The protective role of carnosine against type 2 diabetes-induced cognitive impairment.

The morbidity and mortality associated with type 2 diabetes mellitus (T2DM) have grown exponentially over the last 30 years. Together with its associated complications, the mortality rates have increased. One important complication in those living with T2DM is the acceleration of age-related cognitive decline. T2DM-induced cognitive impairment seriously affects memory, executive function, and quality of life. However, there is a lack of effective treatment for both diabetes and cognitive decline. Thus, finding novel treatments which are cheap, effective in both diabetes and cognitive impairment, are easily accessible, are needed to reduce impact on patients with diabetes and health-care systems. Carnosine, a histidine containing dipeptide, plays a protective role in cognitive diseases due to its antioxidant, anti-inflammation, and anti-glycation properties, all of which may slow the development of neurodegenerative diseases and ischemic injury. Furthermore, carnosine is also involved in regulating glucose and insulin in diabetes. Herein, we discuss the neuroprotective role of carnosine and its mechanisms in T2DM-induced cognitive impairment, which may provide a theoretical basis and evidence base to evaluate whether carnosine has therapeutic effects in alleviating cognitive dysfunction in T2DM patients.

Differential responses to aging amongst the transcriptome and proteome of mesenchymal progenitor populations.

The biological aging of stem cells (exhaustion) is proposed to contribute to the development of a variety of age-related conditions. Despite this, little is understood about the specific mechanisms which drive this process. In this study, we assess the transcriptomic and proteomic changes in three different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues. To do this, we harvested primary bone marrow mesenchymal stem and progenitor cells (MPCs), circulating osteoprogenitors (COP), and adipose-derived stem cells (ADSCs) from younger and older donors, with an equal number of samples from males and females. These samples underwent RNA sequencing and label-free proteomic analysis, comparing the younger samples to the older ones. There was a distinct transcriptomic phenotype in the analysis of pooled older stem cells, suggestive of suppressed proliferation and differentiation; however, these changes were not reflected in the proteome of the cells. Analyzed independently, older MPCs had a distinct phenotype in both the transcriptome and proteome consistent with altered differentiation and proliferation with a pro-inflammatory immune shift in older adults. COP cells showed a transcriptomic shift to pro-inflammatory signaling but no consistent proteomic phenotype. Similarly, ADSCs displayed transcriptomic shifts in physiologies associated with cell migration, adherence, and immune activation but no proteomic change with age. These results show that there are underlying transcriptomic changes with stem cell aging that may contribute to a decline in tissue regeneration. However, the proteome of the cells was inconsistently regulated.

Transcriptome analysis of the effects of polarized photobiomodulation on human dermal fibroblasts.

BACKGROUND: Photobiomodulation (PBM), the therapeutic use of light, is used to treat a myriad of conditions, including the management of acute and chronic wounds. Despite the presence of clinical evidence surrounding PBM, the fundamental mechanisms underpinning its efficacy remain unclear. There are several properties of light that can be altered in the application of PBM, of these, polarization-the filtering of light into specified plane(s)-is an attractive variable to investigate. AIMS: To evaluate transcriptomic changes in human dermal fibroblasts in response to polarized PBM. RESULTS: A total of 71 Differentially Expressed Genes (DEGs) are described. All DEGs were found in the polarized PBM group (P-PBM), relative to the control group (PC). Of the 71 DEGs, 10 genes were upregulated and 61 were downregulated. Most DEGs were either mitochondrial or extracellular matrix (ECM)-related. Gene Ontology (GO) analysis was then performed using the DEGs from the P-PBM vs. PC group. Within biological processes there were 95 terms found (p < 0.05); in the molecular function there were 18 terms found (p < 0.05); while in the cellular component there were 32 terms enriched (p < 0.05). A KEGG pathways analysis was performed for the DEGs found in the P-PBM vs. PC group. This revealed 21 significantly enriched pathways (p < 0.05). Finally, there were 24 significantly enriched reactome pathways when comparing the DEGs of the P-PBM vs. PC groups (p < 0.05). DISCUSSION AND CONCLUSIONS: The P-PBM DEGs were almost always down regulated compared to the comparator groups. This may be explained by the P-PBM treatment conditions decreasing the amount of cellular stress, hence causing a decreased mitochondria and ECM protective response. Alternatively, it could point to an alternate mechanism, outside the mitochondria, by which PBM exerts its effects. Additionally, PBM appears to have a more widespread effect on the mitochondria than previously thought, opening up many new avenues of investigation in the process.

