IntroductionGreater sympathetic drive has been established in the early stages of essential hypertension, suggesting that neurohormonal dysregulation may be key to its aetiology and progression. The aims of this review are to discuss evidence of the role of autonomic dysfunction in essential hypertension and proposed mechanisms, and also some applications of this knowledge to current management strategies of essential hypertension.MethodsA computer search was performed using the PUBMED database for peer reviewed original articles comparing autonomic function tested via heart rate variability (HRV), muscle sympathetic nerve activity (MSNA) or plasma noradrenaline levels in normotensive (mean blood pressure (BP) of ≤140/90 mmHg or ≤135/85 mmHg if measured via home BP measurements) and hypertensive groups (mean resting BP of ≥140/90 mmHg (or ≥135/85 mmHg if measured via home BP measurements). Subjects were excluded with secondary causes of hypertension or autonomic dysfunction.ResultsA total of 17 studies were included for discussion. The main findings of this study include that of reduced baroreflex sensitivity, believed to be secondary to increased arterial stiffness, is hypothesised to be implicated in the pathogenesis of essential hypertension. Also, angiotensin converting enzyme inhibitors were not as effective on markers of autonomic control of blood pressure when compared with alternative anti-hypertensive drugs.ConclusionsConsistent research is needed to establish the effectiveness of pharmacotherapies at each of stage of hypertension, and on markers of autonomic dysfunction. Consistent study designs will enable more accurate accumulation of data across multiple studies, and appropriate application of such data into clinical practice.

The biogenic amine, histamine, has been shown to critically modulate inflammatory processes as well as the properties of neurons and synapses in the brain, and is also implicated in the emergence of neurodevelopmental disorders. Indeed, a reduction in the synthesis of this neuromodulator has been associated with the disorders Tourette’s syndrome and obsessive-compulsive disorder, with evidence that this may be through the disruption of the corticostriatal circuitry during development. Furthermore, neuroinflammation has been associated with alterations in brain development, e.g., impacting synaptic plasticity and synaptogenesis, and there are suggestions that histamine deficiency may leave the developing brain more vulnerable to proinflammatory insults. While most studies have focused on neuronal sources of histamine it remains unclear to what extent other (non-neuronal) sources of histamine, e.g., from mast cells and other sources, can impact brain development. The few studies that have started exploring this in vitro, and more limited in vivo, would indicate that non-neuronal released histamine and other preformed mediators can influence microglial-mediated neuroinflammation which can impact brain development. In this Review we will summarize the state of the field with regard to non-neuronal sources of histamine and its impact on both neuroinflammation and brain development in key neural circuits that underpin neurodevelopmental disorders. We will also discuss whether histamine receptor modulators have been efficacious in the treatment of neurodevelopmental disorders in both preclinical and clinical studies. This could represent an important area of future research as early modulation of histamine from neuronal as well as non-neuronal sources may provide novel therapeutic targets in these disorders.

The prevalence of obstructive sleep apnoea (OSA) increases with age, yet the risk factors for OSA in older people remain poorly understood.This study aimed to define the age-related changes in upper airway morphology in carefully matched groups of healthy older (.60 years, n511) and younger (,40 years, n514) males, using direct (magnetic resonance imaging (MRI)) and indirect (acoustic reflection) imaging.The median (interquartile range) combined retropalatal and retroglossal pharyngeal length was greater in older than in younger males (older 8.8 (7.8-9.0) cm, younger 7.8 (7.0-8.3) cm; p50.03), as was the soft palate cross-sectional area (older 43.1 (36.0-48.8) cm 2 , younger 35.3 (30.5-40.5) cm 2 ; p50.03), parapharyngeal fat pad diameter (older 1.7 (1.4-2.2) cm, younger 1.2 (1.0-1.8) cm; p50.03) and crosssectional area of the fat pads (older 13.8 (9.1-17.1) cm 2 ; younger 7.4 (5.9-13.0) cm 2 ; p50.02) as measured by MRI. Using acoustic reflection, pharyngeal calibre (older 4.8 (3.8-6.6) cm 2 , younger 3.4 (2.8-4.6) cm 2 ; p50.03), pharyngeal volume (older 35.1 (30.9-55.4) cm 3 , younger 27.2 (22.7-44.2) cm 3 ; p50.04) and glottis area (older 2.7 (2.1-3.9) cm 2 , younger 1.3 (1.1-1.9) cm 2 ; p50.003) were also larger in older participants compared with younger participants. There was no difference in craniofacial measures between groups, including volumetric data and hyoid bone position.The larger pharyngeal calibre observed in older males may be compensating for an age-related enlargement in pharyngeal soft tissue that predisposes to OSA. @ERSpublications Pharyngeal factors predisposing to sleep apnoea increase with age; a larger calibre protected against airway collapse

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SUMMARY Autism spectrum disorders (ASDs) are a group of lifelong neurodevelopmental disorders characterised by difficulties in social interactions and social communication, and restricted and repetitive behaviours. Relative to the general population, individuals with ASDs are likely to be overrepresented in secure psychiatric care and custodial settings. Outcomes vary and can be problematic in the context of co-occurring intellectual disability, psychiatric disorder and challenging behaviours. To date, there is little in the way of specialised clinical guidance on the prescription of psychotropic medicines for individuals with ASDs, particularly information on any differences in efficacy and/or tolerability of specific medications. This review summarises the key research to date on the prescription of psychotropic medication in ASD with and without comorbid psychiatric or neurodevelopmental disorders, within the context of the existing clinical guidance. Some critical analysis is provided to aid clinicians in following a safe, effective and individualised approach to prescribing for people with ASDs.