Targeted drug delivery using beeswax-derived albendazole-loaded solid lipid nanoparticles in Haemonchus contortus, an albendazole-tolerant nematode.

Targeted delivery has not been achieved for anthelmintic treatment, resulting in the requirement of excess drug dose leading to side effects and therapeutic resistance. Gastrointestinal helminths take up lipid droplets from digestive fluid for energy production, egg development, and defense which inspired us to develop biocompatible and orally administrable albendazole-loaded solid lipid nanoparticles (SLN-A) that were derived from beeswax and showed drug loading efficiency of 83.3 ± 6.5 mg/g and sustained-release properties with 84.8 ± 2.5% of drug released at pH 6.4 within 24 h at 37 °C. Rhodamine B-loaded SLN showed time-dependent release and distribution of dye in-vitro in Haemonchus contortus. The sustained-release property was shown by the particles that caused enhancement of albendazole potency up to 50 folds. Therefore, this formulation has immense potential as an anthelminthic drug delivery vehicle that will be able to reduce the dose and drug-induced side effects by enhancing the bioavailability of the drug.

A Systematic Review of the Efficacy and Safety of Tranexamic Acid in Facelift Surgery.

Tranexamic acid (TXA) has become widely utilized in different specialities including facelift surgery. The aim of this review was to robustly evaluate the quality of available evidence on the efficacy and safety of TXA use in facelift surgery. We searched the MEDLINE (National Institutes of Health, Bethesda, MD), Embase (Elsevier, Amsterdam, the Netherlands), CINAHL (EBSCO Information Services, Ipswich, MA), Cochrane Central Register of Controlled Trials (CENTRAL; Wiley, Hoboken, NJ), Google Scholar (Alphabet Inc. Mountain View, CA), Science Citation Index (Clarivate, London, UK), and Latin American and Caribbean Center on Health Sciences Information (LILACS; São Paulo, Brazil) databases for randomized controlled trials (RCTs) and observational studies. Primary outcomes were blood loss, postoperative hematoma, ecchymosis, and swelling, in addition to technical considerations and complications. We assessed review quality with the AMSTAR 2 tool, study quality with Grading of Recommendations, Assessment, Development, and Evaluations approach (GRADE) tool, and the risk of bias with Cochrane's RoB 2.0 tool for RCTs and ROBINS-I for nonrandomized studies. Of the 368 articles, a total of 3 studies including 150 patients met the inclusion criteria. The RCT reported a significant reduction in postoperative serosanguineous collections in the TXA group (P < .01), and in surgeon-rated postoperative ecchymosis and bruising. The prospective cohort study reported reduced drainage output in first 24 hours in the TXA group (P < .01). The retrospective cohort study reported lower intraoperative blood loss, mean postoperative day 1 drain output, percentage of drain removal on postoperative day 1, and number of days to drain removal in the TXA group (all P < .01). The quality of studies was moderate, and this review was the highest rated compared to previous reviews, as per the AMSTAR 2 tool. Based on limited literature, TXA improves clinical outcomes regardless of the route of administration. Topical TXA is an emerging route, expediting drain removal and reducing blood loss. Future Level I high-quality studies are required.

Use of eHealth for HIV Medical Education: a Narrative Review.

PURPOSE OF REVIEW: The complexity of HIV care and its expanding clinical workforce has created a need for new distance learning models to deliver medical education. We conducted a narrative review to assess the acceptability and effectiveness of recent eHealth HIV education interventions supporting HIV healthcare providers. RECENT FINDINGS: Evidence from 24 articles revealed that synchronous (real time), asynchronous (any time), and hybrid (combination) models of eHealth education are feasible and acceptable. Only two interventions (one asynchronous, one hybrid) of 19 included in the review utilized a randomized controlled design. Some studies showed improvement in confidence and perceived quality of case management, but few studies were designed to demonstrate impact. Successful eHealth education interventions require a thorough understanding of the target community's capacity and needs. Both synchronous and asynchronous strategies appear acceptable and potentially effective, but more studies are needed to assess impact on knowledge and practices to determine the most effective delivery models.

