Unveiling novel metabolic alterations in postmenopausal osteoporosis and type 2 diabetes mellitus through NMR-based metabolomics: A pioneering approach for identifying early diagnostic markers.

BACKGROUND AND AIMS: Postmenopausal osteoporosis (PMO) and type 2 diabetes mellitus (T2DM) frequently coexist in postmenopausal women. The study aimed to explore metabolic variations linked to these circumstances and their simultaneous presence through proton nuclear magnetic resonance metabolomics (1H NMR). MATERIALS AND METHODS: Serum samples from 80 postmenopausal women, including 20 PMO individuals, 20 T2DM, 20 T2DM + PMO, and 20 healthy postmenopausal women, were analyzed using 1H NMR spectroscopy. RESULTS: Our study revealed significant metabolic profile differences among the four groups. Notably, the T2DM + PMO group showed elevated levels of alanine, pyruvate, glutamate, lactate, and aspartate, indicating their involvement in lipid metabolism, energy, and amino acids. Importantly, our multivariate statistical analysis identified a metabolite set that accurately distinguished the groups, suggesting its potential as an early diagnostic marker. CONCLUSION: The 1H NMR metabolomics approach uncovered metabolic biomarkers intricately linked to postmenopausal osteoporosis (PMO), type 2 diabetes mellitus (T2DM), and their concurrent presence. Among these biomarkers, alanine emerged as a pivotal player, showing its significant role in the metabolic landscape associated with PMO and T2DM. These findings shed light on the pathophysiological mechanisms underlying these conditions and underscore alanine's potential as a diagnostic biomarker.

Nanotechnology-Based Approaches for Cosmeceutical and Skin Care: A Systematic Review.

Cosmeceuticals have gained great importance and are among the top-selling products used for skin care. Because of changing lifestyles, climate, and increasing pollution, cosmeceuticals are utilized by every individual, thereby making cosmeceuticals a fruitful field for research and the economy. Cosmeceuticals provide incredibly pleasing aesthetic results by fusing the qualities of both cosmetics and medicinal substances. Cosmeceuticals are primarily utilized to improve the appearance of skin by making it smoother, moisturized, and wrinkle-free, in addition to treating dermatological conditions, including photoaging, burns, dandruff, acne, eczema, and erythema. Nanocosmeceuticals are cosmetic products that combine therapeutic effects utilizing nanotechnology, allowing for more precise and effective target-specific delivery of active ingredients, and improving bioavailability.

RNA-Small-Molecule Interaction: Challenging the "Undruggable" Tag.

RNA targeting, specifically with small molecules, is a relatively new and rapidly emerging avenue with the promise to expand the target space in the drug discovery field. From being "disregarded" as an "undruggable" messenger molecule to FDA approval of an RNA-targeting small-molecule drug Risdiplam, a radical change in perspective toward RNA has been observed in the past decade. RNAs serve important regulatory functions beyond canonical protein synthesis, and their dysregulation has been reported in many diseases. A deeper understanding of RNA biology reveals that RNA molecules can adopt a variety of structures, carrying defined binding pockets that can accommodate small-molecule drugs. Due to its functional diversity and structural complexity, RNA can be perceived as a prospective target for therapeutic intervention. This perspective highlights the proof of concept of RNA-small-molecule interactions, exemplified by targeting of various transcripts with functional modulators. The advent of RNA-oriented knowledge would help expedite drug discovery.

QbD-driven development and characterization of superparamagnetic iron oxide nanoparticles (SPIONS) of a bone-targeting peptide for early detection of osteoporosis.

