Selective Extraction and Quantification of Hemoglobin Based on a Novel Molecularly Imprinted Nanopolymeric Structure of Poly(acrylamide-vinyl imidazole).

Imbalances in hemoglobin (Hb) levels can lead to conditions such as anemia or polycythemia, emphasizing the importance of precise Hb extraction from blood. To address this, a novel synthetic imprinted polymer was meticulously developed for capturing and separating Hb. Poly(acrylamide-vinylimidazole) nanopolymer (poly(AAm-VIM)) was synthesized using acrylamide and vinyl imidazole as functional monomers through surfactant-free emulsion polymerization. Characterization using FTIR, particle size, zeta potential, and SEM ensured the polymer's structure. The Hb-imprinted nanopolymer (Hb-poly(AAm-VIM)) demonstrated notable specificity, with a calculated Hb-specific adsorption value (Qmax) of 3.7377 mg/g in a medium containing 2.5 mg/mL Hb. The molecularly imprinted polymer (MIP) exhibited approximately 5 times higher Hb adsorption than the nonimprinted polymer (NIP). Under the same conditions, the imprinted nanopolymer displayed 2.39 and 2.17 times greater selectivity for Hb over competing proteins such as bovine serum albumin (BSA) and lysozyme (Lys), respectively. Also, SDS-PAGE analysis results confirmed the purification of Hb by the molecularly imprinted nanopolymer. These results underscore the heightened specificity and efficacy of the molecularly imprinted nanopolymer in selectively targeting Hb atoms among other proteins. Incorporating such polymers is justified by their notable affinity, cost-effectiveness, and facile production. This research contributes valuable insights into optimizing synthetic imprinted polymers for efficient Hb extraction, with potential in medical diagnostics and treatment applications.

BRAT1-Associated Leukodystrophy Exacerbated by Classic Hodgkin Lymphoma-Directed Therapy.

INTRODUCTION: BRCA1-associated ataxia-telangiectasia-mutated activator-1 (BRAT1) is responsible for cell cycle surveillance and mitochondrial function. The implications of adult-onset BRAT1-variant and the resulting phenotypic neurocognitive and imaging features have not been previously described. CASE REPORT: A 66-year-old man with a recent diagnosis of classic Hodgkin lymphoma was referred to neuro-oncology for cognitive and motor decline, and progressive cerebral white matter changes noted on magnetic resonance imaging (MRI). A neurological examination revealed global weakness, broad-based gait, and bilateral extensor plantar responses. Brain MRI demonstrated periventricular, deep, and subcortical white matter T2/FLAIR hyperintensities without contrast enhancement. Cerebral spinal fluid studies were unremarkable. A GeneDX genetic leukodystrophy panel conduction revealed a pathogenic variant (c.294dupA; p.L99TfsX92) resulting in a truncated protein of BRAT1, along with a variant of uncertain significance (c.746A>G;p.E249G). A presumptive diagnosis of late-onset leukoencephalopathy secondary to the BRAT1 variant was made. In an attempt to combat his mitochondrial dysfunction, he was initiated on a mitochondrial cocktail, including B-100 complex and coenzyme Q10. He began lymphoma-directed combination chemotherapy and developed precipitous functional decline after 2 cycles of therapy. Compared with prechemotherapy imaging, repeat positron emission tomography/computed tomography metabolic imaging showed a response after 3 cycles of chemotherapy; however, repeat brain MRI showed worsening diffuse white matter hyperintensities and cerebral atrophy. CONCLUSION: Given the variability in phenotypes and clinical onset, leukodystrophies can be a diagnostic challenge. This case demonstrated progressive BRAT1-associated leukodystrophy exacerbated by chemotherapy-induced toxic leukoencephalopathy. Mitochondrial energy deficiency in the context of multiple metabolic insults was likely underlying the progressive neurological decline observed in this case of genetic leukodystrophy.

Wearable Nano-Based Gas Sensors for Environmental Monitoring and Encountered Challenges in Optimization.

