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Purpose: Although personality has been widely researched in patients with anorexia nervosa (AN) and bulimia nervosa (BN), the nature of this relationship has not yet been clearly articulated. The pathoplasty model theorizes that personality might shape symptomatic presentation and thus affect therapeutic outcomes, but more research is needed. The present study aimed at investigating the predictive value of a broad spectrum of personality traits in determining AN and BN treatment outcomes, considering both the statistical and clinical significance of the therapeutic change., Methods: Eighty-four female patients with AN and BN treated in a residential program were evaluated at treatment onset using the Shedler-Westen Assessment Procedure-200-a clinician-rated measure of personality disorders and healthy personality functioning. At both intake and discharge, patients completed the Eating Disorder Inventory-3 to assess eating symptoms and the Outcome Questionnaire-45.2 to evaluate overall impairment., Results: Considering overall ED symptomatic change, multiple regression analyses showed that, even when controlling for baseline symptoms and DSM-5 categories, schizoid (B = 0.41, p ≤ 0.01), avoidant (B = 0.31, p ≤ 0.05), and paranoid (B = 0.25, p ≤ 0.05) personality features predicted worse therapeutic outcomes. Similar results were found when applying the clinical significance approach, with the emotionally dysregulated factor as an additional negative predictor of significant/reliable change (B =  - 0.09; p < 0.01). Healthy personality functioning predicted better therapeutic outcomes (B =  - 0.34, p ≤ 0.001)., Conclusions: Pathoplastic models and personality-based research in this clinical population have the potential to inform effective treatment strategies by targeting relevant individual factors., Level of Evidence: Level III, longitudinal cohort study.

Purpose: The present study evaluated the statistical and clinical significance of symptomatic change at discharge and after 6 months of an intensive residential treatment for patients with eating disorders (ED), and explored the individual factors that may affect therapeutic outcomes., Methods: A sample of 118 female ED patients were assessed at intake and discharge on the following dimensions: BMI, ED-specific symptoms, depressive features, and overall symptomatic distress. A subsample of 59 patients filled out the same questionnaires at a 6-month follow-up after discharge., Results: Findings evidenced statistically significant changes in all outcome measures at both discharge and follow-up. Between 30.1 and 38.6% of patients at discharge and 35.2-54.2% at the 6-month follow-up showed clinically significant symptomatic change; additionally, 19.8-29.1% of patients at discharge and 22.9-38.3% at follow-up improved reliably. However, 34.9-39.8% remained unchanged and 2-4.8% worsened. At the 6-month follow-up, 21.3-25.9% showed no symptomatic change and 0-3.7% had deteriorated. Unchanged and deteriorated patients had an earlier age of ED onset and were more likely to suffer a comorbid personality pathology and to be following concurrent pharmacological treatment., Conclusions: Results suggested that intensive and multimodal residential treatment may be effective for the majority of ED patients, and that therapeutic outcomes tend to improve over time. Prevention strategies should focus on early onset subjects and those with concurrent personality pathology., Level of Evidence: Level III, evidence obtained from a longitudinal cohort study.

In the wake of the sudden spread of COVID-19, a large amount of the Italian population practiced incongruous behaviors with the protective health measures. The present study aimed at examining psychological and psychosocial variables that could predict behavioral compliance. An online survey was administered from 18-22 March 2020 to 2766 participants. Paired sample t -tests were run to compare efficacy perception with behavioral compliance. Mediation and moderated mediation models were constructed to explore the association between perceived efficacy and compliance, mediated by self-efficacy and moderated by risk perception and civic attitudes. Machine learning algorithms were trained to predict which individuals would be more likely to comply with protective measures. Results indicated significantly lower scores in behavioral compliance than efficacy perception. Risk perception and civic attitudes as moderators rendered the mediating effect of self-efficacy insignificant. Perceived efficacy on the adoption of recommended behaviors varied in accordance with risk perception and civic engagement. The 14 collected variables, entered as predictors in machine learning models, produced an ROC area in the range of 0.82-0.91 classifying individuals as high versus low compliance. Overall, these findings could be helpful in guiding age-tailored information/advertising campaigns in countries affected by COVID-19 and directing further research on behavioral compliance.

