Pain Intensity, coping and maternal satisfaction in Low-Risk labouring Women: A prospective descriptive correlational study.

OBJECTIVES: The primary aim of the study was to explore pain intensity (PI) and pain coping (PC) scores and the relationship between them. The secondary aim was to explore the correlation between PI and PC scores with labour progress, parity, labour acceleration, labour augmentation and maternal satisfaction. METHODS: A prospective descriptive correlational study was conducted in a maternity hospital in Northern Italy. The sample included 54 low-risk women in active labour at term of pregnancy. A data record sheet was used to collect the relevant variables and the Italian Birth Satisfaction Scale Revised (I-BSS-R) was administered to participants at least 24 h after birth. RESULTS: In the first labour stage, the average PI score was 6.99 (SD = 1.95) and the average PC score was 6.5 (SD = 2.22). During the second labour stage, the average PI score was 7.75 (SD = 1.74) and the average PC score was 4.97 (SD = 2.76). The average PI score trend increased with labour progress. The average PC score improved between 4 and 7 cm of cervical dilatation. A significant positive correlation between PI scores and oxytocin augmentation (p < 0.001) and labour progression (p < 0.001) was noted. A significant positive correlation between PC scores and oxytocin augmentation (p = 0.02) was also observed. No significant differences were found for maternal satisfaction in regard to PI and PC scores. CONCLUSION: coping in labour do not solely depend on PI but also on labour progress and oxytocin augmentation. Additional support to empower women to cope with pain may be required in case of labour augmentation.

Midwifery students' perspectives of physical and virtual mobility activities including preferences for e-learning: A cross-sectional survey.

BACKGROUND: Contemporary higher education requires that all midwifery students have insight and understanding of global health practice and demonstrate intercultural sensitivity. However, the mobility models currently offered do not often fit the lives of large numbers of midwifery students. OBJECTIVES: To investigate midwifery students' international physical mobility activities and factors that affect mobility; to determine midwifery students' learning needs and preferences for related e-learning packages. DESIGN: Multi-centre, descriptive quantitative survey. SETTINGS: Four European Higher Education Institutions based in the United Kingdom, Estonia, Italy and the Netherlands offering an undergraduate midwifery programme. PARTICIPANTS: The sample included 205 midwifery students from Italy (n = 93), the Netherlands (n = 51); United Kingdom (n = 35) and Estonia (n = 26). METHODS: Data were collected in June-July 2020 through an online cross-sectional, bespoke questionnaire and analysed using summary statistical analysis. RESULTS: There is a high level of interest across a range of mobility opportunities, especially those of shorter duration. Barriers to mobility comprised finance, caring responsibilities, concerns about fitting mobility activities into the midwifery programme, negative impact on studies and language barriers. The most frequently identified facilitators of mobility included professional perspectives such as interest in other cultures and midwifery in other settings and an endorsement that mobility would add value to their development as a midwife. When engaging in virtual learning, the most preferred resources mentioned by the students were videos, video calls with peers, choice quiz and discussion forum. CONCLUSIONS: The barriers identified require new approaches to enable all midwifery students to benefit from transnational learning. The survey findings provide insights into midwifery students' perspectives from which a new mobility model can be developed.

Targeted deletions of complement lectin pathway genes improve outcome in traumatic brain injury, with MASP-2 playing a major role.

