Bioinspired Heparin Nanosponge Prepared by Photo-crosslinking for Controlled Release of Growth Factors

Indexación: Scopus.Growth factors have great therapeutic potential for various disease therapy and tissue engineering applications. However, their clinical efficacy is hampered by low bioavailability, rapid degradation in vivo and non-specific biodistribution. Nanoparticle based delivery systems are being evaluated to overcome these limitations. Herein, we have developed a thermosensitive heparin nanosponge (Hep-NS) by a one step photopolymerization reaction between diacrylated pluronic and thiolated heparin molecules. The amount of heparin in Hep-NS was precisely controlled by varying the heparin amount in the reaction feed. Hep-NS with varying amounts of heparin showed similar size and shape properties, though surface charge decreased with an increase in the amount of heparin conjugation. The anticoagulant activity of the Hep-NS decreased by 65% compared to free heparin, however the Hep-NS retained their growth factor binding ability. Four different growth factors, bFGF, VEGF, BMP-2, and HGF were successfully encapsulated into Hep-NS. In vitro studies showed sustained release of all the growth factors for almost 60 days and the rate of release was directly dependent on the amount of heparin in Hep-NS. The released growth factors retained their bioactivity as assessed by a cell proliferation assay. This heparin nanosponge is therefore a promising nanocarrier for the loading and controlled release of growth factors.https://www.nature.com/articles/s41598-017-14040-5.pd

Risk factors of delayed diagnosis of acute appendicitis in children: for early detection of acute appendicitis

PurposeThis study examined the risk factors of a delayed diagnosis of acute appendicitis in children undergoing an appendectomy.MethodsThis retrospective study involved children aged below 18 years, who underwent an appendectomy. After dividing them into a delayed diagnosis group and nondelayed diagnosis group according to the time interval between the initial hospital visit and final diagnosis, the risk factors of delayed diagnosis were identified using logistic regression analysis.ResultsAmong 712 patients, 105 patients (14.7%) were classified in the delayed diagnosis group; 92 patients (12.9%) were diagnosed using ultrasonography (US), and both US and computed tomography were performed in 38 patients (5.3%). More patients in the delayed diagnosis group underwent US (P=0.03). Spring season and prior local clinic visit were significantly associated with a delayed diagnosis. Fever and diarrhea were more common in the delayed diagnosis group (fever: odds ratio [OR], 1.37; 95% confidence interval [CI], 1.05–1.81; diarrhea: OR, 1.94; 95% CI, 1.08–3.46; P<0.05). These patients showed symptoms for a longer duration (OR, 2.59; 95% CI, 1.78–3.78; P<0.05), and the admission course (OR, 1.26; 95% CI, 1.11–1.44; P<0.05) and C-reactive protein (CRP) levels (OR, 1.47; 95% CI, 1.19–1.82; P<0.05) were associated with the delayed diagnosis.ConclusionTo decrease the rate of delayed diagnoses of acute appendicitis, symptoms such as fever and diarrhea, seasonal variations, admission course, and CRP levels should be considered and children with a longer duration of symptoms should be closely monitored

Influences of vaccination and public health strategies on COVID-19 dynamics in the United States: Evaluating policy impacts, behavioral responses, and variant proliferation

Background and Aim: The United States (US) government implemented interventions against COVID-19, but their effects on variant-related risks remain inconclusive. We aimed to assess the causal effects of vaccination rates, booster uptakes, face mask mandates, and public area mobility (societal behavioral factor) on early-stage COVID-19 case and death growth rates and identify the most effective public health response for controlling COVID-19 in the US. Materials and Methods: We performed retrospective analyses using four standard correlated random effects models, analyzing a robust panel dataset that encompasses 16,700 records across all fifty US states. Models 1 and 3 analyzed COVID-19 case rates and death growth rates, respectively, from January 2021 to November 2021. In contrast, using the data from August 2021 to November 2021, Models 2 and 4 assessed the effect of Delta variants and booster shots on COVID-19 case and death growth rates, respectively. Results: We found that face mask mandate (p < 0.01) and workplace mobility (p < 0.05) led to lower COVID-19 case growth rates. COVID-19 vaccination uptake rate reduced COVID-19 death growth rates (p < 0.01). Furthermore, contrary to Epsilon variant (p < 0.01), which contributed to reduced COVID-19 case growth rates, Delta variant led to significant increases in COVID-19 cases (p < 0.001). Conclusion: This study suggests that immediate public health interventions, like mask mandates, are crucial for crisis mitigation, while long-term solutions like vaccination effectively address pandemics. The findings of this study not only sheds light on the recent pandemic but also equips policy-makers and health professionals with tools and knowledge to tackle future public health emergencies more effectively

Comparative Genomic Analysis of the 2016 Vibrio cholerae Outbreak in South Korea

In August 2016, South Korea experienced a cholera outbreak that caused acute watery diarrhea in three patients. This outbreak was the first time in 15 years that an outbreak was not linked to an overseas source. To identify the cause and to study the epidemiological implications of this outbreak, we sequenced the whole genome of Vibrio cholerae isolates; three from each patient and one from a seawater sample. Herein we present comparative genomic data which reveals that the genome sequences of these four isolates are very similar. Interestingly, these isolates form a monophyletic Glade with V. cholerae strains that caused an outbreak in the Philippines in 2011. The V. cholerae strains responsible for the Korean and Philippines outbreaks have almost identical genomes in which two unique genomic islands are shared, and they both lack SXT elements. Furthermore, we confirm that seawater is the likely source of this outbreak, which suggests the necessity for future routine surveillance of South Korea's seashore.