This paper investigates if therapists' attachment classifications are linked to different types of therapists' attunement in session. We present coding procedures and validation of the Therapist Attunement Scales (TASc), a transcript-based instrument that assesses attunement in therapy and that we hypothesized would be associated with therapists' attachment classifications. Fifty therapists were administered the Adult Attachment Interview (AAI), and therapy sessions with each therapist were rated with the TASc. Therapists also completed the WAI-T to assess the therapeutic alliance and divergent validity of the TASc. Results indicate strong inter-rater reliability and stability across consecutive sessions of the TASc, as well as high convergent validity between one session rated with the TASc and the AAI rated independently ( κ  = .81). No significant associations were found with the WAI-T, which offers preliminary evidence of divergent validity of the TASc. These results suggest that therapists of different attachment classifications may attune to patients in distinct ways. These results also present the TASc as a valid measure of therapists' attachment in psychotherapy and as a promising tool for training and supervision.

This study provides an argument cautioning against the use of adaptive-beamforming (ABF) techniques in conjunction with a known method for estimating the bottom reflection loss from natural marine ambient noise. This application of ABF has been investigated in the past with rather inconsistent results. Furthermore, no formal proof that ABF algorithms do indeed provide an estimate of the bottom reflection loss is available. This study moves from a recent derivation of the relationship between the bottom reflection coefficient and the Fourier transform of the marine-noise spatial coherence function. The circumstances under which the beamforming operation approximates a discrete Fourier transform (DFT) of the spatial coherence function estimated from array data are analyzed. It is shown that, under certain conditions, conventional beamforming is equivalent to directly computing the DFT of the coherence function, as long as some subtle details are properly taken into account. Furthermore, it is shown that ABF cannot be guaranteed, in general, to perform this operation, and therefore provide an estimate of the bottom reflection coefficient. The conclusions are demonstrated on simulated and measured data.

Background: Despite growing attention to the general therapist effects in a wide range of clinical settings, little is known about the individual, cross-situational, and therapy-nonspecific variables that impact on the differential effectiveness of clinicians. The current study is a systematic review of the evidence relating to the influence of therapist's subjective characteristics on outcomes of psychodynamic psychotherapies., Method: A multistage and systematic search of articles published between 1987 and 2017 identified 30 relevant studies, which were organized into 6 areas according to the specific therapist's variable considered., Results: Therapists' interpersonal functioning and skills showed the strongest evidence of a direct effect on treatment outcomes. Furthermore, there were preliminary evidence that therapists' attachment styles, their interpersonal history with caregivers, and their self-concept might affect outcomes through interaction effects with other constructs, such as technical interventions, patient's pathology, and therapeutic alliance. The high variability between studies on therapists' overall reflective or introspective abilities and personality characteristics suggested the need for more systematic research in these areas, whereas therapists' values and attitudes showed small effects on therapeutic outcome., Conclusions: The present review clarifies how a deep examination of the contribution of therapists' subjective characteristics can help elucidate the complex association between relational and technical factors related to the outcome of psychodynamic treatments., (Copyright © 2017 John Wiley & Sons, Ltd.)

Mentalization, operationalized as reflective functioning (RF), can play a crucial role in the psychological mechanisms underlying personality functioning. This study aimed to: (a) study the association between RF, personality disorders (cluster level) and functioning; (b) investigate whether RF and personality functioning are influenced by (secure vs. insecure) attachment; and (c) explore the potential mediating effect of RF on the relationship between attachment and personality functioning. The Shedler-Westen Assessment Procedure (SWAP-200) was used to assess personality disorders and levels of psychological functioning in a clinical sample (N = 88). Attachment and RF were evaluated with the Adult Attachment Interview (AAI) and Reflective Functioning Scale (RFS). Findings showed that RF had significant negative associations with cluster A and B personality disorders, and a significant positive association with psychological functioning. Moreover, levels of RF and personality functioning were influenced by attachment patterns. Finally, RF completely mediated the relationship between (secure/insecure) attachment and adaptive psychological features, and thus accounted for differences in overall personality functioning. Lack of mentalization seemed strongly associated with vulnerabilities in personality functioning, especially in patients with cluster A and B personality disorders. These findings provide support for the development of therapeutic interventions to improve patients' RF., (Copyright © 2017 Elsevier B.V. All rights reserved.)

