Negative Treatment Effects Research Articles

Sexually dimorphic gene expression and neurite sensitivity to estradiol in fetal arcuate Kiss1 cells.

Kiss1 neurons of the arcuate (ARC) nucleus form an interconnected network of cells that communicate via neurokinin B (encoded by Tac2) and its receptor (encoded by Tacr3) and play key roles in the control of the reproductive axis through sex hormone-regulated synthesis and release of kisspeptin peptides (Kp, encoded by Kiss1). The aim of this study was to determine whether the Kiss1 cell population of the ARC already displays sexually dimorphic features at embryonic age E16.5 in mice. At this time of development, Kiss1-GFP- and Kp-immunoreactive cell bodies were restricted to the ARC and not found in the pre-optic area (POA). The Kiss1-GFP cell population was identical in size between sexes but had significantly lower Kiss1, Tac2, and Tacr3 mRNA levels and lower Kp-ir fiber density in the POA in male compared to female fetuses. Receptors for androgen (Ar) and estrogen (Esr1, Esr2, Gpr30) and the Cyp19a1 gene (encoding the estradiol-producing enzyme aromatase) transcripts were also detected in fetal ARC Kiss1-GFP cells with significant sex differences for Ar (higher in males) and Esr1 (higher in females). Functional studies on primary cultures of sorted fetal Kiss1-GFP cells revealed a significant negative effect of estradiol treatment on neurite outgrowth on the fourth day of culture in the female group specifically. We conclude that the ARC Kiss1 cell population is already sexually differentiated at E16.5 and that its morphogenetic development may be particularly vulnerable to estradiol exposure at this early developmental time.

Protocol for the Optimune trial: a randomized controlled trial evaluating a novel Internet intervention for breast cancer survivors

IntroductionDepression and fatigue are common in breast cancer survivors, and their presence is associated with personal suffering and worse prognosis. While many women receive short-term psychological support in the acute treatment phase, this is rarely available in subsequent phases. Internet interventions for breast cancer survivors could provide additional psychological support, as they are easily accessible and may be effective. However, no trial has yet examined the effectiveness of an Internet intervention that provides cognitive behavioural therapy techniques plus lifestyle advice for this population. This trial aims to test whether Optimune, a novel Internet intervention we developed for that purpose, leads to improvements in quality of life and relevant lifestyle habits over the course of 3 to 6 months.MethodsThis randomized controlled trial (RCT) will include 360 female breast cancer survivors who have completed the active tumour eradication phase. Participants will be recruited from various settings, including web-based advertisements and Internet forums in German-speaking countries. The main inclusion criteria are a breast cancer diagnosis less than 5 years ago and completion of acute treatment at least 1 month ago, as verified by discharge letter from an oncology treatment centre. Participants will be randomly assigned to either (1) a control group, in which they receive care as usual (CAU) and are given access to Optimune after a delay of 3 months (CAU/wait list control), or (2) a treatment group that may also use CAU and will receive 12-month access to Optimune immediately after randomization. The three primary endpoints are quality of life, physical activity and diet quality, assessed with the World Health Organization Quality of Life Questionnaire, the International Physical Activity Questionnaire and the Food Quality Questionnaire, at 3 months post-baseline; secondary outcomes include cancer-related fatigue, emotional stress, depression, anxiety, fear of progression, insomnia, usefulness of the programme and negative treatment effects. Online assessments are conducted at baseline (T0), 3 months (T1) and 6 months (T2).DiscussionResults of this RCT are expected to extend the body of knowledge with regard to the effectiveness of CBT-based Internet interventions for female breast cancer survivors.Trial registrationClinicalTrials.gov, NCT03643640. Registered on 23 August 2018.

Beneficial effects of a negative ion patch on eccentric exercise-induced muscle damage, inflammation, and exercise performance in badminton athletes.

