Negative Treatment Effects Research Articles

Effects of long-term oral administration of methimazole on femur and tibia properties in male Wistar rats

Physiological concentrations of thyroid hormones are crucial for skeletal growth and development, physiological bone turnover and bone homeostasis maintenance. Methimazole (1-methyl-2-mercaptoimidazole) is an antithyroid drug used for the treatment of the hyperthyroidism in humans and animals. The aim of the study was to determine effects of long-term oral methimazole treatment in male Wistar rats on biochemical bone metabolism markers, as well as morphological, geometric, densitometric and mechanical properties of femur and tibia. Experimental rats were subjected to 90-day-long oral treatment with 0.05% water solution of methimazole and were kept under identical environmental conditions and received the same diet ad libitum as the control group. Serum concentration of osteocalcin (OC) and C-terminal telopeptides of type I collagen (CTX-I) was determined. Femur and tibia were evaluated using quantitative computed tomography (QCT), peripheral QCT (pQCT) and three-point bending test. Final body weight of the experimental group was significantly decreased by 30% (P=0.01). Methimazole treatment significantly decreased serum OC concentration by 21% (P=0.02) and increased CTX-I concentration by 17% (P=0.06). Methimazole decreased morphological, geometric and densitometric parameters of femur and tibia in rats. Mechanical evaluation of bones has shown significantly decreased maximum elastic strength and ultimate strength of femur in rats treated with methimazole by 36% and 40% when compared to the control group (P<0.05). In conclusion, this study has shown that long-term treatment with methimazole inhibits bone formation and accelerates bone resorption processes. The observed negative effects of methimazole treatment on body weight gain and skeletal properties may be considered as additional possible side effects in living organisms to those reported in the previous studies. It may be suggested that long-term antithyroid treatment should be combined with prevention of the negative effects of methimazole on bone tissue and whole body metabolism.

Effect of 11β-hydroxyandrostenedione on European whitefish Coregonus lavaretus (Linnaeus, 1758)

The goal of the present research was to evaluate the efficiency of 11β-hydroxyandrostenedione (OHA) applied in the diet to achieve sex reversal in the European whitefish (Coregonus lavaretus). At 32day post-hatching, fish were reared in four groups: fish fed with 10ppm of OHA (10 OHA), fish fed with 20ppm of OHA (20 OHA), fish fed without OHA (C) and fish fed without OHA and reared in the water from 20 OHA group (R). The experimental groups were conducted in separate recirculation systems and the first phase of the experiment lasted 63days. For the histological analysis of the gonads, fish from all groups were reared without OHA treatment for an additional 91days (second phase). At the end of the first phase of the experiment, survival of the whitefish ranged from 34.5±11.1% to 51.5±7.3%. The final body weight and coefficient of variation in the weight ranged from 5.6±1.2g to 6.9±1.5g and from 21.5 to 22.7%, respectively. No negative effects of OHA treatment on the growth and the survival of the whitefish were found. Six histological categories of the whitefish gonads were observed. Apart from the typical ovaries and testes, two types of the intersexual gonads (ovotestis and testis-ova) and two types of the sterile-altered gonads were distinguished. No gonadal females were found among fish from any of OHA groups. Gonadal males constituted of 60% and 50% of the fish from 10 OHA and 20 OHA groups, respectively. Intersexes were observed in all groups with the highest proportion found among fish from R variant. Rate of sterile individuals in 10 OHA and 20 OHA groups was 17% and 30%, respectively. The proportion of fish with normal testes to fish with other types of gonad varied from 0.43:1 to 1.5:1 with the higher ratio observed in both OHA groups. Lack of the females among fish from OHA groups suggested OHA affected growth and development of ovaries in the whitefish. However, a high percentage of the sterile fish in both OHA treated groups indicated application of lower doses of OHA for masculinization of the whitefish in the further research.

