Variations of rest-activity rhythm and sleep-wake in schizophrenic patients versus healthy subjects: An actigraphic comparative study

The objective of the present study was to compare the pattern of motor activity in unmedicated schizophrenia patients and healthy subjects, and to examine whether the pattern was affected by treatment with typical and atypical antipsychotics. Twenty unmedicated schizophrenic patients wore a wrist actigraph for five days. The actigraph recorded activity levels in one-minute epochs. Patients' pattern of activity was compared with that of healthy subjects. Patients were randomly assigned to treatment with low-dose haloperidol or risperidone. The impact of treatment on the pattern of activity was examined. Compared to controls, untreated patients showed a diminished mean activity count during morning, early and late night periods. Treatment with haloperidol or risperidone at effective doses showed a significant effect on activity level, being more prominent with haloperidol. The results suggest that unmedicated schizophrenic patients exhibit abnormally low levels of motor activity as measured with an objective activity meter. This persists after antipsychotic treatment even though symptoms improve. Future studies should clarify whether motor disturbances are a primary effect of the illness, or related to the illness-related lifestyle.     

Tartrate-resistant acid phosphatase 5b as a serum marker of bone metastasis in breast cancer patients

Diagnosis and follow-up of bone metastases in breast cancer patients usually rely on symptoms and imaging studies. Tartrate-resistant acid phosphatase 5b (TRACP 5b) is a specific marker of osteoclasts and is herein proposed as a marker of bone metastasis in breast cancer patients. An immunoassay using a monoclonal antibody, 14G6, was used to measure the activity of serum TRACP 5b at pH 6.1 in 30 early breast cancer patients without bone metastasis and in 30 aged-matched breast cancer patients with bone metastasis. Another 60 normal volunteers were recruited as controls. Bone alkaline phosphatase (BAP), a traditional marker of bone turnover, was also measured in selected cases. The overall mean TRACP 5b activity in normal women was 2.83 ± 1.1 U/I, and it increased with age. The mean TRACP 5b activity in early breast cancer patients did not differ from that of the normal group (2.93 ± 0.64 vs. 2.83 ± 1.1 U/I; p=0.66), whereas it was significantly higher in breast cancer patients with bone metastasis (5.42 ± 2.5 vs. 2.83 ± 1.1 U/I; p<0.0001). BAP activity was significantly higher in breast cancer patients with bone metastasis than in early breast cancer patients (p=0.004). Serum TRACP 5b activity correlated well with BAP activity in breast cancer patients with bone metastasis (p<0.0001), but not in normal individuals or in patients without bone metastasis. TRACP 5b activity can be considered a surrogate indicator of bone metastasis in breast cancer patients.     

Matrix metalloproteases and TIMPs as prognostic biomarkers in breast cancer patients treated with radiotherapy: A pilot study

Breast cancer (BC) is the most common tumour in women and one of the most important causes of cancer death worldwide. Radiation therapy (RT) is widely used for BC treatment. Some proteins have been identified as prognostic factors for BC (Ki67, p53, E‐cadherin, HER2). In the last years, it has been shown that variations in the expression of MMPs and TIMPs may contribute to the development of BC. The aim of this pilot work was to study the effects of RT on different MMPs (‐1, ‐2, ‐3, ‐7, ‐8, ‐9, ‐10, ‐12 and ‐13) and TIMPs (‐1 to ‐4), as well as their relationship with other variables related to patient characteristics and tumour biology. A group of 20 BC patients treated with RT were recruited. MMP and TIMP serum levels were analysed by immunoassay before, during and after RT. Our pilot study showed a slight increase in the levels of most MMP and TIMP with RT. However, RT produced a significantly decrease in TIMP‐1 and TIMP‐3 levels. Significant correlations were found between MMP‐3 and TIMP‐4 levels, and some of the variables studied related to patient characteristics and tumour biology. Moreover, MMP‐9 and TIMP‐3 levels could be predictive of RT toxicity. For this reason, MMP‐3, MMP‐9, TIMP‐3 and TIMP‐4 could be used as potential prognostic and predictive biomarkers for BC patients treated with RT.     

