Impact of human papillomavirus infection on semen parameters and reproductive outcomes.

BACKGROUND: Human papillomavirus (HPV) has been shown to adversely affect human reproduction. We aimed to evaluate the prevalence of human papillomavirus (HPV) infection in men and its correlation with semen parameters and reproductive outcomes. METHODS: Semen samples and penile swabs were collected from potential sperm donors (SD, n = 97) and male partners of infertile couples (IM, n = 328). The presence of HPV DNA in semen samples and penile swabs was analyzed. Associations between hrHPV positive status and fertility outcomes as well as socio-behavioral and health characteristics were evaluated using the R software package. RESULTS: High-risk HPV (hrHPV) genotypes were detected in 28.9% of SD and 35.1% of IM (P = 0.312). Penile swabs were more frequently positive for hrHPV genotypes than semen samples in both IM (32.3% vs. 11.9%, P < 0.001) and SD (26.8% vs. 6.2%, P = 0.006). Men with hrHPV positive semen samples had lower semen volume (median volume 2.5 ml vs. 3 ml, P = 0.009), sperm concentration (median concentration 16 × 106/ml vs. 31 × 106/ml, P = 0.009) and total sperm count (median count 46 × 106 vs. 82 × 106, P = 0.009) than men with hrHPV negative samples. No association was identified between penile hrHPV status and semen parameters. CONCLUSIONS: Our findings indicate that penile HPV infection is common in both potential sperm donors and men from infertile couples. Although HPV positivity is higher in penile swabs, only HPV infection in semen samples affects sperm parameters. However, there was no association between hrHPV positivity in semen and fertility outcomes including abortion rate.

Prevalence and genotype distribution of human papillomavirus in Czech non-vaccinated heterosexual couples.

BACKGROUND: Data about the genotype-specific human papillomavirus (HPV) prevalence in the Czech Republic is limited. We aimed to evaluate the prevalence and concordance of genotype-specific HPV infection detected in semen samples, penile swabs and cervical swabs from non-vaccinated heterosexual couples without HPV-associated disease. METHODS: Semen samples and penile swabs were collected from male partners and cervical swabs were collected from female partners of heterosexual couples treated for infertility (n = 195). Presence of HPV DNA in semen samples and cervical swabs was analyzed using the cobas® HPV Test and PapilloCheck®. Only the PapilloCheck® test was used to detect HPV in penile swabs. The genotype-specific prevalence and concordance of HPV infection not targeted by vaccine were evaluated using Fisher exact test. RESULTS: Both partners were infected with any HPV type in 13.8% (27/195) of couples and, of these couples, 55.6% (15/27) harbored at least one mutual genotype. High-risk HPV (hrHPV) genotypes were detected in 12.3% (24/195) of semen samples, 31.3% (61/195) of penile swabs, and 19.5% (38/195) of cervical swabs (P < 0.001). The most prevalent hrHPV genotype were HPV53 (2.56%; 5/195) in semen samples, HPV16 (6.67%, 13/195) in penile swabs and HPV39 (3.59%, 7/195) in cervical swabs. Low-risk (lrHPV) genotypes were detected in 5.13% (10/195) of semen samples, 15.9% (31/195) of penile swabs, and 4.10% (8/195) of cervical swabs (P < 0.001). Male sexual partners of HPV-positive women were more likely to be infected with at least one of the same HPV types than female sexual partners of HPV-positive men (34.9% vs. 17.9%, P = 0.055). CONCLUSIONS: This study showed that the detection of HPV infection differ by anatomic site and gender. Regardless the anatomic site, high prevalence of HPV genital infection was found in both Czech men and women.

Recurrence of surgically treated parasagittal meningiomas: a meta-analysis of risk factors.

