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The article discusses issues on federal rule of civil procedure 19(B), particularly on the compulsory joinder of indispensable parties. Also cited are the 1854 U.S. Supreme Court ruling in the case Shields v. Barrow on said parties, Rule 19 of the Federal Rules of Civil Procedure, and a comparative analysis of the rule to that of the Italian and German legal systems.

Aim: To assess the predictive validity of the Functional Evaluation of Eating Difficulties Scale (FEEDS) on long-term eating developmental outcomes in infants with neurodevelopmental disorders.Method: In total, 144 infants (69 females, 75 males) aged 0 to 12 months (mean [SD] 5.34mo [3.42]) with neurodevelopmental disorders and requiring enteral nutrition support, hospitalized between January 2004 and December 2017, were included. The FEEDS was administered at the onset of hospitalization. Follow-up evaluations of feeding modalities occurred at discharge and at 6 months, 12 months, and 24 months after discharge. FEEDS score was tested as a predictor of infants' feeding modality (percutaneous endoscopic gastrostomy, nasogastric tube, mixed, oral feeding) and time to autonomous oral feeding. Percentages of false-positive and negative cases were checked.Results: Lower FEEDS scores significantly predicted infants' feeding modality (0.40≤R2 ≤0.61). A 1-point increase in FEEDS score was associated with increased risk (6%-14%; p<0.05) of being non-autonomous feeders at the different follow-up points in infants who had a FEEDS score above the clinical cut-off.Interpretation: The FEEDS appears to be a clinically valid assessment to predict the presence of eating difficulties in infants with neurodevelopmental disabilities.What This Paper Adds: Functional Evaluation of Eating Difficulties Scale (FEEDS) significantly predicted eating difficulties in infants with neurodevelopmental disabilities. Lower FEEDS score is significantly associated with autonomous feeding at the 24-month follow-up. FEEDS cut-off identified infants at low-risk and high-risk for eating disorder. [ABSTRACT FROM AUTHOR]

Objective: To define the role of cavernosal venous occlusive dysfunction (CVOD) as the only cause of erectile dysfunction (ED).Materials and Methods: Patients meeting the CVOD criteria without any risk factors for organic ED were randomized into 2 groups; the end-diastolic velocity (EDV), peak systolic velocity (PSV), and resistive index (RI) of their cavernosal arteries were assessed using color duplex Doppler ultrasound (CDDU) after intracavernous injection (ICI) of 10 µg alprostadil. Group 1 (153 patients) underwent repeated CDDU + ICI assessments (a maximum of 3 rounds). Group 2 (149 patients) underwent CDDU + ICI before and after sexological counseling. The percentage data were analyzed using the Cochran-Mantel-Haenszel test; the numerical data were analyzed using the Wilcoxon test.Results: For group 1, the PSVs (median values: first round 42 cm/s; second round 54 cm/s; third round 66 cm/s) and RIs (median values: first round 70%; second round 89%; third round 92%) increased significantly in each CDDU + ICI round, whereas the EDVs were significantly lower (median values: first round 11 cm/s; second round 5 cm/s; third round 1 cm/s). For group 2, the PSVs (median values: from 44 to 67 cm/s) and RIs (from 72% to 93%) increased significantly after sexological counseling, whereas the EDVs (median values: from 12 to 1 cm/s) were significantly lower.Conclusion: Repeated CDDU + ICI and counseling strongly diminished the percentage of patients meeting the CVOD criteria, leading to the suspicion that CVOD is linked to psychological issues in highly selected young healthy men with ED. [ABSTRACT FROM AUTHOR]