Development of a computer-tailored physical activity intervention for prostate and colorectal cancer patients and survivors: OncoActive

BackgroundCancer and cancer treatment coincide with substantial negative physical, psychological and psychosocial problems. Physical activity (PA) can positively affect the negative effects of cancer and cancer treatment and thereby increase quality of life in CPS. Nevertheless, only a minority of CPS meet PA guidelines. We developed the OncoActive (OncoActief in Dutch) intervention: a computer-tailored PA program to stimulate PA in prostate and colorectal CPS, because to our knowledge there are only a few PA interventions for these specific cancer types in the NetherlandsMethodsThe OncoActive intervention was developed through systematic adaptation of a proven effective, evidence-based, computer-tailored PA intervention for adults over fifty, called Active Plus. The Intervention Mapping (IM) protocol was used to guide the systematic adaptation. A literature study and interviews with prostate and colorectal CPS and health care professionals revealed that both general and cancer-specific PA determinants are important and should be addressed. Change objectives, theoretical methods and applications and the actual program content were adapted to address the specific needs, beliefs and cancer-related issues of prostate and colorectal CPS. Intervention participants received tailored PA advice three times, on internet and with printed materials, and a pedometer to set goals to improve PA. Pre- and pilot tests showed that the intervention was highly appreciated (target group) and regarded safe and feasible (healthcare professionals). The effectiveness of the intervention is being evaluated in a randomized controlled trial (RCT) (n = 428), consisting of an intervention group and a usual care waiting-list control group, with follow-up measurements at three, six and twelve months. Participants are recruited from seventeen hospitals and with posters, flyers and calls in several media.DiscussionUsing the Intervention Mapping protocol resulted in a systematically adapted, theory and evidence-based intervention providing tailored PA advice to prostate and colorectal CPS. If the intervention turns out to be effective in increasing PA, as evaluated in a RCT, possibilities for nationwide implementation and extension to other cancer types will be explored.Trial registrationThe study is registered in the Dutch Trial Register (NTR4296) on November 23rd 2013 and can be accessed at http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4296.

Nutritional (Fe, Mn, Ni, and Cr) and growth responses of rice plant affected by perennial application of two bio-solids.

Trace toxic elements often restrict the land application of different bio-solids in agriculture. In order to evaluate the separate influence of the municipal solid waste compost (MSW), sewage sludge (SS) and combined application with inorganic fertilizers (chemical fertilizer (CF)) on nutritional (Fe, Mn, Ni, and Cr) and growth responses of rice plant, a research was conducted on paddy soil from 2013 to 2015. Obtained results showed that SS levels were superior to MSW in most studied traits. The maximum chlorophyll content (46.52), plant height (162.6cm), biomass (23.33tha-1), soil available Fe (206.26ppm), Ni concentration in the root (14.41ppm) and shoots (3.16ppm), Cr concentration in the root (12.43ppm) and grain (3.65ppm), and Mn concentration in grain (66.938ppm) belonged to SS levels, specially enriched 40tha-1, when it was added to the soil for three continuous years. The highest 1000-grain weight (29.89g), yield (6.86tha-1), harvest index (48.17%), and soil available Mn (712.7ppm), Fe, and Ni concentration in grain (107.92 and 8.79ppm, respectively) were recorded in 3years of applying the enriched 40tha-1 MSW. Accumulation of Ni in grain in critical levels and negative effects of CF treatments on toxic element entry to soil and plant were two important findings of this research that need management.

Cardiac Complications, Earlier Treatment, and Initial Disease Severity in Kawasaki Disease

To assess if observed higher observed risks of cardiac complications for patients with Kawasaki disease (KD) treated earlier may reflect bias due to confounding from initial disease severity, as opposed to any negative effect of earlier treatment. We used data from Japanese nationwide KD surveys from 1997 to 2004. Receipt of additional intravenous immunoglobulin (IVIG) (data available all years) or any additional treatment (available for 2003-2004) were assessed as proxies for initial disease severity. We determined associations between earlier or later IVIG treatment (defined as receipt of IVIG on days 1-4 vs days 5-10 of illness) and cardiac complications by stratifying by receipt of additional treatment or by using logistic modeling to control for the effect of receiving additional treatment. A total of 48 310 patients with KD were included in the analysis. In unadjusted analysis, earlier IVIG treatment was associated with a higher risk for 4 categories of cardiac complications, including all major cardiac complications (risk ratio, 1.10; 95% CI, 1.06-1.15). Stratifying by receipt of additional treatment removed this association, and earlier IVIG treatment became protective against all major cardiac complications when controlling for any additional treatment in logistic regressions (OR, 0.90; 95% CI, 0.80-1.00). Observed higher risks of cardiac complications among patients with KD receiving IVIG treatment on days 1-4 of the illness are most likely due to underlying higher initial disease severity, and patients with KD should continue to be treated with IVIG as early as possible.