BACKGROUND: As the predictive role of many risk factors for parasagittal meningioma (PM) recurrence remains unclear, the objective of the meta-analysis was to make a comprehensive assessment of the predictive value of selected risk factors in these lesions. METHODS: Studies including data on selected risk factors, such as histology, tumor and sinus resection, sinus invasion, tumor localization, and immediate postoperative radiotherapy for PMs recurrence, were searched in the NCBI/NLM PubMed/MEDLINE, EBM Reviews/Cochrane Central, ProQuest, and Scopus databases, and analyzed using random effects modeling. RESULTS: Thirteen observational studies involving 1243 patients met the criteria for inclusion in the meta-analysis. WHO grading of meningiomas was identified as the most powerful risk factor for recurrence. WHO grade II meningiomas (OR 11.61; 95% CI 4.43-30.43; P < .01; I2 = 31%) or composite group of WHO grades II and III (OR 14.84; 95% CI 5.10-43.19; P < .01; I2 = 48%) had a significantly higher risk of recurrence than benign lesions. Moreover, an advanced sinus involvement (types IV-VI according to the Sindou classification) (OR 3.49; 95% CI 1.30-9.33; P = .01; I2 = 0%) and partial tumor resection (Simpson grades III-V) (OR 2.73; 95% CI 1.41-5.30; P = .03; I2 = 52%) were associated with a significantly higher risk of recurrence than their counterparts. CONCLUSION: Among the selected risk factors, high-grade WHO lesions, advanced sinus invasion, and partial tumor resection were associated with a higher risk of PM recurrence, with WHO grading system being the most powerful risk factor.

Toll-Like Receptor 7/8 Ligand, S28463, Suppresses Ascaris suum-induced Allergic Asthma in Nonhuman Primates.

S28463 (S28), a ligand for Toll-like receptor 7/8, has been shown to have antiinflammatory properties in rodent models of allergic asthma. The principle goal of this study was to assess whether these antiinflammatory effects can also be observed in a nonhuman primate (NHP) model of allergic asthma. NHPs were sensitized then challenged with natural allergen, Ascaris suum extract. The animals were treated with S28 orally before each allergen challenge. The protective effect of S28 in NHPs was assessed by measuring various asthma-related phenotypes. We also characterized the metabolomic and proteomic signatures of the lung environment and plasma to identify markers associated with the disease and treatment. Our data demonstrate that clinically relevant parameters, such as wheal and flare response, blood IgE levels, recruitment of white blood cells to the bronchoalveolar space, and lung responsiveness, are decreased in the S28-treated allergic NHPs compared with nontreated allergic NHPs. Furthermore, we also identified markers that can distinguish allergic from nonallergic or allergic and drug-treated NHPs, such as metabolites, phosphocreatine and glutathione, in the plasma and BAL fluid, respectively; and inflammatory cytokines, IL-5 and IL-13, in the bronchoalveolar lavage fluid. Our preclinical study demonstrates that S28 has potential as a treatment for allergic asthma in primate species closely related to humans. Combined with our previous findings, we demonstrate that S28 is effective in different models of asthma and in different species, and has the antiinflammatory properties clinically relevant for the treatment of allergic asthma.

Frequency of chromosome 17 polysomy in relation to CEP17 copy number in a large breast cancer cohort.

Eligibility to anti-HER2 therapy for breast tumors strictly depends on demonstrating HER2 overexpression (by immunohistochemistry) or HER2 gene amplification by in situ hybridization (ISH), usually defined by the ratio of HER2 gene to chromosome 17 centromere (CEP17) copies. However, the CEP17 copy number increase (CNI) has been proven responsible for misleading HER2 FISH results and recent small cohort studies suggest that chromosome 17 polysomy is actually very rare. Here we investigated by FISH the frequency of true chromosome 17 polysomy in a consecutive cohort of 5,477 invasive breast cancer patients. We evaluated and selected the LSI 17p11.2 probe for chromosome 17 enumeration on a training cohort of 67 breast cancer samples (CEP17 ≥ 2.5). LSI 17p11.2 was used in the 297/5,477 patients from the validation cohort displaying CEP17 CNI (CEP17 ≥ 3.0). Using HER2/17p11.2 scoring criteria, 37.3%/1.5% patients initially classified as equivocal/non-amplified were reclassified as amplified. For a more accurate assessment of chromosome 17 and ploidy in the samples, we tested six markers located on chromosome 17 and centromeric regions of chromosome 8 (CEP8) and 11 (CEP11) in 67 patients with CEP17 and LSI 17p11.2 CNI. True polysomy (hyperdiploidy) according to these markers was found in 0.48% of cases (24/5,020). CEP8 and CEP11 CNI (≥3.0) was more frequent in the hyperdiploid than CEP17 non-polysomic group (55.6% vs. 6.1% and 25% vs. 2.3%, respectively). Our results suggest that chromosome 17 polysomy is a rare event found in <1% breast cancer cases and that polysomy of other chromosomes frequently occurs with chromosome 17 polysomy.

