Polygenic Scores and Networks of Psychopathology Symptoms.

Importance: Studies on polygenic risk for psychiatric traits commonly use a disorder-level approach to phenotyping, implicitly considering disorders as homogeneous constructs; however, symptom heterogeneity is ubiquitous, with many possible combinations of symptoms falling under the same disorder umbrella. Focusing on individual symptoms may shed light on the role of polygenic risk in psychopathology. Objective: To determine whether polygenic scores are associated with all symptoms of psychiatric disorders or with a subset of indicators and whether polygenic scores are associated with comorbid phenotypes via specific sets of relevant symptoms. Design, Setting, and Participants: Data from 2 population-based cohort studies were used in this cross-sectional study. Data from children in the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in the primary analysis, and data from children in the Twins Early Development Study (TEDS) were included in confirmatory analyses. Data analysis was conducted from October 2021 to January 2024. Pregnant women based in the Southwest of England due to deliver in 1991 to 1992 were recruited in ALSPAC. Twins born in 1994 to 1996 were recruited in TEDS from population-based records. Participants with available genetic data and whose mothers completed the Short Mood and Feelings Questionnaire and the Strength and Difficulties Questionnaire when children were 11 years of age were included. Main Outcomes and Measures: Psychopathology relevant symptoms, such as hyperactivity, prosociality, depression, anxiety, and peer and conduct problems at age 11 years. Psychological networks were constructed including individual symptoms and polygenic scores for depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), body mass index (BMI), and educational attainment in ALSPAC. Following a preregistered confirmatory analysis, network models were cross-validated in TEDS. Results: Included were 5521 participants from ALSPAC (mean [SD] age, 11.8 [0.14] years; 2777 [50.3%] female) and 4625 participants from TEDS (mean [SD] age, 11.27 [0.69] years; 2460 [53.2%] female). Polygenic scores were preferentially associated with restricted subsets of core symptoms and indirectly associated with other, more distal symptoms of psychopathology (network edges ranged between r = -0.074 and r = 0.073). Psychiatric polygenic scores were associated with specific cross-disorder symptoms, and nonpsychiatric polygenic scores were associated with a variety of indicators across disorders, suggesting a potential contribution of nonpsychiatric traits to comorbidity. For example, the polygenic score for ADHD was associated with a core ADHD symptom, being easily distracted (r = 0.07), and the polygenic score for BMI was associated with symptoms across disorders, including being bullied (r = 0.053) and not thinking things out (r = 0.041). Conclusions and Relevance: Genetic associations observed at the disorder level may hide symptom-level heterogeneity. A symptom-level approach may enable a better understanding of the role of polygenic risk in shaping psychopathology and comorbidity.

Neglected cardiometabolic risk factors and subclinical target organ damage in post-menopausal women with normal glucose tolerance.

BACKGROUND: Menopausal transition is a crucial step in the women's cardiovascular health, and the risk stratification in apparently health post-menopausal females has been rarely assessed. Heart ultrasonography, unusually performed in such subjects, would be able to detect initial signs of organ damage. We described the cardiovascular risk profile of non-diabetic post-menopausal women, evaluating how easily computed, biochemistry-derived scores were related to ultrasonographic measures of target organ damage. METHODS: We analyzed the characteristics of a cohort of two-hundred and seventy-three women consecutively referring to a prevention program of Azienda Ospedaliero-Universitaria Pisana (years 2017-2022) who underwent clinical evaluation, complete routine biochemical analyses with proxies of insulin resistance, heart and carotid ultrasonography. The cohort was further divided into four groups according to presence of isolated hypercholesterolemia (HC, 37%), isolated hypertension (HT, 5%), both HC/HT (38%), or none of them. RESULTS: In HC and HC/HT, LDL cholesterol was sharply above the recommended values (149 [134-171] mg/dL and 141 [123-159] mg/dL, respectively). E/e' ratio and left atrium size were augmented in HT women and further worsened in HT/HC, with an independent effect of hypertension (E/e' ß=0.055, P=0.013, left atrium volume ß=0.059, P=0.003). Presence of carotid plaques was independently linked to hypertension (ß=0.474, P=0.003). In HC and HC/HT, the Triglycerides-Glucose Index, a surrogate of insulin resistance, was higher than in the other classes (P=0.0013), and it was associated with E/A in HC and HT/HC, with a significative interaction (P=0.0004) with hypertension. Past hormone replacement therapy did not influence clinical, biochemical or echocardiographic parameters. CONCLUSIONS: Postmenopausal women display a high cardiovascular risk burden; a simple clinical and biochemistry screening would be advisable to identify and treat those more at risk. Cardiac ultrasonographic parameters were worse in hypertensive, hypercholesterolemic and insulin-resistant subjects, who may also deserve a deep and early instrumental characterization, especially when these conditions are associated.

