Prevalence of Slam-dependent hemophilins in Gram-negative bacteria.

Iron acquisition systems are crucial for pathogen growth and survival in iron-limiting host environments. To overcome nutritional immunity, bacterial pathogens evolved to use diverse mechanisms to acquire iron. Here, we examine a heme acquisition system that utilizes hemophores called hemophilins which are also referred to as HphAs in several Gram-negative bacteria. In this study, we report three new HphA structures from Stenotrophomonas maltophilia, Vibrio harveyi, and Haemophilus parainfluenzae. Structural determination of HphAs revealed an N-terminal clamp-like domain that binds heme and a C-terminal eight-stranded ß-barrel domain that shares the same architecture as the Slam-dependent Neisserial surface lipoproteins. The genetic organization of HphAs consists of genes encoding a Slam homolog and a TonB-dependent receptor (TBDR). We investigated the Slam-HphA system in the native organism or the reconstituted system in Escherichia coli cells and found that the efficient secretion of HphA depends on Slam. The TBDR also played an important role in heme uptake and conferred specificity for its cognate HphA. Furthermore, bioinformatic analysis of HphA homologs revealed that HphAs are conserved in the alpha, beta, and gammaproteobacteria. Together, these results show that the Slam-dependent HphA-type hemophores are prevalent in Gram-negative bacteria and further expand the role of Slams in transporting soluble proteins. IMPORTANCE: This paper describes the structure and function of a family of Slam (Type IX secretion System) secreted hemophores that bacteria use to uptake heme (iron) while establishing an infection. Using structure-based bioinformatics analysis to define the diversity and prevalence of this heme acquisition pathway, we discovered that a large portion of gammaproteobacterial harbors this system. As organisms, including Acinetobacter baumannii, utilize this system to facilitate survival during host invasion, the identification of this heme acquisition system in bacteria species is valuable information and may represent a target for antimicrobials.

Neurocognitive functioning among children and young people with Duchenne Muscular Dystrophy: A systematic review and meta-analysis.

Objective: The neurocognitive aspects of DMD have received less attention than the physiological sequalae. This study conducted a systematic review and meta-analysis of available literature on the neurocognitive profile of children and young people with DMD. Method: Five databases (EMBASE, Medline, PsycInfo, Scopus and Web of Science) and the grey literature was searched on 27th January 2023. Eligible articles were available in English and reported neurocognitive outcomes. Neurocognitive domains reported in a comparable way across a minimum of three studies were included. The neurocognitive domains of Full-Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ) and Working memory (WMI) derived from Wechsler scales and receptive vocabulary ability derived from the Peabody Picture Verbal Test (PPVT) were included. A single mean meta-analysis was completed. Results: Relevant data was extracted and presented for 38 eligible studies; 2 of which are from grey literature. Results suggest children with DMD perform around 1SD below non-clinical norms for FSIQ, PIQ, VIQ and WMI. Unlike VIQ, scores derived from the PPVT were within the non-clinical norms. Studies were of moderate - high quality, there was significant heterogeneity and no publication bias. Conclusion: A systematic review of working memory has not previously been completed, it appears that children with DMD perform around 1SD below the mean, like FSIQ, PIQVIQ and WMI. The PPVT is a measure of receptive verbal ability and caution is recommended around the interchangeability of PPVT scores and the wider construct of verbal intelligence.

Contributing factors to secondary traumatic stress and vicarious posttraumatic growth in therapists.