Osteoporosis is a metabolic disorder that leads to deterioration of bones. The major challenges confronting osteoporosis therapy include early-stage detection and regular disease monitoring. The present studies employed D-aspartic acid octapeptide (-D-Asp-)8 as bone-targeting peptide for evaluating osteoporosis manifestation, and superparamagnetic iron oxide nanoparticles (SPIONs) as nanocarriers for MRI-aided diagnosis. Thermal decomposition technique was employed to synthesize SPIONs, followed by surface-functionalization with hydrophilic ligands. Failure mode effect analysis and factor screening studies were performed to identify concentrations of SPIONs and ligand as critical material attributes, and systematic optimization was subsequently conducted employing face-centered cubic design. The optimum formulation was delineated using desirability function, and design space demarcated with 178.70 nm as hydrodynamic particle size, -24.40 mV as zeta potential, and 99.89 % as hydrophilic iron content as critical quality attributes. XRD patterns ratified lattice structure and SQUID studies corroborated superparamagnetic properties of hydrophilic SPIONs. Bioconjugation of (-D-Asp-)8 with SPIONs (1:1) was confirmed using UV spectroscopy, FTIR and NMR studies. Cell line studies indicated successful targeting of SPIONs to MG-63 human osteoblasts, ratifying enormous bone-targeting and safety potential of peptide-tethered SPIONs as MRI probes. In vivo MRI imaging studies in rats showcased promising contrast ability and safety of peptide-conjugated SPIONs.

A Path of Novelty from Nanoparticles to Nanobots: Theragnostic Approach for Targeting Cancer Therapy.

Pharmaceutical development of cancer therapeutics is a dynamic area of research. Even after decades of intensive work, cancer continues to be a dreadful disease with an ever-increasing global incidence. The progress of nanotechnology in cancer research has overcome inherent limitations in conventional cancer chemotherapy and fulfilled the need for target-specific drug carriers. Nanotechnology uses the altered patho-physiological microenvironment of malignant cells and offers various advantages like improved solubility, reduced toxicity, prolonged drug circulation with controlled release, circumventing multidrug resistance, and enhanced biodistribution. Early cancer detection has a crucial role in selecting the best drug regime, thus, diagnosis and therapeutics go hand in hand. Furthermore, nanobots are an amazing possibility and promising innovation with numerous significant applications, particularly in fighting cancer and cleaning out blood vessels. Nanobots are tiny robots, ranging in size from 1 to 100 nm. Moreover, the nanobots would work similarly to white blood cells, watching the bloodstream and searching for indications of distress. This review articulates the evolution of various organic and inorganic nanoparticles and nanobots used as therapeutics, along with their pros and cons. It also highlights the shift in diagnostics from conventional methods to more advanced techniques. This rapidly growing domain is providing more space for engineering desired nanoparticles that can show miraculous results in therapeutic and diagnostic trials.

Nanomedicine at the Pulmonary Frontier: Immune-Centric Approaches for Respiratory Disease Treatment.

Respiratory diseases (RD) are a group of common ailments with a rapidly increasing global prevalence, posing a significant threat to humanity, especially the elderly population, and imposing a substantial burden on society and the economy. RD represents an unmet medical need that requires the development of viable pharmacotherapies. While various promising strategies have been devised to advance potential treatments for RD, their implementation has been hindered by difficulties in drug delivery, particularly in critically ill patients. Nanotechnology offers innovative solutions for delivering medications to the inflamed organ sites, such as the lungs. Although this approach is enticing, delivering nanomedicine to the lungs presents complex challenges that require sophisticated techniques. In this context, we review the potential of novel nanomedicine-based immunomodulatory strategies that could offer therapeutic benefits in managing this pressing health condition.

Exploring the therapeutic potential of sodium deoxycholate tailored deformable-emulsomes of etodolac for effective management of arthritis.

The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (- 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.

Overexpression of gamma-glutamyl cyclotransferase 2;1 (CsGGCT2;1) reduces arsenic toxicity and accumulation in Camelina sativa (L.).

