Psychological Stress and Cancer: New Evidence of An Increasingly Strong Link.

To date stress, a highly complex process that disrupts homeostasis and involves environmental and psychosocial factors, is considered as one of the most crucial factor that affects our daily life, especially urban dweller's life. Clinical and experimental studies widely support the notion that adrenergic stimulation due to chronic stress affects inflammation and metabolism. In this work, supported by several recent scientific evidences, we show how stress plays a positive role in cancer initiation, progression and cancer metastasis, a negative role for anti-tumor immune function and therapy response. Understanding the intricacies of this interaction could provide an additional help on how act in cancer prevention and therapy.

Longitudinal Strain Stress-Echo Evaluation of Aged Marginal Donor Hearts: Feasibility in the Adonhers Project.

BACKGROUND: The Adonhers (aged donor heart rescue by stress-echo protocol) Project was created to resolve the current shortage of donor hearts. One of the great limits of stress echo is the operator dependency. Speckle-tracking echocardiography (STE), offering a quantitative objective analysis of myocardial deformation, may help to overcome this limit. This study aimed to verify feasibility of a stress-strain echo analysis in selection of aged donor hearts for heart transplant. METHODS: From February 2014 to October 2015, 22 marginal candidate donors (16 men) ages 58 ± 4 years were initially enrolled. After legal declaration of brain death, all marginal donors underwent bedside echocardiography, with baseline and (when resting echocardiography was normal) dipyridamole (0.84 mg/kg in 6 minutes) stress echo. In all patients, left ventricular (LV) longitudinal myocardial deformation was obtained by STE in the 4-, 2-, and 3-chamber views, obtaining the average global longitudinal strain (GLS). GLS was assessed at baseline and at the peak of stress echo. RESULTS: Baseline echocardiography showed wall motion abnormalities in 9 patients (excluded from donation). Stress echocardiography was performed in the remaining 13 patients. Results were normal in 8, who were uneventfully transplanted in marginal recipients. Stress results were abnormal in 5 (excluded from donation). STE was obtained in all cases (100% feasibility) and ΔGLS was significantly different between normal and pathological stress-echo (+13.2 ± 5.2 versus -6.1% ± 3.1%, P = .0001, respectively). CONCLUSIONS: STE showed an excellent feasibility in analysis of LV myocardial longitudinal strain at baseline and at the peak of stress echo of marginal heart donors. Further experience is needed to confirm STE as a valuable additional mean to better interpret stress echo in marginal donors.

FK506 binding protein 51 positively regulates melanoma stemness and metastatic potential.

Melanoma is the most aggressive skin cancer; there is no cure in advanced stages. Identifying molecular participants in melanoma progression may provide useful diagnostic and therapeutic tools. FK506 binding protein 51 (FKBP51), an immunophilin with a relevant role in developmental stages, is highly expressed in melanoma and correlates with aggressiveness and therapy resistance. We hypothesized a role for FKBP51 in melanoma invasive behaviour. FKBP51 promoted activation of epithelial-to-mesenchymal transition (EMT) genes and improved melanoma cell migration and invasion. In addition, FKBP51 induced some melanoma stem cell (MCSC) genes. Purified MCSCs expressed high EMT genes levels, suggesting that genetic programs of EMT and MCSCs overlap. Immunohistochemistry of samples from patients showed intense FKBP51 nuclear signal and cytoplasmic positivity for the stem cell marker nestin in extravasating melanoma cells and metastatic brains. In addition, FKBP51 targeting by small interfering RNA (siRNA) prevented the massive metastatic substitution of liver and lung in a mouse model of experimental metastasis. The present study provides evidence that the genetic programs of cancer stemness and invasiveness overlap in melanoma, and that FKBP51 plays a pivotal role in sustaining such a program.

[Assessment of risk of burden in construction: improvement interventions and contribution of the competent physician]. / Valutazione del rischio da movimentazione carichi in edilizia: interventi migliorativi e contributo del medico competente.

