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6 nm, respectively. Optimal NLC and nanoemulsion carriers were selected for morphological assessment, encapsulation efficiency, thermal analysis, and release study. Scanning and transmission electron microscopy revealed that particles had approximately spherical shape. In gastric simulated solution (pH = 1.2), NLC and nanoemulsion form of vitamin D3 released 9.3% and 26.9% of vitaminD3, respectively. see more This indicated that our formulation is able to protect vitamin D3 under acidic conditions. The results of this study revealed that NLC and nanoemulsion could be an optimal carrier for food fortification in order to improve bioavailability of bioactive compounds such as vitamin D.SARS-CoV-2 has caused more than 3.8 million deaths worldwide, and several types of COVID-19 vaccines are urgently approved for use, including adenovirus vectored vaccines. However, the thermal instability and pre-existing immunity have limited its wide applications. To circumvent these obstacles, we constructed a self-biomineralized adenovirus vectored COVID-19 vaccine (Sad23L-nCoV-S-CaP) by generating a calcium phosphate mineral exterior (CaP) based on Sad23L vector carrying the full-length gene of SARS-CoV-2 spike protein (S) under physiological condition. This Sad23L-nCoV-S-CaP vaccine was examined for its characteristics of structure, thermostability, immunogenicity and avoiding the problem of preexisting immunity. In thermostability test, Sad23L-nCoV-S-CaP could be stored at 4 °C for over 45 days, 26 °C for more than 8 days and 37 °C for approximately 2 days. Furthermore, Sad23L-nCoV-S-CaP induced higher level of S-specific antibody and T cell responses, and was not affected by the pre-existing anti-Sad23L immunity, suggesting it could be used as boosting immunization on Sad23L-nCoV-S priming vaccination. The boosting with Sad23L-nCoV-S-CaP vaccine induced high titers of 105.01 anti-S1, 104.77 anti-S2 binding antibody, 103.04 pseudovirus neutralizing antibody (IC50), and robust T-cell response of IFN-γ (1466.16 SFCs/106 cells) to S peptides, respectively. In summary, the self-biomineralization of the COVID-19 vaccine Sad23L-nCoV-S-CaP improved vaccine efficacy, which could be used in prime-boost regimen for prevention of SARS-CoV-2 infection in humans.Coxsackievirus B1 (CVB1) is a leading causative agent of severe infectious diseases in humans and has been reported to be associated with outbreaks of aseptic meningitis, myocarditis, and the development of chronic diseases such as type 1 diabetes mellitus (T1DM). There is no approved vaccine or effective antiviral therapy to treat CBV1 infection. And animal models to assess the effects of antiviral agents and vaccine remain limited. In this study, we established a neonatal mouse model of CVB1 using a clinically isolated strain to characterize the pathological manifestations of virus infection and to promote the development of vaccines and antiviral drugs against CVB1. One-day-old BALB/c mice were susceptible to CVB1 infection by intraperitoneal injection. Mice challenged with CVB1 at a low dose [10 median tissue culture infective dose (TCID50)] exhibited a series of clinical symptoms, such as inactivity, emaciation, limb weakness, hair thinning, hunching and even death. Pathological examination and tissue viral load analysis showed that positive signals of CVB1 were detected in the heart, spinal cord, limb muscle and kidney without pathological damage. Particularly, CVB1 had a strong tropism towards the pancreas, causing severe cellular necrosis with inflammatory infiltration, and was spread by viraemia. Notably, the monoclonal antibody (mAb) 6H5 and antisera elicited from CVB1-vaccinated mice effectively protected the mice from CVB1 infection in the mouse model. In summary, the established neonatal mouse model is an effective tool for evaluating the efficacy of CVB1 antiviral reagents and vaccines.Numerous studies suggest that disturbed shear, causing endothelium dysfunction, can be related to neighboring vortex structures. With this motivation, this study presents a methodology to characterize the vortex structures. Precisely, we use mapping and characterization of vortex structures' changes to relate it with the hemodynamic indicators of disturbed shear. Topological features of vortex core lines (VCLs) are used to quantify the changes in vortex structures. We use the Sujudi-Haimes algorithm to extract the VCLs from the flow simulation results. The idea of relating vortex structures with disturbed shear is demonstrated for cerebral arteries with aneurysms virtually treated by inserting foam in the sac. To get physiologically realistic flow fields, we simulate blood flow in two patient-specific geometries before and after foam insertion, with realistic velocity waveform imposed at the inlet, using the Carreau-Yasuda model to mimic the shear-thinning behavior. With homogenous porous medium assumption, flow through the foam is modeled using the Forchheimer-Brinkman extended Darcy model. Results show that foam insertion increases the number of VCLs in the parent lumen. The average length of VCL increases by 168.9% and 55.6% in both geometries. For both geometries under consideration, results demonstrate that the region with increased disturbed shear lies in the same arterial segment exhibiting an increase in the number of oblique VCLs. Based on the findings, we conjecture that an increase in oblique VCLs is related to increased disturbed shear at the neighboring portion of the arterial wall.Blood pressure variability is an emerging risk factor for dementia but relationships with markers of neurodegeneration and Alzheimer's disease risk are understudied. We investigated blood pressure variability over one year and follow-up medial temporal brain volume change in apolipoprotein ϵ4 carriers and non-carriers, and in those with and without Alzheimer's disease biomarker abnormality. 