The lectin pathway (LP) of complement activation is believed to contribute to brain inflammation. The study aims to identify the key components of the LP contributing to TBI outcome as possible novel pharmacological targets. We compared the long-term neurological deficits and neuropathology of wild-type mice (WT) to that of mice carrying gene deletions of key LP components after experimental TBI. WT or MASP-2 (Masp2-/-), ficolin-A (Fcna-/-), CL-11 (Colec11-/-), MASP-1/3 (Masp1-/-), MBL-C (Mbl2-/-), MBL-A (Mbl1-/-) or MBL-/- (Mbl1-/-/Mbl2-/-) deficient male C57BL/6J mice were used. Mice underwent sham surgery or TBI by controlled cortical impact. The sensorimotor response was evaluated by neuroscore and beam walk tests weekly for 4 weeks. To obtain a comparative analysis of the functional outcome each transgenic line was rated according to a health score calculated on sensorimotor performance. For selected genotypes, brains were harvested 6 weeks after injury for histopathological analysis. MASP-2-/-, MBL-/- and FCN-A-/- mice had better outcome scores compared to WT. Of these, MASP-2-/- mice had the best recovery after TBI, showing reduced sensorimotor deficits (by 33% at 3 weeks and by 36% at 4 weeks). They also showed higher neuronal density in the lesioned cortex with a 31.5% increase compared to WT. Measurement of LP functional activity in plasma from MASP-2-/- mice revealed the absence of LP functional activity using a C4b deposition assay. The LP critically contributes to the post-traumatic inflammatory pathology following TBI with the highest degree of protection achieved through the absence of the LP key enzyme MASP-2, underlining a therapeutic utility of MASP-2 targeting in TBI.

Timing of hospital admission in labour: latent versus active phase, mode of birth and intrapartum interventions. A correlational study.

BACKGROUND: Hospitalization of women in latent labour often leads to a cascade of unnecessary intrapartum interventions, to avoid potential disadvantages the recommendation should be to stay at home to improve women's experience and perinatal outcomes. AIM: The primary aim of this study was to investigate the association between hospital admission diagnosis (latent vs active phase) and mode of birth. The secondary aim was to explore the relationship between hospital admission diagnosis, intrapartum intervention rates and maternal/neonatal outcomes. METHODS: A correlational study was conducted in a large Italian maternity hospital. Data from January 2013 to December 2014 were collected from the hospital electronic records. 1.446 records of low risk women were selected. These were dichotomized into two groups based on admission diagnosis: 'latent phase' or 'active phase' of labour. FINDINGS: 52.7% of women were admitted in active labour and 47.3% in the latent phase. Women in the latent phase group were more likely to experience a caesarean section or an instrumental birth, artificial rupture of membranes, oxytocin augmentation and epidural analgesia. Admission in the latent phase was associated with higher intrapartum interventions, which were statistically correlated to the mode of birth. CONCLUSIONS: Women admitted in the latent phase were more likely to experience intrapartum interventions, which increase the probability of caesarean section. Maternity services should be organized around women and families needs, providing early labour support, to enable women to feel reassured facilitating their admission in labour to avoid the cascade of intrapartum interventions which increases the risk of caesarean section.

Adiponectin in outpatients with coronary artery disease: independent predictors and relationship with heart failure.

BACKGROUND AND AIMS: Chronic heart failure (HF) is characterised by a neurohormonal dysfunction associated with chronic inflammation. A role of metabolic derangement in the pathophysiology of HF has been recently reported. Adiponectin, an adipose-tissue-derived cytokine, seems to play an important role in cardiac dysfunction. We investigated the variation of circulating adiponectin in patients with coronary artery disease (CAD), with or without HF, in order to identify its independent predictors. METHODS AND RESULTS: A total of 107 outpatients with CAD were enrolled in the study and divided into three groups: CAD without left ventricular systolic dysfunction (group 1); CAD with left ventricular dysfunction without HF symptoms (group 2) and CAD with overt HF (group 3). Plasma adiponectin was determined by enzyme-linked immunosorbent assay. Adiponectin concentrations increased progressively from group 1 (7.6 ± 3.6 ng ml⁻¹) to group 2 (9.1 ± 6.7 ng ml⁻¹) and group 3 (13.7 ± 7.6 ng ml⁻¹), with the difference reaching statistical significance in group 3 versus 1 and 2 (p < 0.001). A multivariable model of analysis demonstrated that the best predictors of plasma adiponectin were body mass index, N-terminal pro-brain natriuretic peptide and high-density lipoprotein cholesterol. However, even after adjusting for all three independent predictors, the increase of adiponectin in group 3 still remained statistically significant (p = 0.015). CONCLUSION: Our data confirm the rise of adiponectin in overt HF. The levels of circulating adipokine seem to be mainly predicted by the metabolic profile of patients and by biohumoral indicators, rather than by clinical and echocardiographic indexes of HF severity.

