Exploring the Significance of Vitamin D Levels as a Biomarker in Ear Diseases: A Narrative Review.

This narrative review examines the role of vitamin D as a biomarker in ear disorders, including benign paroxysmal positional vertigo (BPPV), otitis media, bell's palsy, Meniere's disease, and hearing loss. PubMed, The Cochrane Library, and Google Scholar were utilized to conduct a comprehensive literature search, and findings were combined from studies from 2014 to 2024. As highlighted in this review, there is a consistent association between vitamin D deficiency and an increased risk and recurrence of disease especially in BPPV and otitis media. Its importance as a prognostic biomarker is emphasized in Bell's palsy, where higher levels of deficiencies in vitamin D are associated with higher grades of severity on the House Brackmann grading system. Vitamin D deficiency can also lead to sensorineural hearing loss due to its receptors present in the inner ear or its effect on calcium metabolism. Serum levels of vitamin D have also been shown to influence treatment outcome of sensorineural hearing loss. The role of vitamin D in Meniere's disease is unclear as no cause has been identified for the increase in endolymphatic fluid. The findings of this review emphasize the importance of serum vitamin D as a biomarker in ear disorders and advocate for more studies to be conducted to assess the importance of optimal dosing of vitamin D for the progression and outcome of these diseases.

Metasurface for Engineering Superimposed Ince-Gaussian Beams.

Ince-Gaussian beams (IGBs) are the third complete family of exact and orthogonal solutions of the paraxial wave equation and have been applied in many fields ranging from particle trapping to quantum optics. IGBs play a very important role in optics as they represent the exact and continuous transition modes connecting Laguerre-Gaussian and Hermite-Gaussian beams. The method currently in use suffers from the high cost, complexity, and large volume of the optical system. The superposition of IGBs can generate complicated structured beams with multiple phase and polarization singularities. A metasurface approach is proposed to realizing various superpositions of IGBs without relying on a complicated optical setup. By superimposing IGBs with even and odd modes, multiple phase, and polarization singularities are observed in the resultant beams. The phase and polarization singularities are modulated by setting the initial phase in the design and controlling the incident linear polarization. The compactness of the developed metasurface devices and the unique properties of the generated beams have the potential to impact many practical applications such as particle manipulation, orbital angular momentum spectrum manipulation, and optical communications.

Longitudinally variable 3D optical polarization structures.

Generation and manipulation of three-dimensional (3D) optical polarization structures have received considerable interest because of their distinctive optical features and potential applications. However, the realization of multiple 3D polarization structures in a queue along the light propagation direction has not yet been reported. We propose and experimentally demonstrate a metalens to create longitudinally variable 3D polarization knots. A single metalens can simultaneously generate three distinct 3D polarization knots, which are indirectly validated with a rotating polarizer. The 3D polarization profiles are dynamically modulated by manipulating the linear polarization direction of the incident light. We further showcase the 3D image steganography with the generated 3D polarization structures. The ultrathin nature of metasurfaces and unique properties of the developed metalenses hold promise for lightweight polarization systems applicable to areas such as 3D image steganography and virtual reality.

Dynamic control of hybrid grafted perfect vector vortex beams.

Perfect vector vortex beams (PVVBs) have attracted considerable interest due to their peculiar optical features. PVVBs are typically generated through the superposition of perfect vortex beams, which suffer from the limited number of topological charges (TCs). Furthermore, dynamic control of PVVBs is desirable and has not been reported. We propose and experimentally demonstrate hybrid grafted perfect vector vortex beams (GPVVBs) and their dynamic control. Hybrid GPVVBs are generated through the superposition of grafted perfect vortex beams with a multifunctional metasurface. The generated hybrid GPVVBs possess spatially variant rates of polarization change due to the involvement of more TCs. Each hybrid GPVVB includes different GPVVBs in the same beam, adding more design flexibility. Moreover, these beams are dynamically controlled with a rotating half waveplate. The generated dynamic GPVVBs may find applications in the fields where dynamic control is in high demand, including optical encryption, dense data communication, and multiple particle manipulation.

Compact multi-foci metalens spectrometer.

