Immune checkpoint analysis in ear cancer.

BACKGROUND: Among cutaneous squamous cell carcinomas, the ear (ecSCC) is one of the most common sites. Loco regional lymph node metastasis is found in six to eleven percent of cases, corresponding to increased metastasis compared to other sites. The aim of this study was to test the markers PD-L1, PD-1, CD4, CD8, and FoxP3 for suitability as prognostic predictive markers. METHODS: Sixty-four patients with ecSCC were included in this study. The expression of immunohistochemical markers (PD-L1, PD-1, CD4, CD8, FOXP3) was correlated with retrospective clinic pathological parameters (lymph node metastasis, distant metastasis, lymph node metastasis during follow-up, disease progression, disease-specific death). RESULTS: There was a correlation between increased disease specific death and a weak Foxp3 (p = 0.003) or reduced CD8 (p = 0.04). A PD-L1 expression > 1% was found in 39.1% of patients. CONCLUSION: The investigated markers (CD4, CD8, FoxP3, PD-1, PD-L1) seem overall rather inappropriate for prognostic evaluation in ecSCC. Only the correlation of disease specific death with CD8 or FoxP3 seems to be worth testing in larger collectives.

VersKiK: Study protocol of an observational registry-based study on the current state of follow-up care and adherence to follow-up guidelines after cancer in childhood or adolescence.

BACKGROUND: This article describes the study design of the quantitative part of the VersKiK study, The primary objectives of this study are to examine the occurrence of late effects in survivors of childhood or adolescent cancer (module 1), investigate health-related vulnerabilities and medical service utilization within this survivor group (modules 1 and 3), and assess the alignment between documented follow-up care for cardiological and audiological late effects with guideline recommendations, along with evaluating the extent of adherence among paediatric cancer survivors (module 3). METHODS: This is a non-interventional retrospective observational cohort study. It is based on stochastically linked insurance claims data from approximately 150,000 statutory insured persons with information concerning around 25,000-30,000 cancer survivors recorded in the German Childhood Cancer Register (GCCR). To explore adherence to selected follow-up guidelines, intention to treat treatment data from clinical study groups for particular diagnostic entities will be additionally included. DISCUSSION: The growing group of survivors after cancer in childhood and adolescence is representing a special population with an increasing demand for life-long healthcare services through relative high probability of late effects. Currently, there is a limited evidence in Germany on utilization of corresponding medical services and adherence to follow-up guidelines. With this study design, we are aiming to address these gaps and, consequently, suggest improvements to existing follow-up guidelines and follow-up care provision in Germany.

Decellularization techniques of human foreskin for tissue engineering application.

The rapid development of tissue engineering (TE) and regenerative medicine brings an acute need for biocompatible and bioactive biological scaffolds to regenerate or restore damaged tissue. Great attention is focused on the decellularization of tissues or even whole organs, and the subsequent colonization of such decellularized extracellular matrices by recipient cells. The foreskin is an integral, normal part of the external genitalia that forms the anatomical covering of the glans penis and the urinary meatus of all human and non-human primates. It is mucocutaneous tissue that marks the boundary between mucosa and skin. In this work, we compared two innovative decellularization techniques for human foreskins obtained from donors. We compared the efficacy and feasibility of these protocols and the biosafety of prepared acellular dermal matrixes that can serve as a suitable scaffold for TE. The present study confirms the feasibility of foreskin decellularization based on enzymatic or detergent methods. Both techniques conserved the ultrastructure and composition of natural ECM while being DNA-free and non-toxic, making it an excellent scaffold for follow-up research and TE applications.

Experiences of Users with an Online Self-Guided Mental Health Training Program Using Gamification.