The reemergence of long-term potentiation in aged Alzheimer's disease mouse model

Mouse models of Alzheimer’s disease (AD) have been developed to study the pathophysiology of amyloid β protein (Aβ) toxicity, which is thought to cause severe clinical symptoms such as memory impairment in AD patients. However, inconsistencies exist between studies using these animal models, specifically in terms of the effects on synaptic plasticity, a major cellular model of learning and memory. Whereas some studies find impairments in plasticity in these models, others do not. We show that long-term potentiation (LTP), in the CA1 region of hippocampal slices from this mouse, is impared at Tg2576 adult 6–7 months old. However, LTP is inducible again in slices taken from Tg2576 aged 14–19 months old. In the aged Tg2576, we found that the percentage of parvalbumin (PV)-expressing interneurons in hippocampal CA1-3 region is significantly decreased, and LTP inhibition or reversal mediated by NRG1/ErbB signaling, which requires ErbB4 receptors in PV interneurons, is impaired. Inhibition of ErbB receptor kinase in adult Tg2576 restores LTP but impairs depotentiation as shown in aged Tg2576. Our study suggests that hippocampal LTP reemerges in aged Tg2576. However, this reemerged LTP is an insuppressible form due to impaired NRG1/ErbB signaling, possibly through the loss of PV interneurons

Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

<p>Abstract</p> <p>Background</p> <p>Dimeric human erythropoietin (dHuEPO) peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg) mice expressing dHuEPO and to investigate the characteristics of these mice.</p> <p>Methods</p> <p>A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile), was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice.</p> <p>Results</p> <p>A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47) of tg mice expressing the <it>dHuEPO </it>gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11). We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females) were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764). Reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time PCR (qRT-PCR) were used for validating the results of the microarray analysis of mRNA expression.</p> <p>Conclusions</p> <p>In conclusion, dHuEPO tg mice caused excessive erythrocytosis that led to abnormal blood composition, short lifespan, and abnormal splenomegaly. Further, we identified 2,672 genes associated with splenomegaly by microarray analysis. These results could be useful in the development of dHuEPO-producing tg animals.</p

Does gender influence the impact of impaired renal function on prognosis after ST-segment elevated myocardial infarction?

Background: A limited number of studies have investigated the impact of gender on renal function and clinical outcomes after ST-segment elevated myocardial infarction (STEMI), and these studies have provided discrepant results.Methods and Results: This study was based on a retrospective cohort, the Korean Acute Myocardial Infarction Registry (KAMIR). Patients (n = 7,679) with a discharge diagnosis of STEMI were analyzed to investigate association of gender with renal function and clinical outcomes. Compared to men, women were older and exhibited more comorbidity, including impaired renal function. Women showed higher mortality compared to men (1-month mortality,5.6% in men vs. 12.6% in women, p &lt; 0.001; 1-year mortality, 6.8% in men vs. 14.4% in women, p &lt; 0.001). The risk of death proportionally increased as estimated glomerular filtration rate (eGFR) decreased in both genders. After adjusting for potential confounders, hazard ratios for women did not significantly differ from those for men at each eGFR level.The interaction test showed no significant interaction between gender and eGFR in 1-month mortality and 1-year mortality.Conclusions: Impaired renal function was an independent prognostic factor after STEMI in both genders, and the impact of impaired renal function on prognosis after STEMI did not significantly differ between genders

Confining the Sol-Gel Reaction at the Water/Oil Interface:Creating Compartmentalized Enzymatic Nano-Organelles for Artificial Cells

Living organisms compartmentalize their catalytic reactions in membranes for increased efficiency and selectivity. To mimic the organelles of eukaryotic cells, we develop a mild approach for in situ encapsulating enzymes in aqueous-core silica nanocapsules. In order to confine the sol-gel reaction at the water/oil interface of miniemulsion, we introduce an aminosilane to the silica precursors, which serves as both catalyst and an amphiphilic anchor that electrostatically assembles with negatively charged hydrolyzed alkoxysilanes at the interface. The semi-permeable shell protects enzymes from proteolytic attack, and allows the transport of reactants and products. The enzyme-carrying nanocapsules, as synthetic nano-organelles, are able to perform cascade reactions when enveloped in a polymer vesicle, mimicking the hierarchically compartmentalized reactions in eukaryotic cells. This in situ encapsulation approach provides a versatile platform for the delivery of biomacromolecules.</p

Duodenal Duplication Cysts of Ampulla of Vater Containing Stone

Duodenal duplication cysts are rare congenital malformations. Most symptomatic cases are diagnosed in children and usually present with obstructive findings or bleeding symptoms. Treatment traditionally involves surgical resection, which can be often difficult because of the close proximity of the cysts to the papilla and bilopancreatic confluence. Endoscopic therapy has been used as an alternative to open surgery in a few selected cases. We report a case with a duodenal duplication cyst containing a brown pigmented stone within the cystic lumen. He was visited because of sudden right upper quadrant abdominal pain. An abdominal computed tomography revealed the presence of a cyst with a stone, which was finally removed by endoscopic resection