Italian guidelines for the management of adult individuals with overweight and obesity and metabolic comorbidities that are resistant to behavioral treatment.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. METHODS: Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. RESULTS: The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. CONCLUSION: The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

Anoxygenic phototroph of the Chloroflexota uses a type I reaction centre.

Scientific exploration of phototrophic bacteria over nearly 200 years has revealed large phylogenetic gaps between known phototrophic groups that limit understanding of how phototrophy evolved and diversified1,2. Here, through Boreal Shield lake water incubations, we cultivated an anoxygenic phototrophic bacterium from a previously unknown order within the Chloroflexota phylum that represents a highly novel transition form in the evolution of photosynthesis. Unlike all other known phototrophs, this bacterium uses a type I reaction centre (RCI) for light energy conversion yet belongs to the same bacterial phylum as organisms that use a type II reaction centre (RCII) for phototrophy. Using physiological, phylogenomic and environmental metatranscriptomic data, we demonstrate active RCI-utilizing metabolism by the strain alongside usage of chlorosomes3 and bacteriochlorophylls4 related to those of RCII-utilizing Chloroflexota members. Despite using different reaction centres, our phylogenomic data provide strong evidence that RCI-utilizing and RCII-utilizing Chloroflexia members inherited phototrophy from a most recent common phototrophic ancestor. The Chloroflexota phylum preserves an evolutionary record of the use of contrasting phototrophic modes among genetically related bacteria, giving new context for exploring the diversification of phototrophy on Earth.

Anatomical and biochemical studies of Spartium junceum infected by Xylella fastidiosa subsp. multiplex ST 87.

Spartium junceum L. is a typical species of Mediterranean shrubland areas, also grown in gardens and parks as an ornamental. In recent years in Europe, S. junceum has been recurrently found to be infected by different subspecies and genotypes of the quarantine regulated bacterium Xylella fastidiosa (Xf). This work presents for the first time the anatomy of S. junceum plants that we found, by means of genetic and immunochemistry analysis, to be naturally infected by Xf subsp. multiplex ST87 (XfmST87) in Monte Argentario (Grosseto, Tuscany, Italy), a new outbreak area within the EU. Our anatomical observations showed that bacteria colonized exclusively the xylem conductive elements and moved horizontally to adjacent vessels through pits. Interestingly, a pink/violet matrix was observed with Toluidine blue staining in infected conduits indicating a high content of acidic polysaccharides. In particular, when this pink-staining matrix was observed, bacterial cells were either absent or degenerated, suggesting that the matrix was produced by the host plant as a defense response against bacterial spread. In addition, a blue-staining phenolic material was found in the vessels and, at high concentration, in the pits and inter-vessels. SEM micrographs confirmed that polysaccharide and phenolic components showed different structures, which appear to be related to two different morphologies: fibrillary and granular, respectively. Moreover, our LM observations revealed bacterial infection in xylem conductive elements of green shoots and leaves only, and not in those of other plant organs such as roots and flowers.

Anoxygenic photosynthesis and iron-sulfur metabolic potential of Chlorobia populations from seasonally anoxic Boreal Shield lakes.

Aquatic environments with high levels of dissolved ferrous iron and low levels of sulfate serve as an important systems for exploring biogeochemical processes relevant to the early Earth. Boreal Shield lakes, which number in the tens of millions globally, commonly develop seasonally anoxic waters that become iron rich and sulfate poor, yet the iron-sulfur microbiology of these systems has been poorly examined. Here we use genome-resolved metagenomics and enrichment cultivation to explore the metabolic diversity and ecology of anoxygenic photosynthesis and iron/sulfur cycling in the anoxic water columns of three Boreal Shield lakes. We recovered four high-completeness and low-contamination draft genome bins assigned to the class Chlorobia (formerly phylum Chlorobi) from environmental metagenome data and enriched two novel sulfide-oxidizing species, also from the Chlorobia. The sequenced genomes of both enriched species, including the novel "Candidatus Chlorobium canadense", encoded the cyc2 gene that is associated with photoferrotrophy among cultured Chlorobia members, along with genes for phototrophic sulfide oxidation. One environmental genome bin also encoded cyc2. Despite the presence of cyc2 in the corresponding draft genome, we were unable to induce photoferrotrophy in "Ca. Chlorobium canadense". Genomic potential for phototrophic sulfide oxidation was more commonly detected than cyc2 among environmental genome bins of Chlorobia, and metagenome and cultivation data suggested the potential for cryptic sulfur cycling to fuel sulfide-based growth. Overall, our results provide an important basis for further probing the functional role of cyc2 and indicate that anoxygenic photoautotrophs in Boreal Shield lakes could have underexplored photophysiology pertinent to understanding Earth's early microbial communities.

