Can hospitalists improve COVID-19 vaccination rates?

Three years after the start of the SARS-CoV-2 virus (COVID-19) pandemic, its effects continue to affect society and COVID-19 vaccination campaigns continue to be a topic of controversy and inconsistent practice. After experiencing spikes in COVID-19 cases, our University of California Davis Health Division of Hospital Medicine sought to understand the reasons underlying the low COVID-19 vaccination rates in our county and find approaches to improve the number of vaccinations among adults admitted to the inpatient setting. This quality improvement project aimed to increase COVID-19 primary and booster vaccine efforts through a multi-pronged approach of increased collaboration with specialised staff and optimisation of use of our electronic health record system.Our key interventions focused on developing a visual reminder of COVID-19 vaccine status using the functionality of our electronic medical record (EMR), standardising documentation of COVID-19 vaccine status and enhancing team-based vaccination discussions through team huddles and partnering with inpatient care coordinators. While our grassroots approach enhanced COVID-19 vaccination rates in the inpatient setting and had additional benefits such as increased collaboration among teams, system-level efforts often made a greater impact at our healthcare centre. For other institutions interested in increasing COVID-19 vaccination rates, our top three recommendations include integrating vaccination into pre-existing workflows, optimising EMR functionality and increasing vaccine accessibility in the inpatient setting.

Gelatin/Polyacrylamide-Based Antimicrobial and Self-Healing Hydrogel Film for Wound Healing Application.

In this study, a self-healing, adhesive, and superabsorbent film made of gelatin, poly(acrylamide), and boric acid (GelAA) was successfully synthesized using a free radical reaction mechanism. The optimized film showed a remarkable 2865 ± 42% water absorptivity and also exhibited excellent self-healing behavior. The GelAA films were further loaded with silver nanoclusters (AgNCs) and ursodeoxycholic acid (UDC) (loading efficiency = 10%) to develop UDC/Ag/GelAA films. The loading of AgNCs in UDC/Ag/GelAA films helped in exhibiting 99.99 ± 0.01% antibacterial activity against both Gram-positive and Gram-negative bacteria, making them very effective against bacterial infections. Additionally, UDC/Ag/GelAA films had 77.19 ± 0.52% porosity and showed 90% of UDC release in 30 h, which helps in improving the cell proliferation. Our research provides an easy but highly effective process for synthesizing a hydrogel film, which is an intriguing choice for wound healing applications without the use of antibiotics.

Biodegradable Dextrin-Based Microgels for Slow Release of Dual Fertilizers for Sustainable Agriculture.

In this research, we report dextrin-based biodegradable microgels (PDXE MGs) having phosphate-based cross-linking units for slow release of urea and a potential P source to improve fertilization. PDXE MGs (∼200 nm) are synthesized by cross-linking the lauroyl-functionalized dextrin chains with sodium tripolyphosphate. The developed PDXE MGs exhibit high loading (∼10%) and encapsulation efficiency (∼88%) for urea. It is observed that functionalization of PDXE MGs with lauroyl chains slows down the release of urea (90% in ∼24 days) as compared to nonfunctionalized microgels (PDX MGs) (99% in ∼17 days) in water. Further studies of the developed formulation display that Urea@PDXE MGs significantly boost maize seed germination and overall plant growth as compared to pure urea fertilizer. Moreover, analysis of maize leaves obtained from plants treated with Urea@PDXE MGs reveals 3.5 ± 0.3% nitrogen content and 90 ± 0.7 mg/g chlorophyll content. These values are significantly higher than 1.4 ± 0.6% nitrogen content and 48 ± 0.05 mg/g chlorophyll content obtained by using bare urea. Further, acid phosphatase activity in roots is reduced upon treatment with PDXE MGs and Urea@PDXE MGs, suggesting the availability of P upon degradation of PDXE MGs by the amylase enzyme in soil. These experimental results present the developed microgel-based biodegradable formulation with a slow release feature as a potential candidate to move toward sustainable agriculture practices.

Impact of COVID-19 pandemic on pharmacologic treatment of patients newly diagnosed with osteoporosis.