Three construction companies in three years have changed the operating modes, making use of innovative carpentry, with little amount of equipment, improved usability of the site, reduced cleaning time, less manual handling and reduced risk of accidents. The Competent Doctor has participated in the review of the risk assessment of manual handling: data has been acquired on musculoskeletal disorders to compare, in terms of this innovation, the average trend and changes, with encouraging results in terms of incidence of musculoskeletal disorders, absenteeism due to illness by these causes, new cases of lumbar diseases. It remains difficult in building to assess manual handling risk, but the collaboration between the Employer, Prevention and Protection Service and Competent Doctor, thanks to the greater attention that the design subject to these issues, suggests improvements and further steps to extend to all phases of operation of building.

Changes in the gene expression profile of gastric cancer cells in response to ibuprofen: a gene pathway analysis.

Nonsteroidal anti-inflammatory drugs possess antiproliferative activities that can affect cancer cells. The aim of this study was to examine the antiproliferative effects of ibuprofen on the MKN-45 cell line. Cells were treated with ibuprofen for 24, 48 or 72 h, and cell proliferation was evaluated by cell counting and [(3)H]-thymidine incorporation. Using microarray technology, we studied changes in the gene expression profiles over time after ibuprofen treatment. Ibuprofen induced a dose- and time-dependent reduction in cell number without altering cell viability. Genes involved in the 'biological oxidation' and 'G(1)/S checkpoint' pathways were the most significantly represented at 24 h, whereas genes involved in the 'cell cycle' and 'DNA replication' pathways were represented at 48 and 72 h. Genes associated with the 'apoptosis' pathway were also significantly represented at 72 h. Modulation of the expression of p53 and p53-induced genes (CDKN1A/p21 and GADD45), which are involved in the G(1)/S transition, suggested an effect of ibuprofen on cell-cycle progression. Using flow cytometry, we observed an early block in the G(1) phase of the cell cycle after ibuprofen treatment. In addition, P450 family transcripts were upregulated and intracellular reactive oxygen species (ROS) was increased following 12 h of ibuprofen treatment. Ibuprofen induced ROS, which resulted in cellular alterations that promoted a p53-dependent G(1) blockade. These findings suggest that ibuprofen exerts its antiproliferative actions through cell-cycle control and the induction of apoptosis. Both of these mechanisms appear to be independent of ibuprofen's anti-inflammatory effects.

Fast neutrons measured in copper from the Hiroshima atomic bomb dome.

The first measurements of (63)Ni produced by A-bomb fast neutrons (above approximately 1 MeV) in copper samples from Hiroshima encompassed distances from approximately 380 to 5062 m from the hypocenter (the point on the ground directly under the bomb). They included the region of interest to survivor studies (approximately 900 to 1500 m) and provided the first direct validation of fast neutrons in that range. However, a significant measurement gap remained between the hypocenter and 380 m. Measurements close to the hypocenter are important as a high-value anchor for the slope of the curve for neutron activation as a function of distance. Here we report measurements of (63)Ni in copper samples from the historic Hiroshima Atomic Bomb Dome, which is located approximately 150 m from the hypocenter. These measurements extend the range of our previously published data for (63)Ni providing a more comprehensive and consistent A-bomb activation curve. The results are also in good agreement with calculations based on the current dosimetry system (DS02) and give further experimental support to the accuracy of this system that forms the basis for radiation risk estimates worldwide.

Electromyographic analysis of the rectus abdominis muscle in pelvic retroversion and the decrease of the lower limbs.

We often face patients searching for rehabilitation for lower back disorders during the physiotherapeutic routine, and it is known that the abdominal muscle, specially the rectus abdominis muscle, aid the stabilization of the pelvis. Therefore, this paper analyzes the electrical activity of the rectus abdominis muscle in the pelvic retroversion in dorsal decubitus and in orthostatic position and in the lowering of the lower limbs. 30 healthy students, male and female, 17 - 40 yr, divided into two groups--Group 1 : 15 volunteers (pelvic balance); Group 2 (pelvic unbalance) took part in this study. The electrical activity of the right and left supra-umbilical and infra-umbilical portions of the rectus abdominis muscle was detected. The mean RMS values from three attempts from the electromyographic traces were used for the analysis of the electrical activity. The RMS value was submitted to the normalization process. The data were submitted to statistic treatment by the Friedman test, and the analyses of the means and standard deviation towards a level of significance of 95%. The results demonstrated that the portions of the rectus abdominis muscle presented low electrical activity for the groups studied for pelvic retroversion either in dorsal decubitus or and orthostatic position. However, the decreasing movement of the lower limbs towards the portions of the rectus abdominis muscle presented more significant electrical activity whereas the lower portions presented higher activity than the higher ones for Group 2.