Lifting patients in bed with and without a drawsheet: a comparative ergonomics study

Two techniques for lifting a patient in bed, namely with and without the use of a drawsheet, have been compared from an ergonomics point of view. Forty-two nurses of a Thai university hospital were studied before and after using each method by measuring back strengths and by using a questionnaire for feelings of fatigue and for musculoskeletal fatigue and pain. Decreases in back strength 10 minutes after and immediately after lifting with each method were found to be significant (90% confidence). The decrease 10 minutes after lifting was found to be significantly smaller with a drawsheet than without one (98% confidence). Immediately after lifting there was less difference between the two methods, which indicates that the use of a drawsheet reduced the recovery time and the decrease in back strength. Increases in feelings of fatigue from lifting with each method were also found to be significant (90% confidence), and the results indicate that the increase was lower with a drawsheet than without one. Musculoskeletal fatigue and pain immediately after lifting were more common without a drawsheet than with one. In conclusion, the lifting technique with a drawsheet is ergonomically superior and should be used by nursing personnel.     

The role of plasma IDO activity as a diagnostic marker of patients with colorectal cancer

High levels of indoleamine 2,3-dioxygenase (IDO) are involved in tumour escape mechanisms. The aim of this study is the evaluation of l-kynurenine of plasma as marker of diagnostic and prognostic in patients with colorectal cancer. The study included 78 patients with colorectal cancer, of whom 15 % were in stage I/II, 30 % in stage III, and 55 % in stage IV, and was compared with a control group of 70 healthy subjects. The receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.917, with a specificity of 100 % and with a sensitivity to detect cancer of the colon of 85.2 %, taking 1.83 μM as a cut-off point. The overall survival analysis also indicated that patients with low levels of l-kynurenine in plasma increased survival rate after 45 months of follow-up (P = 0.032). These results show that the plasma levels of l-kynurenine could be a good biomarker to differentiate individuals with colorectal cancer from healthy individuals.     

Physical activity and lung cancer among non-smokers: a pilot molecular epidemiological study within EPIC

The association between physical activity, potential intermediate biomarkers and lung cancer risk was investigated in a study of 230 cases and 648 controls nested within the European Prospective Investigation of Cancer and Nutrition. Data on white blood cell aromatic-DNA adducts by ³²P-post-labelling and glutathione (GSH) in red blood cells were available from a subset of cases and controls. Compared with the first quartile, the fourth quartile of recreational physical activity was associated with a lower lung cancer risk (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35–0.90), higher GSH levels (+1.87 μmol GSH g^?1 haemoglobin, p = 0.04) but not with the presence of high levels of adducts (OR 1.05, 95% CI 0.38–2.86). Despite being associated with recreational physical activity, in these small-scale pilot analyses GSH levels were not associated with lung cancer risk (OR 0.95, 95% CI 0.84–1.07 per unit increase in GSH levels). Household and occupational activity was not associated with lung cancer risk or biomarker levels.     

Discrepancies between metabolic activity and DNA content as tool to assess cell proliferation in cancer research

Cell proliferation is a critical and frequently studied feature of molecular biology in cancer research. Therefore, various assays are available using different strategies to measure cell proliferation. Metabolic assays such as AlamarBlue, water‐soluble tetrazolium salt and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide, which were originally developed to determine cell toxicity, are used to assess cell numbers. Additionally, proliferative activity can be determined by quantification of DNA content using fluorophores such as CyQuant and PicoGreen. Referring to data published in high ranking cancer journals, these assays were applied in 945 publications over the past 14 years to examine the proliferative behaviour of diverse cell types. In these studies, however, mainly metabolic assays were used to quantify changes in cell growth yet these assays may not accurately reflect cellular proliferation rates due to a miscorrelation of metabolic activity and cell number. Testing this hypothesis, we compared the metabolic activity of different cell types, human cancer cells and primary cells, over a time period of 4 days using AlamarBlue and the fluorometric assays CyQuant and PicoGreen to determine their DNA content. Our results show certain discrepancies in terms of over‐estimation of cell proliferation with respect to the metabolic assay in comparison to DNA binding fluorophores.     