With a rising emphasis on public safety and quality of life, there is an urgent need to ensure optimal air quality, both indoors and outdoors. Detecting toxic gaseous compounds plays a pivotal role in shaping our sustainable future. This review aims to elucidate the advancements in smart wearable (nano)sensors for monitoring harmful gaseous pollutants, such as ammonia (NH3), nitric oxide (NO), nitrous oxide (N2O), nitrogen dioxide (NO2), carbon monoxide (CO), carbon dioxide (CO2), hydrogen sulfide (H2S), sulfur dioxide (SO2), ozone (O3), hydrocarbons (CxHy), and hydrogen fluoride (HF). Differentiating this review from its predecessors, we shed light on the challenges faced in enhancing sensor performance and offer a deep dive into the evolution of sensing materials, wearable substrates, electrodes, and types of sensors. Noteworthy materials for robust detection systems encompass 2D nanostructures, carbon nanomaterials, conducting polymers, nanohybrids, and metal oxide semiconductors. A dedicated section dissects the significance of circuit integration, miniaturization, real-time sensing, repeatability, reusability, power efficiency, gas-sensitive material deposition, selectivity, sensitivity, stability, and response/recovery time, pinpointing gaps in the current knowledge and offering avenues for further research. To conclude, we provide insights and suggestions for the prospective trajectory of smart wearable nanosensors in addressing the extant challenges.

Sex and Gender Influence Urinary Symptoms and Management in Multiple System Atrophy.

OBJECTIVE: Multiple system atrophy (MSA) is characterized by urinary dysfunction, yet the influence of sex and gender on urinary symptoms and treatment is unclear. We sought to characterize sex and gender differences in the symptomatology, evaluation, and management of urinary dysfunction in patients with MSA. METHODS: Patients with MSA evaluated at our institution were reviewed and stratified by sex. RESULTS: While the prevalence of urinary symptoms was similar in male and female patients, incontinence was more common in females. Despite this, males and females underwent postvoid residual (PVR) measurement at similar rates. While catheterization rates were similar when PVR was measured, males were more than twice as likely to be catheterized than females in the absence of PVR measurement. CONCLUSION: Urinary symptoms are common in MSA, but their presentation differs between males and females. The difference in catheterization rates may be driven by a gender disparity in referrals for PVR, which can guide treatment.

Antioxidant Effects of Bioactive Glasses (BGs) and Their Significance in Tissue Engineering Strategies.

Elevated levels of oxidative stress are usually observed following injuries, leading to impaired tissue repair due to oxidation-related chronic inflammation. Several attempts have been made to manage this unfavorable situation, and the use of biomaterials with antioxidant activity is showing great promise in tissue engineering and regenerative medicine approaches. Bioactive glasses (BGs) are a versatile group of inorganic substances that exhibit an outstanding regenerative capacity for both hard and soft damaged tissues. The chemical composition of BGs provides a great opportunity for imparting specific biological activities to them. On this point, BGs may easily become antioxidant substances through simple physicochemical modifications. For example, particular antioxidant elements (mostly cerium (Ce)) can be added to the basic composition of the glasses. On the other hand, grafting natural antioxidant substances (e.g., polyphenols) on the BG surface is feasible for making antioxidant substitutes with promising results in vitro. Mesoporous BGs (MBGs) were demonstrated to have unique merits compared with melt-derived BGs since they make it possible to load antioxidants and deliver them to the desired locations. However, there are actually limited in vivo experimental studies on the capability of modified BGs for scavenging free radicals (e.g., reactive oxygen species (ROS)). Therefore, more research is required to determine the actual potential of BGs in decreasing oxidative stress and subsequently improving tissue repair and regeneration. The present work aims to highlight the potential of different types of BGs in modulating oxidative stress and subsequently improving tissue healing.

Outcomes of initial and repeat micro-pulse transscleral cyclophotocoagulation in adult glaucoma patients.