A lightweight and portable spectrometer is desirable for miniaturization and integration. The unprecedented capability of optical metasurfaces has shown much promise to perform such a task. We propose and experimentally demonstrate a compact high-resolution spectrometer with a multi-foci metalens. The novel metalens is designed based on wavelength and phase multiplexing, which can accurately map the wavelength information into its focal points located on the same plane. The measured wavelengths in the light spectra agree with simulation results upon the illumination of various incident light spectra. The uniqueness of this technique lies in the novel metalens that can simultaneously realize wavelength splitting and light focusing. The compactness and ultrathin nature of the metalens spectrometer render this technology have potential applications in on-chip integrated photonics where spectral analysis and information processing can be performed in a compact platform.

Metasurface-Enabled 3-in-1 Microscopy.

Edge enhancement and polarization detection are critical to image transparent or low-contrast samples. However, currently available systems are limited to performing only a single functionality. To meet the requirement of system integration, there is a pressing need for a microscope with multiple functionalities. Here, we propose and develop a microscope with three different functionalities based on spatial multiplexing and polarization splitting. A novel geometric metasurface (MS) is used to realize a spiral phase profile and two phase gradient profiles along two vertical directions, which can perform such an extremely challenging optical task. This is the first demonstration of a 3-in-1 microscope that can simultaneously obtain five images with different optical properties in an imaging plane for the same sample. Imaging experiments with different samples verify its capability to simultaneously perform edge imaging, polarimetric imaging, and conventional microscope imaging. Benefiting from the compactness and multifunctionality of the optical MS device, the integration does not increase the volume of the microscope. This approach can enable users to visualize the multiple facets of samples in real-time.

Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects.

The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022.

Study of trioleoylglycerol two-layer and adiposome cross-section mimicking four-layer systems through atomic-level simulations.

Adiposomes are artificially prepared lipid droplet (LD)-mimetic structures, which, unlike LDs, do not harbor proteins. The dynamics of interaction between triacylglycerols (TAGs), drug molecule, and phospholipids in adiposomes is currently not well-established. Trioleoylglycerol (TOG) molecule was divided into three parts: two oleoyl tails and one 2-monooleoylglycerol (MOG). Forcefield parameters for two oleoyl tails were adopted from the AMBER18 repository while that of the MOG forcefield was taken from the literature. Charge correction was performed on the MOG forcefield before its utilization. After charge correction, the resulting TOG molecule had zero charge. TOG bilayer (2L) and tetralayer (4L) systems were prepared and simulated. TOG bilayer (2L) systems-modeled from two different initial conformations, the TOG3 conformation and the TOG2:1 conformation-showed that TOG2:1 conformation was more prevailing irrespective of the starting conformation and was subsequently used in further simulations. The hydrated TOG 2L system showed TOG-water solution solubility of 0.051 mol L-1 which is near experimental values. This validated the correct parameterization of the TOG molecule. The simulations of 4L systems showed stable membrane behaviors toward the end of simulations. It was also observed that in the 4L system, the TOG molecules showed the formation of micelles with the drug molecule. Almost six TOGs remained continuously in contact with the drug molecule throughout the simulation. The availability of charge-corrected TOG parameterization is expected to equip future studies with a framework for molecular dynamics simulations of adiposomes and/or LDs at the atomic level.

Color-selective three-dimensional polarization structures.

Polarization as an important degree of freedom for light plays a key role in optics. Structured beams with controlled polarization profiles have diverse applications, such as information encoding, display, medical and biological imaging, and manipulation of microparticles. However, conventional polarization optics can only realize two-dimensional polarization structures in a transverse plane. The emergent ultrathin optical devices consisting of planar nanostructures, so-called metasurfaces, have shown much promise for polarization manipulation. Here we propose and experimentally demonstrate color-selective three-dimensional (3D) polarization structures with a single metasurface. The geometric metasurfaces are designed based on color and phase multiplexing and polarization rotation, creating various 3D polarization knots. Remarkably, different 3D polarization knots in the same observation region can be achieved by controlling the incident wavelengths, providing unprecedented polarization control with color information in 3D space. Our research findings may be of interest to many practical applications such as vector beam generation, virtual reality, volumetric displays, security, and anti-counterfeiting.

Multichannel Superposition of Grafted Perfect Vortex Beams.

Inspired by plant grafting, grafted vortex beams can be formed through grafting two or more helical phase profiles of optical vortex beams. Recently, grafted perfect vortex beams (GPVBs) have attracted much attention due to their unique optical properties and potential applications. However, the current method to generate and manipulate GPVBs requires a complex and bulky optical system, hindering further investigation and limiting its practical applications. Here, a compact metasurface approach for generating and manipulating GPVBs in multiple channels is proposed and demonstrated, which eliminates the need for such a complex optical setup. A single metasurface is utilized to realize various superpositions of GPVBs with different combinations of topological charges in four channels, leading to asymmetric singularity distributions. The positions of singularities in the superimposed beam can be further modulated by introducing an initial phase difference in the metasurface design. The work demonstrates a compact metasurface platform that performs a sophisticated optical task that is very challenging with conventional optics, opening opportunities for the investigation and applications of GPVBs in a wide range of emerging application areas, such as singular optics and quantum science.

