Systematic Review of Clinical, Radiologic, and Histologic Features of Benign Notochordal Cell Tumors: Implications for Patient Management

BACKGROUND: There are no absolute defining criteria for benign notochordal cell tumors; the diagnosis is usually based on small size and the absence of aggressive features. Therefore, by definition, the diagnosis is subjective and usually determined by multidisciplinary consensus. A benign notochordal cell tumor should not grow during surveillance, and this may be used to confirm the diagnosis, but is a tautologic definition. Diagnostic ambiguity leads to uncertainty in management. If a tumor is a small chordoma then early surgery is likely to provide a better outcome. However, unnecessary treatment of a benign tumor may incur unjustified risk. OBJECTIVE: To propose clearer guidelines for the definition and management of benign notochordal tumors. METHODS: We performed a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) review of the reported definitions for benign notochordal tumors and their management. RESULTS: The accepted features of benign notochordal tumors vary considerably: a typical tumor may be diagnosed in the absence of neurology, radiologically well-corticated bony margins, size <35 mm, no enhancement with contrast, no soft tissue extension, no dural penetration, no progression on scans, histologic absence of extracellular myxoid matrix, and low Ki67 index. If these criteria are fulfilled, it is reasonable to use radiologic surveillance in the first instance. Biopsy may be offered depending on the relative risks of performing the biopsy, or if there are atypical features. CONCLUSIONS: We suggest a clearer definition for a benign notochordal tumor and a management algorithm that incorporates a level of diagnostic uncertainty

Working with prisoners who self-harm: a qualitative study on stress, denial of weakness, and encouraging resilience in a sample of correctional staff

Background: Rates of self‐harm are high among prisoners. Most research focuses on the vulnerable prisoner, and there is little on the impact of these behaviours on staff. Aims: To investigate staff perceptions of self‐harming behaviours by prisoners, including their views on its causes, manifestation, prevention in institutions, and impact on them. Methods: Semi-structured interviews were conducted with 20 administrative and 21 therapeutic prison staff who are responsible in various ways for prisoners who self‐harm. Their narratives were explored using interpretative phenomenological analysis. Results: Despite prison staff being experienced with prisoners' self‐harming behaviours, including severe acts of self‐harm, they were apt to reject any negative impact on their own mental health or well‐being. This denial of negative impact was accompanied by perceptions of the inmate's actions being manipulative and attention seeking. Prison staff also perceived institutional responses to self‐harming behaviours by prisoners as being mixed, ambiguous, or showing preference for relying on existing suicide protocols rather than task‐specific guidance. Conclusions: Although staff gave explanations of prisoner self‐harm in terms of “manipulative behaviour”, prisoners' self‐harm is, in fact, complex, challenging, and often severe. This staff perception may reflect denial of impact of often distressing behaviours on them personally and their own coping mechanisms. This could be feeding in to a perceived lack of clear and effective institutional responses to the self‐harm, so further research is needed to determine how staff could broaden their views, and respond more effectively to prisoners. Psychologically informed group work and/or reflective practice are among the candidates for such help for staff

Using DNA Barcoding to Investigate Patterns of Species Utilisation in UK Shark Products Reveals Threatened Species on Sale

This is the final version. Available on open access from Nature Research via the DOI in this recordMany shark populations are in decline, primarily due to overexploitation. In response, conservation measures have been applied at differing scales, often severely restricting sales of declining species. Therefore, DNA barcoding was used to investigate sales of shark products in fishmongers and fish and chip takeaways in England. The majority of samples were identified as Spiny Dogfish (Squalus acanthias), which is critically endangered in the Northeast Atlantic and landings have been prohibited (although there is evidence of importation of this species). Significant differences in the species sold between retailer types were also identified, suggesting differing supply chains. The results underline issues surrounding the use of ‘umbrella’ sales terms where many species are labelled with the same designation. This denies consumer choice as purchasers cannot easily avoid declining species or those associated with high levels of toxicants. For the first time in Europe, minibarcodes are also used to identify species from dried shark fins. Despite a small sample size, analysis of UK wholesaler fins identified threatened sharks, including the endangered and CITES listed Scalloped Hammerhead (Sphyrna lewini). This highlights the global nature of the damaging trade in endangered shark species, in which Europe and the UK have a continuing role.Fisheries Society of the British IslesHampshire & Isle of Wight Wildlife TrustUniversity of Exete

Health Professionals' Attitudes Towards Traditional Healing for Mental Illness: A Systematic Review.