Complementary and alternative medicines (CAMs) are widely applied and accepted for therapeutic purposes because of their numerous benefits. Negative ion treatment belongs to one of the critical categories defined by the National Center for CAM, with such treatment capable of air purification and ameliorating emotional disorders (e.g., depression and seasonal affective disorder). Negative ions can be produced naturally and also by a material with activated energy. Exercise-induced muscle damage (EIMD) often occurs due to inadequate warm up, high-intensity exercise, overload, and inappropriate posture, especially for high-intensive competition. Few studies have investigated the effects of negative ion treatment on muscular injury in the sports science field. In the current study, we enrolled badminton athletes and induced muscle damage in them through eccentric exercise in the form of a high-intensity squat program. We evaluated the effects of negative ion patches of different intensities at three points (preexercise, postexercise, and recovery) by analyzing physiological indexes (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-10, creatine kinase [CK], and lactate dehydrogenase [LDH] levels) and performing a functional assessment (a countermovement jump [CMJ] test). We found that a high-intensity negative ion patch could significantly reduce the levels of TNF-α, an injury-associated inflammatory cytokine, and related markers (CK and LDH). In addition, muscular overload-caused fatigue could be also ameliorated, as indicated by the functional CMJ test result, and related muscular characteristics (tone and stiffness) could be effectively improved. Thus, the negative ion treatment could effectively improve physiological adaption and muscular fatigue recovery after EIMD in the current study. The negative ion patch treatment can be further integrated into a taping system to synergistically fulfill exercise-induced damage protection and functional elevation. However, the effects of this treatment require further experimental validation.

Telomere dynamics from hatching to sexual maturity and maternal effects in the 'multivariate egg'.

Avian eggs contain a large number of molecules deposited by the mother that provide the embryo with energy but also potentially influence its development via the effects of maternally derived hormones and antibodies: the avian egg is thus 'multivariate'. Multivariate effects on offspring phenotype were evaluated in a study on captive zebra finches, by simultaneously manipulating maternally derived antibodies (MAb) by lipopolysaccharide (LPS) treatment of mothers and injection of testosterone into the egg yolk. LPS treatment had a positive effect on body mass growth at 30 days after hatching and immune response at sexual maturity, while egg testosterone treatment positively influenced immune response at fledging and courtship behaviour in sexually mature male offspring. Maternal effects are known to modulate offspring telomere length (TL). However, the multivariate effects of egg-derived maternal components on offspring telomere dynamics from hatching to sexual maturity are undefined. Here, we tested: (1) the effects of LPS and testosterone treatments on TL from hatching to sexual maturity (day 82); (2) how LPS treatment modulated TL over reproduction in adult females; and (3) the relationship between maternal and offspring TL. We predicted that TL would be shorter in LPS fledglings (as a cost of faster growth) and that TL would be longer in sexually mature adults after yolk testosterone treatment (as a proxy of individual quality). In adult females, there was an overall negative relationship between laying and rearing investments and TL, this relationship was weaker in LPS-treated females. In chicks, there was an overall negative effect of LPS treatment on TL measured at fledging and sexual maturity (day 25-82). In addition, at fledging, there was a Sex×LPS×Testosterone interaction, suggesting the existence of antagonistic effects of our treatments. Our data partially support the hypothesis that telomeres are proxies of individual quality and that individual differences in TL are established very early in life.

The Mode of Detection Is Not Associated with Quality of Life in Women with Breast Cancer

Introduction: Apart from saving lives, mammography screening programs (MSP) are expected to reduce negative side effects of treatment by detecting cancer earlier, when it is more responsive to less aggressive treatment. This study compared quality of life (QoL) among women with breast cancers that were detected either by screening mammography, as interval cancers, or clinically among women not participating in the MSP. Methods: Retrospective study of first-ever invasive breast cancers detected among MSP-eligible women aged 50–69 years between 2006 and 2012 in Münster, Germany. EORTC QLQ-C30 and -BR23 questionnaires were mailed to 1,399 cases still alive in 2015 (response rate 64.1%). Results: Women’s responses were obtained on average 6.1 years after diagnosis. Mean crude and age-adjusted scores for overall QoL, breast and body image (BBI), and five functional scales (FS) were comparable between groups of detection mode. Clearly lower adjusted means for most scores were observed in women with interval cancers, if time since diagnosis was less than 5 years. Cases younger than 60 years showed lower values for some FS, particularly among interval and screen-detected cases. Discussion/Conclusion: In summary, cases with breast cancer showed health-related score values that were similar to the general population of the same age. There was also no indication that mode of detection markedly influenced these scores. However, after adjusting for tumor stage and other influential factors, screening participants appeared more susceptible to score declines after a diagnosis of cancer than non-participants.