Alongside the recognized potential negative repercussions of working as a psychological therapist, there is growing interest in the potential positive impacts of engaging in such work. The current study used a cross-sectional online survey design to explore the impact of a range of demographic, work-related, and compassion-related factors on levels of secondary traumatic stress (STS) and vicarious posttraumatic growth (VPTG) in an international sample of 359 psychological therapists. Hierarchical multiple regressions demonstrated that burnout, lower levels of self-compassion, having a personal trauma history, reporting a higher percentage of working time with a trauma focus, and being female were the statistically significant contributors to STS scores, explaining 40.8% of the variance, F(9, 304) = 23.2, p <.001. For VPTG, higher compassion satisfaction, higher self-compassion, higher STS, a higher percentage of working time with a trauma focus, fewer years qualified, being male, and having a personal trauma history were all statistically significant contributors, explaining 27.3% of the variance, F (10, 304) = 11.37, p <.001. The findings illustrate the potential risk and protective factors for developing STS and clarify factors that may increase the likelihood of experiencing VPTG. Implications for psychological therapists and the organizations and institutions for which they work are considered along with potential directions for future research in the discussion.

Drug Dissolution in Oral Drug Absorption: Workshop Report.

The in-person workshop "Drug Dissolution in Oral Drug Absorption" was held on May 23-24, 2023, in Baltimore, MD, USA. The workshop was organized into lectures and breakout sessions. Three common topics that were re-visited by various lecturers were amorphous solid dispersions (ASDs), dissolution/permeation interplay, and in vitro methods to predict in vivo biopharmaceutics performance and risk. Topics that repeatedly surfaced across breakout sessions were the following: (1) meaning and assessment of "dissolved drug," particularly of poorly water soluble drug in colloidal environments (e.g., fed conditions, ASDs); (2) potential limitations of a test that employs sink conditions for a poorly water soluble drug; (3) non-compendial methods (e.g., two-stage or multi-stage method, dissolution/permeation methods); (4) non-compendial conditions (e.g., apex vessels, non-sink conditions); and (5) potential benefit of having both a quality control method for batch release and a biopredictive/biorelevant method for biowaiver or bridging scenarios. An identified obstacle to non-compendial methods is the uncertainty of global regulatory acceptance of such methods.

A systematic review of quality of life and health-related quality of life as outcomes in substance and behavioural addictions.

ISSUES: Consideration of an individual's quality of life (QoL) can benefit assessment and treatment of addictive disorders, however, uncertainty remains over operationalisation of the construct as an outcome and the appropriateness of existing measures for these populations. This systematic review aimed to identify and evaluate QoL and health-related QoL outcome instruments used in addiction-related risk and harm research and map their conceptualised domains. APPROACH: Three electronic databases and a specialised assessment library were searched on 1 February 2022 for QoL or health-related QoL outcome instruments used with addiction-related risk and harm populations. PRISMA reporting guidance was followed and included outcome instruments were appraised using mixed methods. Psychometric evidence supporting their use was summarised. The COSMIN risk of bias tool was used to assess validation studies. KEY FINDINGS: A total of 298 articles (330 studies) used 53 outcome instruments and 41 unique domains of QoL. Eleven instruments' psychometric properties were evaluated. No instrument was assessed for any parameter in at least five studies for meta-analytic pooling. Cronbach's alpha (α) internal consistency was the most widely assessed parameter with the AQoLS, WHOQOL-BREF, ALQoL-9, Q-LES-Q-SF, SF-12, DUQoL, QLI and SF-36 displaying promising statistics (α > 0.70). IMPLICATIONS AND CONCLUSION: Many instruments have been utilised. However, a significant proportion of studies applied a small number of instruments with minimal high-quality validation evidence supporting their use within addiction-related risk and harm. Promising instruments are recommended, however, the paucity of supporting evidence limits confidence in the reliability and validity of QoL measurement in these populations.

Reverse vaccinology-based identification of a novel surface lipoprotein that is an effective vaccine antigen against bovine infections caused by Pasteurella multocida.