1051 Alzheimer's Disease Neuroimaging Initiative participants without history of dementia or stroke underwent 3-4 blood pressure measurements over 12 months and ≥ 1 MRI thereafter. A subset (n = 252) underwent lumbar puncture to determine Alzheimer's disease cerebral spinal fluid amyloid-beta and phosphorylated tau biomarker abnormality. Blood pressure variability over 12 months was calculated as variability independent of mean. Longitudinal hippocampal and entorhinal cortex volume data were extracted from serial brain MRI scans obtained after the final blood pressure measurement. Apolipoprotein ϵ4 carrier status was defined as at least one ϵ4 allele. Bayesian growth modelling revealed a significant interaction of blood pressure variability by ϵ4 by time on hippocampal (ß -2.61 [95% credible interval -3.02, -2.12]) and entorhinal cortex (ß -1.47 [95% credible interval -1.71, -1.17]) volume decline. A similar pattern emerged in subsets with Alzheimer's disease pathophysiology (i.e., abnormal levels of both amyloid-beta and phosphorylated tau). Findings suggest that elevated blood pressure variability is related to medial temporal volume loss specifically in ϵ4 carriers, and in those with Alzheimer's disease biomarker abnormality. Findings could implicate blood pressure variability in medial temporal neurodegeneration observed in older ϵ4 carriers and those with prodromal Alzheimer's disease.Esophagectomy is a high-risk operation, regardless of technique. Minimally invasive transthoracic esophagectomy could reduce length of stay and pulmonary complications compared to traditional open approaches, but the benefits of minimally invasive transhiatal esophagectomy are unclear. link2 We performed a retrospective review of prospectively gathered data for open transhiatal esophagectomies (THEs) and transhiatal robot-assisted minimally invasive esophagectomies (TH-RAMIEs) performed at a high-volume academic center between 2013 and 2017. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for outcomes. 465 patients met inclusion criteria (378 THE and 87 TH-RAMIE). THE patients more likely had an ASA score of 3 + (89.1% vs 77.0%, p = 0.012), whereas TH-RAMIE patients more likely had a pathologic staging of 3+ (43.7% vs. 31.2%, p = 0.026). TH-RAMIE patients were less likely to receive epidurals (aOR 0.06, 95% confidence interval [CI] 0.03-0.14, p  less then  0.001), but epidural use itself was not associated with differences in outcomes. TH-RAMIE patients experienced higher rates of pulmonary complications (adjusted odds ratio [OR] 1.82, 95% CI 1.03-3.22, p = 0.040), particularly pulmonary embolus (aOR 5.20, 95% CI 1.30-20.82, p = 0.020). There were no statistically significant differences in lymph node harvest, unexpected ICU admission, length of stay, in-hospital mortality, or 30-day readmission or mortality rates. The TH-RAMIE approach had higher rates of pulmonary complications. There were no statistically significant advantages to the TH-RAMIE approach. Further investigation is needed to understand the benefits of a minimally invasive approach to the open transhiatal esophagectomy.Studies comparing right (RC) and left colectomies (LC) show higher rates of ileus in RC and higher wound infection and anastomotic leak rates in LC. However, prior studies did not include robotic procedures. We compared short-term outcomes of laparoscopic and robotic RC and LC for cancer, with sub-analysis of robotic procedures. In a retrospective review of a prospective database, preoperative factors, intraoperative events, and 30-day postoperative outcomes were compared. Student's t tests and Chi-square tests were used for continuous and categorical variables, respectively. link3 A logistic binomial regression was performed to assess whether type of surgery was associated with postoperative complications. Between January 2014 and August 2020, 115 patients underwent minimally invasive RC or LC for cancer. Sixty-eight RC [30 (44.1%) laparoscopic, 38 (55.9%) robotic] and 47 LC [13 (27.6%) laparoscopic, 34 (72.4%) robotic] cases were included. On univariate analysis, RC patients had significantly higher overall postoperative complications but no differences in rates of ileus/small bowel obstruction, wound infection, time to first flatus/bowel movement, length of hospital stay, and 30-day readmissions. On multivariate analysis, there was no significant difference in overall complications and laparoscopic surgery had a 2.5 times higher likelihood of complications than robotic surgery. In sub-analysis of robotic cases, there was no significant difference among all outcome variables. Previously reported outcome differences between laparoscopic RC and LC for cancer may be mitigated by robotic surgery.Cancer vaccination using tumor antigen-primed dendritic cells (DCs) was introduced in the clinic some 25 years ago, but the overall outcome has not lived up to initial expectations. In addition to the complexity of the immune response, there are many factors that determine the efficacy of DC therapy. These include accurate administration of DCs in the target tissue site without unwanted cell dispersion/backflow, sufficient numbers of tumor antigen-primed DCs homing to lymph nodes (LNs), and proper timing of immunoadjuvant administration. To address these uncertainties, proton (1H) and fluorine (19F) magnetic resonance imaging (MRI) tracking of ex vivo pre-labeled DCs can now be used to non-invasively determine the accuracy of therapeutic DC injection, initial DC dispersion, systemic DC distribution, and DC migration to and within LNs. Magnetovaccination is an alternative approach that tracks in vivo labeled DCs that simultaneously capture tumor antigen and MR contrast agent in situ, enabling an accurate quantification of antigen presentation to T cells in LNs.
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