Holistic evaluation of the environmental impacts of shipping in the sensitive region of Ria de Aveiro.

Shipping activity can be a substantial source of pollution and impact on the environment, including air, water and ecosystems, as well as adverse health and climatic effects. Due to the distribution of maritime transport activity routes in the EU, a large portion of the population is exposed to shipping pollution throughout Europe. The ongoing European project EMERGE aims to investigate and quantify these impacts over Europe, and in more detail, in specific case studies regions. The Aveiro lagoon region in Portugal is one of these case studies. This region is a Natura 2000 area, and also includes a medium-sized port. Both air quality and water modelling tools were applied to assess the impact of the emissions and discharges from shipping (to air and water) in the region in 2018. Additionally, ecotoxicological impacts were determined by bioassays to evaluate the impact of scrubber-water discharges on the most sensitive stages of marine invertebrates, and on the post-exposure feeding inhibition of crustacean and bivalve species. The results show that there was a substantial increase in atmospheric pollutant concentrations due to emissions attributed to shipping, which was most relevant for NOx and SO2 (up to a 30 % shipping contribution). There was no significant degradation of the water quality, mainly as the ships operating in this area did not have scrubber equipment. The ecotoxicological tests were performed with three samples of scrubber water, including one artificial sample and two samples collected on-board ships. If scrubber water would have been discharged in this area, the results indicated that the majority of the tested species would be exposed to lowest observed effect concentration (LOEC) for the different scrubber-water samples, as well as to substantial concentrations of metals, PAHs, and alkylated PAHs.

Prognostic impact of pretreatment cell-free DNA concentration in newly diagnosed peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell-free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre-treatment cfDNA was strongly associated with clinical risk factors and was identified as a superior predictor for shorter progression-free survival in multivariable analysis, outweighing canonical risk parameters. Furthermore, we identified a cfDNA value above which survival worsens. In conclusion, pre-treatment cfDNA concentration represents an easily usable predictive biomarker that is highly associated with survival of PTCL patients.

Expanding the product portfolio of carbon dioxide and hydrogen-based gas fermentation with an evolved strain of Clostridium carboxidivorans.

CO2:H2-based gas fermentation with acetogenic Clostridium species are at an early stage of development. This work exploited the Adaptive Laboratory Evolution technique to improve the growth of C. carboxidivorans P7 on CO2 and H2. An adapted strain with decreased growth lag phase and improved biomass production was obtained. Genomic analysis revealed a conserved frameshift mutation in the catalytic subunit of the hexameric hydrogenase gene. The resulted truncated protein variant, most likely lacking its functionality, suggests that other hydrogenases might be more efficient for H2-based growth of this strain. Furthermore, the adapted strain generated hexanol as primary fermentation product. For the first time, hexanol was produced directly from CO2:H2 blend, achieving the highest maximum productivity reported so far via gas fermentation. Traces of valerate, pentanol, eptanol and octanol were observed in the fermentation broth. The adapted strain shows promising to enrich the product spectrum targetable by future gas fermentation processes.

Strength-based methods - a narrative review and comparative multilevel meta-analysis of positive interventions in clinical settings.

OBJECTIVE: In psychotherapy, strength-based methods (SBM) represent efforts to build on patients' strengths while addressing the deficits and challenges that led them to come to therapy. SBM are incorporated to some extent in all major psychotherapy approaches, but data on their unique contribution to psychotherapy efficacy is scarce. METHODS: First, we conducted a systematic review and narrative synthesis of eight process-outcome psychotherapy studies that investigated in-session SBM and their relation to immediate outcomes. Second, we conducted a systematic review and multilevel comparative meta-analysis contrasting strength-based bona fide psychotherapy vs. other bona fide psychotherapy at post-treatment (57 effect sizes nested in 9 trials). RESULTS: Despite their methodological variability, the pattern of results in the process-outcome studies was generally positive, such that SBM were linked with more favorable immediate, session-level patient outcomes. The comparative meta-analysis found an overall weighted average effect size of g = 0.17 (95% CIs [0.03, 0.31], p < .01) indicating a small but significant effect in favor of strength-based bona fide psychotherapies. There was non-significant heterogeneity among the effect sizes (Q(56) = 69.1, p = .11; I2 = 19%, CI [16%, 22%]). CONCLUSION: Our findings suggest that SBMs may not be a trivial by-product of treatment progress and may provide a unique contribution to psychotherapy outcomes. Thus, we recommend integration of SBM to clinical training and practice across treatment models.