Purpose: To determine the efficacy of bimanual microincision cataract surgery (B-MICS) performed by surgeons in training, evaluating clinical results, posterior capsule opacification (PCO) incidence, and clear corneal incision (CCI) architecture in a long-term follow-up and comparing results with those obtained by experienced surgeons. Patients and methods: Eighty eyes of 62 patients operated on by three surgeons in training who used B-MICS technique for the first time were included in the study (Group A). Eighty eyes of 59 patients who underwent B-MICS by three experienced surgeons were included as a control group (Group B). Best corrected visual acuity, astigmatism, corneal pachymetry, and endothelial cell count were evaluated before surgery and at 1 month and 18 months after surgery. Anterior segment optical coherence tomography images were obtained to study the morphology of CCIs. PCO incidence was evaluated using EPCO2000 software. Results: Out of 160 surgeries included in the study, mean best-corrected visual acuity improvement at 18 months was 0.343±0.246 logMAR for Group A, and 0.388±0.175 logMAR for Group B, respectively. We found no statistically significant induced astigmatism nor corneal pachymetry changes in either group, while we noticed a statistically significant endothelial cell loss postoperatively in both groups (P<0.05). In Group A, mean PCO score was 0.163±0.196, while for Group B, it was 0.057±0.132 (P=0.0025). Mean length and inclination of the CCIs for Group A and Group B were, respectively, 1,358±175 μm and 1,437±256 μm and 141.8°±6.4° and 148.7°±5.1°. As regards corneal architecture in the 320 CCIs considered, we found posterior wound retractions and endothelial gaps, respectively, 9.8% and 11.6% for Group A and 7.8% and 10.8% for Group B.Conclusion: B-MICS performed by surgeons in training is an effective surgical technique even when assessed after a long-term follow-up. PCO incidence resulted in being higher for less experienced surgeons. Corneal incisions were shorter and less angled in surgeons in training in comparison with results obtained by expert surgeons. [ABSTRACT FROM AUTHOR]

Objectives Theory of Mind (ToM) is a complex human ability that allows people to make inferences on others’ mental states such as beliefs, emotions and desires. Previous studies on ToM in normal aging have provided heterogeneous findings. In the present study we examined whether a mixed calculation of different aspects of ToM may have contributed to these conflicting results. We had two aims. First, we explored the age-related changes in the performance of cognitive vs. affective ToM. Second, we investigated the extent to which the effect of aging on cognitive vs. affective ToM is mediated by age-related differences in executive functions. Method To address these issues three age groups (young, young-old, and old-old adults) were compared on cognitive and affective ToM using the faux pas test. In addition, participants were tested using a battery of executive function tasks tapping on inhibition, working memory updating, and word fluency. Results The analyses indicated that young adults outperform both young-old and old-old adults on cognitive ToM but not on affective ToM. Correlations showed that, whereas cognitive ToM was significantly associated with age, working memory updating, and inhibition, affective ToM was not. Finally, analyses revealed that individual differences in working memory updating (but not inhibition) mediated the effect of age on cognitive ToM. Conclusion Our findings support the view of selective age-related differences on cognitive, but not affective, ToM in normal aging. The distinction between the two ToM components is further supported by a dissociable pattern of correlations with executive functions. [ABSTRACT FROM AUTHOR]

The use of peracetic acid (PAA) in the disinfection of sanitary effluents provides an opportunity for the study of analytic methods that permit the determination of the residual concentration of the disinfectant in the effluent. The object of the present study is to compare different methodologies for the determination of residual PAA in concentrations recommended for disinfection of wastewater. The methodologies adopted in this study include three redox titration methods and one spectrophotometric method. Preliminary tests were performed by adding PAA (0.1; 0.5; 1.0; 5.0 and 10.0 mg L−1) to distilled water, and later reevaluated by applying the same concentrations of the disinfectant in wastewater. The results obtained were statistically evaluated and showed that the concentrations between 0.5 and 10 mg L−1of PAA could be determined both by the cerimetric/iodometric titration method and by the spectrophotometric method using DPD chromophore with catalase. For concentrations between 0.1 and 0.5 mg L−1, only the spectrophotometric method provided satisfactory results. [ABSTRACT FROM AUTHOR]

