Dynamics of Microbiome Changes in the Endometrium and Uterine Cervix during Embryo Implantation: A Comparative Analysis.

BACKGROUND The microbiome is the collection of all micro-organisms and their genes, which naturally live in and on the body. The cervical and endometrial bacterial microbiome has previously been reported to affect fertility and influence the outcomes of assisted reproductive therapy (ART), including embryo transfer. This study aimed to evaluate the cervical and endometrial bacterial microbiome in 177 women treated for infertility before, during, and after embryo implantation, and the outcomes. MATERIAL AND METHODS Cervical and endometrial swabs were collected from 177 women diagnosed with infertility at 3 time points: (1) during the initial examination, (2) during implantation, (3) 10-14 days after implantation. Next-generation sequencing (NGS) was used to analyze the bacterial microbiome. Taxonomic identification was performed with the Usearch algorithm. RESULTS There was a significant change in the number of patients with Escherichia coli depending on the collection time. For the first swab collection, there were significant negative relationships between the percentage of Gardnerella vaginalis and Lactobacillus spp. For the second collection, there was a negative relationship between Lactobacillus helveticus and Lactobacillus jensenii. For the third collection, negative relationships were found between Escherichia coli and Lactobacillus spp. A similar distribution of the bacterial microbiome was observed in all 3 swab collections. CONCLUSIONS Lactobacillus spp. were the main bacteria identified in the cervix and endometrium, present before, during, and after successful embryo transfer. E. coli and G. vaginalis reduced the protective effect of Lactobacilli before, during, and after embryo transfer.

Reinfections from SARS-CoV-2: A Retrospective Study from the Gyncentrum Genetic Laboratory in Sosnowiec, Poland, April 2020 to July 2022.

BACKGROUND The increasing number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections has opened a new research direction related to analyzing long-term immune response and accurately characterizing individual cases of reinfection to understand its mechanism and estimate the risk of widespread reinfection both locally and globally. This retrospective study from the Gyncentrum Genetic Laboratory in Sosnowiec, Poland aimed to evaluate reinfections from SARS-CoV-2 between April 2020 and July 2022. MATERIAL AND METHODS The study extended the previously published report on SARS-CoV-2 infection cases in Poland by analyzing 8041 reinfections diagnosed with real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. Data were collected on the amount of time elapsed from the first infection to the next and, based on these data, all results were divided into several groups for statistical analysis: 0-44, 45-90, 91-200, 201-310, 311-420, and >420 (days). RESULTS The study showed that of the 8041 patients who experienced reinfection, the vast majority (5505) became reinfected more than 310 days after the original infection, even though the average time between infections was 354.3 days. Statistical analysis revealed that the risk of SARS-CoV-2 reinfection increases with time and that this relationship becomes statistically significant after the 200th day following the initial infection (p<0.01). CONCLUSIONS We have shown that acquired immunity to SARS-CoV-2 infection is relatively short-lived - it starts diminishing about 6 months after the initial positive test. Moreover, the risk of reinfection is very high more than 1 year after the initial infection.

A Retrospective Population Study of 385 191 Positive Real-Time Reverse Transcription-Polymerase Chain Reaction Tests For SARS-CoV-2 from a Single Laboratory in Katowice, Poland from April 2020 to July 2022.