Estimating cumulative wastewater treatment plant discharge influences on acesulfame and Escherichia coli in a highly impacted watershed with a fully-integrated modelling approach.

Wastewater treatment plant (WWTP) discharge is often considered a principal source of surface water contamination. In this study, a three-dimensional fully-integrated groundwater-surface water model was used to simulate the transport characteristics and cumulative loading of an artificial sweetener (acesulfame) and fecal indicator bacteria (Escherichia coli) from WWTPs within a 6800 km2 mixed-use, highly impacted watershed in Ontario, Canada. The model, which employed 3.5 × 106 computational nodes and 15 layers, facilitated a comprehensive assessment of groundwater-surface water interactions under high and low flow conditions; processes typically not accounted for in WWTP cumulative effects models. Simulations demonstrate that the model had significant capacity in reproducing the average and transient multi-year groundwater and surface water flow conditions in the watershed. As a proxy human-specific conservative tracer, acesulfame was useful for model validation and to help inform the representation of watershed-scale transport processes. Using a uniform WWTP acesulfame loading rate of 7.14 mg person-1 day-1, the general spatial trends and magnitudes of the acesulfame concentration profile along the main river reach within the watershed were reproduced; however, model performance was improved by tuning individual WWTP loading rates. Although instream dilution and groundwater-surface water interactions were strongly dependent on flow conditions, the main reach primarily consisted of groundwater discharge zones. For this reason, hydrodynamic dispersion in the hyporheic zone is shown as the predominant mechanism driving acesulfame into near-stream shallow groundwater, while under high flow conditions, the simulations demonstrate the potential for advective flushing of the shallow groundwater. Regarding the cumulative impact of the WWTPs on E. coli concentrations in the surface flow system, simulated transient E. coli levels downstream of WWTPs in the watershed were significantly lower than observed values, thus highlighting the potential importance of other sources of E. coli in the watershed.

Contemporary limnology of the rapidly changing glacierized watershed of the world's largest High Arctic lake.

Glacial runoff is predicted to increase in many parts of the Arctic with climate change, yet little is known about the biogeochemical impacts of meltwaters on downstream freshwater ecosystems. Here we document the contemporary limnology of the rapidly changing glacierized watershed of the world's largest High Arctic lake (Lake Hazen), where warming since 2007 has increased delivery of glacial meltwaters to the lake by up to 10-times. Annually, glacial meltwaters accounted for 62-98% of dissolved nutrient inputs to the lake, depending on the chemical species and year. Lake Hazen was a strong sink for NO3--NO2-, NH4+ and DOC, but a source of DIC to its outflow the Ruggles River. Most nutrients entering Lake Hazen were, however, particle-bound and directly transported well below the photic zone via dense turbidity currents, thus reinforcing ultraoligotrophy in the lake rather than overcoming it. For the first time, we apply the land-to-ocean aquatic continuum framework in a large glacierized Arctic watershed, and provide a detailed and holistic description of the physical, chemical and biological limnology of the rapidly changing Lake Hazen watershed. Our findings highlight the sensitivity of freshwater ecosystems to the changing cryosphere, with implications for future water quality and productivity at high latitudes.

Improving the magnetoelectric performance of Metglas/PZT laminates by annealing in a magnetic field.