Distinguishable DNA methylation defines a cardiac-specific epigenetic clock.

BACKGROUND: The present study investigates whether epigenetic differences emerge in the heart of patients undergoing cardiac surgery for an aortic valvular replacement (AVR) or coronary artery bypass graft (CABG). An algorithm is also established to determine how the pathophysiological condition might influence the human biological cardiac age. RESULTS: Blood samples and cardiac auricles were collected from patients who underwent cardiac procedures: 94 AVR and 289 CABG. The CpGs from three independent blood-derived biological clocks were selected to design a new blood- and the first cardiac-specific clocks. Specifically, 31 CpGs from six age-related genes, ELOVL2, EDARADD, ITGA2B, ASPA, PDE4C, and FHL2, were used to construct the tissue-tailored clocks. The best-fitting variables were combined to define new cardiac- and blood-tailored clocks validated through neural network analysis and elastic regression. In addition, telomere length (TL) was measured by qPCR. These new methods revealed a similarity between chronological and biological age in the blood and heart; the average TL was significantly higher in the heart than in the blood. In addition, the cardiac clock discriminated well between AVR and CABG and was sensitive to cardiovascular risk factors such as obesity and smoking. Moreover, the cardiac-specific clock identified an AVR patient's subgroup whose accelerated bioage correlated with the altered ventricular parameters, including left ventricular diastolic and systolic volume. CONCLUSION: This study reports on applying a method to evaluate the cardiac biological age revealing epigenetic features that separate subgroups of AVR and CABG.

Kounis syndrome: an underestimated emergency.

Summary: Background. Kounis syndrome (KS) is defined as a rare cause of an acute coronary syndrome associated with systemic allergic reactions. To establish the prevalence of KS among the patients with diagnosis of anaphylaxis, we described clinical features, cardiological and allergological outcomes of patients evaluated in our allergy outpatient clinic. Methods. A retrospective study was carried out in the Allergy Unit of Novara hospital, from January 2008 to March 2020. Skin tests and in vitro tests were performed with suspected etiological agents. Results. We found 9 adults with KS (2%) out of 444 subjects who had experienced anaphylactic reactions (4/9 to Hymenoptera stings, 5/9 to drugs). Conclusions. The present study highlights the importance of suspicion of KS that appears not so uncommon in patients with anaphylaxis. KS seems to be a rare disease because unrecognized in diagnosis of anaphylaxis.

The relative efficacy of bona fide cognitive behavioral therapy and applied relaxation for generalized anxiety disorder at follow-up: A longitudinal multilevel meta-analysis.

OBJECTIVE: This meta-analysis examined the relative efficacy of bona fide psychotherapy conditions in generalized anxiety disorder (GAD) from posttreatment to follow-up in adults. METHODS: Omnibus tests of relative efficacy across bona fide psychotherapies for primary and secondary outcomes were conducted. Longitudinal multilevel subgroup analyses investigated, (a) applied relaxation versus cognitive behavioral therapy (CBT) without applied relaxation and (b) well-established CBT versus augmented integrative CBT. RESULTS: In total, 54 repeated effect sizes nested in 23 studies were included in this meta-analysis. Omnibus test of relative efficacy indicated no significant differences among the bona fide psychotherapy contrasts in primary and some differences in secondary outcomes. When contrasting applied relaxation with CBT without applied relaxation, negligible relative efficacy differences were found at each assessment time. There were small efficacy differences in favor of augmented integrative CBT in comparison to well-established CBT. CONCLUSION: Small relative efficacy differences were found between bona fide psychotherapies in GAD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Production and persistence of specific antibodies in COVID-19 patients with hematologic malignancies: role of rituximab.