Young adulthood is a period of high risk for the development of mental health concerns. Increasing well-being among young adults is important to prevent mental health concerns and their consequences. Self-compassion has been identified as a modifiable trait with the potential to protect against mental health concerns. An online self-guided mental health training program using gamification was developed and the user experience was evaluated in a 6-week experimental design. During this period, 294 participants were allocated to use the online training program via a website. User experience was assessed via self-report questionnaires, and interaction data for the training program were also collected. Results showed that those who completed the intervention (n= 47) visited the website on average 3.2 days a week, with a mean of 45.8 interactions during the 6 weeks. Participants report positive user experiences of the online training, on average a System Usability Scale Brooke (1) score of 79.1 (out of 100) at the end-point. Participants showed positive engagement with story elements of the training, based on an average score of 4.1 (out of 5) in the evaluation of the story at the end-point. This study found the online self-compassion intervention for youth to be acceptable, although some features seem preferred by users as compared to others. Gamification in the form of a guiding story and a reward structure seemed to be a promising element for successfully motivating participants and serving as a guiding metaphor for self-compassion.

Human pegivirus viremia in HCV/HIV co-infected patients: Direct acting antivirals exert anti-pegivirus effects.

BACKGROUND: Human pegivirus (HPgV) is a single-stranded RNA virus​ that is closely related to hepatitis C virus (HCV)​. HPgV has also been shown to infect patients with human immunodeficiency virus (HIV). The mechanisms and disease outcomes of HPgV infections are largely unknown, although it has been implicated in both cancer and neurological diseases. There are no established therapies for HPgV. OBJECTIVES: To estimate the prevalence of HPgV in a cohort of HCV/HIV co-infected patients undergoing treatment for HCV with direct acting antivirals (DAA) and investigate the effect of DAA therapy on HPgV infection. STUDY DESIGN: RNA was extracted from plasma samples collected at time points before, during, and after DAA. HPgV RNA abundance was quantified by droplet digital PCR assays targeting the NS5A and 5'UTR domains and confirmed by RT-qPCR. Clinical, demographic and treatment data were analysed. RESULTS: HPgV RNA was detected and quantified in 26 of 100 patients' plasma (26%) before starting DAA. Patients with detectable HPgV were more likely to be male, had higher peak HIV plasma levels, and a history of injection drug use. Patients receiving sofosbuvir/ledipasvir (n = 9) displayed significantly lower HPgV levels at time of DAA completion and had lower post-DAA HPgV rebound​ levels compared to patients receiving sofosbuvir/velpatasvir (n = 11) although both regimens significantly reduced viremia directly following DAA completion. Sustained suppression of HPgV was â€‹also observed among patients (n = 2) receiving pegylated-interferon. CONCLUSIONS: HPgV RNA ​was frequently detected in HCV/HIV co-infected patients and ​was​ supressed by DAA and pegylated interferon therapies with sofosbuvir-ledipasvir showing greatest antiviral activity. These findings suggest potential treatment strategies for HPgV infections​.

Symptom networks in glioma patients: understanding the multidimensionality of symptoms and quality of life.

PURPOSE: To comprehend the complex relationship between symptoms and health-related quality of life (HRQoL) in patients with diffuse glioma, we applied symptom network analysis to identify patterns of associations between depression, cognition, brain tumor-related symptoms, and HRQoL. Additionally, we aimed to compare global strength between symptom networks to understand if symptoms are more tightly connected in different subgroups of patients. METHODS: We included 256 patients and stratified the sample based on disease status (preoperative vs. postoperative), tumor grade (grade II vs. III/IV), and fatigue status (non-fatigued vs. fatigued). For each subgroup of patients, we constructed a symptom network. In these six networks, each node represented a validated subscale of a questionnaire and an edge represented a partial correlation between two nodes. We statistically compared global strength between networks. RESULTS: Across the six networks, nodes were highly correlated: fatigue severity, depression, and social functioning in particular. We found no differences in GS between the networks based on disease characteristics. However, global strength was lower in the non-fatigued network compared to the fatigued network (5.51 vs. 7.49, p < 0.001). CONCLUSIONS: Symptoms and HRQoL are highly interrelated in patients with glioma. Interestingly, nodes in the network of fatigued patients were more tightly connected compared to non-fatigued patients. IMPLICATIONS FOR CANCER SURVIVORS: We introduce symptom networks as a method to understand the multidimensionality of symptoms in glioma. We find a clear association between multiple symptoms and HRQoL, which underlines the need for integrative symptom management targeting fatigue in particular.