A comprehensive investigation of magnetostriction optimization in Metglas 2605SA1 ribbons is performed to enhance magnetoelectric performance. We explore a range of annealing conditions to relieve remnant stress and align the magnetic domains in the Metglas, while minimizing unwanted crystallization. The magnetostriction coefficient, magnetoelectric coefficient, and magnetic domain alignment are correlated to optimize magnetoelectric performance. We report on direct magnetostriction observed by in-plane Doppler vibrometer and domain imagining using scanning electron microscopy with polarization analysis for a range of annealing conditions. We find that annealing in an oxygen-free environment at 400 °C for 30 min yields an optimal magnetoelectric coefficient, magnetostriction and magnetostriction coefficient. The optimized ribbons had a magnetostriction of 50.6 ± 0.2 µm m-1 and magnetoelectric coefficient of 79.3 ± 1.5 µm m-1 mT-1. The optimized Metglas 2605SA1 ribbons and PZT-5A (d31 mode) sensor achieves a magnetic noise floor of approximately 600 pT Hz-1/2 at 100 Hz and a magnetoelectric coefficient of 6.1 ± 0.03 MV m-1 T-1.

Millions of Boreal Shield Lakes can be used to Probe Archaean Ocean Biogeochemistry.

Life originated in Archaean oceans, almost 4 billion years ago, in the absence of oxygen and the presence of high dissolved iron concentrations. Early Earth oxidation is marked globally by extensive banded iron formations but the contributing processes and timing remain controversial. Very few aquatic habitats have been discovered that match key physico-chemical parameters of the early Archaean Ocean. All previous whole ecosystem Archaean analogue studies have been confined to rare, low sulfur, and permanently stratified lakes. Here we provide first evidence that millions of Boreal Shield lakes with natural anoxia offer the opportunity to constrain biogeochemical and microbiological aspects of early Archaean life. Specifically, we combined novel isotopic signatures and nucleic acid sequence data to examine processes in the anoxic zone of stratified boreal lakes that are naturally low in sulfur and rich in ferrous iron, hallmark characteristics predicted for the Archaean Ocean. Anoxygenic photosynthesis was prominent in total water column biogeochemistry, marked by distinctive patterns in natural abundance isotopes of carbon, nitrogen, and iron. These processes are robust, returning reproducibly after water column re-oxygenation following lake turnover. Evidence of coupled iron oxidation, iron reduction, and methane oxidation affect current paradigms of both early Earth and modern aquatic ecosystems.

Atypical small acinar proliferation (ASAP): Is a repeat biopsy necessary ASAP? A multi-institutional review.

BACKGROUND: Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30-40% of patients with ASAP may develop prostate cancer (PCa) within a 5-year period. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis. Our objective was to examine the association between ASAP and subsequent diagnosis of high-grade PCa and to evaluate the need for immediate repeat biopsy. METHODS: A retrospective multi-institutional review identified 264 patients who underwent prostate biopsy from 2000 to 2013 (Brown), 2008 to 2013 (University of Massachusetts) and 1994 to 2005 (Mayo) and were diagnosed with ASAP. Patients underwent transrectal ultrasound-guided biopsies for elevated PSA and/or abnormal digital rectal exam. Clinicopathologic features were assessed, including rates of subsequent PCa detection of any high-grade (Gleason 7-10) PCa. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology. RESULTS: All 264 patients included underwent repeat biopsy with a median follow-up of 5.4 years (interquartile range: 4.6, 6.7). Of these patients, 89 (34%) were subsequently diagnosed with PCa including 21 (8%) with high-grade PCa. Pre-biopsy PSA was higher among patients subsequently diagnosed with (6.7 vs 5.8, P<0.001). Of those diagnosed with subsequent PCa, 69/89 (78%) had less than or equal to Gleason 3+3 disease and only 15/89 (17%) had Gleason 7 and 6/89 (6%) revealed Gleason ⩾8-10. Radical prostatectomy was performed on 36/89 (40%) patients. Surgical pathology revealed 11 patients ⩾Gleason 8-10 PCa. CONCLUSIONS: Although 34% of patients with an initial diagnosis of ASAP who had repeat biopsy were subsequently diagnosed with PCa only, only 22% (8% of the total cohort) were found to have high-grade disease. Higher PSA was associated with increased risk of identifying PCa on repeat biopsy. These findings suggest that immediate repeat biopsy may be omitted in the majority of men with ASAP.