An existing technique for passive bottom-loss estimation from natural marine surface noise (generated by waves and wind) is adapted to use noise generated by ships. The original approach-based on beamforming of the noise field recorded by a vertical line array of hydrophones-is retained; however, additional processing is needed in order for the field generated by a passing ship to show features that are similar to those of the natural surface-noise field. A necessary requisite is that the ship position, relative to the array, varies over as wide a range of steering angles as possible, ideally passing directly over the array to ensure coverage of the steepest angles. The methodology is illustrated through simulation and applied to data from a field experiment conducted offshore of San Diego, CA in 2009.

Narcissistic personality disorder (NPD) is one of the most challenging clinical syndromes to treat in psychotherapy, especially due to the difficulties of establishing a good enough therapist-patient relationship. Countertransference responses to NPD can be particularly intense, frustrating, and difficult to manage, as is often reported in the clinical literature though not clearly supported empirically. The aims of this study were to (a) investigate the relationship between patients' NPD and therapists' responses; (b) examine the associations between patient, clinician, therapy variables and clinicians' reactions during treatment of NPD patients; and (c) provide an empirically derived portrait of countertransference with NPD. A sample of psychiatrists and clinical psychologists (N = 67) completed the Therapist Response Questionnaire to identify patterns of countertransference, the Shedler-Westen Assessment Procedure-200, and the Global Assessment of Functioning Scale to assess the personality pathology and psychosocial functioning of a patient in their care. The results showed that NPD was positively associated with hostile/angry, criticized/devalued, helpless/inadequate, and disengaged countertransference and negatively associated with therapists' positive response, regardless of patients' personality and psychosocial functioning. NPD patients with stronger traits of cluster B personality pathology tended to elicit more negative and heterogeneous countertransference reactions than NPD patients without these features. The countertransference patterns with NPD patients were not strongly influenced by the variables of clinicians and therapy, with the exception of clinical experience. Overall, the portrait of therapists' reactions to NPD provided a clinically nuanced and empirically founded description strongly resembling theoretical-clinical accounts. The therapeutic implications of these findings were discussed. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

This article reviews the theoretical and empirical contributions of Blatt's two-polarities model of personality development and psychopathology to the second edition of the Psychodynamic Diagnostic Manual (PDM-2). First, we briefly provide an overview of the manual's main features and describe the guiding principles of the revision process. We then discuss in more detail how Blatt's model, which is focused on the dialectic interaction between anaclitic-introjective and relatedness vs self-definition dimensions in both normal and disrupted personality development, increases the PDM-2's theoretical and empirical comprehensiveness and clinical utility, especially concerning the classification and assessment of personality and overall mental functioning in adult populations. Finally, we address the implications for the therapeutic process, showing how anaclitic and introjective patients may be differentially responsive to different psychodynamic techniques ( e.g. , supportive or expressive interventions). Taken together, these considerations demonstrate the importance of a more theory-driven and empirically informed diagnostic system that embraces, in accordance with Sidney Blatt's empirically supported and psychoanalytically-oriented ideas, the complexities of human experience (both normal and pathological) and captures the subjective and underlying dynamics of psychological symptoms and syndromes., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest., (©Copyright V. Lingiardi et al., 2017.)