Theory of mind (ToM) refers to humans' ability to recognize the existence of mental states, such as beliefs, emotions, and desires. The literature on ToM in aging and on the relationship between ToM and other cognitive functions, like executive functions, is not homogenous. The aim of the present study was to explore the course of ToM and to investigate the role of working memory, inhibition, and language on the possible age differences in ToM. To address these issues, we examined ToM using the Strange Stories task and executive function task in three age groups. Results showed that young adults outperform both old groups on the ToM stories. This difference remains significant also when controlling for working memory and inhibitory control. Our findings suggest a specific impairment in inferring mental states starting from 60 years of age that seems to be independent of changes in executive functions. [ABSTRACT FROM AUTHOR]

Objective: To look for a link between compensation of diabetes in patients with uncompensated/undiagnosed diabetes with chronic Peyronie''s disease (PD) and improvement of their PD symptoms. Methods: Thirty-six nonsmoking patients with uncompensated diabetes and PD were studied. The plaque area and pain (ie, PD symptoms) were compared before and after a strict control of hemoglobin A1c and of glycemia at a timeframe of 37 ± 13 weeks. Thirty-two nonsmoking nondiabetic patients with PD who had their PD symptoms assessed twice with a mean time lag of 39 ± 11 weeks were used as controls. The differences in PD symptoms between the 2 assessments were evaluated using the Wilcoxon test. A Spearman rank correlation test was used to identify any correlation between glycemia before diabetic compensation and the percentage of decrease in the size of plaque of patients with diabetes. Results: Plaque area and pain diminished in patients with diabetes, coincidentally with diabetes compensation and antidiabetic therapy administration. On the other hand, the controls had their plaque area significantly increased while their pain was not modified. The Spearman tests found a significant correlation between glycemia before diabetic compensation and the percentage of decrease in the size of plaque of patients with diabetes. Conclusion: Diabetes compensation and/or antidiabetic therapy improved PD symptoms. [Copyright &y& Elsevier]

Objective: To establish a standard location for examining penile cavernosal arteries (CAs) using dynamic duplex Doppler ultrasound (PDDU) examination in the diagnosis of non-arterial erectile dysfunction (ED) or arterial insufficiency.Patients and Methods: Two groups of 105 patients each were enrolled. The first group (age 56.3 ± 6.0 years) displayed clinical patterns of arterial insufficiency; the second group (age 35.2 ± 4.7 years) displayed clinical patterns of non-arterial ED. The patients had their peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI = PSV - EDV/PSV × 100), and acceleration time of the CAs measured using PDDU at the crura and at the midpoint between the penoscrotal junction and the coronal sulcus (mid penis). Intra- and interoperator variability were assessed. The PSV, RI, acceleration time, and EDV data obtained from the penoscrotal junction or from the "mid penis" in group 1 and in group 2 were compared using analysis of variance.Results: The PSV, EDV, and acceleration time were significantly higher when measured at the crura penis than when measured at the "mid penis" in both groups, whereas the RI was higher at the "mid penis" than at the "crura." Thus, arterial ED was better diagnosed with the data from the mid penis, whereas non-arterial ED was better diagnosed at the "crura."Conclusion: The location of the sampling site of the CAs using PDDU is critical for a correct diagnosis of ED. [ABSTRACT FROM AUTHOR]

Objectives: The COVID-19 pandemic resulted in a particularly adverse and stressful environment for expecting mothers, possibly enhancing feelings of anxiety and parenting stress. The present work assesses mothers' anxiety levels at delivery and parenting stress after 3 months as moderated by home-visiting sessions. Methods: Women (n = 177) in their second or third trimester of pregnancy during the COVID-19 lockdown were enrolled in northern Italy and split into those who did and did not receive home visits. After 3 months, the association between anxiety at delivery and parenting stress was assessed with bivariate correlations in the whole sample and comparing the two groups. Results: Higher anxiety at birth correlated with greater perceived stress after 3 months. Mothers who received at least one home-visiting session reported lower parenting stress at 3 months than counterparts who did not receive home visits. Conclusions for Practice: The perinatal period is a sensitive time window for mother-infant health, especially during a critical time like the COVID-19 pandemic. We suggest that home-visiting programs could be beneficial during global healthcare emergencies to promote maternal well-being after delivery. [ABSTRACT FROM AUTHOR]

