OBTURATOR HOOK SIGN — WHEN THE COMMON ILIAC VEIN DISAPPEARANCE ELUDES VISUAL DETECTION

Introduction: Diagnosis of chronic iliac venous outflow obstruction is challenging, and no ideal imaging method has yet been defined. Even with imaging with superb detail, common iliac vein disappearance as occurs in Post-Thrombotic Syndrome (PTS) may be missed even by the most experienced radiologist. This scanning error occurs due to psychophysiological factors of human visual perception. The purpose of this paper is to report on the “obturator hook sign”, evidencing obturator vein engorgement as a collateral pathway and hence a marker for hemodynamically significant chronic iliac venous outflow lesion, supporting this diagnosis. Methods: Retrospective review of Indirect and Direct Computed Tomography Venography (CTV) and Magnetic Resonance Venography (MRV) imaging of the obturator hook sign and comprehensive literature review regarding iliac vein outflow obstruction diagnosis focusing on collateral vein development. Results : The obturator hook sign is identified in Direct CTV, Indirect CTV and MRV of patients with chronic iliac venous outflow obstruction. The sign was never identified in imaging studies with no chronic iliac obstruction, suggesting high specificity. Discussion: Venous collateralization is poorly understood, but it has been shown that when the main venous path is stenosed or occluded and the venous pressure rises, flow is side-tracked through alternative pathways. When the main venous path lesion is stented, flow once again takes the lower resistance pathway and the collaterals withdraw. The obturator hook sign can be easily recognisable in CTV and MRV due to its peculiar anatomy and immediately points us towards hemodynamically significant chronic iliac venous outflow obstruction

What enhances the formation of social bonds & facilitates better engagement & retention in an addiction service?

The study explored whether there are key skills that staff use to relate to service users which help with the formation of social bonds, which in turn leads to increased levels of service user engagement and retention. Data for the study was collected through a literature review, ethnographic observation, interviews and focus groups with staff and service users. The findings showed that staff are successful at engaging and retaining service users and it is their ability to form strong social bonds which is the key to its success. This is achieved through the philosophy of the project which is made up of three central tenets: a non-punitive approach, person-centred care and trauma informed care. The person-centred care approach facilitates the formation of a partnership between staff and service users in which they work together to achieve personalised recovery goals unique to each individual service user. The non-punitive approach stipulates that service users are not punished or judged for having a relapse, which results in the reduction of shame and the promotion of honesty. This non-punitive stance is experienced by service users as facilitative to their recovery, with some participants reporting that this approach was less evident in other models of addiction treatment. Trauma Informed Care allows service users to seek appropriate treatment for any possible underlying issues they may have, allowing them to fully engage in the service. The three interrelated strands of the philosophy produce an approach to the treatment of substance misuse that is considered to be unique and different to many mainstream addiction models and provides a platform for the formation of social bonds. There are some trade-offs as a result of adopting such a philosophy. It was discovered that staff place a large emphasis on trauma informed care; it is commendable that staff have committed to an approach which endeavours to identify people who have been exposed to trauma and are impacted by symptoms of Post-Traumatic Stress Disorder, as well as their recognition of the value of referral to appropriate treatment services. Given that there are a number of other confounding factors which may also be decisive, it is recommended that staff consider a balanced approach which remains open to other factors besides trauma such as the community reinforcement approach, motivational interviewing and the person centred approach. Secondly, the desire to unconditionally support service users while supportive and empowering has the possible drawback of fostering dependency and impeding autonomy. It is recommended that the balance between high levels of support and promoting independence continues to be a central element of the service approach to active discharge planning. Finally, the research identified a need to upskill in areas such as mental health and couple counselling to further support service users who may have dual diagnosis or who are experiencing relationship problems due to substance misuse

Semaphorin 6A knockout mice display abnormalities across ethologically-based topographies of exploration and in motor learning