Nuclear-mitochondrial communication involving miR-181c plays an important role in cardiac dysfunction during obesity.

AIMS: In cardiomyocytes, there is microRNA (miR) in the mitochondria that originates from the nuclear genome and matures in the cytoplasm before translocating into the mitochondria. Overexpression of one such miR, miR-181c, can lead to heart failure by stimulating reactive oxygen species (ROS) production and increasing mitochondrial calcium level ([Ca2+]m). Mitochondrial calcium uptake 1 protein (MICU1), a regulatory protein in the mitochondrial calcium uniporter complex, plays an important role in regulating [Ca2+]m. Obesity results in miR-181c overexpression and a decrease in MICU1. We hypothesize that lowering miR-181c would protect against obesity-induced cardiac dysfunction. METHODS AND RESULTS: We used an in vivo mouse model of high-fat diet (HFD) for 18 weeks and induced high lipid load in H9c2 cells with oleate-conjugated bovine serum albumin in vitro. We tested the cardioprotective role of lowering miR-181c by using miR-181c/d-/- mice (in vivo) and AntagomiR against miR-181c (in vitro). HFD significantly upregulated heart levels of miR-181c and led to cardiac hypertrophy in wild-type mice, but not in miR-181c/d-/- mice. HFD also increased ROS production and pyruvate dehydrogenase activity (a surrogate for [Ca2+]m), but the increases were alleviated in miR-181c/d-/- mice. Moreover, miR-181c/d-/- mice fed a HFD had higher levels of MICU1 than did wild-type mice fed a HFD, attenuating the rise in [Ca2+]m. Overexpression of miR-181c in neonatal ventricular cardiomyocytes (NMVM) caused increased ROS production, which oxidized transcription factor Sp1 and led to a loss of Sp1, thereby slowing MICU1 transcription. Hence, miR-181c increases [Ca2+]m through Sp1 oxidation and downregulation of MICU1, suggesting that the cardioprotective effect of miR-181c/d-/- results from inhibition of Sp1 oxidation. CONCLUSION: This study has identified a unique nuclear-mitochondrial communication mechanism in the heart orchestrated by miR-181c. Obesity-induced overexpression of miR-181c increases [Ca2+]m via downregulation of MICU1 and leads to cardiac injury. A strategy to inhibit miR-181c in cardiomyocytes can preserve cardiac function during obesity by improving mitochondrial function. Altering miR-181c expression may provide a pharmacologic approach to improve cardiomyopathy in individuals with obesity/type 2 diabetes.

Novel nano-insulin formulation modulates cytokine secretion and remodeling to accelerate diabetic wound healing.

Little is known about insulin's wound healing capability in normal as well as diabetic conditions. We here report specific interaction of silver nanoparticles (AgNPs) with insulin by making a ~2 nm thick coat around the AgNPs and its potent wound healing efficacy. Characterization of the interaction of human insulin with silver nanoparticles showed confirmed alteration of amide-I in insulin whereas amide-II and III remained unaltered. Further, nanoparticles protein interaction kinetics showed spontaneous interaction at physiological temperature with ΔG, ΔS, Ea and Ka values -7.48, 0.076, 3.84 kcal mol-1 and 6 × 105 s-1 respectively. Insulin loaded AgNPs (IAgNPs) showed significant improvement in healing activity in vitro (HEKa cells) and in vivo (Wister Rats) in comparison with the control in both normal and diabetic conditions. The underlying mechanism was attributed to a regulation of the balance between pro (IL-6, TNFα) and anti-inflammatory cytokines (IL-10) at the wound site to promote faster wound remodeling.

Increased Doses Lead to Higher Drug Exposures of Levofloxacin for Treatment of Tuberculosis.