Quantitative T2 Mapping of Acute Pancreatitis.

BACKGROUND: Quantification of the T2 signal by means of T2 mapping in acute pancreatitis (AP) has the potential to quantify the parenchymal edema. Quantitative T2 mapping may overcome the limitations of previously reported scoring systems for reliable assessment of AP. PURPOSE: To evaluate MR-derived pancreatic T2 mapping values in AP and correlate them with markers of disease severity. STUDY TYPE: Prospective single-center study. POPULATION: 76 adults with AP (20-91 years, females/males: 39/37). FIELD STRENGTH/SEQUENCE: Fat suppressed multiecho spin-echo prototype sequence to quantify T2 signal at 3T MRI. ASSESSMENT: The severity of AP was assessed clinically, biologically, and by contrast-enhanced CT (CECT) performed 48-72 hours after symptom onset. MRI was then performed ≤24 hours after CT. Two readers blinded to any clinical information independently evaluated the T2 values by placing three regions of interest inside the pancreatic head, body, and tail on the T2 mapping MR sequence. Results were compared with corresponding CECT images as the standard and clinical severity parameters, using the length of hospital stay as our primary endpoint. STATISTICAL TESTS: Continuous variables were compared using the Spearman's rank correlation coefficient, analysis of variance (ANOVA) or Student's t-test. RESULTS: T2 values significantly correlated with the length of hospital stay (rs (74) = 0.29), CT severity index (CTSI) (rs (73) = 0.61; CTSI 0-3: 72 ± 14 msec, CTSI 4-10: 88 ± 15), intensive care unit (ICU) admission (t(2.77) = -3.41) and presence of organ failure (t(6.72) = -3.42), whereas the CTSI and Ranson score were not significantly related with ICU admission (CTSI: P = 0.24; Ranson score: P = 0.24) and organ failure (CTSI: P = 0.11; Ranson score P = 0.11). CONCLUSION: T2 mapping correlates with AP severity parameters and is useful for assessing the severity of AP with higher sensitivity than the usual clinical and radiological scoring systems. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

A survey of the training experiences and needs on Wellcome Trust PhD programmes.

Background: Training for PhD researchers was previously identified by the Wellcome Trust funded Emerging Research Cultures project as an area for further investigation to ensure an inclusive culture which enables PhD students to become well-rounded researchers. Methods: The Taskforce on Training conducted a survey of 35 Wellcome Trust funded PhD students and 10 programme administrators to evaluate the provision of training in eight key areas. This survey examined a number of issues, such as availability and knowledge of training, potential gaps in training, and the perceived usefulness of training. Results: PhD students reported that training was generally useful and viewed as important; with technical training being particularly highly valued. However, the survey identified that students desired additional training in project management and personal development. Surveying programme administrators highlighted the wide variety in training availability for students across different Wellcome Trust programmes currently running in the UK. Conclusion: In response to these findings, several recommendations were suggested. Examples include; promotion of peer mentoring for PhD students, and alternative methods for delivery of wellbeing training. However, this report only explores the views of a small number of Wellcome Trust funded PhD students and would benefit from further research into the experiences of PhD students, programme administrators, and PhD supervisors.