Performance predictors of brain-computer interfaces in patients with amyotrophic lateral sclerosis.

OBJECTIVE: Patients with amyotrophic lateral sclerosis (ALS) may benefit from brain-computer interfaces (BCI), but the utility of such devices likely will have to account for the functional, cognitive, and behavioral heterogeneity of this neurodegenerative disorder. APPROACH: In this study, a heterogeneous group of patients with ALS participated in a study on BCI based on the P300 event related potential and motor-imagery. RESULTS: The presence of cognitive impairment in these patients significantly reduced the quality of the control signals required to use these communication systems, subsequently impairing performance, regardless of progression of physical symptoms. Loss in performance among the cognitively impaired was accompanied by a decrease in the signal-to-noise ratio of task-relevant EEG band power. There was also evidence that behavioral dysfunction negatively affects P300 speller performance. Finally, older participants achieved better performance on the P300 system than the motor-imagery system, indicating a preference of BCI paradigm with age. SIGNIFICANCE: These findings highlight the importance of considering the heterogeneity of disease when designing BCI augmentative and alternative communication devices for clinical applications.

Use of an Artificial Sweetener to Identify Sources of Groundwater Nitrate Contamination.

The artificial sweetener acesulfame (ACE) is a potentially useful tracer of waste water contamination in groundwater. In this study, ACE concentrations were measured in waste water and impacted groundwater at 12 septic system sites in Ontario, Canada. All samples of septic tank effluent (n = 37) had ACE >6 µg/L, all samples of groundwater from the proximal plume zones (n = 93) had ACE >1 µg/L and, almost all samples from the distal plume zones had ACE >2 µg/L. Mean mass ratios of total inorganic nitrogen/ACE at the 12 sites ranged from 680 to 3500 for the tank and proximal plume samples. At five sites, decreasing ratio values in the distal zones indicated nitrogen attenuation. These ratios were applied to three aquifers in Canada that are nitrate-stressed and an urban stream where septic systems are present nearby to estimate the amount of waste water nitrate contamination. At the three aquifer locations that are agricultural, low ACE values (<0.02-0.15 µg/L) indicated that waste water contributed <15% of the nitrate in most samples. In groundwater discharging to the urban stream, much higher ACE values (0.2-11 µg/L) indicated that waste water was the likely source of >50% of the nitrate in most samples. This study confirms that ACE is a powerful tracer and demonstrates its use as a diagnostic tool for establishing whether waste water is a significant contributor to groundwater contamination or not.

Degradation of sucralose in groundwater and implications for age dating contaminated groundwater.

The artificial sweetener sucralose has been in use in Canada and the US since about 2000 and in the EU since 2003, and is now ubiquitous in sanitary wastewater in many parts of the world. It persists during sewage treatment and in surface water environments and as such, has been suggested as a powerful tracer of wastewater. In this study, longer-term persistence of sucralose was examined in groundwater by undertaking a series of three sampling snapshots of a well constrained wastewater plume in Canada (Long Point septic system) over a 6-year period from 2008 to 2014. A shrinking sucralose plume in 2014, compared to earlier sampling, during this period when sucralose use was likely increasing, provides clear evidence of degradation. However, depletion of sucralose from a mean of 40 µg/L in the proximal plume zone, occurred at a relatively slow rate over a period of several months to several years. Furthermore, examination of septic tank effluent and impacted groundwater at six other sites in Canada, revealed that sucralose was present in all samples of septic tank effluent (6-98 µg/L, n = 32) and in all groundwater samples (0.7-77 µg/L, n = 64). Even though sucralose degradation is noted in the Long Point plume, its ubiquitous presence in the groundwater plumes at all seven sites implies a relatively slow rate of decay in many groundwater septic plume environments. Thus, sucralose has the potential to be used as an indicator of 'recent' wastewater contamination. The presence of sucralose identifies groundwater that was recharged after 2000 in Canada and the US and after 2003 in the EU and many Asian countries.