The Long-Term Effects of Antipsychotic Medication on Clinical Course in Schizophrenia.

Concerns have been raised that treatment with antipsychotic medication might adversely affect long-term outcomes for people with schizophrenia. The evidence cited for these concerns includes the association of antipsychotic treatment with brain volume reduction and with dopamine receptor sensitization, which might make patients vulnerable to relapse and illness progression. An international group of experts was convened to examine findings from clinical and basic research relevant to these concerns. Little evidence was found to support a negative long-term effect of initial or maintenance antipsychotic treatment on outcomes, compared with withholding treatment. Randomized controlled trials strongly support the efficacy of antipsychotics for the acute treatment of psychosis and prevention of relapse; correlational evidence suggests that early intervention and reduced duration of untreated psychosis might improve longer-term outcomes. Strategies for treatment discontinuation or alternative nonpharmacologic treatment approaches may benefit a subgroup of patients but may be associated with incremental risk of relapse and require further study, including the development of biomarkers that will enable a precision medicine approach to individualized treatment.

Mechanistic insight into the suppressive effects of stem cell factor during IgE-mediated activation in bone marrow-derived mast cells.

Abstract Treatment of bone marrow derived mast cells (BMMCs) with stem cell factor (SCF) is common practice when differentiating mast cells for experimentation. The enhanced growing potential from including SCF during mast cell culture and differentiation allows for easier maintenance and quicker experiments. Recent publications have begun to identify potentially negative effects of treatment with SCF regarding mast cell activation. The mechanism of SCF inhibition on mast cell activation is mostly unknown, but BMMCs derived with the addition of SCF function differently than untreated cells when mast cells are primed and subsequently activated. This study provides insight into the specific targets of SCF treatment and the impact SCF has on the ability of mast cells to activate. Running ELISAs in conjunction with real-time qPCR, we identified differentially expressed proteins involved in FCɛRI signaling and mast cell activation in BMMCs exposed to SCF. We examine the effects of SCF on Fyn, Lyn, Syk and Stat5 protein expression compared to mast cells raised without SCF. These data are also placed in the context of other immunosuppressive mechanism, (e.g. TGFβ). The presented data allow researchers to better understand the implications that may result from SCF treatment of BMMCs, especially with respect to examining IgE-mediated functions.

Patients\u2019 perceptions of the negative effects following different prostate cancer treatments and the impact on psychological well-being: a nationwide survey

Background:Although the prognosis of localised prostate cancer is good, the negative effects of prostate cancer treatment often impair patient quality of life. A growing number of men experience these negative effects over a longer time because of the increased incidence of and prolonged survival in prostate cancer, and the ageing of the population. Only a few studies have investigated the adverse effects of different prostate cancer treatments using large population-based samples.Methods:We conducted a nationwide survey (n=1239) to collect detailed information regarding the negative effects (i.e., the occurrence, perceived level and perceived bother since the beginning of the treatment) of prostate cancer treatments: radical prostatectomy, external beam radiotherapy, brachytherapy, hormone therapy and surveillance. Furthermore, we measured patient satisfaction with the outcome of the treatment and their psychological well-being (i.e., psychological symptoms and satisfaction with life) 5 years after diagnosis. The negative effects between the treatments were compared, and the determinants of satisfaction and psychological well-being were investigated.Results:The negative effects of all types of active prostate cancer treatments were common and persistent (33–48% reported symptoms at 5 years) and showed the known differences between the treatments. Prostatectomy and the radiotherapies caused urinary leakage; radiotherapy also caused symptoms of urinary irritation; and external radiation also caused bowel dysfunction. Most symptoms were considered highly bothersome. Most respondents (81−93%) reported that their treatment negatively affected their sex lives; 70–92% reported sexual dysfunction; and 20–58% reported that their sex lives with their spouses had ended. Urinary symptoms were especially associated with poorer psychological outcomes. The perception of symptom level and bother had a greater effect on patient satisfaction and well-being than the symptoms per se.Conclusion:Multiple and persistent negative effects follow active prostate cancer treatment, and these effects predict long-term patient satisfaction and psychological well-being. The harms and benefits associated with prostate cancer treatments should be considered when selecting whether and how to actively treat prostate cancer.