Pasteurella multocida can infect a multitude of wild and domesticated animals, with infections in cattle resulting in hemorrhagic septicemia (HS) or contributing to bovine respiratory disease (BRD) complex. Current cattle vaccines against P. multocida consist of inactivated bacteria, which only offer limited and serogroup specific protection. Here, we describe a newly identified surface lipoprotein, PmSLP, that is present in nearly all annotated P. multocida strains isolated from cattle. Bovine associated variants span three of the four identified phylogenetic clusters, with PmSLP-1 and PmSLP-2 being restricted to BRD associated isolates and PmSLP-3 being restricted to isolates associated with HS. Recombinantly expressed, soluble PmSLP-1 (BRD-PmSLP) and PmSLP-3 (HS-PmSLP) vaccines were both able to provide full protection in a mouse sepsis model against the matched P. multocida strain, however no cross-protection and minimal serum IgG cross-reactivity was identified. Full protection against both challenge strains was achieved with a bivalent vaccine containing both BRD-PmSLP and HS-PmSLP, with serum IgG from immunized mice being highly reactive to both variants. Year-long stability studies with lyophilized antigen stored under various temperatures show no appreciable difference in biophysical properties or loss of efficacy in the mouse challenge model. PmSLP-1 and PmSLP-3 vaccines were each evaluated for immunogenicity in two independent cattle trials involving animals of different age ranges and breeds. In all four trials, vaccination with PmSLP resulted in an increase in antigen specific serum IgG over baseline. In a blinded cattle challenge study with a recently isolated HS strain, the matched HS-PmSLP vaccine showed strong efficacy (75-87.5% survival compared to 0% in the control group). Together, these data suggest that cattle vaccines composed of PmSLP antigens can be a practical and effective solution for preventing HS and BRD related P. multocida infections.

Clinicians' implicit and explicit attitudes about the legitimacy of functional neurological disorders correlate with referral decisions.

OBJECTIVES: Uncertainty regarding the legitimacy of functional neurological disorder (FND) remains among some health care professionals. Despite treatment guidelines and consensus recommendations, variability in clinical practice referral decisions persists. Evidence from other conditions suggests such clinical decision making is impacted by practitioners' implicit and explicit attitudes. We aimed to identify whether health care professionals hold implicit and/or explicit attitudes about the legitimacy of FND and whether these attitudes are associated with referral decision making. DESIGN/METHODS: We included 66 health care professionals who work with people with neurological conditions: n = 37 medical doctors, mainly neurologists (n = 18) and psychiatrists (n = 10), and n = 29 doctoral level practitioner psychologists. Participants completed an Implicit Association Test (IAT), Implicit Relational Assessment Procedure (IRAP), a referral decision-making vignette task and self-report measures of explicit attitudes on FND-legitimacy, therapeutic optimism and clinician confidence. Multiple Sclerosis (MS) was used as a comparator condition. RESULTS: Participants self-reported strong explicit FND-legitimate and MS-legitimate attitudes but demonstrated an implicit FND-illegitimate/MS-legitimate bias. Deeper examination provided by the IRAP data indicated pro-FND-legitimate attitudes, but no bias for or against FND-illegitimate-contrasting the pro-MS-legitimate, anti-MS-illegitimate attitudes for the comparator condition. Attitudes about FND-illegitimacy were negatively associated with likelihood of referral to physical interventions such as physiotherapy. Medical doctors had lower treatment optimism and stronger explicit attitudes that FND is illegitimate than psychologists. CONCLUSIONS: At an implicit level, clinicians are uncertain about the illegitimacy of FND, and such attitudes are associated with lower likelihood of referral to physiotherapy in particular. Improved education on FND among health care professionals is indicated.

Empirically Derived Patterns of Posttraumatic Stress and Growth: A Systematic Review.

The relationship between posttraumatic stress (PTS) and posttraumatic growth (PTG) has been extensively studied; however, the nature of the relationship remains unclear. Inconsistencies in the literature could be, in part, due to the use of variable level approaches. Person centered methods may further our understanding of this relationship, as they enable the identification of clinically meaningful subgroups based on PTS/PTG scores. This review aimed to identify commonly found subgroups of PTS and PTG, clinically relevant factors that distinguish the subgroups and to critically appraise the utility of categorizing individuals into subgroups based on PTS/PTG scores. Five databases (Embase, Medline, Web of Science, PILOTS, and PsycINFO) were searched. Seven studies (with a total of eight study samples; n = 6,776) met the eligibility criteria. A narrative synthesis of the findings revealed that the majority of the analyses (n = 6) found three patterns of PTS/PTG. These were categorized as: (1) low PTS/PTG (representing 26.89% of the entire sample), (2) high PTS/PTG (weighted mean percentage = 20.05%), and (3) low PTS/high PTG (weighted mean percentage = 43.1%). The role of social support was examined in five studies and higher social support was consistently found to predict membership in the low PTS/high PTG class. All five studies that examined the role of trauma characteristics found that it was a significant predictor of class membership. These findings could inform the developments of tailored interventions. The utility of person-centered approaches was discussed and recommendations to improve the application and reporting of such methods were made.