Biological predictive factors in rectal cancer treated with preoperative radiotherapy or radiochemotherapy.

We analysed the expression of microsatellite instability, p53, p21, vascular endothelial growth factor and thymidylate synthase (TS) in pretreatment biopsy specimens from 57 locally advanced rectal cancers. The aim of the study was to correlate the expression of these markers with pathological response. Nineteen patients were treated with preoperative concomitant radiotherapy (RT) and fluorouracil/oxaliplatin-based chemotherapy (RCT), while 38 had RT alone. Pathological complete remission (pCR) and microfoci residual tumour (micR) occurred more frequently in patients treated with RCT (P=0.002) and in N0 tumours (P=0.004). Among patients treated with RCT, high TS levels were associated with a higher response rate (pCR+micR; P=0.015). No such correlation was found in the RT group. The other molecular factors were of no predictive value. Multivariate analysis confirmed a significant interaction between nodal status and the probability of achieving a pathological response (P=0.023) and between TS expression and treatment, indicating that a high TS level is predictive of a higher pathological response in the RCT subset (P=0.007). This study shows that lymph node status is the most important predictive factor of tumour response to preoperative treatment. Thymidylate synthase expression assessed immunohistochemically from pretreatment tumour biopsies may be a useful predictive marker of rectal tumour response to preoperative RCT.

Neutron-induced 63Ni in copper samples from Hiroshima and Nagasaki: a comprehensive presentation of results obtained at the Munich Maier-Leibnitz Laboratory.

Those inhabitants of Hiroshima and Nagasaki who were affected by the A-bomb explosions, were exposed to a mixed neutron and gamma radiation field. Few years later about 120,000 survivors of both cities were selected, and since then radiation-induced late effects such as leukemia and solid tumors are being investigated in this cohort. When the present study was initiated, the fast neutron fluences that caused the neutron doses of these survivors had never been determined experimentally. In principle, this would have been possible if radioisotopes produced by fast neutrons from the A-bomb explosions had been detected in samples from Hiroshima and Nagasaki at distances where the inhabitants survived. However, no suitable radioisotope had so far been identified. As a contribution to a large international effort to re-evaluate the A-bomb dosimetry, the concentration of the radionuclide (63)Ni (half-life 100.1 years) has been measured in copper samples from Hiroshima and Nagasaki. These measurements were mainly performed at the Maier-Leibnitz-Laboratory in Munich, Germany, by means of accelerator mass spectrometry. Because the (63)Ni had been produced in these samples by fast A-bomb neutrons via the reaction (63)Cu(n,p)(63)Ni, these measurements allow direct experimental validation of calculated neutron doses to the members of the LSS cohort, for the first time. The results of these efforts have already been published in a compact form. A more detailed discussion of the methodical aspects of these measurements and their results are given in the present paper. Eight copper samples that had been significantly exposed to fast neutrons from the Hiroshima A-bomb explosion were investigated. In general, measured (63)Ni concentrations decreased in these samples with increasing distance to the hypocenter, from 4 x 10(6 ) (63)Ni nuclei per gram copper at 391 m, to about 1 x 10(5 ) (63)Ni nuclei per gram copper at about 1,400 m. Additional measurements performed on three large-distant copper samples from Hiroshima (distance to the hypocenter 1,880-7,500 m) and on three large-distant copper samples from Nagasaki (distance to the hypocenter 3,931-4,428 m) that were not exposed significantly to A-bomb neutrons, suggest a typical background concentration of about 8 x 10(4 ) (63)Ni nuclei per gram copper. If the observed background is accounted for, the results are consistent with state-of-the-art neutron transport calculations for Hiroshima, in particular for those distances where the victims survived and were included in the life span study cohort.

[Cervical, thoracic and upper limb load assessment in dental professionals]. / Studio del carico posturale cervico-dorsale e dell'arto superiore nell'attività dell'odontoiatra.