BACKGROUND This retrospective population study identified 385 191 positive real-time reverse transcription-polymerase chain reaction (RT-PCR) tests for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from a single laboratory in Katowice, Poland, from April 2020 to July 2022. MATERIAL AND METHODS The material was nasopharyngeal, nasopharyngeal swab or bronchial lavage, and bronchoalveolar lavage (BAL) to confirm or exclude SARS-CoV-2 infection with the RT-PCR technique. Personal data are use according to the Provisions on the Protection of Personal Data by the Gyn-Centrum laboratory. RESULTS In 9 months of 2020, the number of SARS-CoV-2 results was 88 986; in 2021, it was 168 439, and in the first 7 months of 2022, it was 12 786. In 2020, the highest number of positive results was recorded in the third quarter (83 094 cases); 2021, in the 1st, 2nd, and 4th quarters (58 712; 37 720; and 71 753 cases, respectively), and in 2022, in the 1st quarter (127 613 cases) of the year. A positive result was observed more often in women and people aged 30-39, followed by those 40-49 years. Patients aged 10-19 years comprised the smallest population of SARS-CoV-2-positive cases. CONCLUSIONS In the Polish population studied, from April 2020 to July 2022, the detection rates of SARS-CoV-2 positivity were significantly higher for women than for men and in the 30-49 age group for both sexes. Also, the infection detection rate of 385 191 out of 1 332 659 patient samples, or 28.9%, supports that the Polish society adhered to public health recommendations for infection control during the COVID-19 pandemic.

Endothelin-3 is epigenetically silenced in endometrioid endometrial cancer.

PURPOSE: Changes in the activity of endothelins and their receptors may promote neoplastic processes. They can be caused by epigenetic modifications and modulators, but little is known about endothelin-3 (EDN3), particularly in endometrial cancer. The aim of the study was to determine the expression profile of endothelin family and their interactions with miRNAs, and to assess the degree of EDN3 methylation. METHODS: The study enrolled 45 patients with endometrioid endometrial cancer and 30 patients without neoplastic changes. The expression profile of endothelins and their receptors was determined with mRNA microarrays and RT-qPCR. The miRNA prediction was based on the miRNA microarray experiment and the mirDB tool. The degree of EDN3 methylation was assessed by MSP. RESULTS: EDN1 and EDNRA were overexpressed regardless of endometrial cancer grade, which may be due to the lack of regulatory effect of miR-130a-3p and miR-485-3p, respectively. In addition, EDN3 and EDNRB were significantly downregulated. CONCLUSION: The endothelial axis is disturbed in endometrioid endometrial cancer. The observed silencing of EDN3 activity may be mainly due to DNA methylation.

Crossroad between current knowledge and new perspective of diagnostic and therapy of late-onset schizophrenia and very late-onset schizophrenia-like psychosis: An update.

Schizophrenia is a chronic, highly individualized disease with many symptoms that can occur with varying severity in different patients. Schizophrenia affects 1% of the population, but occurs in almost 20% of patients after 40 years of age. It should be noted that the next peak in the incidence of schizophrenia occurs at the age of 60 years, affects mostly females, and is closely associated with a high risk of developing memory disorders. Therefore, postadolescent schizophrenia includes two distinct groups of patients: those whose symptoms onset at the age of 45 or 60. The purposes of this literature review were as follows: (1) synthetically characterize the clinical manifestations of schizophrenia; (2) discuss difficulties in the diagnosis of schizophrenia, especially in patients over 40 years of age; (3) discuss the clinical utility of different classes of marker in diagnostic and differentiating schizophrenia from neurodegenerative diseases in elderly people; (4) discuss therapeutic options for schizophrenia, pharmacotherapy, and psychotherapy, emphasizing the role of caregivers of people with psychosis in therapy, in preadolescence and postadolescence schizophrenia. We have tried to primarily discuss the findings of original articles from the last 10 years with an indication of their clinical implications with the issues discussed in the various subsections. Moreover, despite many years of research, no specific, precise algorithm has been developed that can be used in clinical practice during the diagnosis of schizophrenia. For this reason, the diagnosis of schizophrenia is primarily based on an interview with the patient and his family, as well as on the experience of a psychiatrist. It also seems that schizophrenia treatment should be carried out holistically, including pharmacotherapy, psychotherapy, and the support of caregivers of patients who have this psychosis, which increases the achievement of therapeutic success. Finally, we must be aware of the difficulties in diagnosing schizophrenia in the elderly and the need to modify pharmacological treatment. Currently, no guidelines have been developed for the differentiation of negative symptoms in elderly patients with schizophrenia from amotivation/avolition/apathy symptoms in elderly patients with neurodegenerative disorders.

Semen dysbiosis-just a male problem?