PURPOSE: This study determined whether initiation of pharmacologic treatment was delayed for newly diagnosed osteoporosis patients during the COVID-19 pandemic. METHODS: 1,189 patients ≥50 years with newly diagnosed osteoporosis using dual-energy x-ray absorptiometry (DXA) screening at a single academic institution were included. Patients with previous osteoporosis were excluded. Patients diagnosed between March 1, 2018-January 31, 2020 (pre-pandemic cohort, n = 576) were compared to those diagnosed between March 1, 2020-January 31, 2022 (pandemic cohort, n = 613). Age, sex, race, ethnicity, ordering providers (primary vs specialty), and pharmacological agents were evaluated. Primary outcomes included proportion of patients prescribed therapy within 3 and 6-months of diagnosis, and mean time from diagnosis to treatment initiation. RESULTS: The pre-pandemic cohort had more White patients (74.3 vs 68.4%, p = .02) and no differences between remaining demographic variables. Only 40.5% of newly diagnosed patients initiated pharmacologic therapy within 6 months. Patients treated at 3-months (31.8 vs 35.4%, p = 0.19) and 6-months (37.8 vs 42.9, p = 0.08) were comparable between cohorts (47.2 vs 50.2% p = 0.30). Mean time from diagnosis to treatment initiation was similar (46 vs 45 days, p = 0.72). There were no treatment differences based on gender, race, or ethnicity or between ordering providers (65.1 vs 57.4% primary care, p = 0.08). Bisphosphonates were most often prescribed in both cohorts (89% vs 82.1%). CONCLUSIONS: This is the first study assessing COVID-19's impact on pharmacologic treatment of newly diagnosed osteoporosis. 40.5% of newly diagnosed patients were treated pharmacologically within six months of diagnosis, and the pandemic did not significantly affect treatment rates.

Gd/hafnium oxide@gold@chitosan core-shell nanoparticles as a platform for multimodal theranostics in oncology research.

In the current study, we synthesized thiolated chitosan-stabilized gold-coated, gadolinium-doped hafnium oxide nanoparticles (CAuGH NPs) with the capability of acting as a multifunctional system to deliver anticancer drug doxorubicin (DOX), to enhance radiosensitization by ROS generation, and to provide magnetic resonance (MR) imaging contrast for biomedical applications.

Polysaccharides, proteins, and synthetic polymers based multimodal hydrogels for various biomedical applications: A review.

Nature-derived or biologically encouraged hydrogels have attracted considerable interest in numerous biomedical applications owing to their multidimensional utility and effectiveness. The internal architecture of a hydrogel network, the chemistry of the raw materials involved, interaction across the interface of counter ions, and the ability to mimic the extracellular matrix (ECM) govern the clinical efficacy of the designed hydrogels. This review focuses on the mechanistic viewpoint of different biologically driven/inspired biomacromolecules that encourages the architectural development of hydrogel networks. In addition, the advantage of hydrogels by mimicking the ECM and the significance of the raw material selection as an indicator of bioinertness is deeply elaborated in the review. Furthermore, the article reviews and describes the application of polysaccharides, proteins, and synthetic polymer-based multimodal hydrogels inspired by or derived from nature in different biomedical areas. The review discusses the challenges and opportunities in biomaterials along with future prospects in terms of their applications in biodevices or functional components for human health issues. This review provides information on the strategy and inspiration from nature that can be used to develop a link between multimodal hydrogels as the main frame and its utility in biomedical applications as the primary target.

Biodegradable redox sensitive chitosan based microgels for potential agriculture application.