An NMR HSQC method has recently been proposed for the quantitative determination of the mono- and disaccharide subunits of heparin and low molecular weight heparins (LMWH). The focus of the current study was the validation of this procedure to make the 2D-NMR method suitable for pharmaceutical quality control applications. Pre-validation work investigated the effects of several experimental parameters to assess robustness and to optimize critical factors. Important experimental parameters were pulse sequence selection, equilibration interval between pulse trains and temperature. These observations were needed so that the NMR method was sufficiently understood to enable continuous improvement. A standard validation study on heparin then examined linearity, repeatability, intermediate precision and limits of detection and quantitation; selected validation parameters were also determined for LMWH., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Accurate modeling of acoustic propagation in the ocean waveguide is important to SONAR-performance prediction. Particularly in shallow waters, a crucial contribution to the total transmission loss is the bottom refection loss, which can be estimated passively by beamforming the natural surface-noise acoustic field recorded by a vertical line array of hydrophones. However, the performance in this task of arrays below 2 m of length is problematic for frequencies below 10 kHz It is shown in this paper that, when the data are free of interference from sources other than wind and wave surface noise, data from a shorter array can be used to approximate the coherence function of a longer array. This improves the angular resolution of the estimated bottom loss, often making use of data at frequencies above the array design frequency. Application to simulated and experimental data shows that the technique, rigorously justified for a halfspace bottom, is effective also on more complex bottom types. Dispensing with active sources, small autonomous underwater vehicles equipped with short arrays can be envisioned as compact, efficient seabed-characterization systems. The proposed technique is shown to improve significantly the reflection-loss estimate of an array that would be a candidate for such application.

Functionalized carbon nanotubes (CNTs) have shown great promise in several biomedical contexts, spanning from drug delivery to tissue regeneration. Thanks to their unique size-related properties, single-walled CNTs (SWCNTs) are particularly interesting in these fields. However, their use in nanomedicine requires a clear demonstration of their safety in terms of tissue damage, toxicity and pro-inflammatory response. Thus, a better understanding of the cytotoxicity mechanisms, the cellular interactions and the effects that these materials have on cell survival and on biological membranes is an important first step for an appropriate assessment of their biocompatibility. In this study we show how bovine serum albumin (BSA) is able to generate homogeneous and stable dispersions of SWCNTs (BSA-CNTs), suggesting their possible use in the biomedical field. On the other hand, this study wishes to shed more light on the impact and the interactions of protein-stabilized SWCNTs with two different cell types exploiting multidisciplinary techniques. We show that BSA-CNTs are efficiently taken up by cells. We also attempt to describe the effect that the interaction with cells has on the dielectric characteristics of the plasma membrane and ion flux using electrorotation. We then focus on the BSA-CNTs' acute toxicity using different cellular models. The novel aspect of this work is the evaluation of the membrane alterations that have been poorly investigated to date.