Semaphorins are secreted or membrane-bound proteins implicated in neurodevelopmental processes of axon guidance and cell migration. Exploratory behaviour and motor learning was examined ethologically in Semaphorin 6A (Sema6A) mutant mice. The ethogram of initial exploration in Sema6A knockout mice was characterised by increased rearing to wall with decreased sifting; over subsequent habituation, locomotion, sniffing and rearing to wall were increased, with reduced habituation of rearing seated. Rotarod analysis indicated delayed motor learning in Sema6A heterozygous mutants. Disruption to the axonal guidance and cell migration processes regulated by Sema6A is associated with topographically specific disruption to fundamental aspects of behaviour, namely the ethogram of initial exploration and subsequent habituation to the environment, and motor learning

Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat

Gut microbiota colonization is a key event for host physiology that occurs early in life. Disruption of this process leads to altered brain development which ultimately manifests as changes in brain function and behaviour in adulthood. Studies using germ-free mice highlight the extreme impact on brain health that results from life without commensal microbes, however the impact of microbiota disturbances occurring in adulthood is less studied. To this end, we depleted the gut microbiota of 10-week-old male Sprague Dawley rats via chronic antibiotic treatment. Following this marked, sustained depletion of the gut bacteria, we investigated behavioural and molecular hallmarks of gut-brain communication. Our results reveal that depletion of the gut microbiota during adulthood results in deficits in spatial memory as tested by Morris water maze, increased visceral sensitivity and a greater display of depressive-like behaviours in the forced swim test. In tandem with these clear behavioural alterations we found change in altered CNS serotonin concentration along with changes in the mRNA levels of corticotrophin releasing hormone receptor 1 and glucocorticoid receptor. Additionally, we found changes in the expression of BDNF, a hallmark of altered microbiota-gut-brain axis signaling. In summary, this model of antibiotic-induced depletion of the gut microbiota can be used for future studies interested in the impact of the gut microbiota on host health without the confounding developmental influence of early-life microbial alterations

Disruption to social dyadic interactions but not emotional/anxiety-related behaviour in mice with heterozygous \u27knockout\u27 of the schizophrenia risk gene neuregulin-1.

Clinical genetic studies have implicated neuregulin-1 [NRG1] as a leading susceptibility gene for schizophrenia. NRG1 is known to play a significant role in the developing brain, which is consistent with the prevailing neurodevelopmental model of schizophrenia. Thus, the emotional and social phenotype of adult mice with heterozygous \u27knockout\u27 of transmembrane [TM]-domain NRG1 was examined further in both sexes. Emotional/anxiety-related behaviour was assessed using the elevated plus-maze and the light-dark test. Social behaviour was examined in terms of dyadic interactions between NRG1 mutants and an unfamiliar C57BL6 conspecific in a novel environment. There was no effect of NRG1 genotype on performance in either test of emotionality/anxiety. However, previous reports of hyperactivity in NRG1 mutants were confirmed in both paradigms. In the test of social interaction, aggressive following was increased in NRG1 mutants of both sexes, together with an increase in walkovers in female mutants. These findings elaborate the specificity of the NRG1 phenotype for the social rather than the emotional/anxiety-related domain. They indicate that NRG1 is involved in the regulation of reciprocal social interaction behaviour and thus suggest a putative role for NRG1 in a schizophrenia-related endophenotype

A monocyte-TNF-endothelial activation axis in sickle transgenic mice: Therapeutic benefit from TNF blockade