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with elevated levels of pancreatic enzymes and pancreatitis. Gabexate, a protease inhibitor, has been used to prevent pancreatic damage related to ERCP. Methods: We conducted a multicenter, double-blind comparison of gabexate (1 g given by intravenous infusion starting 30 to 90 minutes before endoscopy and continuing for 12 hours afterward) with placebo (mannitol and sodium chloride, administered in the same fashion). A total of 435 adults scheduled to undergo ERCP and, when indicated, endoscopic sphincterotomy underwent randomization; 17 were excluded from the final analysis for various reasons. The remaining 418 patients (mean age, 60.4 years) — 208 in the gabexate group and 210 in the placebo group — were analyzed. Acute pancreatitis was considered to be present if serum amylase or lipase levels (or both) were five times greater than the upper limits of normal in association with the onset of pancreatic pain. Results: After the procedures, 276 patients (66 percent) had elevated pancreatic-enzyme levels; the frequency was similar in the two groups. Mean serum amylase values were higher in the placebo group than in the gabexate group through 24 hours of observation (P = 0.03). Twelve patients in the gabexate group and 29 in the placebo group had abdominal pain (6 percent vs. 14 percent, P = 0.009). Sixteen patients in the placebo group and five in the gabexate group had acute pancreatitis (8 percent vs. 2 percent, P = 0.03). Two patients treated with gabexate and six given placebo had adverse events, all of which resolved. Two patients given placebo died of acute pancreatitis; one was excluded from the evaluation because pancreatitis was present before endoscopy. One patient in the gabexate group died, from a myocardial infarction. Conclusions: Prophylactic treatment with gabexate reduced pancreatic damage related to ERCP, as reflected by reductions in the extent but not the frequency of elevated enzyme levels and in the frequency of pancreatic pain and acute pancreatitis. (N Engl J Med 1996;335:919-23.) [ABSTRACT FROM AUTHOR]

Purpose: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is increasingly used to guide salvage radiation therapy (sRT) in patients with prostate cancer and biochemical recurrence/persistence after prostatectomy. This work examined (1) metastasis-free survival (MFS) after PSMA-PET guided sRT and (2) the metastatic patterns on PSMA-PET images after sRT.Methods and Materials: This retrospective, multicenter (9 centers, 5 countries) study included patients referred for PSMA-PET due to recurrent/persistent disease after prostatectomy. Patients with distant metastases (DM) on PSMA-PET before sRT were excluded. Cox regression was performed to assess the effect of clinical parameters on MFS. The distribution of PSMA-PET detected DM after sRT and their respective risk factors were analyzed.Results: All (n = 815) patients received intensity modulated RT to the prostatic fossa. In the case of PET-positive pelvic lymph nodes (PLN-PET) (n = 275, 34%), pelvic lymphatics had been irradiated. Androgen deprivation therapy had been given in 251 (31%) patients. The median follow-up after sRT was 36 months. The 2-/4-year MFS after sRT were 93%/81%. In multivariate analysis, the presence of PLN-PET was a strong predictor for MFS (hazard ratio, 2.39; P < .001). After sRT, DM were detected by PSMA-PET in 128/198 (65%) patients, and 2 metastatic patterns were observed: 43% had DM in sub-diaphragmatic para-aortic LNs (abdominal-lymphatic), 45% in bones, 9% in supra-diaphragmatic LNs, and 6% in visceral organs (distant). Two distinct signatures with risk factors for each pattern were identified.Conclusions: MFS in our study is lower compared with previous studies, obviously due to the higher detection rate of DM in PSMA-PET after sRT. Thus, it remains unclear whether MFS is a surrogate endpoint for overall survival in PSMA PET-staged patients in the post-sRT setting. PLN-PET may be proposed as a new surrogate parameter predictive of MFS. Analysis of recurrence patterns in PET after sRT revealed risk factor signatures for 2 metastatic patterns (abdominal-lymphatic and distant), which may allow individualized sRT concepts in the future. [ABSTRACT FROM AUTHOR]