Care dependency may help and hurt psychological treatment: A treatment-analogue study with students in clinical training.

Care dependency in mental health care has been considered a negative side effect of treatments. The current treatment-analogue study tested whether care dependency was (a) distinguishable from trait dependency, (b) related to a clearer passive stance and lower therapeutic alliance quality, and predicted (c) less symptom reduction and (d) a stronger wish to continue treatment. A total of 136 students following a training in psychotherapy participated in the study. The students received treatment for psychological symptoms as part of their professional schooling, conducted by a fellow student as their therapist. Students' care dependency levels, passive stance, wish for treatment continuation, therapeutic alliance, and symptom levels were administered multiple times during treatment by means of self-report questionnaires. Results showed that 2 dimensions of care dependency, submissive stance and the lack of perceived alternatives, were positively associated with students' passive stance. The latter also predicted students' wish to continue treatment. A third dimension of care dependency, the need for contact, was positively associated with a better therapeutic alliance. These results suggest negative as well as potential positive effects of dependency. Future research should provide further insight into this dilemma and test whether the results could be generalized to patient settings.

Experimental investigation of Microcystis aeruginosa cyanobacteria thickening to obtain a biomass for the energy production

AbstractThe purpose of the presented research is to analyse possible methods of thickening of the Microcystis aeruginosa (Kützing) Kützing cyanobacteria using the obtained concentrate as a biomass for the production of energy carriers and biologically valuable substances. Method of cyanobacteria thickening under the action of electric current and in the electric field, as well as the method of coagulation–flocculation and gravity thickening, was experimentally investigated in labscale conditions. Electrical methods didn't show positive results for the Microcystis aeruginosa thickening, despite the reports of their potential efficiency in a number of previous studies. The high efficiency of the method of coagulation– flocculation and gravity thickening of Microcystis aeruginosa suspensions was obtained. The optimum concentrations of industrial polymeric coagulants and flocculants for the thickening of Microcystis aeruginosa suspensions were defined in the range of about 10 ppm for the coagulants and about 1 ppm for the flocculants. Negative effect of the previous cavitational treatment of the diluted suspensions of Microcystis aeruginosa on the effectiveness of the coagulation–flocculation and gravitational thickening was confirmed experimentally. Hydrodynamic cavitation should be recommended to use after the thickening as the next step of processing of concentrated suspensions of Microcystis aeruginosa to achieve maximum extraction of energy carriers and biologically valuable substances.

Chapitre 9. Oncofertility and prepubescent girls: A ‘right to an open future’?.

Chemotherapy and radiotherapy have increased the life expectancy of cancer patients but may cause premature ovarian failure and irreversible loss of fertility. In the context of childhood cancers, it is now acknowledged that possible negative effects of treatment on future reproductive autonomy are a major concern. While a few options are open to patients post-puberty, the only option currently open to prepubescent girls is cryopreservation of ovarian tissue and subsequent transplantation. Yet, this procedure raises ethical concerns related to its experimental nature and to risks involved in surgery and general anesthesia. In addition, the risk of malignant cells being reintroduced in the future following autologous transplantation of the ovarian tissue is still poorly evaluated. A number of ethical issues arise surrounding this procedure. While the girl’s future reproductive autonomy is at stake, it is important to also consider risks associated with the procedure. Fertility preservation through cryopreservation of ovarian tissue thus raises a conflict between the principles of beneficence and non-maleficence. We argue that the ethical complexity surrounding fertility preservation for prepubescent girls should be resolved by applying the principle of “the child’s right to an open future”. We propose to consider ‘beneficence’ through the lens of the reproductive autonomy and her potentialin becoming a genetic parent.

