A randomised controlled trial of cognitive behavioural treatment for obsessive compulsive disorder in children and adolescents

Cognitive behaviour therapy (CBT) for young people with obsessive compulsive disorder (OCD) has become the treatment of first choice. However, the literature is largely based on studies emphasising exposure and response prevention. In this study, we report on a randomised controlled trial of CBT for young people carried out in typical outpatient clinic conditions which focused on cognitions. A randomised controlled trial compares 10 sessions of manualised cognitive behavioural treatment with a 12-week waiting list for adolescents and children with OCD. Assessors were blind to treatment allocation. 21 consecutive patients with OCD aged between 9 and 18 years were recruited. The group who received treatment improved more than a comparison group who waited for 3 months. The second group was treated subsequently using the same protocol and made similar gains. In conclusion, CBT can be delivered effectively to young people with OCD in typical outpatient settings

Congenital bovine spinal dysmyelination is caused by a missense mutation in the SPAST gene

Bovine spinal dysmyelination (BSD) is a recessive congenital neurodegenerative disease in cattle (Bos taurus) characterized by pathological changes of the myelin sheaths in the spinal cord. The occurrence of BSD is a longstanding problem in the American Brown Swiss (ABS) breed and in several European cattle breeds upgraded with ABS. Here, we show that the disease locus on bovine chromosome 11 harbors the SPAST gene that, when mutated, is responsible for the human disorder hereditary spastic paraplegia (HSP). Initially, SPAST encoding Spastin was considered a less likely candidate gene for BSD since the modes of inheritance as well as the time of onset and severity of symptoms differ widely between HSP and BSD. However, sequence analysis of the bovine SPAST gene in affected animals identified a R560Q substitution at a position in the ATPase domain of the Spastin protein that is invariant from insects to mammals. Interestingly, three different mutations in human SPAST gene at the equivalent position are known to cause HSP. To explore this observation further, we genotyped more than 3,100 animals of various cattle breeds and found that the glutamine allele exclusively occurred in breeds upgraded with ABS. Furthermore, all confirmed BSD carriers were heterozygous, while all affected calves were homozygous for the glutamine allele consistent with recessive transmission of the underlying mutation and complete penetrance in the homozygous state. Subsequent analysis of recombinant Spastin in vitro showed that the R560Q substitution severely impaired the ATPase activity, demonstrating a causal relationship between the SPAST mutation and BSD

A Meta-Analysis of Seaweed Impacts on Seagrasses: Generalities and Knowledge Gaps

Seagrasses are important habitat-formers and ecosystem engineers that are under threat from bloom-forming seaweeds. These seaweeds have been suggested to outcompete the seagrasses, particularly when facilitated by eutrophication, causing regime shifts where green meadows and clear waters are replaced with unstable sediments, turbid waters, hypoxia, and poor habitat conditions for fishes and invertebrates. Understanding the situations under which seaweeds impact seagrasses on local patch scales can help proactive management and prevent losses at greater scales. Here, we provide a quantitative review of available published manipulative experiments (all conducted at the patch-scale), to test which attributes of seaweeds and seagrasses (e.g., their abundances, sizes, morphology, taxonomy, attachment type, or origin) influence impacts. Weighted and unweighted meta-analyses (Hedges d metric) of 59 experiments showed generally high variability in attribute-impact relationships. Our main significant findings were that (a) abundant seaweeds had stronger negative impacts on seagrasses than sparse seaweeds, (b) unattached and epiphytic seaweeds had stronger impacts than ‘rooted’ seaweeds, and (c) small seagrass species were more susceptible than larger species. Findings (a) and (c) were rather intuitive. It was more surprising that ‘rooted’ seaweeds had comparatively small impacts, particularly given that this category included the infamous invasive Caulerpa species. This result may reflect that seaweed biomass and/or shading and metabolic by-products like anoxia and sulphides could be lower for rooted seaweeds. In conclusion, our results represent simple and robust first-order generalities about seaweed impacts on seagrasses. This review also documented a limited number of primary studies. We therefore identified major knowledge gaps that need to be addressed before general predictive models on seaweed-seagrass interactions can be build, in order to effectively protect seagrass habitats from detrimental competition from seaweeds

Caregiver stress in traumatic brain injury

Aims Many patients experience physical, behavioural, cognitive and emotional problems following traumatic brain injury (TBI). They may require continuing care for many years, most of which is provided by informal caregivers, such as spouses, parents, or other family members. The caregiving role is associated with a range of adverse effects including anxiety, depression, poor physical health and lowered quality of life. This article explores issues around caregiver stress; highlighting interventions for this group and areas for further research. Methods Literature exploring the impact of caregiving, its influencing and alleviating factors and interventions for caregivers of people with TBI is discussed, with brief critical analysis of key studies. Findings Research suggests that caregiver characteristics, coping strategies, their appraisal of the situation and social networks may be associated with the amount of distress experienced. Many caregivers have unmet needs such as respite care and information provision on TBI. Providing information may help to alleviate strain. Community-based family therapies providing education, support and counselling can help to decrease distress and improve aspects of family functioning, although evidence for these is lacking. Conclusions There is a need for more well-designed, controlled studies evaluating the impact of interventions to alleviate caregiver strain

