Garciabjerring1760

Cytokine-based therapies present an alternative immune strategy to target the pleiotropic prostate cancer tumor microenvironment beyond T-cells. Future immunotherapy strategies in prostate cancer should address these immune cell populations, which may play more important roles in the prostate cancer tumor microenvironment.

Local drug delivery facilitiates higher concentrations of drug molecules at or near the treatment site to enhance treatment efficiency and reduce drug toxicity and other systemic side effects. However, local drug delivery systems face challenges in terms of encapsulation, delivery, and controlled release of therapeutics.

We provide an overview of naturally derived biopolymer-based drug delivery systems for localized, sustained, and on-demand treatment. We introduce the advantages and limitations of these systems for drug encapsulation, delivery, and local release, as well as recent applications.

Naturally derived biopolymers like cellulose, silk fibroin, chitosan, alginate, hyaluronic acid, and gelatin are good candidates for localized drug delivery because they are readily chemically modified, biocompatible, biodegradable (with the generation of metabolically compatible degradation products), and can be processed in aqueous and ambient environments to maintain the bioactivity of various therapeutics. Ttrategies to design tunable and controlled biodegradation rates, as well as to explore commercial utility in substituting biopolymer-based systems for currently utilized synthetic polymers for implants for drug delivery.This study aims to examine how the process of online support obtainment may affect cognitive and behavioral coping during a public crisis. A cross-sectional online survey (N = 555) was conducted during the early stage of the COVID-19 pandemic in the U.S. Our findings revealed that informational support, obtained primarily through passive and private online involvement, led to increased risk perceptions of COVID-19; emotional support, obtained mainly via private online involvement, appeared to elicit higher perceived efficacy to cope with the crisis. People's engagement in preventive behaviors was found to be affected by efficacy perceptions, but not by risk perceptions. The results suggested that online social support functioned as a double-edged sword to affect people's coping with a public crisis.

Kidney transplant recipients with cancer are at higher risk of kidney transplant rejection (KTR), and the safety of immune checkpoint inhibitors (ICIs) is unclear. The present study investigates the relationship between ICIs and KTR using data from the Food and Drug Administration Adverse Event Reporting System (FAERS).

Case reports of KTR inducted by ICIs in FAERS from 1 January 2011, to 30 June 2021, were collected, and a disproportionate analysis was performed to assess the correlation between ICIs and KTR.

A total of 99 cases of ICI-related KTR were reported in the FAERS database. Most of them were male patients (n=63, 84.0%), and more than half of patients suffered from malignant melanoma (n=46, 52.9%). The median onset time after the medication was 22days, the withdrawal rates of ICIs were 78.0%, and the overall death rate was 29.3%. In general, there was a significant relevance between ICIs and KTR (ROR=3.92[3.21-4.79] IC025=1.56), of which PD-1 was the most prominent (n=81 ROR=5.26[4.22-6.57] IC025=1.86).

ICIs may increase the risk of KTR in organ transplant recipients with cancer.

ICIs may increase the risk of KTR in organ transplant recipients with cancer.There is limited information about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the first trimester of pregnancy on the risk of major congenital malformations (MCMs). The International Registry of Coronavirus Exposure in Pregnancy (IRCEP) was designed to estimate the relative risk of adverse perinatal outcomes among women with Coronavirus Disease 2019 (COVID-19) at specific times during gestation. Adult women were eligible to enroll if they had a SARS-CoV-2 test, regardless of the results, or clinically confirmed COVID-19 during pregnancy. Self-administered questionnaires collected data on SARS-CoV-2 infection, pregnancy outcomes (including detailed questions on MCMs), and potential confounders. The analysis of MCMs includes women with either a positive SARS-CoV-2 PCR test or a clinical diagnosis of COVID-19 during the first trimester (exposed group) or a negative SARS-CoV-2 test (reference) that enrolled while pregnant. Sensitivity analyses were restricted to pts associated with maternal SARS-CoV-2 infection, RR estimates were imprecise and larger studies are warranted.The electronic properties of a bilayer graphene nanoflake (BLGNF) depend sensitively upon the strength of the inter-layer electronic coupling (IEC) energy. Upon tuning the IEC via changing the twist angle between the layer, a ferromagnetic gap state emerges in a BLGNF due to spontaneous symmetry breaking at the magic-twist. Herein, using first-principles density functional theory, we demonstrate the magic twist angle (θM) in a bilayer graphene nanoflake at which the transition from a nonmagnetic to a ferromagnetic phase occurs can be tuned by exerting uniaxial electronic pressure (Pe). Electronic pressure, which provides another route to control the IEC, is simulated by varying the interlayer spacing in the nanoflake. Our result shows a Pe of 0.125 GPa corresponding to interlayer spacing (h) of 3.58 Å yielding a magic twist angle of ∼1° and a negative value of Pe (-0.042 GPa) at h = 3.38 Å producing a θM of ∼2.4°. The higher value of θM at a negative Pe (smaller h) is attributed to an increase in the energy gap due to strong inter-layer electronic coupling energy in the nanoflake under uniaxial compression. This finding in the nanoflake agrees with the experimental observation in two-dimensional bilayer graphene (M. Yankowitz, S. Chen, H. Polshyn, Y. Zhang, K. Watanabe, T. Taniguchi, D. Graf, A. F. Young and C. R. Dean, Science, 2019, 363, 1059-1064) that indicated an increase in the magic angle value for the phase transition upon application of hydrostatic pressure.

