Adaptive response of resistant cancer cells to chemotherapy

Despite advances in cancer therapeutics and the integration of personalized medicine, the development of chemoresistance in many patients remains a significant contributing factor to cancer mortality. Upon treatment with chemotherapeutics, the disruption of homeostasis in cancer cells triggers the adaptive response which has emerged as a key resistance mechanism. In this review, we summarize the mechanistic studies investigating the three major components of the adaptive response, autophagy, endoplasmic reticulum (ER) stress signaling, and senescence, in response to cancer chemotherapy. We will discuss the development of potential cancer therapeutic strategies in the context of these adaptive resistance mechanisms, with the goal of stimulating research that may facilitate the development of effective cancer therapy.     

Mindfulness and psychoeducation to manage stress in amnestic mild cognitive impairment: A pilot study

Objectives: Amnestic mild cognitive impairment (aMCI) often corresponds to the prodromal stage of Alzheimer disease (AD). The aMCI stage represents a crucial time window to apply preventive interventions in an attempt to delay cognitive decline. Stress, one of AD’s modifiable risk factors frequently co-occurring with aMCI, stands out as a key intervention target. The goal of this study was to assess the impacts of two non-pharmacological interventions, mindfulness and psychoeducation, on stress at the psychological and physiological levels among aMCI older adults.

Methods: Forty-eight aMCI participants were randomized between a mindfulness-based intervention (MBI) and a psychoeducation-based intervention (PBI) for eight weekly sessions. Anxiety symptoms, perceived stress levels, cortisol awakening response (CAR), and coping strategies were assessed pre- and post-intervention. Mindfulness attitudes and time dedicated to at-home meditative practices were evaluated in the MBI group.

Results: The main results revealed a slight reduction of the CAR among MBI participants who practiced meditation at home the most and a decrease in perceived stress levels in the PBI group. Both interventions enhanced problem-focused coping strategies.

Conclusion: In sum, this pilot study supports the potential of MBI and PBI to reduce stress at the physiological and psychological level, respectively, and increase coping strategies in older adults at risk for AD.     

Depressive symptoms in caregivers immediately after stroke

Background: Caregivers of stroke survivors often suffer depressive symptoms that interfere with their own health. Early recognition may lead to attenuation of symptoms and better health and well-being for caregivers.

Objective: We examined characteristics of caregivers and stroke survivors associated with caregivers’ depressive symptoms in the early poststroke period.

Methods: We conducted a prospective, longitudinal exploratory observational study with a convenience sample of 63 caregivers of older adult (≥ 65 years) stroke survivors recruited from urban acute-care settings. We enrolled caregivers by 2 weeks poststroke (T1) and revisited them 4 weeks later (T2). Depressive symptoms were measured using the Patient Health Questionnaire-9. A separate unadjusted linear mixed model was computed to explore significant associations between each caregiver or stroke-survivor characteristic and depressive symptoms.

Results: Caregivers, on average, reported mild depressive symptoms at T1 and T2. Each of the following characteristics was independently associated with caregiver depressive symptoms over the first 6 weeks poststroke: caregiver uncertainty (p < 0.001), perceived stress (p < 0.001) but not cortisol levels (p = 0.858 on waking, p = 0.231 evening), coping (p < 0.001), social support (p = 0.006), race (p = 0.022), income (p = 0.001), time spent on care (p = 0.039), and stroke-survivor race (p = 0.033) and functional status (p = 0.003). At T2, caregiver depressive symptoms were correlated with evening cortisol level (p = 0.001).

Conclusions: Caregiver and stroke-survivor characteristics may help identify caregivers at highest risk for early depressive symptoms and guide interventions aimed at their resolution.     