Acute hyperammonaemia induces a sustained decrease in vigilance, which is modulated by caffeine.

UNLABELLED: Hyperammonaemia is observed after prolonged, intense exercise, or in patients with hepatic failure. In the latter, it is associated with a set of neurological and psychiatric abnormalities termed hepatic encephalopathy. THE AIMS OF OUR STUDY WERE: 1. to measure vigilance in a condition of induced hyperammonaemia; 2. to assess whether caffeine modulates the effects of hyperammonaemia on vigilance, if any. Ten healthy volunteers (28.5 ± 5 years; 5 males) underwent three experimental sessions consisting of two-hourly measurements of capillary ammonia, subjective sleepiness (Karolinska Sleepiness Scale) and vigilance (Psychomotor Vigilance Task, PVT), in relation to the intake of breakfast (+/-coffee), an amino acid mixture which induces hyperammonaemia (amino acid challenge; AAC), and AAC+coffee (only for participants who had coffee with their standard breakfast). The AAC resulted in: 1. the expected increase in capillary ammonia levels, with highest values at approximately 4 h after the administration; 2. a significant increase in subjective sleepiness ratings; 3. a sustained increase in PVT-based reaction times. When caffeine was administered after the AAC, both subjective sleepiness and the slowing in RTs were significantly milder than in the AAC-only condition. In conclusion, acute hyperammonaemia induces an increase in subjective sleepiness and a sustained decrease in vigilance, which are attenuated by the administration of a single espresso coffee.

Insight into the relationship between brain/behavioral speed and variability in patients with minimal hepatic encephalopathy.

OBJECTIVE: Intra-individual variability (IIV) of response reaction times (RTs) and psychomotor slowing were proposed as markers of brain dysfunction in patients with minimal hepatic encephalopathy (MHE), a subclinical disorder of the central nervous system frequently detectable in patients with liver cirrhosis. However, behavioral measures alone do not enable investigations into the neural correlates of these phenomena. The aim of this study was to investigate the electrophysiological correlates of psychomotor slowing and increased IIV of RTs in patients with MHE. METHODS: Event-related potentials (ERPs), evoked by a stimulus-response (S-R) conflict task, were recorded from a sample of patients with liver cirrhosis, with and without MHE, and a group of healthy controls. A recently presented Bayesian approach was used to estimate single-trial P300 parameters. RESULTS: Patients with MHE, with both psychomotor slowing and higher IIV of RTs, showed higher P300 latency jittering and lower single-trial P300 amplitude compared to healthy controls. In healthy controls, distribution analysis revealed that single-trial P300 latency increased and amplitude decreased as RTs became longer; however, in patients with MHE the linkage between P300 and RTs was weaker or even absent. CONCLUSIONS: These findings suggest that in patients with MHE, the loss of the relationship between P300 parameters and RTs is related to both higher IIV of RTs and psychomotor slowing. SIGNIFICANCE: This study highlights the utility of investigating the relationship between single-trial ERPs parameters along with RT distributions to explore brain functioning in normal or pathological conditions.

Model-based rational feedback controller design for closed-loop deep brain stimulation of Parkinson's disease.

OBJECTIVE: To explore the use of classical feedback control methods to achieve an improved deep brain stimulation (DBS) algorithm for application to Parkinson's disease (PD). APPROACH: A computational model of PD dynamics was employed to develop model-based rational feedback controller design. The restoration of thalamocortical relay capabilities to patients suffering from PD is formulated as a feedback control problem with the DBS waveform serving as the control input. Two high-level control strategies are tested: one that is driven by an online estimate of thalamic reliability, and another that acts to eliminate substantial decreases in the inhibition from the globus pallidus interna (GPi) to the thalamus. Control laws inspired by traditional proportional-integral-derivative (PID) methodology are prescribed for each strategy and simulated on this computational model of the basal ganglia network. MAIN RESULTS: For control based upon thalamic reliability, a strategy of frequency proportional control with proportional bias delivered the optimal control achieved for a given energy expenditure. In comparison, control based upon synaptic inhibitory output from the GPi performed very well in comparison with those of reliability-based control, with considerable further reduction in energy expenditure relative to that of open-loop DBS. The best controller performance was amplitude proportional with derivative control and integral bias, which is full PID control. We demonstrated how optimizing the three components of PID control is feasible in this setting, although the complexity of these optimization functions argues for adaptive methods in implementation. SIGNIFICANCE: Our findings point to the potential value of model-based rational design of feedback controllers for Parkinson's disease.

