Endothelial Vascular Function in Hypertensive Patients After Renin—Angiotensin System Blockad

It is unclear whether single and combined pharmacologic inhibition of the renin-angiotensin-aldosterone system have similar effects on endothelial function and blood pressure (BP). The authors evaluated 63 hypertensive patients divided into 4 groups (hydrochlorothiazide 25 mg/d; irbesartan [IRBE] 150 mg/d; quinapril [QUIN] 20 mg/d; or IRBE 150 mg/d + QUIN 20 mg/d) and 25 healthy normotensive subjects (normal) followed for 12 weeks. Endothelium-dependent dysfunction measured as flow-mediated dilation at Weeks 0 and 12 were: normal, 11.5%±2.4% vs 13.5%±2.0%; hydrochlorothiazide, 7.3%±2.0% vs 12.8%±3.1%; QUIN, 7.2%±2.8% vs 13.2%±2.1%; IRBE, 7.1%±2.8% vs 13.0%±2.9%; and IRBE + QUIN, 7.5%±1.9% vs 12.8%±3.0%. Nitroglycerin-mediated responses were: normal, 26.0%±1.9% vs 24.0%±2.5%; hydrochlorothiazide, 17.0%±2.2% vs 18.3%±2.6%; QUIN, 17.8%±3.2% vs 23.4%±3.0%; IRBE, 16.8%±3.6% vs 24.7%±2.0%; and IRBE + QUIN, 17.3%±3.0% vs 25.1%±2.5%. Antihypertensive therapy restored BP to normal and improved the endothelium-dependent and -independent dysfunction after renin-angiotensin-aldosterone system blockade. In a further finding, the combined effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade was not superior to the action of either of these treatments separately.     

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.     

The effect of vitamin E on sperm motility and viability in asthenoteratozoospermic men: In vitro study

Induction of oxidative stress during the sperm preparation process for assisted reproductive techniques (ART) in men can weaken sperm parameters. Vitamin E (VE) is considered a factor in boosting male fertility. This experimental study (in vitro) aimed to assess the impact of VE supplementation on sperm quality and lipid peroxidation during sperm sampling at different times. For this mention, semen samples were collected from 50 asthenoteratozoospermic men. Samples were divided into control and test groups for 2, 4 and 6 hr that the test group was incubated with VE (2 mM). In two groups, total motility, progressive motility and viability based on the WHO 2010 criteria were assessed. Moreover, malondialdehyde (MDA) levels were evaluated in each group. In the control group, total and progressive motility and sperm viability were decreased significantly after 2 hr; however, MDA levels were increased significantly after 6 hr. Also, in the test group, sperm parameters were increased significantly after 2 hr, and MDA levels were decreased significantly after 6 hr compared to the control group. In outcome, in vitro VE supplementation may protect spermatozoa from the adverse effect of oxidative stress during sperm preparation via preservation antioxidant processes in normal condition.     

Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics.     

Comparison of continuous vs. pulsed focused ultrasound in treated muscle tissue as evaluated by magnetic resonance imaging, histological analysis, and microarray analysis

The purpose of this study was to investigate the effect of different application modes of high intensity focused ultrasound (HIFU) to muscle tissue. HIFU was applied to muscle tissue of the flank in C3H/Km mice. Two dose regimes were investigated, a continuous HIFU and a short-pulsed HIFU mode. Three hours after HIFU treatment pre- and post-contrast T1-weighted, T2-weighted images and a diffusion-weighted STEAM sequence were obtained. After MR imaging, the animals were euthenized and the treated, and the non-treated tissue was taken out for histology and functional genomic analysis. T2 images showed increased signal intensity and post-contrast T1 showed a decreased contrast uptake in the central parts throughout the tissue of both HIFU modes. A significantly higher diffusion coefficient was found in the muscle tissue treated with continuous wave focused ultrasound. Gene expression analysis revealed profound changes of 54 genes. For most of the analyzed genes higher expression was found after treatment with the short-pulse mode. The highest up-regulated genes encoded for the MHC class III (FC ≈84), HSP 70 (FC ≈75) and FBJ osteosarcoma related oncogene (FC ≈21). Immunohistology and the immunoblot analysis confirmed the presence of HSP70 protein in both applied HIFU modes. The use of HIFU treatment on muscle tissue results in dramatic changes in gene expression; however, the same genes are up-regulated after the application of continuous or pulsed HIFU, indicating that the tissue reaction is independent of the type of tissue damage. Hundt and Yuh contributed equally to this paper. Supported in part by the Lucas Foundation and the Phil Allen Truse.     