Corrosion and tribocorrosion behaviours of AISI 321, AISI 431 and FDMA borided and non-borided steels

Corrosion and tribocorrosion behaviours of non-borided and borided steel materials were evaluated under sliding contact in a 3.5 wt% NaCl solution, using an alternative tribometer integrated with a potentiostat for electrochemical control. Alloy-steel samples were borided by a powder-pack boriding process during 1 h at 950 °C. Microstructural examinations and phase analysis were performed employing Scanning Electron Microscopy (SEM) and x-ray diffraction. The surface profiles of wear tracks were obtained using a high resolution surface profilometer. Under corrosion conditions, it was found that a negative effect of boriding treatment was observed in the corrosion resistance of the investigated steels due to the presence of porosity and microcracks within FeB and Fe2B coating layers. On the other hand, the tribocorrosion tests indicated the positive effect of boride coating which induced a shift of the polarization curves of the borided steels to higher corrosion potentials contrary to the Tafel polarization curves of the non-borided steel materials which shifted to lower corrosion potentials. Moreover, even though the borided steels presented lower corrosion performances, the synergistic effect between corrosion and wear acting together resulted in a decrease of their coefficient of friction (COF) values and material losses with respect to the non-borided steel materials. In addition, the line profile of their surfaces exhibited less pronounced wear behaviour showing shallowed wear depth leading subsequently to a lower wear volume and loss compared to the non-borided steel materials. Microscopic observations revealed that wear-induced corrosion was more dominant in the corrosion-wear synergism.

Antioxidative system response of pedunculate oak (Quercus robur L.) seedlings to Cd exposure

The use of pedunculate oak (Quercus robur L.), along with other tree species, for the afforestation of heavy metal contaminated lands is an attractive prospect. Little, however, is known of Q. robur tolerance and its antioxidative system response to heavy metal exposure. The main objective of the study was to determine the cadmium-induced changes in antioxidative system of pedunculate oak in an attempt to identify molecular mechanisms underlying Cd tolerance. This may be of great importance in respect of using Q. robur for phytoremediation purposes. As the response of the antioxidative system to heavy metal contamination can vary within species, the research was conducted on oak seedlings from two different regions of origin. Differences in antioxidative system response of seedlings derived from tested regions of origin were noticed both at the transcript and enzyme activity levels. The obtained results indicate that ascorbate peroxidase (APX; EC 1.11.1.11) and superoxide dismutase (SOD; EC 1.15.1.1) play a first barrier role in oak seedlings response to the oxidative stress caused by Cd exposure. Catalase (CAT; EC 1.11.1.6) is involved in reducing the negative effects of prolonged Cd treatment.

Design of a batch ultrasonic reactor for rapid pasteurization of juices

Juices are usually thermally pasteurized, but high temperatures negatively affect their nutritional and sensory qualities. For this reason, nonthermal pasteurization techniques with little or no heat applied have been developed to minimize the quality losses. Among them, high-intensity ultrasound has been considered as a promising technique for juice pasteurization. Despite the extensive studies, a long pasteurization time is needed to achieve the required 5-log microbial reduction when a liquid is ultrasonically processed in an existing typical ultrasonic reactor, while inactivating some bacteria with a high tolerance to ultrasound is still a challenge. This is because there exist passive zones in the reactor as revealed by numerical simulations using COMSOL Multiphysics. This problem was successfully resolved by developing a new batch ultrasonic reactor which delivered almost uniform high intensity ultrasound throughout the reactor during processing, and therefore, substantially shortened the pasteurization time. Using this reactor to inactivate Escherichia coli at 60 °C and Staphylococcus aureus at 62 °C in peptone water, a 5-log microbial reduction was achieved in 0.38 min and 0.55 min, respectively. This was the first reported study that reached a 5-log reduction of S. aureus using ultrasonic processing. SEM images illustrated that high intensity ultrasound imposed physical lethal damages to the cell structure, resulting in microbial inactivation. The substantially shortened pasteurization time can reduce processing costs and negative effects of ultrasound treatment on organoleptic and nutritional properties of juices.