Improving healthcare worker hand hygiene adherence before patient contact: a before-and-after five-unit multimodal intervention in Tuscany.

BACKGROUND: Despite the importance of hand hygiene in reducing infection, healthcare worker compliance with hand hygiene recommendations remains low. In a previous study, we found a generally low level of compliance at baseline, with substantial differences between doctors and nurses and between hospital units. We describe here the results of our multimodal intervention intended to improve levels of healthcare worker hand hygiene. METHODS: A 6-month, before-and-after, multimodal interventional study in five hospital units in Florence, Italy. We used direct observation to assess hand hygiene rates for doctors and nurses, focusing on hygiene before touching the patient. We explored reasons for unit variability via interviews of doctor and nurse leaders on the units. RESULTS: Overall healthcare worker hand hygiene increased from 31.5% to 47.4% (p<0.001). Hand hygiene adherence among nurses increased from 33.7% to 47.9% (p<0.001); adherence among doctors increased from 27.5% to 46.6% (p<0.001). Improvement was statistically significant in three out of five units, and units differed in the magnitude of their improvement. Based on the interviews, variability appeared related to the "champion" on each unit, as well as the level of motivation each physician leader exhibited when the preintervention results were provided. CONCLUSIONS: Although overall healthcare worker adherence with hand hygiene procedures before patient contact substantially increased after the multimodal intervention, considerable variability-for both nurses and doctors and across the 5 units-was seen. Although adherence substantially increased, overall hand hygiene in these units could still be greatly improved.

Severe hyponatremia due to hypopituitarism with adrenal insufficiency: a case report.

OBJECTIVE: Adrenal insufficiency due to hypopituitarism can lead to severe hyponatremia with potentially fatal consequences. Prompt diagnosis and adequate hormonal replacement therapy are essential to block an otherwise unfavorable course and to re-establish a healthy life. Unfortunately, this condition is often misdiagnosed. DESIGN: Case report. SETTING: Intensive Care Unit of a teaching hospital. PATIENT: A 76-yr-old man with refractory hypotension, acute myocardial infarction, and left ventricular dysfunction, secondary to severe chronic pan-hypopituitarism, associated with severe hyponatremia. METHODS AND MAIN RESULTS: The patient underwent mechanical ventilation and continuous venous-venous hemodiafiltration, for severe respiratory and renal insufficiency. A hormonal replacement therapy with T4, hydrocortisone, and nandrolone was started and the patient was discharged to a rehabilitation facility after 31 days of hospitalization. CONCLUSIONS: Hypopituitarism with secondary adrenal insufficiency is often misdiagnosed at an early stage and a high degree of suspicion is necessary for early diagnosis. Determination of plasma cortisol level in patients with hyponatremia not explained by other causes should always be obtained.

Novel mode of action of iloprost: in vitro down-regulation of endothelial cell adhesion molecules.

Iloprost is a stable prostacyclin analog commonly employed in the treatment of peripheral vascular disease and also indicated in the treatment of patients affected by systemic sclerosis (SSc) in the presence of severe Raynaud's phenomenon (RP). Several mechanisms of action of the drug other than vasodilation and antiplatelet effect have been demonstrated that may be involved in the exertion of its clinical efficacy. Aim of the present study was to investigate whether iloprost down-regulated lymphocyte adhesion to endothelium through a modulation of adhesion molecule expression on the surface of endothelial cells. In the presence of iloprost, both lymphocyte adhesion and IL-1 stimulated expression of ICAM-1 and ELAM-1 exhibited a significant reduction, while unstimulated adhesion molecule expression was not significantly affected. Our results confirm that iloprost is able to down-regulate lymphocyte adhesion to endothelial cells and indicate that endothelium itself could be target of iloprost administration. Attenuation of the inflammatory response through modulation of cellular interactions could be suggested as a potential mechanism of action of iloprost, when used in the treatment of pathological conditions characterized by endothelial activation.

