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.

Role of lncRNAs in Helicobacter pylori and Epstein-Barr virus associated gastric cancers.

Helicobacter pylori infection is a risk factor for the development of gastric cancer (GC), and the role of co-infection with viruses, such as Epstein-Barr virus, in carcinogenesis cannot be ignored. Furthermore, it is now known that genetic factors such as long non-coding RNAs (lncRNAs) are involved in many diseases, including GC. On the other side, they can also be used as therapeutic goals. Modified lncRNAs can cause aberrant expression of genes encoding proximal proteins, which are essential for the development of carcinoma. In this review, we present the most recent studies on lncRNAs in GC, concentrating on their roles in H. pylori and EBV infections, and discuss some of the molecular mechanisms of these GC-related pathogens. There was also a discussion of the research gaps and future perspectives.

Cancer therapy with the viral and bacterial pathogens: The past enemies can be considered the present allies.

Cancer continues to be one of the leading causes of mortality worldwide despite significant advancements in cancer treatment. Many difficulties have arisen as a result of the detrimental consequences of chemotherapy and radiotherapy as a common cancer therapy, such as drug inability to penetrate deep tumor tissue, and also the drug resistance in tumor cells continues to be a major concern. These obstacles have increased the need for the development of new techniques that are more selective and effective against cancer cells. Bacterial-based therapies and the use of oncolytic viruses can suppress cancer in comparison to other cancer medications. The tumor microenvironment is susceptible to bacterial accumulation and proliferation, which can trigger immune responses against the tumor. Oncolytic viruses (OVs) have also gained considerable attention in recent years because of their potential capability to selectively target and induce apoptosis in cancer cells. This review aims to provide a comprehensive summary of the latest literature on the role of bacteria and viruses in cancer treatment, discusses the limitations and challenges, outlines various strategies, summarizes recent preclinical and clinical trials, and emphasizes the importance of optimizing current strategies for better clinical outcomes.

Progress in biomechanical stimuli on the cell-encapsulated hydrogels for cartilage tissue regeneration.

BACKGROUND: Worldwide, many people suffer from knee injuries and articular cartilage damage every year, which causes pain and reduces productivity, life quality, and daily routines. Medication is currently primarily used to relieve symptoms and not to ameliorate cartilage degeneration. As the natural healing capacity of cartilage damage is limited due to a lack of vascularization, common surgical methods are used to repair cartilage tissue, but they cannot prevent massive damage followed by injury. MAIN BODY: Functional tissue engineering has recently attracted attention for the repair of cartilage damage using a combination of cells, scaffolds (constructs), biochemical factors, and biomechanical stimuli. As cyclic biomechanical loading is the key factor in maintaining the chondrocyte phenotype, many studies have evaluated the effect of biomechanical stimulation on chondrogenesis. The characteristics of hydrogels, such as their mechanical properties, water content, and cell encapsulation, make them ideal for tissue-engineered scaffolds. Induced cell signaling (biochemical and biomechanical factors) and encapsulation of cells in hydrogels as a construct are discussed for biomechanical stimulation-based tissue regeneration, and several notable studies on the effect of biomechanical stimulation on encapsulated cells within hydrogels are discussed for cartilage regeneration. CONCLUSION: Induction of biochemical and biomechanical signaling on the encapsulated cells in hydrogels are important factors for biomechanical stimulation-based cartilage regeneration.

Engineered substrates incapable of induction of chondrogenic differentiation compared to the chondrocyte imprinted substrates.

It is well established that surface topography can affect cell functions. However, finding a reproducible and reliable method for regulating stem cell behavior is still under investigation. It has been shown that cell imprinted substrates contain micro- and nanoscale structures of the cell membrane that serve as hierarchical substrates, can successfully alter stem cell fate. This study investigated the effect of the overall cell shape by fabricating silicon wafers containing pit structure in the average size of spherical-like chondrocytes using photolithography technique. We also used chondrocyte cell line (C28/I2) with spindle-like shape to produce cell imprinted substrates. The effect of all substrates on the differentiation of adipose-derived mesenchymal stem cells (ADSCs) has been studied. The AFM and scanning electron microscopy images of the prepared substrates demonstrated that the desired shapes were successfully transferred to the substrates. Differentiation of ADSCs was investigated by immunostaining for mature chondrocyte marker, collagen II, and gene expression of collagen II, Sox9, and aggrecan markers. C28/I2 imprinted substrate could effectively enhanced chondrogenic differentiation compared to regular pit patterns on the wafer. It can be concluded that cell imprinted substrates can induce differentiation signals better than engineered lithographic substrates. The nanostructures on the cell-imprinted patterns play a crucial role in harnessing cell fate. Therefore, the patterns must include the nano-topographies to have reliable and reproducible engineered substrates.

Modulation of bioactive calcium phosphate micro/nanoparticle size and shape during in situ synthesis of photo-crosslinkable gelatin methacryloyl based nanocomposite hydrogels for 3D bioprinting and tissue engineering.