The impact of motivational interviewing on behavioural change and health outcomes in cancer patients and survivors. A systematic review and meta-analysis.

BACKGROUND: Cancer patients and survivors commonly have poorer health behaviours and subsequent outcomes, often as a result of negative impacts of diagnosis and treatment. Motivational interviewing is reported to be an effective psychological tool to produce a shift in one's behaviour resulting in improved outcomes. However, there is a lack of analyses investigating this tool's impact on healthy behaviours and health outcomes in cancer populations. OBJECTIVE: To investigate the effect of motivational interviewing on behaviours and health outcomes in cancer populations. METHODS: The studies were identified from four databases using variations of the terms "cancer" and "motivational interviewing". Randomised trials, non-randomised trials and quasi-experimental studies which contained control (or usual care) comparators were included. Risk of bias was assessed using the Cochrane Risk of Bias Version 5.1.0 and the Risk of Bias In Non-Randomised Studies of Interventions tools. The quality of evidence was assessed using the GRADE framework. Means difference and standardised mean differences and 95 % confidence intervals were used to report the pooled effects using a random effects model. RESULTS: Twenty-one studies were included in the review and 17 studies were included in the meta-analysis. A total of 1752 cancer patients and survivors received MI as an intervention (or part thereof). Quality of life, anxiety, depression, functional tasks (6-minute walk test), body mass index and body weight (BMI/BW), physical activity (PA), self-efficacy and fatigue were outcomes measured in the selected studies. Effects were seen in functional tasks, physical activity, BMI/BW, depression and self-efficacy. All of these outcomes were from studies that were classed as very low-quality evidence except for BMI/BW and PA, which were from moderate-quality evidence. CONCLUSION: Motivational interviewing had positive effects on functional tasks, PA, BMI/BW, depression and self-efficacy in people diagnosed with cancer. However, more higher-quality studies need to be conducted to further ascertain the effect of this intervention.

Differential responses to aging amongst the transcriptome and proteome of mesenchymal progenitor populations.

The biological aging of mesenchymal stem cells is proposed to contribute to the development of a range of musculoskeletal and systemic diseases associated with older adults, such as osteoporosis, sarcopenia, and frailty. Despite this, little is understood about the specific mechanisms which drive this stem cell exhaustion, with most studies evaluating indirect effects of other aging changes, such as DNA damage, senescence, and inflammaging. In this study, we assess the transcriptomic and proteomic changes in three different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues. To do this, we harvested primary bone marrow mesenchymal stem and progenitor cells (MPCs), circulating osteoprogenitors (COP), and adipose-derived stem cells (ADSCs) from younger and older donors, with an equal number of samples from males and females. These samples underwent RNA sequencing and label-free proteomic analysis, comparing the younger samples to the older ones. There was a distinct transcriptomic phenotype associated with the pooled older stem cells, indicative of suppressed proliferation and differentiation; however, there was no consistent change in the proteome of the cells. Older MPCs had a distinct phenotype in both the transcriptome and proteome, again consistent with altered differentiation and proliferation, but also a pro-inflammatory immune shift in older adults. COP cells showed a strong transcriptomic shift to pro-inflammatory signaling but no consistent proteomic phenotype. Similarly, ADSCs displayed transcriptomic shift in physiologies associated with cell migration, adherence, and immune activation, but no consistent proteomic change with age. These results show that there are underlying transcriptomic changes with stem cell aging that likely contribute to a decline in tissue regeneration; however, contextual factors such as the microenvironment and general health status also have a strong role in this.