Lymphocyte-endothelium interaction in systemic sclerosis and Raynaud's phenomenon.

OBJECTIVE: To investigate interactions of immune cells with vascular endothelium in patients with systemic sclerosis (SSc) and in patients with idiopathic or autoimmune Raynaud's phenomenon (RP). METHODS: Lymphocytes obtained from 11 patients with SSc, 9 with RP and 14 control subjects were pre-stimulated in vitro with alloantigens and cultured together with human umbilical vein endothelial cells (HUVECs). Lymphocyte adhesion and induction of endothelial HLA-class 11 molecules were measured by flow cytometry. Lymphocyte cytotoxicity against HUVECs was also evaluated. In some cases cells were cultured under experimental conditions of hypoxia and reoxygenation. RESULTS: Lymphocyte adhesion and induction of endothelial cell expression of HLA-DR molecules were similar in controls and SSc patients, but significantly lower in RP (p < 0.05 and p < 0.03, respectively). Cytotoxic activity of lymphoblasts against endothelial cells was negligible in all patient groups. Under experimental conditions of hypoxia and reoxygenation lymphocyte adhesion was significantly greater than in normoxic conditions in SSc patients, while it was similar to normoxia in control subjects and RP patients. CONCLUSION: These results suggest that in RP patients there may be regulatory mechanisms of lymphocyte response able to control the processes that lead to lymphocyte adhesion and endothelial HLA-DR molecule induction. These mechanisms could play an important role in RP, and might possibly be lost in clinically evident SSc.

Cardiopulmonary resuscitation of older, inhospital patients: immediate efficacy and long-term outcome.

OBJECTIVE: To determine the independent effect of advancing age on prognosis after cardiopulmonary resuscitation (CPR). DESIGN AND SETTING: Retrospective analysis of clinical records of patients who received CPR in a geriatric department equipped with an intensive care unit. PATIENTS: A total of 245 patients (146 men, 99 women; mean age, 70+/-11 yrs) received CPR. Of these, 221 had a cardiocirculatory arrest (CA) in the intensive care unit and 24 had a CA in the general ward of the department. Acute myocardial infarction was the most frequent admission diagnosis. INTERVENTIONS: CPR according to standard guidelines in all cases. MEASUREMENTS AND MAIN RESULTS: Immediate, short-term (hospital discharge), and long-term (median follow-up, 31.5 months; range, <1-124 months) survival. Older patients had a lower immediate survival (<70 yrs [72/137] 52.6% vs. > or =70 yrs [43/108] 39.4%; p < .05) and, less frequently, ventricular tachycardia/ fibrillation (VT/VF) as a cause of CA. VT/VF bore the lowest immediate mortality rate (19/104; 18.3%) as compared with asystole/complete heart block (66/102; 64.7%) or pulseless electrical activity (40/49; 81.6%; p < .001). Acute myocardial infarction, acute heart failure, hypotension, and occurrence of CA in the intensive care unit were also univariate predictors of unfavorable, immediate prognosis. However, in a multiple logistic analysis model, the mechanism of CA (asystole/complete heart block or pulseless electrical activity vs. VT/VF), acute myocardial infarction, heart failure, and hypotension were independent predictors of unfavorable immediate prognosis, whereas advancing age was not. Similarly, after initially successful CPR, short-term survival was independently associated with acute myocardial infarction, hypotension before CA, initial rhythm at CA, and need for mechanical ventilatory support after CPR, but not with age. Longterm survival (42 patients; 17.2% of the original cohort; median survival, 32 months) was also independent of age, whereas it was negatively associated with heart failure. CONCLUSION: Immediate, short- and long-term prognosis after in hospital CPR is independent of age, at least when possible confounders are simultaneously taken into account.