Among the natural histone deacetylase inhibitors (HDACi), the bicyclic depsipeptide macrolactone FK228 stands out for its unique chemical structure and mechanism of action. In order to expand the chemical diversity, exploiting the FK228 peculiar structure, we have synthesized a collection of 24 simplified novel analogs. A first series consists of bicyclic macrolactones, where the carboxy terminus of the natural compound was substituted by peptidomimetic aminomethylphenylacetic acid derivatives. These analogs, 7a-i, showed submicromolar cytotoxic activity, even though very low inhibitory activity against HDAC enzymes, suggesting that most probably they behave with a mechanism different from the natural compound. One of the most active members in the group, 7g, was evaluated in vivo and exhibited significant antitumor activity. This evidence supports that the activity is unrelated to HDAC inhibition and these compounds represent a novel series of promising active agents. Another analog series consists of monocyclic macrolactones, 9a-c and 10a-d which lack the disulfide bridge and bear the protected sulfur on the linear external chain; they showed similar cytotoxic activities compared to the natural compound, but proved to be very sensitive to the nature of the sulfur protection. In fact, when the sulfur was protected by an 1-octanoyl residue, like in 9b, the product displayed a one digit nanomolar activity. The results provide evidence that our approach may be followed to develop novel series of FK228 analogs., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The use of platinum-based chemotherapeutic drugs in cancer therapy still suffers from severe disadvantages, such as lack of appropriate selectivity for tumor tissues and insurgence of multi-drug resistance. Moreover, drug efficacy can be attenuated by several mechanisms such as premature drug inactivation, reduced drug uptake inside cells and increased drug efflux once internalized. The use of functionalized carbon nanotubes (CNTs) as chemotherapeutic drug delivery systems is a promising strategy to overcome such limitations due to their ability to enhance cellular internalization of poorly permeable drugs and thus increase the drug bioavailability at the diseased site, compared to the free drug. Furthermore, the possibility to encapsulate agents in the nanotubes' inner cavity can protect the drug from early inactivation and their external functionalizable surface is useful for selective targeting. In this study, a hydrophobic platinum(IV) complex was encapsulated within the inner space of two different diameter functionalized multi-walled CNTs (Pt(IV)@CNTs). The behavior of the complexes, compared to the free drug, was investigated on both HeLa human cancer cells and RAW 264.7 murine macrophages. Both CNT samples efficiently induced cell death in HeLa cancer cells 72 hours after the end of exposure to CNTs. Although the larger diameter CNTs were more cytotoxic on HeLa cells compared to both the free drug and the smaller diameter nanotubes, the latter allowed a prolonged release of the encapsulated drug, thus increasing its anticancer efficacy. In contrast, both Pt(IV)@CNT constructs were poorly cytotoxic on macrophages and induced negligible cell activation and no pro-inflammatory cytokine production. Both CNT samples were efficiently internalized by the two types of cells, as demonstrated by transmission electron microscopy observations and flow cytometry analysis. Finally, the platinum levels found in the cells after Pt(IV)@CNT exposure demonstrate that they can promote drug accumulation inside cells in comparison with treatment with the free complex. To conclude, our study shows that CNTs are promising nanocarriers to improve the accumulation of a chemotherapeutic drug and its slow release inside tumor cells, by tuning the CNT diameter, without inducing a high inflammatory response.

The seabed reflection loss (shortly "bottom loss") is an important quantity for predicting transmission loss in the ocean. A recent passive technique for estimating the bottom loss as a function of frequency and grazing angle exploits marine ambient noise (originating at the surface from breaking waves, wind, and rain) as an acoustic source. Conventional beamforming of the noise field at a vertical line array of hydrophones is a fundamental step in this technique, and the beamformer resolution in grazing angle affects the quality of the estimated bottom loss. Implementation of this technique with short arrays can be hindered by their inherently poor angular resolution. This paper presents a derivation of the bottom reflection coefficient from the ambient-noise spatial coherence function, and a technique based on this derivation for obtaining higher angular resolution bottom-loss estimates. The technique, which exploits the (approximate) spatial stationarity of the ambient-noise spatial coherence function, is demonstrated on both simulated and experimental data.

This paper considers extrapolation of the vertical coherence of surface-generated oceanic ambient noise to simulate measurements made on a longer sensor array. The extrapolation method consists of projecting the noise coherence measured with a limited aperture array into the domain spanned by prolate spheroidal wave functions, which are an orthogonal basis defined by array parameters and the noise frequency. Using simulated data corresponding to selected multi-layered seabeds as ground truth, the performance of the extrapolation method is explored. Application of the technique is also demonstrated on experimental data.

The first use of statistical correlation spectroscopy to extract chemical information from 2D-HSQC spectra, termed HSQC correlation spectroscopy (HSQCcos), is reported. HSQCcos is illustrated using heparin, a heterogeneous polysaccharide, whose diverse composition causes signals in HSQC spectra to disperse. HSQCcos has been used to probe the chain modifications that cause this effect and reveals hitherto unreported structural details. An interesting finding was that the signal for position 2 of trisulfated glucosamine [N-, 3-O-, and 6-O-sulfated] (A*) is bifurcated, owing to the presence of A* residues in both the "normal" antithrombin binding site and also at the nonreducing end of the molecule, which is reported in intact heparin for the first time. The method was also applied to investigating the environment around other rare sequences/disaccharides, suggesting that the disaccharide; 2-O-sulfated iduronic acid linked to 6-O-sulfated N-glucosamine, which contains a free amine at position 2, is adjacent to the heparin linkage region. HSQCcos can extract chemically related signals from information-rich spectra obtained from complex mixtures such as heparin.

