Molecular mechanisms of dietary restriction promoting health and longevity.

Dietary restriction with adequate nutrition is the gold standard for delaying ageing and extending healthspan and lifespan in diverse species, including rodents and non-human primates. In this Review, we discuss the effects of dietary restriction in these mammalian model organisms and discuss accumulating data that suggest that dietary restriction results in many of the same physiological, metabolic and molecular changes responsible for the prevention of multiple ageing-associated diseases in humans. We further discuss how different forms of fasting, protein restriction and specific reductions in the levels of essential amino acids such as methionine and the branched-chain amino acids selectively impact the activity of AKT, FOXO, mTOR, nicotinamide adenine dinucleotide (NAD+), AMP-activated protein kinase (AMPK) and fibroblast growth factor 21 (FGF21), which are key components of some of the most important nutrient-sensing geroprotective signalling pathways that promote healthy longevity.

Promoting health and longevity through diet: from model organisms to humans.

Reduced food intake, avoiding malnutrition, can ameliorate aging and aging-associated diseases in invertebrate model organisms, rodents, primates, and humans. Recent findings indicate that meal timing is crucial, with both intermittent fasting and adjusted diurnal rhythm of feeding improving health and function, in the absence of changes in overall intake. Lowered intake of particular nutrients rather than of overall calories is also key, with protein and specific amino acids playing prominent roles. Nutritional modulation of the microbiome can also be important, and there are long-term, including inter-generational, effects of diet. The metabolic, molecular, and cellular mechanisms that mediate both improvement in health during aging to diet and genetic variation in the response to diet are being identified. These new findings are opening the way to specific dietary and pharmacological interventions to recapture the full potential benefits of dietary restriction, which humans can find difficult to maintain voluntarily.

Regulators of gut motility revealed by a gnotobiotic model of diet-microbiome interactions related to travel.

To understand how different diets, the consumers' gut microbiota, and the enteric nervous system (ENS) interact to regulate gut motility, we developed a gnotobiotic mouse model that mimics short-term dietary changes that happen when humans are traveling to places with different culinary traditions. Studying animals transplanted with the microbiota from humans representing diverse culinary traditions and fed a sequence of diets representing those of all donors, we found that correlations between bacterial species abundances and transit times are diet dependent. However, the levels of unconjugated bile acids-generated by bacterial bile salt hydrolases (BSH)-correlated with faster transit, including during consumption of a Bangladeshi diet. Mice harboring a consortium of sequenced cultured bacterial strains from the Bangladeshi donor's microbiota and fed a Bangladeshi diet revealed that the commonly used cholekinetic spice, turmeric, affects gut motility through a mechanism that reflects bacterial BSH activity and Ret signaling in the ENS. These results demonstrate how a single food ingredient interacts with a functional microbiota trait to regulate host physiology.

Intermittent fasting in the prevention and treatment of cancer.

Chronic caloric restriction (CR) has powerful anticarcinogenic actions in both preclinical and clinical studies but may be difficult to sustain. As an alternative to CR, there has been growing interest in intermittent fasting (IF) in both the scientific and lay community as a result of promising study results, mainly in experimental animal models. According to a survey by the International Food Information Council Foundation, IF has become the most popular diet in the last year, and patients with cancer are seeking advice from oncologists about its beneficial effects for cancer prevention and treatment. However, as discussed in this review, results from IF studies in rodents are controversial and suggest potential detrimental effects in certain oncologic conditions. The effects of IF on human cancer incidence and prognosis remain unknown because of a lack of high-quality randomized clinical trials. Preliminary studies suggest that prolonged fasting in some patients who have cancer is safe and potentially capable of decreasing chemotherapy-related toxicity and tumor growth. However, because additional trials are needed to elucidate the risks and benefits of fasting for patients with cancer, the authors would not currently recommend patients undergoing active cancer treatment partake in IF outside the context of a clinical trial. IF may be considered in adults seeking cancer-prevention benefits through means of weight management, but whether IF itself affects cancer-related metabolic and molecular pathways remains unanswered.

Randomised controlled trial of intermittent calorie restriction in people with multiple sclerosis.