Association between light exposure at night and insomnia in the general elderly population: The HEIJO-KYO cohort

Chronic circadian misalignment between the internal and environmental rhythms, which is typically related to night-shift work and clock-gene variants, is associated with disruption of suprachiasmatic nucleus function and increased risk of insomnia. Under controlled laboratory conditions, light at night (LAN) suppresses melatonin secretion, delays the internal biological rhythm, and reduces sleepiness. Therefore, LAN exposure may cause circadian misalignment and insomnia, though it remains unclear in real-life situations whether LAN exposure is associated with insomnia. To evaluate an association between LAN exposure and sleep quality in home settings, we conducted a cross-sectional community-based study in 857 elderly individuals (mean age, 72.2 years). We evaluated bedroom light intensity using a light meter and subjectively and objectively measured sleep quality using the Pittsburgh Sleep Quality Index and an actigraph, respectively, along with urinary 6-sulfatoxymelatonin excretion. Compared with the lowest quartile group of LAN intensity, the highest quartile group revealed a significantly higher odds ratio (OR) for subjective insomnia in a multivariate model adjusted for age, gender, body mass index, daytime physical activity, urinary 6-sulfatoxymelatonin excretion, bedtime, rising time, and day length (adjusted OR, 1.61, 95% confidence interval, 1.05–2.45, p?=?0.029). In addition, higher OR for subjective insomnia was significantly associated with the increase in quartiles of LAN intensity (p_trend?=?0.043). Consistently, we observed significant association trends between the increase in quartiles of LAN intensity and poorer actigraphic sleep quality, including decreased sleep efficiency, prolonged sleep-onset latency, increased wake-after-sleep onset, shortened total sleep time, and delayed sleep-mid time in multivariate models adjusted for the covariates mentioned above (all p_trend?<?0.001). In conclusion, we demonstrated that LAN exposure in home settings is significantly associated with both subjectively and objectively measured sleep quality in a community-based elderly population.     

Suicides among cancer patients in Lithuania: A population-based census-linked study

Background: This study aims to estimate suicide risk and its socio-demographic determinants among cancer patients in the country showing the highest suicide rates among developed countries. Methods: The study is based on a unique census-linked dataset based on the linkages between the records from death and cancer registers and the 2001 population census records. Standardized mortality ratios for suicide (SMRs) were calculated for patients diagnosed with cancer in Lithuania between April 6, 2001 and December 31, 2009, relative to suicide rates in the general population. Results: We found that the relative suicide risk was elevated for both males and females, with SMRs of 1.43 (95% CI 1.23–1.66) and 1.32 (95% CI 0.95–1.80), respectively. This relationship for females became statistically significant and stronger after excluding skin cancers. The highest suicide risks were observed at older ages and during the period shortly after the diagnosis. The groups showing an increased suicide risk include lower educated, non-married, and rural male patients. Conclusion: The results of our study point to inadequacies of the health care system in dealing with mental health problems of cancer patients. Interventions allowing early detection of depression or suicidal ideation may help to prevent suicide among cancer patients in Lithuania.     

Quantitative proteomics study of breast cancer cell lines isolated from a single patient: Discovery of TIMM17A as a marker for breast cancer

