Bisphenol A analogues and metabolic syndrome in women with polycystic ovary syndrome.

Bisphenols (BPs) have become a chemical group of special interest due to their ability to interfere with the endocrine system and their ubiquitous presence in the environment. As some of them possess mild estrogenic and anti-androgenic effects, they might be associated with the diagnosis of polycystic ovary syndrome (PCOS). Acting on multiple tissues, BPs exposure may lead to metabolic derangements characteristic for metabolic syndrome (MetS). Therefore, the aim of this study was to determine the potential relationship between exposure to some BPA analogues and features of the MetS in women with PCOS. Serum BPE, BPC, BPG, BPM, BPP, BPZ, BPFL, and BPBP concentrations did not differ significantly between the PCOS (n = 135) and the control subjects (n = 104). However, women whose serum BPM and BPP concentrations were in the highest tertile were more likely to be diagnosed with PCOS (adjusted OR; [95%CI] 0.43; [0.20; 0.89], P < 0.001 and 0.56; [0.27; 0.96], P = 0.049, consequently). Serum concentrations of BPs were not associated with the MetS diagnosis in the PCOS group. There was a negative correlation between the concentrations of serum BPBP and total serum cholesterol (r = - 0.153; P = 0.019), BPE and serum testosterone (r = - 0.160; P = 0.014) as well as BPC and HDL-cholesterol (r = - 0.138; P = 0.036). There was a positive correlation between the concentrations of BPP and serum triglycerides (r = 0.138; P = 0.036). Our results point to the potential association between exposure to BPM, BPP, and the diagnosis of PCOS, along with the impact of BPBP, BPE, BPC, and BPP on the metabolic features of the MetS.

Phage Interactions with the Nervous System in Health and Disease.

The central nervous system manages all of our activities (e.g., direct thinking and decision-making processes). It receives information from the environment and responds to environmental stimuli. Bacterial viruses (bacteriophages, phages) are the most numerous structures occurring in the biosphere and are also found in the human organism. Therefore, understanding how phages may influence this system is of great importance and is the purpose of this review. We have focused on the effect of natural bacteriophages in the central nervous system, linking them to those present in the gut microbiota, creating the gut-brain axis network, as well as their interdependence. Importantly, based on the current knowledge in the field of phage application (e.g., intranasal) in the treatment of bacterial diseases associated with the brain and nervous system, bacteriophages may have significant therapeutic potential. Moreover, it was indicated that bacteriophages may influence cognitive processing. In addition, phages (via phage display technology) appear promising as a targeted therapeutic tool in the treatment of, among other things, brain cancers. The information collected and reviewed in this work indicates that phages and their impact on the nervous system is a fascinating and, so far, underexplored field. Therefore, the aim of this review is not only to summarize currently available information on the association of phages with the nervous system, but also to stimulate future studies that could pave the way for novel therapeutic approaches potentially useful in treating bacterial and non-bacterial neural diseases.

Serum bisphenol A analogues in women diagnosed with the polycystic ovary syndrome - is there an association?

Due to the endocrine disrupting effects of bisphenol A (BPA) several governmental authorities have banned its use and the manufacturers had to find alternative substances with similar chemical properties. This led to the increase in the use of so-called BPA analogues, which however also turn out to possess mild estrogenic and ani-androgenic properties and thus, may cause fertility problems and sex-hormone dependent endocrinopathies. The aim of this study was to evaluate the potential association between the exposure to BPA and its two analogues: BPS and BPF, with the diagnosis of the polycystic ovary syndrome (PCOS), which remains the most common female endocrinopathy. Serum concentrations of BPA, BPS and BPF were measured using high performance liquid chromatography method with tandem mass spectrometry (HPLC-MS/MS) among 199 women with PCOS and 158 control subjects. In women with PCOS serum BPS concentrations were significantly higher compared to the control subjects (geometric mean [95% CI]: 0.14 ng/mL [0.10; 1.17] vs. 0.08 ng/mL [0.06; 0.09], P = 0.023). Serum BPA and BPF concentrations did not differ between the studied groups. There was however a negative correlation between serum BPA and HOMA-IR (r = - 0.233, P = 0.001) and TST (r = - 0.203, P = 0.006) in women with PCOS. No correlations were found between the serum BPs and other metabolic parameters such as serum lipids, insulin, DHEA-S, androstenedione and FAI. When studying the association between serum BPA analogues and PCOS it turned out that women whose serum BPS concentrations were in the first tertile were more likely to be diagnosed with this endocrinopathy (OR [95% CI]: 1.21 [1.04; 3.46], P = 0.017). This association was also statistically significant when adjusted for age, education, BMI, smoking, income, and alcohol consumption (adjusted OR [95% CI]: 1.12 [1.03; 3.71], P = 0.029). These results point to the potential association between the exposure to BPS and the diagnosis of PCOS. The role of BPA is not clear and warrants further studies.

Application of 16S rRNA gene sequencing in Helicobacter pylori detection.