BACKGROUND: The gelatin-methacryloyl (GelMA) polymer suffers shape fidelity and structural stability issues during 3D bioprinting for bone tissue engineering while homogeneous mixing of reinforcing nanoparticles is always under debate. METHOD: In this study, amorphous calcium phosphates micro/nanoparticles (CNP) incorporated GelMA is synthesized by developing specific sites for gelatin structure-based nucleation and stabilization in a one-pot processing. The process ensures homogenous distribution of CNPs while different concentrations of gelatin control their growth and morphologies. After micro/nanoparticles synthesis in the gelatin matrix, methacrylation is carried out to prepare homogeneously distributed CNP-reinforced gelatin methacryloyl (CNP GelMA) polymer. After synthesis of CNP and CNP GelMA gel, the properties of photo-crosslinked 3D bioprinting scaffolds were compared with those of the conventionally fabricated ones. RESULTS: The shape (spindle to spherical) and size (1.753 µm to 296 nm) of the micro/nanoparticles in the GelMA matrix are modulated by adjusting the gelatin concentrations during the synthesis. UV cross-linked CNP GelMA (using Irgacure 2955) has significantly improved mechanical (three times compressive strength), 3D printability (160 layers, 2 cm self-standing 3D printed height) and biological properties (cell supportiveness with osteogenic differentiation). The photo-crosslinking becomes faster due to better methacrylation, facilitating continuous 3D bioprinting or printing. CONCLUSION: For 3D bioprinting using GelMA like photo cross-linkable polymers, where structural stability and homogeneous control of nanoparticles are major concerns, CNP GelMA is beneficial for even bone tissue regeneration within short period.

Cell-imprinted substrates: in search of nanotopographical fingerprints that guide stem cell differentiation.

Cell-imprinted substrates direct stem cell differentiation into various lineages, suggesting the idea of lineage-specific nanotopography. We herein examined the surface topography of five different imprinted cell patterns using AFM imaging and statistical analysis of amplitude, spatial, and hybrid roughness parameters. The results suggest that different cell imprints possess distinguished nanotopographical features.

Randomised clinical trial: Bifidobacterium lactis NCC2818 probiotic vs placebo, and impact on gut transit time, symptoms, and gut microbiology in chronic constipation.

BACKGROUND: Constipation is a prevalent gastrointestinal disorder. Patient dissatisfaction with prescribed medications is common, and there is need for alternative management strategies. Evidence shows that Bifidobacterium species may be beneficial in constipation. AIM: To investigate changes in physiological and clinical measures of gut function in patients with chronic constipation following the consumption of Bifidobacterium lactis NCC2818, compared to placebo. METHODS: Participants were randomised to a 4-week supplementation with B. lactis NCC2818 (1.5 x 1010 CFU/d) or placebo. Gut transit time was measured using a radio-opaque marker, while symptoms and quality of life were assessed using validated questionnaires. Gut microbiota composition was assessed using quantitative polymerase chain reaction. Analysis of covariance was used for normally distributed variables, and Mann-Whitney test for non-normally distributed variables. RESULTS: Seventy-five participants were randomised. There was no significant difference between the probiotic and placebo groups in gut transit time change from baseline to week 2 (-11.7 hours, SD 33.0 hours vs -12.9 hours, SD 33.6 hours; P = 0.863) or to week 4 (-20.4 hours, SD 32.5 h vs -8.7 hours, SD 33.8 hours; P = 0.103). There were also no improvements in stool output, symptoms, or quality of life. No differences were found in Bifidobacterium concentrations between the probiotic and placebo groups at week 4 (9.5 log10 /g dry faeces, SD 0.3 vs 9.4 log10 /g, SD 1.0; P = 0.509). CONCLUSIONS: Bifidobacterium lactis NCC2818 was not effective in the management of mild chronic constipation. This study highlights the importance of further studies and their publication to better understand the strain-specific effects of probiotics.

Low-volume versus high-volume initiated trans-anal irrigation therapy in adults with chronic constipation: study protocol for a randomised controlled trial.

BACKGROUND: Constipation is common in adults and up to 20% of the population report this symptom. Chronic constipation (CC), usually defined as more than 6 months of symptoms, is less common but results in 0.5 million UK GP consultations per annum. The effect of symptoms on measured quality of life (QOL) is significant, and CC consumes significant health care resources. In the UK, it is estimated that 10% of district nursing time is spent on constipation. Trans-anal irrigation therapy has become a widely used treatment despite a lack of robust efficacy data to support its use. The long-term outcome of treatment is also unclear. A randomised comparison of two different methods of irrigation (high- and low-volume) will provide valuable evidence of superiority of one system over the other, as well as providing efficacy data for the treatment as a whole. METHODS: Participants will be recruited based on predetermined eligibility criteria. Following informed consent, they will be randomised to either high-volume (HV) or low-volume (LV) irrigation and undergo standardised radiological and physiological investigations. Following training, they will commence home irrigation with the allocated device. Data will be collected at 1, 3, 6 and 12 months according to a standardised outcomes framework. The primary outcome is PAC-QOL, measured at 3 months. The study is powered to detect a 10% difference in outcome between systems at 3 months; this means that 300 patients will need to be recruited. DISCUSSION: This study will be the first randomised comparison of two different methods of trans-anal irrigation. It will also be the largest prospective study of CC patients treated with irrigation. It will provide evidence for the effectiveness of irrigation in the treatment of CC, as well as the comparative effectiveness of the two methods. This will enable more cost-effective and evidence-based use of irrigation. Also, the results will be combined with the other studies in the CapaCiTY programme to generate an evidence-based treatment algorithm for CC in adults. TRIAL REGISTRATION: ISRCTN, identifier: ISRCTN11093872 . Registered on 11 November 2015. Trial not retrospectively registered. Protocol version 3 (22 January 2016).