A systematic review of the pharmacological modulation of autobiographical memory specificity.

Background: Over-general autobiographical memory (AM) retrieval is proposed to have a causal role in the maintenance of psychological disorders like depression and PTSD. As such, the identification of drugs that modulate AM specificity may open up new avenues of research on pharmacological modeling and treatment of psychological disorders. Aim: The current review summarizes randomized, placebo-controlled studies of acute pharmacological modulation of AM specificity. Method: A systematic search was conducted of studies that examined the acute effects of pharmacological interventions on AM specificity in human volunteers (healthy and clinical participants) measured using the Autobiographical Memory Test. Results: Seventeen studies were identified (986 total participants), of which 16 were judged to have low risk of bias. The presence and direction of effects varied across drugs and diagnostic status of participants (clinical vs. healthy volunteers). The most commonly studied drug-hydrocortisone-produced an overall impairment in AM specificity in healthy volunteers [g = -0.28, CI (-0.53, -0.03), p = 0.03], although improvements were reported in two studies of clinical participants. In general, studies of monoamine modulators reported no effect on specificity. Conclusion: Pharmacological enhancement of AM specificity is inconsistent, although monaminergic modulators show little promise in this regard. Drugs that reduce AM specificity in healthy volunteers may be useful experimental-pharmacological tools that mimic an important transdiagnostic impairment in psychological disorders. Systematic review registration: PROSPERO, identifier CRD42020199076, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020199076.

Calcification traits for cryptic species identification: Insights into coralline biomineralization.

Calcareous red algae are foundation species and ecosystem engineers with a global distribution. The principles governing their calcification pathways are still debated and the morphological characters are frequently unreliable for species segregation, as shown by molecular genetics. The recent description of the new species Lithophyllum pseudoracemus, previously undetected and morphologically confused with Lithophyllum racemus, offered a challenging opportunity to test the effectiveness of microanatomy and ultrastructural calcification traits as tools for the identification of these two species, for integrative taxonomy. High resolution SEM images of molecularly identified samples showed that the different size of the perithallial cells and the features of the asexual conceptacle chambers may contribute to the separation of the two species. The two species share the same crystallite morphology in the primary and secondary cell-wall calcification, as previously described in other species belonging to the same clade. However, the perithallial secondary calcification was significantly thicker in L. racemus than in L. pseudoracemus. We described a granular calcified layer in the innermost part of the cell wall, as a putative precursor phase in the biomineralization and formation of the secondary calcification. The hypothesis of different pathways for the formation of the primary and secondary calcification is supported by the observed cell elongation associated with thicker and higher Mg/Ca primary calcification, the inverse correlation of primary and secondary calcification thickness, and the absence of primary calcification in the newly formed wall cutting off an epithallial cell from the meristem.

The effects of response inhibition training following binge memory retrieval in young adults binge eaters: a randomised-controlled experimental study.

Binge eating is increasingly prevalent among adolescents and young adults and can have a lasting harmful impact on mental and physical health. Mechanistic insights suggest that aberrant reward-learning and biased cognitive processing may be involved in the aetiology of binge eating. We therefore investigated whether recently developed approaches to catalyse brief interventions by putatively updating maladaptive memory could also boost the effects of cognitive bias modification training on binge eating behaviour. A non-treatment-seeking sample of 90 binge eating young adults were evenly randomised to undergo either selective food response inhibition training, or sham training following binge memory reactivation. A third group received training without binge memory reactivation. Laboratory measures of reactivity and biased responses to food cues were assessed pre-post intervention and bingeing behaviour and disordered eating assessed up to 9 months post-intervention. The protocol was pre-registered at https://osf.io/82c4r/ . We found limited evidence of premorbid biased processing in lab-assessed measures of cognitive biases to self-selected images of typical binge foods. Accordingly, there was little evidence of CBM reducing these biases and this was not boosted by prior 'reactivation' of binge food reward memories. No group differences were observed on long-term bingeing behaviour, caloric consumption or disordered eating symptomatology. These findings align with recent studies showing limited impact of selective inhibition training on binge eating and do not permit conclusions regarding the utility of retrieval-dependent memory 'update' mechanisms as a treatment catalyst for response inhibition training.