Patients with multidrug-resistant tuberculosis in Peru and South Africa were randomized to a weight-banded nominal dose of 11, 14, 17, or 20 mg/kg/day levofloxacin (minimum, 750 mg) in combination with other second-line agents. A total of 101 patients were included in noncompartmental pharmacokinetic analyses. Respective median areas under the concentration-time curve from 0 to 24 h (AUC0-24) were 109.49, 97.86, 145.33, and 207.04 µg · h/ml. Median maximum plasma concentration (Cmax) were 11.90, 12.02, 14.86, and 19.17 µg/ml, respectively. Higher levofloxacin doses, up to 1,500 mg daily, resulted in higher exposures. (This study has been registered at ClinicalTrials.gov under identifier NCT01918397.).

Sensitising natural wool with green and brown coffee using a facile extraction method to optimise dye process parameters.

Green coffee powder is the raw powder of coffee cherries and all coffee's potential components are held within this green powder. A new natural colourant was extracted from Green Coffee using water as an extractant. To obtain a green-colored solution, a specific amount of green coffee was mixed with distilled water and left for 24 h at room temperature. Furthermore, the colouring performance of extracted colour has been studied using the conventional exhaust dyeing method on wool fabric. Different parameters viz. concentration of Green coffee powder, the temperature of the dye bath, the period for immersion, and solution pH were made to set to obtain a fine tone of green colour. The dyeing parameters (amount of the coffee: 2 g, 100 °C, 70 min & 6.7 pH) were optimised and selected to draw a comparison with the conventional Brown coffee powder. In experiments on wool, this potential solution of Green coffee offered rich green hues with good tonal variation. In addition, the colour fastness to washing was found superior in the case of both Green and Brown coffee and colour fastness to light, rubbing as well as perspiration also showed good performance. In this study, our main focus was to obtain the true and fast green tone of the fabric using Green Coffee and compare it with brown coffee using the same conditions used for dyeing with green coffee. The application of these dyes as natural dyes results in obtaining innovative natural fast colour with remarkable dyeing properties and a new inclusion to the existing commercial spectra of natural dyes.

Protein-modified nanomaterials: emerging trends in skin wound healing.

Prolonged inflammation can impede wound healing, which is regulated by several proteins and cytokines, including IL-4, IL-10, IL-13, and TGF-ß. Concentration-dependent effects of these molecules at the target site have been investigated by researchers to develop them as wound-healing agents by regulating signaling strength. Nanotechnology has provided a promising approach to achieve tissue-targeted delivery and increased effective concentration by developing protein-functionalized nanoparticles with growth factors (EGF, IGF, FGF, PDGF, TGF-ß, TNF-α, and VEGF), antidiabetic wound-healing agents (insulin), and extracellular proteins (keratin, heparin, and silk fibroin). These molecules play critical roles in promoting cell proliferation, migration, ECM production, angiogenesis, and inflammation regulation. Therefore, protein-functionalized nanoparticles have emerged as a potential strategy for improving wound healing in delayed or impaired healing cases. This review summarizes the preparation and applications of these nanoparticles for normal or diabetic wound healing and highlights their potential to enhance wound healing.

Chitosan-insulin nano-formulations as critical modulators of inflammatory cytokines and Nrf-2 pathway to accelerate burn wound healing.

Burn injuries are characterized by prolonged inflammatory phases, neurovascular damage, and hypermetabolism, eventually causing improper tissue regeneration. Insulin has gained considerable attention in normal and diabetic wound healing, yet its role in burn wounds remains poorly understood. In this study, insulin-chitosan nano-formulations (ICNP) were synthesized using a simple and robust mechanism and characterized to monitor specific interactions between insulin and chitosan, and the particles measuring approximately 30 nm in size exhibited mild alterations in the amide I, II, and III bonds of the insulin protein along with impressive insulin loading efficiency of 88.725 ± 0.295% under physiological conditions, and significantly improved burn wound healing in vitro (HEKa cells) and in vivo (murine third-degree burn model). The underlying mechanism behind superior wound closure and tissue remodeling was attributed to significant early phase reduction of pro-inflammatory cytokine IL-6 levels in ICNP-treated mice, while anti-inflammatory cytokine IL-10 levels became markedly elevated, resulting in enhanced re-epithelialization and collagen deposition. Furthermore, treatment of ICNP was associated with unregulated expression of Nrf-2, a key regulator of oxidative stress and inflammation, indicating their molecular crosstalk. These findings highlight the potential of ICNP as a promising therapeutic formulation for burn wound healing, promoting wound closure by modulating inflammatory phases, making it a valuable candidate for further clinical development in burn care.