Seminal microflora is crucial to male fertility. Dysbiosis-disturbance of quantitative ratios of individual bacteria or appearance of pathogenic species-rarely results in symptomatic disease. Inflammation results in decreased sperm production, lower motility, or morphological changes and, in the long term, can cause ejaculatory duct obstruction, leading to infertility. Moreover, it may cause infection of the partner's female genital tract. Dysbiosis in both partners results in fertility problems, disorders in embryo implantation, or miscarriages. In addition, chronic inflammation of the male genitourinary system may accelerate the appearance of antisperm antibodies. A comprehensive examination of seminal microflora can clarify the causes of infertility or prevent pathological conditions that affect seminal parameters. Seminal microflora as a direct impact on fertility problems as well as a decrease in the effectiveness of assisted reproduction methods, insemination, or in vitro procedures.

From Alpha to Delta-Genetic Epidemiology of SARS-CoV-2 (hCoV-19) in Southern Poland.

In Poland, the first case of SARS-CoV-2 infection was confirmed in March 2020. Since then, many circulating virus lineages fueled rapid pandemic waves which inflicted a severe burden on the Polish healthcare system. Some of these lineages were associated with increased transmissibility and immune escape. Mutations in the viral spike protein, which is responsible for host cell recognition and serves as the primary target for neutralizing antibodies, are of particular importance. We investigated the molecular epidemiology of the SARS-CoV-2 clades circulating in Southern Poland from February 2021 to August 2021. The 921 whole-genome sequences were used for variant identification, spike mutation, and phylogenetic analyses. The Pango B.1.1.7 was the dominant variant (n = 730, 89.68%) from March 2021 to July 2021. In July 2021, the B.1.1.7 was displaced by the B.1.617.2 lineage with 66.66% in July 2021 and 92.3% in August 2021 frequencies, respectively. Moreover, our results were compared with the sequencing available on the GISAID platform for other regions of Poland, the Czech Republic, and Slovakia. The analysis showed that the dominant variant in the analyzed period was B.1.1.7 in all countries and Southern Poland (Silesia). Interestingly, B.1.1.7 was replaced by B.1.617.2 earlier in Southern Poland than in the rest of the country. Moreover, in the Czech Republic and Slovakia, AY lineages were predominant at that time, contrary to the Silesia region.

Marking the Profile of the Microflora of the Endometrium and Uterine Cervix in Women as a Potential Factor Determining the Effectiveness of In Vitro Fertilization.

One promising research trend involves evaluating the influence of microbiota in the reproductive system of women on becoming pregnant and maintaining pregnancy. The goal of this study was to define the microflora profile of the endometrium and uterine cervix in women qualified for an in vitro fertilization (IVF) procedure, which is expected to contribute to increasing the percentage of successful IVF implantations. Based on the conducted molecular analysis in the collected swabs, 22 bacterial strains were identified. Eleven strains (57%) that were isolated belong to the physiological microflora, the most common strain of which was Lactobacillus. Eight of the isolated strains (33%) were pathological microflora, among which the most common bacteria were from the Enterobacteriaceae family (which includes E. coli, Shigella, and Salmonella). Finally, three of the bacterial strains (10%) may be a component of both physiological or pathological microflora of the vagina: Bifidobacterium breve, Bifidobacterium longum group, and Alloscardovia omnicolens. The presence of Escherichia coli was detected in six women, Staphylococcus aureus also in six patients, Atopobium parvulum in three, Streptococcus salivarius group in three, Enterococcus faecalis in four, and Aerococcus christensenii in two patients. We found statistically significant relationships (p < 0.05) between Lactobacillus fermentum and Enterococcus faecalis, Lactobacillus delbrueckii and Escherichia coli groups, Lactobacillus FN667084_s and Staphylococcus aureus groups, as well as Lactobacillus fermentum and Streptococcus agalactiae. Based on the conducted study, it may be confirmed that the endometrium is, to a large extent, colonized by lactic acid bacilli. Apart from that, endometrial dysbiosis was not noted in patients qualified for the IVF procedure.