Background prior statin treatment has been shown to have favourable effects on short- and long-term prognosis in patients with acute coronary syndrome (ACS). There are limited data in older patients. The aim of this study was to investigate the association of previous statin therapy and presentation characteristics, infarct size and clinical outcome in older patients, with or without atherosclerotic cardiovascular disease (ASCVD), included in the Elderly-ACS 2 trial. Methods data on statin use pre-admission were available for 1,192 of the 1,443 patients enrolled in the original trial. Of these, 531 (44.5%) were already taking statins. Patients were stratified based on established ASCVD and statin therapy. ACS was classified as non-ST elevation or ST elevation myocardial infarction (STEMI). Infarct size was measured by peak creatine kinase MB (CK-MB). All-cause death in-hospital and within 1 year were the major end points. Results there was a significantly lower frequency of STEMI in statin patients, in both ASCVD and No-ASCVD groups. Peak CK-MB levels were lower in statin users (10 versus 25 ng/ml, P  < 0.0001). There was lower all-cause death in-hospital and within 1 year for subjects with ASCVD already on statins independent of other baseline variables. There were no differences in all-cause death for No-ASCVD patients whether or not on statins. Conclusions statin pretreatment was associated with more favourable ACS presentation and lower myocardial damage in older ACS patients both ASCVD and No-ASCVD. The incidence of all-cause death (in-hospital and within 1 year) was significantly lower in the statin treated ASCVD patients. [ABSTRACT FROM AUTHOR]

Abstract: The conduction and valence band structure of high-purity 4H-SiC epilayers have been studied by surface photovoltage spectroscopy (SPS). A comparison between defect-free and single-layer stacking fault affected areas is reported. Electronic transitions, determined by SPS, are in good agreement with ab initio calculations. Electronic transitions and changes in band occupation have been observed in stacking fault rich areas below the band gap. Moreover, stacking faults induce the presence of a split-off band below the conduction band and a modification of the electron density of states in the conduction band always at the M point. [Copyright &y& Elsevier]

Background: Red blood cells (RBCs) contain the majority of α-synuclein (α-syn) in blood, representing an interesting model for studying the peripheral pathological alterations proved in neurodegeneration.Objective: The current study aimed to investigate the diagnostic value of total α-syn, amyloid-β (Aβ1-42), tau, and their heteroaggregates in RBCs of Lewy body dementia (LBD) and Alzheimer's disease (AD) patients compared to healthy controls (HC).Methods: By the use of enzyme-linked immunosorbent assays, RBCs concentrations of total α-syn, Aβ1-42, tau, and their heteroaggregates (α-syn/Aβ1-42 and α-syn/tau) were measured in 27 individuals with LBD (Parkinson's disease dementia, n = 17; dementia with Lewy bodies, n = 10), 51 individuals with AD (AD dementia, n = 37; prodromal AD, n = 14), and HC (n = 60).Results: The total α-syn and tau concentrations as well as α-syn/tau heterodimers were significantly lower in the LBD group and the AD group compared with HC, whereas α-syn/Aβ1-42 concentrations were significantly lower in the AD dementia group only. RBC α-syn/tau heterodimers had a higher diagnostic accuracy for differentiating patients with LBD versus HC (AUROC = 0.80).Conclusion: RBC α-syn heteromers may be useful for differentiating between neurodegenerative dementias (LBD and AD) and HC. In particular, RBC α-syn/tau heterodimers have demonstrated good diagnostic accuracy for differentiating LBD from HC. However, they are not consistently different between LBD and AD. Our findings also suggest that α-syn, Aβ1-42, and tau interact in vivo to promote the aggregation and accumulation of each other. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate whether limited vitrectomy is as effective as complete vitrectomy in eyes with epiretinal membrane (ERM) and to compare the surgical times and rates of complications. Methods. In this multicentre European study, data of eyes with ERM that underwent vitrectomy from January 2017 to July 2018 were analyzed retrospectively. In the limited vitrectomy group, a posterior vitreous detachment (PVD) was induced up till the equator as opposed to complete PVD induction till the vitreous base in the comparison group. Incidence of iatrogenic retinal breaks, retinal detachment, surgical time, and visual outcomes were compared between groups. Results. We included 139 eyes in the analysis with a mean age being 72.2 ± 6.9 years. In this, sixty-five eyes (47%) underwent limited vitrectomy and 74 eyes (53%) underwent complete vitrectomy. Iatrogenic retinal tears were seen in both groups (5% in limited vitrectomy versus 7% in complete vitrectomy, p = 0.49). Retinal detachment occurred in 2 eyes in the limited vitrectomy group (3%) compared to none in the complete vitrectomy group (p = 0.22). Best-corrected visual acuity (BCVA) and central macular thickness improved significantly with no intergroup differences (p = 0.18). Surgical time was significantly shorter in the limited vitrectomy group with 91% surgeries taking less than 1 hour compared to 71% in the complete vitrectomy group (p < 0.001). Conclusion. A limited vitrectomy is a time-efficient and effective surgical procedure for removal of epiretinal membrane with no additional complications. [ABSTRACT FROM AUTHOR]