The role of metallothionein in oncogenesis and cancer treatment.

Metallothionein is cysteine-rich low molecular mass protein. The involvement of MT in many physiological and pathophysiological processes such as apoptosis, proliferation, angiogenesis, and the detoxification of heavy metals suggested participation of this protein in carcinogenesis and tumor therapy. Depending on the type of tissue and classification of carcinoma various it was observed relation between MT expression and tumor type, stage, grade, poor prognosis and body resistance to radiotherapy and chemotherapy. MT in tumor cell plays important role in defense mechanism against the effect of radiation by inhibiting the processes that lead to the apoptosis. A number of studies have shown an increased expression of MT in various human tumors of larynx, pancreas, kidney, uterus and breast, whereas lower MT expression was detected in liver tumors. Variable MT expression was detected in case of thyroid, prostate, lung, stomach and central nervous system tumors. Also MT plays crucial role in the cytostatics treatment. MT can bind cis-platinum compounds and removes them from the cells, which may lead to multidrug resistance. However, the same functions of MT protect against the negative effects of chemotherapeutic treatment. It is especially important in case of heart cells. Analysis of MT expression in tumor cells may be useful in choosing method of treatment. It is difficult to determine whether increased expression of MT is only a inducing factor of the development of the carcinogenesis, its malignances and multidrug resistance, or it is a factor inhibiting the induction and development of cancer.

Protocol for the ENCODE trial: evaluating a novel online depression intervention for persons with epilepsy

BackgroundDepression is common among persons with epilepsy (PwE), affecting roughly one in three individuals, and its presence is associated with personal suffering, impaired quality of life, and worse prognosis. Despite the availability of effective treatments, depression is often overlooked and treated inadequately in PwE, in part because of assumed concerns over drug interactions or proconvulsant effects of antidepressants. Internet-administered psychological interventions might complement antidepressant medication or psychotherapy, and preliminary evidence suggests that they can be effective. However, no trial has yet examined whether an Internet intervention designed to meet the needs of PwE can achieve sustained reductions in depression and related symptoms, such as anxiety, when offered as adjunct to treatment as usual.Methods/DesignThis randomized controlled trial will include 200 participants with epilepsy and a current depressive disorder, along with currently at least moderately elevated depression (Patient Health Questionnaire (PHQ-9) sum score of at least 10). Patients will be recruited via epilepsy treatment centers and other sources, including Internet forums, newspaper articles, flyers, posters, and media articles or advertisements, in German-speaking countries. Main inclusion criteria are: self-reported diagnosis of epilepsy and a depressive disorder, as assessed with a phone-administered structured diagnostic interview, none or stable antidepressant medication, no current psychotherapy, no other major psychiatric disorder, no acute suicidality. Participants will be randomly assigned to either (1) a care-as-usual/waitlist (CAU/WL) control group, in which they receive CAU and are given access to the Internet intervention after 3 months (that is, a CAU/WL control group), or (2) a treatment group that may also use CAU and in addition immediately receives six-month access to the novel, Internet-administered intervention. The primary outcome measure is the PHQ-9, collected at three months post-baseline; secondary measures include self-reported anxiety, work and social adjustment, epilepsy symptoms (including seizure frequency and severity), medication adherence, potential negative treatment effects and health-related quality of life. Measurements are collected online at pre-treatment (T0), three months (T1), six months (T2), and nine months (T3).DiscussionResults of this trial are expected to extend the body of knowledge with regard to effective and efficient treatment options for PwE who experience elevated depression and anxiety.Trial registrationClinicalTrials.gov: NCT02791724. Registered 01 June 2016.