Family history increases the risk for inflammatory bowel diseases (IBDs). However, data on differences in phenotypic characteristics among patients with a strong family history of IBD are scarce and controversial. The aim of the study was to compare the phenotypic features of IBD patients with four or more affected first-degree relatives with sporadic cases of IBD.

Patients with familial and sporadic IBD were identified from the institutional IBD database. IBD patients from families with at least four first-degree affected relatives were selected for analysis and were compared to non-matched sporadic cases with IBD chosen randomly. Comparison for type of IBD (Crohn's disease (CD) vs. ulcerative colitis (UC)), age at onset as well as for disease extent, behavior, extraintestinal manifestations and indicators of severe disease were analyzed.

Thirty-five patients with familial IBD (28 CD, seven UC) were compared to 88 sporadic IBD patients (61 CD, 24 UC and three IBDU). Disease duration was 10.3 ± 8.2 in the familial and 8.0 ± 7.2years in the sporadic cases,

=.13. The familial cases were younger at diagnosis (19.3 ± 8.6 vs. 25.7 ± 11.8,

=.004). Patients with familial compared to sporadic IBD were significantly more likely to require steroid treatment (80% vs. 54.5%,

=.009), biological treatment (94.3%, vs. 63.6%,

<.001) or surgery (25.7%, vs. 11.4%,

=.048).

IBD with a very strong positive family history is associated with younger age at onset and a more adverse IBD phenotype compared to sporadic IBD.

IBD with a very strong positive family history is associated with younger age at onset and a more adverse IBD phenotype compared to sporadic IBD.

Erectile dysfunction is associated with diabetes mellitus with an estimated prevalence of 52.5% in the diabetic population. The first-line therapy for erectile dysfunction is phosphodiesterase type 5 inhibitors, but data suggest that diabetic men may be less responsive than non-diabetic men. Thus, other treatments, including intracavernosal injections, intraurethral prostaglandin, vacuum erection devices and penile prosthetic surgery, should be considered in management of diabetic men with erectile dysfunction refractory to phosphodiesterase type 5 inhibitors. Furthermore, combination therapy of phosphodiesterase type 5 inhibitors and other oral treatments such as arginine or l-carnitine may have synergistic effects resulting in better outcomes. In addition, there are novel therapies such as low-intensity shockwave therapy and stem-cell therapy, which may also be effective in targeted treatment modalities. Furthermore, studies suggest that erectile dysfunction can be improved by targeting concurrent comorbidities or metabolic diseases such as depression, hypertension, hypogonadism, and dyslipidaemia. We present an evidence-based narrative review focusing on the management of erectile dysfunction in diabetic men who have not responded to phosphodiesterase type 5 inhibitors.

Both clinicians and patients should be aware of the different management options in diabetic patients who have not responded to phosphodiesterase type 5 inhibitors.

Both clinicians and patients should be aware of the different management options in diabetic patients who have not responded to phosphodiesterase type 5 inhibitors.

To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC).

Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (11) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription.

The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). SAHA Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only.

High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.

High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.