Cognitive impairment among alcohol treatment service users in South Wales: an exploratory examination of typologies of behaviour, impairment, and service attendance.

Introduction: Alcohol dependence is a global issue with many negative consequences, including alcohol-related brain damage (ARBD). Assessment of the sociodemographic and cognitive characteristics of individuals with confirmed or suspected ARBD presenting to alcohol services warrants further investigation. Methods: This study retrospectively examined rates of cognitive impairment using Montreal Cognitive Assessment (MoCA) data from 300 adults who visited three alcohol support services. We demonstrate that 55.3% of the sample had significant levels of cognitive impairment. Females' cognitive performance was disproportionately negatively affected by historical alcohol use relative to males. Results: The analysis identified four categories of participants, and the majority had a long history (+10 years) of alcohol use and were still actively drinking. Those taking part in active treatment for ARBD or practising abstinence demonstrated lower levels of cognitive impairment. Additionally, prior access to specialised ARBD care was associated with higher MoCA scores. Discussion: This research has identified a range of key service engagement, sociodemographic and cognitive characteristics that could be used to optimise support for those with alcohol dependence, whilst also highlighting some critical questions to be addressed in future research.

Detecting Poly (ADP-Ribose) In Vitro and in Cells Using PAR Trackers.

ADP-ribosylation (ADPRylation) is a reversible posttranslational modification resulting in the covalent attachment of ADP-ribose (ADPR) moieties on substrate proteins. Naturally occurring protein motifs and domains, including WWEs, PBZs (PAR binding zinc fingers), and macrodomains, act as "readers" for protein-linked ADPR. Although recombinant, antibody-like ADPR detection reagents containing these readers have facilitated the detection of ADPR, they are limited in their ability to capture the dynamic nature of ADPRylation. Herein, we describe the preparation and use of poly(ADP-ribose) (PAR) Trackers (PAR-Ts)-optimized dimerization-dependent or split-protein reassembly PAR sensors containing a naturally occurring PAR binding domain fused to both halves of dimerization-dependent GFP (ddGFP) or split nano luciferase (NanoLuc), respectively. We also describe how these tools can be used for the detection and quantification of PAR levels in biochemical assays with extracts and in living cells. These protocols will allow users to explore the broad utility of PAR-Ts for detecting PAR in various experimental and biological systems.

Alcohol-related brain damage: an umbrella (term) for the approaching post-COVID monsoon.

Individuals with alcohol-related brain damage (ARBD) represent a population whose healthcare needs often go unmet. This is the result of a lack of not only an awareness surrounding the condition by healthcare professionals, but also healthcare service inclusion and delivery, more broadly. The Coronavirus 2019 (COVID-19) pandemic and the associated lockdowns dramatically affected the accessibility and availability of addiction services globally, while also driving changes in alcohol consumption among the most vulnerable. In the absence of change, this culmination of increased high-risk drinking behaviour, lack of awareness by healthcare professionals and severely limited service delivery for individuals living with ARBD post COVID-19, represents a perfect storm that is rapidly approaching our health and care services world-wide. Collectively, this will reduce positive health outcomes in an already at-risk group.

Applicability of the ACE-III and RBANS Cognitive Tests for the Detection of Alcohol-Related Brain Damage.