Clinical and cost-effectiveness of guided internet-based interventions in the indicated prevention of depression in green professions (PROD-A): study protocol of a 36-month follow-up pragmatic randomized controlled trial

BackgroundPeople in green professions are exposed to a variety of risk factors, which could possibly enhance the development of depression. Amongst possible prevention approaches, internet- and mobile-based interventions (IMIs) have been shown to be effective and scalable. However, little is known about the effectiveness in green professions. The aim of the present study is to examine the (cost-)effectiveness of a tailored IMI program for reducing depressive symptoms and preventing the onset of clinical depression compared to enhanced treatment as usual (TAU+).MethodsA pragmatic randomized controlled trial (RCT) will be conducted to evaluate a tailored and therapeutically guided preventive IMI program in comparison to TAU+ with follow-ups at post-treatment (9 weeks), 6-, 12-, 24-, and 36-months. Entrepreneurs in green professions, collaborating spouses, family members and pensioners (N = 360) with sufficient insurance status and at least subthreshold depression (PHQ-9 ≥ 5) are eligible for inclusion. Primary outcome is depressive symptom severity (QIDS-SR16). Secondary outcomes include incidence of depression (QIDS-SR16), quality of life (AQoL-8D) and negative treatment effects (INEP). A health-economic evaluation will be conducted from a societal perspective. The IMI program is provided by psychologists of an external service company and consists of six guided IMIs (6–8 modules, duration: 6–8 weeks) targeting different symptoms (depressive mood, depressive mood with comorbid diabetes, perceived stress, insomnia, panic and agoraphobic symptoms or harmful alcohol use). Intervention choice depends on a screening of participants’ symptoms and individual preferences. The intervention phase is followed by a 12-months consolidating phase with monthly contact to the e-coach.DiscussionThis is the first pragmatic RCT investigating long-term effectiveness of a tailored guided IMI program for depression prevention in green professions. The present trial builds on a large-scale strategy for depression prevention in green professions. The intended implementation of the IMI program with a nationwide rollout has the potential to reduce overall depression burden and associated health care costs in case of given effectiveness.Trial registrationGerman Clinical Trial Registration: DRKS00014000. Registered on 09 April 2018.

Internet-Based Supportive Education Intervention to Physical Activity of Cancer Survivors: A Scoping Review

Cancer survivors are at risk of decreasing health and psychosocial problems. Physical activity can reduce the risk of recurrence, death, and negative effects of cancer treatment. Severalstudies have investigated how the use of internet technology can increase the physical activity of survivors of cancer. The purpose of this review is to explore and identify the types of internet-based supportive education interventions to increase the physical activity of cancer survivors. We followed the methodology for scoping studies which consists of identifying the research question, locating relevant studies, selecting studies, charting the data, and collating, summarizing, and reporting the results. The search method used several electronic databases namely Google Scholar, Proquest, PubMed, and Scopus. Articles obtained from keywords: internet-based; supportive education; physical activity; cancer survivors. The inclusion criteria are: peer reviewed articles, publication year from 2008 to 2018 and has a minimal research design quasi experiment. Out of 5375 original articles identified in the literature search, 15 articles were analysed. Online support groups are the most frequently studied method of educational intervention, followed by interactive messages and webforums. Most studies showed improved results on intensity of physical activity. Online groups can improve the wellbeing of survivors of cancer by providing opportunities to engage in social networking, connect with others with similar cancer experiences, and obtain cancer related information. Based on the findings of this review. Supportive education through internet technology approaches can encourage increased physical activity and changes in health behavior of survivors of cancer. Future research should consider the potential role of social media in addressing the unmet needs of survivors of cancer and in particular the implications for clinical and public health practice

The impact of fungicide treatments on yeast biota of Verdicchio and Montepulciano grape varieties.