Determinants of exercise tolerance after acute myocardial infarction in older persons.

OBJECTIVES: Exercise tolerance is reduced with advancing age. Identification of potentially reversible determinants of the age-related decrement in exercise tolerance, which remain largely unexplored in older subjects and in patients recovering from a recent myocardial infarction (MI), may have useful therapeutic implications. The objective of this study was to identify the independent determinants of exercise tolerance in older patients with a recent MI. DESIGN, SETTING, AND PARTICIPANTS: Data is from baseline assessment of 265 post-MI patients (age range 45-85 years) enrolled in the Cardiac Rehabilitation in Advanced Age randomized, controlled trial. Patients with major comorbidities or severe MI complications were excluded from the trial. Exercise tolerance was determined from symptom-limited exercise testing and expressed as total work capacity (TWC, kg.m) or peak oxygen consumption (VO2peak, mL/kg/min). The associations between both TWC and VO2peak and baseline demographic, social, clinical, and neuropsychological variables and an index of health-related quality of life were determined with univariate and multivariate analysis. RESULTS: With univariate analysis, TWC decreased by 1285 kg.m per decade of increasing age between 45 and 85 years of age. With multivariate analysis, TWC decreased by 922 kg.m per decade. Increasing age (P < .001), female gender (P < .001), a small body surface area (P < .001), a low level of usual physical exercise before MI (P < .002), and the presence of post-MI depressive symptoms (P < .024) were independently associated with a lower TWC. The same factors, in addition to a small arm muscle area (P < .002), were also independently associated with a lower VO2peak. CONCLUSIONS: Age per se accounts for approximately 70% of the age-related decay in TWC or VO2peak. However, the inclusion of modifiable factors such as physical exercise and depression in the prediction model reinforces the importance of a multidimensional approach to the evaluation and treatment of older patients with a recent MI.

Heart failure in community-dwelling older persons: aims, design and adherence rate of the ICARe Dicomano project: an epidemiologic study. Insufficienza Cardiaca negli Anziani Residenti a Dicomano.

BACKGROUND: The prevalence of heart failure (HF) increases with age, and HF is a major cause of disability and mortality in older persons. Detection of HF in epidemiological studies has relied on criteria validated only in young and middle-age adults, and, therefore, may prove inadequate in older subjects, because they do not take into account the pathophysiologic and clinical peculiarities of HF in old age. Thus, the true prevalence of HF in the older general population remains uncertain and has probably been underestimated in previous studies. Moreover, the mechanism and the extent by which HF hinders physical functioning in older people has not been fully elucidated. OBJECTIVES: This paper describes the design of the ICARe study, carried out in an older home-dwelling population to collect data about: (1) the sensitivity and specificity of diagnostic criteria used previously in epidemiological studies of HF; (2) the prevalence of the different pathophysiologic forms of HF; and (3) the impact of HF on overall health status, and on physical functioning, in the absence or presence of chronic comorbidity. DESIGN AND SETTING: This was a cross-sectional survey. Eligible were all community-dwelling persons aged 65 years or older recorded in the Registry Office of Dicomano, a small town nearby Florence (Italy). All the domains of multidimensional geriatric assessment were explored through different phases of the study (home interview, laboratory testing, geriatric visit) that comprised an extensive cardiopulmonary instrumental assessment including: color Doppler echocardiography, echotomography of the carotid arteries used in an original method to determine arterial compliance, and bell spirometry. Presence of major chronic conditions was ascertained by predefined, standard algorithms that were based largely on clinical examination. RESULTS: There were 864 older persons eligible for the ICARe study. Even with a substantial decline from home interview (91.2%) to the cardiopulmonary study (71.1%), the adherence rate remained high throughout the study, and the population examined was fairly representative of the original eligible population. Thus, we believe that the data collected in this study offer a unique opportunity to assess the validity of the diagnostic clinical criteria for HF in the general older population, to identify the pathophysiology underlying the syndrome, and to investigate the relationship between HF, comorbidity, and disability.