In order to analyze the effect of working posture on the level of neck, back and shoulder muscular activity, a clinico-anamnestic, electromyographic and postural study of 34 dentistry was undertaken. Using surface electrodes, the level of muscular activity was recorded. The results showed that neck flexed working posture is prevalent: using stereomicroscope gave lower levels than with or without enlarging systems, such as glasses.

[Risk assessment in upper limb overload]. / Studio del sovraccarico biomeccanico dell'arto superiore attraverso l'applicazione di quattro diversi metodi di valutazione del rischio.

One of the most important factors of the work-related musculoskeletal disorders of the upper extremities (WMSDs) is the biomechanical overload. The purpose of this study is to evaluate the possibility to predict the upper limb repetitive stress, according to risk assessment procedures. In order to this aim, we gathered clinical-anamnestic data and risk assessment considerations of a cohort of workers in a car industry.

Anemia may influence the outcome of patients undergoing neo-adjuvant treatment of rectal cancer.

BACKGROUND: We hypothesized that anemia could represent one of the major factors influencing the outcome of patients undergoing neo-adjuvant treatment of rectal cancer. PATIENTS AND METHODS: This analysis included all the consecutive patients who underwent neo-adjuvant treatment (chemotherapy and/or radiotherapy) before surgery for rectal cancer in three oncology/radiotherapy departments from June 1996 to December 2003. RESULTS: Three hundred and seventeen patients were eligible for our analysis. Median age at diagnosis was 64 years (range 26-88 years); male/female ratio was 184/133. Two hundred and eighty-five patients (89.9%) were diagnosed with adenocarcinoma, while 32/317 (10.1%) with mucinous adenocarcinoma. Neo-adjuvant treatments carried out were as follows: radiotherapy alone in 75/317 patients (23.7%), radiotherapy plus chemotherapy in 242/317 patients (76.3%). At univariate and multivariate analysis, only the hemoglobin (Hb) level (group 1: < or=12 g/dl versus group 2: >12 g/dl) resulted in a significant factor for disease-free survival. The role of the Hb level seemed to be confirmed further by the clinical downstaging obtained in approximately 55% of patients in group 2, in comparison with 35% of the patients achieving a significant downstaging in group 1. CONCLUSION: Our results indicated that anemia could represent an important parameter able to influence the outcome in patients receiving neo-adjuvant treatment of rectal cancer.

Differential effects of egg albumen content on barn swallow nestlings in relation to hatch order.

In diverse animal taxa, egg mass variation mediates maternal effects with long-term consequences for offspring ontogeny and fitness. Patterns of egg mass variation with laying order differ considerably among birds, but no study has experimentally investigated the function of variation in albumen or yolk egg content in the wild. In barn swallows (Hirundo rustica), absolute and relative albumen mass increased with egg laying order. Experimental albumen removal delayed hatching, had larger negative effects on growth of late-hatched nestlings, and reduced nestling survival. Laying order positively predicted hatch order. Because nestling competitive ability depends on size, and albumen egg content influences hatchling size, present results suggest that by increasing albumen content of late eggs mothers reduce hatching asynchrony and enhance growth particularly of late-hatched nestlings. Thus, variation in albumen mass with laying order may function to mitigate the negative phenotypic consequences of hatching late in species that adopt a 'brood-survival' strategy.

[Breathing sleep disturbances and occupational medicine: study of 20 clinical cases]. / Disturbi respiratori del sonno e medicina del lavoro: considerazioni su 20 casi clinici.

During 2004, in the Center for Sleep Disorders, a questionnaire including Epworth sleepiness scale (ES) was administered to 120 subjects; 20 male subjects of this group with elevated score (ES >14) were selected and submitted to polysomnography. Subjects, all in working age, were represented by 3 (15%) shift-workers, 9 (45%) drivers, 17 (85%) industrial workers (among those 5 building workers) and 3 (15%) employers. By polysomnography, moderatelsevere OSAHS was diagnosed in all subjects (40% moderate, 60% severe). CPAP (Continuous Positive Airway Pressure) therapy led to an improvement of clinical symptoms since the first month. Counselling of Occupational Medicine Physician with the Center for Sleep Disorders, was useful to direct the action of Competent Doctor, especially for jobs requiring high vigilance (drivers or shift-worker). The pass certificate for jobs with an high risk (alone, in high places, heavy means drivers) cannot avoid to evaluate this pathology, that is often associated to other related risk factors (obesity, hypertension, diabetes), because it compromises both the specific suitability and the protection of common health and safety.

