Lipid-Based Nanocarriers via Nose-to-Brain Pathway for Central Nervous System Disorders.

Neurodegenerative disorders are distinguished by the gradual deterioration of the nervous system's structure and function due to oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and neuroinflammation. Among these NDs, Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis characterized an increasing dysfunction and loss of neuronal structure leading to neuronal cell death. Although there is currently no drug to totally reverse the effects of NDs, such novel formulations and administration routes are developed for better management and nose-to-brain delivery is one of delivery for treating NDs. This review aimed to highlight advances in research on various lipid based nanocarriers such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and cubosomes which are reported to treat and alleviate the symptoms of NDs via nose-to-brain route. The challenges during clinical translation of lipid nanocarriers from bench to bed side is also discussed.

Microneedles enable the development of skin-targeted vaccines against coronaviruses and influenza viruses.

Throughout the COVID-19 pandemic, many have seriously worried that the plus burden of seasonal influenza that might create a destructive scenario, resulting in overwhelmed healthcare capacities and onwards loss of life. Many efforts to develop a safe and efficacious vaccine to prevent infection by coronavirus and influenza, highlight the importance of vaccination to combat infectious pathogens. While vaccines are traditionally given as injections into the muscle, microneedle (MN) patches designed to precisely deliver cargos into the cutaneous microenvironment, rich in immune cells, provide a noninvasive and self-applicable vaccination approach, reducing overall costs and improving access to vaccines in places with limited supply. The current review aimed to highlight advances in research on the development of MNs-mediated cutaneous vaccine delivery. Concluding remarks and challenges on MNs-based skin immunization are also provided to contribute to the rational development of safe and effective MN-delivered vaccines against these emerging infectious diseases.

Kinetic Study on Chlorophyll and Antioxidant Activity from Polyscias fruticosa (L.) Harms Leaves via Microwave-Assisted Extraction.

Polyscias fruticosa (L.) leaves contain significant bioactive compounds with high antioxidant activity such as chlorophylls, total polyphenols, etc. but these have still been underutilized. In this study, the kinetics of chlorophyll and antioxidant activity extraction from P. fruticosa leaves by microwave-assisted extraction (MAE) were investigated. Microwave power was 300, 450, or 600 (W); the ratio of material/solvent varied from 1:40 to 1:80 (g/mL). In this study, the second-order kinetic model successfully predicted the change of chlorophyll and antioxidant activity during MAE. The increase of microwave power or/and the solvent amount increased saturated extraction efficiency and the extraction rate constant. However, the saturated concentration of chlorophyll and antioxidant activity increased with the increment of microwave power and the decrease in solvent amount.

Comparison of Phytochemical Contents, Antioxidant and Antibacterial Activities of Various Solvent Extracts Obtained from 'Maluma' Avocado Pulp Powder.

Although avocado is a superfood rich in phytochemicals with high antioxidant activities, studies on the antibacterial properties of its pulp are limited, except for seed and peel portions. In this study, three types of solvent (acetone, methanol, and diethyl ether) were used to obtain the extracts from "Maluma" avocado pulp powder prepared by infrared drying. The extracts were analyzed for total polyphenols, phytopigments (total chlorophylls and carotenoids), antioxidant activities (ferric-reducing antioxidant power (FRAP), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), and 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays), and antibacterial activities against seven pathogens (Shigella sonnei ATCC 9290, Escherichia coli ATCC 8739, Salmonella typhi ATCC 6539, Vibrio parahaemolyticus ATCC 17802, Proteus mirabilis ATCC 25933, Staphylococcus aureus ATCC 6538, and Bacillus cereus ATCC 11778). The results showed that the acetone solvent could extract the highest polyphenols and chlorophylls with the highest antioxidant activity in terms of ABTS and DPPH assays. In contrast, diethyl ether exhibited the most significant content of carotenoids and FRAP values. However, the methanol extract was the best solvent, exerting the strongest antibacterial and meaningful antioxidant activities. For the bacterial activities, Gram-positive pathogens (Bacillus cereus and Staphylococcus aureus) were inhibited more efficiently by avocado extracts than Gram-negative bacteria. Therefore, the extracts from avocado powder showed great potential for applications in food processing and preservation, pharmaceuticals, and cosmetics.

Cross-sectional and prospective relationships of passive and mentally active sedentary behaviours and physical activity with depression.

BACKGROUND: Sedentary behaviour can be associated with poor mental health, but it remains unclear whether all types of sedentary behaviour have equivalent detrimental effects. AIMS: To model the potential impact on depression of replacing passive with mentally active sedentary behaviours and with light and moderate-to-vigorous physical activity. An additional aim was to explore these relationships by self-report data and clinician diagnoses of depression. METHOD: In 1997, 43 863 Swedish adults were initially surveyed and their responses linked to patient registers until 2010. The isotemporal substitution method was used to model the potential impact on depression of replacing 30 min of passive sedentary behaviour with equivalent durations of mentally active sedentary behaviour, light physical activity or moderate-to-vigorous physical activity. Outcomes were self-reported depression symptoms (cross-sectional analyses) and clinician-diagnosed incident major depressive disorder (MDD) (prospective analyses). RESULTS: Of 24 060 participants with complete data (mean age 49.2 years, s.d. 15.8, 66% female), 1526 (6.3%) reported depression symptoms at baseline. There were 416 (1.7%) incident cases of MDD during the 13-year follow-up. Modelled cross-sectionally, replacing 30 min/day of passive sedentary behaviour with 30 min/day of mentally active sedentary behaviour, light physical activity and moderate-to-vigorous activity reduced the odds of depression symptoms by 5% (odds ratio 0.95, 95% CI 0.94-0.97), 13% (odds ratio 0.87, 95% CI 0.76-1.00) and 19% (odds ratio 0.81, 95% CI 0.93-0.90), respectively. Modelled prospectively, substituting 30 min/day of passive with 30 min/day of mentally active sedentary behaviour reduced MDD risk by 5% (hazard ratio 0.95, 95% CI 0.91-0.99); no other prospective associations were statistically significant. CONCLUSIONS: Substituting passive with mentally active sedentary behaviours, light activity or moderate-to-vigorous activity may reduce depression risk in adults.

Role of Insulin Resistance in the Alzheimer's Disease Progression.

Recent studies continue to find evidence linking Type 2 diabetes (T2D) with Alzheimer's disease (AD), the most common cause of dementia, a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. Insulin resistance or dysfunction of insulin signaling is a universal feature of T2D, the main culprit for altered glucose metabolism and its interdependence on cell death pathways, forming the basis of linking T2D with AD as it may exacerbate Aß accumulation, tau hyperphosphorylation and devastates glucose transportation, energy metabolism, hippocampal framework and promulgate inflammatory pathways. The current work demonstrates the basic mechanisms of the insulin resistance mediates dysregulation of bioenergetics and progress to AD as a mechanistic link between diabetes mellitus and AD. This work also aimed to provide a potential and feasible zone to succeed in the development of therapies in AD by enhanced hypometabolism and altered insulin signaling.

Associations of sedentary behavior in leisure and occupational contexts with symptoms of depression and anxiety.

Sedentary behaviors (SB) can be associated with poorer mental health, but it remains unclear whether contexts for these behaviors may be important. We assessed relationships of SB in leisure-time and occupational contexts with frequent symptoms of depression and anxiety. Data originate from the Swedish Health Profile Assessment (HPA) database, a health assessment offered to employees working for companies or organizations connected to healthcare services. Analyses are based on data from 2017 onwards (N = 23,644; 57% male, mean age = 42 years). Two self-report questions assessed proportions of time spent in SB in leisure contexts and in the occupational setting. Logistic regressions examined relationships of SB in each context with the self-reporting of frequent symptoms of depression/anxiety. A separate model for the leisure plus occupational SB was also generated. Fully-adjusted models included exercise frequency. Compared to those reporting that they were 'almost never' sedentary in leisure-time contexts, a detrimental dose-response with frequent depression/anxiety symptoms was observed with increasing proportions of sedentary time: 50% of the time (OR = 1.44; 1.23-1.70), 75% (OR = 2.95; 2.45-3.54), almost always (OR = 3.85; 2.84-5.22). For occupational SB, the only associations were among those who reported being sedentary almost always, compared to almost never (OR = 1.47; 1.25-1.73). Associations of 'overall' SB with depression/anxiety symptoms mirrored the dose-response relationship for leisure-time SB. Exercise frequency attenuated the association for leisure-time SB only, but it remained statistically significant. Adults who spend ≥50% of their leisure-time in sedentary pursuits experience more frequent symptoms of depression and anxiety, compared to those who are less sedentary in that context.

Type 3 Diabetes and Its Role Implications in Alzheimer's Disease.

The exact connection between Alzheimer's disease (AD) and type 2 diabetes is still in debate. However, poorly controlled blood sugar may increase the risk of developing Alzheimer's. This relationship is so strong that some have called Alzheimer's "diabetes of the brain" or "type 3 diabetes (T3D)". Given more recent studies continue to indicate evidence linking T3D with AD, this review aims to demonstrate the relationship between T3D and AD based on the fact that both the processing of amyloid-ß (Aß) precursor protein toxicity and the clearance of Aß are attributed to impaired insulin signaling, and that insulin resistance mediates the dysregulation of bioenergetics and progress to AD. Furthermore, insulin-related therapeutic strategies are suggested to succeed in the development of therapies for AD by slowing down their progressive nature or even halting their future complications.

Prospective associations between physical activity and clinician diagnosed major depressive disorder in adults: A 13-year cohort study.

Regular physical activity (PA) appears to protect against the emergence of depression, but prospective studies linked to clinician diagnoses of major depressive disorder (MDD) remain scarce. It is also unclear whether PA levels recommended for general health are prospectively related to depression onset. We explored these relationships in a cohort of adults followed over 13 years. In total, 43,863 Swedish adults were surveyed in 1997 and responses linked to clinician-diagnosed MDD obtained from specialist medical registers until 2010. Weekly durations of habitual moderate (including walking) and vigorous PA were self-reported. Relationships between total durations of PA, 0-149 ('below'), 150-299 ('achieve'), and ≥300 min ('exceed') with incident MDD were explored using survival analysis with Cox proportional hazards regression. Models were adjusted for relevant covariates. Those with indications of depression at baseline were removed from the primary analyses. Of 25,520 participants with complete data (mean age = 49 years, SD = 16, 65% female), 76% met the recommended weekly duration of PA (≥150 min), and 38% exceeded this duration (≥300 min). During 13-years follow-up 549 MDD cases (1.5%) were identified (incidence rate = 111 cases per 100,000 person-years). Compared to participants who were below, those who exceeded the recommended weekly duration (≥300 min/week) had 29% reduced risk of depression onset (HR 0.71, 95% CI = 0.53-0.96). A non-significant inverse association was observed among those who achieved the minimum duration of 150-min/week (HR 0.86, 95% CI = 0.64-1.14). Habitual PA levels that exceed the duration recommended for general health may reduce the risk of clinician-diagnosed major depression in adults.

Randomised controlled study of two counselling models at the Swedish alcohol helpline: Effectiveness and sustainability outcomes at 12-month follow-up.

Aim: This two-arm parallel randomised controlled trial explored the effectiveness of a brief counselling model compared with the usual multi-session counselling at an alcohol telephone helpline. Methods: A total of 320 callers who contacted the Swedish Alcohol Helpline (SAH) because of hazardous or harmful alcohol use were randomised to either brief structured intervention (self-help booklet plus one proactive call) or usual care (multi-session telephone counselling). The primary outcome was a downward shift in risk level at 12-month follow-up compared with baseline, based on self-reports. Sustained risk level reduction throughout the whole follow-up was also assessed as secondary outcome. Results: Both interventions were significantly associated with a shift to a lower level of risky alcohol use (75% among participants in the brief structured intervention, and 70% in the usual care group) after 12 months. There was no difference between the two interventions in the proportions changing alcohol use or sustaining risk level reduction. Conclusion: In the context of telephone helplines, minimal and extended interventions appear to be equally effective in promoting long-term change in alcohol use.

Advances of microneedles in hormone delivery.

The skin is recognized as a potential target for local and systemic drug delivery and hormone. However, the transdermal route of drug administration seems to be limited by substantial barrier properties of the skin. Recently, delivering hormone via the skin by transdermal patches is a big challenge because of the presence of the stratum corneum that prevents the application of hormone via this route. In order to overcome the limitations, microneedle (MN), consisting of micro-sized needles, are a promising approach to drill the stratum corneum and release hormone into the dermis via a minimal-invasive route. This review aimed to highlight advances in research on the development of MNs-based therapeutics for their implications in hormone delivery. The challenges during clinical translation of MNs from bench to bedside are also discussed.

Microencapsulation of roselle (Hibiscus sabdariffa L.) anthocyanins: Effects of drying conditions on some physicochemical properties and antioxidant activities of spray-dried powder.

Anthocyanins are important phytochemical compounds in nature that are of interest not only for their health benefits such as antioxidant, anti-inflammatory, and anti-carcinogenic properties, but also for their role in imparting attractive and characteristic color to food products. In this study, anthocyanins from hibiscus (Hibiscus sabdariffa L.) calyces were microencapsulated by spray-drying technique using maltodextrin as the carrier. The experiment was carried out in the full factorial design with two factors, namely inlet temperature (150, 160, and 170°C) and anthocyanin to maltodextrin mass ratio (1:50, 1:60, 1:70, 1:80, 1:90, and 1:100) with the aim of investigating the effect of spray drying conditions on phenolic content, anthocyanin, antioxidant activity, and color of spray-dried hibiscus powder. The results showed that increasing the carrier ratio significantly reduced the antioxidant content and their activities in the powder. However, the high level of carriers exhibited a protective effect in encapsulating anthocyanin compounds into the maltodextrin matrix, which was demonstrated by high encapsulation efficiency (>85%) observed in the samples prepared at a ratio of 1:100. It should be highlighted that although high temperature (170°C) reduced total anthocyanin concentration, it actually enhanced total phenolic content. In addition, the moisture content of the powder declined with increasing carrier ratio and inlet temperature, and it was found to be in the range of 5.57%-10.19% in the powder. With solubility greater than 93.71%, the total phenolic and total anthocyanin content of spray-dried hibiscus powder were 31.5-41.9 (mg gallic acid equivalent/g of dry powder) and 6.08-10.47 (mg cyanidin-3-glucoside/g of dry powder), respectively.

Physical Activity, Sedentary Behavior, and Cardiorespiratory Fitness in Hazardous and Non-Hazardous Alcohol Consumers.

PURPOSE: To describe physical activity habits, sedentary behavior, and cardiorespiratory fitness levels among alcohol abstainers, hazardous and non-hazardous drinkers. DESIGN: Cross-sectional study with data collected between 2017-19. SETTING: Sweden. SUBJECTS: Adults aged 18-65 years (n = 47,559; 59.4% male). MEASURES: During a routine health assessment, participants answered validated single-item questions regarding: habitual physical activity, structured exercise, and the percentage of time spent sedentary during leisure-time (past 30 days), and completed a 6-minute cycle ergometer test (V02max) to determine cardiorespiratory fitness (CRF). Participants were categorized as alcohol abstainers, non-hazardous drinkers or hazardous drinkers (low/high) based on the Alcohol Use Disorders Identification Test (AUDIT-C) cut-points for men and women. ANALYSIS: Logistic regression models stratified by sex and age. RESULTS: Compared to non-hazardous drinkers, the heaviest drinkers were less physically active (males: OR = 1.38, CI = 1.13-1.67, p = .001; females: OR = 1.41, CI = 1.01-1.97, p = .040) and more sedentary during leisure time (males: OR = 1.94, CI = 1.62-2.32, p = .000; females: OR = 1.62, CI = 1.21-2.16, p = .001). Apart from young females, the heaviest drinkers also did less structured exercise than non-hazardous drinkers (males: OR = 1.22, CI = 1.15-1.51, p = .000; females: OR = 1.43, CI = 1.15-1.78, p = .001). The strongest associations were seen among adults aged 40-65 years (shown here). High-hazardous drinking was associated with low CRF among older males only (OR = 1.19, CI = 1.00-1.41). CONCLUSION: Middle-aged adults with AUDIT-C scores of ≥6 (women) and ≥7 (men) were less physically active and more sedentary during leisure time and may be appropriate targets for physical activity interventions.

Advances in developing therapeutic strategies for Alzheimer's disease.

Alzheimer's disease (AD) is a progressive deterioration of brain function, initially characterized by cognitive deficits, with loss of recent memory and language ability, impairment of orientation, problem solving, and abstract thinking. While existing drug treatments help reduce the symptoms of AD and improve people's quality of life, they neither slow its progression nor cure it. Currently, targeted drug delivery to the central nervous system (CNS), for therapy of AD, is confined by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Among new strategies to overcome these limitations and successfully deliver drugs to the CNS, nanoparticles (NPs) are able to overcome these limitations, offering new therapeutic designations in term of driving drugs to cross the BBB and enter the brain more effectively. The current article aimed to summary and highlight advances in recent research on the development of nanotechnology-based therapeutics for their implications in therapy of AD.

Serum hs-CRP measured prior transplantation predicts of new-onset diabetes after transplantation in renal transplant recipients.

BACKGROUND: To assess the incidence of new-onset diabetes after transplantation (NODAT) for the first year post-transplantation and the predictive value of high-sensitivity C-reactive Protein (hs-CRP) before transplantation for NODAT prediction in kidney transplantation patients. MATERIAL AND METHODS: A study of 251 consecutive adult end-stage kidney disease patients transplanted kidneys from living donors, follow-up during the first year to find NODAT. We diagnosed NODAT based on blood glucose or HbA1c following to the criteria of the American Diabetes Association. RESULTS: The ratio of NODAT was 12.4%. The mean age, mean BMI, the proportion of arteriosclerosis, and the median hs-CRP level in NODAT group were significantly higher than those of non-NODAT group with p < 0.05. Age, BMI and serum hs-CRP had a predictive value for NODAT (Age: AUC = 0.62, p < 0.05, BMI: AUC = 0.626, hs-CRP: AUC = 0.748, p < 0.001). CONCLUSION: Serum hs-CRP level measured prior transplantation is a good predictor for NODAT in renal transplant recipients.

Advances in non and minimal-invasive transcutaneous delivery of immunotherapy for cancer treatment.

Cancer research has focused on figuring out what was the difference between cancer cells and the tissues within which cancer arose and developing targeted treatments for those differences. With FDA-approved treatments for more ten different cancers and more than thousand new clinical trials, immunotherapy has recently emerged as the most promising area of cancer research by improving efficacy and controlling the adverse effects. Transcutaneous delivery drug delivery offers a number of advantages for the patient because of not only its noninvasive and convenient nature but also factors such as avoidance of first-pass metabolism and prevention of gastrointestinal degradation. The purpose of this review was to highlight technological recent approaches to non and minimal-invasive delivery of immunotherapy for cancer treatment. Finally, some practical considerations and discussions for future studies in the field of transdermal immunomodulation are also included.

Role of Body-Fluid Biomarkers in Alzheimer's Disease Diagnosis.

Alzheimer's disease (AD) is a complex neurodegenerative disease that requires extremely specific biomarkers for its diagnosis. For current diagnostics capable of identifying AD, the development and validation of early stage biomarkers is a top research priority. Body-fluid biomarkers might closely reflect synaptic dysfunction in the brain and, thereby, could contribute to improving diagnostic accuracy and monitoring disease progression, and serve as markers for assessing the response to disease-modifying therapies at early onset. Here, we highlight current advances in the research on the capabilities of body-fluid biomarkers and their role in AD pathology. Then, we describe and discuss current applications of the potential biomarkers in clinical diagnostics in AD.

School-related physical activity interventions and mental health among children: a systematic review and meta-analysis.

BACKGROUND: Low levels of physical activity, sedentary behaviour and mental health problems are issues that have received considerable attention in the last decade. The aim of this systematic review and meta-analysis was to investigate effects of interventions targeting school-related physical activity or sedentary behaviour on mental health in children and adolescents and to identify the features of effective interventions. METHODS: Scientific articles published between January 2009 and October 2019 fulfilling the following criteria were included: general populations of children and adolescents between age 4 and 19, all types of school-related efforts to promote physical activity or reduce sedentary behaviour. Study selection, data extraction and quality assessment were done by at least two authors independently of each other. Data were analysed with a random effects meta-analysis and by narrative moderator analyses. RESULTS: The literature search resulted in 10265 unique articles. Thirty-one articles, describing 30 interventions, were finally included. Eleven relevant outcomes were identified: health-related quality of life, well-being, self-esteem and self-worth, resilience, positive effect, positive mental health, anxiety, depression, emotional problems, negative effect and internalising mental health problems. There was a significant beneficial effect of school-related physical activity interventions on resilience (Hedges' g = 0.748, 95% CI = 0.326; 1.170, p = 0.001), positive mental health (Hedges' g = 0.405, 95% CI = 0.208; 0.603, p = < 0.001), well-being (Hedges' g = 0.877, 95% CI = 0.356; 1.398, p = < 0.001) and anxiety (Hedges' g = 0.347, 95% CI = 0.072; 0.623, p = 0.013). Heterogeneity was moderate to high (I2 = 59-98%) between studies for all outcomes except positive effect, where heterogeneity was low (I2 = 2%). The narrative moderator analyses of outcomes based on 10 or more studies showed that age of the children moderated the effect of the intervention on internalising mental health problems. Interventions in younger children showed a significantly negative or no effect on internalising mental health problems while those in older children showed a significant positive or no effect. Moreover, studies with a high implementation reach showed a significant negative or no effect while those with a low level of implementation showed no or a positive effect. No signs of effect moderation were found for self-esteem, well-being or positive mental health. Risk of publication bias was evident for several outcomes, but adjustment did not change the results. CONCLUSIONS: School-related physical activity interventions may reduce anxiety, increase resilience, improve well-being and increase positive mental health in children and adolescents. Considering the positive effects of physical activity on health in general, these findings may reinforce school-based initiatives to increase physical activity. However, the studies show considerable heterogeneity. The results should therefore be interpreted with caution. Future studies should report on implementation factors and more clearly describe the activities of the control group and whether the activity is added to or replacing ordinary physical education lessons in order to aid interpretation of results. TRIAL REGISTRATION: PROSPERO, CRD42018086757.

Associations of interruptions to leisure-time sedentary behaviour with symptoms of depression and anxiety.

Interruptions to time spent sitting can ameliorate detrimental metabolic-health consequences of high volumes of sedentary time, but their potential mental health benefits have not been examined. We used the Swedish Health Profile Assessment database, a general health assessment offered to all employees working for companies or organisations connected to occupational and health services. Cross-sectional analyses examined data from 40,550 employees (60% male, mean age = 42 years), collected in 2017-2019. Participants reported the proportion of time (almost always; 75% of the time; 50% of the time; 25% of the time; and almost never) usually spent in leisure-time sedentary behaviours; and, separately, the frequency (never; rarely; sometimes; often; and very often) of interruptions (every 30 min) to sedentary time. Logistic regression models assessed associations of sedentary time, and the frequency of interruptions to sedentary time, with depression/anxiety symptoms. Fully adjusted models included physical exercise. Compared to those in the lowest sedentary time category, those in the medium and high categories had 1.52 (95% confidence interval (CI) = 1.40-1.66) and 3.11 (95% CI = 2.82-3.42) higher odds of frequent depression/anxiety symptoms, respectively. Compared to those who never/rarely interrupted their sedentary time, those who reported interruptions sometimes, often and very often had 0.72 (95% CI = 0.65-0.80), 0.59 (95% CI = 0.53-0.65), and 0.53 (95% CI = 0.46-0.59) lower odds of depression/anxiety symptoms, respectively. In stratified analyses, more frequent interruptions to sedentary time were associated with lower odds of depression/anxiety symptoms, except among those in the lowest interruptions categories (never/25% of the time). More regularly interrupting sitting during leisure-time may reduce the odds of experiencing symptoms of depression and anxiety.