CaJ mice, ovariectomy decreases mRNA expression of Gsta4, and the levels of GSTA4 protein in the inner ears. Thus, our findings suggest that GSTA4-dependent detoxification may play a role in estrogen-mediated neuroprotection.

Behaviors and Attitudes toward the Use of Complementary and Alternative Medicine among Korean Cancer Patients.

PURPOSE: A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea. MATERIALS AND METHODS: Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution. RESULTS: In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians. CONCLUSION: Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.