Creating Composite Vortex Beams with a Single Geometric Metasurface.

Composite vortex beams (CVBs) have attracted considerable interest recently due to the unique optical properties and potential applications. However, these beams are mainly generated using spatial light modulators, which suffer from large volume, high cost, and limited resolution. Benefiting from the ultrathin nature and unprecedented capability in light manipulation, optical metasurfaces provide a compact platform to perform this task. A metasurface approach to creating these CVBs is proposed and experimentally demonstrated. The design is based on the superposition of multiple circularly polarized vortex beams with different topological charges, which is realized based on a geometric metasurface consisting of metallic nanorods with spatially variant orientations. The effects of the initial phases, amplitude coefficients, incident polarization state, and propagation distance on the generated CVBs, which are in good agreement with the theoretical prediction, are experimentally analyzed. This work has opened a new avenue for engineering CVBs with a minimal footprint, which has promising applications ranging from multiple optical traps to quantum science.

TGF-ß1 signaling can worsen NAFLD with liver fibrosis backdrop.

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of fats in the liver. Relatively benign NAFLD often progresses to fibrosis, cirrhosis, and liver malignancies. Although NAFLD precedes fibrosis, continuous lipid overload keeps fueling fibrosis and the process of disease progression remains unhindered. It is well known that TGF-ß1 plays its part in liver fibrosis, yet its effects on liver lipid overload remain unknown. As TGF-ß1 signaling has been increasingly attempted to manage liver fibrosis, its actions on the primary suspect (NAFLD) are easily ignored. The complex interaction of inflammatory stress and lipid accumulation aided by mediators scuh as pro-inflammatory interleukins and TGF-ß1 forms the basis of NAFLD progression. Anticipatorily, the inhibition of TGF-ß1 signaling during anti-fibrotic treatment should reverse the NAFLD though the data remain scattered on this subject to date. TGF-ß1 signaling pathway is an important drug target in liver fibrosis and abundant literature is available on it, but its direct effects on NAFLD are rarely studied. This review aims to cover the pathogenesis of NAFLD focusing on the role of the TGF-ß1 in the disease progression, especially in the backdrop of liver fibrosis.

The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19-Results from a pragmatic randomized clinical trial.

Background: Curcumin (CUR) and quercetin (QUE), two natural polyphenols, possess diverse biological activities including broad-spectrum antiviral, antioxidant, and immunomodulatory effects. Both CUR and QUE have shown inhibition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in in vitro assays. Objective: In the present study we aimed to assess the possible treatment benefits of a combined curcumin and quercetin (CUR-QUE) oral supplement, alongside standard of care (SOC), in the early-stage COVID-19 infection. Methods: This was an exploratory, pragmatic, open-label, randomized controlled clinical trial, conducted at the Department of Pathology, Liaquat University of Medical and Health Sciences, Jamshoro, PK. The study compared the treatment effect of an oral CUR-QUE supplement plus SOC vs. SOC alone, in the early-stage/mild to moderately symptomatic COVID-19 outpatients. Patients were randomized in a 1:1 ratio to CUR-QUE (n = 25) and control (n = 25) treatment groups. The CUR-QUE supplementation consisted of a daily intake of 168 mg curcumin and 260 mg quercetin, as two soft capsules, to be taken twice a day at home for 14 days. Results: After one-week of treatment, most of the patients in the CUR-QUE group showed an expedited clearance of the viral infection i.e., 18 (72.0%) vs. 6 (24.0%) patients in the control group tested negative for SARS-CoV-2 in the nasal-oropharyngeal swab reverse transcription-polymerase chain reaction (RT-PCR) analysis (p = 0.0002). In addition, COVID-19-associated acute symptoms were also speedily resolved in the CUR-QUE treated patients, i.e., 10 (40.0%) vs. 4 (16.0%) patients in the control group (p = 0.061). The CUR-QUE supplementation therapy was well-tolerated by all 25 patients and no treatment-emergent effects or serious adverse events were reported. Conclusion: The results revealed in this exploratory study suggest a possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19. It is proposed that the two agents possibly acting in synergy, interfere the SARS-CoV-2 replication, and thus help a speedy recovery in the early-stage of COVID-19. Further research is highly encouraged. Clinical trial registration: Clinicaltrials.gov, Identifier NCT04603690.