Pharmacological modelling of dissociation and psychosis: an evaluation of the Clinician Administered Dissociative States Scale and Psychotomimetic States Inventory during nitrous oxide ('laughing gas')-induced anomalous states.

RATIONALE: A significant obstacle to an improved understanding of pathological dissociative and psychosis-like states is the lack of readily implemented pharmacological models of these experiences. Ketamine has dissociative and psychotomimetic effects but can be difficult to use outside of medical and clinical-research facilities. Alternatively, nitrous oxide (N2O) - like ketamine, a dissociative anaesthetic and NMDAR antagonist - has numerous properties that make it an attractive alternative for modelling dissociation and psychosis. However, development and testing of such pharmacological models relies on well-characterized measurement instruments. OBJECTIVES: To examine the factor structures of the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) administered during N2O inhalation in healthy volunteers. METHODS: Secondary analyses of data pooled from three previous N2O studies with healthy volunteers. RESULTS: Effect sizes for N2O-induced dissociation and psychotomimesis were comparable to effects reported in experimental studies with sub-anaesthetic ketamine in healthy volunteers. Although, like ketamine, a three-factor representation of N2O-induced dissociation was confirmed, and a more parsimonious two-factor model might be more appropriate. Bayesian exploratory factor analysis suggested that N2O-induced psychosis-like symptoms were adequately represented by two negative and two positive symptom factors. Hierarchical cluster analysis indicated minimal item overlap between the CADSS and PSI. CONCLUSION: N2O and ketamine produce psychometrically similar dissociative states, although parallels in their psychosis-like effects remain to be determined. The CADSS and PSI tap largely non-overlapping experiences under N2O and we propose the use of both measures (or similar instruments) to comprehensively assess anomalous subjective states produced by dissociative NMDAR antagonists.

Probability of Postoperative Complication after Liver Resection: Stratification of Patient Factors,Operative Complexity, and Use of Enhanced Recovery after Surgery.

BACKGROUND: The current study aimed to assess the performance of the 3-level complexity classification that stratified liver resection procedures into 3 complexity grades (grade I, low; grade II, intermediate; and grade III, high complexity) and to evaluate whether the Enhanced Recovery after Surgery (ERAS) protocol improves postoperative outcomes for each complexity grade. STUDY DESIGN: Consecutive patients undergoing open liver resection and laparoscopic liver resection at Lausanne University Hospital during 2010 to 2020 were assessed. RESULTS: A total of 437 patients were included. Operative time, estimated blood loss, and length of hospital stay increased significantly, with a stepwise increase of the grades from I to III in open liver resection and laparoscopic liver resection (all, p < 0.05). The same trend for Comprehensive Complication Index was found in open liver resection (p < 0.005). Age (p = 0.004), 3-level complexity classification (grade II vs I; p = 0.001; grade III vs I; p < 0.001), no use of the ERAS protocol (p = 0.016), and biliary reconstruction (p < 0.001) were significant predictors for postoperative complication, defined as Comprehensive Complication Index ≥ 26.2 in a multivariable logistic regression analysis. The prediction model incorporating the 4 factors had a calculated Concordance Index of 0.735 and 0.742 based on the bootstrapping method. The use of ERAS protocol was associated with lower probability of postoperative complication for each complexity grade and age. CONCLUSIONS: The use of ERAS protocol can decrease the probability of postoperative complication for each surgical complexity of liver resection and patient age. This finding emphasized the importance of tailoring perioperative management according to surgical complexity and patient age to improve outcomes after liver resection.

