Adjuvants : an essential component of neisseria vaccines

Adjuvants may be classified into delivery systems and immune potentiator or modulator molecules based on their mechanism of action. Neisseria vaccines containing traditional adjuvants such as aluminium salts have existed for long time, but meningitis caused by Neisseria meningitidis serogroups, particularly serogroup B, continues to be a global health problem. Novel strategies have applied in silico and recombinant technologies to develop "universal" antigens (e.g. proteins, peptides and plasmid DNA) for vaccines, but these antigens have been shown to be poorly immunogenic even when alum adjuvanted, implying a need for better vaccine design. In this work we review the use of natural, detoxified, or synthetic molecules in combination with antigens to activate the innate immune system and to modulate the adaptive immune responses. In the main, antigenic and imune potentiator signals are delivered using nano-, micro-particles, alum, or emulsions. The importance of interaction between adjuvants and antigens to activate and target dendritic cells, the bridge between the innate and adaptive immune systems, will be discussed. In addition, nasal vaccine strategies based on the development of mucosal adjuvants and Neisseria derivatives to eliminate the pathogen at the site of infection provide promising adjuvants effective not only against respiratory pathogens, but also against pathogens responsible for enteric and sexually transmitted diseases

Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®)

Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful.210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement.Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram - (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA.Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone.NCT02130713Date of trial Registration: 30/04/2014

Clinical correlation among male infertility and overall male health: a systematic review of the literature

Purpose: Ongoing evidence has suggested the role of male factor infertility as a potential predictor of mortality and general health status. The aim of the present review is to update the current knowledge base regarding the association between male factor infertility and general health through a critical review of the literature. Materials and Methods: A systematic review of the literature was carried out from inception to November 2019 in order to evaluate significant associations between male infertility and adverse health outcomes such as cardiovascular, oncologic, metabolic and autoimmune diseases as well as overall mortality. Results: In all, 27 studies met inclusion criteria and were critically examined. Five studies examined male infertility and cardiovascular disease risk, 11 examined oncologic risk (e.g., overall cancer risk, testis and prostate cancer), 8 examined aggregate chronic medical diseases and 5 infertility related to incidence of mortality, for a total of 599,807 men diagnosed with any male factor infertility covering a period from 1916 to 2016. Conclusions: A man’s fertility and overall health appear to be interconnected. Therefore, a diagnosis of male infertility may allow a window into future comorbidity and/or mortality which may help guide clinical decisions and counseling. Several possible etiologies such as genetic, epigenetic, developmental, and lifestyle-based factors need to be further evaluated in order to establish the underlying mechanisms between male infertility and health

Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®)

Background: Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful. Methods: 210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was > 3 months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600 mg for 21 days and an association of Serenoa repens 320 mg, Lactobacillus Sporogens 200 mg, Arbutin 100 mg for 30 days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement. Results: Biological recurrence at 2 months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram – (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA. Conclusions: Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone. Trial registration: NCT02130713 Date of trial Registration: 30/04/201

Mutant p53 improves cancer cells\u2019 resistance to endoplasmic reticulum stress by sustaining activation of the UPR regulator ATF6

Missense mutations in the TP53 gene are frequent in human cancers, giving rise to mutant p53 proteins that can acquire oncogenic properties. Gain of function mutant p53 proteins can enhance tumour aggressiveness by promoting cell invasion, metastasis and chemoresistance. Accumulating evidences indicate that mutant p53 proteins can also modulate cell homeostatic processes, suggesting that missense p53 mutation may increase resistance of tumour cells to intrinsic and extrinsic cancer-related stress conditions, thus offering a selective advantage. Here we provide evidence that mutant p53 proteins can modulate the Unfolded Protein Response (UPR) to increase cell survival upon Endoplasmic Reticulum (ER) stress, a condition to which cancer cells are exposed during tumour formation and progression, as well as during therapy. Mechanistically, this action of mutant p53 is due to enhanced activation of the pro-survival UPR effector ATF6, coordinated with inhibition of the pro-apoptotic UPR effectors JNK and CHOP. In a triple-negative breast cancer cell model with missense TP53 mutation, we found that ATF6 activity is necessary for viability and invasion phenotypes. Together, these findings suggest that ATF6 inhibitors might be combined with mutant p53-targeting drugs to specifically sensitise cancer cells to endogenous or chemotherapy-induced ER stress