BACKGROUND: Micro-pulse transscleral cyclophotocoagulation (MP-TSCPC) has continued to gain popularity as a treatment in adult glaucoma patients. Thus far there is limited evidence reporting the efficaciousness and safety of retreatment. OBJECTIVE: To evaluate safety and efficacy of primary and repeat MP-TSCPC procedures. METHODS: Thirty-four of 67 eyes who failed to achieve target IOP from initial MP-TSCPC underwent repeat MP-TSCPC and followed for a minimum of 6 months. All treatments were performed using the laser power of 2000 or 2250 mW, duration of 100-200 s, and a velocity 16-20 s per hemisphere swipe. Success criteria were defined as intraocular pressure (IOP) reduction of greater than 20% from baseline or any medication reduction without additional glaucoma procedures at 6 months after repeat MP-TSCPC. The 6-month success rate after repeat MP-TSCPC was also compared to that of initial MP-TSCPC in the same group of eyes. RESULTS: Mean baseline IOP before the repeat MP-TSCPC was 23.0 + /- 5.3 on 3.0 + /- 1.4 medications. At 6 months, mean post-op IOP was 18.2 + /- 5.4 (21.9% reduction, p < 0.002), with mean medication staying relatively the same (p = .976). Success rate was increased from 23.5% to 44.1% with the repeat procedure compared to that of initial procedure (p = 0.123). Mean IOP reduction was also greater after repeat MP-TSCPC (18.7%, p < 0.002) when compared to initial MP-TSCPC (10.4%). No adverse events occurred. CONCLUSIONS: MP-TSCPC is a safe and effective non-invasive means to lower IOP in a variety of glaucoma patients. While over 50% (34/67) of eyes required repeat MP-TSCPC, repeat treatment resulted in greater success rates and IOP reduction without any adverse events when using the total energy between 112 and 150 J.

Osteogenic Potential of Magnesium (Mg)-Doped Multicomponent Bioactive Glass: In Vitro and In Vivo Animal Studies.

The use of bioactive glasses (BGs) has been quite fruitful in hard tissue engineering due to the capability of these materials to bond to living bone. In this work, a melt-derived magnesium (Mg)-doped BG (composition: 45SiO2-3P2O5-26CaO-15Na2O-7MgO-4K2O (mol.%)) was synthesized for being used in bone reconstruction. The prepared BGs were then manufactured as three-dimensional (3D) scaffolds by using the sponge replica approach. The microstructure of the samples was assessed by X-ray diffraction (XRD) and the surface morphology was observed by using scanning electron microscopy (SEM). The in vitro bioactivity and the release of osteo-stimulatory Mg2+ ions from the prepared samples were investigated over 7 days of incubation in simulated body fluids (SBF). In vitro cellular analyses revealed the compatibility of the Mg-doped BGs with human osteosarcoma cells (MG-63 cell line). Moreover, the Mg-doped BGs could induce bone nodule formation in vitro and improve the migratory ability of human umbilical vein endothelial cells (HUVECs). In vivo osteogenic capacity was further evaluated by implanting the BG-derived scaffolds into surgically-created critical-size bone defects in rats. Histological and immunohistological observations revealed an appropriate bone regeneration in the animals receiving the glass-based scaffolds after 12 weeks of surgery. In conclusion, our study indicates the effectiveness of the Mg-doped BGs in stimulating osteogenesis in both in vitro and in vivo conditions.

Transition Metal Dichalcogenides (TMDC)-Based Nanozymes for Biosensing and Therapeutic Applications.

Nanozymes, a type of nanomaterial with enzyme-like properties, are a promising alternative to natural enzymes. In particular, transition metal dichalcogenides (TMDCs, with the general formula MX2, where M represents a transition metal and X is a chalcogen element)-based nanozymes have demonstrated exceptional potential in the healthcare and diagnostic sectors. TMDCs have different enzymatic properties due to their unique nano-architecture, high surface area, and semiconducting properties with tunable band gaps. Furthermore, the compatibility of TMDCs with various chemical or physical modification strategies provide a simple and scalable way to engineer and control their enzymatic activity. Here, we discuss recent advances made with TMDC-based nanozymes for biosensing and therapeutic applications. We also discuss their synthesis strategies, various enzymatic properties, current challenges, and the outlook for future developments in this field.