Rewarding Subjective Effects of the NMDAR Antagonist Nitrous Oxide (Laughing Gas) Are Moderated by Impulsivity and Depressive Symptoms in Healthy Volunteers.

BACKGROUND: Nitrous oxide (N2O) is an anesthetic gas with both therapeutic and abuse potential. Because N2O is an NMDA receptor (NMDAR) antagonist, its effects are expected to resemble those of the prototypical NMDAR antagonist, ketamine. In this study, we examined the subjective rewarding effects of N2O using measures previously employed in studies of ketamine. We also tested for moderation of these effects by bipolar phenotype, depressive symptoms, and impulsivity. METHODS: Healthy volunteers were randomly assigned to either 50% N2O (n = 40) or medical air (n = 40). Self-reported rewarding (liking and wanting), and alcohol-like effects were assessed pre-, peri- and post inhalation. RESULTS: Effect sizes for the various rewarding/alcohol-like effects of N2O were generally similar to those reported in studies of moderate-dose ketamine. Impulsivity moderated the subjective reinforcing (liking) effects of inhaled gas, while depressive symptoms moderated motivational (wanting [more]) effects. However, depression and impulsivity had opposite directional influences, such that higher impulsivity was associated with higher N2O liking, and higher depression, with lower N2O wanting. CONCLUSION: To the extent that static (versus longitudinal) subjective rewarding effects are a reliable indicator of future problematic drug use, our findings suggests that impulsivity and depression may predispose and protect, respectively, against N2O abuse. Future studies should examine if these moderators are relevant for other NMDAR antagonists, including ketamine, and novel ketamine-like therapeutic and recreational drugs. Similarities between moderate-dose N2O and moderate-dose ketamine in the intensity of certain subjective effects suggest that N2O may, at least to some extent, serve as substitute for ketamine as a safe and easily implemented experimental tool for probing reward-related NMDAR function and dysfunction in humans.

Preserving Surgical Professionalism in Social Media; Long Live the Media, But Let Live the Surgeon.

The positive impact of social media in surgery is ever increasing, although they present some challenging aspects, as preservation of medical professionalism. Physicians should respect patient privacy and integrity through their online presence. However, their personal expression also deserves respect, not being labeled "unprofessional" just for conveying private attitudes and beliefs.

The Use of Demoralization Scale in Italian Kidney Transplant Recipients.

Demoralization is a commonly observed syndrome in medically ill patients. The risk of demoralization may increase in patients after a kidney transplant (KTRs) because of the stressful nature of renal transplantation, psychosocial challenges, and adjustment needs. No study is available on demoralization amongst KTRs. The purpose of our study was to evaluate the validity of the Italian version of the Demoralization Scale (DS-IT) and the prevalence of demoralization in KTRs. Also, we aimed at exploring the association of the DS-IT with International Classification of Diseases (ICD) psychiatric diagnoses, post-traumatic growth (PTG), psychological and physical symptoms, and daily-life problems. A total of 134 KTRs were administered the MINI International Neuropsychiatric Interview 6.0. and the Diagnostic Criteria for Psychosomatic Research-Demoralization (DCPR/D) Interview. The DS-IT, the Edmonton Symptom Assessment System (ESAS), the Canadian Problem Checklist (CPC), were used to measure demoralization, physical and psychological symptoms, and daily-life problems; also, positive psychological experience of kidney transplantation was assessed with the PTG Inventory. Routine biochemistry and sociodemographic data were collected. Exploratory factor analysis demonstrated a four-dimensional factor structure of the DS-IT, explaining 55% of the variance (loss of meaning and purpose, disheartenment, dysphoria, and sense of failure). DS-IT Cronbach alpha coefficients indicated good or acceptable level of internal consistency. The area under the Receiving Operating Characteristics (ROC) curve for DS-IT (against the DCPR/D interview as a gold standard) was 0.92. The DS-IT optimal cut-off points were ≥20 (sensitivity 0.87, specificity 0.82). By examining the level of demoralization, 14.2%, 46.3%, 24.6%, and 14.6% of our sample were classified as having no, low, moderate, and high demoralization, respectively, with differences according to the ICD psychiatric diagnoses (p < 0.001). DS-IT Total and subscales scores were positively correlated with scores of ESAS symptoms and CPC score. A correlation between DS-IT loss of meaning and purpose subscale and PTGI appreciation of life subscale (p < 0.05) was found. This study shows, for the first time, a satisfactory level of reliability of the DS-IT and a high prevalence of severe demoralization in KTRs.