In this work, we report redox sensitive, 2,3-dihydroxybenzoic acid (DH) functionalized chitosan/stearic acid microgels (DH-ChSt MGs) for controlled delivery of insecticide and capturing of heavy metal ions. DH-ChSt MGs (≈146 nm) are prepared by disulfide crosslinking of SH functionalized chitosan and stearic acid rendering them biodegradable. DH-ChSt MGs exhibit high loading (≈8 %) and encapsulation (≈85 %) efficiency for imidacloprid insecticide, and offer its prolonged release (≈75 % after 133 h) under reducing conditions. Functionalization with DH provides enhanced foliar adhesion on pea leaves. DH-ChSt MGs also bind Fe3+ very efficiently due to the strong chelation of Fe3+ by DH, offering the opportunity of supplying Fe3+ nutrient for plant care. MTT assay results using different cells confirm that DH-ChSt MGs are nontoxic up to the experimental concentration of 120 µg/mL. Additionally, reduced DH-ChSt MGs having free thiol groups are also capable of binding heavy metal ions, thus presenting the reported formulation as a promising platform for agriculture application.

Dextran/eudragit S-100 based redox sensitive nanoparticles for colorectal cancer therapy.

Herein, we present disulfide crosslinked dextran/eudragit S-100 nanoparticles (DEEU NPs) (≈55 nm) for colorectal cancer treatment. These redox environment sensitive DEEU NPs are synthesized by simple oxidation of thiolated polymers in air. This approach allows avoiding the use of any additional chemical crosslinker. These DEEU NPs have high encapsulation efficiency for the doxorubicin (DOX) model drug (≈95%). The prepared DEEU NPs are redox sensitive owing to disulfide units and exhibit ≈80% DOX release in the reducing environment of GSH. Additionally, DOX-DEEU NPs display enhanced cytotoxicity for HCT116 cancer cells as compared to free DOX. Annexin V staining results also support the higher anticancer efficiency of DOX-DEEU NPs via induction of apoptosis. In vivo biodistribution results demonstrate that DEEU NPs can remain in the colon region for up to 24 hours. These results indicate that DEEU NPs can act as a promising platform for colorectal cancer treatment.

Biodegradable dual stimuli responsive alginate based microgels for controlled agrochemicals release and soil remediation.

To meet the growing food demand of increasing world population while reducing the harmful environmental effects of agrochemicals, development of smart nanoformulation is of prime importance. Herein, dual stimuli responsive alginate based microgels (OAlgDP MGs) (≈160 nm) are developed for controlled release of agrochemicals and soil remediation. These microgels are prepared using octyl amine functionalized alginate which is crosslinked by 3, 3'-dithiopropionohydrazide crosslinker providing both hydrazone and disulfide bonds in microgels network. OAlgDP MGs are further loaded with hydrophobic diuron herbicide displaying ≈85 % encapsulation efficiency. Sustained release of diuron is obtained in 2 mM GSH (≈100 % after 380 h) and at pH 5 (≈72 % after 240 h). Furthermore, OAlgDP MGs are nontoxic up to 150 µg/mL against HEK293T cells while their reduced form is capable of capturing the heavy metal ions (Cu2+ and Hg2+) showing the potential of the developed system for moving toward sustainable agriculture.

Redox responsive poly(allylamine)/eudragit S-100 nanoparticles for dual drug delivery in colorectal cancer.

Herein, we report redox responsive, colon cancer targeting poly(allylamine) (PA)/eudragit S-100 (EU) nanoparticles (PAEU NPs) (≈59 nm). These disulfide crosslinked PAEU NPs are developed via air oxidation of thiolated PA and thiolated EU, eliminating the need of any external crosslinking agent for dual drug delivery. PAEU NPs can effectively encapsulate both hydrophilic doxorubicin (DOX) and hydrophobic curcumin (Cur) drug with ≈85 % and ≈97 % encapsulation efficiency respectively. Here, the combination of drugs having different anticancer mechanism offers the possibility of developing nanosystem with enhanced anticancer efficacy. The developed PAEU NPs show good colloidal stability and low drug release under physiological conditions, while high DOX (≈98 %) and Cur (≈93 %) release is observed in reducing environment (10 mM GSH). Further, DOX and Cur loaded PAEU NPs exhibit higher cancer cell killing efficiency as compared to individual free drugs. In vivo biodistribution studies with Balb/C mice display the retention of PAEU NPs in the colon region up to 24 h presenting the developed approach as an efficient way for colorectal cancer therapy.

Alginate based hydrogel inks for 3D bioprinting of engineered orthopedic tissues.