Ammonia-related changes in cerebral electrogenesis in healthy subjects and patients with cirrhosis.

OBJECTIVE: To study the effect of hyperammonaemia on the wake electroencephalogram (EEG) of patients with cirrhosis and healthy volunteers. METHODS: Wake EEGs were recorded prior to and after the induction of controlled hyperammonaemia in 10 patients with cirrhosis and 10 matched healthy volunteers. RESULTS: At baseline, patients had higher ammonaemia than healthy volunteers and their dominant EEG rhythm was slower and of higher amplitude. Induced hyperammonaemia resulted in increased spectral power over most of the scalp in healthy volunteers and decreased frequency along the anterior-posterior midline in patients. CONCLUSIONS: These findings suggest different effects of hyperammonaemia on the wake EEG in relation to baseline/peak ammonia levels. SIGNIFICANCE: The wake EEG is sensitive to hyperammonaemia and power-based EEG parameters may help in its neurophysiological definition, which, to date, has generally been based on EEG frequency indices.

Modulation of affective symptoms and resting state activity by brain stimulation in a treatment-resistant case of obsessive-compulsive disorder.

The effect of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) on psychopathological symptoms and resting state brain activity was assessed in a patient with obsessive-compulsive disorder (OCD). tDCS and rTMS had no effect on OC symptoms. tDCS, however, improved depression and anxiety. Functional magnetic resonance imaging at baseline showed an interhemispheric asymmetry with hyperactivation of the left and hypoactivation of the right anterior neural circuits. A reduction of interhemispheric imbalance was detected after tDCS but not after rTMS. tDCS seems to be more effective than rTMS in restoring interhemispheric imbalance and improving anxiety and depression in OCD.

A patients' and caregivers' perspective on hepatic encephalopathy.

Awareness of previous hepatic encephalopathy (HE) and compliance with treatment can probably reduce HE recurrence. The aim of this study was to assess the degree of awareness of previous HE and its treatment in a group of cirrhotic patients and their caregivers. Thirty-five cirrhotic patients with a history of HE and their caregivers (n = 31) were enrolled. Patients underwent evaluation of HE (clinical, psychometry and electroencephalography), quality of life (SF36 questionnaire), and awareness of HE/treatment on an ad hoc questionnaire (QAE). Caregivers underwent the QAE plus the Caregiver Burden Inventory. On the day of study, 7 patients were unimpaired, 8 had minimal and 20 low-grade overt HE. Of the patients, 37 % were aware of previous HE, 6 % of being on treatment and 6 % understood treatment effects. Of the caregivers, 48 % were aware of previous HE, 6 % of their relative being on treatment and 6 % understood treatment effects. Significant correlations were observed between neuropsychiatric status/linear HE indices and both the patients' quality of life and the caregivers' burden. In conclusion, HE awareness was poor in both patients and caregivers, most likely in relation to insufficient/inadequate provision of information.

Neuropsychological tools in hepatology: a survival guide for the clinician.

Neuropsychological assessment has three main applications in clinical hepatology: (i) to detect, grade and monitor liver failure-related cognitive alterations in end-stage liver disease (hepatic encephalopathy), (ii) to substantiate complaints of attention or concentration difficulties in patients with non-cirrhotic chronic hepatitis C viral infection, and (iii) to screen patients who are being considered for liver transplantation for early signs of dementia. However, there is limited agreement on how cognitive assessment should be conducted in these patients, and how results should be interpreted and used to implement clinical decisions. In this review, we summarize the available literature on neuropsychological dysfunction in patients with cirrhosis and with chronic hepatitis C viral infection and provide some guidance on how to utilize neuropsychological assessment in practice.