BCL2 is an independent predictor of outcome in basal-like triple-negative breast cancers treated with adjuvant anthracycline-based chemotherapy.

Neither targeted therapies nor predictors for chemotherapy sensitivity are available for triple-negative breast cancer (TNBC). Our study included 187 patients with TNBC, 164 of whom were treated with anthracycline-based adjuvant chemotherapy. Eleven molecular biomarkers were analyzed. BCL2, epidermal growth factor receptor (EGFR), MYC, TOP2A, and Ki-67 protein expression was evaluated by immunohistochemistry. The status of the EGFR, MYC, and TOP2A genes and chromosomes 7, 8, and 17 was assessed using fluorescence in situ hybridization. High BCL2 expression predicted poor relapse-free survival (RFS) in patients treated with anthracycline-based adjuvant chemotherapy (p = 0.035), poor breast cancer-specific survival (BCSS) (p = 0.048), and a trend to poor overall survival (OS) (p = 0.085). High levels of BCL2 expression predicted poor OS in basal-like (BL) TNBC patients treated with adjuvant anthracycline-based regimens (log-rank p = 0.033, hazard ratio (HR) 3.04, 95 % confidence interval (CI) 1.04-8.91) and a trend to poor RFS (log-rank p = 0.079) and poor BCSS (log-rank p = 0.056). Multivariate analysis showed that BCL2 status, tumor size, and nodal status all had independent predictive significance for RFS (p = 0.005, p = 0.091, p = 0.003, respectively; likelihood ratio test for the whole model, p = 0.003), BCSS (p = 0.012, p = 0.077, p = 0.01, respectively; likelihood ratio test for the whole model, p = 0.016), and OS (p = 0.008, p = 0.004, p = 0.004, respectively; likelihood ratio test for the whole model, p = 0.0006). Similarly, multivariate analysis for BL TNBC showed BCL2, tumor size, and nodal status all had independent predictive significance for RFS (likelihood ratio test for the whole model, p = 0.00125), BCSS (p = 0.00035), and OS (p = 0.00063). High EGFR expression was associated with poor BCSS (p = 0.039) in patients treated with anthracycline-based adjuvant chemotherapy. Patients who underwent anthracycline-based adjuvant chemotherapy and exhibited CMYC amplification had a trend to worse BCSS (p = 0.066). In conclusion, high BCL2 expression is a significant independent predictor of poor outcome in TNBC patients treated with anthracycline-based adjuvant chemotherapy, and this is the first study showing the BCL2 prediction in BL TNBC. BCL2 expression analysis could facilitate decision making on adjuvant treatment in TNBC patients.

Are High Proanthocyanidins Key to Cranberry Efficacy in the Prevention of Recurrent Urinary Tract Infection?

Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n = 89) or a placebo group (n = 93) and received daily 500 mg of cranberry for 6 months. The number of UTI diagnoses was counted. The intent-to-treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p = 0.04, with an age-standardized 12-month UTI history (p = 0.01)]. The Kaplan-Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p = 0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs.

Pooling of samples to optimise SARS-CoV-2 detection in nasopharyngeal swabs and gargle lavage self-samples for covid-19 diagnostics and surveillance.

BACKGROUND: Testing of pooled samples is an effective strategy for increasing testing capacity while saving resources and time. This study aimed to validate pooled testing and gather real-life data on its use for Covid-19 surveillance with a gargle lavage (GL) self-sampling strategy. METHODS: Two-stage pooled testing with pools of 6 and 12 samples was used for preventive testing of an asymptomatic population and Covid-19 surveillance in Czech schools. Both GL and nasopharyngeal swabs were used for sampling. RESULTS: In total, 61,111 samples were tested. The use of pooled testing for large-scale Covid-19 surveillance reduced consumable costs by almost 75% and increased testing capacity up to 3.8-fold compared to standard methods. RT-PCR experiments revealed a minimal loss of sensitivity (0-2.2%) when using pooled samples, enabling the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes with Ct values >35. The minor loss of sensitivity was counterbalanced by a significantly increased throughput and the ability to substantially increase testing frequencies. CONCLUSIONS: Pooled testing is considerably more cost-effective and less time-consuming than standard testing for large-scale Covid-19 surveillance even when the prevalence of SARS-CoV-2 is fluctuating. Gargle lavage self-sampling is a non-invasive technique suitable for sample collection without a healthcare worker's assistance.