Nitrogen and sulphur management: challenges for organic sources in temperate agricultural systems

A current global trend towards intensification or specialization of agricultural enterprises has been accompanied by increasing public awareness of associated environmental consequences. Air and water pollution from losses of nutrients, such as nitrogen (N) and sulphur (S), are a major concern. Governments have initiated extensive regulatory frameworks, including various land use policies, in an attempt to control or reduce the losses. This paper presents an overview of critical input and loss processes affecting N and S for temperate climates, and provides some background to the discussion in subsequent papers evaluating specific farming systems. Management effects on potential gaseous and leaching losses, the lack of synchrony between supply of nutrients and plant demand, and options for optimizing the efficiency of N and S use are reviewed. Integration of inorganic and organic fertilizer inputs and the equitable re-distribution of nutrients from manure are discussed. The paper concludes by highlighting a need for innovative research that is also targeted to practical approaches for reducing N and S losses, and improving the overall synchrony between supply and demand

A unique therapeutic approach to emesis and itch with a proanthocyanidin-rich genonutrient

<p>Abstract</p> <p>Background</p> <p>We examined the therapeutic potential of a proprietary <it>Croton palanostigma </it>extract (Zangrado^®) in the management of emesis and itch.</p> <p>Methods</p> <p>Emesis was induced in ferrets with morphine-6-glucuronide (0.05 mg/kg sc) in the presence of Zangrado (3 mg/kg, ip) and the cannabinoid receptor 1 antagonist, AM 251 (5 mg/kg, ip). Topical Zangrado (1%) was assessed for anti-pruretic actions in the 5-HT-induced scratching model in rats and evaluated in capsaicin-induced gastric hyperemia as measured by laser doppler flow. In the <it>Apc</it>^<it>Min</it>mouse model of precancerous adenomatosis polyposis, mice received Zangrado (100 μg/ml in drinking water) from the age of 6 – 16 weeks for effects on polyp number. In RAW 264.7 cells Zangrado was examined for effects on lipopolysaccharide-induced nitrite production.</p> <p>Results</p> <p>Zangrado was a highly effective anti-emetic, reducing morphine-induced vomiting and retching by 77%. These benefits were not associated with sedation or hypothermia and were not reversed by cannabinoid receptor antagonism. Itch responses were blocked in both the morphine and 5-HT models. Zangrado did not exacerbate the <it>Apc</it>^<it>Min</it>condition rather health was improved. Capsaicin-induced hyperemia was blocked by Zangrado, which also attenuated the production of nitric oxide by activated macrophages.</p> <p>Conclusion</p> <p>Zangrado is an effective anti-emetic and anti-itch therapy that is devoid of common side-effects, cannabinoid-independent and broadly suppresses sensory afferent nerve activation. This complementary medicine represents a promising new approach to the management of nausea, itch and irritable bowel syndrome.</p

Targeting the Neurokinin Receptor 1 with Aprepitant: A Novel Antipruritic Strategy

Chronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment with e.g. antihistamines. Therefore antipruritic therapies which target physiological mechanisms of pruritus need to be developed. Substance P (SP) is a major mediator of pruritus. As it binds to the neurokinin receptor 1 (NKR1), we evaluated if the application of a NKR1 antagonist would significantly decrease chronic pruritus.Twenty hitherto untreatable patients with chronic pruritus (12 female, 8 male; mean age, 66.7 years) were treated with the NKR1 antagonist aprepitant 80 mg for one week. 16 of 20 patients (80%) experienced a considerable reduction of itch intensity, as assessed by the visual analog scale (VAS, range 0 to 10). Considering all patients, the mean value of pruritus intensity was significantly reduced from 8.4 VAS points (SD +/-1.7) before treatment to 4.9 VAS points (SD +/-3.2) (p<0.001, CI 1.913-5.187). Patients with dermatological diseases (e.g. atopic diathesis, prurigo nodularis) had the best profit from the treatment. Side-effects were mild (nausea, vertigo, and drowsiness) and only occurred in three patients.The high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial

A closer look at neuron interaction with track-etched microporous membranes

Microporous membranes support the growth of neurites into and through micro-channels, providing a different type of neural growth platform to conventional dish cultures. Microporous membranes are used to support various types of culture, however, the role of pore diameter in relation to neurite growth through the membrane has not been well characterised. In this study, the human cell line (SH-SY5Y) was differentiated into neuron-like cells and cultured on track-etched microporous membranes with pore and channel diameters selected to accommodate neurite width (0.8 µm to 5 µm). Whilst neurites extended through all pore diameters, the extent of neurite coverage on the non-seeded side of the membranes after 5 days in culture was found to be directly proportional to channel diameter. Neurite growth through membrane pores reduced significantly when neural cultures were non-confluent. Scanning electron microscopy revealed that neurites bridged pores and circumnavigated pore edges – such that the overall likelihood of a neurite entering a pore channel was decreased. These findings highlight the role of pore diameter, cell sheet confluence and contact guidance in directing neurite growth through pores and may be useful in applications that seek to use physical substrates to maintain separate neural populations whilst permitting neurite contact between cultures