Predicting transmission loss in the ocean often strongly depends on the bottom loss. Bottom loss can be estimated using ocean noise and vertical array beam-forming [Harrison and Simons, J. Acoust. Soc. Am. 112, 1377-1389 (2002)]. With finite length arrays, the bottom loss estimate using this method can be smoothed due to beam widths. This paper describes how the noise coherence function can be synthetically expanded, which is similar to extending the length of an array. A full wave ocean noise model is used to demonstrate, in simulation, how this leads to improvements in the resolution of bottom loss estimates.

Risks of contamination of the major clinical anticoagulant heparin can arise from deliberate adulteration with unnatural or natural polysaccharides, including heparin from other animal sources, other natural products, or artifacts of manufacture, and these can escape detection by conventional means. Currently, there is no generally applicable, objective test recommended by regulators that can detect these in pharmaceutical heparin, and this continues to leave heparin exposed to contamination risks. Two-dimensional correlation spectroscopic-filtering with iterative random sampling (2D-COS-firs) is reported. It employs a difference covariance matrix with iterative random sampling, and is capable of revealing contamination in pharmaceutical heparin to a high level of sensitivity irrespective of the nature of those features. The technique is suitable to any situation in which a comparison of a single entity to a family of heterogeneous entities, particularly natural products and biosimilars, needs to be made, and will find application in pharmaceutical monitoring, manufacturing quality control, materials science, biotechnology, and metabolomic investigations.

Eight conjugates of a novel camptothecin derivative (Namitecan, NMT) with RGD peptides have been synthesized and biologically evaluated. This study focused on factors that optimize the drug linkage to the transport vector. The different linkages investigated consist of heterofunctional glycol fragments and a lysosomally cleavable peptide. The linkage length and conformation were systematically modified with the purpose to understand their effect on receptor affinity, systemic stability, cytotoxicity, and solubility of the corresponding conjugates. Among the new conjugates prepared, C6 and C7 showed high receptor affinity and tumor cell adhesion, acceptable stability in murine blood, and high cytotoxic activity (IC₅₀ = 8 nM). The rationale, synthetic strategy, and preliminary biological results will be presented.

In the critically ill, acute renal failure (ARF) and "Multiple Organ Dysfunction Syndrome" (MODS) can be associated with significant modifications of many pharmacokinetic parameters, such as protein binding, volume of distribution and total body clearance. The start of renal replacement therapy (RRT) represents an additional variable to take in consideration for drug-dosing adjustments. Drugs significantly eliminated by the kidney are likely to be removed during RRT and a supplemental dose or further dosing adjustments are required if extracorporeal clearance is more than 25-30% of total body clearance. The impact of RRT on plasma drug concentrations can be substantially different in relation to the type of treatment (diffusive, convective or both), membrane characteristics (low-flux or high-flux), filter surface area and prescribed dialysis dose. The molecular weight cut-offs of high-flux membrane are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the drugs most commonly used in the critically ill undergoing continuous renal replacement therapy (CRRT). However, diffusive clearance could be significantly lower than convective clearance for drugs in the middle molecular weight range. In any case, the extracorporeal clearances report-ed with the use of high-volume CRRT (>50-60 L/2 h) are often surprisingly elevated and can lead to drug underdosing in clinical conditions where adequate antibiotic treatment is essential.

Acute renal failure (ARF) develops in 1-30% of patients who undergo cardiac surgery and is associated with a high mortality rate (15-30%). Several risk factors (pre- and intra-operative) for ARF have been identified. Pre-operative factors are strictly related to cardiovascular disease, advanced age and baseline renal dysfunction, while intra-operative factors are linked with the type of cardiac surgery, the duration of cardiopulmonary bypass and aortic cross-clamping. These factors provide an opportunity to quantify the risk of ARF based on pre-operative data, and for this purpose a clinical score to predict post-operative ARF has recently been developed. Moreover, this score could allow the identification of those patients who may take advantage of preventive strategies. Mortality in patients who develop severe ARF requiring dialysis is particularly high (50-80%). Therefore, an early diagnosis of ARF and a timely and aggressive renal replacement therapy could improve the outcome.