The effects of polarized photobiomodulation on cellular viability, proliferation, mitochondrial membrane potential and apoptosis in human fibroblasts: Potential applications to wound healing.

Photobiomodulation (PBM) is a widely used therapeutic intervention used to treat several chronic conditions. Despite this, fundamental research underpinning its effectiveness is lacking, highlighted by the lack of a definitive mechanism of action. Additionally, there are many treatment variables which remain underexplored, one of those being the effect of polarization the property of light that specifies the direction of the oscillating electric field. When applied to PBM, using linearly polarized light, when compared to otherwise identical non-polarized light, may enhance its biological efficacy. As such, we investigated the potential biological effects of polarized PBM when compared to non-polarized and non-irradiated controls in the domains of cellular viability, proliferation, apoptosis and mitochondrial membrane potential (ΔΨ) within cells exposed to oxidative stress. It was noted that polarized PBM, when compared to non-polarized PBM and non-irradiated controls, demonstrated mostly increased levels of cellular proliferation and ΔΨ, whilst decreasing the amount of cellular apoptosis. These results indicate that polarization may have utility in the clinical application of PBM. Future research is needed to further elucidate the underpinning mechanisms of PBM and polarization.

Higher Levels of Circulating Osteoprogenitor Cells Are Associated With Higher Bone Mineral Density and Lean Mass in Older Adults: A Cross-Sectional Study.

Circulating osteo progenitor (COP) cells are a heterogeneous population of cells that circulate within the peripheral blood with characteristics of the bone marrow mesenchymal stem and progenitor pool. Little is known about the behavior of this cell population in humans. The aim of this study was to identify whether a relationship exists between COP cells (as a percentage of the peripheral blood monocytic cells) and musculoskeletal morphometry and to identify if COP have potential clinical utility as a biomarker for osteoporosis. We recruited 57 older adults (median age: 69 years; IQR: 65, 75 years) living independently in the community and performed cross-sectional analysis to identify associations between the percentage of COP cells and body composition parameters, and through receiver operating characteristic analysis, we evaluated their ability to act as a biomarker of osteoporosis. COP cells were moderately associated with whole-body bone mineral density (BMD) (r = 0.323, p = 0.014) and bone mineral content (BMC) (r = 0.387, p = 0.003), neck of femur BMD (r = 0.473, p < 0.001), and BMC (r = 0.461, p < 0.001) as well as appendicular lean mass (ALM) (p = 0.038) and male sex (p = 0.044) in univariable analysis. In multivariable analysis controlling for age, gender, height, and weight, COP cells remained strongly associated with neck of femur BMD (p = 0.001) and content (p = 0.003). COP cells were also a good predictor of osteoporosis (dual-energy X-ray absorptiometry [DXA] T-score < -2.5) at the neck of femur (cutoff: 0.4%; sensitivity: 100%; specificity 79%) and total body (cutoff: 0.35%; sensitivity: 80%; specificity: 81%). This study shows strong relationships between bone parameters and COP cell number and male sex. They also have potential as a biomarker of osteoporosis, which may provide a new tool for advanced detection and screening in clinical settings. Future larger evaluation studies should verify the cutoffs for biomarker use, and further explore the relationship between COP cells and muscle. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The effect of low-level red and near-infrared photobiomodulation on pain and function in tendinopathy: a systematic review and meta-analysis of randomized control trials.