Background and Purpose: The BAT, BRAIN, and HEP scores have been proposed to predict hematoma expansion (HE) with noncontrast computed tomography (NCCT). We sought to validate these tools and compare their diagnostic performance.Methods: We retrospectively analyzed two cohorts of patients with primary intracerebral hemorrhage. HE expansion was defined as volume growth > 33% or > 6 mL. Two raters analyzed NCCT scans and calculated the scores, blinded to clinical and imaging data. The inter-rater reliability was assessed with the interclass correlation statistic. Discrimination and calibration were calculated with area under the curve (AUC) and Hosmer-Lemeshow χ2 statistic, respectively. AUC comparison between different scores was explored with DeLong test. We also calculated the sensitivity, specificity, positive, and negative predictive values of the dichotomized scores with cutoffs identified with the Youden's index.Results: A total of 230 subjects were included, of whom 86 (37.4%) experienced HE. The observed AUC for HE were 0.696 for BAT, 0.700 for BRAIN, and 0.648 for HEP. None of the scores had a significantly superior AUC compared with the others (all p > 0.4). All the scores had good calibration (all p > 0.3) and good-to-excellent inter-rater reliability (interclass correlation > 0.8). BAT ≥ 3 showed the highest specificity (0.81), whereas BRAIN ≥ 6 had the highest sensitivity (0.76).Conclusions: The BAT, BRAIN, and HEP scores can predict HE with acceptable discrimination and require just a baseline NCCT scan. These tools may be used to stratify the risk of HE in clinical practice or randomized controlled trials. [ABSTRACT FROM AUTHOR]

The individual methods of disinfection peracetic acid (PAA) and UV radiation and combined process PAA/UV in water (synthetic) and sanitary wastewater were employed to verify the individual and combined action of these advanced oxidative processes on the effectiveness of inactivation of microorganisms indicators of fecal contamination E. coli, total coliforms (in the case of sanitary wastewater), and coliphages (such as virus indicators). Under the experimental conditions investigated, doses of 2, 3, and 4 mg/L of PAA and contact time of 10 minutes and 60 and 90 s exposure to UV radiation, the results indicated that the combined method PAA/UV provided superior efficacy when compared to individual methods of disinfection. [ABSTRACT FROM AUTHOR]

