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Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.

Emergence of novel treatment modalities provides effective therapeutic options, apart from conventional cytotoxic chemotherapy, to fight against colorectal cancer. Unfortunately, drug resistance remains a huge challenge in clinics, leading to invariable occurrence of disease progression after treatment initiation. While novel drug development is unfavorable in terms of time frame and costs, drug repurposing is one of the promising strategies to combat resistance. This approach refers to the application of clinically available drugs to treat a different disease. With the well-established safety profile and optimal dosing of these approved drugs, their combination with current cancer therapy is suggested to provide an economical, safe and efficacious approach to overcome drug resistance and prolong patient survival. Here, we review both preclinical and clinical efficacy, as well as cellular mechanisms, of some extensively studied repurposed drugs, including non-steroidal anti-inflammatory drugs, statins, metformin, chloroquine, disulfiram, niclosamide, zoledronic acid and angiotensin receptor blockers. The three major treatment modalities in the management of colorectal cancer, namely classical cytotoxic chemotherapy, molecular targeted therapy and immunotherapy, are covered in this review.

ObjectiveGut microbiota is a key player in dictating immunotherapy response. We aimed to explore the immunomodulatory effect of probiotic Lactobacillus gallinarum and its role in improving anti-programmed cell death protein 1 (PD1) efficacy against colorectal cancer (CRC).DesignThe effects of L. gallinarum in anti-PD1 response were assessed in syngeneic mouse models and azoxymethane/dextran sulfate sodium-induced CRC model. The change of immune landscape was identified by multicolour flow cytometry and validated by immunohistochemistry staining and in vitro functional assays. Liquid chromatography-mass spectrometry was performed to identify the functional metabolites.ResultsL. gallinarum significantly improved anti-PD1 efficacy in two syngeneic mouse models with different microsatellite instability (MSI) statuses (MSI-high for MC38, MSI-low for CT26). Such effect was confirmed in CRC tumourigenesis model. L. gallinarum synergised with anti-PD1 therapy by reducing Foxp3+ CD25+ regulatory T cell (Treg) intratumoural infiltration, and enhancing effector function of CD8+ T cells. L. gallinarum-derived indole-3-carboxylic acid (ICA) was identified as the functional metabolite. Mechanistically, ICA inhibited indoleamine 2,3-dioxygenase (IDO1) expression, therefore suppressing kynurenine (Kyn) production in tumours. ICA also competed with Kyn for binding site on aryl hydrocarbon receptor (AHR) and antagonised Kyn binding on CD4+ T cells, thereby inhibiting Treg differentiation in vitro. ICA phenocopied L. gallinarum effect and significantly improved anti-PD1 efficacy in vivo, which could be reversed by Kyn supplementation.ConclusionL. gallinarum-derived ICA improved anti-PD1 efficacy in CRC through suppressing CD4+Treg differentiation and enhancing CD8+T cell function by modulating the IDO1/Kyn/AHR axis. L. gallinarum is a potential adjuvant to augment anti-PD1 efficacy against CRC.

ObjectiveUsing faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential antitumourigenic role of L. gallinarum in colorectal tumourigenesis.DesignThe tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry.ResultsL. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum-treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size <3 kDa suppressed proliferation in CRC cells. Using LC-MS/MS, enrichments of indole-3-lactic acid (ILA) was identified in both L. gallinarum culture-supernatant and the gut of L. gallinarum-treated mice. ILA displayed anti-CRC growth in vitro and inhibited intestinal tumourigenesis in vivo.ConclusionL. gallinarum protects against intestinal tumourigenesis by producing protective metabolites that can promote apoptosis of CRC cells.

This study examined the relationship between ethnicity and dually diagnosed individuals who received outpatient treatment with a dataset by the Substance Abuse Mental Health Service Administration (SAMHSA). The survey administered nationwide in the United States was the National Survey on Drug Use and Health (NSDUH) with an 83% response rate. The rate of which ethnicities sought treatment for dual diagnosis was investigated through the framework of service utilization and help seeking behaviors. Results indicated there is a relationship between ethnicity and dual diagnosis with a 4.6% likelihood that they affect each other. There is an association between ethnicity and whether individuals sought outpatient treatment with a 7.9% likelihood of affect to each other. There is also an association between dually diagnosed individuals and their likelihood to seek treatment with 14.9% of affect to each other. When all three components are analyzed together, it was found that dually diagnosed individuals sought treatment 21.6% of the time. The ethnicity that did not find significance and sought outpatient treatment at the same rate (96%) as whites was more than one race. All other ethnicities, Blacks/African Americans (47.6%), Native Americans (33.2%), Hawaiian/Other Pacific Islanders (54.8%), Asians (53.7%), and Hispanics (52.9%) were less likely to seek outpatient treatment. The results described that more whites with dual diagnosis sought outpatient treatment at a higher rate than any other ethnicity. Even with the high participation rate, it is noteworthy that more attention is needed on ethnic representation for treatment facilities to become more effective. Whites dominated the data by 61.1%. The current research suggests a need for continued research and execution in cultural competence combined with dual diagnosis treatment.

