Development of a Digital Health Intervention to Support Patients on a Waitlist for Orthopedic Specialist Care: Co-Design Study.

BACKGROUND: The demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care. OBJECTIVE: This study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage. METHODS: The stakeholders involved in the co-design process included the research team; end users (patients); clinicians; academic experts; senior hospital staff; and a research, design, and development agency. The iterative co-design process comprised several key phases, including the collation and refinement of evidence-based information by the research team, with assistance from academic experts. Structured interviews with 16 clinicians (female: n=10, 63%; male: n=6, 38%) and 11 end users (age: mean 64.3, SD 7.2 y; female: n=7, 64%; male: n=4, 36%) of 1-hour duration were completed to understand the requirements for the intervention. Weekly workshops were held with key stakeholders throughout development. A different cohort of 15 end users (age: mean 61.5, SD 9.7 y; female: n=12, 80%; male: n=3, 20%) examined the feasibility of the study during a 2-week testing period. The System Usability Scale was used as the primary measure of intervention feasibility. RESULTS: Overall, 7 content modules were developed and refined over several iterations. Key themes highlighted in the clinician and end user interviews were the diverse characteristics of patients, the hierarchical structure with which patients view health practitioners, the importance of delivering information in multiple formats (written, audio, and visual), and access to patient-centered information as early as possible in the health care journey. All content was translated into Vietnamese, the most widely spoken language following English in the local government areas included in this study. Patients with hip and knee osteoarthritis from culturally and linguistically diverse backgrounds tested the feasibility of the intervention. A mean System Usability Scale score of 82.7 (SD 16) was recorded for the intervention, placing its usability in the excellent category. CONCLUSIONS: Through the co-design process, we developed an evidence-based, holistic, and patient-centered digital health intervention. The intervention was specifically designed to be used by patients from diverse backgrounds, including those with low health, digital, and written literacy levels. The effectiveness of the intervention in improving the physical and mental health of patients will be determined by a high-quality randomized controlled trial.

High-Dose Vitamin B6 (Pyridoxine) Displays Strong Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated Monocytes.

Vitamin B6 is shown to have anti-inflammatory properties, which makes it an interesting nutraceutical agent. Vitamin B6 deficiency is well established as a contributor to inflammatory-related conditions, whilst B6 supplementation can reverse these inflammatory effects. There is less information available regarding the effects of high-dose vitamin B6 supplementation as a therapeutic agent. This study set out to examine the effects of high-dose vitamin B6 on an LPS-stimulated monocyte/macrophage cell population via an analysis of protein and gene expression using an RT2 profiler PCR array for Human Innate and Adaptive Immune responses. It was identified that high-dose vitamin B6 has a global anti-inflammatory effect on lipopolysaccharide-induced inflammation in monocyte/macrophage cells by downregulating the key broad-spectrum inflammatory mediators CCL2, CCL5, CXCL2, CXCL8, CXCL10, CCR4, CCR5, CXCR3, IL-1ß, IL-5, IL-6, IL-10, IL-18, IL-23-a, TNF-α, CSF2, DDX58, NLRP3, NOD1, NOD2, TLR-1 -2 -4 -5 -7 -8 -9, MYD88, C3, FOXP3, STAT1, STAT3, STAT6, LYZ, CASP-1, CD4, HLA-E, MAPK1, MAPK8 MPO, MX-1, NF-κß, NF-κß1A, CD14, CD40, CD40LG, CD86, Ly96, ICAM1, IRF3, ITGAM, and IFCAM2. The outcomes of this study show promise regarding vitamin B6 within the context of a potent broad-spectrum anti-inflammatory mediator and could prove useful as an adjunct treatment for inflammatory-related diseases.

Combination of Taurine and Black Pepper Extract as a Treatment for Cardiovascular and Coronary Artery Diseases.

The shift in modern dietary regimens to "Western style" and sedentary lifestyles are believed to be partly responsible for the increase in the global burden of cardiovascular diseases. Natural products have been used throughout human history as treatments for a plethora of pathological conditions. Taurine and, more recently, black pepper have gained attention for their beneficial health effects while remaining non-toxic even when ingested in excess. Taurine, black pepper, and the major terpene constituents found in black pepper (i.e., ß-caryophyllene; α-pinene; ß-pinene; α-humulene; limonene; and sabinene) that are present in PhytoCann BP® have been shown to have cardioprotective effects based on anti-inflammatory, antioxidative, anti-hypertensive and anti-atherosclerotic mechanisms. This comprehensive review of the literature focuses on determining whether the combination of taurine and black pepper extract is an effective natural treatment for reducing cardiovascular diseases risk factors (i.e., hypertension and hyperhomocysteinemia) and for driving anti-inflammatory, antioxidative and anti-atherosclerotic mechanisms to combat coronary artery disease, heart failure, myocardial infarction, and atherosclerotic disease.

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.

Advanced Phytochemical-Based Nanocarrier Systems for the Treatment of Breast Cancer.