Mechanism of rectification and negative differential resistance in single-molecule junctions with asymmetric anchoring groups: a DFT study.

CONTEXT: This study aims to investigate the electronic transport properties of tetracene molecule connected to gold (Au) electrodes with asymmetric anchoring groups. More specifically, we investigate the effect of asymmetric electrode coupling on the rectification ratio of tetracene-based molecular device. To introduce coupling asymmetry in these junctions, one end of the tetracene molecule is terminated with thiol (-SH) or isocyanide (-NC) while the other end with amine (-NH2) or nitro (-NO2) anchoring group. The results indicate that the electronic transport behavior is affected by the nature of molecule-electrode coupling, and the rectification ratio can be modulated by a proper choice of the anchoring groups. We reveal that the tetracene molecule when connected with isocyanide and amine combination exhibits remarkable rectifying performance (with a rectification ratio of 74) in contrast with other configurations. Furthermore, a prominent negative differential resistance (NDR) feature is observed when the molecule is connected with thiol as one of the anchors. Our present findings with excellent rectifying performance and negative differential resistance pave a new roadmap for designing multifunctional molecular devices. METHODS: By applying non-equilibrium Green's function (NEGF) formalism combined with density functional theory (DFT) Atomistic Tool Kit software package, the electronic transport properties of tetracene molecule connected to gold electrodes with asymmetric anchoring groups have been investigated. The calculations were performed using the Perdew-Burke-Ernzerhof (PBE) parameterization of DFT within generalized gradient approximation (GGA) exchange-correlation functional. To improve calculation precision and save computational efforts, the molecule and anchor groups were double-ζ (DZ) polarized, while single-ζ (SZ) polarized basis set was used for gold electrodes.

Arterolane maleate plus piperaquine phosphate for treatment of uncomplicated Plasmodium falciparum malaria: a comparative, multicenter, randomized clinical trial.

BACKGROUND: Artemisinin-based combination therapy is the first-line treatment for uncomplicated falciparum malaria. This study assessed the antimalarial efficacy and safety of a combination of 150 mg of arterolane maleate and 750 mg of piperaquine phosphate (AM-PQP) in comparison to Coartem (artemether and lumefantrine) in patients with acute uncomplicated P. falciparum malaria. METHODS: In this open-label, randomized, multicentric, parallel group clinical trial, 240 patients were randomized to receive AM-PQP (160 patients) or Coartem (80 patients). Patients with P. falciparum monoinfection and initial parasite densities ranging from 1000 to 100 000 asexual parasites/µL of blood were followed for 28 days. Polymerase chain reaction-corrected adequate clinical and parasitologic response on day 28, parasite clearance time, and fever clearance time were evaluated. RESULTS: A total of 151 (94.4%) of 160 patients in the AM-PQP group completed the trial, while 77 (96.3%) of 80 patients in the Coartem group completed the trial. No treatment failure was noted in the AM-PQP group, while one patient receiving Coartem failed treatment on day 28. There was no difference in the median parasite clearance time (30 hours in both groups) or median fever clearance time (24 hours in both groups) after administration of the 2 study treatments. CONCLUSIONS: The available data support the evaluation of a drug combination in a larger population as a fixed-dose combination. Clinical Trials Registration. CTRI/2007/091/000031.

Functionality of receptor targeted zinc-insulin quantum clusters in skin tissue augmentation and bioimaging.

