Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Functional dystonia and the borderland between neurology and psychiatry: New concepts.

Mind-brain dualism has dominated historical commentary on dystonia, a dichotomous approach that has left our conceptual grasp of it stubbornly incomplete. This is particularly true of functional dystonia, most diagnostically challenging of all functional movement disorders, in which the question of inherent psychogenicity remains a focus of debate. Phenomenological signs considered in isolation lack the specificity to distinguish organic and nonorganic forms, and dystonia's variability has frustrated attempts to develop objective laboratory-supported standards. Diagnostic criteria for functional dystonia that place emphasis on psychiatric symptoms perform poorly in studies of reliability, partly explained by the high frequency of psychopathology in organic dystonia. Novel approaches from the cognitive neurosciences may offer a way forward. Theory on Bayesian statistical prediction in cognitive processing is supported by sufficient experimental evidence for this model to be taken seriously as a way of reconciling contradictory notions about voluntary and unconscious motor control in functional movement disorders. In a Bayesian formulation of functional dystonia, misallocation of attention and abnormal predictive beliefs generate movements that are executed without a sense of agency. Building on this framework, there is a consensus that a biopsychosocial approach is required and that a unified philosophy of brain and mind is the best way to locate dystonia in the neurology-psychiatry borderland. At a practical level, movement disorder neurologists are best placed to differentiate organic from functional dystonia. The main role of psychiatrists is in the diagnosis and management of the primarily psychiatric disorders that often accompany dystonia. © 2016 International Parkinson and Movement Disorder Society.

Geste Antagoniste Effects on Motor Performance in Dystonia-A Kinematic Study.

Background: The kinematic effects of gestes have not previously been studied. The mechanism(s) by which these sensory tricks modify dystonic movement is not well understood. Objectives: A kinematic investigation of the geste phenomenon in patients with dystonia. Methods: Twenty-three patients with dystonia associated with a geste were studied. Twenty-nine healthy controls also participated. Fifteen seconds of finger tapping was recorded by electromagnetic sensors, and the task was repeated with geste. Separable motor components were extracted using a custom-written MATLAB script. Performance with and without geste was compared using Wilcoxon signed ranks testing. Results: Speed and fluency of finger tapping is impaired in dystonia. When patients executed their geste, speed of movement (amplitude × frequency) increased (P < 0.0001), and halts decreased (P = 0.007). Conclusions: That gestes improve not only dystonic muscle contraction but also the efficiency of voluntary movement suggests a broad influence at the premotor control stage.

Raised visual contrast thresholds with intact attention and metacognition in functional motor disorder.

Functional motor disorders (FMDs) are distinguished by signs that lack congruence with recognised patterns of organic disease and show inconsistency over time. Their pathophysiology is poorly understood, but there is evidence that irregularities in perceptual and cognitive processing lie at the heart of these conditions. Here, we draw on a predictive coding account of functional neurological disorders to study perceptual decision-making in three groups: 20 patients with FMDs (14 with functional movements and 6 with functional weakness), 20 with phenotypically-matched organic motor disorders, and 20 age-matched healthy controls. We examine four cognitive domains with putative roles in FMD pathogenesis: attention, expectations, sensory processing (perceptual sensitivity), and metacognition (introspective evaluation of performance). We augmented a dual-task paradigm, manipulating the visual contrast required for target detection to examine these domains in one design. With sensory input (stimulus contrast) psychometrically adjusted to staircase target detection at a fixed level for all groups, the FMD group exhibited statistically equivalent attentional, expectational and metacognitive processing to healthy controls. However, we demonstrate Bayesian evidence and a frequentist trend that FMD patients require higher visual contrast than controls to maintain the same detection sensitivity (BF10 = 8.1, pholm = .066). This was statistically equivalent to the visual contrast required by the organic group, and unlikely to be accounted for by medication use or comorbid psychopathology. The organic group showed differences in processing of attention and expectations for target detection that were not observed in either healthy controls or the functional group. The distinctive behavioural profile of FMDs may arise from abnormalities in basic sensory processing, while higher attentional, expectational and metacognitive mechanisms remain intact. Conceptualising functional neurological disorders under a predictive coding account may consolidate and refine existing pathophysiological theories about them.