The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.

The role of radiotherapy in Kimura's disease: a multicenter systematic review of literature.

OBJECTIVE: From a clinical point of view, Kimura's disease is typically characterized by a subcutaneous mass occurring predominantly in the head and neck region. It occurs predominantly in young men of Asian descent, with a peak incidence in the second and third decades of life. However, KD has been also reported in other ethnic groups and in children. The most frequently used local treatments are surgical excision, radiotherapy, and surgical excision followed by radiotherapy. The aim of this multicenter systematic review is to highlight the available literature evidence about the outcome of RT in this setting. MATERIALS AND METHODS: A systematic review of any relevant literature in the principal medical databases, such as PubMed, Scopus and Cochrane library, was conducted. The inclusion criteria were original articles specifically reporting about KD and RT, including both prospective and retrospective studies. RESULTS: We were able to identify 11 studies, published from 1989 to 2021, eligible for inclusion in this review. Overall, data on 124 patients were recorded and are presented in this systematic review. The median recurrence rate, considering all patients, was 11% (ranging from 0% to 41.2%). In seven out of 11 studies, the relapse rate was less than 20%. Moreover, the relapse rate was 0% in four studies. CONCLUSIONS: The results of this multicenter systematic literature review show that evidence on RT of KD is limited and derives only from retrospective studies. In this setting RT seems to be well-tolerated and able to produce very high response rates in unresected lesions and reasonable results in terms of local control both as an exclusive and adjuvant treatment.

Examining therapist effects in the alliance-outcome relationship: A multilevel meta-analysis.

OBJECTIVE: The relationship between the therapeutic alliance and outcome has been supported consistently over time. More recently, studies have examined therapist effects in the alliance-outcome relationship and came up with somewhat mixed findings. The purpose of this study was to replicate and extend previous meta-analytic work using a much larger data set, permitting not only the verification of the overall impact of the therapists' contribution but, at the same time, controlling for several potential covariates effecting this relationship. METHOD: We conducted two- and three-level mixed-effects meta-analyses (k = 152; 827 total effect sizes) to examine the significance of several potential moderators of the alliance-outcome correlation. These moderators included (a) Patient-Therapist Ratio (PTR; Patient N divided by therapist N to test therapist effects), (b) Alliance and Outcome Rater's contribution (patient, therapist, observer, and other), (c) Alliance Measures, (d) Research Design (RCT, Other) and (e) Personality Disorder. RESULTS: The PTR, an index of the therapist's contribution to the alliance, was a significant moderator of the alliance-outcome correlation in both the two- and three-level models. When several potential confounds were simultaneously tested in a three-level multipredictor metaregression, including rater of alliance and outcome, research design, alliance measure, and personality disorder, PTR remained a significant moderator of the alliance-outcome correlation. CONCLUSION: Replicating and extending previous research, this study supported the significance of therapists' impact in the alliance-outcome relationship. These results remained significant even when, using three-level metaregressions, several potential covariates were simultaneously controlled. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Surgical wound infection prevention using topical negative pressure therapy on closed abdominal incisions - the 'SWIPE IT' randomized clinical trial.