Long-term care, care needs and wellbeing of individuals after cancer in childhood or adolescence (VersKiK): study protocol of a large scale multi-methods non-interventional study.

BACKGROUND: It has been shown previously that a relevant proportion of childhood cancer survivors suffers from late effects, which are often directly related to the cancer itself or its therapy, resulting in particular follow-up needs, additionally burdening healthcare systems. Being diagnosed with cancer at a vulnerable stage of development, this group of cancer survivors is at comparatively higher risk of relapse or subsequent cancer. Although national and international follow-up guidelines based on treatment modalities have been developed, their implementation seems to leave room for improvement. Additionally, they lack a sufficient consideration of the survivors' psychosocial needs, affecting their adherence to them. The aim of the VersKiK study is to provide representative information on late effects in childhood and adolescence cancer survivors in Germany. The main research objectives are: (1) to describe the state of follow-up care among survivors after a cancer diagnosis in childhood or adolescence; (2) to quantify the occurrence of late effects among this group of survivors; (3) to examine the adherence to selected audiological and cardiological follow-up guidelines and to identify factors affecting it; (4) to explore actual follow-up needs of paediatric cancer survivors; (5) to review selected follow-up guidelines with the aim to improve and expand them. METHODS: VersKiK is designed as a mixed-methods non-interventional study. We will use claims data from statutory health insurance companies in combination with individually linked population-based registry data from the German Childhood Cancer Registry (GCCR). This data base will permit us to quantify diagnoses and procedures in comparison to the general population as well as the adherence to existing follow-up guidelines. Additional information will be obtained through interviews with childhood and adolescence cancer survivors and their informal caregivers, as well as in focus groups with healthcare professionals. DISCUSSION: The present study aims to research the actual needs of individuals after cancer diagnosis and treatment in childhood or adolescence - physical, psychological and organisational - in order to improve existing follow-up guidelines. These improvements might further positively affect not only actual care provided to paediatric cancer survivors, but also benefit healthcare systems in general while decreasing consequent medical visits in this group of patients. TRIAL REGISTRATION: Registered at German Clinical Trial Register (ID: DRKS00025960 and DRKS00026092).

Quality of life and functional outcomes after transanal total mesorectal excision for rectal cancer-results from the implementation period in Denmark.

BACKGROUND: The standard operation for mid- and low rectal cancer total mesorectal excision (TME) is routinely performed as minimally invasive surgery. TME is associated with temporary or permanent functional impairment of pelvic organs, causing reduced quality of life (QoL). Concerns have been raised that the newest minimally invasive approach, transanal TME (TaTME), may further reduce urogenital and anorectal functions. OBJECTIVE: To determine if functional outcomes affecting QoL are altered after TaTME. Primary end-point is the impact of TaTME on QoL and functional outcomes. Secondary end-point is assessing differences in QoL and functional outcomes after TME surgery from below (TaTME) or above (transabdominal TME). DESIGN, SETTING, AND PARTICIPANTS: Observational study consisting of prospectively registered self-reported questionnaire data collected at baseline and follow-ups after TaTME. All patients who underwent TaTME during the Danish national implementation phase were included. Central surveillance of the implementation included questionnaires concerning QoL and functional outcomes. Analyses of functional results from the Danish cohort of the ROLARR trial (Jayne et al. in JAMA 318:1569-1580, (2017) are reported separately for perspective, representing the transabdominal approach to TME, i.e., laparoscopic- or robotic-assisted TME (LaTME/RoTME). Applied questionnaires include EORTC QLQ-C30, SF-36, LARS, ICIQ-MLUTS, ICIQ-FLUTS, IPSS, IIEF, SVQ, and FSFI. RESULTS: A total of 115 TaTME procedures were registered August 2016 to April 2019. LaTME/RoTME patients (n = 92) were operated on January 2011 to September 2014. A temporary postoperative decrease of QoL (global health status and functional scales) was observed, yet long-term results were unaffected by surgery in both groups. In TaTME patients, the anorectal dysfunction increased significantly (p < 0.001) from preoperative baseline to 13.5 months follow-up, where 67.5% (n = 52) reported major LARS symptoms. Urinary function was not significantly impaired after TME regardless of technique. The paucity of responses concerning sexual function precludes conclusions. CONCLUSIONS: Although an initial reduction in QoL after TME occurs, it normalizes within the first year postoperatively. In concurrence with international results, we found that significant anorectal dysfunction is common after TaTME. No data on anorectal function was available for LaTME/RoTME patients for comparison. We found no indications that transanal TME is inferior to transabdominal TME surgery concerning urogenital functions or health-related QoL.

