Cell Patterning via Laser Micro/nano Structured Silicon Surfaces

The surface topography of biomaterials can have an important impact on cellular adhesion, growth and proliferation. Apart from the overall roughness, the detailed morphological features, at all length scales, significantly affect the cell-biomaterial interactions in a plethora of applications including structural implants, tissue engineering scaffolds and biosensors. In this study, we present a simple, one-step direct laser patterning technique to fabricate nanoripples and dual-rough hierarchical micro/nano structures to control SW10 cell attachment and migration. It is shown that, depending on the laser processing conditions, distinct cell-philic or cell-repellant patterned areas can be attained with a desired motif. We envisage that our technique could enable spatial patterning of cells in a controllable manner, giving rise to advanced capabilities in cell biology research

Habit training versus habit training with direct visual biofeedback in adults with chronic constipation: A randomized controlled trial

Aim: The aim was to determine whether specialist-led habit training using Habit Training with Biofeedback (HTBF) is more effective than specialist-led habit training alone (HT) for chronic constipation and whether outcomes of interventions are improved by stratification to HTBF or HT based on diagnosis (functional defaecation disorder vs. no functional defaecation disorder) by radio-physiological investigations (INVEST). Method: This was a parallel three-arm randomized single-blinded controlled trial, permitting two randomized comparisons: HTBF versus HT alone; INVEST- versus no-INVEST-guided intervention. The inclusion criteria were age 18–70 years; attending specialist hospitals in England; self-reported constipation for >6 months; refractory to basic treatment. The main exclusions were secondary constipation and previous experience of the trial interventions. The primary outcome was the mean change in Patient Assessment of Constipation Quality of Life score at 6 months on intention to treat. The secondary outcomes were validated disease-specific and psychological questionnaires and cost-effectiveness (based on EQ-5D-5L). Results: In all, 182 patients were randomized 3:3:2 (target 384): HT n = 68; HTBF n = 68; INVEST-guided treatment n = 46. All interventions had similar reductions (improvement) in the primary outcome at 6 months (approximately −0.8 points of a 4-point scale) with no statistically significant difference between HT and HTBF (−0.03 points; 95% CI −0.33 to 0.27; P = 0.85) or INVEST versus no-INVEST (0.22; −0.11 to 0.55; P = 0.19). Secondary outcomes showed a benefit for all interventions with no evidence of greater cost-effectiveness of HTBF or INVEST compared with HT. Conclusion: The results of the study at 6 months were inconclusive. However, with the caveat of under-recruitment and further attrition at 6 months, a simple, cheaper approach to intervention may be as clinically effective and more cost-effective than more complex and invasive approaches

Evaluating metallic artefact of biodegradable magnesium-based implants in magnetic resonance imaging

Magnesium (Mg) implants have shown to cause image artefacts or distortions in magnetic resonance imaging (MRI). Yet, there is a lack of information on how the degradation of Mg-based implants influences the image quality of MRI examinations. In this study, Mg-based implants are analysed in vitro, ex vivo, and in the clinical setting for various magnetic field strengths with the aim to quantify metallic artefact behaviour. In vitro corroded Mg-based screws and a titanium (Ti) equivalent were imaged according to the ASTM F2119. Mg-based and Ti pins were also implanted into rat femurs for different time points and scanned to provide insights on the influence of soft and hard tissue on metallic artefact. Additionally, MRI data of patients with scaphoid fractures treated with CE-approved Mg-based compression screws (MAGNEZIX(®)) were analysed at various time points post-surgery. The artefact production of the Mg-based material decreased as implant material degraded in all settings. The worst-case imaging scenario was determined to be when the imaging plane was selected to be perpendicular to the implant axis. Moreover, the Mg-based implant outperformed the Ti equivalent in all experiments by producing lower metallic artefact (p < 0.05). This investigation demonstrates that Mg-based implants generate significantly lower metallic distortion in MRI when compared to Ti. Our positive findings suggest and support further research into the application of Mg-based implants including post-operative care facilitated by MRI monitoring of degradation kinetics and bone/tissue healing processes

Effects of a healthy lifestyle intervention and COVID-19-adjusted training curriculum on firefighter recruits

There are knowledge gaps regarding healthy lifestyle (HLS) interventions in fire academy settings and also concerning the impacts of the pandemic on training. We enrolled fire recruits from two fire academies (A and B) in New England in early 2019 as the historical control group, and recruits from academies in New England (B) and Florida (C), respectively, during the pandemic as the intervention group. The three academies have similar training environments and curricula. The exposures of interest were a combination of (1) an HLS intervention and (2) impacts of the pandemic on training curricula and environs (i.e. social distancing, masking, reduced class size, etc.). We examined the health/fitness changes throughout training. The follow-up rate was 78%, leaving 92 recruits in the historical control group and 55 in the intervention group. The results show an HLS intervention improved the effects of fire academy training on recruits healthy behaviors (MEDI-lifestyle score, 0.5 ± 1.4 vs. - 0.3 ± 1.7), systolic blood pressure (- 7.2 ± 10.0 vs. 2.9 ± 12.9 mmHg), and mental health (Beck Depression score, - 0.45 ± 1.14 vs. - 0.01 ± 1.05) (all P < 0.05). The associations remained significant after multivariable adjustments. Moreover, a 1-point MEDI-lifestyle increment during academy training is associated with about 2% decrement in blood pressures over time, after multivariable adjustments (P < 0.05). Nonetheless, the impacts of pandemic restrictions on academy procedures compromised physical fitness training, namely in percent body fat, push-ups, and pull-ups