Life expectancy in glioblastoma patients who had undergone stereotactic biopsy: a retrospective single-center study.

OBJECTIVE: The best results in glioblastoma (GBM) are obtained through aggressive treatment comprising maximally radical but safe resection followed by chemoradiotherapy. However, certain patients will undergo only stereotactic biopsy. This paper aims to evaluate life expectancy in GBM patients who underwent only stereotactic biopsy, including the effect of subsequent oncological treatment. PATIENTS AND METHODS: Patients with confirmed GBM histology who had undergone stereotactic biopsy between June 2006 and December 2016 were retrospectively selected. Each patient had received a CT scan, followed by an MRI scan with a contrast agent. None of the patients were amenable to microsurgical resection. RESULTS: Of the 60 patients, 41 (69%) received no subsequent oncological treatment, while 14 (23%) underwent isolated radiotherapy. Mean survival time of all patients was 2.8 months. Those who received no additional treatment had an average survival time of 2.3 months; patients who received any type of oncological treatment was 3.7 months. Of these, those receiving radiotherapy alone had a mean survival of 3.1 months. Patients who received oncological treatment with the Stupp protocol had a survival time of 6.6 months. CONCLUSION: Diagnostic and surgical advances related to GBM treatment mean that radical resections can be performed even in eloquent brain areas. However, patients not indicated for resection will experience a major reduction in life expectancy. Patients who underwent stereotactic biopsy and received some form of oncological treatment experienced slightly increased overall survival relative to patients with a natural disease course. Patients with favorable clinical factors reacted better to treatment.

Effects of Reoperation Timing on Survival among Recurrent Glioblastoma Patients: A Retrospective Multicentric Descriptive Study.

Glioblastoma inevitably recurs, but no standard regimen has been established for treating this recurrent disease. Several reports claim that reoperative surgery can improve survival, but the effects of reoperation timing on survival have rarely been investigated. We, therefore, evaluated the relationship between reoperation timing and survival in recurrent GBM. A consecutive cohort of unselected patients (real-world data) from three neuro-oncology cancer centers was analyzed (a total of 109 patients). All patients underwent initial maximal safe resection followed by treatment according to the Stupp protocol. Those meeting the following criteria during progression were indicated for reoperation and were further analyzed in this study: (1) The tumor volume increased by >20-30% or a tumor was rediscovered after radiological disappearance; (2) The patient's clinical status was satisfactory (KS ≥ 70% and PS WHO ≤ gr. 2); (3) The tumor was localized without multifocality; (4) The minimum expected tumor volume reduction was above 80%. A univariate Cox regression analysis of postsurgical survival (PSS) revealed a statistically significant effect of reoperation on PSS from a threshold of 16 months after the first surgery. Cox regression models that stratified the Karnofsky score with age adjustment confirmed a statistically significant improvement in PSS for time-to-progression (TTP) thresholds of 22 and 24 months. The patient groups exhibiting the first recurrence at 22 and 24 months had better survival rates than those exhibiting earlier recurrences. For the 22-month group, the HR was 0.5 with a 95% CI of (0.27, 0.96) and a p-value of 0.036. For the 24-month group, the HR was 0.5 with a 95% CI of (0.25, 0.96) and a p-value of 0.039. Patients with the longest survival were also the best candidates for repeated surgery. Later recurrence of glioblastoma was associated with higher survival rates after reoperation.

Clinical and prognostic significance of detecting CEA, EGFR, LunX, c-met and EpCAM mRNA-positive cells in the peripheral blood, tumor-draining blood and bone marrow of non-small cell lung cancer patients.