BACKGROUND AND AIMS: Recent investigations have highlighted the value of neuropsychological testing for the assessment and screening of Alcohol-Related Brain Damage (ARBD). The aim of the present study was to evaluate the suitability of the Addenbrooke's Cognitive Examination (ACE-III) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for this purpose. METHODS: Comparing 28 participants with ARBD (11 with Korsakoff's Syndrome and 17 with the umbrella "ARBD" diagnosis) and 30 alcohol-dependent participants without ARBD (ALs) we calculated Area Under the Curve (AUC) statistics, sensitivity and specificity values, base-rate adjusted predictive values, and likelihood ratios for both tests. RESULTS: High levels of screening accuracy were found for the total scores of both the ACE-III (AUC = 0.823, 95% CIs [0.714, 0.932], SE = 0.056; optimal cut-off ≤86: sensitivity = 82%, specificity = 73%) and RBANS (AUC = 0.846, 95% CIs [0.746, 0.947], SE = 0.052; optimal cut-off ≤83: sensitivity = 89%, specificity = 67%) at multiple cut-off points. Removing participants with a history of polysubstance from the samples (10 ALs and 1 ARBD) improved the diagnostic capabilities of the RBANS substantially (AUC = 0.915, 95% CIs [0.831, 0.999], SE = 0.043; optimal cut-off ≤85: sensitivity = 98%, specificity = 80%), while only minor improvements to the ACE-III's accuracy were observed (AUC = 0.854, 95% CIs [0.744, 0.963], SE = 0.056; optimal cut-off ≤88: sensitivity = 85%, specificity = 75%). CONCLUSION: Overall, both the ACE-III and RBANS are suitable tools for ARBD screening within an alcohol-dependent population, though the RBANS is the superior of the two. Clinicians using these tools for ARBD screening should be cautious of false-positive outcomes and should therefore combine them with other assessment methods (e.g., neuroimaging, clinical observations) and more detailed neuropsychological testing before reaching diagnostic decisions.

Generating Protein-Linked and Protein-Free Mono-, Oligo-, and Poly(ADP-Ribose) In Vitro.

ADP-ribosylation is a covalent posttranslational modification of proteins that is catalyzed by various types of ADP-ribosyltransferase (ART) enzymes, including members of the poly(ADP-ribose) polymerase (PARP) family. ADP-ribose (ADPR) modifications can occur as mono(ADP-ribosyl)ation, oligo(ADP-ribosyl)ation, or poly(ADP-ribosyl)ation, depending on the particular ART enzyme catalyzing the reaction, as well as the specific reaction conditions. Understanding the biology of ADP-ribosylation requires facile and robust means of generating and detecting the modification in all of its forms. Here we describe how to generate protein-linked mono(ADP-ribose), oligo(ADP-ribose), and poly(ADP-ribose) (MAR, OAR, and PAR, respectively) in vitro as an automodification of PARPs 1 or 3. First, epitope-tagged PARP-1 (a PARP polyenzyme) and PARP-3 (a PARP monoenzyme) are expressed individually in insect cells using baculovirus expression vectors, and purified using immunoaffinity chromatography. Second, the purified recombinant PARPs are incubated individually in the presence of different concentrations of NAD+ (as a donor of ADPR groups) and sheared DNA (to activate their catalytic activities) resulting in various forms of auto-ADP-ribosylation. Third, the products are confirmed using ADPR detection reagents that can distinguish among MAR, OAR, and PAR. Finally, if desired, the OAR and PAR can be deproteinized. The protein-linked and free MAR, OAR, and PAR generated in these reactions can be used as standards, substrates, or binding partners in a variety of ADPR-related assays.

Ethical aspects of diagnosis and interventions for children with fetal alcohol Spectrum disorder (FASD) and their families.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) is an umbrella term covering several conditions for which alcohol consumption during pregnancy is taken to play a causal role. The benefit of individuals being identified with a condition within FASD remains controversial. The objective of the present study was to identify ethical aspects and consequences of diagnostics, interventions, and family support in relation to FASD. METHODS: Ethical aspects relating to diagnostics, interventions, and family support regarding FASD were compiled and discussed, drawing on a series of discussions with experts in the field, published literature, and medical ethicists. RESULTS: Several advantages and disadvantages in regards of obtaining a diagnosis or description of the condition were identified. For instance, it provides an explanation and potential preparedness for not yet encountered difficulties, which may play an essential role in acquiring much needed help and support from health care, school, and the social services. There are no interventions specifically evaluated for FASD conditions, but training programs and family support for conditions with symptoms overlapping with FASD, e.g. ADHD, autism, and intellectual disability, are likely to be relevant. Stigmatization, blame, and guilt are potential downsides. There might also be unfortunate prioritization if individuals with equal needs are treated differently depending on whether or not they meet the criteria for a specific condition. CONCLUSIONS: The value for the concerned individuals of obtaining a FASD-related description of their condition - for instance, in terms of wellbeing - is not established. Nor is it established that allocating resources based on whether individuals fulfil FASD-related criteria is justified, compared to allocations directed to the most prominent specific needs.