Modelling intramuscular drug fate in vitro with tissue-relevant biomimetic hydrogels.

Parenteral administrations are a mainstay of clinical drug delivery. Intramuscular (IM) injections deposit drug directly into skeletal muscle bellies, providing rapid systemic uptake due to the highly vascularized nature of this site. The potential to inject particulate or non-aqueous materials have also made IM injections useful for long-acting formulations. These attributes have supported a plethora of medicines being approved for IM administration. Despite these many approvals across multiple pharmaceutical categories, mechanisms that control drug release from the injection site, and thus its pharmacokinetic properties, remain poorly understood. Several pre-clinical in vivo animals have been used to model IM drug fate in patients, but these approaches have not consistently predicted clinical outcomes. This lack of a predictive in vivo model and no standardized in vitro tools have limited the options of pharmaceutical scientists to rationally design formulations for IM delivery. Here, we describe a novel, tractable in vitro model informed by dominant extracellular matrix (ECM) components present at the IM injection site. Three charge variants of green florescent protein (GFP) and the impact of three common formulation components were examined in an initial test of this in vitro model. A strongly positively charged GFP was restricted in its release from hydrogels composed of ECM components type I collagen and hyaluronic acid compared to standard and strongly negatively charged GFP. Introduction of commonly used buffers (histidine or acetate) or the non-ionic surfactant polysorbate 20 altered the release properties of these GFP variants in a manner that was dependent upon ECM element composition. In sum, this Simulator of IntraMuscular Injections, termed SIMI, demonstrated distinct release profiles of a protein biopharmaceutical surrogate that could be exploited to interrogate the impact of formulation components to expedite novel drug development and reduce current dependence on potentially non-predictive pre-clinical in vivo models.

Cognitive and psychosocial outcomes following stereotactic radiosurgery for acoustic neuroma.

BACKGROUND: Acoustic Neuroma (AN) is a benign tumour of the eighth cranial nerve. Stereotactic Radiosurgery (SRS) is a common treatment approach. Studies have explored the primary effects of SRS and documented equivalent efficacy for tumour control compared to neurosurgery. OBJECTIVE: Examine the longer term cognitive and psychosocial outcomes of SRS in non-Neurofibromatosis Type II patients utilising both objective and subjective cognitive outcomes associated with quality of life and health related distress. METHODS: Nineteen individuals treated via SRS were assessed using a battery of standardised psychometric tests as well as measures of quality of life and psychological distress. RESULTS: Participants had largely preserved cognitive function except for processing speed, aspects of attention and visual memory relative to age norms. Self-reported quality of life was better than in other AN population studies. Level of psychological distress was equivalent to general population norms. More than half of participants reported subjective cognitive decline though this was not fully supported by objective testing. Subjective cognitive complaints may be associated with lower reported quality of life. CONCLUSIONS: Results are largely consistent with previous findings on the effects of SRS in other clinical groups, which supports SRS as a targeted radiation treatment for AN.

Exploring the relationship between alienation appraisals, trauma, posttraumatic stress, and depression.