In Silico and In Vivo: Evaluating the Therapeutic Potential of Kaempferol, Quercetin, and Catechin to Treat Chronic Epilepsy in a Rat Model.

Recently, alternative therapies are gaining popularity in the treatment of epilepsy. The present study aimed to find out the antiepileptic potential of quercetin, catechin, and kaempferol. In vivo and in silico experiments were conducted to investigate their therapeutic potential. 25 mg/kg/day of pentylenetetrazole was administered for 4 weeks after epilepsy was induced in the rats; this was followed by the behavioral studies and histological analysis of rat brain slices. Binding affinities of kaempferol, quercetin, and catechin were assessed by performing in silico studies. Kaempferol, quercetin, and catechin were found to have the highest binding affinity with the synaptic vesicle 2A (SV2A) protein, comparable to standard levetiracetam (LEV). The mRNA levels of SV2A, as well as the expression of TNF, IL 6, IL 1 beta, NFkB, IL 1Ra, IL 4, and IL 10, were investigated using qPCR. Our results indicate for the first time that SV2A is also a transporter of understudied phytoflavonoids, due to which a significant improvement was observed in epileptic parameters. The mRNA levels of SV2A were found to be significantly elevated in the PF-treated rats when compared with those of the control rats with epilepsy. Additionally, downregulation of the pro-inflammatory cytokines and upregulation of the anti-inflammatory cytokines were also noted in the PF-treated groups. It is concluded that kaempferol, quercetin, and catechin can effectively decrease the epileptic seizures in our chronic epilepsy rat model to a level that is comparable to the antiepileptic effects induced by levetiracetam drug.

Abutilon indicum Exhibits Anxiolytic and Antidepressant Effects in Mice Models.

Abutilon indicum Linn (A. indicum) is native to tropical and subtropical zones and traditionally used in ulcer, diabetes, piles, jaundice, gonorrhoea and leprosy. Erstwhile phytochemical analysis showed the presence of flavonoids, sesquiterpenes, gallic acid, ß-sitosterols, geraniol, and caryophyllene. The study identifies the antidepressant potential of the crude methanolic extract of A. indicum (Ai.Cr). Crude methanolic extract of leaves and bark was prepared using maceration and freeze-drying. Forty Swiss-albino mice were divided into five groups containing eight mice each. Designated groups were administered with normal saline, Ai.Cr (30, 50, and 100 mg/kg) and diazepam (1 mg/kg) or fluoxetine (10 mg/kg) intra-peritoneally. Light and Dark Exploration (LDE), Elevated Plus Maze (EPM) and Hole Board (HB) test were used for anxiolytic activity testing, while forced swim and tail suspension model were used for the evaluation of antidepressant potential of Ai.Cr. Results showed that mice spent more time in light; passed more duration in open arms and raised number of head poking in respective anxiolytic LDE, EPM, and HB tests. Similarly, mobility time was raised in forced swim and tail suspension antidepressant testing. Ai.Cr has significant dose dependent antidepressant and anxiolytic potential, which peaks at highest dose (100 mg/kg) used in this study. A. indicum has significant pharmacological potential against anxiety and depression.

Complexity of antidiabetic medication regimen is associated with increased diabetes-related distress in persons with type 2 diabetes mellitus.