Spinal Cord Injury Management through the Combination of Stem Cells and Implantable 3D Bioprinted Platforms.

Spinal cord injury (SCI) has a major impact on affected patients due to its pathological consequences and absence of capacity for self-repair. Currently available therapies are unable to restore lost neural functions. Thus, there is a pressing need to develop novel treatments that will promote functional repair after SCI. Several experimental approaches have been explored to tackle SCI, including the combination of stem cells and 3D bioprinting. Implanted multipotent stem cells with self-renewing capacity and the ability to differentiate to a diversity of cell types are promising candidates for replacing dead cells in injured sites and restoring disrupted neural circuits. However, implanted stem cells need protection from the inflammatory agents in the injured area and support to guide them to appropriate differentiation. Not only are 3D bioprinted scaffolds able to protect stem cells, but they can also promote their differentiation and functional integration at the site of injury. In this review, we showcase some recent advances in the use of stem cells for the treatment of SCI, different types of 3D bioprinting methods, and the combined application of stem cells and 3D bioprinting technique for effective repair of SCI.

Current and Upcoming Treatment Modalities in Myasthenia Gravis.

ABSTRACT: Myasthenia gravis (MG) is one of the extensively studied autoimmune disorder. There has been a dramatic increase in research to further understand molecular pathogenesis of MG and clinical trials for new drugs in MG treatment in the past decade. This review article is to consolidate the available information in simple terms with students, residents, and fellows as target audience for easy learning and help application of this knowledge to clinical practice.

Cardiomyopathy, Proximal Myopathy, Camptocormia, and Novel Filamin C (FLNC) Variant: A Case Report.

BACKGROUND Filamin C (FLNC) is an actin crosslinking protein that provides structural support for the sarcomere. The exact function of FLNC is unknown; however, mutations have been reported in myopathies and cardiomyopathies, but rarely both. In this paper, we describe a case of adult-onset camptocormia, proximal myopathy, and cardiomyopathy and an intronic FLNC mutation. CASE REPORT A 56-year-old man was referred to the neurology clinic for truncal weakness. The patient reported having curvature of his spine, which he said his mother also had prior to her dying suddenly due to a "cardiac issue." The patient was found to have fatty infiltration of the periscapular and paraspinal muscles. Additionally, electromyography revealed irritable myopathy of the paraspinal muscles, and an echocardiogram revealed an ejection fraction of 40%. A genetic panel conducted through PerkinElmer Genomics revealed a heterozygous mutation c.1210+3A>G in the intron region of FLNC. Due to his low ejection fraction and family history of sudden cardiac death, he received an implantable cardioverter-defibrillator and began carvedilol. The patient received physical therapy for camptocormia. CONCLUSIONS The variability in genotypic-phenotypic relationships of FLNC mutations is a growing area of research. It is important to increase awareness to further the development of gene-targeted therapies. We hope this unique clinical presentation of co-occurring skeletal and cardiomyopathy secondary to an intronic mutation will increase awareness of the broad phenotypic spectrum of FLNC mutations.

Mesoporous Silica Nanoparticles and Mesoporous Bioactive Glasses for Wound Management: From Skin Regeneration to Cancer Therapy.

Exploring new therapies for managing skin wounds is under progress and, in this regard, mesoporous silica nanoparticles (MSNs) and mesoporous bioactive glasses (MBGs) offer great opportunities in treating acute, chronic, and malignant wounds. In general, therapeutic effectiveness of both MSNs and MBGs in different formulations (fine powder, fibers, composites etc.) has been proved over all the four stages of normal wound healing including hemostasis, inflammation, proliferation, and remodeling. The main merits of these porous substances can be summarized as their excellent biocompatibility and the ability of loading and delivering a wide range of both hydrophobic and hydrophilic bioactive molecules and chemicals. In addition, doping with inorganic elements (e.g., Cu, Ga, and Ta) into MSNs and MBGs structure is a feasible and practical approach to prepare customized materials for improved skin regeneration. Nowadays, MSNs and MBGs could be utilized in the concept of targeted therapy of skin malignancies (e.g., melanoma) by grafting of specific ligands. Since potential effects of various parameters including the chemical composition, particle size/morphology, textural properties, and surface chemistry should be comprehensively determined via cellular in vitro and in vivo assays, it seems still too early to draw a conclusion on ultimate efficacy of MSNs and MBGs in skin regeneration. In this regard, there are some concerns over the final fate of MSNs and MBGs in the wound site plus optimal dosages for achieving the best outcomes that deserve careful investigation in the future.