Initiation of lactation and the provision of human milk to preterm infants in German neonatal intensive care units from the mothers' perspective.

BACKGROUND: If infants with a very low birth weight (VLBW) are to be fed exclusively with human milk, it is essential to focus on lactation initiation. The aim of the study is to learn more about the current state of lactation initiation and human milk provision in neonatal intensive care units in Germany from the mothers' perspective. METHODS: Written surveys were conducted with mothers of VLBW infants to learn more about the timing of initiation of lactation, pumping frequency during the first three days postpartum and feeding of the preterm infant during hospitalisation. RESULTS: The data of 437 mothers (response rate: 44.7%) were included in the analyses. Of these, only 7.8% stated that they had initiated lactation immediately after delivery and 38.2% within 6 h. In terms of pumping frequency, 50.1% pumped 7-9 times a day within the first 3 days postpartum; 60.9% reported that their infant received formula feedings during the hospital stay. CONCLUSION: Overall, deficits were still evident with regard to the initiation of lactation in mothers of VLBW infants in Germany, resulting in a large proportion of VLBW infants receiving formula in the hospital. TRIAL REGISTRATION: German Clinical Trial Register: DRKS00017755 .

Is there a Need to Change the Basic Principles of Histology? Educational, Functional and Embryological Perspective.

Although it is not an easy task to classify cells into different types, or in turn cell types into tissue types, a clear, understandable, didactically and clinically relevant tissue classification is indispensable for undergraduate medical education, expert discussions in biomedical research as well as for clinical practice. From the earliest discovery of the light microscope on, tissue classification has been a dynamic process. Historically, it was not a rare occurrence that different textbooks offered different tissue classifications. Nowadays, classifications have almost become uniform - the most common is the histological classification into four basic tissue types (epithelial, connective, muscle, nervous), which is recognized by the majority of modern histology and pathology textbooks. The reason is that, with some exceptions, this classification seems to be the most relevant not only for educational purposes but also from an embryological perspective and clinical-histopathological practice. Recently, attempts have been made to abandon this established classification and replace it with a new one. Any new classification, which would improve the presently used is welcomed. However, if the proposed innovation does not satisfy the needs of modern education and clinical practice, it should be handled with great caution or reconsidered.

From a Passive Conduit to Highly Dynamic Organ. What are the Roles of Uterine Tube Epithelium in Reproduction?

It is well known that the mammalian uterine tube (UT) plays a crucial role in female fertility, where the most important events leading to successful fertilization and pre-implantation embryo development occur. The known functions of these small intra-abdominal organs are: an uptake and transport of oocytes; storage, transportation, and capacitation of spermatozoa, and finally fertilization and transport of the fertilized ovum and early embryo through the isthmus towards the uterotubal junction. The success of all these events depends on the interaction between the uterine tube epithelium (UTE) and gametes/embryo. Besides that, contemporary research revealed that the tubal epithelium provides essential nutritional support and the most suitable environment for early embryo development. Moreover, recent discoveries in molecular biology help understand the role of the epithelium at the cellular and molecular levels, highlighting the factors involved in regulating the UT signaling, that affects different steps in the fertilization process. According to the latest research, the extracellular vesicles, as a major component of tubal secretion, mediate the interaction between gametes/embryo and epithelium. This review aims to provide up-to-date knowledge on various aspects concerning tubal epithelium activity and its cross-talk with spermatozoa, oocytes and preimplantation embryo and how these interactions affect fertilization and early embryo development.

The Overview of Anatomical Variations and Congenital Anomalies of the Uterine Tubes and Their Impact on Fertility.