The proteins involved in breast cancer initiation and progression are still largely elusive. To gain insights into these processes, we conducted quantitative proteomic analyses with 21T series of breast cell lines, which include a normal, primary tumor and a metastatic tumor that were isolated from a single patient. Stable isotope labeling of amino acid in cell culture followed by LC‐MS/MS analysis was performed and deregulated proteins were identified using statistical analysis. Gene ontology analysis revealed that proteins involved in metabolic processes were the most deregulated in both tumorigenesis and metastasis. Interaction network analysis indicated that ERBB2 signaling played a critical role in tumorigenesis. In addition to known markers such as ERBB2 and E‐cadherin, novel markers, including BRP44L, MTHFD2 and TIMM17A, were found to be overexpressed in 21T breast cancer cells and verified in additional breast cell lines. mRNA expression analysis as well as immunohistochemistry analysis in breast cancer tissues indicated that expression level of TIMM17A was directly correlated with tumor progression, and survival analysis suggested that TIMM17A was a powerful prognosis factor in breast cancer. More interestingly, overexpression and siRNA knockdown experiments indicated an oncogenic activity of TIMM17A in breast cancer. Our study provides a list of potential novel markers for breast cancer tumorigenesis and metastasis using a unique cell model. Further studies on TIMM17A as well as other markers on the list may reveal mechanisms that result in more effective therapeutics for cancer treatment.     

The association between benzo[a]pyrene-DNA adducts and body mass index,calorie intake and physical activity

Prior work suggests that body size and fat content may influence carcinogen-DNA adduct levels measured in white blood cells. Here we consider energy balance more broadly by assessing the impact of body mass index (BMI), physical activity and calorie intake on the presence of benzo[a]pyrene-DNA (BP-DNA) adducts in white blood cell DNA. Our cross-sectional study employed subjects from a separately conducted intervention trial. Physical activity and food intake data were collected at 12 and 15 months of follow-up, respectively. BP-DNA adducts were measured by high-performance liquid chromatography (HPLC) in white blood cell samples collected at 12 months of follow-up. Complete data on all variables were available from 143 subjects. Logistic regression showed that BMI was inversely associated with the presence of detectable adducts (OR = 0.90, p=0.02), and that hours of moderate-intensity physical activity were positively associated with the presence of detectable adducts (OR = 1.04, p=0.04). These results provide further evidence that body fat content influences carcinogen-DNA adduct levels, probably by altering the distribution of the lipophilic parent compound.     

The association between benzo[a]pyrene-DNA adducts and body mass index, calorie intake and physical activity

Prior work suggests that body size and fat content may influence carcinogen-DNA adduct levels measured in white blood cells. Here we consider energy balance more broadly by assessing the impact of body mass index (BMI), physical activity and calorie intake on the presence of benzo[a]pyrene-DNA (BP-DNA) adducts in white blood cell DNA. Our cross-sectional study employed subjects from a separately conducted intervention trial. Physical activity and food intake data were collected at 12 and 15 months of follow-up, respectively. BP-DNA adducts were measured by high-performance liquid chromatography (HPLC) in white blood cell samples collected at 12 months of follow-up. Complete data on all variables were available from 143 subjects. Logistic regression showed that BMI was inversely associated with the presence of detectable adducts (OR = 0.90, p=0.02), and that hours of moderate-intensity physical activity were positively associated with the presence of detectable adducts (OR = 1.04, p=0.04). These results provide further evidence that body fat content influences carcinogen-DNA adduct levels, probably by altering the distribution of the lipophilic parent compound.     

The significance of galectin-3 as a new basal cell marker in prostate cancer

Prostate cancer may originate from distinct cell types, resulting in the heterogeneity of this disease. Galectin-3 (Gal-3) and androgen receptor (AR) have been reported to play important roles in the progression of prostate cancer, and their heterogeneous expressions might be associated with different cancer subtypes. Our study found that in various prostate cancer cell lines Gal-3 expression was always opposite to AR expression and other luminal cell markers but consistent with basal cell markers including glutathione S-transferase-π and Bcl-2. This expression pattern was confirmed in human prostate cancer tissues. Our results also showed that prostate cancer cells positive with basal cell markers were more aggressive. Downregulation of Gal-3 expression resulted in increased apoptotic potential and decreased metastasis potential of prostate cancer cells. Our findings demonstrate for the first time that Gal-3 may serve as a new marker for basal characteristics of prostate cancer epithelium. This study helps us to better understand the heterogeneity of prostate cancer. The clinical significance of this study lies in the application of Gal-3 to distinguish prostate cancer subtypes and improve treatment efficacy with designed personalized therapy.     