Depression and psychosis in ADCY5-related dyskinesia-part of the phenotypic spectrum?

This report details prominent neuropsychiatric features in one family with an ADCY5 gene mutation. ADCY5 mutations cause a variable motor phenotype, though most cases have some core involuntary movement features. The psychiatric aspects of the disorder have not been emphasised in previous publications. We discuss possible pathogenesis.

Antimicrobial activity of a novel bioengineered honey against non-typeable Haemophilus influenzae biofilms: an in vitro study.

The opportunistic pathogen non-typeable Haemophilus influenzae (NTHi) plays an important role in many chronic respiratory diseases including otitis media, chronic rhinosinusitis, cystic fibrosis and chronic obstructive pulmonary disease. Biofilm formation has been implicated in NTHi colonisation, persistence of infection and recalcitrance towards antimicrobials. There is therefore a pressing need for the development of novel treatment strategies that are effective against NTHi biofilm-associated diseases. SurgihoneyRO is a honey-based product that has been bioengineered to enable the slow release of H2O2, a reactive oxygen species to which H. influenzae is susceptible. Treatment of established NTHi biofilms with SurgihoneyRO significantly reduced biofilm viability through enhanced H2O2 production and was shown to be more effective than the conventional antibiotic co-amoxiclav.

A History of Dystonia: Ancient to Modern.

Before 1911, when Hermann Oppenheim introduced the term dystonia, this movement disorder lacked a unifying descriptor. While words like epilepsy, apoplexy, and palsy have had their meanings since antiquity, references to dystonia are much harder to identify in historical documents. Torticollis is an exception, although there is difficulty distinguishing dystonic torticollis from congenital muscular torticollis. There are, nevertheless, possible representations of dystonia in literature and visual art from the pre-modern world. Eighteenth century systematic nosologists such as Linnaeus, de Sauvages, and Cullen had attempted to classify some spasmodic conditions, including torticollis. But only after Charcot's contributions to clinical neuroscience were the various forms of generalized and focal dystonia clearly delineated. They were categorized as névroses: Charcot's term for conditions without an identifiable neuroanatomical cause. For a time thereafter, psychoanalytic models of dystonia based on Freud's ideas about unconscious conflicts transduced into physical symptoms were ascendant, although there was always a dissenting "organic" school. With the rise of subspecialization in movement disorders during the 1970s, the pendulum swung strongly back toward organic causation. David Marsden's clinical and electrophysiological research on the adult-onset focal dystonias was particularly important in establishing a physical basis for these disorders. We are still in a period of "living history" of dystonia, with much yet to be understood about pathophysiology. Rigidly dualistic models have crumbled in the face of evidence of electrophysiological and psychopathological overlap between organic and functional dystonia. More flexible biopsychosocial frameworks may address the demand for new diagnostic and therapeutic rationales.

Reactive oxygen: A novel antimicrobial mechanism for targeting biofilm-associated infection.

Reactive oxygen species (ROS) is a novel therapeutic strategy for topical or local application to wounds, mucosa or internal structures where there may be heavy bacterial bioburden with biofilm and chronic inflammation. Bacterial biofilms are a significant problem in clinical settings owing to their increased tolerance towards conventionally prescribed antibiotics and their propensity for selection of further antibacterial resistance. There is therefore a pressing need for the development of alternative therapeutic strategies that can improve antibiotic efficacy towards biofilms. ROS has been successful in treating chronic wounds and in clearing multidrug-resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA), and carbapenemase-producing isolates from wounds and vascular line sites. There is significant antifungal activity of ROS against planktonic and biofilm forms. Nebulised ROS has been evaluated in limited subjects to assess reductions in bioburden in chronically colonised respiratory tracts. The antibiofilm activity of ROS could have great implications for the treatment of a variety of persistent respiratory conditions. Use of ROS on internal prosthetic devices shows promise. A variety of novel delivery mechanisms are being developed to apply ROS activity to different anatomical sites.