Quantum clusters with target specificity are suitable for tissue-specific imaging. In the present work, amorphous zinc insulin quantum clusters (IZnQCs) had been synthesised to promote and monitor wound recovery. Easy synthesis, biocompatibility, stability, enhanced quantum yield, and solubility made the cluster suitable for preclinical/clinical exploration. Zn2+ is known for its binding to insulin hexamer. Here we report the reformation of the structure in a quantum cluster form in the presence of Zn2+. The formation of IZnQCs was confirmed by the change in zeta potential from -25.6 mV to -17.9 mV and also the formation of protein metal interaction was confirmed in FTIR bands at 450, 480, and 613 cm-1 for Zn-O, Zn-N, and Zn-S, respectively. HRTEM-EDS and SAED data analysis showed an amorphous nature of the cluster. The binding of IZnQCs to the cells has been confirmed using confocal microscopy. IZnQCs showed a synergistic effect in wound recovery than insulin or Zn2+ alone. Further due to high fluorescence this recovery process can be monitored under an appropriate setup. Wound healing promotional activity, target specificity, and fluorescence properties make the IZnQCs ideal to use for bioimaging along with promoting and monitoring of wound recovery agent.

Protection of lead-induced cytotoxicity using paramagnetic nickel-insulin quantum clusters.

Pb-toxicity is associated with inflammation which leads to delay in wound healing. Pb2+ utilizes calcium ion channels to enter the cell. Therefore, to achieve effective healing in a Pb-poisoned system, capturing Pb2+ from the circulatory system would be an effective approach without hampering the activity of the calcium ion channel. In this work insulin-nickel fluorescent quantum clusters (INiQCs) have been synthesized and used for the specific detection of Pb2+ ions in vitro and in cell-free systems. INiQCs (0.09 µM) can detect Pb2+ concentrations as low as 10 pM effectively in a cell-free system using the fluorescence turn-off method. In vitro INiQCs (0.45 µM) can detect Pb2+ concentrations as low as 1 µM. INiQCs also promote wound healing which can easily be monitored using the bright fluorescence of INiQCs. INiQCs also help to overcome the wound recovery inhibitory effect of Pb2+ in vitro using lead nitrate. This work helps to generate effective biocompatible therapeutics for wound recovery in Pb2+ poisoned individuals.

Metals associated neurodegeneration in Parkinson's disease: Insight to physiological, pathological mechanisms and management.

Parkinson's disease (PD) is a deliberately progressive neurological disorder, arises due to degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of dopaminergic nerves and dopamine deficiency leads to motor symptoms characterized by rigidity, tremor, and bradykinesia. Heavy metals and trace elements play various physiological and pathological roles in the nervous system. Excessive exposure to toxic metals like mercury (Hg), lead (Pb), copper (Cu), zinc (Zn), iron (Fe), manganese (Mn), aluminium (Al), arsenic (As), cadmium(cd), and selenium (Se) cross the blood-brain barrier to enter into the brain and leads to dopaminergic neuronal degeneration. Excessive concentrations of heavy metals in the brain promote oxidative stress, mitochondrial dysfunction, and the formation of α-synuclein leads to dopaminergic neuronal damage. There is increasing evidence that heavy metals normally present in the human body in minute concentration also cause accumulation to initiate the free radical formation and affecting the basal ganglia signaling. In this review, we explored how these metals affect brain physiology and their roles in the accumulation of toxic proteins (α-synuclein and Lewy bodies). We have also discussed the metals associated with neurotoxic effects and their prevention as management of PD. Our goal is to increase the awareness of metals as players in the onset and progression of PD.

Biomedical Evaluation of Lansium parasiticum Extract-Protected Silver Nanoparticles Against Haemonchus contortus, a Parasitic Worm.

Here we show the novel anti-helminthic potential of Lansium parasiticum aqueous extract-protected silver nanoparticles (LAgNPs) against albendazole-resistant gastrointestinal parasite Haemonchus contortus. LAgNPs showed LD50 values of 65.6 ± 32.8 nM (12 h), 139.6 ± 39.9 nM (12 h), and 64.3 ± 8.5 nM (24 h) against adult male, female, and L3 larvae, respectively. LAgNPs was also quite effective in inhibiting egg hatching, with an IC50 value of 144.4 ± 3.1 nM at 48 h of exposure. Exposure to LAgNPs generated oxidative stress and mediated physical damage in the worms' tissue. A sharp increase in reactive oxygen species and nitric oxide synthase levels was prominent due to LAgNPs' exposure. In response to oxidative stress, a sharp increase of stress-responsive enzymes' activity, like catalase, superoxide dismutase, and glutathione peroxidase activity, along with the concentration of glutathione, was observed in worm tissue, which indicated a LAgNP-responsive alteration of metabolism. The results give rise to the opportunity for the development of alternative treatment for drug-resistant parasitic worms.