BACKGROUND: Calorie restriction (CR) ameliorates preclinical models of multiple sclerosis (MS) via multiple mechanisms. These include decreased leptin, a proinflammatory adipokine, but mechanistic studies in humans are lacking. Tests of daily and intermittent CR (iCR) in people with MS (pwMS) showed improvements in fatigue and well-being measures. This trial studied the effects of 12-week iCR on metabolic, immunological, and clinical outcomes in pwMS. METHOD: Relapsing-remitting MS participants were randomised to iCR or a control group. Study visits were conducted at baseline, 6 and 12 weeks. The primary outcome was reduction in serum leptin levels at 12 weeks. Feasibility and safety were assessed by diet adherence and adverse events (AEs). Secondary outcomes included changes in anthropometric and body composition measures, metabolic and immunologic profiling, and clinical measures. Mixed effects linear regression models were used to evaluate outcome differences between and within groups over time. RESULTS: Forty-two pwMS were randomised, 34 completed the study (17/group). Leptin serum levels at 12 weeks were significantly lower in the iCR versus the control group (mean decrease -6.98 µg/dL, 95% CI: -28.02 to 14.06; p=0.03). Adherence to iCR was 99.5% and 97.2% at 6 and 12 weeks, respectively, and no serious AEs were reported. An increase in blood CD45RO+ regulatory T-cell numbers was seen after 6 weeks of iCR. Exploratory cognitive testing demonstrated a significant improvement in the Symbol Digit Modality Test Score in the iCR group at 12 weeks. CONCLUSIONS: iCR has the potential to benefit metabolic and immunologic profiles and is safe and feasible in pwMS. TRIAL REGISTRATION NUMBER: NCT03539094 .

Contribution of Nutritional, Lifestyle, and Metabolic Risk Factors to Parkinson's Disease.

BACKGROUND: Modifiable risk factors for Parkinson's disease (PD) are poorly known. OBJECTIVES: The aim is to evaluate independent associations of different nutritional components, physical activity, and sedentary behavior and metabolic factors with the risk of PD. METHODS: In this population-based prospective cohort study using the data of the United Kingdom Biobank (from 2006-2010), 502,017 men and women who were free from PD (International Classification of Diseases 10th edition; "G20") at baseline were included. We implemented a Cox proportion hazard's model to evaluate the associations of different levels of physical activity, sitting time, sleep habits, diet quality, alcohol and coffee consumption, smoking, and body mass index with PD risk, adjusting for several confounding variables. RESULTS: During a median follow-up of 12.8 years, lifestyle factors including vigorous physical activity (hazard ration [HR] = 0.84; 95% confidence interval [CI], 0.75-0.94), low-to-moderate sitting time (HR = 0.89; 95% CI, 0.81-0.97), and high sleep quality (HR = 0.89; 95% CI, 0.80-0.99) were associated with a reduced risk of PD. Small amounts of coffee (HR = 0.88; 95% CI, 0.82-0.95), red meat (HR = 0.86; 95% CI, 0.76-0.97), and current smoking (HR = 0.65; 95% CI, 0.56-0.75) were also associated with a lower risk of PD, whereas alcohol intake (HR = 1.29; 95% CI, 1.06-1.56) with higher PD risk. Secondary analysis, including metabolic risk factors, confirmed these findings and highlighted the potential protective effect of plasma vitamin D and uric acid, but of low-density lipoprotein-cholesterol, triglycerides, and C-reactive protein as well. CONCLUSIONS: Vigorous physical activity, reduced sitting time, good sleep quality together with small coffee intake and vitamin D supplementation are potentially neuroprotective lifestyle interventions for the prevention of PD. © 2024 International Parkinson and Movement Disorder Society.

Management of corneal melting after collagen cross-linking for keratoconus: a case report and a review of the literature.

PURPOSE: We describe the management of a case of severe corneal melting after corneal cross-linking (CXL) treated with a staged approach using a conjunctival flap followed by deep anterior lamellar keratoplasty (DALK). METHODS: A 12-year-old male developed severe corneal melting with pending perforation after an accelerated epithelium-off CXL protocol. We initially treated the patient with a conjunctival flap to prevent perforation. Three months later, we performed DALK to restore vision. RESULTS: Conjunctival flap surgery allowed us to avoid corneal perforation and penetrating keratoplasty (PK) à chaud. Once the inflammation had resolved, we recessed the conjunctiva and performed DALK for optical purposes. Twelve months later, the graft was clear and the corrected visual acuity was 20/25 (Snellen). No complications occurred after surgery. CONCLUSIONS: Although CXL is considered a safe procedure, in rare cases it can lead to serious complications, such as corneal haze, infectious and non-infectious keratitis, stromal melting and perforation. Corneal melting and perforation are usually managed by emergency PK. Herein we suggest a staged approach involving an emergency conjunctival flap followed by DALK at a later time that allowed us to avoid PK à chaud.

Bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus infection: a case report.

BACKGROUND: To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement. CASE PRESENTATION: A 78-year-old Italian woman was admitted to our emergency department because she noticed blurry vision in both eyes. She did not report fever, fatigue, or neurological symptoms in the last few days. Multimodal imaging showed the presence of bilateral hyperfluorescent lesions with a linear distribution, that corresponded to hypocyanescent spots on indocyanine green angiography. Antibody serology showed the presence of IgM antibodies, IgG antibodies, and ribonucleic acid (RNA) for WNV. Magnetic resonance imaging (MRI) of the brain ruled out central nervous system involvement. Three months later, the patient reported spontaneous resolution of her symptoms and remission of the chorioretinal infiltrates. CONCLUSIONS: In endemic areas, it is important to think of acute WNV infection as an explanatory etiology in cases of multifocal chorioretinitis, even without neurological involvement.

Pneumatic retinopexy for primary rhegmatogenous retinal detachment: from a clinical trial to the real-life experience.

BACKGROUND: To report real-world outcomes of patients with primary Reghmatogenous Retinal Detachment (RRD) treated with Pneumatic Retinopexy (PnR) according to the indications of the Pneumatic Retinopexy versus Vitrectomy for management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) trial. METHODS: Multicenter, retrospective study. Patients treated with PnR for RRD between 2021 and 2023 and a follow-up of at least 6 months were included. Single-procedure anatomical success, final anatomical success, complications, causes of failures, best corrected visual acuity (BCVA) after surgery, and the vision-related quality of life using the 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were reported. RESULTS: A total of 76 eyes of 76 patients were included. Mean age was 60 ± 8.1 years. Primary anatomic reattachment was achieved by 84.3% of patients and final anatomical reattachment after pars plana vitrectomy was obtained in 100% of patients. BCVA improved from 0.32 (20/40) to 0.04 (20/20) logMar (p < 0.001) at 6 months. The main cause of failure was related to the presence of additional (likely missed) retinal breaks (66.6% of cases). Also, primary PnR failure was more frequent in eyes of patients with older age, macular involvement, worse baseline BCVA, greater extent of the RRD, and increased duration from diagnosis to treatment. Overall, the mean NEI-VFQ 25 composite score was 93.9% ± 6.4 at 6 months. CONCLUSIONS: The criteria of the PIVOT trial can be applied to real-world scenarios in the decision-making process for the treatment of primary RRD, with excellent anatomical and functional outcomes.

Vegetarian and vegan diets: benefits and drawbacks.

Plant-based diets have become increasingly popular thanks to their purported health benefits and more recently for their positive environmental impact. Prospective studies suggest that consuming vegetarian diets is associated with a reduced risk of developing cardiovascular disease (CVD), diabetes, hypertension, dementia, and cancer. Data from randomized clinical trials have confirmed a protective effect of vegetarian diets for the prevention of diabetes and reductions in weight, blood pressure, glycosylated haemoglobin and low-density lipoprotein cholesterol, but to date, no data are available for cardiovascular event rates and cognitive impairment, and there are very limited data for cancer. Moreover, not all plant-based foods are equally healthy. Unhealthy vegetarian diets poor in specific nutrients (vitamin B12, iron, zinc, and calcium) and/or rich in highly processed and refined foods increase morbidity and mortality. Further mechanistic studies are desirable to understand whether the advantages of healthy, minimally processed vegetarian diets represent an all-or-nothing phenomenon and whether consuming primarily plant-based diets containing small quantities of animal products (e.g. pesco-vegetarian or Mediterranean diets) has beneficial, detrimental, or neutral effects on cardiometabolic health outcomes. Further, mechanistic studies are warranted to enhance our understanding about healthy plant-based food patterns and the biological mechanisms linking dietary factors, CVD, and other metabolic diseases.

In vivo assessment of the ocular biomechanical properties in patients with idiopathic normal pressure hydrocephalus.