Signaling mechanisms and their regulation during in vivo or in vitro maturation of mammalian oocytes.

In vitro fertilization (IVF) is currently one of the most effective methods of infertility treatment. An alternative to commonly used ovarian hyperstimulation can become extracorporeal maturation of oocytes (in vitro maturation; IVM). Fertilization and normal development of the embryo depends on the cytoplasmic, nuclear and genomic maturity of the oocyte. The microenvironment of the ovarian follicle and maternal signals, which mediate bidirectional communication between granulosa, cumulus and oocyte cells, influence the growth, maturation and acquisition of oocyte development capability. During oogenesis in mammals, the meiosis is inhibited in the oocyte at the prophase I of the meiotic division due to the high cAMP level. This level is maintained by the activity of C-type natriuretic peptide (CNP, NPPC) produced by granulosa cells. The CNP binds to the NPR2 receptor in cumulus cells and is responsible for the production of cyclic guanosine monophosphate (cGMP). The cGMP penetrating into the oocyte through gap junctions inhibits phosphodiesterase 3A (PDE3A), preventing cAMP hydrolysis responsible for low MPF activity. The LH surge during the reproductive cycle reduces the activity of the CNP/NPR2 complex, which results in a decrease in cGMP levels in cumulus cells and consequently in the oocyte. Reduced cGMP concentration unblocks the hydrolytic activity of PDE3A, which decreases cAMP level inside the oocyte. This leads to the activation of MPF and resumption of meiosis. The latest IVM methods called SPOM, NFSOM or CAPA IVM consist of two steps: prematuration and maturation itself. Taking into account the role of cAMP in inhibiting and then unblocking the maturation of oocytes, they have led to a significant progress in terms of the percentage of mature oocytes in vitro and the proportion of properly developed embryos in both animals and humans.

Endocrine disorders and fertility and pregnancy: An update.

It is estimated that more and more couples suffer from fertility and pregnancy maintenance disorders. It is associated with impaired androgen secretion, which is influenced by many factors, ranging from genetic to environmental. It is also important to remember that fertility disorders can also result from abnormal anatomy of the reproductive male and female organ (congenital uterine anomalies - septate, unicornuate, bicornuate uterus; acquired defects of the uterus structure - fibroids, polyps, hypertrophy), disturbed hormonal cycle and obstruction of the fallopian tubes resulting from the presence of adhesions due to inflammation, endometriosis, and surgery, abnormal rhythm of menstrual bleeding, the abnormal concentration of hormones. There are many relationships between the endocrine organs, leading to a chain reaction when one of them fails to function properly. Conditions in which the immune system is involved, including infections and autoimmune diseases, also affect fertility. The form of treatment depends on infertility duration and the patient's age. It includes ovulation stimulation with clomiphene citrate or gonadotropins, metformin use, and weight loss interventions. Since so many different factors affect fertility, it is important to correctly diagnose what is causing the problem and to modify the treatment regimen if necessary. This review describes disturbances in the hormone secretion of individual endocrine organs in the context of fertility and the maintenance of pregnancy.

Crosstalk between Statins and Cancer Prevention and Therapy: An Update.

The importance of statins in cancer has been discussed in many studies. They are known for their anticancer properties against solid tumors of the liver or lung, as well as diffuse cancers, such as multiple myeloma or leukemia. Currently, the most commonly used statins are simvastatin, rosuvastatin and atorvastatin. The anti-tumor activity of statins is largely related to their ability to induce apoptosis by targeting cancer cells with high selectivity. Statins are also involved in the regulation of the histone acetylation level, the disturbance of which can lead to abnormal activity of genes involved in the regulation of proliferation, differentiation and apoptosis. As a result, tumor growth and its invasion may be promoted, which is associated with a poor prognosis. High levels of histone deacetylases are observed in many cancers; therefore, one of the therapeutic strategies is to use their inhibitors. Combining statins with histone deacetylase inhibitors can induce a synergistic anticancer effect.