As the world's most prevalent cancer, breast cancer imposes a significant societal health burden and is among the leading causes of cancer death in women worldwide. Despite the notable improvements in survival in countries with early detection programs, combined with different modes of treatment to eradicate invasive disease, the current chemotherapy regimen faces significant challenges associated with chemotherapy-induced side effects and the development of drug resistance. Therefore, serious concerns regarding current chemotherapeutics are pressuring researchers to develop alternative therapeutics with better efficacy and safety. Due to their extremely biocompatible nature and efficient destruction of cancer cells via numerous mechanisms, phytochemicals have emerged as one of the attractive alternative therapies for chemotherapeutics to treat breast cancer. Additionally, phytofabricated nanocarriers, whether used alone or in conjunction with other loaded phytotherapeutics or chemotherapeutics, showed promising results in treating breast cancer. In the current review, we emphasize the anticancer activity of phytochemical-instigated nanocarriers and phytochemical-loaded nanocarriers against breast cancer both in vitro and in vivo. Since diverse mechanisms are implicated in the anticancer activity of phytochemicals, a strong emphasis is placed on the anticancer pathways underlying their action. Furthermore, we discuss the selective targeted delivery of phytofabricated nanocarriers to cancer cells and consider research gaps, recent developments, and the druggability of phytoceuticals. Combining phytochemical and chemotherapeutic agents with nanotechnology might have far-reaching impacts in the future.

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.

Non-oestrogenic modalities to reverse urogenital aging.

Urogenital aging is a common process affecting all women in the post-menopausal period of their life, and it is substantially due to oestrogen deprivation after ovarian function cessation. These changes can lead to a progressive, chronic, and complex association of symptoms identified as the genitourinary syndrome of menopause, which has a significant impact on quality of life. Genitourinary syndrome and urogenital aging do not resolve spontaneously and usually recur when treatment is stopped. Therefore, appropriate long-term management is of paramount importance, and local oestrogen is the most effective treatment to reverse urogenital aging and to improve symptoms of genitourinary syndrome as replacement therapy. In some women, topical oestrogen may be inconvenient, it may not achieve complete response, or it may be contra-indicated. Several non-hormonal therapies have been investigated, but few treatments have been reported as potentially able to reverse the urogenital aging process similarly to exogenous oestrogens. Laser seems the most promising, although further studies to define its safety and efficacy are mandatory. Vitamin D and E, and phytotherapy have returned conflicting results and require further confirmation. Lifestyle modifications, physiotherapy, and electrical stimulation represent inexpensive and applicable treatments that might slow urogenital aging. Among the hormonal non-oestrogenic therapies, the use of vaginal oxytocin and dehydroepiandrosterone have been found to be effective compared to placebo, as well as the use of oral ospemifene, which partially relieves vulvovaginal atrophy.

The Effects of Bariatric Surgery on Vitamin B Status and Mental Health.

Diet is a modifiable factor that ensures optimal growth, biochemical performance, improved mood and mental functioning. Lack of nutrients, notably vitamin B, has an impact on human health and wellbeing. The United Arab Emirates is facing a serious problem of micronutrient deficiencies because of the growing trend for bariatric surgery, including Roux-en-Y gastric bypass and sleeve gastrectomy. People undergoing bariatric surgery are at high risk of developing neurological, cognitive, and mental disabilities and cardiovascular disease due to deficiency in vitamin B. Vitamin B is involved in neurotransmitter synthesis, including γ-aminobutyric acid, serotonin, dopamine, and noradrenaline. Deficiency of vitamin B increases the risk of depression, anxiety, dementia and Alzheimer's disease. In addition, vitamin B deficiency can disrupt the methylation of homocysteine, leading to hyperhomocysteinemia. Elevated homocysteine levels are detrimental to human health. Vitamin B deficiency also suppresses immune function, increases the production of pro-inflammatory cytokines and upregulates NF-κB. Considering the important functions of vitamin B and the severe consequences associated with its deficiency following bariatric surgery, proper dietary intervention and administration of adequate supplements should be considered to prevent negative clinical outcomes.

Nutritional Interventions for COVID-19: A Role for Carnosine?

As COVID-19 continues to take an enormous toll on global health, the effort to find effective preventive and treatment strategies has been unparalleled in recent history [...].

Anti-cancer effects of polyphenol-rich sugarcane extract.

Plant polyphenols have an array of health benefits primarily thought to be related to their high content of anti-oxidants. These are commonly undervalued and knowledge of their biological properties have grown exponentially in the last decade. Polyphenol-rich sugarcane extract (PRSE), a natural extract from sugar cane, is marketed as high in anti-oxidants and polyphenols, but its anti-cancer activity has not been reported previously. We show that, PRSE exerts anti-cancer properties on a range of cancer cells including human (LIM2045) and mouse (MC38, CT26) colon cancer cells lines; human lung cancer (A549), human ovarian cancer (SKOV-3), pro-monocytic human leukemia (U937) and to mouse melanoma (B16) cell lines; whereas no effects were noted on human breast (ZR-75-1) and human colon (HT29) cancer cell lines, as well as to human normal colon epithelial cell line (T4056). Anti-proliferative effects were shown to be mediated via alteration in cytokines, VEGF-1 and NF-κB expression.