Satisfaction of Telehealth in Patients With Established Neuromuscular Disorders.

Introduction/aims: Determine established neuromuscular disease patients' satisfaction with telehealth during the COVID-19 pandemic. Methods: We received 50 completed Utah telehealth satisfaction surveys from a cohort of 90 from April 2020 to June 2020. Returning neuromuscular disease patients rated seven aspects from 1 (strongly disagree) to 5 (strongly agree): Communication, timeliness of physician, picture quality, sound quality, protection of privacy, the comfort of the physical exam, the ease of healthcare, and whether patients would prefer "in-person" visits despite safety precaution. A favorable response was defined as a response of "Agree" or "Strongly Agree" to the survey questions. An independent t-test, Fisher's or chi-square test were used to compare demographic factors on outcomes for each survey question. Results: The average age was 47.54 ± 20.63, 54% were female, 70% from rural areas, 60% had family present "webside," and 14% had family present remotely. The majority of patients reported "Agree" or "Strongly Agree" to each survey question assessing their telehealth satisfaction, except for whether patients preferred in-person appointments. Demographic factors, including location and clinical diagnosis, did not influence survey responses. Discussion: The vast majority of established neuromuscular disease patients responded favorably to their telehealth experience during the COVID-19 pandemic.

Protective effects of a standardized extract of Iris germanica on pancreas and liver in streptozotocin-induced diabetic rats.

BACKGROUND AND PURPOSE: Previous studies have shown the antioxidant, anti-inflammatory, immunomodulatory, and hypolipidemic activities of Iris germanica. The aim of the present study was to evaluate the protective effects of hydroalcoholic extract of Iris germanica rhizomes on streptozotocin-induced diabetic rats. EXPERIMENTAL APPROACH: Twenty-four male Wistar rats were randomly assigned into four groups including a normal control group, diabetic control group, diabetic groups treated for 4 weeks with 100 and 200 mg/kg/day of the Iris germanica extract (IGE). FINDINGS/RESULTS: Induction of diabetes significantly decreased the body weight gain and considerably increased the serum levels of glucose, triglyceride, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Diabetes also diminished the antioxidant capacity of the liver (decrease of thiol groups) and significantly degenerated pancreatic islands. The IGE at both doses of 100 and 200 mg/kg significantly reduced the levels of glucose, triglyceride, AST, ALT, and ALP. Moreover, IGE increased the total antioxidant capacity of the liver and ameliorated pancreatic island morphology. The extract had no significant effect on body weight and BUN level. CONCLUSION AND IMPLICATION: These findings suggest that Iris germanica rhizomes inhibits the progression of hyperglycemia and hypertriglyceridemia and has protective effects against diabetes-induced injury of the liver and pancreas. Therefore, this plant has the potential to be used as a natural product for controlling diabetes.

Protective Effects of Morus nigra and Its Phytochemicals against Hepatotoxicity: A Review of Preclinical Studies.

BACKGROUND: Our liver has a variety of vital functions including removing poisons, storing energy, immunological roles, and secretory and excretory functions. It may face some kinds of diseases caused by viruses, hepatotoxic chemicals, drugs, alcohol, and inherited disorders. Oxidative stress and inflammation are in the core of mechanisms of liver damages induced by viruses or chemical agents. SUMMARY: Morus nigra (M. nigra), generally known as black mulberry, exhibited wide-spectrum pharmacological effects including antidiabetic, antinociceptive, anticancer, and hepatoprotective activities. Different parts of this plant particularly the fruit and leaf have shown beneficial effects on hepatocytes in cell culture and animal models of liver damages induced by chemicals (e.g., CCl4), drugs (e.g., paracetamol), diet (e.g., high fat), diabetes, etc. The beneficial effects of M. nigra on the liver are attributed to the presence of considerable amounts of phenolic compounds such as anthocyanins, flavonols, and phenolic acids. The present review is aimed to focus on the hepatoprotective activities of M. nigra and its phytochemicals and the mechanisms responsible for these activities. Key Messages: The evidence reviewed in this study can help design clinical trials on M. nigra in patients with liver disorders and develop a hepatoprotective herbal medicine.