Abstract C43: Glucocorticoid-mediated upregulation of stress oncoproteins: Implications for prostate cancer health disparities

Abstract Prostate cancer (PCa) presents the greatest US cancer health disparity in terms of incidence and mortality, disproportionately affecting African American (AA) men. The biological characteristics of prostate tumors are exaggerated in AA men compared to European American (EA) men at time of diagnosis, including higher PSA levels, higher Gleason scores, and advanced tumor stage. These factors influence the relatively poorer prognosis and worse overall survival rate observed in AA men. There is, however, a gap in our understanding of the mechanisms underlying increased PCa aggressiveness in AA men; therefore, there is a critical need to identify biological determinants contributing to PCa mortality disparities. Glucocorticoids—a type of steroid hormone produced in the human biological response to stress—have been implicated as driving factors in PCa progression. The underlying mechanism involves endogenous glucocorticoid (cortisol) binding to its glucocorticoid receptor (GR) and activating genes that promote tumor aggressiveness and therapy resistance. Results from phase 3 of clinical trial AFFIRM revealed that men receiving glucocorticoids to reduce the negative side effects of advanced PCa and treatment showed a significantly worse survival rate than those not receiving glucocorticoids. A clinical dilemma exists as glucocorticoids, important in the palliative care of PCa patients are now emerging as accelerators of disease progression and shortened survival. Chronically elevated levels of cortisol, which promote metabolic disorders, have been documented in AA men compared to EA men. This unhealthy cortisol production has been linked to stressful life events, which occur more frequently in the AA population. In addition, AAs are more sensitive to glucocorticoid exposure than EAs. These observations support the hypothesis that chronic stress leading to elevated cortisol in AA men may contribute to PCa health disparities. This study focused on examining the effects of glucocorticoid agonists and antagonists on the expression of stress oncoproteins, particularly LEDGF/p75 and clusterin, which are upregulated in PCa tumors and promote features of tumor aggressiveness, including resistance to clinically relevant taxanes used for advanced PCa treatment. We exposed a racially diverse panel of PCa cell lines, MDA-PCa-2b, 22Rv1, PC3, and DU145, to glucocorticoids (cortisol and dexamethasone), and observed by immunoblotting a time and dose-dependent upregulation of LEDGF/p75 and clusterin, particularly and more robustly in AA cells. Treatment of cells with mifepristone, a GR antagonist, attenuated this glucocorticoid-induced upregulation. In addition, shRNA-mediated depletion of LEDGF/p75 in PC3 cells resulted in decreased GR expression, suggesting a functional interplay between these two proteins in PCa cells. Interestingly, we also observed, using ELISA, increased circulation levels of LEDGF/p75 in AA PCa patients compared to EA patients and non-PCa controls, suggesting that this stress oncoprotein might play a more prominent role in AA PCa patients. These findings imply that activation of GR-signaling by glucocorticoids contributes to the activation of stress survival pathways associated with PCa aggressiveness. These results add to the emerging contribution of GR signaling in PCa, particularly in the context of PCa health disparities. Citation Format: Leanne Woods-Burnham, Arthur Love, Christina K. Cajigas-Du Ross, Anamika Basu, Laura Stiel, Susanne Montgomery, Colwick Wilson, Carlos A. Casiano. Glucocorticoid-mediated upregulation of stress oncoproteins: Implications for prostate cancer health disparities. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr C43.

For better or worse: An individual patient data meta-analysis of deterioration among participants receiving Internet-based cognitive behavior therapy.