Anatomical variations and congenital anomalies of the uterine tubes (UTAVsCAs) are rare conditions, which are often undiagnosed, or accidentally diagnosed upon imaging, laparotomy, laparoscopy for unrelated condition, or during the Cesarean section. UTAVsCAs are often asymptomatic, but their clinical relevance lies in their possibly adverse impact on fertility. Since their rare occurrence, they are usually published as case reports. The most typically described are: agenesis of the uterine tubes (UTs), accessory UT (UT duplication), accessory UT ostium, and paratubal cysts (e.g. the hydatid cyst of Morgagni). UTAVsCAs are classified into an umbrella category of Müllerian duct anomalies (MDAs) which comprises anomalous development of all the organs developing from the paramesonephric (Müllerian) ducts, i.e., UTs, uterus and upper portion of the vagina. Interestingly, most of the classification systems of MDAs discuss solely the uterine and vaginal anomalies, while the UTs are often utterly ignored. This probably originates from the fact that UTs are no longer interesting for many clinicians as they think of UTs as superfluous organs whose function can be easily replaced in the in vitro fertilization (IVF) laboratory. Indeed, the modern reproductive medicine has been helping enormously with the conception of infertile couples. In many instances, the UTs are in fact successfully bypassed and a "test-tube" baby is born. Nevertheless, the UTs are still absolutely unique in providing suitable environment for fertilization and early embryo development - processes that hasn´t been still completely understood. This fact could partially explain why the success rate of IVF is "only" around 30-50 % depending on age. Therefore, the research of the UTAVsCAs is still clinically relevant in the context of reproductive medicine and should not be omitted from research endeavors.

Our First Experience Implementing "Clinical Embryology and Reproductive Medicine" as a Curriculum Course of the Study Program General Medicine at the Faculty of Medicine in Bratislava, Slovakia.

There is no separate course in the medical curriculum summarizing all aspects of human reproduction in most medical school curricula. At the same time, such a course would logically connect knowledge from clinical embryology and assisted reproduction, encompassing the issue of female and male infertility, mechanisms of birth defect formation, their prenatal diagnosis and subsequent specialized neonatal care. The aim of a wide team of university teachers comprising embryologists, gynecologists, neonatologists, endocrinologists, geneticists and others was to create and implement a new course entitled "Clinical Embryology and Reproductive Medicine" into the fourth-year curriculum of the study program General Medicine at the Faculty of Medicine, Comenius University in Bratislava. There has been a great interest in the course, as evidenced by the number of medical students enrolled. The lecture syllabuses have been divided into several thematic areas: 1) Clinical embryology including a laboratory part of assisted reproduction, 2) Cause and treatment options of female and male infertility, 3) A comprehensive view of the issue of birth defects, 4) The issue of preconception education, prenatal and childbirth training, family planning, 5) Reproductive immunology and endocrinology. Despite the complexity of human reproduction being a mainstay of gynecology and obstetrics, it is underemphasized in the medical school curricula worldwide. It is often reflected in shorter hospital / practical trainings during undergraduate studies and lower requirements at the final exam. Therefore, as students almost unanimously valued, this new course is extremely helpful in preparing for the final state exam.

When Less Is More - Pipelle Endometrial Sampling for Quantification of Uterine Natural Killer Cells in Patients With Recurrent Implantation Failure or Habitual Abortion.

Despite recent advancements in reproductive medicine, recurrent implantation failure and habitual abortion remain ongoing issues. One of the most important aspects of successful implantation is the intricate immune response and regulation necessary for the acceptance of the hemiallogenic embryo. The most numerous immune cells in the decidua are uterine natural killer cells (uNK). Studies suggest that changes in the uNK count and physiology may be responsible for the aforementioned pathological conditions. Thus, testing for uNK may provide valuable insights into their pathogenesis. The study compared Pipelle endometrial sampling with conventional curettage to find out whether the less invasive Pipelle method is a viable alternative of tissue collection. Tissue samples from 14 patients obtained by both methods were examined. The average size of tissue samples obtained with Pipelle was 17 mm2, samples obtained with curettage had on average 34 mm2. Using immunohistochemical visualization of CD56 (NK cells) and granzyme B antigens (serine protease-expressing activation state of NK cells), it was found that the average total count of CD56 / mm2 was for Pipelle 115 and 120 for curettage, respectively. The study also proved a correlation between granzyme B positivity and identification of NK cells clusters. The results indicated that Pipelle endometrial sampling seems a suitable method of tissue harvesting for the purpose of uNK cells examination. Pipelle endometrial sampling is safe, cost-effective and can be performed on an outpatient basis without the need of anesthesia or analgesia. Several issues remain yet to be solved: how to standardize the subsequent uNK testing, how to interpret the results and finally yet importantly, how to use this knowledge in personalized treatment protocols.