Helicobacter pylori is one of the major stomach microbiome components, promoting development of inflammation and gastric cancer in humans. H. pylori has a unique ability to transform into a coccoidal form which is difficult to detect by many diagnostic methods, such as urease activity detection, and even histopathological examination. Here we present a comparison of three methods for H. pylori identification: histological assessment (with eosin, hematoxylin, and Giemsa staining), polymerase chain reaction (PCR) detection of urease (ureA specific primers), and detection by 16S rRNA gene sequencing. The study employed biopsies from the antral part of the stomach (N = 40). All samples were assessed histologically which revealed H. pylori in eight patients. Bacterial DNA isolated from the bioptates was used as a template for PCR reaction and 16S rRNA gene sequencing that revealed H. pylori in 13 and in 20 patients, respectively. Thus, 16S rRNA gene sequencing was the most sensitive method for detection of H. pylori in stomach biopsy samples.

Safety Studies of Pneumococcal Endolysins Cpl-1 and Pal.

Bacteriophage-derived endolysins have gained increasing attention as potent antimicrobial agents and numerous publications document the in vivo efficacy of these enzymes in various rodent models. However, little has been documented about their safety and toxicity profiles. Here, we present preclinical safety and toxicity data for two pneumococcal endolysins, Pal and Cpl-1. Microarray, and gene profiling was performed on human macrophages and pharyngeal cells exposed to 0.5 µM of each endolysin for six hours and no change in gene expression was noted. Likewise, in mice injected with 15 mg/kg of each endolysin, no physical or behavioral changes were noted, pro-inflammatory cytokine levels remained constant, and there were no significant changes in the fecal microbiome. Neither endolysin caused complement activation via the classic pathway, the alternative pathway, or the mannose-binding lectin pathway. In cellular response assays, IgG levels in mice exposed to Pal or Cpl-1 gradually increased for the first 30 days post exposure, but IgE levels never rose above baseline, suggesting that hypersensitivity or allergic reaction is unlikely. Collectively, the safety and toxicity profiles of Pal and Cpl-1 support further preclinical studies.

Polish Cross-Cultural Adaptation and Validation of the Knee Outcome Survey Activities of Daily Living Scale (KOS-ADLS) in Patients Undergoing Total Knee Arthroplasty.

BACKGROUND The Knee Outcome Survey Activities of Daily Living Scale (KOS-ADLS) is a self-reported questionnaire used for the evaluation of the overall health of patients with knee dysfunctions. The purpose of this study was to perform a cross-cultural adaptation of the Polish version of KOS-ADLS and to evaluate its psychometric properties in patients at the end-stage of knee osteoarthritis who were qualified for a total knee replacement (TKR). MATERIAL AND METHODS Seventy patients consecutively qualified for surgical TKR procedure participated in this study. To adapt the KOS-ADLS, the following scales and reference tests were used: Knee injury and Osteoarthritis Outcome Score (KOOS), Visual Analogue Scale (VAS), Time Up and Go test (TUG), and Five Times Sit to Stand test (5×STS). The studies were conducted 3 times: 2 weeks before surgery (first study), 6 to 13 days later (retest), and 6 months after surgery. RESULTS The Polish version of KOS-ADLS showed excellent reliability (ICC=0.89 SEM=2.68, MDC=7.43) and high responsiveness (ES=4.76, SRM=3.18). The internal consistency was poor in the first assessment (Cronbach's alpha=0.68), but acceptable in the post-surgery evaluation (Cronbach's alpha=0.86). There were fair and moderate correlations found between KOS-ADLS and VAS scales in the first examination, TUG, and 5×STS. Stronger correlations were observed between the results obtained in KOS-ADLS and KOOS. CONCLUSIONS The Polish version of the KOS-ADLS demonstrated good reliability, validity, and responsiveness for use in patients who have undergone TKR surgery.

The Assessment of Static Balance in Patients after Total Hip Replacement in the Period of 2-3 Years after Surgery.

INTRODUCTION: The aim of this study was to assess static balance of patients after Total Hip Replacement (THR) compared with the age-matched, asymptomatic control group, considering the subject's gender and the time since the surgery. MATERIALS AND METHODS: The Total Hip Replacement (THR) group consisted of 55 subjects (mean age: 56.3 ± 8.7 years) and the control group consisted of 48 subjects (mean age: 58 ± 6.2 years). For the assessment of static balance, a stabilometric force platform was used. All subjects performed two 30-second trials in the double-leg stance position with eyes opened and closed. In the study group, the stabilometric assessment was performed once within the period of 24 to 36 months after the surgery. RESULTS: Subjects from the study group had significantly increased mediolateral COP velocity in the test with eyes opened, as well as the values of most of the COP parameters (excluding COP path area) in the test with eyes closed, compared to the control group. Higher values of the selected COP parameters were observed in the male subjects from the study group. CONCLUSION: In contrast to a number of papers, our study revealed some deficits in static balance in patients after THR up to 2-3 years after surgery.

