Does bracing affect bone health in women with adolescent idiopathic scoliosis?

Purpose: Adolescent idiopathic scoliosis (AIS) is often associated with low bone mineral content and density (BMC, BMD). Bracing, used to manage spine curvature, may interfere with the growth-related BMC accrual, resulting in reduced bone strength into adulthood. The purpose of this study was to assess the effects of brace treatment on BMC in adult women, diagnosed with AIS and braced in early adolescence. Methods: Participants included women with AIS who: (i) underwent brace treatment (AIS-B, n = 15, 25.6 ± 5.8 yrs), (ii) underwent no treatment (AIS, n = 15, 24.0 ± 4.0 yrs), and (iii) a healthy comparison group (CON, n = 19, 23.5 ± 3.8 yrs). BMC and body composition were assessed using dual-energy X-ray absorptiometry. Differences between groups were examined using a oneway ANOVA or ANCOVA, as appropriate. Results: AIS-B underwent brace treatment 27.9 ± 21.6 months, for 18.0 ± 5.4 h/d. Femoral neck BMC was lower (p = 0.06) in AIS-B (4.54 ± 0.10 g) compared with AIS (4.89 ± 0.61 g) and CON (5.07 ± 0.58 g). Controlling for lean body mass, calcium and vitamin D daily intake, and strenuous physical activity, femoral neck BMC was statistically different (p = 0.02) between groups. A similar pattern was observed at other lower extremity sites (p < 0.05), but not in the spine or upper extremities. BMC and BMD did not correlate with duration of brace treatment, duration of daily brace wear, or overall physical activity. Conclusion: Young women with AIS, especially those who were treated with a brace, have significantly lower BMC in their lower limbs compared to women without AIS. However, the lack of a relationship between brace treatment duration during adolescence and BMC during young adulthood, suggests that the brace treatment is not the likely mechanism of the low BMC

Amplified antimicrobial action of chlorhexidine encapsulated in PDAC-functionalized acrylate copolymer nanogel carriers

We have developed and tested a novel functionalised nanocarrier for chlorhexidine (CHX) which provides a very strong enhancement of its antimicrobial action. The nanocarrier was based on lightly-cross-linked acrylate copolymer nanogel particles loaded with CHX followed by a surface functionalisation with the cationic polyelectrolyte poly(diallyldimethylammonium chloride (PDAC). We explored the antimicrobial effect of the PDAC-coated CHX-loaded nanogel carriers on E. coli, S. auresus, C. cerevisiae and C. reinhardtii and discovered that it is much higher than that of solution with equivalent overall concentration of free CHX. Our experiments also showed a marked increase of the cationic CHX-loaded nanocarriers antimicrobial action on these microorganisms at shorter incubation times compared with the non-coated CHX-loaded nanogel particles at the same CHX concentration and other conditions. We attribute the increase in the antimicrobial activity of the cationically-functionalised nanogel carrier to its electrostatic adhesion to the microbial cells walls which allows much higher CHX concentration to be delivered directly onto the cell surface. The results of this study can be used for development of novel more efficient antialgal, antifungal and antbacterial formulations based on cationically functionalised nanogels. Our method can also be used for boosting the effect of other cationic antimicrobial agents by encapsulating them in cationically-functionalised nanogel carriers. This nanotechnological approach could lead to developing more effective antimicrobial and disinfecting agents, dental formulations for plaque control, wound dressings, antialgal/antibiofouling formulations and novel antifungal agents

Evidence summaries (decision boxes) to prepare clinicians for shared decision-making with patients: a mixed methods implementation study

Background: Decision boxes (Dboxes) provide clinicians with research evidence about management options for medical questions that have no single best answer. Dboxes fulfil a need for rapid clinical training tools to prepare clinicians for clinician-patient communication and shared decision-making. We studied the barriers and facilitators to using the Dbox information in clinical practice. Methods: We used a mixed methods study with sequential explanatory design. We recruited family physicians, residents, and nurses from six primary health-care clinics. Participants received eight Dboxes covering various questions by email (one per week). For each Dbox, they completed a web questionnaire to rate clinical relevance and cognitive impact and to assess the determinants of their intention to use what they learned from the Dbox to explain to their patients the advantages and disadvantages of the options, based on the theory of planned behaviour (TPB). Following the 8-week delivery period, we conducted focus groups with clinicians and interviews with clinic administrators to explore contextual factors influencing the use of the Dbox information. Results: One hundred clinicians completed the web surveys. In 54% of the 496 questionnaires completed, they reported that their practice would be improved after having read the Dboxes, and in 40%, they stated that they would use this information for their patients. Of those who would use the information for their patients, 89% expected it would benefit their patients, especially in that it would allow the patient to make a decision more in keeping with his/her personal circumstances, values, and preferences. They intended to use the Dboxes in practice (mean 5.6 ± 1.2, scale 1–7, with 7 being “high”), and their intention was significantly related to social norm, perceived behavioural control, and attitude according to the TPB (P < 0.0001). In focus groups, clinicians mentioned that co-interventions such as patient decision aids and training in shared decision-making would facilitate the use of the Dbox information. Some participants would have liked a clear “bottom line” statement for each Dbox and access to printed Dboxes in consultation rooms. Conclusions: Dboxes are valued by clinicians. Tailoring of Dboxes to their needs would facilitate their implementation in practic