When myopathy breaks the rules: a late-onset distal presentation.

Myopathies typically present with proximal or generalised muscle weakness, but it is important for clinicians to recognise they may also have other distributions. This paper describes a case of distal myopathy that was confirmed genetically as ZASP (Z-band alternatively spliced PDZ motif-containing protein) myofibrillar myopathy (MFM). MFMs are particularly topical because the genetic basis of several have recently been established, enabling diagnosis of conditions previously labelled 'idiopathic myopathy', and shedding new light on their pathophysiology. This paper describes a purely distal lower limb phenotype of ZASP MFM, the pathophysiology of ZASP and other MFMs, and the differential diagnosis of late-onset distal symmetrical weakness. The case includes several learning points: ZASP MFM is a new diagnosis; it should be included in differential diagnoses for late-onset myopathy, especially if there is a distal pattern or autosomal dominant inheritance; testing for cardiomyopathy is recommended, and a genetic test is now available.

Taking steps together: a family- and community-based obesity intervention for urban, multiethnic children.

OBJECTIVES: Successful childhood obesity intervention models that build sustainable behavioral change are needed, particularly in low-income, ethnic minority communities disparately affected by this problem. METHOD: Families were referred to Taking Steps Together (TST) by their primary care provider if at least one child had a body mass index ≥85%. The TST intervention comprised 16 weekly 2-hour classes including educational activities, group cooking/eating, and physical activities for parents and children. TST's approach emphasized building self-efficacy, targeting both children and parents for healthy change, and fostering intrinsic motivation for healthier living. Pre-post intervention data were collected on health-related behaviors using a survey, and trained staff measured weight and height. RESULTS: Adults (n = 33) and children (n = 62) were largely Hispanic/Latino and low-income. Adults and children significantly increased their fruit and vegetable consumption and weekly physical activity, and adults significantly decreased sugared beverage consumption and screen time. No change in body mass index was observed for adults or children. CONCLUSIONS: This family-focused childhood obesity intervention integrated evidence-based principles with a nonprescriptive approach and produced significant improvements in key healthy behaviors for both adults and children.

Potential of real-time measurement of GFP-fusion proteins.

Building on the basic design concepts of Randers-Eichhorn [Biotechnol. Bioeng. 55 (1997) 921], an on-line, real-time robust, steam sterilisable optical sensor for monitoring green fluorescent protein (GFP) has been developed. A general cloning vector for fusion expression proteins was constructed, allowing expression of both GFP and the target protein as a fusion. Cultivations were carried out at the 20l scale with the signal from the sensor being relayed directly to the control system of the bioreactors. The production of GFP was then measured on-line, the signal was interfaced directly with other controlling parameters, thereby allowing the microbial process to be controlled directly based on recombinant protein expression. A positive expression correlation between on-line and off-line data was obtained. Protein accretion measured off-line was quantified using both LC-MS and plate reader assays. The potential of such a sensor for many aspects of process development is considerable and we have developed a working system which allows the optimisation of production conditions, for example, linking pH control directly to the fusion protein. Results are also presented that illustrate GFP does not alter the cultivation characteristics of the target protein when compared to the native construct. Whether GFP expressed as a fusion influences the solubility of the target protein is also discussed.

A case of mosaic trisomy 19q12-q13.2 with high BMI, macrocephaly, and speech delay: does USF2 determine size in the 19q phenotypes?