Uterine Natural Killer Cells in the Context of Implantation: Immunohistochemical Analysis of Endometrial Samples from Women with Habitual Abortion and Recurrent Implantation Failure.

Infertility affects approximately 48 million couples globally. Despite the enormous progress of the methods of reproductive medicine that has been made since the first test-tube baby was born in 1978, the implantation rate of day-3 embryos is only around 15-20 % and 30 % of day-5 embryos. Numerous strategies aim to improve implantation rates and prevent repeated implantation failure, however there is no specific general recommendation leading to satisfying results. One of the many risk factors relevant in this regard is the uterine immunological make-up, mainly the uterine Natural Killer (uNK) cells. They orchestrate the overall immune response during implantation by influencing trophoblast invasion and vascular remodeling and throughout pregnancy, uNK cells are also the main immune cells at the maternal-foetal interface. Previously, uNK count has been correlated with various fertility issues including idiopathic reccurent miscarriage. The present study used endometrial samples collected from 256 patients with recurrent implantation failure (RIF), habitual abortion (HA) and idiopathic sterility. Samples were collected between day 19 and 21 of the menstrual cycle mainly by Pipelle endometrial sampling. The samples were fixed in formalin for 24 hours and further processed for immunohistochemistry using anti-CD56 to visualize this antigen marker of uNK cells. Immunohistochemical counting was performed to assess the low, normal, or elevated count of uNK cells. According to the one-way ANOVA test, the age of our patients did not have any influence on the count of uNK cells. With Spearman correlation analysis, we found statistically significant correlation (p-value 0.05) of -0.133 between prior miscarriage and lower uNK cell count. Using the same analysis we found statistically significant correlation (correlation 0.233 with p-value 0.01) between number of uNK cells and activation status. Patients with higher uNK cells were more frequenty diagnosed with endometriosis (p-value 0.05, correlation 0.130). Patients with an immunological factor of sterility (defined by a clinical immunologist) had a lower chance of gravidity (-0.203 with p-value 0.01). Based on our results, we can confirm that there is a correlation between RIF, HA, idiopathic sterility, endometriosis, and immunological factor of sterility (uNK cell count). The true predictive value with regard to fertility outcomes needs to be addressed in future research.

Immunohistochemical and Scanning Electron Microscopic Confirmation of the Lymphatic Lacunae in the Uterine Tube Mucosal Folds. What Are the Clinical Implications?

Uterine tubes (UTs) are essential during physiological reproduction. The most intriguing part of its wall is the mucosa. Apart from the epithelial cells vital for its normal function, the connective tissue lamina propria contains wide spaces whose function, morphology and structure are yet to be elucidated. The present study used bioptic samples from 25 premenopausal (mean age 48,33 years, ?=3,56) and 25 postmenopausal women (mean age 57,8 years, ?=7,79). In both study groups, samples were obtained from two anatomically distinct parts of the UT - ampulla and infundibulum with fimbriae. The specimens were processed for scanning electron microscopy (SEM) and immunohistochemical detection of podoplanin (clone D2-40) and VEGFR-3 - two markers of lymphatic endothelial cells. The results showed that specimens from premenopausal and postmenopausal women contain wide lymphatic spaces, also known as lymphatic lacunae. The most probable function of the lacunae in the fimbriae is oocyte pick-up upon ovulation thanks to their ability to get engorged with lymph, thus serving as an erectile-like tissue. The ampullary lacunae are probably responsible for tubal fluid maintenance and recirculation. These results indicate that they are vital for normal reproduction because tubal fluid dynamics are as important as fluid composition. Further research on this topic is highly warranted because more detailed insights into UT function have a great potential to refine the methods of reproductive medicine, e.g. in vitro fertilization (IVF), which are still far from optimal regarding fertility outcomes.