Differential equations for multi-loop integrals and two-dimensional kinematics

In this paper we consider multi-loop integrals appearing in MHV scattering amplitudes of planar N=4 SYM. Through particular differential operators which reduce the loop order by one, we present explicit equations for the two-loop eight-point finite diagrams which relate them to massive hexagons. After the reduction to two-dimensional kinematics, we solve them using symbol technology. The terms invisible to the symbols are found through boundary conditions coming from double soft limits. These equations are valid at all-loop order for double pentaladders and allow to solve iteratively loop integrals given lower-loop information. Comments are made about multi-leg and multi-loop integrals which can appear in this special kinematics. The main motivation of this investigation is to get a deeper understanding of these tools in this configuration, as well as for their application in general four-dimensional kinematics and to less supersymmetric theories.Comment: 25 pages, 7 figure

Prevalence of Dal blood type and dog erythrocyte antigens (DEA) 1, 4, and 7 in canine blood donors in Italy and Spain

BackgroundThe aim of this study was to determine the prevalence of Dal, and DEA 1, 4, 7 blood types, in a population of canine blood donors from Italy and Spain. Three hundred and twenty blood donor dogs receiving an annual health evaluation were included in the study. DEA 1 blood type was determined using an immunochromatographic strip technique while Dal, DEA 4 and 7 blood types were determined with polyclonal antisera using agglutination on gel columns.ResultsOut of 320 dogs blood typed 7 (2 Cane Corso and 5 Doberman Pinschers) (2.2%) were Dal negative; 137 (42.8%) were positive for DEA 1; 320 (100%) were positive for DEA 4 and 43 (13.4%) were positive for DEA 7.ConclusionThis study showed a similar prevalence of DEA 1, 7 and 4 to that reported in previous studies in the same, and in different, geographic areas, and provides new data on the prevalence of the Dal blood group in Italy and Spain. There was no significant difference (P=0.8409) between prevalence of Dal negative blood types found in our population (2.2%) and the prevalence reported in a canine blood donor population from the USA (2.5%). Our study identified Dal negative dogs in a previously tested breed i.e. Doberman Pinschers, but also the Cane Corso breed was found to have Dal negative dogs

Hyperhomocysteinemia as an early predictor of erectile dysfunction: International index of erectile function (IIEF) and penile doppler ultrasound correlation with plasma levels of homocysteine

Erectile dysfunction (ED) is inability to achieve and maintain an erection to permit satisfactory sexual activity. Homocysteine (Hcys) is a sulfur-containing amino acid synthesized from the essential amino acid methionine. Experimental models have elucidated the role of hyperhomocysteinemia (HHcys) as a strong and independent predictor for atherosclerosis progression and impaired cavernosal perfusion. The aim of this study is to investigate the serum levels of Hcys in our cohort of patients with ED, to compare these values with these of control population and to examine Hcys as a predictive marker for those patients who are beginning to complain mild-moderate ED. A total of 431 patients were enrolled in the study. The whole cohort was asked to complete the International Index of Erectile Function (IIEF) questionnaire. The study population was divided in 3 main groups: Group A: 145 patients with no ED serving as a control group; Group B: 145 patients with mild or mild-moderate ED; Group C: 141 patients with moderate or severe ED. Each participant underwent blood analysis. All patients underwent baseline and dynamic penile Doppler ultrasonography. We found in our cohort mean Hcys plasma concentrations significantly higher than the cut-off point in both groups B and C (18.6 ± 4.7 and 28.38 ± 7.8, respectively). Mean IIEF score was 27.9 ± 1.39, 19.5 ± 2.6, and 11.1 ± 2.5 for groups A, B, and C, respectively (P < 0.0001). In the penile Doppler ultrasonography studies, a high significant inverse correlation was detected between the mean values of the 10th minute's peak-systolic velocity (PSV) and Hcys levels for the groups B and C. This establishes a dose-dependent association between Hcys and ED. Furthermore, we showed that Hcys was an earlier predictor of ED than Doppler studies, as the Hcys increase was present in patients with mild ED even before abnormal Doppler values