Chronic Alcoholic Liver Disease and Mortality Risk in Spontaneous Bacterial Peritonitis: Analysis of 6,530 Hospitalizations.

Objective Our study aimed to assess the risk of in-hospital mortality due to chronic alcoholic liver disease (CALD) and other comorbidities in spontaneous bacterial peritonitis (SBP) inpatients. Methods We conducted a cross-sectional study using the Nationwide Inpatient Sample (NIS, 2012 to 2014) from the United States and included 6,530 patients (age 18-50 years) with a primary diagnosis of SBP. Logistic regression was used to evaluate the odds ratio (OR) for in-hospital mortality in SBP by comorbidities. Results The prevalence of CALD in SBP patients is 43.6%, and a higher proportion were males (68.8%) and whites (67%). Middle-aged adults (OR 2.8, 95% CI 1.74-4.45) had higher odds of in-hospital mortality in SBP patients. Race and sex were non-significant predictors for mortality risk. Patients with comorbid coagulopathy (OR 1.9, 95% CI 1.45-2.48) and heart failure (OR 3.9, 95% CI 2.46-6.36) have increased mortality in SBP inpatients. After controlling confounders, CALD was significantly associated with increased in-hospital mortality (OR 1.5, 95% CI 1.12-1.94) in SBP inpatients. Conclusion CALD is an independent factor in increasing the risk of in-hospital mortality in SBP patients by 48%. Alcohol use screening, and alcohol abstinence and supportive therapy need to be implemented at an earlier stage to improve health-related quality of life and reduce in-hospital mortality in SBP patients.

Medical Comorbidities and Association With Mortality Risk in Alzheimer's Disease: Population-Based Study of 132,405 Geriatric Inpatients.

Objectives We used the Nationwide Inpatient Sample (NIS) to identify the demographic predictors and study the impact of chronic comorbidities on the risk of in-hospital mortality in Alzheimer's disease (AD). Methods We included 132,405 AD patients from the NIS (2012-2014). We used descriptive statistics to discern the differences in demographics and comorbidities by in-hospital mortality. Logistic regression analysis was used to evaluate the predictors and impact of comorbidities that increase the risk of association with in-hospital mortality. Results The in-hospital mortality in AD inpatients is 1.69%, and a greater proportion were female (58.4%) and white (81.5%). Male and hispanic had a higher mortality risk than their counterparts. Hypertension (72%) is the most prevalent comorbidity. Congestive cardiac failure (CCF) and renal failure were significantly associated with a higher risk of in-hospital mortality in AD inpatients by 1.4 and 1.5 times, respectively. Psychiatric comorbidities (depression 20.4%, and psychosis 21.4%) were prevalent in AD inpatients but were negatively associated with mortality. Comorbid tumors without metastasis (1.2%) and metastatic cancer (0.3%) were least prevalent but significantly increased the risk of in-hospital mortality by 1.6 times and 2.2 times, respectively. Conclusion CCF and renal failure were significantly associated with a higher risk of in-hospital mortality in AD patients. Less prevalent comorbidities, tumors with/without metastasis increased in-hospital mortality by 59% to 117%. An integrated care model is required to manage comorbidities in AD patients to improve health-related quality of life and reduce morbidity and mortality.

Insulin-copper quantum clusters preparation and receptor targeted bioimaging.