Psychological treatments can relieve mental distress and improve well-being, and the dissemination of evidence-based methods can help patients gain access to the right type of aid. Meanwhile, Internet-based cognitive-behavioral therapy (ICBT) has shown promising results for many psychiatric disorders. However, research on the potential for negative effects of psychological treatments has been lacking. An individual patient data meta-analysis of 29 clinical trials of ICBT (N = 2,866) was performed using the Reliable Change Index for each primary outcome measures to distinguish deterioration rates among patients in treatment and control conditions. Statistical analyses of predictors were conducted using generalized linear mixed models. Missing data was handled by multiple imputation. Deterioration rates were 122 (5.8%) in treatment and 130 (17.4%) in control conditions. Relative to receiving treatment, patients in a control condition had higher odds of deteriorating, odds ratios (ORs) = 3.10, 95% confidence interval (CI) [2.21, 4.34]. Clinical severity at pretreatment was related to lower odds, OR = 0.62, 95% CI [0.50, 0.77], and OR = 0.51, 95% CI [0.51, 0.80], for treatment and control conditions. In terms of sociodemographic variables, being in a relationship, OR = 0.58, 95% CI [0.35, 0.95], having at least a university degree, OR = 0.54, 95% CI [0.33, 0.88], and being older, OR = 0.78, 95% CI, [0.62, 0.98], were also associated with lower odds of deterioration, but only for patients assigned to a treatment condition. Deterioration among patients receiving ICBT or being in a control condition can occur and should be monitored by researchers to reverse and prevent a negative treatment trend. (PsycINFO Database Record

Academic performance in adolescents born after ART-a nationwide registry-based cohort study.

Is academic performance in adolescents aged 15-16 years and conceived after ART, measured as test scores in ninth grade, comparable to that for spontaneously conceived (SC) adolescents? ART singletons had a significantly lower mean test score in the adjusted analysis when compared with SC singletons, yet the differences were small and probably not of clinical relevance. Previous studies have shown similar intelligence quotient (IQ) levels in ART and SC children, but only a few have been on adolescents. Academic performance measured with standardized national tests has not previously been explored in a complete national cohort of adolescents conceived after ART. A Danish national registry-based cohort including all 4766 ART adolescents (n = 2836 singletons and n = 1930 twins) born in 1995-1998 were compared with two SC control cohorts: a randomly selected singleton population (n = 5660) and all twins (n = 7064) born from 1995 to 1998 in Denmark. Nine children who died during the follow-up period were excluded from the study. Mean test scores on a 7-point-marking scale from -3 to 12 were compared, and adjustments were made for relevant reproductive and socio-demographic covariates including occupational and educational level of the parents. The crude mean test score was higher in both ART singletons and ART twins compared with SC adolescents. The crude mean differences were +0.41 (95% CI 0.30-0.53) and +0.45 (95% CI 0.28-0.62) between ART and SC singletons and between ART and SC twins, respectively. However, the adjusted mean overall test score was significantly lower for ART singletons compared with SC singletons (adjusted mean difference -0.15 (95% CI -0.29-(-0.02))). For comparison, the adjusted mean difference was +2.05 (95% CI 1.82-2.28) between the highest and the lowest parental educational level, suggesting that the effect of ART is weak compared with the conventional predictors. The adjusted analyses showed significantly lower mean test scores in mathematics and physics/chemistry for ART singletons compared with SC singletons. Comparing ART twins with SC twins yielded no difference in academic performance in the adjusted analyses. Similar crude and adjusted overall mean test scores were found when comparing ART singletons and ART twins. Missing data on educational test scores occurred in 6.6% of adolescents aged 15-16 years for the birth cohorts 1995-1997, where all of the children according to their age should have passed the ninth grade exam at the time of data retrieval. As sensitivity analyses yielded no significant difference in the adjusted risk of having missing test scores between any of the groups, it is unlikely that this should bias our results. Adjustment for body mass index and smoking during pregnancy was not possible. As our results are based on national data, our findings can be applied to other populations. The findings of this paper suggest that a possible small negative effect of parental subfertility or ART treatment is counterbalanced by the higher educational level in the ART parents. The Danish Medical Association in Copenhagen (KMS) funded this study with a scholarship grant. None of the authors had any competing interests. 704676.