BACKGROUND: Tendinopathy is a common clinical condition that can significantly affect a person's physical function and quality of life. Despite exercise therapy being the mainstay of tendinopathy management, there are many potential adjunct therapies that remain under investigated, one of which is photobiomodulation (PBM). PBM uses varied wavelengths of light to create a biological effect. While PBM is used frequently in the management of tendinopathy, high quality evidence supporting its utility is lacking. METHODS: A systematic search of the Pubmed, CINAHL, SCOPUS, Cochrane Database, Web of Science and SPORTSDICUS databases was performed for eligible articles in August 2020. Randomized Control Trials that used red or near-infrared PBM to treat tendinopathy disorders that made comparisons with a sham or 'other' intervention were included. Pain and function data were extracted from the included studies. The data were synthesized using a random effects model. The meta-analysis was performed using the mean difference (MD) and standardized mean difference (SMD) statistics. RESULTS: A total of 17 trials were included (n = 835). When compared solely to other interventions PBM resulted in similar decreases in pain (MD -0.09; 95% CI - 0.79 to 0.61) and a smaller improvement in function (SMD -0.52; 95% CI - 0.81 to - 0.23). When PBM plus exercise was compared to sham treatment plus exercise, PBM demonstrated greater decreases in pain (MD 1.06; 95% CI 0.57 to 1.55) and improved function (MD 5.65; 95% CI 0.25 to 11.04). When PBM plus exercise was compared to other interventions plus exercise, no differences were noted in pain levels (MD 0.31; 95% CI - 0.07 to 0.70). Most studies were judged as low-risk of bias. The outcome measures were classified as very low to moderate evidence quality according to the Grading of Recommendation, Development and Evaluation tool. CONCLUSION: There is very-low-to-moderate quality evidence demonstrating that PBM has utility as a standalone and/or adjunctive therapy for tendinopathy disorders. TRIAL REGISTRATION: PROPERO registration number: CRD42020202508 .

The effect of vitamin D supplementation on circulating osteoprogenitor cells: A pilot randomized controlled trial.

Circulating osteoprogenitor (COP) cells are a relatively newly discovered mesenchymal precursors population in the peripheral blood. While some aspects of their physiology have been documented in vitro, little is known about their behavior in vivo. To facilitate understanding regarding their potential role in the management of musculoskeletal disease, more research into how these cells respond to growth factors and hormones in vivo is still required. To this end, we performed a randomized controlled pilot study investigating the effect of vitamin D supplementation on COP cells in healthy older adults. Twenty-two individuals were recruited and stratified through their baseline vitamin D levels into deficient (<35 nmol/L), insufficient (35-49 nmol/L) and sufficient (>50 nmol/L) groups, and then randomized to receive either a 50,000 IU bolus dose of vitamin D, along with a 1000 IU daily supplement for six weeks, or the 1000 IU supplement alone. Participants were assessed at baseline, week three, and week six, with the primary outcome being a change in the number of COP cells. Secondary outcomes were vitamin D, markers of bone formation and resorption, parathyroid hormone, and calcium. The study showed that, independently of the dosing, increasing vitamin D levels led to a concomitant 52% increase in COP cell number (p < 0.001). There were no differences between strata, or any of the secondary outcomes in the trial. This suggests that COP cells are regulated in some way by vitamin D, similar to the bone marrow mesenchymal stem cell. Future studies are needed to evaluate the long-term effects of vitamin D supplementation, and how COP cells may be involved in chronic musculoskeletal disease.

The twilight of the immune system: The impact of immunosenescence in aging.

Cellular senescence is a critical part of human anti-tumor defence; however, the accumulation of senescent cells with age underpins a wide range of pathologies. Senescent change in immune cells, or immunosenescence, has a wide range of physiological effects and is at least partially responsible for many diseases associated with aging. Immunosenescence underpins inflammaging, increased vulnerability to infectious disease with age, malignant change in the elderly, and auto-immunity. Understanding the effects and mechanisms of immunosenescence will improve disease outcomes and prevention in older adults, and generate new treatments for common illnesses. In this review we summarize the key changes occurring in immunosenescence across each facet of the immune system, and identify their clinical correlates.

The effects of photobiomodulation on human dermal fibroblasts in vitro: A systematic review.