Echocardiographic assessment at rest and during stress in patients with intermittent claudication

Objective. Skeletal muscle perfusion during walking relies on complex interactions between cardiac activity and vascular control mechanisms, why cardiac dysfunction may contribute to intermittent claudication (IC) symptoms. The study aims were to describe cardiac function at rest and during stress in consecutive IC patients, to explore the relations between cardiac function parameters and treadmill performance, and to test the hypothesis that clinically silent myocardial ischemia during stress may contribute to IC limb symptomatology. Design. Patients with mild to severe IC (n?=?111, mean age 67 y, 52% females, mean treadmill distance 195 m) underwent standard echocardiography, dobutamine stress echocardiography (SE) and treadmill testing. The patient cohort was separated in two groups based on treadmill performance (HIGH and LOW performance). Results. Ten patients (9%) had regional wall motion abnormalities of which three had left ventricular ejection fraction <50% at standard echocardiography. A majority had lower than expected systolic- and diastolic ventricular volumes. LOW performers had smaller diastolic left ventricular volumes and lower global peak systolic velocity during dobutamine stress. No patient demonstrated significant cardiac dysfunction during dobutamine provocation that was not also evident at standard echocardiography. Conclusions. Most IC patients were without signs of ischemic heart disease or cardiac failure. The majority had small left ventricular volumes. The hypothesis that clinically silent myocardial ischemia impairing left ventricular function during stress may contribute to IC limb symptomatology was not supported.

Trial registration: ClinicalTrials.gov identifier: NCT01219842.     

Big Five and psychological and subjective well-being in Colombian older adults

The goal of the current study was to investigate the relationships between the Five Factor Model of personality and the dimensions of subjective well-being (positive affect, negative affect, and life satisfaction), and psychological well-being (self-acceptance, personal growth, environmental mastery, autonomy, positive relations with others, and purpose in life). Participants included 618 Colombian adults aged 60–92 years. Multiple linear regression analyses were conducted. Regarding the subjective well-being, neuroticism was associated with lower scores on life satisfaction, and positively associated with negative affect, whereas extroversion and conscientiousness were associated with higher scores on life satisfaction and positive affect. For psychological well-being, neuroticism showed a negative and significant association with all of the psychological well-being dimensions, except purpose in life, whereas extroversion and conscientiousness showed a significant and positive relationship with the six dimensions. Neuroticism, extraversion, and conscientiousness represent personality predispositions for general well-being. Extraversion and conscientiousness are predictors of optimal aging. Neuroticism was the only significant predictor of negative affect.     

口服硝酸盐对大鼠背部随意皮瓣的保护作用及机制探讨

目的 探讨口服硝酸盐对大鼠背部随意皮瓣的影响,以硝酸盐-亚硝酸盐-NO通路为切入点,探讨其可能的机制。方法 将24只雄性Wistar大鼠随机分为硝酸盐组、氯化钠组和对照组,每组8只。采用改良大鼠背部随意皮瓣制作方法造模。硝酸盐干预组在术前7 d及术后每天口服0.5 mmol/L硝酸钠,氯化钠组每天口服等量氯化钠,对照组每天口服蒸馏水。术后第7天,检测各组皮瓣的存活情况,大鼠血清中硝酸盐、亚硝酸盐、肿瘤坏死因子（tumor necrosis factor alpha,TNF-a）和白介素6（interleukin-6,IL-6）水平,以及皮瓣组织中超氧化物歧化酶（superoxide dismutase,SOD）和丙二醛（malondialdehyde,MDA）水平。采用SPSS 20.0软件包对数据进行t检验。结果 硝酸盐组皮瓣的存活面积显著高于对照组（P<0.05）。H-E染色显示,硝酸盐明显减轻了皮瓣的组织学损伤。硝酸钠显著增加了血清中硝酸盐和亚硝酸盐水平（P<0.05）,并显著下调血清中TNF-a和IL-6水平（P<0.05）。此外,硝酸盐组皮瓣组织内MDA表达显著减少（P<0.05）,SOD表达显著增加（P<0.05）。结论 口服硝酸盐可通过调控皮瓣的氧化应激和炎症反应保护皮瓣。