Stepped-wedge randomised trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation: Study protocol for a randomized controlled trial

BACKGROUND: Laparoscopic ventral mesh rectopexy (LVMR) is an established treatment for external full-thickness rectal prolapse. However, its clinical efficacy in patients with internal prolapse is uncertain due to the lack of high-quality evidence. METHODS: An individual level, stepped-wedge randomised trial has been designed to allow observer-blinded data comparisons between patients awaiting LVMR with those who have undergone surgery. Adults with symptomatic internal rectal prolapse, unresponsive to prior conservative management, will be eligible to participate. They will be randomised to three arms with different delays before surgery (0, 12 and 24 weeks). Efficacy outcome data will be collected at equally stepped time points (12, 24, 36 and 48 weeks). The primary objective is to determine clinical efficacy of LVMR compared to controls with reduction in the Patient Assessment of Constipation Quality of Life (PAC-QOL) at 24 weeks serving as the primary outcome. Secondary objectives are to determine: (1) the clinical effectiveness of LVMR to 48 weeks to a maximum of 72 weeks; (2) pre-operative determinants of outcome; (3) relevant health economics for LVMR; (4) qualitative evaluation of patient and health professional experience of LVMR and (5) 30-day morbidity and mortality rates. DISCUSSION: An individual-level, stepped-wedge, randomised trial serves the purpose of providing an untreated comparison for the active treatment group, while at the same time allowing the waiting-listed participants an opportunity to obtain the intervention at a later date. In keeping with the basic ethical tenets of this design, the average waiting time for LVMR (12 weeks) will be shorter than that for routine services (24 weeks)

Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study

BACKGROUND: Celiac disease has a strong genetic association with HLA. However, this association only explains approximately half of the sibling risk for celiac disease. Therefore, other genes must be involved in susceptibility to celiac disease. We tested for linkage to genes or loci that could play a role in pathogenesis of celiac disease. METHODS: DNA samples, from members of 62 families with a minimum of two cases of celiac disease, were genotyped at HLA and at 13 candidate gene regions, including CD4, CTLA4, four T-cell receptor regions, and 7 insulin-dependent diabetes regions. Two-point and multipoint heterogeneity LOD (HLOD) scores were examined. RESULTS: The highest two-point and multipoint HLOD scores were obtained in the HLA region, with a two-point HLOD of 3.1 and a multipoint HLOD of 5.0. For the candidate genes, we found no evidence for linkage. CONCLUSIONS: Our significant evidence of linkage to HLA replicates the known linkage and association of HLA with CD. In our families, likely candidate genes did not explain the susceptibility to celiac disease

Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial

Background: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D. Methods: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron. Discussion: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond

Perceptions of Oncology Providers and Cancer Survivors on the Role of Nutrition in Cancer Care and Their Views on the “NutriCare” Program

Cancer patients and survivors can experience treatment related side effects that impact nutrition status, as well as unwanted weight loss, weight gain and poor dietary quality. Therefore, they are a group that would benefit from nutrition intervention. A qualitative study was conducted online (six focus groups and two interviews) with 12 oncology providers and 12 survivors in the United States. Participants were asked about the role of nutrition in survivors&rsquo; health, appropriate components of nutrition care for cancer patients, and strategies to integrate nutrition into oncology care. Feedback on a proposed program, &ldquo;NutriCare&rdquo;, was also sought. Focus groups were recorded, transcribed verbatim, and analyzed for themes. Four main themes emerged: (1) nutrition is an important component of oncology care and source of empowerment for cancer patients; (2) in the NutriCare program, the prescription pad component was viewed as a critical aspect, and there was also a preference for dealing with patients and survivors separately; (3) for implementation, the most appropriate time for providers to talk to patients about nutrition is during the development of the treatment plan. Reinforcement of key nutrition messages by providers was also highlighted; (4) major barriers included lack of time and motivation by providers. Survivors were interested in and providers supportive of integrating nutrition into oncology care

When all seems lost: management of refractory constipation—Surgery, rectal irrigation, percutaneous endoscopic colostomy, and more

© 2018 John Wiley & Sons Ltd While the pharmacological armamentarium for chronic constipation has expanded over the past few years, a substantial proportion of constipated patients do not respond to these medications. This review summarizes the pharmacological and behavioral options for managing constipation and details the management of refractory constipation. Refractory constipation is defined as an inadequate improvement in constipation symptoms evaluated with an objective scale despite adequate therapy (ie, pharmacological and/or behavioral) that is based on the underlying pathophysiology of constipation. Minimally invasive (ie, rectal irrigation and percutaneous endoscopic colostomy) and surgical therapies are used to manage refractory constipation. This review appraises these options, and in particular, percutaneous endoscopic colostomy, which as detailed by an article in this issue, is a less invasive option for managing refractory constipation than surgery. While these options benefit some patients, the evidence of the risk: benefit profile for these therapies is limited

Surgery for constipation: systematic review and practice recommendations: Results V: Sacral Nerve Stimulation

This project was funded by the National Institute for Health Research (NIHR) Programme Grant for Applied Research (RP-PG-0612-20001). The views and opinions expressed in this report are those of the authors and are not those of the PGfAR Programme, NIHR, the UK National Health Service, or the UK Department of Health