Photobiomodulation (PBM) is reported to impart a range of clinical benefits, from the healing of chronic wounds to athletic performance enhancement. The increasing prevalence of this therapy conflicts with the lack of understanding concerning specific cellular mechanisms induced by PBM. Herein, we systematically explore the literature base, specifically related to PBM (within the range 600-1070 nm) and its influence on dermal fibroblasts. The existing research in this field is appraised through five areas: cellular proliferation and viability; cellular migration; ATP production and mitochondrial membrane potential; cellular protein expression and synthesis; and gene expression. This review demonstrates that when fibroblasts are irradiated in vitro within a set range of intensities, they exhibit a multitude of positive effects related to the wound healing process. However, the development of an optimal in vitro framework is paramount to improve the reliability and validity of research in this field.

Twelve tips for developing feedback literacy in health professions learners.

Despite feedback being widely-used by health professions educators as a tool to develop clinical competencies, strategies to guide its successful implementation remain limited. In addition, health professions learners are often dissatisfied with the quality and/or volume of feedback they receive. Efforts to better engage learners in feedback processes have resulted in the development of a number of theoretical frameworks to guide educators, one being feedback literacy. Feedback literacy can be conceptualised as a learner's ability to recognise, comprehend, generate, and take action on feedback they encounter during their learning to aid health professions learners' clinical competency development. Here, we draw on both a conceptual framework of feedback literacy and other contemporary feedback literature to provide 12 practical tips by which feedback literacy can be developed in health professions learners.

The Impact of Three-Dimensional Printed Anatomical Models on First-Year Student Engagement in a Block Mode Delivery.

Student engagement is known to have several positive effects on learning outcomes and can impact a student's university experience. High levels of engagement in content-heavy subjects can be difficult to attain. Due to a major institutional restructure, the anatomy prosection laboratory time per subject was dramatically reduced. In response, the authors set out to redesign their anatomy units with a focus on engaging the learning activities that would increase time-on-task both within and outside of the classroom. One of these curriculum changes was the implementation of a suite of anatomy learning activities centered on sets of three-dimensional printed upper limb skeleton models. A two-part mixed-method sequential exploratory design was used to evaluate these activities. Part one was a questionnaire that evaluated the students' engagement with and perceptions of the models. Part two involved focus groups interviews, which were an extension of the survey questions in part one. The results of the study indicated that the majority of students found the models to be an engaging resource that helped improve their study habits. As a result, students strongly felt that the use of the models inspired greater academic confidence and overall better performance in their assessments. Overall, the models were an effective way of increasing the engagement and deep learning, and reinforced previous findings from the medical education research. Future research should investigate the effects of these models on student's grades within osteopathy and other allied health courses.

Good, better, best? The effects of polarization on photobiomodulation therapy.

Photobiomodulation therapy (PBMT) is a widely adopted form of phototherapy used to treat many chronic conditions that effect the population at large. The exact physiological mechanisms of PBMT remain unsolved; however, the prevailing theory centres on changes in mitochondrial function. There are many irradiation parameters to consider when investigating PBMT, one of which is the state of polarization. There is some evidence to show that polarization of red and near-infrared light may promote different and/or increased biological activity when compared to otherwise identical non-polarized light. These enhanced cellular effects may also be present when the polarized light is applied linear to the tissue direction. Herein, we synthesize the current experimental and clinical evidence pertaining to polarized photobiomodulation therapy; ultimately, to better inform future research into this area of phototherapy.

Polarized light therapy: Shining a light on the mechanism underlying its immunomodulatory effects.

This study investigates the immunomodulatory effects of polychromatic polarized light therapy (PLT) on human monocyte cells. While there is some evidence demonstrating a clinical effect in the treatment of certain conditions, there is little research into its mechanism of action. Herein, U937 monocyte cells were cultured and exposed to PLT. The cells were then analyzed for change in expression of genes and cell surface markers relating to inflammation. It was noted that 6 hours of PLT reduced the expression of the CD14, MHC I and CD11b receptors, and increased the expression of CD86. It was also shown that PLT caused downregulation of the genes IL1B, CCL2, NLRP3 and NOD1, and upregulation of NFKBIA and TLR9. These findings imply that PLT has the capacity for immunomodulation in human immune cells, possibly exerting an anti-inflammatory effect.