Hall et al. (2010) describe a boy with mosaic trisomy of the proximal part of 19q, with obesity, macrocephaly and global developmental delay. The patient is interesting with regard to his cytogenetic abnormality, which is smaller than those previously reported, and does not include the candidate obesity and insulin-resistance genes identified by other authors (Zung et al., 2007; Davidsson et al., 2010) as possible causes of the overweight/obesity seen in four of five previously documented patients. This suggests that a novel obesity locus may reside in the duplicated region 19q13.11­q13.2. We present a phenotypically similar boy with intrachromosomal insertion of material derived from proximal 19q into proximal 19p, causing mosaic trisomy 19q12­q13.2, and consider the role of USF2, a master transcriptional regulator of metabolic genes, in 19q phenotypes.

Cryptic EWSR1-FLI1 fusions in Ewing sarcoma: potential pitfalls in the diagnostic use of fluorescence in situ hybridization probes.

Detection of EWSR1 translocations - particularly t(11;22)(q24;q12) - is of great value in the differential diagnosis of the Ewing family of tumors. We report two cases that highlight the problems and pitfalls of identifying Ewing tumors using conventional chromosome analysis and a commercial EWSR1 fluorescence in situ hybridization (FISH) probe. In both cases, the tumor karyotype was abnormal, but a visible t(11;22)(q24;q12) was not present. The commercial EWSR1 "break-apart" probe was not split in either case. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, however, identified EWSR1-FLI1 fusion transcripts in both tumors, and the gene fusions were corroborated by FISH analysis with "in house" probes and confirmed by sequencing RT-PCR products. The occurrence of cryptic EWSR1-FLI1 fusions mandates that RT-PCR should be performed, particularly in those cases in which the genetic findings are not in agreement with the histologic picture.

Geographical variation in relationships between parental body size and offspring phenotype at birth.

BACKGROUND: Size and body proportions at birth are partly determined by maternal body composition, but most studies of mother-baby relationships have only considered the effects of maternal height and weight on offspring birth weight, and few have examined the size of effects. Paternal size and body composition also play a role, primarily through the fetal genome, although few studies have investigated relationships with neonatal phenotype. METHODS: Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria and Jamaica were used to investigate the effects of maternal measures (derived at 30 weeks' gestation, n=16,418), and also paternal size (n=3,733) on neonatal phenotype, for singleton, live-born, term births. RESULTS: After accounting for variation in maternal size and shape across populations, differences in neonatal phenotype were markedly reduced. Mother-baby relationships were similar across populations, although some were stronger in developing countries. Maternal height was generally the strongest predictor of neonatal length, maternal head circumference of neonatal head and maternal skinfold thickness of neonatal skinfolds. Relationships with maternal arm muscle area were generally weak. Effects of paternal height and body mass index were weaker than the equivalent maternal measurements in most studies. CONCLUSIONS: Differences in maternal body composition account for a large part of the geographical variation in neonatal phenotype. The size of the effects of all maternal measures on neonatal phenotype suggests that nutrition at every stage of the mother's life cycle may influence fetal growth. Further research is needed into father-baby relationships and the genetic mechanisms that influence fetal growth.

Geographical variation in neonatal phenotype.

BACKGROUND: Recent studies have shown associations between size and body proportions at birth and health outcomes throughout the life cycle, but there are few data on how neonatal phenotype varies in different populations around the world. METHODS: Data from the UK, Finland, India, Sri Lanka, China, DR Congo, Nigeria, and Jamaica (n=22,067) were used to characterize geographical differences in phenotype in singleton, live-born newborns. Measurements included birth weight, placental weight, length, head, chest, abdominal and arm circumferences, and skinfolds. RESULTS: Neonates in Europe were the largest, followed by Jamaica, East Asia (China), then Africa and South Asia. Birth weight varied widely (mean values 2,730-3,570 g), but in contrast, head circumference was similar in all except China (markedly smaller). The main difference in body proportions between populations was the head to length ratio, with small heads relative to length in China and large heads relative to length in South Asia and Africa. CONCLUSIONS: These marked geographical differences in neonatal phenotype need to be considered when investigating determinants of fetal growth, and optimal phenotype for short-term and long-term outcomes.