KEY MESSAGE: Overexpressing CsGGCT2;1 in Camelina enhances arsenic tolerance, reducing arsenic accumulation by 40-60%. Genetically modified Camelina can potentially thrive on contaminated lands and help safeguard food quality and sustainable food and biofuel production. Environmental arsenic contamination is a serious global issue that adversely affects human health and diminishes the quality of harvested produce. Glutathione (GSH) is known to bind and detoxify arsenic and other toxic metals. A steady level of GSH is maintained within cells via the γ-glutamyl cycle. The γ-glutamyl cyclotransferases (GGCTs) have previously been shown to be involved in GSH degradation and increased tolerance to toxic metals in plants. In this study, we characterized the GGCT2;1 homolog from Camelina sativa for its role in arsenic tolerance and accumulation. Overexpression of CsGGCT2;1 in Camelina under CaMV35S constitutive promoter resulted in strong tolerance to arsenite (AsIII). The overexpression (OE) lines had 2.6-3.5-fold higher shoots and sevenfold to tenfold enhanced root biomass on media supplemented with AsIII, relative to wild-type plants. The CsGGCT2;1 OE lines accumulated 40-60% less arsenic in root and shoot tissues compared to wild-type plants. Further, the OE lines had ~ twofold higher chlorophyll content and 35% lesser levels of malondialdehyde (MDA), an indicator of membrane damage via lipid peroxidation. There was a slight but non-significant increase in 5-oxoproline (5-OP), a product of GSH degradation, in OE lines. However, the transcript levels of Oxoprolinase 1 (OXP1) were upregulated, indicating the accelerated conversion of 5-OP to glutamate, which is further utilized for the resynthesis of GSH to maintain GSH homeostasis. Overall, this research suggests that genetically modified Camelina may have the potential for cultivation on contaminated marginal lands to reduce As accumulation; thereby could help in addressing food safety issues as well as future food and biofuel needs.

Disseminated Histoplasmosis in Central California Seen in an Immunocompromised Patient.

Histoplasma capsulatum is a dimorphic fungus found in certain parts of North, Central, and South America. Transmission is primarily through airborne inoculation from inhaled fungal microconidia. Histoplasmosis is typically a self-limited mycosis; however, in patients with immunodeficiency, disseminated disease can occur and may lead to high disease burden. This report studies a case of disseminated histoplasmosis in a patient newly diagnosed with human immunodeficiency virus. His presentation on admission was consistent with infectious pulmonary granulomatous disease, and further imaging and laboratory results showed evidence of multi-organ involvement. It is likely his presentation in Central California was a reactivation infection after inoculation in Central America many years ago.

Screening of potential inhibitors against structural proteins from Monkeypox and related viruses of Poxviridae family via docking and molecular dynamics simulation.

Monkeypox virus (MPXV) is an orthopoxvirus which causes zoonotic infection in humans. Even though sporadic cases of this infection are limited to the African continent, but if the infection continues to increase unabated, it can be a cause of serious concern for the human populace. Smallpox vaccination has been in use against monkeypox infection but it only provides mild protection. In the current study, we have screened novel small molecules (estrone fused heterocycles (EH1-EH7)) exhibiting good binding with monkeypox virus protein and related proteins from Poxviridae family of viruses via computational approaches. EH1-7 series of small molecules selected for the work have been synthesized via cycloaddition methodology. Docking and Molecular Dynamics (MD) results highlight EH4 compound to have strong binding affinity towards monkeypox and other related viral proteins selected for the study. Thus, computational outcomes suggest EH4 as a good candidate against monkeypox. Currently, no antiviral medication has been approved against monkeypox and the treatment is only via therapeutics available for smallpox and related conditions that may be helpful against monkeypox. Our study is thus an attempt to screen novel compounds against monkeypox infection, which would, in turn, facilitate development of novel therapeutics against Poxviridae family. HIGHLIGHTSMonkeypox infection is a public health emergency and necessitates immediate drug discovery.Molecular docking study to screen estrone-fused heterocycles compounds against Monkeypox and other orthopoxviruses.Molecular dynamics simulations revealed interaction/high binding affinities among EH4 heterocyclic compound and profilin-like protein from the monkeypox virus.Estrone-fused heterocycles compounds are promising anti-viral agents as per our in silico analysis.Our study provides evidence for investigating estrone-fused heterocycles compounds for further pharmacological interventions.Communicated by Ramaswamy H. Sarma.