Evaluation of Selected Gait Parameters in Patients Prior to and at 6 Months Following Early Anterior Cruciate Ligament Reconstruction.

[b]Background. [/b]ACL rupture and reconstruction may lead to impairment of spatiotemporal and kinematic gait parameters. The purpose of this study was to evaluate patient's gait following a complete tear of the ACL and its endoscopic reconstruction.[b]Material and methods.[/b] 3D gait analysis was performed using the BTS Smart optoelectronic system (6 IR cameras, 120 Hz). The study group included 40 patients with complete unilateral ACL rupture and 37 healthy matched subjects. In the study group gait analysis was performed twice, within one to two weeks prior to the ACL reconstruction and the follow-up study six months after surgery. In the control group single gait analysis was performed.[b]Results. [/b]Six months after the ACL reconstruction the duration of the stance phase for the non-operated limb (p&amp;amp;lt;0,0000) and the initial double stance phase for the operated limb (p&amp;amp;lt;0,0000) were reduced. A statistically significant increase in the step length for both lower limbs was observed. Additionally patients gait cadence (p=0,0003) and mean gait speed (p=0,0006) have also increased. Nevertheless, in the second study, these parameters were still significantly different comparing to the control group. Analysing the kinematic parameters of patients" gait after surgery it was demonstrated, that the hip and knee joints range of motion in both limbs has increased in a statistically significant way. The range of motion of the ankle joint of the operated limb has also improved.[b]Conclusions.[/b] 1. Within six months after the ACL reconstruction there was significant improvement and normalization of the patient's gait pattern, though we may still observe significant differences when compared to the control group, which indicates the need for further rehabilitation focused on the re-education of patients gait pattern. 2. Results of our study indicates a need of long-term observation in the group of patients after ACL reconstruction to determine, whether the gait pattern impairment demonstrate further tendency to improve in time.

Mammalian Host-Versus-Phage immune response determines phage fate in vivo.

Emerging bacterial antibiotic resistance draws attention to bacteriophages as a therapeutic alternative to treat bacterial infection. Examples of phage that combat bacteria abound. However, despite careful testing of antibacterial activity in vitro, failures nevertheless commonly occur. We investigated immunological response of phage antibacterial potency in vivo. Anti-phage activity of phagocytes, antibodies, and serum complement were identified by direct testing and by high-resolution fluorescent microscopy. We accommodated the experimental data into a mathematical model. We propose a universal schema of innate and adaptive immunity impact on phage pharmacokinetics, based on the results of our numerical simulations. We found that the mammalian-host response to infecting bacteria causes the concomitant removal of phage from the system. We propose the notion that this effect as an indirect pathway of phage inhibition by bacteria with significant relevance for the clinical outcome of phage therapy.

Oral Application of T4 Phage Induces Weak Antibody Production in the Gut and in the Blood.

A specific humoral response to bacteriophages may follow phage application for medical purposes, and it may further determine the success or failure of the approach itself. We present a long-term study of antibody induction in mice by T4 phage applied per os: 100 days of phage treatment followed by 112 days without the phage, and subsequent second application of phage up to day 240. Serum and gut antibodies (IgM, IgG, secretory IgA) were analyzed in relation to microbiological status of the animals. T4 phage applied orally induced anti-phage antibodies when the exposure was long enough (IgG day 36, IgA day 79); the effect was related to high dosage. Termination of phage treatment resulted in a decrease of IgA again to insignificant levels. Second administration of phage induces secretory IgA sooner than that induced by the first administrations. Increased IgA level antagonized gut transit of active phage. Phage resistant E. coli dominated gut flora very late, on day 92. Thus, the immunological response emerges as a major factor determining phage survival in the gut. Phage proteins Hoc and gp12 were identified as highly immunogenic. A low response to exemplary foreign antigens (from Ebola virus) presented on Hoc was observed, which suggests that phage platforms can be used in oral vaccine design.

Bacteriophages displaying anticancer peptides in combined antibacterial and anticancer treatment.

AIMS: Novel anticancer strategies have employed bacteriophages as drug carriers and display platforms for anticancer agents; however, bacteriophage-based platforms maintain their natural antibacterial activity. This study provides the assessment of combined anticancer (engineered) and antibacterial (natural) phage activity in therapies. MATERIALS & METHODS: An in vivo BALB/c mouse model of 4T1 tumor growth accompanied by surgical wound infection was applied. The wounds were located in the areas of tumors. Bacteriophages (T4) were modified with anticancer Tyr-Ile-Gly-Ser-Arg (YIGSR) peptides by phage display and injected intraperitoneally. RESULTS & CONCLUSION: Tumor growth was decreased in mice treated with YIGSR-displaying phages. The acuteness of wounds, bacterial load and inflammatory markers in phages-treated mice were markedly decreased. Thus, engineered bacteriophages combine antibacterial and anticancer activity.