PURPOSE: Idiopathic normal pressure hydrocephalus (iNPH) is associated with an increased prevalence of open-angle glaucoma, attributed to variations of the pressure gradient between intraocular and intracranial compartments at the level of the lamina cribrosa (LC). As ocular biomechanics influence the behavior of the LC, and a lower corneal hysteresis (CH) has been associated to a higher risk of glaucomatous optic nerve damage, in this study we compared ocular biomechanics of iNPH patients with healthy subjects. METHODS:  Twenty-four eyes of 24 non-shunted iNPH patients were prospectively recruited. Ocular biomechanical properties were investigated using the ocular response analyzer (Reichert Instruments) for the calculation of the CH, corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal-compensated intraocular pressure (IOPcc). Results were compared with those of 25 eyes of 25 healthy subjects. RESULTS:  In iNPH eyes, the median CH value and interquartile range (IQR) were 9.7 mmHg (7.8-10) and 10.6 mmHg (9.3-11.3) in healthy controls (p = 0.015). No significant differences were found in IOPcc [18.1 mmHg (14.72-19.92) vs. 16.4 mmHg (13.05-19.6)], IOPg [15.4 mmHg (12.82-19.7) vs. 15.3 mmHg (12.55-17.35)], and CRF [9.65 mmHg (8.07-11.65) vs. 10.3 mmHg (9.3-11.5)] between iNPH patients and controls. CONCLUSIONS:  In iNPH patients, the CH was significantly lower compared to healthy subjects. This result suggests that ocular biomechanical properties may potentially contribute to the risk of development of glaucomatous optic nerve damage in iNPH patients.

Incidence and management of early postoperative complications in lamellar corneal transplantation.

PURPOSE: To provide a comprehensive review of the incidence, risk factors, and management of early complications after deep anterior lamellar keratoplasty (DALK), Descemet stripping automated keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK). METHODS: A literature review of complications, that can occur from the time of the transplant up to 1 month after the transplant procedure, was conducted. Case reports and case series were included in the review. RESULTS: Complications in the earliest postoperative days following anterior and posterior lamellar keratoplasty have shown to affect graft survival. These complications include, but are not limited to, double anterior chamber, sclerokeratitis endothelial graft detachment, acute glaucoma, fluid misdirection syndrome, donor-transmitted and recurrent infection, and Uretts-Zavalia syndrome. CONCLUSION: It is essential for surgeons and clinicians to not only be aware of these complications but also know how to manage them to minimize their impact on long-term transplant survival and visual outcomes.

Aging and chronic inflammation: highlights from a multidisciplinary workshop.

Aging is a gradual, continuous series of natural changes in biological, physiological, immunological, environmental, psychological, behavioral, and social processes. Aging entails changes in the immune system characterized by a decrease in thymic output of naïve lymphocytes, an accumulated chronic antigenic stress notably caused by chronic infections such as cytomegalovirus (CMV), and immune cell senescence with acquisition of an inflammatory senescence-associated secretory phenotype (SASP). For this reason, and due to the SASP originating from other tissues, aging is commonly accompanied by low-grade chronic inflammation, termed "inflammaging". After decades of accumulating evidence regarding age-related processes and chronic inflammation, the domain now appears mature enough to allow an integrative reinterpretation of old data. Here, we provide an overview of the topics discussed in a recent workshop "Aging and Chronic Inflammation" to which many of the major players in the field contributed. We highlight advances in systematic measurement and interpretation of biological markers of aging, as well as their implications for human health and longevity and the interventions that can be envisaged to maintain or improve immune function in older people.

Effects of dietary restriction on gut microbiota and CNS autoimmunity.

Multiple sclerosis (MS) is the most common central nervous system (CNS) autoimmune disease. It is due to the interplay of genetic and environmental factors. Current opinion is that diet could play a pathogenic role in disease onset and development. Dietary restriction (DR) without malnutrition markedly improves health and increases lifespan in multiple model organisms. DR regimens that utilize continuous or intermittent food restriction can induce anti-inflammatory, immuno-modulatory and neuroendocrine adaptations promoting health. These adaptations exert neuroprotective effects in the main MS animal model, experimental autoimmune encephalomyelitis (EAE). This review summarizes the current knowledge on DR-induced changes in gut microbial composition and metabolite production and its impact on underlying functional mechanisms. Studies demonstrating the protective effects of DR regimens on EAE and people with MS are also presented. This is a rapidly developing research field with important clinical implications for personalized dietary interventions in MS prevention and treatment.

Adherence to a healthy lifestyle and multiple sclerosis: a case-control study from the UK Biobank.