Monkeypox: This orthopoxvirus leads to mpox (monkeypox) disease which shows symptoms similar to that smallpox, however to less severe extent.Poxviridae family: This is commonly a family of double-stranded DNA viruses. The natural hosts for these viruses are arthropods and Vertebrates.Molecular Dynamic simulation: MD simulation is crucial for determining the ligand's stability and revealing the duration of its interaction with the respective macromolecular structure.Molecular Docking: Molecular docking aids in determining specific sites where the ligand binds with the macromolecule as well as its binding affinity. Bioinformatics tools such as docking have been widely employed for aiding drug discovery efforts.Protein binding energy: On docking protein with the ligand, the binding energy shows the free energy change during binding process between protein-ligand.

Evaluation of antibiofilm properties of dehydroacetic acid (DHA) grafted spiro-oxindolopyrrolidines synthesized via multicomponent 1,3-dipolar cycloaddition reaction.

The current work involves the use of dehydroacetic acid based chalcone derivatives for the synthesis of spirooxindole grafted pyrrolidine moieties. All the synthesized compounds have been characterized using spectroscopic techniques such as NMR (1H-NMR and 13C-NMR), IR, mass and elemental analysis. Molecular mechanics studies were performed to comprehend the regioselectivity in the product formation. Molecular docking of the synthesized compounds was performed with few bacterial proteins of Bacillus subtilis and Pseudomonas aeruginosa responsible for biofilm formation followed by molecular dynamics simulations with the potential lead compound. Further, to corroborate the results obtained via in silico study, anti-biofilm activity etc. of the synthesized compounds (4a-e) was checked for effectiveness against biofilm formation. Taken together, this study opens up to explore these compounds' multiple roles in diverse fields in the arena of medical sciences.

Nanoscale sulfur alleviates silver nanoparticle toxicity and improves seed and oil yield in Soybean (Glycine max).

Silver nanoparticles (AgNPs) are commonly used in many commercial products due to their antimicrobial properties, and their significant exposure in agricultural systems is anticipated. AgNPs accumulation in soil and subsequent uptake by plants can be harmful to plant growth and exposure to animals and humans through the food chain is a major concern. This study evaluated the potential protective role of nanosulfur (NS) and bulk sulfur (BS) at 200 and 400 mg/kg soil application in alleviating silver nanoparticle (AgNPs; 32 and 64 mg/kg) phytotoxicity to soybean [Glycine max (L) Merr.]. The treatments were added in the soil before soybean transplantation; growth, yield, nutrient, and silver accumulation were measured in the shoot, root, and seeds. Exposure to AgNPs significantly affected plant growth and yield, reducing nodule weight by 40%, fresh shoot weight by 66%, and seed yield by 68% when compared to controls. However, nanosulfur application in soil alleviated AgNPs toxicity, and importantly, this impact was nanoscale specific at the higher concentration because the benefits of corresponding bulk sulfur (BS) treatments were marginal. Specifically, nanosulfur at 400 mg/kg significantly increased seed yield (∼3-fold more than AgNP at 64 mg/kg) and shoot biomass (2.6-fold more than AgNP at 64 mg/kg) upon co-exposure with AgNPs, essentially alleviating AgNPs toxicity. Moreover, NS increased nodule mass by 3.5 times compared to AgNPs-treated plants, which was 170% greater than the Ag- and NS-free controls. Plants treated with NS with AgNPs co-exposure accumulated significantly less Ag in the shoots (∼80% reduction) and roots (∼95% reduction); no Ag contents were detected in seeds. These findings demonstrate the potential of sulfur, especially NS, as a sustainable soil amendment to reduce the accumulation and toxicity of AgNPs and as a valuable nano-enabled strategy to promote food safety and security.