Yeast species that colonize the surface of grape berries at harvest time play an important role during the winemaking process. In this study, the use of culturable microbial techniques permitted a quantitative and qualitative inventory of the different yeast species present on the grape berry surfaces of Montepulciano and Verdicchio varieties when treated with conventional and organic fungicides. The results show that the most widespread yeast species at harvest time were Aureobasidium pullulans and Hanseniaspora uvarum, which are considered normal resident species and independent of the grape varieties and treatments applied. Specific differences when comparing the grape varieties were observed in species and were detected at a lower frequency; Pichia spp. were prevalent in Verdicchio, whereas Lachancea thermotolerans and Zygoascus meyerae were found in Montepulciano. In both vineyards, the farming treatments improved the competitiveness of A. pullulans, which was probably due to its reduced susceptibility to treatments that improved the competition toward other fungi. In contrast, the fermenting yeast H. uvarum was negatively affected by fungicide treatments and showed a reduced presence if compared with untreated grapes. Organic treatments directly impacted the occurrence of Issachenkia terricola in Montepulciano grapes and Debaryomyces hansenii and Pichia membranifaciens in Verdicchio. Conversely, a negative effect of organic treatments was found toward Metschnikowia pulcherrima and Starmerella bacillaris. Overall, the data suggest that the yeast community colonizing the grape berry surface was influenced by both grape variety and farming treatments, which characterized the yeast biota of spontaneous must fermentation.

Prospective Applications of Cold Plasma for Processing Poultry Products: Benefits, Effects on Quality Attributes, and Limitations.

Eliminating the pathogens from the chicken egg and meat is of supreme value for food scientists. In this regard, researchers have explored the potential applications of cold plasma, as a promising technique, to increase the profitability of poultry farming and safety of the poultry products. In the present study, an overview of the conducted research on plasma treatment of poultry products is presented to highlight the potential benefits of this emerging technology for the food and poultry industries. The potential negative effects of plasma treatment on the quality attributes of the product are also discussed. Moreover, the limitations of this technology and considerations for its commercial applications are illustrated. Furthermore, the needs for future research in this area of science are pointed out. Several studies have confirmed the applicability of cold plasma for egg and chicken decontamination. Considering the number of the recently conducted research and on-going advances in plasma science, this technique may assist food producers in enhancing the poultry product safety in the near future.

Effect of antituberculosis treatment on dynamics of carbohydrate and lipid profile

Objective — study the effect of antituberculosis treatment on the dynamics of carbohydrate and lipid profile in patients with newly diagnosed pulmonary tuberculosisMaterials and methods. We examined 76 patients with drug-susceptible pulmonary tuberculosis and 64 patients with drug-resistant pulmonary tuberculosis. The treatment was carried out according to the current order of the Ministry of Health of Ukraine. Material for the study (venous blood) was collected before treatment and one month later in the morning on an empty stomach. Additionally, an oral glucose tolerance test was performed, the fasting insulin level was determined, the lipid profile was measured, the insulin resistance index (HOMA-IR) and atherogenic index of plasma were calculated. For statistical processing used the software package Statistica for Windows version 13.2.Results and discussion. In the process of treatment with І-line antituberculosis drugs, the level of glucose in 2 hour GTT increased from 4.34 mmol/L to 5. 29 mmol/L. In patients who received ІI-line antituberculosis drugs, the glucose level decreased from 5.77 mmol/L to 4.33 mmol/L, and the fasting insulin level also decreased from 16.30 to 14.47 µcU/mL; the median level of insulin resistance decreased from 3.31 to 2.22 (p = 0.0057). In the process of treatment we found a significant decrease in VLDL levels (р = 0.0028) in drug-susceptible tuberculosis patients. Due to treatment, mean value of HDL-c in in drug-susceptible tuberculosis patients increased slightly from 1.01 mmol/L till 1.12 mmol/L, while in drug-resistant tuberculosis patients it decreased significantly (р=0.0171) from 1.07 mmol/L till 0.94 mmol/L.Conclusions. We found the negative effect of І-line antituberculosis drugs on the carbohydrate metabolism of patients with pulmonary tuberculosis, which manifested as impared glucose tolerance, which makes it possible to recommend OGTT for objectivizing the effect of anti-tuberculosis drugs on carbohydrate metabolism. While in patients who were treated with IІ-line antituberculosis drugs, we found a significant decrease in 2-hour glucose level and fasting insulin level, which indicates the modeling effect of these drugs on carbohydrate metabolism. Our findings suggest that drug-susceptible tuberculosis treatment had a positive effect on the lipid metabolism, which was manifested by the growth of the anti-atherogenic pool of lipoproteins and the decrease in very low-density lipoprotein level. At the same time, we found a negative effect of drug-resistant tuberculosis treatment on lipid metabolism, which manifested as increase of atherogenic index of plasma due to increase of total cholesterol level in patients with newly diagnosed pulmonary tuberculosis.