BACKGROUND: Surgical site infections (SSIs) are the most common cause of healthcare-associated infections in surgical patients. It is unclear whether incisional negative pressure wound therapy (NPWT) can reduce the risk of SSIs in patients after open abdominal surgery. METHODS: A prospective, non-blinded multi-centre randomized controlled trial (RCT) was performed to evaluate the incidence of SSI post-laparotomy using incisional NPWT compared with a standard dressing. The primary outcome was the rate of superficial SSI. RESULTS: A total of 124 patients (61 patients in the NPWT arm and 63 patients in the control arm) were included. One hundred and nine (87.9%) patients underwent colorectal surgery; 61 patients (49.2%) had emergency surgery. There were more superficial SSIs in the control group than in the NPWT group, although not statistically significant (20.6% vs 9.8%, P=0.1). Upon multiple logistic regression analysis, control dressings were associated with increased risk of superficial SSI although again, not statistically significant (odds ratio (OR) 2.41, 95% confidence interval (CI) 0.81-7.17, P=0.11). There was no superficial non-SSI related wound dehiscence in the NPWT group compared with 9.5% in the control group (P=0.03). There was no difference in postoperative complications (P=0.15), nor in other wound complications (P=0.79). CONCLUSION: NPWT was not associated with decreased superficial SSI in this RCT. However, there was a statistically significant reduction in superficial wound dehiscence with NWPT dressings. The results of this study should be included in meta-analyses for better evaluation of NPWT on closed abdominal incisions.

The reciprocal relationship between alliance and early treatment symptoms: A two-stage individual participant data meta-analysis.

OBJECTIVE: Even though the early alliance has been shown to robustly predict posttreatment outcomes, the question whether alliance leads to symptom reduction or symptom reduction leads to a better alliance remains unresolved. To better understand the relation between alliance and symptoms early in therapy, we meta-analyzed the lagged session-by-session within-patient effects of alliance and symptoms from Sessions 1 to 7. METHOD: We applied a 2-stage individual participant data meta-analytic approach. Based on the data sets of 17 primary studies from 9 countries that comprised 5,350 participants, we first calculated standardized session-by-session within-patient coefficients. Second, we meta-analyzed these coefficients by using random-effects models to calculate omnibus effects across the studies. RESULTS: In line with previous meta-analyses, we found that early alliance predicted posttreatment outcome. We identified significant reciprocal within-patient effects between alliance and symptoms within the first 7 sessions. Cross-level interactions indicated that higher alliances and lower symptoms positively impacted the relation between alliance and symptoms in the subsequent session. CONCLUSION: The findings provide empirical evidence that in the early phase of therapy, symptoms and alliance were reciprocally related to one other, often resulting in a positive upward spiral of higher alliance/lower symptoms that predicted higher alliances/lower symptoms in the subsequent sessions. Two-stage individual participant data meta-analyses have the potential to move the field forward by generating and interlinking well-replicable process-based knowledge. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The predictive validity of the progress assessment, a clinician administered instrument for use in measurement-based care for substance use disorders.

We tested the predictive validity of the Progress Assessment (PA), a brief counselor administered tool for use in measurement-based care for substance use disorders. The PA includes 5 items assessing relapse risk and 5 items assessing factors protective against relapse. Data were drawn from a completed study of continuing care for cocaine dependence (McKay et al., 2013) and includes 12 months of follow-up on158 participants (76% male) who received brief telephone or face-to-face sessions. Each session began with the administration of the PA, followed by cognitive-behavioral counseling tied to the results of the PA and anticipated risky situations. Outcome was assessed via urine toxicology every 3 months. As administered in an effectiveness trial, average PA risk and protective scales within each 3-month segment of the study predicted urine toxicology results at the end of that period, with higher risk scores and lower protective scores predicting greater rates of cocaine positive urine drug screens. PA scores did not predict dropout from continuing care participation. The 10-item PA shows promise as a pragmatic clinical tool for ongoing monitoring during continuing care for substance dependence.

Assessing the alliance-outcome association adjusted for patient characteristics and treatment processes: A meta-analytic summary of direct comparisons.