Neurological manifestations of SARS-CoV-2: complexity, mechanism and associated disorders.

BACKGROUND: Coronaviruses such as Severe Acute Respiratory Syndrome coronavirus (SARS), Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are associated with critical illnesses, including severe respiratory disorders. SARS-CoV-2 is the causative agent of the deadly COVID-19 illness, which has spread globally as a pandemic. SARS-CoV-2 may enter the human body through olfactory lobes and interact with the angiotensin-converting enzyme2 (ACE2) receptor, further facilitating cell binding and entry into the cells. Reports have shown that the virus can pass through the blood-brain barrier (BBB) and enter the central nervous system (CNS), resulting in various disorders. Cell entry by SARS-CoV-2 largely relies on TMPRSS2 and cathepsin L, which activate S protein. TMPRSS2 is found on the cell surface of respiratory, gastrointestinal and urogenital epithelium, while cathepsin-L is a part of endosomes. AIM: The current review aims to provide information on how SARS-CoV-2 infection affects brain function.. Furthermore, CNS disorders associated with SARS-CoV-2 infection, including ischemic stroke, cerebral venous thrombosis, Guillain-Barré syndrome, multiple sclerosis, meningitis, and encephalitis, are discussed. The many probable mechanisms and paths involved in developing cerebrovascular problems in COVID patients are thoroughly detailed. MAIN BODY: There have been reports that the SARS-CoV-2 virus can cross the blood-brain barrier (BBB) and enter the central nervous system (CNS), where it could cause a various illnesses. Patients suffering from COVID-19 experience a range of neurological complications, including sleep disorders, viral encephalitis, headaches, dysgeusia, and cognitive impairment. The presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of COVID-19 patients has been reported. Health experts also reported its presence in cortical neurons and human brain organoids. The possible mechanism of virus infiltration into the brain can be neurotropic, direct infiltration and cytokine storm-based pathways. The olfactory lobes could also be the primary pathway for the entrance of SARS-CoV-2 into the brain. CONCLUSIONS: SARS-CoV-2 can lead to neurological complications, such as cerebrovascular manifestations, motor movement complications, and cognitive decline. COVID-19 infection can result in cerebrovascular symptoms and diseases, such as strokes and thrombosis. The virus can affect the neural system, disrupt cognitive function and cause neurological disorders. To combat the epidemic, it is crucial to repurpose drugs currently in use quickly and develop novel therapeutics.

Quality by design-steered development and validation of analytical and bioanalytical methods for raloxifene: Application of Monte Carlo simulations and variance inflation factor.

A sensitive, rapid, reproducible, and economical HPLC method is reported for the quantification of raloxifene hydrochloride employing Quality by Design (QbD) principles. Factor screening studies, employing Taguchi design, indicated buffer volume percentage and isocratic flow rate as the critical method parameters (CMPs), which significantly influence the chosen critical analytical attributes, that is, tailing factor and theoretical plate number. Method conditions were subsequently optimized using face-centered cubic design with magnitude of variance inflation factor for assessing multicollinearity among CMPs. Method operable design region (MODR) was earmarked and liquid chromatographic separation optimized using 0.05 M citrate buffer, acetonitrile, and methanol (57:40:3 v/v/v) as ggmobile phase at 0.9 mL min-1 flow rate, λmax of 280 nm, and column temperature of 40°C. Validation of the developed analytical method was accomplished as per International Council on Harmonization (ICH) guidelines confirming high levels of linearity, precision, accuracy, robustness, and sensitivity. Application of Monte Carlo simulations enabled the attainment of best plausible chromatographic resolution and corroboration of the demarcated MODR. Establishment and validation of the bioanalytical method using rat plasma samples, along with forced degradation and stability studies, corroborated the aptness of developed HPLC methods for drug quantification in the biological fluids, as well as in bulk and marketed dosage forms.