Screening Performance of Edmonton Symptom Assessment System in Kidney Transplant Recipients.

An average prevalence of 35% for psychiatric comorbidity has been reported in kidney transplant recipients (KTRs) and an even higher prevalence of other psychosocial syndromes, as defined by the Diagnostic Criteria for Psychosomatic Research (DCPR), has also been found in this population. Consequently, an easy, simple, rapid psychiatric tool is needed to measure physical and psychological symptoms of distress in KTRs. Recently, the Edmonton Symptom Assessment System (ESAS), a pragmatic patient-centred symptom assessment tool, was validated in a single cohort of KTRs. The aims of this study were: to test the screening performances of ESAS for the International Classification of Diseases-10th Revision (ICD-10) psychiatric diagnoses in KTRs; to investigate the optimal cut-off points for ESAS physical, psychological and global subscales in detecting ICD-10 psychiatric diagnoses; and to compare ESAS scores among KTR with ICD-10 diagnosis and DCPR diagnosis. 134 KTRs were evaluated and administered the MINI International Neuropsychiatric Interview 6.0 and the DCPR Interview. The ESAS and Canadian Problem Checklist (CPC) were given as self-report instruments to be filled in and were used to examine the severity of physical and psychological symptoms and daily-life problems. The physical distress sub-score (ESAS-PHYS), psychological distress sub-score (ESAS-PSY) and global distress score (ESAS-TOT) were obtained by summing up scores of six physical symptoms, four psychological symptoms and all single ESAS symptoms, respectively. Routine biochemistry, immunosuppressive agents, socio-demographic and clinical data were collected. Receiving Operating Characteristic (ROC) analysis was used to examine the ability of the ESAS emotional distress (DT) item, ESAS-TOT, ESAS-PSY and ESAS-PHYS, to detect psychiatric cases defined by using MINI6.0. The area under the ROC curve for ESAS-TOT, ESAS-PHYS, ESAS-PSY and DT item were 0.85, 0.73, 0.89, and 0.77, respectively. The DT item, ESAS-TOT and ESAS-PSY optimal cut-off points were ≥4 (sensitivity 0.74, specificity 0.73), ≥20 (sensitivity 0.85, specificity 0.74) and ≥12 (sensitivity 0.85, specificity 0.80), respectively. No valid ESAS-PHYS cut-off was found (sensitivity <0.7, specificity <0.7). Thirty-nine (84.8%) KTRs with ICD-10 diagnosis did exceed both ESAS-TOT and ESAS-PSY cut-offs. Higher scores on the ESAS symptoms (except shortness of breath and lack of appetite) and on the CPC problems were found for ICD-10 cases and DCRP cases than for ICD-10 no-cases and DCPR no-cases. This study shows that ESAS had an optimal screening performance (84.8%) to identify ICD-10 psychiatric diagnosis, evaluated with MINI; furthermore, ESAS-TOT and ESAS-PSY cut-off points could provide a guide for clinical symptom management in KTRs.

Transcatheter aortic root replacement with chimney grafts for coronary perfusion: a preliminary test in a three-dimensional-printed root model.