The alliance is widely recognized as a robust predictor of posttreatment outcomes. However, there is a debate regarding whether the alliance is an epiphenomenon of intake characteristics and/or treatment processes occurring over the course of treatment. This meta-analysis aimed to synthesize the evidence on this issue. We identified 125 effect sizes in 60 independent samples (6,061 participants) of studies that reported alliance-outcome correlations as well as parallel intake or process characteristics. We examined the impact of these potential confounds on the alliance-outcome correlations. We meta-analyzed the studies estimates by computing omnibus effects models as well as multivariate models. We identified 3 variable types that were used to adjust the alliance-outcome correlations: (a) intake characteristics (k = 35); (b) simultaneous processes, such as adherence or competence (k = 13); and (c) both intake and simultaneous processes (k = 24). We found moderate alliance-outcome correlations with or without adjustments for intake and simultaneous processes (range from r = .23 to r = .31). Our results provide robust empirical evidence for the assertion that the alliance-outcome association is an independent process-based factor. Findings suggest that alliance is positively related to outcome above and beyond the studied patient intake characteristics and treatment processes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

First salvage treatment with bendamustine and brentuximab vedotin in Hodgkin lymphoma: a phase 2 study of the Fondazione Italiana Linfomi.

Effective salvage options inducing high complete metabolic response (CMR) rates without significant toxicity are needed for Hodgkin lymphoma (HL) patients failing induction treatment and who are candidate to autologous stem cell transplantation (ASCT). Brentuximab vedotin (BV) and bendamustine are active monotherapies in the relapsed/refractory setting and their combination (the BBV regimen) possibly enhances their activity. This single-arm multicenter phase 2 study investigated the efficacy and safety of BBV as first salvage therapy in 40 patients with relapsed/refractory HL. Thirty-eight patients were evaluable for efficacy: 30 (78.9%) had a CMR and 2 (5.3%) a partial response, leading to an overall response rate (ORR) of 84.2%. The ORR in the primary refractory subset was 75.0%, among relapsed patients it was 94.4%. Thirty-five patients could mobilize peripheral blood stem cells and 33 underwent ASCT. At a median follow-up of 23 months, the estimated 3-year overall survival and progression-free survival are 88.1% and 67.3%. During therapy, only 3 grade IV cases of neutropenia occurred and resolved within a week. No grade 4 extrahematologic toxicities were reported; skin reactions were however rather frequent (65%). These results suggest that the BBV regimen exhibits promising efficacy and a manageable toxicity in a challenging subpopulation of HL patients.

Antimicrobial effect of a local release system containing metronidazole against a Porphyromonas gingivalis biofilm.

The aim of this study was to evaluate a semi-solid system containing metronidazole (MDZ) in presence of challenging conditions for drug release, as well its antimicrobial effect against Porphyromonas gingivalis biofilm. Biofilms grown in culture medium were exposed to a formulation containing MDZ or its vehicle. After 24, 48, and 72 h, biofilm viability were analyzed while MDZ was quantified in culture medium and buffer solution (control). MDZ formulation reduced bacterial viability when compared to control groups. The vehicle formulation also affected bacterial viability in relation to control at all periods. Culture medium impaired MDZ release compared to buffer solution at 24 h. The semi-solid system reported herein is able to release MDZ and maintain its levels at concentrations that control viability of P. gingivalis in 1- to 3-day-old biofilms.

Environmental benchmarks based on ecotoxicological assessment with planktonic species might not adequately protect benthic assemblages in lotic systems.

Freshwater ecosystems face widespread diffuse and point-source contamination. Species Sensitivity Distributions (SSDs) have been used as a tool to determine chemical concentration benchmarks that represent protective levels for most species in the environment. Here we used a SSD approach to assess on the adequacy of standard planktonic organisms to reflect the response of benthic communities, critically supporting the structure and function of lotic ecosystems. For the purpose, SSDs reflecting non-lethal responses of standard planktonic and selected benthic organisms were built based on EC50 values (collected in the literature or estimated following testing herein) regarding three model contaminants: potassium dichromate (PD), 3,5-dichlorophenol (DCP) and lead chloride (LC). The derived HC5 estimates were discriminatory between chemicals and the uncertainty associated with the estimate was remarkably low. The HC5 estimates with corresponding uncertainty were generally within the same order of magnitude for the three chemicals tested, with better discrimination between chemicals regarding their hazardous potential being achieved for benthic organisms: DCP was clearly less hazardous than PD, but LC tends to be as hazardous as PD and DCP (assuming the confidence interval ranges). Moreover, benthic communities were more sensitive to both DCP and PD, in this later case the HC5 being lower by more than one order of magnitude than that found for planktonic communities; for LC, confidence intervals overlapped, preventing a feasible assumption regarding differential sensitivity of the compared communities. Microphytobenthos was highlighted as the most sensitive group to the three tested chemicals in SSDs covering the benthic compartment, while SSDs with planktonic organisms did not consistently show trends in sensitivity ordering. Overall, our results suggest that protective benchmarks retrieved from SSDs built with the responses of standard planktonic organisms (which are the most commonly used for regulation purposes) do not adequately protect benthic communities.