3D printed hydrogels have emerged as a novel tissue engineering and regeneration platform due to their ability to provide a suitable environment for cell growth. To obtain a well-defined scaffold with good post-printing shape fidelity, a proper hydrogel ink formulation plays a crucial role. In this regard, alginate has received booming interest owing to its biocompatibility, biodegradability, easy functionalization, and fast gelling behavior. Hence, this review highlights the significance of alginate-based hydrogel inks for fabricating 3D printed scaffolds for bone and cartilage regeneration. Herein, we discuss the fundamentals of direct extrusion 3D bioprinting method and provide a comprehensive overview of various alginate-based hydrogel ink formulations that have been used so far. We also summarize the requirements of hydrogel inks and 3D printed scaffolds to achieve similarity to the native tissue environment. Finally, we discuss the challenges, and research directions relevant for future clinical translation.

Environmentally benign approach for the efficient sequestration of methylene blue and coomassie brilliant blue using graphene oxide emended gelatin/κ-carrageenan hydrogels.

Herein, we report the synthesis and characterization of gelatin/κ-carrageenan crosslinked polyacrylic acid hydrogel (GT-CAG-cl-polyAA) and graphene oxide incorporated hydrogel nanocomposite (GOHNC) through a free radical crosslinking pathway. Under optimized reaction conditions, GT-CAG-cl-polyAA displayed 486 % maximum swelling percentage. TEM image depicted wrinkled silk veil wave-type surface morphology of graphene oxide (GO), whereas, the SEM analysis indicated the porous nature of the GT-CAG-cl-polyAA and GOHNC capable of accumulating a large number of water/dye molecules. GT-CAG-cl-polyAA exhibited 96.11 % and 82.16 % dye removal potential for the adsorption of methylene blue (MB) and coomassie brilliant blue (CB), respectively under optimized conditions. GOHNC enhanced the % dye removal efficiency (98.39 % for MB and 94.50 % for CB). The maximum adsorption capacity of GOHNC for the removal of CB and MB was 312.7 mg/g and 94.9 mg/g, respectively. The adsorption of CB and MB exhibited best fitting with Flory-Huggins adsorption isotherms data. The negative values of ΔG° and positive values of ΔS° which were obtained from the adsorption isotherm plot suggested the thermodynamic feasibility of the adsorption. Also, the samples were reusable for up to five consecutive cycles without any degradation and hence suggested a considerable pathway for the separation of textile dyes.

Biodegradable disulfide crosslinked chitosan/stearic acid nanoparticles for dual drug delivery for colorectal cancer.

Herein, redox responsive chitosan/stearic acid nanoparticles (CSSA NPs) (≈200 nm) are developed for dual drug delivery. These degradable nanoparticles are prepared based on disulfide (SS) crosslinking chemistry avoiding the use of any external crosslinking agent. CSSA NPs are further loaded with both DOX (hydrophilic) and curcumin (hydrophobic) drugs with ≈86 % and ≈82 % encapsulation efficiency respectively. This approach of combining anticancer therapeutics having different mode of anticancer action allows to develop systems for cancer therapy with enhanced efficacy. In vitro drug release experiments clearly exhibit the low leakage of drug under physiological conditions while ≈98 % DOX and ≈96 % curcumin is released after 136 h under GSH reducing conditions. The cytotoxicity experiments against HCT116 cells demonstrate higher cytotoxicity of dual drug loaded CSSA NPs. In vivo biodistribution experiments with c57bl/6j mice confirms the retention of CSSA NPs in the colon area up to 24 h exhibiting their potential for colorectal cancer therapy.

Polysaccharide-Based Theranostic Systems for Combined Imaging and Cancer Therapy: Recent Advances and Challenges.