Impact of red blood cell transfusion dose density on progression-free survival in patients with lower-risk myelodysplastic syndromes.

Progression-free survival (PFS) of patients with lower-risk myelodysplastic syndromes (MDS) treated with red blood cell transfusions is usually reduced, but it is unclear whether transfusion dose density is an independent prognostic factor. The European MDS Registry collects prospective data at 6-monthly intervals from newly diagnosed lower-risk myelodysplastic syndromes patients in 16 European countries and Israel. Data on the transfusion dose density - the cumulative dose received at the end of each interval divided by the time since the beginning of the interval in which the first transfusion was received - were analyzed using proportional hazards regression with time-varying co-variates, with death and progression to higher-risk MDS/acute myeloid leukemia as events. Of the 1,267 patients included in the analyses, 317 died without progression; in 162 patients the disease had progressed. PFS was significantly associated with age, EQ-5D index, baseline World Health Organization classification, bone marrow blast count, cytogenetic risk category, number of cytopenias, and country. Transfusion dose density was inversely associated with PFS (P<1×10−4): dose density had an increasing effect on hazard until a dose density of 3 units/16 weeks. The transfusion dose density effect continued to increase beyond 8 units/16 weeks after correction for the impact of treatment with erythropoiesis-stimulating agents, lenalidomide and/or iron chelators. In conclusion, the negative effect of transfusion treatment on PFS already occurs at transfusion densities below 3 units/16 weeks. This indicates that transfusion dependency, even at relatively low dose densities, may be considered as an indicator of inferior PFS. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

Analyzing Psychotherapeutic Failures: A Research on the Variables Involved in the Treatment With an Individual Setting of 29 Cases.

The effectiveness of psychotherapeutic treatments has been widely demonstrated and confirmed by many studies in recent decades. The research focused on the factors of change influencing the positive outcomes of a psychotherapy, putting those that are crucial in cases of failure into the background. The dimensions of this phenomenon are relevant as well as the side effects of the psychotherapeutic interventions that reach the same percentages of the pharmacotherapeutic treatments. The study of the variables involved in failure cases therefore seems important to prevent or moderate the negative effects of treatments with a negative outcome. Impasse and deadlock situations, which may result in an early interruption of psychotherapy, are often complex and involve situational, relational, and personal factors at different levels and with different weight. A research was conducted, with a mixed approach, aimed at exploring the situational factors involved in dropout cases. In addition, the evaluation of the psychotherapist’s emotional responses related to patients who terminated psychotherapy prematurely was investigated. The study was attended by a sample of 29 psychologists, experienced psychotherapists from different frameworks. Recent or salient cases of a hesitated psychotherapy with an early interruption were examined. For the first objective, a structured interview (Impasse Interview) was used, while the second one was reached by the administration of the TRQ (Therapist Response Questionnaire). The transcripts of the interviews were analyzed through a textual analysis software and five salient thematic clusters were identified. These were then assimilated to different areas of meaning: severity of the diagnosis, procedural aspects and lack of understanding of the stall in progress. Two other important themes emerged: the critical aspects concerning relational dynamics and a focus on maternal theme. Overall these five thematic areas seem to play an important and specific role compared to dropout cases. Finally, statistical analysis on emotional responses have highlighted some values above the average in these four countertransference factors: Helpless/Inadequate, Parental/Protective, Positive/Satisfied, and Overwhelmed/Disorganized. It is hypothesized that particular emotional responses of the psychotherapist may be prognostic with respect to the outcome of psychotherapy.