Background: Surgical treatment of early-stage non-small cell lung cancer (NSCLC) yields highest expectations for recovery. However, the frequency of further disease progression remains high since micro-metastatic disease may be undetected by conventional diagnostic methods. We test the presence and prognostic impact of circulating tumor cells (CTCs) in peripheral blood (PB), tumor-draining pulmonary blood (TDB) and bone marrow (BM) samples from NSCLC patients. Methods: The presence of circulating/disseminated tumor cells (CTCs/DTCs) was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis in PB, TDB and BM samples before surgery in 119 stage IA-IIIA NSCLC patients (Clinical Trial NS10285). Results: NSCLC patients with the presence of carcinoembryonic antigen (CEA) mRNA-positive CTCs/DTCs in TDB and BM had significantly shorter cancer-specific survival (CSS) (P<0.013, resp. P<0.038). Patients with the presence of epithelial cellular adhesion molecule (EpCAM) mRNA-positive CTCs in TDB samples had significantly shorter CSS and disease-free survival (DFS) (P<0.031, resp. P<0.045). A multivariate analysis identified the presence of CEA mRNA-positive CTCs in the PB as an independent negative prognostic factor for DFS (P<0.005). No significant correlation of CTCs/DTCs presence and other prognostic factors was found. Conclusions: In NSCLC patients undergoing radical surgery, the presence of CEA and EpCAM mRNA-positive CTCs/DTCs is associated with poorer survival.

2­Cl­IB­MECA regulates the proliferative and drug resistance pathways, and facilitates chemosensitivity in pancreatic and liver cancer cell lines.

Specific A3 adenosine receptor (A3AR) agonist, 2­chloro­N6­(3­iodobenzyl)­5'­N­methylcarboxamidoadenosine (2­Cl­IB­MECA), demonstrates anti­proliferative effects on various types of tumor. In the present study, the cytotoxicity of 2­Cl­IB­MECA was analyzed in a panel of tumor and non­tumor cell lines and its anticancer mechanisms in JoPaca­1 pancreatic and Hep­3B hepatocellular carcinoma cell lines were also investigated. Initially, decreased tumor cell proliferation, cell accumulation in the G1 phase and inhibition of DNA and RNA synthesis was found. Furthermore, western blot analysis showed decreased protein expression level of ß­catenin, patched1 (Ptch1) and glioma­associated oncogene homolog zinc finger protein 1 (Gli1), which are components of the Wnt/ß­catenin and Sonic hedgehog/Ptch/Gli transduction pathways. In concordance with these findings, the protein expression levels of cyclin D1 and c­Myc were reduced. Using a luciferase assay, it was revealed for the first time a decrease in ß­catenin transcriptional activity, as an early event following 2­Cl­IB­MECA treatment. In addition, the protein expression levels of multidrug resistance­associated protein 1 and P­glycoprotein (P­gp) were reduced and the P­gp xenobiotic efflux function was also reduced. Next, the enhancing effects of 2­Cl­IB­MECA on the cytotoxicity of conventional chemotherapy was investigated. It was found that 2­Cl­IB­MECA enhanced carboplatin and doxorubicin cytotoxic effects in the JoPaca­1 and Hep­3B cell lines, and a greater synergy was found in the highly tumorigenic JoPaca­1 cell line. This provides a novel in vitro rationale for the utilization of 2­Cl­IB­MECA in combination with chemotherapeutic agents, not only for hepatocellular carcinoma, but also for pancreatic cancer. Other currently used conventional chemotherapeutics, fluorouracil and gemcitabine, showed synergy only when combined with high doses of 2­Cl­IB­MECA. Notably, experiments with A3AR­specific antagonist, N­[9­Chloro­2­(2­furanyl)(1,2,4)­triazolo(1,5­c)quinazolin­5­yl]benzene acetamide, revealed that 2­Cl­IB­MECA had antitumor effects via both A3AR­dependent and ­independent pathways. In conclusion, the present study identified novel antitumor mechanisms of 2­Cl­IB­MECA in pancreatic and hepatocellular carcinoma in vitro that further underscores the importance of A3AR agonists in cancer therapy.