BACKGROUND: Multiple sclerosis (MS) is a common and disabling condition. The importance of healthy lifestyle for this disease is poorly explored. OBJECTIVE: To test whether adherence to healthier lifestyle patterns is associated with a lower presence of multiple sclerosis (MS). METHODS: By using a case-control design, we investigated the combined association of four healthy lifestyle-related factors (no current smoking, healthy diet, exercising regularly, body mass index <30 kg/m2) and the prevalence of MS. A logistic regression analysis, adjusted for potential confounders, was used and data reported as odds ratios (ORs) with their 95% confidence intervals (CIs). RESULTS: 728 participants with MS were matched with healthy controls (n = 2,912) using a propensity score approach. In a multivariable analysis, compared to those who scored low in the composite lifestyle score (0-1 healthy lifestyle factors), people who adopted all four low risk lifestyle factors showed a 71% lower odds of having MS (OR = 0.29; 95% CI: 0.15-0.56). Moreover, there was a strong linear trend, suggesting that the higher number of healthy lifestyle behaviors was associated with lower odds of having MS. CONCLUSION: Following a healthy lifestyle is associated with a lower prevalence of MS. This association should be explored further in cohort studies.

Gonioscopy-assisted transluminal trabeculotomy for chronic angle-closure glaucoma: preliminary results.

PURPOSE: To report the preliminary results of gonioscopy-assisted transluminal trabeculotomy (GATT) in eyes with chronic angle-closure glaucoma (CACG). METHODS: Retrospective, single-center, case series of GATT procedures is performed on patients with CACG. The primary outcome was intraocular pressure (IOP). Success was defined as IOP reduction >30% from baseline at 6 and 12 months with (qualified) or without (complete) glaucoma medication. Secondary outcomes were best-corrected visual acuity (BCVA), visual field (VF), peripheral anterior synechiae (PAS), medications, and complications. RESULTS: Fifteen eyes (15 patients) with a minimum follow-up of 1 year were included for the analysis. Preoperatively, the mean (±SD) IOP was 30.27 (±4.20) mmHg and 15.20 (±2.08) mmHg at 1 year postoperatively (p<0.001). The mean (±SD) percentage of IOP reduction from baseline was 49% (±9.41). At 6 and 12 months, the success rate complete and qualified was 93% (73% and 20%) and 100% (73% and 27%), respectively. BCVA and VF mean deviation were comparable before and after surgery (p=0.167 and p= 0.710, respectively). The median (range) number of glaucoma drugs decreased from 3 (3-4) before to 0 (0-2) after GATT (p<0.001). The absence of PAS was observed in 80% of patients after surgery. Transient hyphema was a common complication requiring aspiration in one case. CONCLUSION: At 12 months of follow-up, our preliminary results indicate that GATT in CACG effectively reduces the IOP and the number of medication with a low risk of complications. Following ab interno trabeculotomy, an open-angle without PAS was achieved in the majority of patients. TRIAL REGISTRATION NUMBER: nr. 2016/0010904.

Malignant glaucoma following gonioscopy-assisted transluminal trabeculotomy: a case report.

BACKGROUND: To report a case of malignant glaucoma that developed after gonioscopy-assisted transluminal trabeculotomy (GATT). CASE PRESENTATION: An 85-year-old male pseudophakic patient affected by pseudoexfoliative glaucoma (PEXG), unresponsive to medical glaucoma treatment, underwent uneventful GATT surgery. On the first day after surgery, the eye showed a shallow central and peripheral anterior chamber (AC) with a raised intraocular pressure (IOP) measured at 55 mmHg. Optical coherence tomography and ultrasound biomicroscopy confirmed the diagnosis of malignant glaucoma. Laser iridotomy, posterior capsulotomy and hyaloidotomy were performed, and the patient was treated with atropine sulphate 1%, maximum topical and systemic ocular hypotensive drugs with no improvement in the IOP. Subsequently, the patient underwent pars plana anterior vitrectomy, resulting in deepening of the AC with opening of the iridocorneal angle and decrease of the IOP. No further postoperative complications were recorded, and the IOP remained controlled 12 months after surgery without antiglaucoma medications. CONCLUSIONS: Despite the minimally invasive profile of GATT, malignant glaucoma may develop after this procedure. Early recognition and prompt treatment are mandatory for preventing permanent visual loss.

Physical activity, diet quality and all-cause cardiovascular disease and cancer mortality: a prospective study of 346 627 UK Biobank participants.