[Evaluation of risks of biomechanical overload of the upper limb in physical kinesis therapists]. / Valutazione del rischio da sovraccarico biomeccanico dell'art superiore nei tecnici di fisiokinesiterapia.

Physical therapists are at risk for work-related musculoskeletal disorders (WMSDs). Contributing risk factors are job-task, mental stress and biomechanical overload, due to fixed and incorrect postures of neck, upper limbs and back. The purpose of this study was to investigate, by questionnaire and the use of muscle superficial EMG recording and analysis, the workload in the physical therapist activity, in order to provide suitable preventive measures.

Intragastric administration of Mycobacterium vaccae inhibits severe pulmonary allergic inflammation in a mouse model.

BACKGROUND: Coexistence with harmless microorganisms such as lactobacilli, saprophytic mycobacteria and some helminths, throughout evolution, may have shaped the host immune system. Exposure to such organisms may have therapeutic benefits by triggering immunoregulatory mechanisms that control inappropriate immune responses to self, gut contents or allergens. OBJECTIVE: We determined whether treatment with Mycobacterium vaccae by gavage influences the host immune response both locally and systemically. We also investigated whether delivery by this route prevents severe symptoms of disease in a murine model of pulmonary allergic inflammation. RESULTS: A single intragastric administration of M. vaccae induced a transient increase in the production of IL-10 and IFN-gamma by mesenteric lymph nodes cells and splenocytes. In addition, in a mouse model of pulmonary allergic inflammation, a single treatment with M. vaccae by gavage not only diminished the total cellular infiltrate and the eosinophilic component induced by subsequent intratracheal allergen challenge, but also biased local and systemic cytokine production towards IL-10. Delivery of M. vaccae by gavage was as effective as subcutaneous treatment. CONCLUSION: This is the first report to suggest that heat-killed mycobacteria can down-regulate symptoms of allergic inflammation by the intragastric route. These data suggest an alternative route of treatment with M. vaccae for patients with allergic conditions.

Cyclophosphamide in the treatment of focal segmental glomerulosclerosis

Prednisone is the initial treatment of primary focal segmental glomerulosclerosis. However, when immunosuppressive agents in combination with steroids are used in the treatment of prednisone-dependent and prednisone-resistant patients the remission rate is variable. We report a long-term trial using cyclophosphamide (2.0 to 3.0 mg/kg body weight for 12 weeks) in combination with prednisone (1.0 to 2.0 mg/kg body weight), as compared with prednisone alone for the treatment of prednisone-resistant and frequently relapsing nephrotic syndrome and focal segmental glomerulosclerosis. Fifty-four patients (34 males and 20 females) with a diagnosis of idiopathic nephrotic syndrome and focal segmental glomerulosclerosis, followed-up for an average of 86.1 ± 82.4 months, were evaluated. Complete remission occurred in 20.4 percent and partial remission in 14.8 percent of the patients treated with steroids and in 26.7 and 20.0 percent of the patients treated with cyclophosphamide + prednisone, respectively. Of the 24 prednisone-resistant patients treated with steroids in combination with cyclophosphamide, 33.3 percent obtained a complete/partial response. At the time of final evaluation, 25 percent of the patients treated with prednisone and 10.0 percent of those treated with prednisone in combination with cyclophosphamide had reached end-stage renal disease. Persistent nephrotic syndrome and progressive renal insufficiency were more frequently observed among the patients treated with prednisone alone (50.0 vs 33.3 percent and 33.3 vs 16.7 percent, respectively). The treatments were well tolerated and no patient experienced adverse reactions requiring discontinuation of medications. Although open-label and non-randomized, the present trial showed that cyclophosphamide is a reasonable choice for the treatment of primary focal segmental glomerulosclerosis and prednisone-resistant nephrotic syndrome.

Cyclophosphamide in the treatment of focal segmental glomerulosclerosis.