OBJECTIVES: Transcatheter aortic root repair is still not available because of the technical challenge of coronary perfusion. The use of chimney grafts for coronary ostia can be an option and we tested the flow-through coronary chimney grafts deployed in a 3-dimensional-printed root model as part of a transcatheter aortic root repair system. METHODS: A 3-dimensional-printed root was used to test the coronary flow after the deployment of 1 root endograft (28 mm diameter) and two 6-mm diameter 10-cm long coronary chimney grafts. Continuous coronary flows were measured in a bench test at different pressure levels (60, 80 and 100 mmHg) and compared to target coronary flows (250 ml/min at rest for the left and 150 ml/min at rest for the right coronary artery). RESULTS: The computed tomography scan-based root was modified with two 5-mm diameter coronary conduits to overcome the limits of the original 3-dimensional-printed coronary ostia. The root was placed in the hydrodynamic system: adjusted coronary free flow at 60, 80 and 100 mmHg of pressure was 1913, 2200 and 2480 ml/min for left coronary and 1633, 2026 and 2366 ml/min for right coronary, respectively. After endografts deployment, mean chimney graft flow at 60, 80 and 100 mmHg of pressure was 1053 ml/min (-45%), 1306 ml/min (-41%) and 1502 ml/min (-40%) for the left coronary and 1100 ml/min (-33%), 1460 ml/min (-28%) and 1626 ml/min (-31%) for the right coronary, respectively. CONCLUSIONS: In this preliminary study, chimney grafts for transcatheter aortic root repair provided 830% of target flow in the right coronary (-31% of free flow) and 414% of target flow in the left coronary (-42% of free flow) which is more than sufficient for both coronaries in real-life conditions. The potential of this approach should be further explored with specifically designed endografts.

The interactive effect of herbivory, nutrient enrichment and mucilage on shallow rocky macroalgal communities.

This paper focuses on the interactive short and long-term effect of three different stressors on a macroalgal assemblage. Three stressors are considered: herbivory, nutrients and mucilage. The experiment was conducted in Tavolara Punta Coda Cavallo Marine Protected Area (Mediterranean Sea) during a bloom of the benthic mucilage-producing microalga Chrysophaeum taylorii (Pelagophyceae); this microalga is recently spreading in the Mediterranean Sea. On a rocky substratum, 36 plots 20 × 20 cm in size were prepared. Factorial combinations of three experimental treatments were applied in triplicate, including three grazing levels crossed with two nutrient enrichment and two mucilage removal treatments. Significant differences were observed among treatments 8 weeks later, at the end of summer. In particular, dark filamentous algae were more abundant in all enriched plots, especially where mucilage and macroalgae had been removed; a higher percent cover of crustose coralline algae was instead observed where nutrients had been increased and no grazing pressure acted. Furthermore, the abundance of Dictyota spp. and Laurencia spp. was significantly higher in enriched mucilage-free plots where the grazing pressure was null or low. However, the effects of the treatments on the overall assemblage of the macroalgal community were not long persistent (36 weeks later). These results illustrate the capacity of a shallow-water macroalgal community to quickly recover from the simultaneous impacts of herbivory, nutrient enrichment, and mucilage.

Suitability of 3D-Printed Root Models for the Development of Transcatheter Aortic Root Repair Technologies.

Transcatheter aortic root repair (TARR) is still not available because of the complex anatomy. In order to develop future TARR technologies, a human-derived bench test model is required before performing animal tests. For this purpose, we aimed to validate computed tomography (CT)-derived 3D-printed root models for TARR technologies. Four human CT-derived roots were printed using different resins: Visijet M3 Crystal, Photopolymer gel SUP705, Formlabs flexible resin, and Materialise HeartPrint Flex. A stress test was performed using a 26-mm balloon-expandable Sapien valve deployed in aortic position. The too rigid Visijet M3 Crystal was not tested. Among the others, all but one (HeartPrint Flex, Materialise, Leuven, Belgium) ruptured during the test showing low wall resistances. Further tests were then performed in two roots made of HeartPrint Flex resin. The anatomic validation was performed comparing human CT scan-derived 3D reconstructions and CT scan measurements: a mean difference of 0.57 ± 0.4 mm for aortic annulus diameter and for the distance between the aortic annulus and the coronary ostia was measured. Concerning the coronary arteries, they are of paramount importance for new TARR technologies, and therefore, we tested the coronary flows of the HeartPrint Flex root at different pressure levels. At 60 mm Hg, right and left mean adjusted coronary flows were 471 and 663 ml/min; at 80 mm Hg, right and left mean coronary flows were 551 and 777 ml/min; and at 100 mm Hg, right and left mean coronary flows were 625 and 858 ml/min. In our study, 3D-printed root models correlate well with human anatomy and guarantee physiologic coronary flows for TARR technologies.