Comparative phytotoxicity of undoped and Er-doped ZnO nanoparticles onLemna minor L.: changes in plant physiological responses

The present study is the first research on the phytotoxicological effects of Er-doped zinc oxide nanoparticles (NPs) on duckweed (Lemna minor L.), as a model aquatic floating macrophyte. It concentrated on the comparison of the physiological effects of different concentrations of undoped and Er-doped zinc oxide NPs on L. minor. Pure and Er-doped zinc oxide samples were synthesized through a sonochemical method and their morphology and chemical composition were studied by scanning electron microscopy and energy dispersive X-ray analysis. Plant growth, photosynthetic pigment contents, and antioxidant enzyme activities were investigated as indices to assess the effects and toxicity of the NPs on L. minor. Moreover, the dissolution of Zn2+ from the suspensions of NPs was investigated to clearly determine whether the Zn2+ released from the NPs was the main source of their toxicity to the plant. The results showed significant changes in the physiological parameters of the plant in response to the treatments. The negative effects of treatments on the growth of L. minor, in order, were Zn2+ >> ZnO-NPs >> EZO-NPs >> bulk-ZnO. The activity of superoxide dismutase was remarkably increased by increasing the concentration of the contaminants in the plant.

Timing and Targeting of Treatment in Left Ventricular Hypertrophy.

In most clinical cases, left ventricular hypertrophy (LVH) occurs over time from persistent cardiac stress. At the molecular level, this results in both transient and long-term changes to metabolic, sarcomeric, ion handling, and stress signaling pathways. Although this is initially an adaptive change, the mechanisms underlying LVH eventually lead to maladaptive changes including fibrosis, decreased cardiac function, and failure. Understanding the regulators of long-term changes, which are largely driven by transcriptional remodeling, is a crucial step in identifying novel therapeutic targets for preventing the downstream negative effects of LVH and treatments that could reverse or prevent it. The development of effective therapeutics, however, will require a critical understanding of what to target, how to modify important pathways, and how to identify the stage of pathology in which a specific treatment should be used.

Using the placebo effect: how expectations and learned immune function can optimize dermatological treatments.

The role of placebo and nocebo effects—that is positive or negative treatment effects that are entirely a consequence of the patient's expectations and beliefs about a treatment outcome in terms of efficacy, safety, usability or side effects—has been shown for almost all types of diseases and physiological response systems. Evidence for the relevance of placebo and nocebo effects in dermatology is also increasing, particularly for symptoms of itch and learned (conditioned) immune function. In addition, increasing knowledge is available about the neurobiological mechanisms of action, such as the role of the dopaminergic system. Studies on this topic offer innovative perspectives to unravel the multifactorial pathways of treatment effects and to use research designs for experimental research that provide full insight into the role of placebo and nocebo effects. Moreover, intervention strategies can be developed for dermatology practice that optimize regular treatments with innovative non‐pharmacological treatment strategies (e.g. optimized doctor–patient communication and treatment adherence, or prevention of nocebo reactions with regard to adverse side effects). In addition, evidence on learned immune function offers new pathways to optimize pharmacological treatments (e.g. dosage adjustments and conditioning of physiological responses), the ultimate goal being to prevent individual treatment failures and maximize regular treatment effects.

Nordic Walking and the Isa Method for Breast Cancer Survivors: Effects on Upper Limb Circumferences and Total Body Extracellular Water - a Pilot Study

Background: The negative side effects of breast cancer treatments can include upper limb lymphoedema. The growing literature indicates that Nordic walking is an effective discipline against several disease symptoms. The aim of this study was to determine whether introduction to Nordic walking alone is effective against total body extracellular water and upper limb circumferences in breast cancer survivors compared to its combination with a series of specifically created exercises (i.e. the Isa method). Methods: 16 breast cancer survivors (49.09 ± 2.24 years) were recruited and randomly assigned to 1 of 2 different training groups. Results: 10 lessons on Nordic walking technique plus the Isa method significantly reduced both extracellular body water and the extracellular-to-total body water ratio (p = 0.01 for both), and also the circumference of the upper limb, (both relaxed arm and forearm circumferences) (p = 0.01 for all), whereas Nordic walking alone did not. Conclusions: Introduction to Nordic walking does not seem to affect lymphoedema in breast cancer survivors. This might be because novice Nordic Walkers do not adequately generate an effective muscular pump through coordination of the alternated bimanual open-close cycle. The Isa method appears to close this gap.