Designing novel systems for efficient cancer treatment and improving the quality of life for patients is a prime requirement in the healthcare sector. In this regard, theranostics have recently emerged as a unique platform, which combines the benefits of both diagnosis and therapeutics delivery. Theranostics have the desired contrast agent and the drugs combined in a single carrier, thus providing the opportunity for real-time imaging to monitor the therapy results. This helps in reducing the hazards related to treatment overdose or underdose and gives the possibility of personalized therapy. Polysaccharides, as natural biomolecules, have been widely explored to develop theranostics, as they act as a matrix for simultaneously loading both contrast agents and drugs for their utility in drug delivery and imaging. Additionally, their remarkable physicochemical attributes (biodegradability, satisfactory safety profile, abundance, and diversity in functionality and charge) can be tuned via postmodification, which offers numerous possibilities to develop theranostics with desired characteristics. Hence, we provide an overview of recent advances in polysaccharide matrix-based theranostics for drug delivery combined with magnetic resonance imaging, computed tomography, positron emission tomography, single photon emission computed tomography, and ultrasound imaging. Herein, we also summarize the toxicity assessment of polysaccharides, associated contrast agents, and nanotoxicity along with the challenges and future research directions.

Imaging application and radiosensitivity enhancement of pectin decorated multifunctional magnetic nanoparticles in cancer therapy.

In this contribution, we report the fabrication of multifunctional nanoparticles with gold shell over an iron oxide nanoparticles (INPs) core. The fabricated system combines the magnetic property of INPs and the surface plasmon resonance of gold. The developed nanoparticles are coated with thiolated pectin (TPGINs), which provides stability to the nanoparticles dispersion and allows the loading of hydrophobic anticancer drugs. Curcumin (Cur) is used as the model drug and an encapsulation efficiency of approximately 80% in TPGINs is observed. Cytotoxicity study with HeLa cells shows that Cur-loaded TPGINs have better viability percent (~30%) than Cur alone (~40%) at a dose of 30 µg of TPGINs. Further, annexin V-PI assay demonstrated the enhanced anticancer activity of Cur-loaded TPGINs via induction of apoptosis. The use of TPGINs leads to a significant enhancement in generating reactive oxygen species (ROS) in HeLa cells through improved radiosensitization by gamma irradiation (0.5 Gy). TPGINs are further evaluated for imparting contrast in magnetic resonance imaging (MRI) with the r2 relaxivity in the range of 11.06-13.94 s-1 µg-1 mL when measured at 7 Tesla. These experimental results indicate the potential of TPGINs for drug delivery and MR imaging.

Rise of the phoenix: Mucormycosis in COVID-19 times.

PURPOSE: Rhino-orbital mucormycosis in times of ongoing COVID-19 pandemic. AIMS: The aim of the study was to document cases of rhino-orbital mucormycosis seen at our Regional Institute of Ophthalmology during COVID-19 (coronavirus disease 2019) times. METHODS: The study is a retrospective, institutional cohort, interventional study. It was carried out at our Regional Institute of Ophthalmology from September 2020 to mid-March 2021. All patients of biopsy-proven mucormycosis were enrolled in the study. The patients were subjected to complete history taking, ophthalmological examination, and imaging studies. The patients were treated via a multidisciplinary approach with intravenous liposomal amphotericin B and debridement of local necrotic tissue. Exenteration was done when indicated. A minimum 75-day follow-up period was accorded to all study patients. Statistical analysis was done using Chi-square test. A P value ≤0.05 was taken as significant. RESULTS: Thirty-one patients were seen, with a mean age of 56.3 years. The major risk factors included uncontrolled diabetes (96.7%) and COVID-19 positivity (61.2%), with concomitant steroid use in 61.2% patients. The most common presentation was diminution of vision (<6/60 in 80.64% patients) and ophthalmoplegia (77.4%). The most common imaging findings were orbital cellulitis (61.29%) and pansinusitis (77.4%). Intravenous liposomal amphotericin B was given to all patients for an average 18.93 days. Exenteration was required in (n = 4) 12.9% of cases. Twenty-eight patients recovered and were alive on follow-up. Mortality was seen in three patients. The presence of cerebral involvement and a HbA1c value of ≥8 were found to be significant in the prediction of survival of patients with mucormycosis. CONCLUSION: We present the largest institutional cohort of rhino-orbital mucormycosis patients during the ongoing COVID-19 pandemic era from our unique perspective.

Redox responsive xylan-SS-curcumin prodrug nanoparticles for dual drug delivery in cancer therapy.