Morus nigra L. extract prolongs survival of rats with hepatocellular carcinoma.

Morus nigra is a rich source of anthocyanins, phytochemicals that have anticancer effects. This study aimed to investigate the effects of M. nigra extract (MNE) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC). Male Sprague-Dawley rats were assigned into four groups (n = 10): control, DEN, and DEN +100 or 400 mg/kg of MNE. After 4 months, the DEN group showed a significant mortality rate, hepatic lipid peroxidation, dysplastic nodules in the cirrhotic liver, and an increase of blood bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Also, the body weight gain, blood albumin and glucose, liver antioxidant capacity (thiol groups), and some hematological parameters (RBC, hematocrit, hemoglobin, and platelet) were significantly decreased in the DEN group. MNE significantly increased survival, reduced the size of HCC nodules, improved liver oxidant/antioxidant status, and prevented the above-mentioned changes in the blood (except ALP, glucose, and platelet). Quantitative real-time PCR showed that MNE decreased the expression of Wnt4 and ß-catenin, while had no significant effect on PI3K, Akt, and PTEN expression. The MNE did not exhibit antiproliferative activity against HepG2 liver cancer cells. In conclusion, MNE exhibits a hepatoprotective effect through inhibiting oxidative stress and Wnt4/ß-catenin pathway and therefore prolongs the survival of rats with HCC.

Preparation and Applications of Superparamagnetic Iron Oxide Nanoparticles in Novel Drug Delivery Systems: An Overview.

Nanocarriers, as drug delivery frameworks, have been intended to enhance the pharmacological and restorative properties of traditional medications. The consolidation of medical atoms as nanocarriers can function as the drug that is required against corruption, as well as offer the desired potential outcomes in regards to targeting and controlled discharge. In the present overview article, applications of magnetic nanoparticles (MNPs) in medication conveyance are outlined. The MNPs have increased the excitement due to their biocompatibility - low poisonous quality, and their capacity to be handled in a magnetic field, which enables their applications as drug-bearing vehicles. The simplicity of surface modification of these particles can provide opportunities for targeting the moieties that are linked to the particle surface. We trust that the intriguing particles will gain further attention alongside achievements in the current ones in the near future.

Cerium Oxide Nanoparticles (Nanoceria): Hopes in Soft Tissue Engineering.

Several biocompatible materials have been applied for managing soft tissue lesions; cerium oxide nanoparticles (CNPs, or nanoceria) are among the most promising candidates due to their outstanding properties, including antioxidant, anti-inflammatory, antibacterial, and angiogenic activities. Much attention should be paid to the physical properties of nanoceria, since most of its biological characteristics are directly determined by some of these relevant parameters, including the particle size and shape. Nanoceria, either in bare or functionalized forms, showed the excellent capability of accelerating the healing process of both acute and chronic wounds. The skin, heart, nervous system, and ophthalmic tissues are the main targets of nanoceria-based therapies, and the other soft tissues may also be evaluated in upcoming experimental studies. For the repair and regeneration of soft tissue damage and defects, nanoceria-incorporated film, hydrogel, and nanofibrous scaffolds have been proven to be highly suitable replacements with satisfactory outcomes. Still, some concerns have remained regarding the long-term effects of nanoceria administration for human tissues and organs, such as its clearance from the vital organs. Moreover, looking at the future, it seems necessary to design and develop three-dimensional (3D) printed scaffolds containing nanoceria for possible use in the concepts of personalized medicine.