Growth hormone and hematopoiesis: A retrospective analysis on a large cohort of children with growth hormone deficiency.

OBJECTIVE: Few large-scale studies regarding the impact of GH deficiency (GHD) on hematopoiesis in children have been reported. Our aim was to investigate hematopoiesis indices in a large cohort of GHD children at diagnosis and during GH treatment (GHT) and any correlation with hormonal parameters. DESIGN: Clinical and biochemical data of children with idiopathic GHD at diagnosis and annually up to 36 months of GHT were retrospectively evaluated. Overall, 255 children reached 12 months, 140 children 24 months and 86 children 36 months of follow-up during GHT. RESULTS: At baseline, 18.4% of GHD children and 10.1% of controls showed normocytic anemia. GHD children showed lower hemoglobin (Hb) (p = 0.007), red blood cells (RBC) (p < 0.001) and hematocrit (Ht) (p = 0.001) than controls. During GHT, the percentage of anemic patients decreased from 18.4 to 5.4-3.5 and 4.6% after 12 (p = 0.001), 24 (p < 0.001) and 36 months (p < 0.001) of GHT, respectively. In both anemic and non-anemic patients, a significant increase in Hb (p < 0.001, <0.001 and 0.002), RBC (all p < 0.001) and Ht (all p < 0.001) was found after 12, 24 and 36 months of GHT. The Hb levels were significantly correlated with the GH peak after stimulation test (p < 0.001) at baseline and with IGF-I levels at 36 months of GHT (p = 0.002). CONCLUSIONS: A significant improvement in erythropoiesis indices occurs during GHT, regardless of any previous presence of anemia.

Insulin Instability in Parenteral Nutrition Admixtures.

BACKGROUND: Biosynthetic human recombinant short-acting insulin is added to parenteral nutrition (PN) admixtures to nourish glucose-intolerant patients. Insulin, however, is electrostatically attracted and inactivated by ethyl-vinyl-acetate (EVA) bags and filling system tubes. Our aim was to verify and quantify the presence of insulin in PN with and without intravenous lipid emulsion (ILE), just after addition (T0) until the infusion's end (T24). METHODS: Four undiluted samples of 12 different PN complete admixtures (6 with ILE and 6 without), each containing 250 g of glucose in a 2000 mL volume, were taken and analyzed at T0 and T24 by an automated electrochemiluminescence immunoassay after the addition of biosynthetic human recombinant short-acting insulin at increasing doses (from 6 to 72 IU/bag) by an automated compounding device. Assay sensitivity was set at 2 µIU/mL. Admixtures with and without ILE were compared in terms of insulin-detected amounts at T0 and T24. RESULTS: Regardless of the amount initially provided, insulin was missing in PN without ILE. In admixtures with ILE, the greater the insulin and ILE doses initially included, the higher the insulin availability at T0 and T24, both in absolute terms and as a percentage of the initial amount (from 3 to 81% at T0 and from 2.5 to 72.5% at T24). ILE may prevent insulin attraction to plastic surfaces. CONCLUSIONS: Insulin is recovered in the presence of ILE in PN even though considerable amounts are untraceable. This aspect needs verification. Until then, insulin should safely be injected in a different manner in uncontrolled situations.