Quorum sensing inhibitors as Therapeutics: Bacterial biofilm inhibition.

The overuse and inappropriate use of antibiotics to treat bacterial infections has led to the development of multiple drug resistant strains. Biofilm is a complex microorganism aggregation defined by the presence of a dynamic, sticky, and protective extracellular matrix made of polysaccharides, proteins, and nucleic acids. The infectious diseases are caused by bacteria that flourish within quorum sensing (QS) mediated biofilms. Efforts to disrupt biofilms have enabled the identification of bioactive molecules produced by prokaryotes and eukaryotes. The QS system is quenched predominantly by these molecules. The phenomenon is also termed as quorum sensing (QS). Both synthetic and natural substances have been discovered to be useful in QS. This review describes natural and synthetic quorum sensing inhibitors (QSIs) with the potential to treat bacterial infections. It includes the discussion on quorum sensing, mechanism of quorum sensing, effect of substituents on the activity. These discoveries could result in effective therapies using far lower dosages of medications, particularly antibiotics, are currently needed.

Immune Control of Avian Influenza Virus Infection and Its Vaccine Development.

The avian influenza A virus (AIV) is naturally prevalent in aquatic birds, infecting different avian species and transmitting from birds to humans. Both AIVs, the H5N1 and H7N9 viruses, have the potential to infect humans, causing an acute influenza disease syndrome in humans, and are a possible pandemic threat. AIV H5N1 is highly pathogenic, whereas AIV H7N9 has comparatively low pathogenicity. A clear insight into the disease pathogenesis is significant to understand the host's immunological response, which in turn facilitates the design of the control and prevention strategies. In this review, we aim to provide comprehensive details on the pathogenesis and clinical features of the disease. Moreover, the innate and adaptive immunological responses to AIV and the recent studies conducted on the CD8+ T cell immunity against AIVs are detailed upon. Further, the current status and advancement in the development of AIV vaccines, along with the challenges, are also discussed. The information provided will be helpful in combating the transmission of AIV from birds to humans and, thus, preventing severe outbreaks leading to pandemics worldwide.

Advanced Overview of Biomarkers and Techniques for Early Diagnosis of Alzheimer's Disease.

The development of early non-invasive diagnosis methods and identification of novel biomarkers are necessary for managing Alzheimer's disease (AD) and facilitating effective prognosis and treatment. AD has multi-factorial nature and involves complex molecular mechanism, which causes neuronal degeneration. The primary challenges in early AD detection include patient heterogeneity and lack of precise diagnosis at the preclinical stage. Several cerebrospinal fluid (CSF) and blood biomarkers have been proposed to show excellent diagnosis ability by identifying tau pathology and cerebral amyloid beta (Aß) for AD. Intense research endeavors are being made to develop ultrasensitive detection techniques and find potent biomarkers for early AD diagnosis. To mitigate AD worldwide, understanding various CSF biomarkers, blood biomarkers, and techniques that can be used for early diagnosis is imperative. This review attempts to provide information regarding AD pathophysiology, genetic and non-genetic factors associated with AD, several potential blood and CSF biomarkers, like neurofilament light, neurogranin, Aß, and tau, along with biomarkers under development for AD detection. Besides, numerous techniques, such as neuroimaging, spectroscopic techniques, biosensors, and neuroproteomics, which are being explored to aid early AD detection, have been discussed. The insights thus gained would help in finding potential biomarkers and suitable techniques for the accurate diagnosis of early AD before cognitive dysfunction.

Theranostic Approach for the Management of Osteoporosis.