OBJECTIVE: Cognitive models posit negative trauma appraisals as maintaining symptoms of posttraumatic stress disorder. Recent research has demonstrated that alienation appraisals (feeling disconnected from the self and others) are salient in trauma-related distress. Studies show that alienation appraisals fully mediated the relationship between trauma exposure and symptoms of posttraumatic stress disorder (PTSD) in trauma-exposed adults. This study explored alienation appraisals in student and clinical samples, assessing whether alienation significantly mediated the relationship between cumulative trauma and trauma-related distress. It also explored whether alexithymia, social support, and loneliness also mediated the relationship between cumulative trauma and markers of trauma-related distress, clarifying the role of alienation. METHOD: Mediation and hierarchical regression models were tested with questionnaire data from a student sample (N = 100) and clinical sample of trauma-exposed treatment-seeking adults (N = 93). RESULTS: In the student sample, alienation (B = 1.27) fully mediated the relationship between cumulative trauma and posttraumatic stress, but not depression. When alexithymia, social support, and loneliness were entered as parallel mediators, only alienation appraisals (B = 1.03) significantly mediated the relationship between cumulative trauma and posttraumatic stress. For the clinical sample, alienation appraisals (ß = .53) were the only significant predictor of posttraumatic stress, while alienation appraisals (ß = .75) and, to a lesser extent, social support (ß = .19) and loneliness (ß = .30) significantly predicted depression. CONCLUSIONS: Alienation was a salient predictor of posttraumatic distress. Clinical assessment of alienation appraisals is recommended to inform psychological interventions for trauma survivors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Meta-Analysis of the Efficacy of Virtual Reality and In Vivo Exposure Therapy as Psychological Interventions for Public Speaking Anxiety.

Public speaking anxiety (PSA) is a prevalent condition with disabling occupational, educational, and social consequences. Exposure therapy is a commonly utilized approach for treating PSA. Traditionally, this intervention has been delivered as in vivo exposure therapy (IVET). Limitations inherent to in vivo as a mode of delivery have been identified and studies have increasingly explored the use of Virtual Reality Exposure Therapy (VRET) as an alternative. Understanding the efficacy of both VRET and IVET as psychological interventions for PSA is important. A systematic search identified 11 studies with 508 participants. Meta-analysis yielded a large significant effect wherein VRET resulted in significant reductions in PSA versus control of -1.39 (Z = 3.96, p < .001) and a similar large significant effect wherein IVET resulted in significant reductions in PSA versus control of -1.41 (Z = 7.51, p < .001). Although IVET was marginally superior to VRET, both interventions proved efficacious. Given the advantages of utilizing VRET over IVET future research and clinical practice could explore VRET as a treatment option for PSA.

Actinobacillus utilizes a binding protein-dependent ABC transporter to acquire the active form of vitamin B6.

Bacteria require high-efficiency uptake systems to survive and proliferate in nutrient-limiting environments, such as those found in host organisms. ABC transporters in the bacterial plasma membrane provide a mechanism for transport of many substrates. In this study, we examine an operon containing a periplasmic binding protein in Actinobacillus for its potential role in nutrient acquisition. The electron density map of 1.76 Å resolution obtained from the crystal structure of the periplasmic binding protein was best fit with a molecular model containing a pyridoxal-5'-phosphate (P5P/pyridoxal phosphate/the active form of vitamin B6) ligand within the protein's binding site. The identity of the P5P bound to this periplasmic binding protein was verified by isothermal titration calorimetry, microscale thermophoresis, and mass spectrometry, leading us to name the protein P5PA and the operon P5PAB. To illustrate the functional utility of this uptake system, we introduced the P5PAB operon from Actinobacillus pleuropneumoniae into an Escherichia coli K-12 strain that was devoid of a key enzyme required for P5P synthesis. The growth of this strain at low levels of P5P supports the functional role of this operon in P5P uptake. This is the first report of a dedicated P5P bacterial uptake system, but through bioinformatics, we discovered homologs mainly within pathogenic representatives of the Pasteurellaceae family, suggesting that this operon exists more widely outside the Actinobacillus genus.

360° Video virtual reality exposure therapy for public speaking anxiety: A randomized controlled trial.