Evaluation of Non-Invasive Gargle Lavage Sampling for the Detection of SARS-CoV-2 Using rRT-PCR or Antigen Assay.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable disruption worldwide. For efficient SARS-CoV-2 detection, new methods of rapid, non-invasive sampling are needed. This study aimed to investigate the stability of SARS-CoV-2 in a novel medium for gargle-lavage (GL) self-sampling and to compare the performance of SARS-CoV-2 detection in paired self-collected GL and clinician-obtained nasopharyngeal swab (NPS) samples. The stability study for SARS-CoV-2 preservation in a novel medium was performed over 14 days (4 °C, 24-27 °C, and 37 °C). In total, 494 paired GL and NPS samples were obtained at the University Hospital in Olomouc in April 2021. SARS-CoV-2 detection in paired samples was performed with a SARS-CoV-2 Nucleic Acid Detection Kit (Zybio, Chongqing Municipality, Chongqing, China), an Elecsys® SARS-CoV-2 Antigen assay (Roche Diagnostics, Mannheim, Germany), and a SARS-CoV-2 Antigen ELISA (EUROIMMUN, Lübeck, Germany). The stability study demonstrated excellent SARS-CoV-2 preservation in the novel medium for 14 days. SARS-CoV-2 was detected in 55.7% of NPS samples and 55.7% of GL samples using rRT-PCR, with an overall agreement of 91.9%. The positive percent agreement (PPA) of the rRT-PCR in the GL samples was 92.7%, and the negative percent agreement (NPA) was 90.9%, compared with the NPS samples. The PPA of the rRT-PCR in the NPS and GL samples was 93.2% when all positive tests were used as the reference standard. Both antigen detection assays showed poor sensitivity compared to rRT-PCR (33.2% and 36.0%). rRT-PCR SARS-CoV-2 detection in self-collected GL samples had a similar PPA and NPA to that of NPSs. GL self-sampling offers a suitable and more comfortable alternative for SARS-CoV-2 detection.

Transcriptomic Profiling Revealed Lnc-GOLGA6A-1 as a Novel Prognostic Biomarker of Meningioma Recurrence.

BACKGROUND: Meningioma is the most common primary central nervous system neoplasm, accounting for about a third of all brain tumors. Because their growth rates and prognosis cannot be accurately estimated, biomarkers that enable prediction of their biological behavior would be clinically beneficial. OBJECTIVE: To identify coding and noncoding RNAs crucial in meningioma prognostication and pathogenesis. METHODS: Total RNA was purified from formalin-fixed and paraffin-embedded tumor samples of 64 patients with meningioma with distinct clinical characteristics (16 recurrent, 30 nonrecurrent with follow-up of >5 years, and 18 with follow-up of <5 years without recurrence). Transcriptomic sequencing was performed using the HiSeq 2500 platform (Illumina), and biological and functional differences between meningiomas of different types were evaluated by analyzing differentially expression of messenger RNA (mRNA) and long noncoding RNA (IncRNA). The prognostic value of 11 differentially expressed RNAs was then validated in an independent cohort of 90 patients using reverse transcription quantitative (real-time) polymerase chain reaction. RESULTS: In total, 69 mRNAs and 108 lncRNAs exhibited significant differential expression between recurrent and nonrecurrent meningiomas. Differential expression was also observed with respect to sex (12 mRNAs and 59 lncRNAs), World Health Organization grade (58 mRNAs and 98 lncRNAs), and tumor histogenesis (79 mRNAs and 76 lncRNAs). Lnc-GOLGA6A-1, ISLR2, and AMH showed high prognostic power for predicting meningioma recurrence, while lnc-GOLGA6A-1 was the most significant factor for recurrence risk estimation (1/hazard ratio = 1.31; P = .002). CONCLUSION: Transcriptomic sequencing revealed specific gene expression signatures of various clinical subtypes of meningioma. Expression of the lnc-GOLGA61-1 transcript was found to be the most reliable predictor of meningioma recurrence.

Glycosylation patterns of HIV-1 gp120 depend on the type of expressing cells and affect antibody recognition.

Human immunodeficiency virus type 1 (HIV-1) entry is mediated by the interaction between a variably glycosylated envelope glycoprotein (gp120) and host-cell receptors. Approximately half of the molecular mass of gp120 is contributed by N-glycans, which serve as potential epitopes and may shield gp120 from immune recognition. The role of gp120 glycans in the host immune response to HIV-1 has not been comprehensively studied at the molecular level. We developed a new approach to characterize cell-specific gp120 glycosylation, the regulation of glycosylation, and the effect of variable glycosylation on antibody reactivity. A model oligomeric gp120 was expressed in different cell types, including cell lines that represent host-infected cells or cells used to produce gp120 for vaccination purposes. N-Glycosylation of gp120 varied, depending on the cell type used for its expression and the metabolic manipulation during expression. The resultant glycosylation included changes in the ratio of high-mannose to complex N-glycans, terminal decoration, and branching. Differential glycosylation of gp120 affected envelope recognition by polyclonal antibodies from the sera of HIV-1-infected subjects. These results indicate that gp120 glycans contribute to antibody reactivity and should be considered in HIV-1 vaccine design.