Higher rates of rejection in HIV‐infected kidney transplant recipients on ritonavir‐boosted protease inhibitors: 3‐year follow‐up study

Rejection rates in HIV‐infected kidney transplant (KTx) recipients are higher than HIV‐negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug‐drug interactions, likely influencing outcomes. This is an IRB‐approved, single‐center, retrospective study of adult HIV‐infected KTx patients between 5/2009 and 12/2014 with 3‐year follow‐up, excluding antibody‐depleting induction. A total of 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre‐transplant dialysis. All patients received IL‐2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir‐boosted PI‐based HAART (rtv+) regimen. Patient and graft survival at 3 years were 93% and 90%. At 1‐, 2‐, and 3‐year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy‐proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P = 0.029), 59% vs 24% (P = 0.029), and 68% vs 24% (P = 0.01). Despite higher rejection rates, HIV‐infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.     

Comparison of sperm morphology and nuclear sperm quality in SPATA16‐ and DPY19L2‐mutated globozoospermic patients

The aim of this study was to compare the sperm morphology and nuclear sperm quality (sperm aneuploidy and DNA fragmentation) in two groups of globozoospermic patients: DPY19L2‐mutated patients (n = 6) and SPATA16‐mutated patients (n = 2). Results for these two groups were also compared to a group of fertile men (n = 25). Fluorescence in situ hybridisation was performed for chromosomes X, Y and 18. Sperm DNA fragmentation was evaluated by TUNEL assay. Sanger sequencing was performed for mutations screening of DPY19L2 and SPATA16 genes. Sperm analysis revealed a classic phenotype of total globozoospermia in DPY19L2‐mutated group and a particular phenotype characterised by a predominance of double/multiple round‐headed (39.00 ± 4.2%) and multi‐tailed spermatozoa (26.00 ± 16.97%) in SPATA16‐mutated group. FISH analysis showed a significantly higher aneuploidy rate in globozoospermic patients compared to controls (p < 0.05), and a higher rate was observed in SPATA16‐mutated group compared to DPY19L2‐mutated group (p < 0.05). DNA fragmentation index was significantly higher in globozoospermic men compared to controls (p < 0.001), and there is no statistically significant difference between the two globozoospermic groups. We showed that SPATA16 defects could be associated with an abnormal meiosis leading to a particular morphological sperm defect of double/multiple round‐headed and multi‐flagella and a higher sperm aneuploidy rate than in case of DPY19L2‐defects in classic globozoospermia.     

Regenerative immunology: the immunological reaction to biomaterials

Regenerative medicine promises to meet two of the most urgent needs of modern organ transplantation, namely immunosuppression‐free transplantation and an inexhaustible source of organs. Ideally, bioengineered organs would be manufactured from a patient's own biomaterials—both cells and the supporting scaffolding materials in which cells would be embedded and allowed to mature to eventually regenerate the organ in question. While some groups are focusing on the feasibility of this approach, few are focusing on the immunogenicity of the scaffolds that are being developed for organ bioengineering purposes. This review will succinctly discuss progress in the understanding of immunological characteristics and behavior of different scaffolds currently under development, with emphasis on the extracellular matrix scaffolds obtained decellularized animal or human organs which seem to provide the ideal template for bioengineering purposes.