Combining modern treatments with traditional healing approaches has been proposed as one way to address mental health problems, especially in low-income countries where the costs of pharmaceuticals often prevent or reduce their use. Despite health professionals' involvement being crucial for the integration of this approach, their involvement has been limited to date. This systematic review is designed to explore the attitudes of health professionals towards traditional healing practices for mental illness. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines were followed. The studies were identified from Scopus, EMBASE, PubMed, PsycINFO, and the Web of Sciences. The qualities of the included articles were assessed using the Mixed Method Appraisal Tool (MMAT) Version 2018, and mixed-method synthesis was used to narrate the results. Of the 2115 identified articles, 36 were included in the data synthesis. From the extracted data, health professionals had negative, mixed, and positive views towards traditional healing approaches for mental illness. Their negative attitude towards traditional healing approaches were due to their concerns that traditional healing may cause harm to service users, and they have no trust in the scientific basis, education, or practices of healers. Despite the fact that it is crucial for healthcare professionals to comprehend the cultural backgrounds of those receiving mental health services in order to offer care appropriately, health professionals' negative and mixed attitudinal expressions towards traditional healing approaches limit their involvement. This might be improved by identifying barriers from the perspective of practitioners and creating culturally appropriate guidelines for communication and referral between traditional healing approaches and biomedical care

Prediction of the environmental impact and sustainability of large-scale irrigation with gypsiferous mine-water on groundwater resources

Irrigation of agricultural crops is one of the most cost-effective options for the utilisation of gypsiferous mine wastewater. In addition, it creates the opportunity to produce crops during the dry season. Gypsum is a slightly soluble salt and concentrating the gypsiferous soil solution through crop evapotranspiration precipitates gypsum in the soil profile, removing it from the water system and reducing the potential for groundwater pollution. In previous research, it was found that crops can be commercially produced under irrigation with gypsiferous mine- water with no obvious impact on groundwater in the short term (3 years). It was, however, recommended that monitoring should continue to confirm findings over a longer period and for different conditions. A research project was therefore initiated in 2001 to determine the impact of  irrigation with several gypsiferous water/soil combinations on crop performance, soil properties and groundwater quality. Field trials were carried out in South Africa on three mines: Kleinkopjé and New Vaal Collieries (Anglo Coal), and at Syferfontein (Sasol). Different crop and pasture species were grown on different soil types under centre-pivot irrigation with different mine-water qualities. Intensive monitoring systems were established in each irrigated field to determine the components of the soil-water and salt balance. Boreholes were also installed to monitor groundwater level and quality. Field water and salt balance data were used for calibration and validation of the mechanistic, generic crop, Soil-Water Balance (SWB) Model. The results of the field trials indicated that high crop and pasture yields can be obtained, provided site selection, land preparation, fertilisation and irrigation water management are appropriate. The results of the soil-water and salt balance studies indicated that considerable volumes of mine-water can be used and substantial amounts of salts can be removed from the water system through precipitation of gypsum in the soil profile. The groundwater impact was limited based on borehole measurements, indicating the presence of a zone of attenuation between the cropped soil profile and groundwater, but this should be monitored over a longer period. With appropriate management, water and salt runoff, and under specific conditions, drainage and salts leached can be intercepted, thereby minimising unwanted impacts on groundwater. Thirty-year scenario simulations were run with SWB and the generated salt loads from this model were used as input into a separate groundwater model in order to predict the likely long-term effects of irrigation with gypsiferous mine-water on groundwater. The results of these simulations showed that while salts reached the groundwater, there was a drop in concentration of the plume as it moved away from the irrigated area. This was due largely to dilution by infiltration from rainfall recharge and the dispersive characteristics of the aquifer. The simulations also showed the importance of matching the amount of drainage from an irrigated site with the transmissivity and storage properties of the aquifer below. These results suggest that large-scale irrigation with gypsiferous water could be viable if irrigated fields are carefully sited to prevent waterlogging and are well managed. A site-specific approach is essential. Water SA Vol 32(1)pp:21-2

Design of a randomised controlled trial on immune effects of acidic and neutral oligosaccharides in the nutrition of preterm infants: carrot study

<p>Abstract</p> <p>Background</p> <p>Prevention of serious infections in preterm infants is a challenge, since prematurity and low birth weight often requires many interventions and high utility of devices. Furthermore, the possibility to administer enteral nutrition is limited due to immaturity of the gastrointestinal tract in the presence of a developing immune system. In combination with delayed intestinal bacterial colonisation compared with term infants, this may increase the risk for serious infections. Acidic and neutral oligosaccharides play an important role in the development of the immune system, intestinal bacterial colonisation and functional integrity of the gut. This trial aims to determine the effect of enteral supplementation of acidic and neutral oligosaccharides on infectious morbidity (primary outcome), immune response to immunizations, feeding tolerance and short-term and long-term outcome in preterm infants. In addition, an attempt is made to elucidate the role of acidic and neutral oligosaccharides in postnatal modulation of the immune response and postnatal adaptation of the gut.</p> <p>Methods/Design</p> <p>In a double-blind placebo controlled randomised trial, 120 preterm infants (gestational age <32 weeks and/or birth weight <1500 gram) are randomly allocated to receive enteral acidic and neutral oligosaccharides supplementation (20%/80%) or placebo supplementation (maltodextrin) between day 3 and 30 of life. Primary outcome is infectious morbidity (defined as the incidence of serious infections). The role of acidic and neutral oligosaccharides in modulation of the immune response is investigated by determining the immune response to DTaP-IPV-Hib(-HBV)+PCV7 immunizations, plasma cytokine concentrations, faecal Calprotectin and IL-8. The effect of enteral acidic and neutral oligosaccharides supplementation on postnatal adaptation of the gut is investigated by measuring feeding tolerance, intestinal permeability, intestinal viscosity, and determining intestinal microflora. Furthermore, short-term and long-term outcome are evaluated.</p> <p>Discussion</p> <p>Especially preterm infants, who are at increased risk for serious infections, may benefit from supplementation of prebiotics. Most studies with prebiotics only focus on the colonisation of the intestinal microflora. However, the pathways how prebiotics may influence the immune system are not yet fully understood. Studying the immune modulatory effects is complex because of the multicausal risk of infections in preterm infants. The combination of neutral oligosaccharides with acidic oligosaccharides may have an increased beneficial effect on the immune system. Increased insight in the effects of prebiotics on the developing immune system may help to decrease the (infectious) morbidity and mortality in preterm infants.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN16211826.</p