Objectives Process model comparison and similar process retrieval is a key issue to be addressed in many real-world situations, and a particularly relevant one in medical applications, where similarity quantification can be exploited to accomplish goals such as conformance checking, local process adaptation analysis, and hospital ranking. In this paper, we present a framework that allows the user to: (i) mine the actual process model from a database of process execution traces available at a given hospital; and (ii) compare (mined) process models. The tool is currently being applied in stroke management. Methods Our framework relies on process mining to extract process-related information (i.e., process models) from data. As for process comparison, we have modified a state-of-the-art structural similarity metric by exploiting: (i) domain knowledge; (ii) process mining outputs and statistical temporal information. These changes were meant to make the metric more suited to the medical domain. Results Experimental results showed that our metric outperforms the original one, and generated output closer than that provided by a stroke management expert. In particular, our metric correctly rated 11 out of 15 mined hospital models with respect to a given query. On the other hand, the original metric correctly rated only 7 out of 15 models. The experiments also showed that the framework can support stroke management experts in answering key research questions: in particular, average patient improvement decreased as the distance (according to our metric) from the top level hospital process model increased. Conclusions The paper shows that process mining and process comparison, through a similarity metric tailored to medical applications, can be applied successfully to clinical data to gain a better understanding of different medical processes adopted by different hospitals, and of their impact on clinical outcomes. In the future, we plan to make our metric even more general and efficient, by explicitly considering various methodological and technological extensions. We will also test the framework in different domains. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intravenous temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is approved for the treatment of advanced renal cell carcinoma (RCC). Sirolimus, the principal metabolite of temsirolimus in humans, also exhibits mTOR inhibitory activity. Objective: The purpose of this study was to compare the pharmacokinetics of temsirolimus and its metabolite, sirolimus, among patients with RCC not receiving dialysis and those receiving hemodialysis. Methods: This was a single-center, unblinded, single-dose study. Patients with histologically confirmed metastatic RCC were eligible. A single 25-mg dose of temsirolimus was administered as a 30-minute intravenous infusion during the first round of chemotherapy. Blood samples were drawn at 0 (predose), 0.5 (end of infusion), 1.5, 2.5, 5.5, 24, 72, and 144 hours after infusion. In patients receiving hemodialysis, an additional blood sample was drawn 1 hour after each treatment to compare pre- and postconcentration. Temsirolimus concentrations were assayed in blood using HPLC coupled to mass spectrometry. Pharmacokinetic parameters (Cmax, Tmax, t½, AUC0-∞, total body clearance, volume of distribution at steady state, AUC ratio [the ratio of sirolimus to temsirolimus AUCs], and AUC sum [the algebraic sum of temsirolimus and sirolimus AUCs]) were calculated and analyzed statistically. Results: In total, 13 consecutive patients (11 men and 2 women; 11 not receiving dialysis and 2 receiving hemodialysis) were included. No patient refused to participate in the study. Of those not receiving dialysis, the median age was 54 years (range, 36–77 years), and of those receiving hemodialysis, the median age was 60.5 years (60–61 years). There were no significant between-group differences in the pharmacokinetic parameters of temsirolimus and sirolimus. Moreover, in patients receiving hemodialy-sis, blood drug concentrations assessed immediately before hemodialysis were similar to those assayed 1 hour after the treatment. Conclusion: This study found that after single-dose administration of 25 mg of temsirolimus as a 30-minute intravenous infusion, neither temsirolimus nor sirolimus concentrations were significantly affected in these patients with RCC receiving hemodi-alysis compared with those not receiving dialysis. [Copyright &y& Elsevier]