Public speaking anxiety (PSA) is a prevalent condition which is highly interrelated with social anxiety. PSA can be effectively treated with exposure therapy. Virtual reality exposure therapy (VRET) is increasingly being explored as a novel and cost-effective mode of treatment. No previous randomized controlled trial has examined whether stand-alone 360° video VRET is an effective intervention for treating PSA and interrelated disorder relevant fears. Further, studies have not explored whether 360° video content influences VRET outcomes. Participants with high PSA (n = 51) were randomly allocated to: 360° video VRET incorporating stimuli of audiences (360°Audience) (n = 17), 360° video VRET incorporating stimuli of empty rooms (360°Empty) (n = 16) and no treatment control (n = 18). Outcomes were measured over five time-points. Mixed ANOVA revealed a significant interaction between time and intervention group for PSA, social anxiety and fear of negative evaluation (FNE). Within-group analysis demonstrated there was a significant pre-intervention to post-intervention reduction across measures for both 360° video VRET groups: PSA 360°Audience (ηp2 = .90, p<.001), 360°Empty (ηp2 = .71, p < .001); social anxiety 360°Audience (ηp2 = .49, p=.002), 360°Empty (ηp2 = .39, p = .009); FNE 360°Audience (ηp2 = .59, p<.001), 360°Empty (ηp2 = .43, p = .006). Active intervention participants showed significant improvement from pre-intervention to 10-week follow-up on all measures. Findings illustrate that 360° video VRET is an efficacious way to significantly reduce PSA, social anxiety and FNE.

Evaluating parameters affecting drug fate at the intramuscular injection site.

Intramuscular (IM) injections are a well-established method of delivering a variety of therapeutics formulated for parenteral administration. While the wide range of commercial IM pharmaceuticals provide a wealth of pharmacokinetic (PK) information following injection, there remains an inadequate understanding of drug fate at the IM injection site that could dictate these PK outcomes. An improved understanding of injection site events could improve approaches taken by formulation scientists to identify therapeutically effective and consistent drug PK outcomes. Interplay between the typically non-physiological aspects of drug formulations and the homeostatic IM environment may provide insights into the fate of drugs at the IM injection site, leading to predictions of how a drug will behave post-injection in vivo. Immune responses occur by design after e.g. vaccine administration, however immune responses post-injection are not in the scope of this article. Taking cues from existing in vitro modelling technologies, the purpose of this article is to propose "critical parameters" of the IM environment that could be examined in hypothesis-driven studies. Outcomes of such studies might ultimately be useful in predicting and improving in vivo PK performance of IM injected drugs.

Effects of non-invasive respiratory support on gas exchange and outcomes in COVID-19 outside the ICU.

Non-invasive respiratory support (NRS) outside of the ICU has played an important role in the management of COVID-19 pneumonia. There is little data to guide selection of NRS modality. We present outcomes of NRS outside the ICU and discuss the effects of NRS on gas exchange with implications for management.

A meta-analytic review of the relationship between attachment styles and posttraumatic growth.

OBJECTIVE: The present review aimed to examine the relationship between attachment styles and posttraumatic growth in adults exposed to traumatizing events. METHOD: A systematic literature search resulted in the inclusion of 14 studies in the review. Four correlational meta-analyses of the relationship between the attachment styles of secure, dismissive, preoccupied, and fearful, and posttraumatic growth, were conducted. RESULTS: These revealed a significant small positive relationship between secure attachment and posttraumatic growth (r = 0.21, p < 0.001); a significant small negative relationship between dismissive attachment and posttraumatic growth (r = -0.12, p < 0.001), and a weak relationship between preoccupied attachment and posttraumatic growth (r = -0.04, p = 0.235), and fearful attachment and posttraumatic growth (r = 0.08, p = 0.248). CONCLUSIONS: The relationship between attachment styles and posttraumatic growth is modest and may be better explained by other variables. Nonetheless, findings provide useful information for clinicians regarding the potential small impact of attachment style following traumatizing exposure. Implications for future research are highlighted with respect to methodological rigor and the role of other potentially influential variables.