Chemotherapeutic agents with different anticancer mechanisms could enhance therapeutic effect in cancer therapy by their combined application. In this study, redox-sensitive prodrug nanoparticles based on Xyl-SS-Cur conjugate were developed for co-delivery of curcumin and 5-FU in cancer therapy. The Xyl-SS-Cur conjugate was synthesized via covalent conjugation of curcumin to xylan through a disulphide (-S-S-) linkage. The Xyl-SS-Cur conjugate could self-assemble in aqueous medium into nanoparticles and the lipophilic 5-fluorouracil-stearic acid (5-FUSA) prodrug was encapsulated into the hydrophobic core of Xyl-SS-Cur NPs through dialysis membrane method. The obtained Xyl-SS-Cur/5-FUSA NPs had an appropriate size (∼217 ±â€¯2.52 nm), high drug loading of curcumin (∼ 31.4 wt%) and 5-FUSA (∼ 11.8 wt%) and high stability. The interaction of Xyl-SS-Cur/5-FUSA NPs with blood components was investigated by hemolysis study. The cytotoxicity study demonstrated that Xyl-SS-Cur/5-FUSA NPs induced higher cytotoxicity than free drugs against the Human colorectal cancer cells (HT-29, HCT-15). These results indicate that Xyl-SS-Cur/5-FUSA NPs can serve as a promising drug delivery system in cancer therapy.

Comparison of Diagnostic Accuracy of Different Sites for Transcutaneous Bilirubin Measurement in Early Preterm Infants.

OBJECTIVE: To evaluate correlation of transcutaneous bilirubin (TcB) measured at different body sites with serum total bilirubin (TSB) in early preterm infants. METHODS: This hospital based prospective comparative study was carried out in the Department of Pediatrics, SMS Medical College, Jaipur between April 2015 to March 2016. Early preterm infants with gestational age ≤ 34 weeks in whom clinical jaundice was significant mandating TSB measurement were included in the study. Study subjects who met the inclusion criteria were chosen consecutively. Neonates in whom phototherapy was already initiated and those with poor perfusion (capillary refill time > 3 s) were excluded from the study. All the measurements were carried out within first postnatal week. Transcutaneous bilirubin was measured from three sites: forehead, sternum and interscapular region and within 15 min of TcB measurement, blood samples were taken and serum bilirubin level was calculated. RESULTS: Correlation coefficients of transcutaneous bilirubin measured from forehead, sternum and interscapular sites were 0.82, 0.84 and 0.86 respectively. TcB measured from all the three sites correlated significantly with serum bilirubin (p < 0.001), but the correlation was best at interscapular site. Sensitivity, specificity and false negative rates were calculated with respect to starting phototherapy. Interscapular site had the highest sensitivity and lowest false negative rate (87.6 and 12.4% respectively) as compared to forehead (79.2 and 20.8% respectively) and sternum (87.1 and 12.9% respectively). CONCLUSIONS: Transcutaneous bilirubin measurement is an acceptable method for identification of hyperbilirubinemia requiring treatment in early preterm newborns. The authors recommend interscapular region as a reliable site in infants of gestational age ≤34 wk for measuring transcutaneous bilirubin.

Functional Microgels: Recent Advances in Their Biomedical Applications.

Here, a spotlight is shown on aqueous microgel particles which exhibit a great potential for various biomedical applications such as drug delivery, cell imaging, and tissue engineering. Herein, different synthetic methods to develop microgels with desirable functionality and properties along with degradable strategies to ensure their renal clearance are briefly presented. A special focus is given on the ability of microgels to respond to various stimuli such as temperature, pH, redox potential, magnetic field, light, etc., which helps not only to adjust their physical and chemical properties, and degradability on demand, but also the release of encapsulated bioactive molecules and thus making them suitable for drug delivery. Furthermore, recent developments in using the functional microgels for cell imaging and tissue regeneration are reviewed. The results reviewed here encourage the development of a new class of microgels which are able to intelligently perform in a complex biological environment. Finally, various challenges and possibilities are discussed in order to achieve their successful clinical use in future.