The Influence of Gene Aberrations on Survival in Resected IDH Wildtype Glioblastoma Patients: A Single-Institution Study.

This prospective population-based study on a group of 132 resected IDH-wildtype (IDH-wt) glioblastoma (GBM) patients assesses the prognostic and predictive value of selected genetic biomarkers and clinical factors for GBM as well as the dependence of these values on the applied therapeutic modalities. The patients were treated in our hospital between June 2006 and June 2015. Clinical data and tumor samples were analyzed to determine the frequencies of TP53, MDM2, EGFR, RB1, BCR, and CCND1 gene aberrations and the duplication/deletion statuses of the 9p21.3, 1p36.3, 19q13.32, and 10p11.1 chromosome regions. Cut-off values distinguishing low (LCN) and high (HCN) copy number status for each marker were defined. Additionally, MGMT promoter methylation and IDH1/2 mutation status were investigated retrospectively. Young age, female gender, Karnofsky scores (KS) above 80, chemoradiotherapy, TP53 HCN, and CCND1 HCN were identified as positive prognostic factors, and smoking was identified as a negative prognostic factor. Cox proportional regression models of the chemoradiotherapy patient group revealed TP53 HCN and CCND1 HCN to be positive prognostic factors for both progression-free survival and overall survival. These results confirmed the influence of key clinical factors (age, KS, adjuvant oncotherapy, and smoking) on survival in GBM IDH-wt patients and demonstrated the prognostic and/or predictive importance of CCND1, MDM2, and 22q12.2 aberrations.

The effectiveness of dried cranberries ( Vaccinium macrocarpon) in men with lower urinary tract symptoms.

Lower urinary tract symptoms (LUTS) are a common condition in older men. The objective of the present study was to evaluate the efficacy and tolerability of cranberry (Vaccinium macrocarpon) powder in men at risk of prostate disease with LUTS, elevated prostate-specific antigen (PSA), negative prostate biopsy and clinically confirmed chronic non-bacterial prostatitis. Forty-two participants received either 1500 mg of the dried powdered cranberries per d for 6 months (cranberry group; n 21) or no cranberry treatment (control group; n 21). Physical examination, International Prostate Symptom Score, quality of life (QoL), five-item version of the International Index of Erectile Function (IIEF-5), basic clinical chemistry parameters, haematology, Se, testosterone, PSA (free and total), C-reactive protein (CRP), antioxidant status, transrectal ultrasound prostate volume, urinary flow rate, ultrasound-estimated post-void residual urine volume at baseline, and at 3 and 6 months, and urine ex vivo anti-adherence activity were determined in all subjects. In contrast to the control group, patients in the cranberry group had statistically significant improvement in International Prostate Symptom Score, QoL, urination parameters including voiding parameters (rate of urine flow, average flow, total volume and post-void residual urine volume), and lower total PSA level on day 180 of the study. There was no influence on blood testosterone or serum CRP levels. There was no statistically significant improvement in the control group. The results of the present trial are the first firm evidence that cranberries may ameliorate LUTS, independent of benign prostatic hyperplasia or C-reactive protein level.

The Percentage of Free PSA and Urinary Markers Distinguish Prostate Cancer from Benign Hyperplasia and Contribute to a More Accurate Indication for Prostate Biopsy.

The main advantage of urinary biomarkers is their noninvasive character and the ability to detect multifocal prostate cancer (CaP). We have previously implemented a quadruplex assay of urinary markers into clinical practice (PCA3, AMACR, TRPM8 and MSMB with KLK3 normalization). In this study, we aimed to validate it in a larger cohort with serum PSA 2.5-10 ng/mL and test other selected transcripts and clinical parameters, including the percentage of free prostate-specific antigen (PSA) (% free PSA) and inflammation. In the main cohort of 299 men, we tested the quadruplex transcripts. In a subset of 146 men, we analyzed additional transcripts (CD45, EPCAM, EZH2, Ki67, PA2G4, PSGR, RHOA and TBP). After a prostate massage, the urine was collected, RNA isolated from a cell sediment and qRT-PCR performed. Ct values of KLK3 (i.e., PSA) were strongly correlated with Ct values of other genes which play a role in CaP (i.e., PCA3, AMACR, TRPM8, MSMB and PSGR). AMACR, PCA3, TRPM8 and EZH2 mRNA expression, as well as % free PSA, were significantly different for BPH and CaP. The best combined model (% free PSA plus PCA3 and AMACR) achieved an AUC of 0.728 in the main cohort. In the subset of patients, the best AUC 0.753 was achieved for the combination of PCA3, % free PSA, EPCAM and PSGR. PCA3 mRNA was increased in patients with inflammation, however, this did not affect the stratification of patients indicated for prostate biopsy. In conclusion, the percentage of free PSA and urinary markers contribute to a more accurate indication for prostate biopsy.