Osteoporosis (OP) is a bone-metabolic disorder, causing micro-architecture degeneration and a decrease in bone density. Nutritional deficiency, i.e., calcium, vitamin D, and hormonal imbalances are the primary cause for the occurrence of OP. Although conventional diagnostic techniques and therapies are available and found to be effective only at a later stage, though still lack prevention strategies. Thus, the patients tend to suffer incidence of fractures and many difficulties to manage their day-to-day activities at an elderly stage. Numerous nanomaterial(s) possessing unique physicochemical, optical, and electrical properties are reported nowadays to be employed for both early-stage detections of disease and its treatment. Amongst these nanomaterials, superparamagnetic iron oxide nanoparticles (SPIONs) possessing strong magnetic susceptibility, less in vivo toxicity, and surface functionalities are extensively employed for MRI contrast imaging agents in the area of disease diagnosis, and drug delivery tools for various therapies. Therefore, this review highlights the pathophysiology of OP, conventional techniques of diagnosis, and the application of SPIONs for diagnostic and treatment purposes of osteoporosis.

Between-day reliability of trunk orientation measured with smartphone sensors during sit-to-stand in asymptomatic individuals.

BACKGROUND: Trunk kinematics during sit-to-stand is often impaired in individuals with musculoskeletal disorders. Trunk kinematics is commonly assessed in laboratories using motion capture; however, this equipment is often not available outside research centers. Smartphones are widely available and may be a suitable alternative to assess trunk orientation during sit-to-stand remotely. OBJECTIVES: We investigated whether trunk orientation in the sagittal plane during sit-to-stand can be measured reliably between days when collected remotely using smartphones. DESIGN: Cross-sectional study. METHOD: Forty-three asymptomatic participants performed 15 sit-to-stand movements in two separate sessions remotely over videoconferencing. Trunk orientation was measured using each participant's smartphone. Absolute peak trunk orientation in the sagittal plane was extracted during standing, sitting, stand up and sit down. Relative trunk orientation was calculated as the difference between sitting and stand up, or sitting and sit down. Reliability was assessed using Intraclass Correlation Coefficient (ICC2,k), Standard Error of Measurement (SEM) and Minimal Detectable change (MDC). Between day bias and between-gender differences were assessed using T tests. RESULTS: All measures showed good reliability (ICC2,k > 0.80; SEM < 5.6°; MDC < 13.6°) and no between-day bias (p > 0.31). Relative measures were more consistent (ICC2,k > 0.88; SEM < 3.6°; MDC < 9.9°). No between-gender differences were observed for relative orientation (p > 0.75). CONCLUSIONS: Sagittal trunk orientation during sitting, standing, and sit-to-stand can be measured reliably when asymptomatic individuals use their own smartphones supervised over videoconferencing. These findings support the use of smartphone sensors for assessing how trunk orientation changes over time, which may assist physiotherapists assess movement patterns of individuals with musculoskeletal disorders remotely.

Role of Tau in Various Tauopathies, Treatment Approaches, and Emerging Role of Nanotechnology in Neurodegenerative Disorders.

A few protein kinases and phosphatases regulate tau protein phosphorylation and an imbalance in their enzyme activity results in tau hyper-phosphorylation. Aberrant tau phosphorylation causes tau to dissociate from the microtubules and clump together in the cytosol to form neurofibrillary tangles (NFTs), which lead to the progression of neurodegenerative disorders including Alzheimer's disease (AD) and other tauopathies. Hence, targeting hyperphosphorylated tau protein is a restorative approach for treating neurodegenerative tauopathies. The cyclin-dependent kinase (Cdk5) and the glycogen synthase kinase (GSK3ß) have both been implicated in aberrant tau hyperphosphorylation. The limited transport of drugs through the blood-brain barrier (BBB) for reaching the central nervous system (CNS) thus represents a significant problem in the development of drugs. Drug delivery systems based on nanocarriers help solve this problem. In this review, we discuss the tau protein, regulation of tau phosphorylation and abnormal hyperphosphorylation, drugs in use or under clinical trials, and treatment strategies for tauopathies based on the critical role of tau hyperphosphorylation in the pathogenesis of the disease. Pathology of neurodegenerative disease due to hyperphosphorylation and various therapeutic approaches including nanotechnology for its treatment.