Target of rapamycin (TOR): balancing the opposing forces of protein synthesis and degradation.

Mitogenic and nutritional signals must be integrated for a cell to grow. The target of rapamycin (TOR) is emerging as an effector for signals which indicate to the cell whether the external environment is conducive for growth. Use of the immunosuppressant rapamycin, a bacterial macrolide, has been instructive in identifying potential signaling components downstream of TOR, leading to the observation that both protein synthesis and turnover are under TOR control. The central issues concerning TOR are the identification of the proliferative and anti-proliferative signals which mediate its function and the mechanisms by which these signals are transduced to downstream molecules.

Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase.

Recent studies have shown that the p70(s6k)/p85(s6k) signaling pathway plays a critical role in cell growth by modulating the translation of a family of mRNAs termed 5'TOPs, which encode components of the protein synthetic apparatus. Here we demonstrate that homozygous disruption of the p70(s6k)/p85(s6k) gene does not affect viability or fertility of mice, but that it has a significant effect on animal growth, especially during embryogenesis. Surprisingly, S6 phosphorylation in liver or in fibroblasts from p70(s6k)/p85(s6k)-deficient mice proceeds normally in response to mitogen stimulation. Furthermore, serum-induced S6 phosphorylation and translational up-regulation of 5'TOP mRNAs were equally sensitive to the inhibitory effects of rapamycin in mouse embryo fibroblasts derived from p70(s6k)/p85(s6k)-deficient and wild-type mice. A search of public databases identified a novel p70(s6k)/p85(s6k) homolog which contains the same regulatory motifs and phosphorylation sites known to control kinase activity. This newly identified gene product, termed S6K2, is ubiquitously expressed and displays both mitogen-dependent and rapamycin-sensitive S6 kinase activity. More striking, in p70(s6k)/p85(s6k)-deficient mice, the S6K2 gene is up-regulated in all tissues examined, especially in thymus, a main target of rapamycin action. The finding of a new S6 kinase gene, which can partly compensate for p70(s6k)/p85(s6k) function, underscores the importance of S6K function in cell growth.

Effective arterial elastance and the hemodynamic effects of intraaortic balloon counterpulsation in patients with coronary heart disease.

OBJECTIVES: The goal of the present study was to analyze the effects of different intraaortic balloon counterpulsation (IABC) inflation volumes on effective arterial elastance (Ea) in patients with complicated coronary heart disease and to determine whether Ea can predict the hemodynamic response to IABC. BACKGROUND: Ea (the central aortic end-systolic pressure to stroke volume ratio) incorporates the principal elements of input arterial impedance and has been proved useful to evaluate the effects of afterload reduction in patients with left ventricular (LV) failure. However, although the hemodynamic action of IABC can be considered as a typical example of "pure" afterload reduction, it has never been assessed in terms of changes in Ea. METHODS: After clinical stabilization, 18 patients treated with IABC for complicated acute myocardial infarction or unstable angina were enrolled in the study. Systemic hemodynamics were measured by use of right cardiac thermodilution catheters with IABC off (control) and IABC on at balloon inflation volumes of 20 and 40 ml, in randomized sequence. Aortic pressure was recorded through the central lumen of the IABC catheter to calculate Ea as the ratio of aortic dicrotic pressure to stroke volume. RESULTS: A higher control Ea was associated with a lower control LV stroke work and a larger IABC-related hemodynamic improvement (that was maximal with the 40 ml inflation volume). The increase in LV stroke work was closely related to the decrease in Ea. Accordingly, hemodynamic benefits from IABC were less evident in patients with lower control Ea. In conclusion, effects of IABC were related to both balloon inflation volume and control hemodynamics, reflecting the afterload dependence of a depressed LV function.