Scanning electron microscopic study of the human uterine tube epithelial lining: surgical biopsy samples and epithelial cell culture.

This article summarizes the importance of the exact morphology of human uterine/fallopian tube epithelium at the scanning electron microscopy (SEM) level for the clinical outcome even nowadays. Visual referential micrographs from SEM reflect two ways to view human epithelial cell lining surfaces: the surface epithelial uterine tube from surgical tissue biopsy and human fallopian tube epithelial cells (HFTEC) culture monolayer surface. One colorized image visualizes ciliated cells, distinguishes them from non-ciliated cells, and provides an educational benefit. A detailed description of the ultrastructure in referential and pathologic human uterine tube epithelium is important in defining the morphological basis of high-grade carcinomas, in the mechanism of pathophysiology, and in discussing options for its prevention. Cell cultures of human fallopian tube epithelial cells offer new approaches in simulating the mechanisms of cancer genesis or may help to elucidate the genetic basis of several diagnoses. New technical approaches in SEM provide higher resolution and detailed surface images. The SEM modality is still one of the current options in diagnostics and may be useful for advancing human reproductive organ cancer research.

Functional Morphology of the Human Uterine Tubes in the 21st Century: Anatomical Novelties and Their Possible Clinical Applications.

The uterine tube (UT) pathologies account for 25-35% of female factor infertility. Although these peculiar organs were first studied several hundred years ago, they have become overlooked and neglected mainly due to the successes of reproductive medicine. Nevertheless, the reproductive medicine still faces many challenges regarding the fertility outcomes of in vitro fertilization (IVF). Many obstacles and problems can be resolved by a more detailed understanding of the UT morphology and function during normal reproduction. Over the course of the 21st century, many new insights have been obtained: the presence of a population of telocytes in the tubal wall responsible for normal motility and hormone sensory function, the demonstration of lymphatic lacunae of the mucosal folds necessary for oocyte capture and tubal fluid recirculation, or a thorough profiling of the immune makeup of the UT epithelial lining with the discovery of regulatory T cells presumably important for maternal tolerance towards the semi-allogenic embryo. New discoveries also include the notion that the UT epithelium is male sex hormone-sensitive, and that the UT is not sterile, but harbors a complex microbiome. The UT epithelial cells were also shown to be the cells-of-origin of high-grade serous ovarian carcinomas. Finally, yet importantly, several modern morphological directions have been emerging recently, including cell culture, development of tubal organoids, in silico modelling, tissue engineering and regenerative medicine. All these novel insights and new approaches can contribute to better clinical practice and successful pregnancy outcomes.

Performance validity in outpatients with multiple sclerosis and cognitive complaints.

BACKGROUND: Suboptimal performance during neuropsychological assessment renders cognitive test results invalid. However, suboptimal performance has rarely been investigated in multiple sclerosis (MS). OBJECTIVES: To investigate potential underlying mechanisms of suboptimal performance in MS. METHODS: Performance validity testing, neuropsychological assessments, neuroimaging, and questionnaires were analyzed in 99 MS outpatients with cognitive complaints. Based on performance validity testing patients were classified as valid or invalid performers, and based on neuropsychological test results as cognitively impaired or preserved. Group comparisons and correlational analyses were performed on demographics, patient-reported, and disease-related outcomes. RESULTS: Twenty percent displayed invalid performance. Invalid and valid performers did not differ regarding demographic, patient-reported, and disease-related outcomes. Disease severity of invalid and valid performers with cognitive impairment was comparable, but worse than cognitively preserved valid performers. Lower performance validity scores related to lower cognitive functioning, lower education, being male, and higher disability levels (p < 0.05). CONCLUSION: Suboptimal performance frequently occurs in patients with MS and cognitive complaints. In both clinical practice and in cognitive research, suboptimal performance should be considered in the interpretation of cognitive outcomes. Identification of factors that differentiate between suboptimal and optimal performers with cognitive impairment needs further exploration.