A series of six arginine-glycine-aspartate (RGD) cyclopeptide analogues containing a C(alpha)-di- or trifluoromethylamino acid (alpha-Dfm or alpha-TfmAaa) at different positions of the ring were synthesized. All peptides were obtained in two diastereomeric forms, which were separated by HPLC. In vitro biological tests of the new cyclopeptides P were carried out in comparison with their corresponding cyclopeptides R lacking the alpha-fluoromethyl group. Five out of the six compounds P-I (containing (S)-alpha-Tfm-Aaa) showed activities in the nanomolar range, while the P-II compounds (containing (R)-alpha-Tfm-Aaa) were much less active or totally inactive. Only cyclo[RGDf-(S)-alphaTfmV] (P1-I) was found to be significantly more active than its model compound cyclo(RGDfV) (R1). The three-dimensional structure in water and DMSO was determined by NMR techniques and molecular dynamics (MD) calculations, but it was not possible to highlight significant differences in the backbone conformation of the peptides examined. Significant interproton distances, derived from nuclear Overhauser effect (NOE) experiments, were used to determine the absolute configuration of the side chains.

Background: The ongoing necessity for systemic heparinization is a well-known disadvantage of continuous renal replacement therapies (CRRT), and alternative methods of anticoagulation may be required. Our aim was to evaluate, in patients with a high risk of bleeding, the possibility of an acceptable filter life with non-anticoagulation CRRT and, in case of early filter failure, the efficacy and safety of bedside monitored regional anticoagulation with heparin and protamine., Methods: Fifty-nine patients underwent CRRT for acute renal failure (ARF) following cardiac surgery. Patients who fulfilled one of the following criteria were selected for non-anticoagulation CRRT: spontaneous bleeding, aPTT > 45 sec, thrombocytopenia and recent surgery (< 48 hr). Filter life < 24 hr without anticoagulation was the cut-off point for starting the regional anticoagulation CRRT. Heparin was infused pre-filter and protamine post-filter at an initial ratio of 1 mg protamine:100 IU heparin. The ratio was adjusted to achieve a patient aPTT < 45 sec and a circuit > 55 sec., Results: Twenty-two (37.3%) patients had been selected for non-anticoagulation. Of them, 12 patients continued to receive non-anticoagulation (filter life: 38.3 +/- 30.5 hr) while 10 switched to regional anticoagulation (filter life: 38.6 +/- 25 hr). During regional anticoagulation no statistical difference was found between baseline aPTT (36.7 +/- 6.4 sec) and patient aPTT (41.5 +/- 12.6 sec) while circuit aPTT (77.7 +/- 43.3 sec) was significantly higher than patient aPTT (p < 0.0001). The probabilities of the circuits remaining free from clotting after 24, 48 and 72 hr were: a) non-anticoagulation: 55.5%, 30.1% and 16.6%, b) regional anticoagulation: 76.2%, 39.6% and 19.8%. There was no rebound anticoagulation observed after regional anticoagulation CRRT ended., Conclusions: Non-anticoagulation CRRT allowed an adequate filter life in most patients with a high risk of bleeding for prolonged aPTT and/or thrombocytopenia. Despite concerns regarding the need for careful monitoring, regional anticoagulation with heparin and protamine can be considered as a safe and valid alternative when non-anticoagulation is unsuitable because of early filter failure.

N(alpha)-Protected alpha-amino acid bromides were easily generated in situ with 1-bromo-N,N-2-trimethyl-1-propenylamine from the corresponding amino acids under very mild conditions. o-Nbs and the azido moieties proved to be compatible with these overactivated halides and were successfully applied in difficult peptide bond formations. N-Deprotection methods and the total step-by-step solution synthesis of a peptide containing up to seven consecutive L-(alphaMe)Valine residues are also reported. The assembly of this homopeptide was achieved in a short time and in very high yields by the azido/bromide system in a single repetitive operation.