Aims, design and enrollment rate of the Cardiac Rehabilitation in Advanced Age (CR-AGE) randomized, controlled trial.

Data regarding the efficacy of cardiac rehabilitation after acute myocardial infarction in advanced age are limited, and are derived from either controlled but non randomized trials, or observational studies. Several aspects of cardiac rehabilitation after myocardial infarction in advanced age, including its effectiveness on exercise tolerance and health-related quality of life, as well as the feasibility of rehabilitation programs, need clarification. The objectives of this randomized, controlled trial, Cardiac Rehabilitation in Advanced Age (CR-AGE), are to examine the effects of an 8-week comprehensive cardiac rehabilitation intervention, comparing 1) supervised outpatient, hospital-based cardiac rehabilitation, 2) home-based cardiac rehabilitation, and 3) usual care in each of three groups of post-myocardial infarction patients, 45-65, 66-75, and 76-85 years of age. The primary objective of the trial is to evaluate the change in physical fitness in each age group assessed by total work capacity at the end of the intervention, and during follow-up over both the medium- (6 months) and the long-term (1 and 2 years). Secondary objectives of the trial include an examination of the feasibility of cardiac rehabilitation in older patients, as well as the determination of the following: exercise complication rates; changes in peak oxygen consumption; changes in other outcome measures, such as health-related quality of life, prevalence of anxiety and depressive symptoms, fluid intelligence, body composition and mass index; incidence of new cardiac and non-cardiac events; and utilization rates of health care services. Enrollment in the CR-AGE trial is expected to be completed within the first half of 1998.

Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k.

Treatment of mammalian cells with the immunosuppressant rapamycin, a bacterial macrolide, selectively suppresses mitogen-induced translation of an essential class of mRNAs which contain an oligopyrimidine tract at their transcriptional start (5'TOP), most notably mRNAs encoding ribosomal proteins and elongation factors. In parallel, rapamycin blocks mitogen-induced p70 ribosomal protein S6 kinase (p70s6k) phosphorylation and activation. Utilizing chimeric mRNA constructs containing either a wild-type or disrupted 5'TOP, we demonstrate that an intact polypyrimidine tract is required for rapamycin to elicit an inhibitory effect on the translation of these transcripts. In turn, a dominant-interfering p70s6k, which selectively prevents p70s6k activation by blocking phosphorylation of the rapamycin-sensitive sites, suppresses the translation of the chimeric mRNA containing the wild-type but not the disrupted 5'TOP. Conversion of the principal rapamycin-sensitive p70s6k phosphorylation site, T389, to an acidic residue confers rapamycin resistance on the kinase and negates the inhibitory effects of the macrolide on 5'TOP mRNA translation in cells expressing this mutant. The results demonstrate that the rapamycin block of mitogen-induced 5'TOP mRNA translation is mediated through inhibition of p70s6k activation.

Item re-scaling of an Italian version of the sickness impact profile: effect of age and profession of the observers.

An Italian version of the Sickness Impact Profile (SIP) obtained by professional and nonprofessional translators was checked for cross-cultural equivalence using a back-translation method followed by two scaling studies. The first scaling study involved 30 health professionals who ranked the items within each category for severity of dysfunction. By comparing Italian and US average ranks, 14 highly discordant items were identified. A revised translation was evaluated in a new study involving 120 observers stratified by age (< 65 versus > or = 65 years) and profession (health versus non health professionals) into 4 groups of the same size. The Italian and American item rank orders were almost equivalent, independently of the age and profession of the observers (93% of the ranks showing differences < 2), suggesting that this Italian version of SIP is cross-culturally unbiased. However, older age was associated with higher variability in the rank orders, and some caution is required for use in the geriatric population.