Modulation of 11β-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation

Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/ inhibition causes hypertension, whereas deficiency/ inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/ inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis

Frequent alterations in p16/CDKN2A identified by immunohistochemistry and FISH in chordoma

The expression of p16/CDKN2A, the second most commonly inactivated tumour suppressor gene in cancer, is lost in the majority of chordomas. However, the mechanism(s) leading to its inactivation and contribution to disease progression have only been partially addressed using small patient cohorts. We studied 384 chordoma samples from 320 patients by immunohistochemistry and found that p16 protein was lost in 53% of chordomas and was heterogeneously expressed in these tumours. To determine if CDKN2A copy number loss could explain the absence of p16 protein expression we performed fluorescence in situ hybridisation (FISH) for CDKN2A on consecutive tissue sections. CDKN2A copy number status was altered in 168 of 274 (61%) of samples and copy number loss was the most frequent alteration acquired during clinical disease progression. CDKN2A homozygous deletion was always associated with p16 protein loss but only accounted for 33% of the p16‐negative cases. The remaining immunonegative cases were associated with disomy (27%), monosomy (12%), heterozygous loss (20%) and copy number gain (7%) of CDKN2A, supporting the hypothesis that loss of protein expression might be achieved via epigenetic or post‐transcriptional regulatory mechanisms. We identified that mRNA levels were comparable in tumours with and without p16 protein expression, but other events including DNA promoter hypermethylation, copy number neutral loss of heterozygosity and expression of candidate microRNAs previously implicated in the regulation of CDKN2A expression were not identified to explain the protein loss. The data argue that p16 loss in chordoma is commonly caused by a post‐transcriptional regulatory mechanism that is yet to be defined

Serum Amino Acid Profiling in Patients with Alkaptonuria Before and After Treatment with Nitisinone.

BackgroundAlkaptonuria (AKU) is a rare inherited disorder of the tyrosine metabolic pathway. Our group is evaluating the use of the homogentisic acid-lowering agent nitisinone in patients with AKU. A major biochemical consequence of this treatment is hypertyrosinaemia. Herein we report the concentration of 20 serum amino acids over a 36-month period pre- and post-treatment with nitisinone.MethodsFasting serum samples were collected at baseline (pre-nitisinone), 3 (2 mg nitisinone every other day), 6, 12, 24 and 36 (2 mg nitisinone daily) months. Amino acids were measured using the Biochrom 30 high-performance liquid chromatography cation exchange system with ninhydrin detection.ResultsFifty patients [21 female, mean age (±standard deviation) 54.1 (15.6) years (range 25-75); 29 male, mean age 49.3 (11.6) years (range 22-70 years)] were included. Following treatment mean tyrosine concentrations increased seven- to eight-fold (baseline, 69.8 μmol/L; 3 months, 670.7 μmol/L; 6 months, 666.4 μmol/L; 12 months, 692.9 μmol/L; 24 months, 649.4 μmol/L; 36 months, 724.8 μmol/L, p = ConclusionsMarked hypertyrosinaemia was observed following treatment with nitisinone. Noteworthy changes were also observed in the ratio of several amino acids following treatment with nitisinone suggesting that the availability of amino acids for neurotransmitter biosynthesis and liver function may be altered following treatment with nitisinone

No change to grey and white matter volumes in bipolar I disorder patients

Background Structural brain imaging is assumed to be a key method to elucidate the underlying neuropathology of bipolar disorder. However, magnetic resonance imaging studies using region of interest analysis and voxel-based morphometry (VBM) revealed quite inconsistent findings. Hence, there is no clear evidence so far for core regions of cortical or subcortical structural abnormalities in bipolar disorder. The aim of this study was to investigate grey and white matter volumes in a large sample of patients with bipolar I disorder. Methods Thirty-five patients with bipolar I disorder and 32 healthy controls matched with respect to gender, handedness and education participated in the study. MRI scanning was performed and an optimized VBM analysis was conducted. Results We could not observe any significant differences of grey or white matter volumes between patients with bipolar disorder and healthy control subjects. Additional analyses did not reveal significant correlations between grey or white matter volume with number of manic or depressive episodes, duration of illness, existence of psychotic symptoms, and treatment with lithium or antipsychotics. Conclusions With this VBM study we were not able to identify core regions of structural abnormalities in bipolar disorder