Studies of Caucasian populations have shown that beta-blockers may exacerbate weight gain, a risk factor for many chronic diseases. Still, beta-blockers are the most prescribed antihypertensives in the Chinese population in Hong Kong. We aimed to explore the association between beta-blocker use, hypertension, and weight status of this population. A post-hoc analysis regarding body mass index (BMI) and the use of beta-blockers was performed based on the medication profile of community-dwelling older adults. Participants' BMI, hypertension diagnosis, name, dose, frequency, route of administration of beta-blockers, and other drugs that may alter body weight were recorded. Of 1053 Chinese individuals aged ≥65 years (mean age 76.9±7.2 years, 80% female) from 32 elderly centres in Hong Kong, 18% (185/1053) of them consumed beta-blockers. That group also had a significantly larger proportion of obese individuals (45.9% vs 32.1%, P=0.002). After adjusting for other weight-altering drugs, beta-blockers remained a significant predictor of overweight and obesity (P=0.001). As the hypertensive population had significantly higher BMI than the normotensive population (24.3±3.6 vs 22.9±3.5, P<0.001), a sub-analysis on those with hypertension diagnosis confirmed that only the hypertensive population taking atenolol had a significantly larger population of obese individuals (BMI ≥25) compared with those who took metoprolol (58.9% vs 38.5%, P=0.03) and those who did not take any beta-blockers (58.9% vs 38.4%, P=0.007). Our findings taken together with other guideline reservations cast doubt on whether beta-blockers, particularly atenolol, should be the major drug prescribed to older adults with hypertension.

Person memory research shows that people recall impression-incongruent information better than impression-congruent or irrelevant information. This experiment was conducted to examine the effects of mood on one's memory for person information. Subjects were randomly placed in 3 (happy, sad or neutral mood) x 2 (low or high motivation) x 2 (5 or 12 seconds processing time) x 2 (friendly or unfriendly trait impression) and read information that were impression-congruent/incongruent/irrelevant. Neutral mood subjects showed the expected incongruency effect. In contrast, happy and sad subjects did not show the recall advantage of incongruent information unless when they had both high motivation to process information carefully and 12 seconds processing time.

Background Markerless motion capture (MMC) technology has been developed to avoid the need for body marker placement during motion tracking and analysis of human movement. Although researchers have long proposed the use of MMC technology in clinical measurement—identification and measurement of movement kinematics in a clinical population, its actual application is still in its preliminary stages. The benefits of MMC technology are also inconclusive with regard to its use in assessing patients’ conditions. In this review we put a minor focus on the method’s engineering components and sought primarily to determine the current application of MMC as a clinical measurement tool in rehabilitation. Methods A systematic computerized literature search was conducted in PubMed, Medline, CINAHL, CENTRAL, EMBASE, and IEEE. The search keywords used in each database were “Markerless Motion Capture OR Motion Capture OR Motion Capture Technology OR Markerless Motion Capture Technology OR Computer Vision OR Video-based OR Pose Estimation AND Assessment OR Clinical Assessment OR Clinical Measurement OR Assess.” Only peer-reviewed articles that applied MMC technology for clinical measurement were included. The last search took place on March 6, 2023. Details regarding the application of MMC technology for different types of patients and body parts, as well as the assessment results, were summarized. Results A total of 65 studies were included. The MMC systems used for measurement were most frequently used to identify symptoms or to detect differences in movement patterns between disease populations and their healthy counterparts. Patients with Parkinson’s disease (PD) who demonstrated obvious and well-defined physical signs were the largest patient group to which MMC assessment had been applied. Microsoft Kinect was the most frequently used MMC system, although there was a recent trend of motion analysis using video captured with a smartphone camera. Conclusions This review explored the current uses of MMC technology for clinical measurement. MMC technology has the potential to be used as an assessment tool as well as to assist in the detection and identification of symptoms, which might further contribute to the use of an artificial intelligence method for early screening for diseases. Further studies are warranted to develop and integrate MMC system in a platform that can be user-friendly and accurately analyzed by clinicians to extend the use of MMC technology in the disease populations.

Mental illness stigma has been a global concern, owing to its adverse effects on the recovery of people with mental illness, and may delay help-seeking for mental health because of the concern of being stigmatized. With technological advancement, internet-based interventions for the reduction of mental illness stigma have been developed, and these effects have been promising. This study aimed to examine the differential effects of internet-based storytelling programs, which varied in the levels of interactivity and stigma content, in reducing mental illness stigma. Using an experimental design, this study compared the effects of 4 storytelling websites that varied in the levels of interactivity and stigma content. Specifically, the conditions included an interactive website with stigma-related content (combo condition), a noninteractive website with stigma-related content (stigma condition), an interactive website without stigma-related content (interact condition), and a noninteractive website without stigma-related content (control condition). Participants were recruited via mass emails to all students and staff of a public university and via social networking sites. Eligible participants were randomized into the following four conditions: combo (n=67), stigma (n=65), interact (n=64), or control (n=67). The participants of each group viewed the respective web pages at their own pace. Public stigma, microaggression, and social distance were measured on the web before the experiment, after the experiment, and at the 1-week follow-up. Perceived autonomy and immersiveness, as mediators, were assessed after the experiment. Both the combo (n=66) and stigma (n=65) conditions were effective in reducing public stigma and microaggression toward people with mental illness after the experiment and at the 1-week follow-up. However, none of the conditions had significant time×condition effects in reducing the social distance from people with mental illness. The interact condition (n=64) significantly reduced public stigma after the experiment (P=.02) but not at the 1-week follow-up (P=.22). The control condition (n=67) did not significantly reduce all outcomes associated with mental illness stigma. Perceived autonomy was found to mediate the effect of public stigma (P=.56), and immersiveness mediated the effect of microaggression (P=.99). Internet-based storytelling programs with stigma-related content and interactivity elicited the largest effects in stigma reduction, including reductions in public stigma and microaggression, although only its difference with internet-based storytelling programs with stigma-related content was not statistically significant. In other words, although interactivity could strengthen the stigma reduction effect, stigma-related content was more critical than interactivity in reducing stigma. Future stigma reduction efforts should prioritize the production of effective stigma content on their web pages, followed by considering the value of incorporating interactivity in future internet-based storytelling programs.