Prednisone is the initial treatment of primary focal segmental glomerulosclerosis. However, when immunosuppressive agents in combination with steroids are used in the treatment of prednisone-dependent and prednisone-resistant patients the remission rate is variable. We report a long-term trial using cyclophosphamide (2.0 to 3.0 mg/kg body weight for 12 weeks) in combination with prednisone (1.0 to 2.0 mg/kg body weight), as compared with prednisone alone for the treatment of prednisone-resistant and frequently relapsing nephrotic syndrome and focal segmental glomerulosclerosis. Fifty-four patients (34 males and 20 females) with a diagnosis of idiopathic nephrotic syndrome and focal segmental glomerulosclerosis, followed-up for an average of 86.1 +/- 82.4 months, were evaluated. Complete remission occurred in 20.4% and partial remission in 14.8% of the patients treated with steroids and in 26.7 and 20.0% of the patients treated with cyclophosphamide + prednisone, respectively. Of the 24 prednisone-resistant patients treated with steroids in combination with cyclophosphamide, 33.3% obtained a complete/partial response. At the time of final evaluation, 25% of the patients treated with prednisone and 10.0% of those treated with prednisone in combination with cyclophosphamide had reached end-stage renal disease. Persistent nephrotic syndrome and progressive renal insufficiency were more frequently observed among the patients treated with prednisone alone (50.0 vs 33.3% and 33.3 vs 16.7%, respectively). The treatments were well tolerated and no patient experienced adverse reactions requiring discontinuation of medications. Although open-label and non-randomized, the present trial showed that cyclophosphamide is a reasonable choice for the treatment of primary focal segmental glomerulosclerosis and prednisone-resistant nephrotic syndrome.

Comparative study of permanent interstitial prostate brachytherapy post-implant evaluation among seven Italian institutes.

BACKGROUND AND PURPOSE: The purposes of this multicentric study are (a) the evaluation of four different commercially available treatment planning systems (TPSs) and (b) to verify whether the dosimetric results are comparable, also when considering the inter-observer variabilities and the different scanning protocols used. This work is to be considered a first step to test the value of multicentric studies based on dosimetric evaluation of the quality of the implants. PATIENTS AND METHODS: Four different TPSs were used and the following tests were performed:Comparison of the parameters and mathematical algorithms used; comparison of the dose distributions generated by three different geometries of sources based on 32 dose-points on each source geometry. An octagonal geometric phantom was used to compare volume algorithms and dose-volume histogram (DVH) calculations (V150(Gy), V100(Gy), V50(Gy) and V25(Gy)). Comparison of the post-plan source distribution performed on a prostate-phantom implanted with (125)I seeds. A CT scan of the phantom was obtained at each participating center. Both the geometrical coordinates (with respect to the most caudal one), and the spread of the geometrical distribution, were calculated. The volumes included within different isodoses were also collected. Comparison of the post-plan source distribution performed on an actual patient. Post-plan V100% and D90(Gy) derived from seed distributions obtained by different operators were calculated, using the same target delineation. RESULTS: All the considered TPSs satisfied the AAPM dosimetric parameter recommendations. Point-dose examinations revealed differences smaller than 5%, except for one of the systems. Although the volume algorithm was not the same for all systems, no statistically significant difference was found in the volume measurements. The DVHs also presented differences smaller than 5%, except for one TPS. The distances between the seeds, based on the same CT images, showed a mean SD of 0.13 mm. The mean maximum difference of the position of each seed was 0.36 mm. The most significant errors were made in the cranio-caudal direction (mean maximal difference: 0.44 mm); here the size of the step between slices played an important role. The algorithm of source positioning of the different TPSs may also help explain this difference. The compiled DVHs showed differences smaller than 5%. Post-plans derived from different seed distributions showed a mild dependence upon operators. We obtained a mean value of 97.8 and 152.7 with a percentage of SD of 0.43 and 1.7, respectively, for V100% and D90(Gy). CONCLUSIONS: Three-dimensional (3D) geometric reconstructions of seed distributions are slightly dependent upon the operators and the scanning protocols have little effect on the dosimetric evaluation. Some relevant discrepancies were found between one of the TPSs and the other three if few sources were used; increasing the number of seeds those differences became less pronounced. Multicentric studies on the quality of prostate implants based on post-implant dosimetry are feasible, provided an accurate step-wise evaluation of the procedure be performed.