Elaboration of tumor necrosis factor (TNF) is a very early event in development of ischemia/reperfusion injury pathophysiology. Therefore, TNF may be a prominent mediator of endothelial cell and vascular wall dysfunction in sickle cell anemia, a hypothesis we addressed using NY1DD, S+SAntilles, and SS‐BERK sickle transgenic mice. Transfusion experiments revealed participation of abnormally activated blood monocytes exerting an endothelial activating effect, dependent upon Egr‐1 in both vessel wall and blood cells, and upon NFκB(p50) in a blood cell only. Involvement of TNF was identified by beneficial impact from TNF blockers, etanercept and infliximab, with less benefit from an IL‐1 blocker, anakinra. In therapeutic studies, etanercept ameliorated multiple disturbances of the murine sickle condition: monocyte activation, blood biomarkers of inflammation, low platelet count and Hb, vascular stasis triggered by hypoxia/reoxygenation (but not if triggered by hemin infusion), tissue production of neuro‐inflammatory mediators, endothelial activation (monitored by tissue factor and VCAM‐1 expression), histopathologic liver injury, and three surrogate markers of pulmonary hypertension (perivascular inflammatory aggregates, arteriolar muscularization, and right ventricular mean systolic pressure). In aggregate, these studies identify a prominent—and possibly dominant—role for an abnormal monocyte‐TNF‐endothelial activation axis in the sickle context. Its presence, plus the many benefits of etanercept observed here, argue that pilot testing of TNF blockade should be considered for human sickle cell anemia, a challenging but achievable translational research goal

Adult microbiota-deficient mice have distinct dendritic morphological changes: Differential effects in the amygdala and hippocampus

Increasing evidence implicates the microbiota in the regulation of brain and behaviour. Germ‐free mice (GF; microbiota deficient from birth) exhibit altered stress hormone signalling and anxiety‐like behaviours as well as deficits in social cognition. Although the mechanisms underlying the ability of the gut microbiota to influence stress responsivity and behaviour remain unknown, many lines of evidence point to the amygdala and hippocampus as likely targets. Thus, the aim of this study was to determine if the volume and dendritic morphology of the amygdala and hippocampus differ in GF versus conventionally colonized (CC) mice. Volumetric estimates revealed significant amygdalar and hippocampal expansion in GF compared to CC mice. We also studied the effect of GF status on the level of single neurons in the basolateral amygdala (BLA) and ventral hippocampus. In the BLA, the aspiny interneurons and pyramidal neurons of GF mice exhibited dendritic hypertrophy. The BLA pyramidal neurons of GF mice had more thin, stubby and mushroom spines. In contrast, the ventral hippocampal pyramidal neurons of GF mice were shorter, less branched and had less stubby and mushroom spines. When compared to controls, dentate granule cells of GF mice were less branched but did not differ in spine density. These findings suggest that the microbiota is required for the normal gross morphology and ultrastructure of the amygdala and hippocampus and that this neural remodelling may contribute to the maladaptive stress responsivity and behavioural profile observed in GF mice

11 C-Metomidate PET/CT is a useful adjunct for lateralization of primary aldosteronism in routine clinical practice.

OBJECTIVE: To describe clinical practice experience of 11 C-Metomidate PET/CT as an adjunct to adrenal vein sampling (AVS) in the lateralization of aldosterone-producing adenomas (APA) in primary aldosteronism (PA). CONTEXT: Accurate lateralization of APA in the setting of PA offers the potential for surgical cure and improved long-term cardiovascular outcomes. Challenges associated with AVS, the current gold standard lateralization modality, mean that only a small proportion of potentially eligible patients currently make it through to surgery. This has prompted consideration of alternative strategies for lateralization, including the application of novel molecular PET tracers such as 11 C-Metomidate. DESIGN: Clinical Service Evaluation/Retrospective audit. PATIENTS: Fifteen individuals with a confirmed diagnosis of PA, undergoing lateralization with 11 C-Metomidate PET/CT prior to final clinical decision on surgical vs medical management. MEASUREMENTS: All patients underwent screening aldosterone renin ratio (ARR), followed by confirmatory testing with the seated saline infusion test, according to Endocrine Society Clinical Practice Guidelines. Adrenal glands were imaged using dedicated adrenal CT. 11 C-Metomidate PET/CT was undertaken due to equivocal or failed AVS. Management outcomes were assessed by longitudinal measurement of blood pressure, ARR, number of hypertensive medications following adrenalectomy or institution of medical therapy. RESULTS: We describe the individual lateralization and clinical outcomes for 15 patients with PA. CONCLUSION: 11 C-Metomidate PET/CT in conjunction with adrenal CT and AVS provided useful information which aided clinical decision-making for PA within a multidisciplinary hypertension clinic