INTRODUCTION: Diabetes-related distress is present in a high proportion of people with type 2 diabetes mellitus. We hypothesized that complexity of the antidiabetic medication regimen is a factor that is associated with diabetes-related distress. RESEARCH DESIGN AND METHODS: This was a retrospective study including a group of 74 patients managed at a tertiary care center. Patients with type 1 diabetes mellitus, steroid-induced diabetes, post-transplant diabetes, and other types of diabetes were excluded. Patients were screened using the Diabetes Distress Scale-2 (DDS-2). A Diabetes Medication Complexity Scoring (DMCS) system was developed to objectively assess the diabetes medication complexity. Based on DMCS, participants were categorized into three groups: low (n=26), moderate (n=22), and high (n=26) medication complexity. RESULTS: Complexity groups were similar in sociodemographic characteristics, diabetes duration, body mass index, and blood pressure as well as the prevalence of hypertension, hyperlipidemia and hypoglycemic episodes. However, there were significant differences for HbA1c with higher HbA1c in the high and moderate complexity groups than in the low group (p=0.006). The microvascular complications were also more common in higher complexity groups (p=0.003). The prevalence of diabetes-related distress (DDS-2 ≥6) was 34.6% in the low, 36.4% in the moderate and 69.2% in the high complexity groups (p=0.021). There were significant differences in DDS-2 score among complexity groups (p=0.009), with higher DDS-2 score in the high complexity group compared with the moderate (p=0.008) and low complexity groups (p=0.009). The difference in DDS-2 score remained significant after adjusting for HbA1c (p=0.024) but did not reach statistical significance after controlling for both HbA1c and microvascular complications (p=0.163). CONCLUSIONS: A complex antidiabetic medication regimen may be associated with high levels of diabetes-related distress.

Comparative proteomics reveals that lipid droplet-anchored mitochondria are more sensitive to cold in brown adipocytes.

Brown adipose tissue (BAT) is specialized for uncoupled heat production through mitochondrion fueled majorly from fatty acids (FAs) of lipid droplets (LDs). How the interaction between the two organelles contributes the generation of heat remains elusive. Here, we report that LD-anchored mitochondria (LDAM) were observed in the BAT of mice raised at three different temperatures, 30 °C, 23 °C, and 6 °C. The biochemical analyses including Western blotting of electron transport chain subunits showed that LDAM were functional. Comparative proteomics analysis was conducted, which revealed differential expressions of proteins between LDAM and cytoplasmic mitochondria (CM) at different temperatures. Higher expressions of proteins at low temperature were observed for i) FA ß-oxidation in LDAM including FA synthesis and uncoupling, ii) pseudo-futile cycle in CM, and iii) two shuttle systems: glycerol 3-phosphate in both CM and LDAM and citrate malate in CM. Together, these results suggest that LDs and LDAM form a preorganized and functional organelle complex that permits the rapid response to cold.

Role of Adaptor Protein Myeloid Differentiation 88 (MyD88) in Post-Subarachnoid Hemorrhage Inflammation: A Systematic Review.

Myeloid differentiation 88 (MyD88) is a well-established inflammatory adaptor protein. It is one of the essential downstream proteins of the toll-like receptor 4 (TLR4) signaling pathway. TLRs are pattern recognition receptors that are usually activated by the damage-associated molecular pattern molecules (DAMPs). Sterile inflammation is triggered by the endogenous DAMPs released in response to global cerebral ischemia and from extravasated blood after subarachnoid hemorrhage (SAH). In this review, we highlight the importance of the neuroinflammatory role of the MyD88 in the SAH. We also explore a few possible pharmacological agents that can be used to decrease SAH-associated neuroinflammation by modulating the MyD88 dependent functions. Pharmacological agents such as flavonoids, melatonin, fluoxetine, pentoxifylline and progesterone have been investigated experimentally to reduce the SAH-associated inflammation. Inhibition of the MyD88 not only reduces the expression of pro-inflammatory cytokines, but also potentially inhibits other processes that can augment the SAH associated inflammation. Further investigations are required to translate these findings in the clinical setting.

Rab18 binds PLIN2 and ACSL3 to mediate lipid droplet dynamics.

Lipid droplet (LD) is a vital organelle governing lipid homeostasis and Rab18 has been linked to lipid metabolism. However, the mechanisms of Rab18-mediated LD dynamics in myoblast cells remain elusive. Here, we report that Rab18 plays an important role in oleic acid (OA)-induced LD accumulation in mouse myoblast C2C12 cells. Rab18 was translocated from the endoplasmic reticulum (ER) to LDs during LD accumulation, which was regulated by perilipin 2 (PLIN2), a major LD protein. LD-associated Rab18 bound with the C terminus of PLIN2 and the LD localization of Rab18 was diminished when PLIN2 was depleted. Moreover, loss of function of Rab18 led to reduced triacylglycerol (TAG) level and fewer but larger LDs. In contrast, overexpression of Rab18 resulted in elevated TAG content and LD number. Furthermore, LD-associated Rab18 interacted with acyl-CoA synthetase long-chain family member 3 (ACSL3), which in turn promoted the LD localization of this protein. These data show that Rab18 interacts with PLIN2 and forms a complex with PLIN2 and ACSL3, which plays a critical role in LD accumulation and dynamics of myoblast cells.