Long-Term Implications of a Positive Posttreatment Biopsy in Patients Treated with External Beam Radiotherapy for Clinically Localized Prostate Cancer.

We determined the prognostic importance of a positive posttreatment biopsy after prostate radiotherapy. A total of 382 patients underwent a posttreatment biopsy after external beam radiotherapy for clinically localized prostate cancer. Posttreatment biopsies were classified as positive (prostatic adenocarcinoma without typical radiation induced changes), negative (no evidence of carcinoma) or adenocarcinoma with a severe treatment effect. Median followup in survivors was 9 years. Competing risks regression was used to assess relationships between prognostic predictors and cause specific mortality, distant metastasis and prostate specific antigen failure. The prevalence of positive biopsy, treatment effect and negative biopsy was 30%, 22% and 48%, respectively. Androgen deprivation therapy omission and high risk disease were associated with a 2.6 and 1.8-fold increase, respectively, in the odds of positive posttreatment biopsy. The 15-year PSA relapse rate associated with negative, severe treatment effect and positive posttreatment biopsies was 34%, 36% and 79%, respectively (p <0.001). After controlling for known predictors the risk of distant metastasis was 2.6-fold higher in patients with a positive biopsy (p <0.001) and cause specific mortality was twice as high in patients with a positive biopsy compared to those with negative and severe treatment effect biopsy outcomes (HR 2.00, p = 0.022). A positive posttreatment biopsy after external beam radiotherapy was associated with a higher risk of distant metastasis and prostate cancer related death. Patients with severe treatment effect classified biopsies have biological characteristics more like patients with a negative biopsy than a positive biopsy. Posttreatment biopsies were more often positive in the setting of external beam radiotherapy alone without androgen deprivation therapy or in the presence of high risk disease.

Concomitant exercise training attenuates the cardioprotective effects of pharmacological therapy in a murine model of acute infectious myocarditis

When administered alone, preinfection exercise training and benznidazole-based chemotherapy induce cardioprotection in Chagas disease. However, the effect of concomitant exercise and benznidazole treatment is unknown. We investigated whether exercise and specific chemotherapy could interact to modulate parasitemia, inflammation, redox status and heart damage in a murine model of T. cruzi infection. Wistar rats were randomized into an uninfected control group (CNT) and four groups infected with T. cruzi: sedentary untreated (SUN) and treated (STR), and trained untreated (TUN) and treated (TTR). Running training was administered 5 days/week for 4 weeks. Treated animals concomitantly received 100 mg/kg/day benznidazole. Heart inflammation and reactive damage were not detected in CNT animals. Compared to SUN, TUN animals presented increased levels of parasitemia, myocarditis, nitric oxide, hydrogen peroxide, protein carbonyl, malondialdehyde, cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10 and IL-17), catalase, superoxide dismutase and glutathione reductase activity, as well as reduced heart non-protein antioxidant levels (P < 0.05). TTR animals exhibited higher levels of parasitemia, myocarditis, hydrogen peroxide, malondialdehyde, IFN-γ, TNF-α and IL-6 than STR animals (P < 0.05), which showed the lowest levels of all analyzed parameters compared to the other groups (P < 0.05). Our findings indicate that exercise aggravates acute infection. When concomitantly administered with benznidazole, exercise training impaired parasitic control and chemotherapy-induced cardioprotection in T. cruzi-infected rats. Considering that exercise training and T. cruzi infection constitute independent metabolic challenges, the negative effects of concomitant treatment are potentially related to the overlapping oxidative and immunoinflammatory demands of exercise and the infection itself.