Protein embedded fluorescence quantum clusters (QCs) have received a great amount of interest among the researchers because of their high aqueous solubility, stability, cost efficiency, and target specificity. Considerable advancement has happened in making functional quantum clusters with target specificity. This work reports the simple synthesis of insulin protected copper quantum clusters (ICuQCs) and its receptor-targeted bioimaging applications. The preparation of copper quantum clusters (CuQCs) was done simply by one-pot synthesis method by changing the pH of the insulin protein firstly to 10.5 basic pH than physiological pH. At physiological pH, the mixture incubated in oven 37 °C at 240 rpm has been developed to process initially polydisperse, non-fluorescent, and unstable CuDs into monodispersed (∼2-3 nm), highly fluorescent, and extremely stable ICuQCs in the same phase (aqueous) using insulin as protein. HRTEM image show uniform distribution of CuDs within the protein matrix. Metal ion binding site prediction and docking server (MIB) results show that chain B of insulin contains 3 templates contains 5 amino acid residues which bind with Cu2+ metal ion. Groove 1 contains GLY8 and HIS10 bind has the highest binding potential towards Cu metal ions. The methodology adopted in this study should largely contribute to the practical applications of this new class of QCs. In view of the protein protection, coupled with direct synthesis and easy functionalization, this hybrid QC-protein system is expected to have numerous optical and bioimaging applications in the future.

Aortic Stenosis Patients With Transcatheter Aortic Valve Replacement: Caution Recommended With Renal Failure During Hospitalization.

Objective Our study aimed to assess the risk of in-patient mortality due to renal failure and other comorbidities in aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR). Methods We conducted a cross-sectional study using a Nationwide Inpatient Sample (NIS, January 2010 to December 2014) from the United States and included 33,325 patients with a primary diagnosis of AS. Logistic regression was used to evaluate the odds ratio (OR) for in-hospital mortality in AS by comorbidities including renal failure. Results The prevalence of renal failure in AS patients is 29.2%, and a higher proportion were males (60.1%) and non-white (14.1%). Major loss of function (96.6%) and in-hospital mortality (5.1%) were also proportionally higher in prevalence. Female patients (OR 1.35, 95% CI 1.20-1.51) had higher odds of in-patient mortality in AS patients. Race was a non-significant predictor for mortality risk. Patients with comorbid coagulopathy (OR 2.02, 95% CI 1.79-2.27) and heart failure (OR 1.62, 95% CI 1.39-1.89) have increased mortality in AS inpatients. After controlling confounders, renal failure was significantly associated with increased in-hospital mortality (OR 1.43, 95% CI 1.28-1.61) in AS patients. Conclusion Renal failure was prevalent in AS patients and was an independent factor that increases the risk of in-hospital mortality by 43%. Due to worse outcomes, more studies are required to evaluate risk-benefit ratio and strategies to improve health-related quality of life in post-TAVR patients with renal failure, and optimally decrease inpatient mortality.

Insulin Promotes Wound Healing by Inactivating NFkßP50/P65 and Activating Protein and Lipid Biosynthesis and alternating Pro/Anti-inflammatory Cytokines Dynamics.

Four hundred and twenty-two million people have diabetes due to excess free body glucose in their body fluids. Diabetes leads to various problems including retinopathy, neuropathy, arthritis, damage blood vessels etc; it also causes a delay in wound healing. Insufficiency of insulin is the main reason for diabetes-I and systemic insulin treatment is a remedy. The perspective of the potential use of insulin/insulin based drugs to treat chronic wounds in diabetic conditions is focused on in this review. At the site of the wound, TNF-ɑ, IFN-ϒ, IL-1ß and IL-6 pro-inflammatory cytokines cause the generation of free radicals, leading to inflammation which becomes persistent in diabetes. Insulin induces expression of IL-4/IL-13, IL-10 anti-inflammatory cytokines etc which further down-regulates NFkßP50/P65 assembly. Insulin shifts the equilibrium towards NFkßP50/P50 which leads to down-regulation of inflammatory cytokines such as IL-6, IL-10 etc through STAT6, STAT3 and c-Maf activation causing nullification of an inflammatory condition. Insulin also promotes protein and lipid biosynthesis which indeed promotes wound recovery. Here, in this article, the contributions of insulin in controlling wound tissue microenvironments and remodulation of tissue have been summarised, which may be helpful to develop novel insulin-based formulation(s) for effective treatment of wounds in diabetic conditions.