1 The modulation exerted by nociceptin/orphanin FQ (NC) on noradrenaline (NE) release in rodent cerebral cortex slices and synaptosomes was studied. 2 Rat, mouse and guinea-pig cortical slices and synaptosomes were preincubated with 0.1 micro M [(3)H]-NE and superfused. NE release was evoked by 2 min of electrical (3 Hz) stimulation in slices and by 1 min pulse of 10 mM KCl in synaptosomes. 3 In rat cortical slices, 0.01-3 micro M NC reduced the evoked [(3)H]-NE efflux (E(max)-54%), with a bell-shaped concentration-response curve, which regained its monotonic nature in the presence of either 0.1 micro M naloxone (NX) or 30 micro M bicuculline. In synaptosomes, the NC effect curve was sygmoidal in shape and reached a plateau at 1 micro M concentration. 4 In the rat, both 1 micro M [Phe(1)psi(CH(2)-NH)Gly(2)]NC(1-13)NH(2) and 10 micro M [Nphe(1)]NC(1-13)NH(2) (NPhe) antagonised NC-induced inhibition, without per se modifying [(3)H]-NE efflux. The effects of 0.3-1 micro M NC concentrations were partially prevented by 1 micro M NX; 1 micro M D-Phe-Cys-Thr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) was also an effective antagonist, but 0.1 micro M norbinaltorphimine was not. 5 In the mouse cerebral cortex, NC-induced inhibition of NE release (pEC(50) 6.87, E(max)-61%, in the slices) was prevented by Nphe but was NX-insensitive. In guinea-pig cortical slices, NC effect (pEC(50) 6.22, E(max)-38%) was prevented by Nphe, but was NX-insensitive. 6 These findings demonstrate that NC inhibits NE release from rodent cerebral cortex via presynaptically located ORL(1) receptors. In the rat, micro opioid and GABA(A) receptors are involved as well. [ABSTRACT FROM AUTHOR]

Background: Worse outcomes have been reported for women, compared with men, after an acute coronary syndrome (ACS). Whether this difference persists in elderly patients undergoing similar invasive treatment has not been studied. We investigated sex-related differences in 1-year outcome of elderly acute coronary syndrome patients treated by percutaneous coronary intervention (PCI).Methods: Patients 75 years and older successfully treated with PCI were selected among those enrolled in 3 Italian multicenter studies. Cox regression analysis was used to assess the independent predictive value of sex on outcome at 12-month follow-up.Results: A total of 2035 patients (44% women) were included. Women were older and most likely to present with ST-elevation myocardial infarction (STEMI), diabetes, hypertension, and renal dysfunction; men were more frequently overweight, with multivessel coronary disease, prior myocardial infarction, and revascularizations. Overall, no sex disparity was found about all-cause (8.3% vs 7%, P = .305) and cardiovascular mortality (5.7% vs 4.1%, P = .113). Higher cardiovascular mortality was observed in women after STEMI (8.8%) vs 5%, P = .041), but not after non ST-elevation-ACS (3.5% vs 3.7%, P = .999). A sensitivity analysis excluding patients with prior coronary events (N = 1324, 48% women) showed a significantly higher cardiovascular death in women (5.4% vs 2.9%, P = .025). After adjustment for baseline clinical variables, female sex did not predict adverse outcome.Conclusions: Elderly men and women with ACS show different clinical presentation and baseline risk profile. After successful PCI, unadjusted 1-year cardiovascular mortality was significantly higher in women with STEMI and in those with a first coronary event. However, female sex did not predict cardiovascular mortality after adjustment for the different baseline variables. [ABSTRACT FROM AUTHOR]

In order to study the pathogenesis of gingival overgrowth induced by the immunosuppressive drug cyclosporine-A (CyA), we investigated its effect on 3H thymidine incorporation and on collagen production and mRNA levels in fibroblast cultures obtained from normal human gingiva. At concentrations of 100, 500 and 1000 ng/ml, CyA did not modify thymidine incorporation after 24 and 72 h of incubation. However, after 24 h it significantly increased the level of 3H proline-containing proteins in the medium. In addition, CyA increased alpha-procollagen chains by up to three times. This CyA-induced change was related to a rise in the level of type I procollagen. The CyA effect on fibroblasts was markedly reduced by cycloheximide, an inhibitor of protein synthesis, and it correlated well with an increase of type I procollagen mRNA. Overall, our data indicate a direct stimulatory action of CyA on collagen synthesis, but not on DNA synthesis, in human gingival fibroblasts. [ABSTRACT FROM AUTHOR]