Survival in HIV-infected patients with lymphoma according to the choice of antiretroviral treatment: an observational multicentre study.

OBJECTIVES: Lymphoproliferative disorders are often observed in HIV-positive patients. Combination antiretroviral treatment (cART) during antineoplastic chemotherapy is beneficial, but little is known about the clinical outcome according to different antiretroviral combinations. The aim of the study was to address this gap in current knowledge. METHODS: A retrospective study was conducted in five large Italian centres for the period from 1998 to 2015; HIV-positive patients diagnosed with lymphoma were included and demographic, clinical and therapeutic variables were recorded and associated with clinical outcomes. Bivariate and multivariate analyses were performed, including Cox proportional hazard models for survival. RESULTS: A total of 399 patients were included in the study. The most common types of lymphoma were diffuse large B-cell lymphoma (DLCLB; n = 164), Hodgkin lymphoma (HL; n = 99) and Burkitt lymphoma (BL; n = 57), followed by plasmablastic lymphoma (PBL; n = 38), T-cell lymphoma (TCL; n = 17), indolent lymphoma (n = 10) and other less common types (n = 14). cART was given to 327 (out of 387 evaluable) patients: in 216 subjects it was protease inhibitor (PI)-based, in 73 it was nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and in 18 it was integrase strand transfer inhibitor (INSTI)-based (the remaining 20 individuals received other regimens). The 5-year overall survival was 57.5% (52.8% for DLCLB, 67.8% for HL, 42.3% for BL, 60.6% for PBL and 64.7% for TCL). PI-based ART compared with other compounds was associated with worse survival in non-Hodgkin lymphoma (NHL) and HL patients combined (P ≤ 0.001) and in NHL patients alone (P < 0.001); grade 3-4 haematological toxicities were more commonly observed in PI-treated individuals. Lymphoma diagnosis in recent years, better immunovirological status, lower lymphoma stage and better prognostic indexes were associated with better survival. CONCLUSIONS: PI-based cART while on chemotherapy was associated with worse overall survival and more frequent haematological complications in HIV-positive patients with lymphoma.

The alliance in adult psychotherapy: A meta-analytic synthesis.

The alliance continues to be one of the most investigated variables related to success in psychotherapy irrespective of theoretical orientation. We define and illustrate the alliance (also conceptualized as therapeutic alliance, helping alliance, or working alliance) and then present a meta-analysis of 295 independent studies that covered more than 30,000 patients (published between 1978 and 2017) for face-to-face and Internet-based psychotherapy. The relation of the alliance and treatment outcome was investigated using a three-level meta-analysis with random-effects restricted maximum-likelihood estimators. The overall alliance-outcome association for face-to-face psychotherapy was r = .278 (95% confidence intervals [.256, .299], p < .0001; equivalent of d = .579). There was heterogeneity among the effect sizes, and 2% of the 295 effect sizes indicated negative correlations. The correlation for Internet-based psychotherapy was approximately the same (viz., r = .275, k = 23). These results confirm the robustness of the positive relation between the alliance and outcome. This relation remains consistent across assessor perspectives, alliance and outcome measures, treatment approaches, patient characteristics, and countries. The article concludes with causality considerations, research limitations, diversity considerations, and therapeutic practices. (PsycINFO Database Record (c) 2018 APA, all rights reserved).