OBJECTIVES: To examine independent and interactive associations of physical activity and diet with all-cause, cardiovascular disease (CVD) and physical activity, diet and adiposity-related (PDAR) cancer mortality. METHODS: This population-based prospective cohort study (n=346 627) is based on the UK Biobank data with linkage to the National Health Service death records to 30 April 2020. A left-truncated Cox proportional hazards model was fitted to examine the associations between exposures (self-reported total moderate-to-vigorous intensity physical activity (MVPA), vigorous-intensity physical activity (VPA) and a diet quality index (score ranged 0-3)) and outcomes (all-cause, CVD and PDAR cancer mortality). RESULTS: During a median follow-up of 11.2 years, 13 869 participants died from all causes, 2650 from CVD and 4522 from PDAR cancers. Compared with quartile 1 (Q1, 0-210 min/week), Q2-Q4 of MVPA were associated with lower risks of all-cause (HR ranged from 0.87 (95% CI: 0.83 to 0.91) to 0.91 (95% CI: 0.87 to 0.96)), CVD (HR ranged from 0.85 (95% CI: 0.76 to 0.95) to 0.90 (95% CI: 0.81 to 1.00)) and PDAR cancer mortality (HR ranged from 0.86 (95% CI: 0.79 to 0.93) to 0.94 (95% CI: 0.86 to 1.02)). Compared with no VPA, any VPA was associated with lower risk for all-cause and CVD mortality (HR ranged from 0.85 (95% CI: 0.80 to 0.89) to 0.88 (95% CI: 0.84 to 0.93) and from 0.75 (95% CI: 0.68 to 0.83) to 0.90 (95% CI: 0.80 to 1.02), respectively). Although not reaching statistical significance for all-cause and CVD mortality, being in the best dietary category (diet quality index=2-3) was associated with a reduction in PDAR cancer mortality (HR=0.86, 95% CI: 0.78 to 0.93). No additive or multiplicative interactions between physical activity categories and dietary quality was found. When comparing across physical activity and diet combinations, the lowest risk combinations consistently included the higher levels of physical activity and the highest diet quality score. CONCLUSIONS: Adhering to both quality diet and sufficient physical activity is important for optimally reducing the risk of mortality from all causes, CVD and PDAR cancers.

Impact of Freeze-Drying on Cord Blood (CB), Serum (S), and Platelet-Rich Plasma (CB-PRP) Preparations on Growth Factor Content and In Vitro Cell Wound Healing.

Blood-based preparations are used in clinical practice for the treatment of several eye disorders. The aim of this study is to analyze the effect of freeze-drying blood-based preparations on the levels of growth factors and wound healing behaviors in an in vitro model. Platelet-rich plasma (PRP) and serum (S) preparations from the same Cord Blood (CB) sample, prepared in both fresh frozen (FF) and freeze-dried (FD) forms (and then reconstituted), were analyzed for EGF and BDNF content (ELISA Quantikine kit). The human MIO-M1 glial cell line (Moorfield/Institute of Ophthalmology, London, UK) was incubated with FF and FD products and evaluated for cell migration with scratch-induced wounding (IncuCyte S3 Essen BioScience), proliferation with cyclin A2 and D1 gene expression, and activation with vimentin and GFAP gene expression. The FF and FD forms showed similar concentrations of EGF and BDNF in both the S and PRP preparations. The wound healing assay showed no significant difference between the FF and FD forms for both S and PRP. Additionally, cell migration, proliferation, and activation did not appear to change in the FD forms compared to the FF ones. Our study showed that reconstituted FD products maintained the growth factor concentrations and biological properties of FF products and could be used as a functional treatment option.

Transdisciplinary research and clinical priorities for better health.

Modern medicine makes it possible for many people to live with multiple chronic diseases for decades, but this has enormous social, financial, and environmental consequences. Preclinical, epidemiological, and clinical trial data have shown that many of the most common chronic diseases are largely preventable with nutritional and lifestyle interventions that are targeting well-characterized signaling pathways and the symbiotic relationship with our microbiome. Most of the research priorities and spending for health are focused on finding new molecular targets for the development of biotech and pharmaceutical products. Very little is invested in mechanism-based preventive science, medicine, and education. We believe that overly enthusiastic expectations regarding the benefits of pharmacological research for disease treatment have the potential to impact and distort not only medical research and practice but also environmental health and sustainable economic growth. Transitioning from a primarily disease-centered medical system to a balanced preventive and personalized treatment healthcare system is key to reduce social disparities in health and achieve financially sustainable, universal health coverage for all. In this Perspective article, we discuss a range of science-based strategies, policies, and structural reforms to design an entire new disease prevention-centered science, educational, and healthcare system that maximizes both human and environmental health.