A Global Review on Short Peptides: Frontiers and Perspectives.

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.

The Role of Bioactive Compounds from Dietary Spices in the Management of Metabolic Syndrome: An Overview.

Metabolic syndrome (MetS) is a combination of physiologically dysregulated parameters that can include elevated fasting blood glucose, high blood pressure, central obesity, increased triglyceride levels, insulin resistance, diabetes, elevated low density lipoprotein levels, and reduced high density lipoprotein levels in the blood. Effective clinical management of MetS is critical as it is strongly associated with long lasting and fatal complications in patients. Alongside standard care of lifestyle changes and medication, dietary supplements derived from herbal resources could be an alternative therapeutic strategy that is safe, efficient, culturally acceptable, and has few side effects. Of the dietary supplements, spicy foods have always been considered a great source of functional bioactive compounds. Herbal therapy is broadly used in many countries as a treatment or as a preventive measure in the management of MetS risk factors, including blood glucose, blood pressure, and blood lipid levels. Herein, an attempt is made to evaluate the recent studies in the management of MetS with herbal alternatives, and to explore the possibility of their use as therapeutic treatments or supplements.

Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?

The world is currently in the grips of the coronavirus disease (COVID-19) pandemic, caused by the SARS-CoV-2 virus, which has mutated to allow human-to-human spread. Infection can cause fever, dry cough, fatigue, severe pneumonia, respiratory distress syndrome and in some instances death. COVID-19 affects the immune system by producing a systemic inflammatory response, or cytokine release syndrome. Patients with COVID-19 have shown a high level of pro-inflammatory cytokines and chemokines. There are currently no effective anti-SARS-CoV-2 viral drugs or vaccines. COVID-19 disproportionately affects the elderly, both directly, and through a number of significant age-related comorbidities. Undoubtedly, nutrition is a key determinant of maintaining good health. Key dietary components such as vitamins C, D, E, zinc, selenium and the omega 3 fatty acids have well-established immunomodulatory effects, with benefits in infectious disease. Some of these nutrients have also been shown to have a potential role in the management of COVID-19. In this paper, evidence surrounding the role of these dietary components in immunity as well as their specific effect in COVID-19 patients are discussed. In addition, how supplementation of these nutrients may be used as therapeutic modalities potentially to decrease the morbidity and mortality rates of patients with COVID-19 is discussed.

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.

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.

Polyphenol Rich Sugar Cane Extract Inhibits Bacterial Growth.

Plants that are primarily used as a food source commonly have undervalued biological properties beyond the basic supply of nutrients. One important example of this are the antimicrobial properties of plants. Inclusion of natural and food grade antimicrobial ingredients in recipes to prevent food spoilage and disease transmission, or in cosmetic products to prevent transient and pathogenic bacteria would have world-wide public health implications. A patented natural polyphenol rich sugar cane extract (PRSE), is marketed as a high anti-oxidant and polyphenol ingredient, but its anti-microbial activity has not been reported previously. We determined the anti-bacterial properties of PRSE on common human pathogens relating to a range of diseases including food poisoning, tooth decay, acne and severe skin infections using disc/well diffusion experiments. Our findings indicate that PRSE is an efficient antimicrobial, which could be included at differing dosages to target a range of food borne and environmental pathogens.

Anti-Tumor Effects of Vitamin B2, B6 and B9 in Promonocytic Lymphoma Cells.

Chronic inflammation can lead to tumour initiation and progression. Vitamin B complex has the ability to regulate the immune response and, therefore, inflammation but many of the mechanistic and molecular processes involved in this regulation are still not fully understood. This study sought to determine some of these processes by studying the effects of vitamin B2 (riboflavin) B6 (pyridoxine) and B9 (folic acid) on un-differentiated pro-monocytic lymphoma cells in regard to their ability to alter the proliferation, migration, apoptosis, cytokines and expression levels of programmed death ligand 1. We show that vitamin B2, B6 and B9, on pro-monocytic lymphoma cells exerted an anti-tumorigenic effect. This data could form the basis for future studies in using vitamin B supplementation to reduce cancer cell growth in vivo.

Therapeutic applications of polarized light: Tissue healing and immunomodulatory effects.

As the population grows and ages, non-pharmaceutical options for the treatment and management of wounds, disease and injury are required to ensure adequate care. Polarized light therapy (PLT) utilizes visible-spectrum polarized light for a number of clinical applications. The advantage of polarized light is that it is able to penetrate the skin to a depth of up to 5 cm, reaching deeper tissues involved in wound healing. PLT has been shown to accelerate the healing process for ulcers, surgical wounds and dermal burns as well as a small number of musculoskeletal injuries. As research into the histological and physiological effects of PLT is largely absent, studies related to other light therapy modalities, largely low-level laser therapy, may pave the way to identify putative mechanisms by which PLT might exert its effects. Changes to cell signalling and secretion of substances required for wound healing have been identified in response to phototherapies. The reviewed literature suggests that PLT may be efficacious in some wound and injury healing contexts, though a gap in the literature exists regarding its mechanisms of action. Future studies should fully explain the therapeutic effects of PLT and the physiological mechanisms underpinning them.