Short intense ion pulses for materials and warm dense matter research

We have commenced experiments with intense short pulses of ion beams on the Neutralized Drift Compression Experiment-II at Lawrence Berkeley National Laboratory, by generating beam spots size with radius r < 1 mm within 2 ns FWHM and approximately 10^10 ions/pulse. To enable the short pulse durations and mm-scale focal spot radii, the 1.2 MeV Li+ ion beam is neutralized in a 1.6-meter drift compression section located after the last accelerator magnet. An 8-Tesla short focal length solenoid compresses the beam in the presence of the large volume plasma near the end of this section before the target. The scientific topics to be explored are warm dense matter, the dynamics of radiation damage in materials, and intense beam and beam-plasma physics including selected topics of relevance to the development of heavy-ion drivers for inertial fusion energy. Here we describe the accelerator commissioning and time-resolved ionoluminescence measurements of yttrium aluminium perovskite using the fully integrated accelerator and neutralized drift compression components.Comment: 7 pages, 9 figure

Tissue tolerance: an essential but elusive trait for salt-tolerant crops

For a plant to persist in saline soil, osmotic adjustment of all plant cells is essential. The more salt-tolerant species accumulate Na+ and Cl– to concentrations in leaves and roots that are similar to the external solution, thus allowing energy-efficient osmotic adjustment. Adverse effects of Na+ and Cl– on metabolism must be avoided, resulting in a situation known as ‘tissue tolerance’. The strategy of sequestering Na+ and Cl– in vacuoles and keeping concentrations low in the cytoplasm is an important contributor to tissue tolerance. Although there are clear differences between species in the ability to accommodate these ions in their leaves, it remains unknown whether there is genetic variation in this ability within a species. This viewpoint considers the concept of tissue tolerance, and how to measure it. Four conclusions are drawn: (1) osmotic adjustment is inseparable from the trait of tissue tolerance; (2) energy-efficient osmotic adjustment should involve ions and only minimal organic solutes; (3) screening methods should focus on measuring tolerance, not injury; and (4) high-throughput protocols that avoid the need for control plants and multiple Na+ or Cl- measurements should be developed. We present guidelines to identify useful genetic variation in tissue tolerance that can be harnessed for plant breeding of salt tolerance

Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS-FTD

BACKGROUND: A new locus for amyotrophic lateral sclerosis – frontotemporal dementia (ALS-FTD) has recently been ascribed to chromosome 9p. METHODS: We identified chromosome 9p segregating haplotypes within two families with ALS-FTD (F476 and F2) and undertook mutational screening of candidate genes within this locus. RESULTS: Candidate gene sequencing at this locus revealed the presence of a disease segregating stop mutation (Q342X) in the intraflagellar transport 74 (IFT74) gene in family 476 (F476), but no mutation was detected within IFT74 in family 2 (F2). While neither family was sufficiently informative to definitively implicate or exclude IFT74 mutations as a cause of chromosome 9-linked ALS-FTD, the nature of the mutation observed within F476 (predicted to truncate the protein by 258 amino acids) led us to sequence the open reading frame of this gene in a large number of ALS and FTD cases (n = 420). An additional sequence variant (G58D) was found in a case of sporadic semantic dementia. I55L sequence variants were found in three other unrelated affected individuals, but this was also found in a single individual among 800 Human Diversity Gene Panel samples. CONCLUSION: Confirmation of the pathogenicity of IFT74 sequence variants will require screening of other chromosome 9p-linked families

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

International evidence-based consensus diagnostic and treatment guidelines for unicentric Castleman disease.

Castleman disease (CD) includes a group of rare and heterogeneous disorders with characteristic lymph node histopathological abnormalities. CD can occur in a single lymph node station, which is referred to as unicentric CD (UCD). CD can also involve multicentric lymphadenopathy and inflammatory symptoms (multicentric CD [MCD]). MCD includes human herpesvirus-8 (HHV-8)-associated MCD, POEMS-associated MCD, and HHV-8-/idiopathic MCD (iMCD). The first-ever diagnostic and treatment guidelines were recently developed for iMCD by an international expert consortium convened by the Castleman Disease Collaborative Network (CDCN). The focus of this report is to establish similar guidelines for the management of UCD. To this purpose, an international working group of 42 experts from 10 countries was convened to establish consensus recommendations based on review of treatment in published cases of UCD, the CDCN ACCELERATE registry, and expert opinion. Complete surgical resection is often curative and is therefore the preferred first-line therapy, if possible. The management of unresectable UCD is more challenging. Existing evidence supports that asymptomatic unresectable UCD may be observed. The anti-interleukin-6 monoclonal antibody siltuximab should be considered for unresectable UCD patients with an inflammatory syndrome. Unresectable UCD that is symptomatic as a result of compression of vital neighboring structures may be rendered amenable to resection by medical therapy (eg, rituximab, steroids), radiotherapy, or embolization. Further research is needed in UCD patients with persisting constitutional symptoms despite complete excision and normal laboratory markers. We hope that these guidelines will improve outcomes in UCD and help treating physicians decide the best therapeutic approach for their patients

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p&lt;0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p&lt;0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark