Microneedle-Based Vaccine Delivery: Review of an Emerging Technology.

Vaccination has produced a great improvement to the global health by decreasing/eradicating many infectious diseases responsible for significant morbidity and mortality. Thanks to vaccines, many infections affecting childhood have been greatly decreased or even eradicated (smallpox, measles, and polio). That is why great efforts are made to achieve mass vaccination against COVID-19. However, developed vaccines face many challenges with regard to their safety and stability. Moreover, needle phobia could prevent a significant proportion of the population from receiving vaccines. In this context, microneedles (MNs) could potentially present a solution to address these challenges. MNs represent single dose administration systems that do not need reconstitution or cold-chain storage. Being self-administered, pain-free, and capable of producing superior immunogenicity makes them a more attractive alternative. This review explores microneedles' types, safety, and efficacy in vaccine delivery. Preclinical and clinical studies for microneedle-based vaccines are discussed and patent examples are included.

Current Topical Strategies for Skin-Aging and Inflammaging Treatment: Science versus Fiction.

Aging is a natural phenomenon that affects the whole body, including the skin. As we age, endogenous and exogenous factors cause our skin to become thinner, paler, and wrinkled. Although the underlying mechanisms of the pathogenesis of skin aging are not entirely known, multiple pathways have been proposed. Inflammaging has recently emerged as a pathway that correlates aging and age-related diseases with inflammation. This review discusses the role and pathways of inflammaging that lead to skin aging. Moreover, strategies and current topical approaches for skin-aging treatment are discussed. Studies over the past 10 years suggested that DNA damage and oxidative stress are the most critical mechanisms in skin aging, and both are interlinked with inflammaging. Several treatments for skin aging have been considered such as antioxidants, hormone replacement therapy, and vitamins. To deliver anti-aging agents topically, researchers adopted numerous approaches to enhance skin penetration including physical, chemical, or biomaterial enhancers and carrier-based formulations. In recent years, consumers' demands for anti-aging products have considerably risen, leading to robust growth in the anti-aging market. Therefore, further in-depth studies are necessary to understand skin-aging mechanisms and evaluate the efficacy of anti-aging products to protect consumers worldwide by providing them safe and effective over-the-counter skin-aging formulations.

Over-the-Counter Herbal Weight Loss Supplements in Egypt: Label Claim, Microbiological and Pharmaceutical Quality, and Safety Assessments.

OBJECTIVES: Nutraceuticals are advertised and sold with the label claim of being natural and safe herbal products. Due to the absence of clear regulations and guidelines for safety assessments of these products, nutraceuticals are commonly adulterated in order to increase sales. The objective of the current study was to design a comprehensive evaluation system to assess the safety, efficacy, authenticity according to label claim, and pharmaceutical quality of herbal slimming products in between 2015 and 2017. METHODS: We designed a comprehensive assessment system to evaluate the safety, authenticity according to label claim, and pharmaceutical quality of slimming nutraceuticals. Six different popular products were evaluated (Zotreem Plus®, Zotreem Extra®, Malaysian Super Slim®, AB Slim®, Chinese Super Slim®, and Metabolites®). The pharmaceutical evaluation included analyzing the samples via high-performance liquid chromatography to determine any possible adulterants. Additionally, the products' physical properties were assessed via pharmacopeial tests. Finally, a microbial evaluation and a cross-sectional observational retrospective prevalence study were conducted to assess the products' safety and efficacy. -Results: The tested products were found to be adulterated with unreported active pharmaceutical ingredients such as sibutramine, sildenafil, phenolphthalein, and orlistat. Furthermore, they contained heterogeneous amounts of adulterants and exhibited an unsatisfactory pharmaceutical and microbial quality. Finally, the observational survey conducted on users showed that high percentages of participants suffered from common side effects such as depression, diarrhea, and hypertension. CONCLUSIONS: These products threaten the health of consumers. There is a need to raise awareness of the lethal consequences of illegal nutraceuticals.

Effect of batch age on potency and dissolution of levothyroxine sodium tablets: impact of BP and USP monograph differences on dissolution results.

Controversies surround levothyroxine sodium as a drug and product, and are reflected in compendia (USP vs BP) differences in levothyroxine sodium tablets specifications concerning potency limit and dissolution test conditions, and in lack of consensus on several issues such as whether the drug BCS class I or III. We have recently published a clinical study in patients comparing the efficacy of multisource 100 mcg levothyroxine sodium tablets (three sources, two brands, a total of five batches). Clinical efficacy and dissolution rate data varied among the tablet batches studied and indicated that brand/source interchangeability could not be claimed. The efficacy parameters showed good correlation with dissolution data generated under BP 2014, but not under USP 2014 dissolution test conditions. In the present study, we decided to expand the number of tablet batches studied in vitro to a total of 12, to report potency and content uniformity data missing in the clinical study, and to further examine the discrepancy in dissolution results based on the medium used. The wide range of batch age in the studied samples allowed investigating the effect of batch age on in-vitro tablet performance parameters. Generated potency values indicated the prevalence of super-potent tablet batches. The dissolution data reflected the effect of compendia monograph differences in dissolution medium. The results also indicated an inverse relationship between tablet potency and batch age and, between dissolution and batch age. The possible effect of potency results on the generated dissolution data was discussed. Statistical significance of correlations examined was assessed by linear and non-linear regression analysis. Statistical significance was evident for the relation between batch age and BP 2014 dissolution data, compared to USP 2014 dissolution results.

Anti-cancer Antibody Trastuzumab-Melanotransferrin Conjugate (BT2111) for the Treatment of Metastatic HER2+ Breast Cancer Tumors in the Brain: an In-Vivo Study.

PURPOSE: The ability of human melanotransferrin (hMTf) to carry a therapeutic concentration of trastuzumab (BTA) in the brain after conjugation (in the form of trastuzumab-melanotransferrin conjugate, BT2111 conjugate) was investigated by measuring the reduction of the number and size of metastatic human HER2+ breast cancer tumors in a preclinical model of brain metastases of breast cancer. METHODS: Human metastatic brain seeking breast cancer cells were injected in NuNu mice (n = 6-12 per group) which then developed experimental brain metastases. Drug uptake was analyzed in relation to metastasis size and blood-tumor barrier permeability. To investigate in-vivo activity against brain metastases, equimolar doses of the conjugate, and relevant controls (hMTf and BTA) in separate groups were administered biweekly after intracardiac injection of the metastatic cancer cells. RESULTS: The trastuzumab-melanotransferrin conjugate (BT2111) reduced the number of preclinical human HER2+ breast cancer metastases in the brain by 68% compared to control groups. Tumors which remained after treatment were 46% smaller than the control groups. In contrast, BTA alone had no effect on reducing number of metastases, and was associated with only a minimal reduction in metastasis size. CONCLUSIONS: The results suggest the novel trastuzumab-melanotransferrin conjugate (BT2111) may have utility in treating brain metastasis and validate hMTf as a potential vector for antibody transport across the Blood Brain Barrier (BBB).

Chitosan Nanoparticles Alleviated the Adverse Effects of Sildenafil on the Oxidative Stress Markers and Antioxidant Enzyme Activities in Rats.

Sildenafil (SF) is widely used for erectile dysfunction and other conditions, though with limitations regarding oral absorption and adverse effects. Despite nanotechnological improvements, the effect of nanocarriers on SF hepatotoxicity has not been documented to date. This study aimed at assessing the impact of chitosan nanoparticles either uncoated (CS NPs) or Tween 80-coated (T-CS NPs) on the effects of SF on oxidative stress markers and antioxidant enzyme activities in rats. Test SF-CS NPs prepared by ionic gelation were uniform positively charged nanospheres (diameter 178-215 nm). SF was administered intraperitoneally to male rats (1.5 mg/kg body weight) in free or nanoencapsulated forms as SF-CS NPs and T-SF-CS NPs for 3 weeks. Free SF significantly suppressed the activity of the antioxidant enzymes glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and superoxide dismutase (SOD), as well as the levels of glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) as in an indirect measure of free radicals. Interestingly, SF-CS NPs and T-SF-CS-NPs treatments significantly attenuated the inhibitory effects of SF on the activity of these enzymes whereas, GST activity was inhibited. Moreover, the protein expression of GST was downregulated upon treatment of rats with free SF, SF-CS-NPs, and T-SF CS-NPs. In contrast, the activity and protein expression of GPx was induced by SF-CS NPs and T-SF-CS-NPs treatments. The histopathological study showed that SF induced multiple adverse effects on the rat liver architecture which were markedly suppressed particularly by T-SF-CS NPs. In conclusion, chitosan nanoencapsulation of SF counteracted the adverse effects of SF on the activity of antioxidant enzymes and liver architecture. Findings might have significant implications in improving the safety and efficacy of SF treatment of the widely expanding disease conditions.

3D-Printed Microfluidics Potential in Combating Future and Current Pandemics (COVID-19).

Coronavirus disease (COVID-19) emerged in China in December 2019. In March 2020, the WHO declared it a pandemic leading to worldwide lockdowns and travel restrictions. By May, it infected 4,789,205 and killed 318,789 people. This led to severe shortages in the medical sector besides devastating socio-economic effects. Many technologies such as artificial intelligence (AI), virtual reality (VR), microfluidics, 3D printing, and 3D scanning can step into contain the virus and hinder its extensive spread. This article aims to explore the potentials of 3D printing and microfluidic in accelerating the diagnosis and monitoring of the disease and fulfilling the shortages of personal protective equipment (PPE) and medical equipment. It highlights the main applications of 3D printers and microfluidics in providing PPE (masks, respirators, face shields, goggles, and isolation chambers/hoods), supportive care (respiratory equipment) and diagnostic supplies (sampling swabs & lab-on-chip) to ease the COVID-19 pressures. Also, the cost of such technology and regulation considerations are addressed. We conclude that 3D printing provided reusable and low-cost solutions to mitigate the shortages. However, safety, sterility, and compatibility with environmental protection standards need to be guaranteed through standardization and assessment by regulatory bodies. Finally, lessons learned from this pandemic can also help the world prepare for upcoming outbreaks.

Mobile-Based Augmented Reality Application in Pharmacy Schools Implemented in Pharmaceutical Compounding Laboratories: Students' Benefits and Reception.

BACKGROUND: Augmented reality (AR) is a technological approach which combines virtual objects such as text, pictures or videos with physical objects (real-world). The study aimed to design, implement and validate a mobile-based AR application, as a self-paced, interactive, student-centered learning tool be used in the pharmaceutical compounding laboratory course for first year pharmacy students. METHOD: A mobile-based AR application (Amplified Rx app; HeyPayLess Inc) compatible with iOS and android operating system was developed. A cross-over study design was conducted where alternatively, one group was subjected to ARx app implementation in 8 formulations and the other group served as control. The reception and benefits to students were assessed via a 10 questions survey. In this case, 69 (2019) and 55 (2020) students participated in the study. RESULT: Students' use of ARx app was increased in 2020 which indicates its usefulness. For acceptability, leaners enjoyed interactive materials and tutorial videos were the most used and appealing item. Learners described the installation, scanning and operation to be very easy in both years. 86.95% of learners were confident conducting the experiments with the assistance of ARx app in 2019 and increased to 92.73% in 2020. 33.33% considered ARx app to be the most helpful resource in 2019, and the percent was significantly increased to 76.36% in 2020. CONCLUSION: AR technology implementation in pharmaceutical education could create student-centered engaging and interactive learning experience in fundamental areas such as pharmaceutical compounding laboratories.

Berberine Nanoencapsulation Attenuates Hallmarks of Scoplomine Induced Alzheimer's-Like Disease in Rats.

BACKGROUND: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, anti-inflammatory, cholesterol-lowering effect, and inhibition of Aß production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-Nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. METHODS: BBR-NPs were formulated using the ionic gelation method, and tripolyphosphate was chosen as a crosslinker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty-six Wistar male rats were randomly distributed into three control groups, received saline, polyethylene glycol or Chitosan- NPs, respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-ß processing intermediates, as well as neuroplasticity markers and histopathological examination were assessed. RESULTS: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands towards AChE and Aß42 formation and significantly down-regulated Tau, iNOS and BACE gene expression in rats' hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-ß toxicity in addition to the improvement of the neuroplasticity markers. CONCLUSION: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake, which need more investigation in future work.

The safety, efficacy and pharmaceutical quality of male enhancement nutraceuticals bought online: Truth versus claim.

OBJECTIVE: Nutraceutical products are widely used for their claimed therapeutic benefits. However, falsified or adulterated nutraceuticals present a major health threat to consumers. This study investigates the pharmaceutical quality, safety and anti-inflammatory effects of six male enhancement nutraceuticals that claim to be 100% natural. METHODS: Three batches of six male enhancement products were tested to detect the presence and levels of adulterants via high-performance liquid chromatography (HPLC). The pharmaceutical quality of the selected nutraceuticals was tested with near infrared spectroscopy (NIR) and SeDeM. The cytotoxic effects of these products on HepG2 cells were determined through cell proliferation (XTT) and lactate dehydrogenase (LDH) cytotoxicity assays. Lastly, the in vitro inflammatory effects of these products were investigated using murine J774 macrophages through cytokine release analysis. RESULTS: HPLC analysis detected the presence of sildenafil citrate, a vasodilator, and the active ingredient in Viagra and Revatio, in all batches of the products we analyzed. Amount of sildenafil citrate ranged from 0.45 mg to 51.85 mg among different batches. NIR assessment showed inter- and intra-batch heterogeneity in product composition. Results of the XTT and LDH assays showed significant cytotoxic effects of the analyzed products. XTT analysis revealed that the viability of HepG2 treated with tested products varied from 27.57% to 41.43%. Interestingly, the male enhancement products also showed anti-inflammatory effects. CONCLUSION: Despite their labeling as 100% natural, all products tested in this study contained levels of sildenafil citrate, which was not reported on the packaging. There was a lack of pharmaceutical uniformity among products of the same batch and across different batches. Additionally, the products we tested had cytotoxic effects. These study findings highlight the adulteration, poor quality and hazard of these nutraceuticals. Therefore, strict regulation of these products and standardization of the definition of nutraceuticals are urgently needed. Further, these falsely advertised products should be withdrawn from the market due to potential adverse effects on the health of their consumers.

Bioconjugation in Drug Delivery: Practical Perspectives and Future Perceptions.

For the past three decades, pharmaceutical research has been mainly converging to novel carrier systems and nanoparticulate colloidal technologies for drug delivery, such as nanoparticles, nanospheres, vesicular systems, liposomes, or nanocapsules to impart novel functions and targeting abilities. Such technologies opened the gate towards more sophisticated and effective multi-acting platform(s) which can offer site-targeting, imaging, and treatment using a single multifunctional system. Unfortunately, such technologies faced major intrinsic hurdles including high cost, low stability profile, short shelf-life, and poor reproducibility across and within production batches leading to harsh bench-to-bedside transformation.Currently, pharmaceutical industry along with academic research is investing heavily in bioconjugate structures as an appealing and advantageous alternative to nanoparticulate delivery systems with all its flexible benefits when it comes to custom design and tailor grafting along with avoiding most of its shortcomings. Bioconjugation is a ubiquitous technique that finds a multitude of applications in different branches of life sciences, including drug and gene delivery applications, biological assays, imaging, and biosensing.Bioconjugation is simple, easy, and generally a one-step drug (active pharmaceutical ingredient) conjugation, using various smart biocompatible, bioreducible, or biodegradable linkers, to targeting agents, PEG layer, or another drug. In this chapter, the different types of bioconjugates, the techniques used throughout the course of their synthesis and characterization, as well as the well-established synthetic approaches used for their formulation are presented. In addition, some exemplary representatives are outlined with greater emphasis on the practical tips and tricks of the most prominent techniques such as click chemistry, carbodiimide coupling, and avidin-biotin system.

High-Dose Gabapentin for the Treatment of Severe Alcohol Withdrawal Syndrome: A Retrospective Cohort Analysis.

STUDY OBJECTIVE: Gabapentin has been proved to be beneficial in promoting abstinence, decreasing alcohol cravings, and improving mood and sleep quality when given at higher doses; however, data are limited regarding the efficacy and safety of using high-dose gabapentin as part of the treatment of alcohol withdrawal syndrome (AWS). The aim of this study was to evaluate the impact of high-dose gabapentin on benzodiazepine requirements, alcohol withdrawal symptoms, and hospital length of stay in patients hospitalized with AWS. DESIGN: Retrospective cohort study. SETTING: Large academic medical center. PATIENTS: All adults presenting to the emergency department between January 2015 and April 2018 with a diagnosis of severe AWS (Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised [CIWA-Ar] score ≥ 15) and prescribed the institution's alcohol withdrawal agitated delirium protocol were eligible for inclusion in the study. Of these, 50 patients who received high-dose gabapentin (≥ 1800 mg/day) in the first 48 hours of hospital admission (treatment group) were propensity score-matched to 50 patients who did not receive gabapentin (control group). MEASUREMENTS AND MAIN RESULTS: Patients who received high-dose gabapentin required a significantly lower overall amount of benzodiazepines (mean ± SD 109.5 ± 53.4 mg vs 88.5 ± 35.6 mg [lorazepam equivalents], p=0.023) and had a significantly lower mean CIWA-Ar score (10.1 ± 4.7 vs 7.7 ± 3.9, p=0.010) and maximum CIWA-Ar score (16.0 ± 7.0 vs 12.6 ± 6.1, p=0.016) on day 3 of hospitalization. The high-dose gabapentin regimen was well tolerated, without an increased risk of oversedation, compared with the control group (Richmond Agitation-Sedation Scale score < -1: 34% in the treatment group vs 20% in the control group, p=0.115). Patients receiving high-dose gabapentin had a shorter length of hospital stay (7.4 ± 4.0 days vs 6.0 ± 2.6 days, p=0.034) and increased likelihood of being discharged home (66% vs 88%, p=0.009) compared with the control group. CONCLUSION: Early initiation of high-dose gabapentin was associated with a significant reduction in benzodiazepine exposure, faster stabilization of alcohol withdrawal-related symptoms, and shorter hospital length of stay. Future studies evaluating gabapentin's effect on long-term safety and hospital readmission are warranted.

Integrated continuous manufacturing in pharmaceutical industry: current evolutionary steps toward revolutionary future.

Continuous manufacturing (CM) has the potential to provide pharmaceutical products with better quality, improved yield and with reduced cost and time. Moreover, ease of scale-up, small manufacturing footprint and on-line/in-line monitoring and control of the process are other merits for CM. Regulating authorities are supporting the adoption of CM by pharmaceutical manufacturers through issuing proper guidelines. However, implementation of this technology in pharmaceutical industry is encountered by a number of challenges regarding the process development and quality assurance. This article provides a background on the implementation of CM in pharmaceutical industry, literature survey of the most recent state-of-the-art technologies and critically discussing the encountered challenges and its future prospective in pharmaceutical industry.

Are multisource levothyroxine sodium tablets marketed in Egypt interchangeable?

A clinical study was initiated in response to patients' complaints, supported by the treating physicians, of suspected differences in efficacy among multisource levothyroxine sodium tablets marketed in Egypt. The study design was a multiple dose (100µg levothyroxine sodium tablet once daily for 6 months) and involved 50 primary hypothyroidism female patients (5 equal groups). Tablets administered included five tablet batches (two brands, three origin locations) purchased from local pharmacies in Alexandria. Assessment parameters (measured on consecutive visits) included the thyroid stimulating hormone, total and free levothyroxine. Tablet dissolution rate was determined (BP/EP 2014 & USP 2014). In vitro vs in vivovs correlations were developed. Clinical and pharmaceutical data confirmed inter-brand and inter-source differences in efficacy. Correlations examined indicated potential usefulness of in vitro dissolution test in detecting poor performing levothyroxine sodium tablets during shelf life.

Adulteration and Counterfeiting of Online Nutraceutical Formulations in the United States: Time for Intervention?

Global prevalence of nutraceuticals is noticeably high. The American market is flooded with nutraceuticals claiming to be of natural origin and sold with a therapeutic claim by major online retail stores such as Amazon and eBay. The objective of this commentary is to highlight the possible problems of online-sold nutraceuticals in the United States with respect to claim, adulterants, and safety. Furthermore, there is a lack of strict regulatory laws governing the sales, manufacturing, marketing, and label claims of nutraceutical formulations currently sold in the U.S. market. Major online retail stores and Internet pharmacies aid the widespread sale of nutraceuticals. Finally, according to the literature, many of these products were found to be either counterfeit or adulterated with active pharmaceutical ingredients (API) and mislabeled as being safe and natural. Therefore, regulatory authorities along with the research community should intervene to draw attention to these products and their possible effects.

Trastuzumab distribution in an in-vivo and in-vitro model of brain metastases of breast cancer.

BACKGROUND: Drug and antibody delivery to brain metastases has been highly debated in the literature. The blood-tumor barrier (BTB) is more permeable than the blood-brain barrier (BBB), and has shown to have highly functioning efflux transporters and barrier properties, which limits delivery of targeted therapies. METHODS: We characterized the permeability of 125I-trastuzumab in an in-vivo, and fluorescent trastuzumab-Rhodamine123 (t-Rho123) in a novel microfluidic in-vitro, BBB and BTB brain metastases of breast cancer model. In-vivo: Human MDA-MB-231-HER2+ metastatic breast cancer cells were grown and maintained under static conditions. Cells were harvested at 80% confluency and prepped for intra-cardiac injection into 20 homozygous female Nu/Nu mice. In-vitro: In a microfluidic device (SynVivo), human umbilical vein endothelial cells were grown and maintained under shear stress conditions in the outer compartment and co-cultured with CTX-TNA2 rat brain astrocytes (BBB) or Met-1 metastatic HER2+ murine breast cancer cells (BTB), which were maintained in the central compartment under static conditions. RESULTS: Tissue distribution of 125I-trastuzumab revealed only ~3% of injected dose reached normal brain, with ~5% of injected dose reaching brain tumors. No clear correlation was observed between size of metastases and the amount of 125I-trastuzumab localized in-vivo. This heterogeneity was paralleled in-vitro, where the distribution of t-Rho123 from the outer chamber to the central chamber of the microfluidic device was qualitatively and quantitatively analyzed over time. The rate of t-Rho123 linear uptake in the BBB (0.27 ± 0.33 × 104) and BTB (1.29 ± 0.93 × 104) showed to be significantly greater than 0 (p < 0.05). The BTB devices showed significant heterogenetic tendencies, as seen in in-vivo. CONCLUSIONS: This study is one of the first studies to measure antibody movement across the blood-brain and blood-tumor barriers, and demonstrates that, though in small and most likely not efficacious quantities, trastuzumab does cross the blood-brain and blood-tumor barriers.

Are Currently Available Wearable Devices for Activity Tracking and Heart Rate Monitoring Accurate, Precise, and Medically Beneficial?

OBJECTIVES: The new wave of wireless technologies, fitness trackers, and body sensor devices can have great impact on healthcare systems and the quality of life. However, there have not been enough studies to prove the accuracy and precision of these trackers. The objective of this study was to evaluate the accuracy, precision, and overall performance of seventeen wearable devices currently available compared with direct observation of step counts and heart rate monitoring. METHODS: Each participant in this study used three accelerometers at a time, running the three corresponding applications of each tracker on an Android or iOS device simultaneously. Each participant was instructed to walk 200, 500, and 1,000 steps. Each set was repeated 40 times. Data was recorded after each trial, and the mean step count, standard deviation, accuracy, and precision were estimated for each tracker. Heart rate was measured by all trackers (if applicable), which support heart rate monitoring, and compared to a positive control, the Onyx Vantage 9590 professional clinical pulse oximeter. RESULTS: The accuracy of the tested products ranged between 79.8% and 99.1%, while the coefficient of variation (precision) ranged between 4% and 17.5%. MisFit Shine showed the highest accuracy and precision (along with Qualcomm Toq), while Samsung Gear 2 showed the lowest accuracy, and Jawbone UP showed the lowest precision. However, Xiaomi Mi band showed the best package compared to its price. CONCLUSIONS: The accuracy and precision of the selected fitness trackers are reasonable and can indicate the average level of activity and thus average energy expenditure.

Novel treatment strategies for brain tumors and metastases.

This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood-brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application.

Novel reducible linear L-lysine-modified copolymers as efficient nonviral vectors.

The development of biodegradable gene delivery systems with high transfection efficiencies is paramount to the clinical translation of nonviral gene carriers. Therefore, to produce a biocompatible, reducible, effective and non-toxic gene delivery system, we have designed and synthesized novel reducible linear L-lysine modified copolymers (LLCs) as an alternative to high molecular weight poly(L-lysine) (PLL). The molecular weight (MW) of the copolymers was found to be approximately 3.2kDa with a polydispersity index of approximately 1.2. Gel retardation assays showed complete condensation of DNA at N/P ratios greater than 20/1 and exceptional LLC/pDNA polyplex stability during incubation with DNase I. Release of DNA from the polyplexes only occurred in the presence of the reducing agent dithiothreitol (DTT). The particle sizes of LLC/pDNA polyplexes were found to be between 100 and 231 nm with surface charges of 0.8-17 mV respectively. The transfection efficiencies of the polyplexes as determined with a luciferase assay showed that LLC polyplexes produced five times higher transfection efficiencies in HDF cells, three times higher transfection efficiencies in MCF-7 cells, and four times higher transfection efficiencies in MA cells as compared to the optimal PLL control. The LLC/pDNA polyplexes showed significantly lower cytotoxicities as compared to the control in HDF, MCF-7 and MA cells at certain N/P ratios. Therefore, these results suggest that these novel LLCs are efficient, reducible and biocompatible polymers for nonviral gene delivery.