Alcohol attention bias in 14-16 year old adolescents: an eye tracking study.

RATIONALE: Theoretical models regarding the automaticity of attentional processes highlight a progression of attentional bias style from controlled to automatic in drinking populations as alcohol use progresses. Previous research has focused on older adolescent and adult drinking populations at later stages in their drinking career. OBJECTIVES: The aim of this study was to investigate alcohol attention bias in 14-16-year-old adolescent social drinkers and abstainers. METHODS: Alcohol attention bias was measured in social drinking and abstaining groups in an eye-tracking paradigm. Questionnaires measured alcohol use, expectancies, exposure and socially desirable response styles. RESULTS: Social drinkers fixated to alcohol stimuli more frequently and spent a larger proportion of their fixation time attending to alcohol stimuli compared to non-drinkers. Groups displayed differences in their style of attentional processing of alcohol-related information, with heavy drinkers fixating significantly longer to alcohol information across alcohol stimulus presentation and exhibiting a delayed disengagement style of alcohol attention bias that differentiated them from light drinking and abstaining peers. All social drinkers fixated significantly more than abstainers in the latter half of alcohol stimulus presentation. CONCLUSION: Alcohol attention bias was present in this adolescent sample. Drinking subgroups are defined from abstaining peers by unique features of their attentional bias that are controlled in nature. These findings are comparable to those in other adolescent and adult social drinking populations. The identification of specific attentional bias features according to drinking subpopulations has implications for our theoretical understanding of developing alcohol attention bias and problematic drinking behaviours, as well as at-risk identification and early intervention.

A meta-analysis of executive functions among survivors of subarachnoid haemorrhage.

Subarachnoid Haemorrhage (SAH) is a type of stroke which is suggested to result in Executive Functioning (EF) deficits. Within the SAH research, EF is typically assessed as a unitary cognitive construct. Therefore, the nature and extent to which the different components of EF are impacted post SAH remain unclear. In this meta-analysis, 10 studies met selection criteria including 248 SAH participants, treated by endovascular coiling. Participants were assessed by EF measures and compared with 230 controls. Searches were conducted in November 2018 including Medline, PsychINFO, Web of Science, Scopus and CINAHL databases. EF measures were assigned to categories including Cognitive Flexibility, Working Memory, Inhibitory Control and Planning/Problem Solving [Diamond, 2013. Executive functions. Annual Review of Psychology, 64(1), 135-168. https://doi.org/10.1146/annurev-psych-113011-143750]. A statistically significant effect was found for overall EF. Cognitive Flexibility (G = -0.76) and Inhibitory Control (G = -0.51) generated moderate effect sizes, while Working Memory and Planning/Problem Solving found a small effect size (G = -0.45 and G = -0.49, respectively). The I2 statistic suggested small to moderate heterogeneity between studies, hypothesized to relate to different cognitive tools. Underlying components of EF appear to be differentially impacted post SAH, with Cognitive flexibility demonstrating the largest degree of deficit. Recommendations for a standardized and uniform assessment of EF post SAH are outlined.

Modeling the metabolic interplay between a parasitic worm and its bacterial endosymbiont allows the identification of novel drug targets.

The filarial nematode Brugia malayi represents a leading cause of disability in the developing world, causing lymphatic filariasis in nearly 40 million people. Currently available drugs are not well-suited to mass drug administration efforts, so new treatments are urgently required. One potential vulnerability is the endosymbiotic bacteria Wolbachia-present in many filariae-which is vital to the worm. Genome scale metabolic networks have been used to study prokaryotes and protists and have proven valuable in identifying therapeutic targets, but have only been applied to multicellular eukaryotic organisms more recently. Here, we present iDC625, the first compartmentalized metabolic model of a parasitic worm. We used this model to show how metabolic pathway usage allows the worm to adapt to different environments, and predict a set of 102 reactions essential to the survival of B. malayi. We validated three of those reactions with drug tests and demonstrated novel antifilarial properties for all three compounds.