Immunopathological aspects of trypanosomal meningoencephalitis in vervet monkeys after relapse following BerenilR treatment

Four quarantined vervet monkeys were treated with intramuscular BerenilR in patent CNS infection after experimental trypanosome inoculation with Trypanosoma brucei rhodesiense or T. brucei brucei. All four animals relapsed in the post-therapeutic survival time of 37 to 209 days when they had fully developed meningoencephalitis in histological sections with the presence of interstitial intracerebral trypanosomes, which were confirmed in two monkeys by electron microscopy. In both, sequential samples of the serum and cerebrospinal fluid were analysed for circulating immune complexes, immunoglobulins and albumin. From these results the intracerebral IgG synthesis and the impairment of the blood-brain-barrier were calculated, both being present in advanced infection. Circulating immune complexes were present in the serum, but could not be demonstrated in the cerebrospinal fluid. The monkey model therefore permits the study of various aspects of cerebral trypanosomiasis. BerenilR treatment is inefficient in patent CNS infection and leads to a protracted, less virulent disease course with terminal meningoencephalitis and intracerebral "persister” trypanosomes. This drug-induced trypanosome shift with meningoencephalitis could be used for chemotherapeutic purposes to test new compounds in late stage diseas

Deconstructing Diagnosis: Four Commentaries on a Diagnostic Tool to Assess Individuals for Autism Spectrum Disorders

This is the final version. Available on open access from Autreach Press via the link in this recordDiagnostic assessment tools are widely used instruments in research and clinical practice to assess and evaluate autism symptoms for both children and adults. These tools typically involve observing the child or adult under assessment, and rating their behaviour for signs or so-called symptoms of autism. In order to examine how autism diagnosis is constructed, how diagnostic tools are positioned, and how their trainings are delivered, we paid for four places on a training course for a diagnostic tool. We asked the attendees (the first four authors) to each produce a critical commentary about their impressions of the training and the diagnostic tool itself. Their commentaries are published here in full. They have various disciplinary backgrounds: one is a social scientist, one an ethicist, one a psychiatrist, and one a developmental psychologist. The commentaries are followed by a concluding section that summarises the themes, commonalities, and differences between their accounts of the training course. Authors differed as to whether the diagnostic tool is a useful and necessary endeavour. Nevertheless, all critiqued of the tool’s lack of transparency, recognizing context, emotion, and differences in interpretation and power imbalances as playing an unidentified role in the assessment process. Based on this project, we recommend that training for raters for such tools should be accessible to a wider group of people, and incorporate more explicit recognition of its own limitations and commercialisation.Wellcome Trus

Neurovisceral phenotypes in the expression of psychiatric symptoms

This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brainbody mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in 'emotional' brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognised factors causing vasodilatation (as noted post prandially, post exertion and with heat) is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety

Selective laser trabeculoplasty: past, present, and future

Over the past two decades, selective laser trabeculoplasty (SLT) has increasingly become an established laser treatment used to lower intraocular pressure in open-angle glaucoma and ocular hypertensive patients. In this review we trace the origins of SLT from previous argon laser trabeculoplasty and review the current role it has in clinical practice. We outline future directions of SLT research and introduce emerging technologies that are further developing this intervention in the treatment paradigm of glaucoma.Eye advance online publication, 5 January 2018; doi:10.1038/eye.2017.273