Tracking and Specialization of High Schools: Does School Choice Matter?

We analyze the causal impact of choosing for an elite high school on the probability of obtaining a high school degree without study delay using a dataset for Belgium. While general schools offer study programs in all tracks, elite schools specialize and only offer programs in the academic track, preparing students for university education. If students underperform in the academic track, they can switch to a lower track to avoid study delay. For students in elite schools, switching also implies choosing for another school. We account for self-selection and heterogeneity in the treatment effect and derive a small and non-significant average effect. However, we find that there is substantial heterogeneity. Students with a high preference for elite schools experience the most negative effects, resulting in a significantly negative average treatment effect on the treated of -11.6 %points. We show that the same group is also unwilling to switch tracks after they entered an elite school. Despite the negative average effect, we also find heterogeneity among the group of treated students with a substantial fraction benefitting from an elite high school.

Effects of olive oil mill wastewater on chemical, microbiological, and physical properties of soil incubated under four different climatic conditions

The objective of this study was to understand the degradation of the organic matter of olive mill wastewater (OMW) and its phytotoxic and water repellent effects in dependence on four different climatic conditions. We hypothesized that warm conditions with sufficient soil moisture ensure optimal biological activity and thus minimize negative effects of the OMW treatment. Therefore, OMW-treated soil was incubated for 60 days under four climatic conditions. During incubation, we monitored pH, contents of nitrate, manganese and phenolic compounds, soil respiration, soil water repellency, and δ13C. Additionally, calorific value and thermal stability of the soil organic matter at the beginning and end of incubation were determined. Soil samples of the wet-cold and moist-warm incubation were tested for phytotoxicity using a seed germination bioassay with Lepidium sativum. As a function of climatic conditions, positive and negative effects, e.g., addition of nutrients, phytotoxicity, and soil water repellency, were observed. Under dry-hot conditions, the soil was still water repellent after 60 days of incubation whereas the wet-hot, moist-warm, and wet-cold incubation show that soil would stay wettable if soil moisture before OMW treatment would be sufficient. Thus, the impact of OMW treatment on soil quality strongly depends on the environmental conditions which should favor an enhancement of microbial activity to minimize negative effects.

Effects of paraffine oil on leaf and berry mycobiota on two grape varieties

Application of fungicides have advantages and also some direct or indirect disadvantages, such as imbalance and/or fungicide resistance in microbe population. To avoid these problems the development of alternative, eco-friendly methods like mostly spraying with oils are in the focus nowadays. The investigations of the effects of fungicides on microbiota in some cultivations can give a more complex view to this topic and developmental possibilities. In the present study, our aim was testing of the effects of paraffine oil (as alternative fungicide) on microbial properties (CFU and rate of filamentous fungi and yeasts) of Chardonnay and Kékfrankos leaves and berries.&#x0D; Our results from 2014 showed that the application of paraffine oil as sole spray agent can decrease the presence of saprophytic filamentous fungi on the berries of Chardonnay (susceptible for fungal infections). In the case of Kékfrankos berries opposite properties were observed, which may be the result of the absorption of oil by the thick wax layer of this variety. The oil treatment did not affect the yeast population of Chardonnay and Kékfrankos berries contrary to negative effect of the regular pesticide treatment. The selective fungicide effect of paraffine oil against filamentous fungal population caused the accumulation of yeast cells in the mycobiota of grape berries. The careful use of this yeasts in spontaneous fermentation can improve the aroma profile of wines. The year of 2015 did no prefer the growth of fungi, therefore no interesting properties were detected in the mycobiota of grape varieties. The occurence of the harmful saprophytic filamentous fungi predicted to be increased in mild climate agricultures as the result of the climate change.&#x0D; In summary, the paraffine oils are seem to be promising tools for the eco-friendly control of harmful fungi of grapes.