Comparison of Bypass and Non-Bypass Surgical Treatments for Internal Carotid Artery Blood Blister-Like Aneurysms: A Meta-Analysis of Efficacy, Safety, and Outcomes.

BACKGROUND: The optimal surgical strategy for treating internal carotid artery (ICA) blood blister-like aneurysms (BBAs) has remained unclear. Although some have preferred bypass surgery, others have favored less-demanding surgical methods. The aim of the present meta-analysis was to assess the efficacy, safety, and outcomes of bypass and non-bypass surgical methods when intended as primary treatment of ICA BBAs. METHODS: Studies reporting data on the outcomes of interest for surgically treated patients with ICA BBAs were searched for in the PubMed/MEDLINE, Evidence-Based Medicine Reviews, Cochrane Central, ProQuest, and Scopus databases. The data were analyzed using random effects modeling. RESULTS: Seven observational studies involving 140 patients met the inclusion criteria. The patients treated with bypass surgery, compared with those treated with non-bypass techniques, had lower odds of poor outcomes (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.28-2.02; P = 0.57; I2 = 0%), postoperative vasospasm (OR, 1.73; 95% CI, 0.38-7.92; P = 0.48; I2 = 19%), intraoperative bleeding (OR, 3.37; 95% CI, 0.82-13.90; P = 0.09; I2 = 0%), postoperative bleeding (OR, 1.91; 95% CI, 0.47-7.76; P = 0.36; I2 = 0%), and postoperative recurrence of BBAs (OR, 2.16; 95% CI, 0.54-8.66; P < 0.28; I2 = 0%). No comparison, however, achieved statistical significance. CONCLUSIONS: For surgeons who use both bypass and non-bypass surgical strategies, the 2 methods seemed comparable in terms of the outcomes of interest, although the bypass technique appeared superior. However, comparisons with studies reporting bypass as the uniquely preferred technique have indicated that specialization in, and preference for, the bypass procedure has been associated with more favorable outcomes.

Head-To-Head Comparison of Biological Behavior of Biocompatible Polymers Poly(Ethylene Oxide), Poly(2-Ethyl-2-Oxazoline) and Poly[N-(2-Hydroxypropyl)Methacrylamide] as Coating Materials for Hydroxyapatite Nanoparticles in Animal Solid Tumor Model.

Nanoparticles (NPs) represent an emerging platform for diagnosis and treatment of various diseases such as cancer, where they can take advantage of enhanced permeability and retention (EPR) effect for solid tumor accumulation. To improve their colloidal stability, prolong their blood circulation time and avoid premature entrapment into reticuloendothelial system, coating with hydrophilic biocompatible polymers is often essential. Most studies, however, employ just one type of coating polymer. The main purpose of this study is to head-to-head compare biological behavior of three leading polymers commonly used as "stealth" coating materials for biocompatibilization of NPs poly(ethylene oxide), poly(2-ethyl-2-oxazoline) and poly[N-(2-hydroxypropyl)methacrylamide] in an in vivo animal solid tumor model. We used radiolabeled biodegradable hydroxyapatite NPs as a model nanoparticle core within this study and we anchored the polymers to the NPs core by hydroxybisphosphonate end groups. The general suitability of polymers for coating of NPs intended for solid tumor accumulation is that poly(2-ethyl-2-oxazoline) and poly(ethylene oxide) gave comparably similar very good results, while poly[N-(2-hydroxypropyl)methacrylamide] was significantly worse. We did not observe a strong effect of molecular weight of the coating polymers on tumor and organ accumulation, blood circulation time, biodistribution and biodegradation of the NPs.