A comparative study of carbonic anhydrase activity in lymphocytes from colorectal cancer tissues and adjacent healthy counterparts

Several carbonic anhydrase (CA, EC 4.2.1.1) isoforms play an essential role in processes connected to tumorigenesis, as they efficiently accelerate the hydration of carbon dioxide to bicarbonate and proton. In this context, examples are CA IX and CA XII, which were proved to be upregulated in many solid malignancies. On the other hand, cancer and the immune system are inextricably linked, and targeting the immune checkpoints recently was shown to efficiently improve the treatment of malignancies. In this study, we have investigated the expression of CA isoforms in tumour-infiltrating lymphocytes (TILs) that, according to the immunosurveillance theory, were suggested to have a crucial role in the development of colorectal cancer (CRC). T lymphocytes isolated from healthy surrounding mucosa showed a higher CA activity compared to those present in tumour and peripheral blood in the same patients. CA I and II were confirmed as enzyme isoforms involved in the process, as determined by proteomic analysis of corresponding TIL samples. These preliminary findings suggest a dysregulation of the local immune response in the CRC tissues and a loss of effective anticancer mechanisms mediated by CAs therein.     

In vitro rooting of Psoralea corylifolia Linn: Peroxidase activity as a marker

Induction of rooting in microshoots of Psoraleacorylifolia was achieved within 6–8 days of cultureon half-strength basal Murashige and Skoog's(1962) medium supplemented with 0.005–0.01 mg/lindole-3-acetic acid (IAA) and 2% (w/v) sucrose. Rooting was drastically reduced and friable callusformed at the cut end of the microshoots when themedium was supplemented with a higher concentration ofauxin. Rooting was totally inhibited when themicroshoots were cultured in vitro undercontinuous light. However, the maximum percentage ofmicroshoots rooted when incubated in continuous lightfor 4 weeks before transfer to the rooting media.Peroxidase activity increased considerably duringroot induction indicating a key role of peroxidase inrooting of microshoots of Psoralea corylifolia invitro.     

A relationship between nightmare content and somatic stimuli in a sleep-disordered population: A preliminary study.

This study aimed to examine the influence of specific sleep disorders on dream content. The authors hypothesized that: (a) waking somatic concerns influence dream content and (b) somatic stimulation associated with specific sleep disorders influence dream content items. The subjects (N = 124) were included if they demonstrated obstructive sleep apnea, narcolepsy, an EEG arousal disorder during sleep, or periodic leg movements during sleep (PLMS), based on standard polysomnography. The 42-item Wahler Physical Symptom Inventory was used to quantify somatic concerns. Dream content and frequency was assessed with a 37-item Dream Questionnaire. Ten symptom-dream pairs were selected as mutually relevant and subjected to chi-square analysis. 84.6% of all subjects reported having bad dreams (N = 105). A significant proportion of patients who complain of excessive perspiration dream about perspiring, and significant proportions of those who report difficulty breathing while awake dream about feelings of choking and suffocation. Recurring dreams and dreams of paralysis are significantly more prominent in patients with narcolepsy. Patients with sleep apnea do not dream of choking/feelings of suffocation with greater frequency than nonapneics. These findings suggest that somatic stimulation associated with specific sleep disorders appears to have an inconsistent influence on certain dream content items. Furthermore, dream mentation appears to feature waking concerns, rather that being related to events associated with during sleep disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biological rhythms,chronodisruption and chrono-enhancement: The role of physical activity as synchronizer in correcting steroids circadian rhythm in metabolic dysfunctions and cancer

