Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project.

BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. METHODS: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters. RESULTS: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions. CONCLUSIONS: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Coupled cycling of iron, manganese and phosphorus in the water column of the Black Sea and its implications for phosphorus burial

Recent work suggests that reduced iron (Fe) phosphates are present in the deep basin sediments of the Black Sea. This could be due to the formation of mixed Fe, manganese (Mn) and phosphorus (P) particles in the redoxcline that survive transport through the sulfidic water column. An alternative hypothesis is that only Fe(III)-rich particles reach the surface sediments, where they are then transformed to Fe(II)-P phases. In this study, we combine various techniques (including SEM-EDS and X-ray absorption spectroscopy) to investigate the water column transformations of Mn, Fe and P in the sulfidic deep basin of the Black Sea. In addition, we performed 33P radiotracer experiments with surface sediments from the deep basin to assess the potential for in-situ Fe(II)-P formation. Our results show that most mixed Fe(III), Mn(III/IV) and P phases present in the redoxcline do not survive transport through the sulfidic water column. However, the deep sulfidic water column does contain particles that are rich in Fe(III), likely in the form of Fe(III)-rich clays. We also observe a fast uptake of 33P in the surface sediments of the deep basin in a form that is extracted with citrate-dithionite-bicarbonate (CDB), a strongly reducing solution (pH 7.6). The nature of this P pool is still under debate. We discuss whether the CDBextractable P fraction may represent Fe(II)-P phases in the deep basin sediments and might be linked to the presence of Fe(III) particles in the deeper water column

Coupled cycling of iron, manganese and phosphorus in the water column of the Black Sea and its implications for phosphorus burial

Recent work suggests that reduced iron (Fe) phosphates are present in the deep basin sediments of the Black Sea. This could be due to the formation of mixed Fe, manganese (Mn) and phosphorus (P) particles in the redoxcline that survive transport through the sulfidic water column. An alternative hypothesis is that only Fe(III)-rich particles reach the surface sediments, where they are then transformed to Fe(II)-P phases. In this study, we combine various techniques (including SEM-EDS and X-ray absorption spectroscopy) to investigate the water column transformations of Mn, Fe and P in the sulfidic deep basin of the Black Sea. In addition, we performed 33P radiotracer experiments with surface sediments from the deep basin to assess the potential for in-situ Fe(II)-P formation. Our results show that most mixed Fe(III), Mn(III/IV) and P phases present in the redoxcline do not survive transport through the sulfidic water column. However, the deep sulfidic water column does contain particles that are rich in Fe(III), likely in the form of Fe(III)-rich clays. We also observe a fast uptake of 33P in the surface sediments of the deep basin in a form that is extracted with citrate-dithionite-bicarbonate (CDB), a strongly reducing solution (pH 7.6). The nature of this P pool is still under debate. We discuss whether the CDBextractable P fraction may represent Fe(II)-P phases in the deep basin sediments and might be linked to the presence of Fe(III) particles in the deeper water column

Phosphorus dynamics in and below the redoxcline in the Black Sea and implications for phosphorus burial

Marine basins with oxygen-depleted deep waters provide a natural laboratory to investigate the consequences of anoxic and sulfidic (i.e. euxinic) conditions for biogeochemical processes in seawater and sediments. In this study, we investigate the dynamics of the key nutrient phosphorus (P) and associated elements such as manganese (Mn), iron (Fe) and calcium (Ca) in the euxinic deep basin of the Black Sea. By examining water column particles with scanning electron microscope – energy dispersive spectroscopy and synchrotron-based X-ray absorption spectroscopy, we show that Mn(III/IV)-P is the key form of particulate P in the redoxcline. Other forms of particulate P include organic P, Fe(III)-P, and inorganic polyphosphates. Most inorganic P particles that are formed in the redoxcline subsequently dissolve in the underlying sulfidic waters, with the exception of some particulate Fe(III)-P that accounts for <1% of all P settling onto the seafloor. Organic P is the dominant source of P to the sediment. Most of this organic P is degraded in the upper 2 cm of the sediment. Results of sequential extractions and a 33P radiotracer experiment point towards the formation of labile Ca-P and P adsorbed onto calcium-carbonate and clays and a role of these phases as a major sink of P in the sediment. The total P burial efficiency in the sediments is ∼27%, which is relatively high when compared to estimates for sediments in other euxinic basins such as the Baltic Sea (<12%). We suggest that the abundant presence of calcium carbonate may contribute to the more efficient sequestration of P in Black Sea sediments

Effects of selective digestive decontamination (SDD) on the gut resistome

Objectives Selective digestive decontamination (SDD) is an infection prevention measure for critically ill patients in intensive care units (ICUs) that aims to eradicate opportunistic pathogens from the oropharynx and intestines, while sparing the anaerobic flora, by the application of non-absorbable antibiotics. Selection for antibiotic-resistant bacteria is still a major concern for SDD. We therefore studied the impact of SDD on the reservoir of antibiotic resistance genes (i.e. the resistome) by culture-independent approaches. Methods We evaluated the impact of SDD on the gut microbiota and resistome in a single ICU patient during and after an ICU stay by several metagenomic approaches. We also determined by quantitative PCR the relative abundance of two common aminoglycoside resistance genes in longitudinally collected samples from 12 additional ICU patients who received SDD. Results The patient microbiota was highly dynamic during the hospital stay. The abundance of antibiotic resistance genes more than doubled during SDD use, mainly due to a 6.7-fold increase in aminoglycoside resistance genes, in particular aph(2¿)-Ib and an aadE-like gene. We show that aph(2¿)-Ib is harboured by anaerobic gut commensals and is associated with mobile genetic elements. In longitudinal samples of 12 ICU patients, the dynamics of these two genes ranged from a ~104 fold increase to a ~10-10 fold decrease in relative abundance during SDD. Conclusions ICU hospitalization and the simultaneous application of SDD has large, but highly individualized, effects on the gut resistome of ICU patients. Selection for transferable antibiotic resistance genes in anaerobic commensal bacteria could impact the risk of transfer of antibiotic resistance genes to opportunistic pathogens