ABSTRACT

Rhythms can be observed at all levels of the biologic integration in humans. The observation that a biological or physiological variable shows a circadian rhythm can be explained by several multifactorial systems including external (exogenous), internal (endogenous) and psychobiological (lifestyle) mechanisms. Our body clock can be synchronized with the environment by external factors, called “synchronizers”, i.e. the light–dark cycle, but it is also negatively influenced by some pathological conditions or factors, called “chronodisruptors,” i.e. aging or low physical activity (PA). The desynchronization of a 24-h rhythm in a chronic manner has been recently defined “chronodisruption” or “circadian disruption.” A very large number of hormonal variables, such as adrenal and gonadal stress steroids, are governed by circadian rhythmicity. Such hormones, in normal conditions, show a peak in the first part of the day, while their typical diurnal fluctuations are totally out of sync in subjects affected by cancer or metabolic diseases, such as obesity, diabetes and metabolic syndrome. In general, a flatter slope with altered peaks in cortisol and testosterone circadian rhythms has been observed in pathological individuals. PA, specifically chronic exercise, seems to play a key role as synchronizer for the whole circadian system in such pathologies even if specific data on steroids circadian pattern are still sparse and contradictory. Recently, it has been proposed that low-intensity chronic PA could be an effective intervention to decrease morning cortisol levels in pathological subjects. The standardization of all confounding factors is needed to reach more clear evidence-based results.     

Multielement analysis in serum of thyroid cancer patients before and after a surgical operation

Concentrations of trace elements Zn, Cu, Fe, Mn, Mg, and Sr in the serum of 50 thyroid cancer patients and 50 healthy controls were analyzed comprehensively by Pattern Recognition Analysis Method. Based on the Principal Component Analysis Method, Zn, Cu, and Sr were found to be the principal elements with significant variations between patients and healthy controls. According to the Mahalanolis Distance Decision and Nonlinear Mapping Methods, the trace elements levels in the serum of cancerous patients were found significantly different from that of controls. For 16 thyroid malignant tumor patients who underwent surgery, sample points of patients after surgery were directional away from corresponding points before surgery. However, an overlapping was found and separation between two groups of points was not complete. This finding suggests that there may be a latency period for the restoration of trace element levels after removal of the malignant tumorous tissue.     

Overview of CD24 as a new molecular marker in ovarian cancer

Ovarian cancer (OC) is the fifth leading cause of cancer-related death among women. The high mortality rate is due to lack of early symptoms, late diagnosis, limited treatment options, and also emerging of drug resistance. Todays, molecular markers have become promising in tumor-targeted therapy. Several molecular markers have been known in OC immunotherapy. Identification of the specific molecular markers with prognostic significance is interested. CD24 is a small sialoglycoprotein which is localized in lipid rafts through its glycosylphosphatidylinositol (GPI) anchor. It has been reported that CD24 is overexpressed in many cancers including OC. Also, CD24 is identified as a cancer stem cell marker in OC. The CD24 expression is associated with the development, invasion, and metastasis of cancer cells. The exact role of CD24 in cancer cells is not clearly understood. Recently, CD24 has been identified as an independent prognostic marker of survival in patients with OC. In this study, we reviewed the molecular targets in OC immune-targeted therapy and also presented an overview of the new molecular marker CD24 and its association with the OC by reviewing the recent literature.     

The interrelationship between physical activity and metabolic regulation of breast cancer progression in obesity via cytokine control

Regular physical activity is known to protect against the development of breast cancer and mediate direct anti-inflammatory effects on adipose tissue. While direct relationships between muscle activity, adipose tissue and breast tissue have been highlighted in recent years, few studies have focused on the effects of obesity and physical activity during the development of breast cancer, particularly at the level of cell signaling. Skeletal muscle and adipose tissue modulate the cell metabolism by secreting myokines and adipokines. These secreted cytokines belong to a crosstalk network via cell signaling pathway modulation. The understanding of the tissue crosstalk is fundamental to the management of physical activity in the care of obese breast cancer patients. Therefore, this review focuses on the effects of obesity and physical activity during the development of breast cancer, particularly at the level of cell signaling. We focuse on the main mediators, secreted by both adipose and muscle tissue, which are implicated in breast cancer development. We presente the variation of these mediators in the physiopathological context of their secreted tissue. Then, we open the discussion on the crosstalk of these tissues in breast carcinogenesis.