Endometrial Metaplastic/Reactive Changes Coexistent with Endometrial Hyperplasia and Carcinoma: A Morphological and Immunohistochemical Study

The aim of this study was to assess the relationship between endometrial metaplastic/reactive changes (EMRCs) and endometrial neoplastic lesions. Twenty cases of “simple” (without architecture complexity) EMRCs coexistent with endometrial malignant/premalignant lesions, twenty cases of neoplasia-unassociated EMRCs, and eight cases of complex metaplastic lesions were assessed by immunohistochemistry. EMRCs coexisted with endometrioid carcinoma (n = 12), atypical endometrial hyperplasia (n = 3), serous carcinoma (n = 2), and clear cell carcinoma (n = 3). Neoplasia-associated EMRCs showed a mean Ki67 labeling index of 12.6% (range 0–30%); with nuclear atypia in 16/20 (80%) cases; diffuse p16 expression in 15/20 (75%) cases; and heterogeneous ER, PR, and vimentin expression. Compared to the associated neoplasia, EMRCs showed a lower Ki67 expression (p < 0.001) and higher p16 expression (p < 0.001). No EMRC case showed mitotic activity, PTEN loss, MMR deficiency, nuclear β-catenin, p53-mutant pattern, Napsin A, or AMACR expression. No significant differences were found between neoplasia-associated and neoplasia-unassociated EMRCs. Complex metaplastic lesions showed a lower Ki67 expression than EMRCs (p = 0.044) and PTEN loss in 5/8 cases, even in the absence of nuclear atypia. In conclusion, neoplasia-associated simple EMRCs may show evident atypia and a worrisome immunophenotype, but no data support their involvement in endometrial carcinogenesis. Architectural complexity appears as a crucial factor to identify precancerous lesions.

Change, Crisis, Perspective, and Identity in Two Novels by Rózsa Ignácz

For Hungarians who remained stuck beyond the borders after WWI, finding themselves in a foreign country from one day to the next, the historical trauma of the Trianon Treaty occasioned intercultural tribulations never experienced before. What the resulting Transylvanian literature discussed here is concerned with, however, is not what Jeffrey C. Alexander’s cultural trauma theory calls “the trauma process”, “the spiral of signification” (Alexander 2004, 11). Rather, it is concerned with “the indelible marks” “the horrendous event” left “upon group consciousness […] changing their future identity in fundamental and irrevocable ways” (Alexander 2004, 1). This literature displays a rich array of the management strategies of minority identity. Earlier I devoted a book to the identity types that ensued from those strategies (Dani 2016a). The present work is based on that monograph and moves on. This time I wish to focus on the key figures of two Rózsa Ignácz novels (Anyanyelve magyar and Született Moldovában) to demonstrate the complex identity patterns that an erosion of minority native language and culture, so destructive to identity, yields. The road that the Hungarian minority travels leads through a succession of active and reactive changes, crises, and modifications of perspective in the maze of minority versus hegemonic intercultural relations.1

A mixed-method investigation into measurement reactivity to the experience sampling method: The role of sampling protocol and individual characteristics

Since the introduction of the experience sampling method (ESM), there have been concerns that the repeated assessments typically related to this method may alter the behavior, thoughts, or feelings of participants. Previous studies have offered mixed results with some studies reporting reactive changes while others failed to find such effects. Our aim was to investigate under which circumstances ESM induces reactive effects.Students (N = 151) were randomly assigned to receive a questionnaire containing 30 or 60 items 3, 6, or 9 times per day for 14 days. A random sample of 50 participants took part in qualitative interviews after the end of the data collection. We investigated changes over time in the data, while taking into account the sampling protocol and characteristics of participants, and analyzed qualitative reports of measurement reactivity.Decreases in completion time, within-person variance of ratings and subjective reports of habituation point towards the existence of a habituation period. While participants also reported increases in emotional awareness in interviews, ESM measures indicated a decrease in emotional awareness over time. Changes in behavior were rare in quantitative and qualitative reports. Positive affect was found to decrease over time in the ESM data and various changes in affect, emotion regulation, and thoughts were reported in interviews. Individual characteristics and sampling protocol had inconsistent effects on changes over time.The current results suggest that ESM induces reactivity. These reactive changes may be particularly relevant to researchers investigating within-person variability, completion times, affect, or emotional awareness.

Reactive changes of gastric mucosa and reduction of desacyl grelin in rat brain due to psychoemotional stress

BACKGROUND: The work is devoted to the analysis of the elements the reactivity of grelin system in the model of psychogenic stress. In recent years, it has been shown that the ghrelin brain system is not limited only to the regulation of energy balance and eating behavior. Along with other peptide regulatory systems, it plays an important role in the mechanisms of stress, reward and addiction. Therefore, the elements of this system should be considered primarily as molecular targets of pharmacological action in order to correct the states of addiction and post-stress disorders. MATERIALS AND METHODS: To produce psychoemotional stress, we used an acute single traumatic situation in male Wistar rats. The animals were placed in the tiger python, one animal died as a result of its nutritional needs, the rest of the rats experienced the death of a partner. One week after exposure to python, the animals were decapitated, and the brain structures were isolated. Aliquots of the brain structures suspensions were examined for the content of desacyl ghrelin (DAG) using a highly sensitive enzyme-linked immunosorbent assay (ELISA). In another group, rats were decapitated on the 4th day after exposure to python, stomachs were removed, which were fixed in 10% formalin solution. In horizontal paraffin sections of the gastric mucosa, after staining with hematoxylin and eosin, the heights of superficial and dimple mucous cells, the height of the dimple stroma, the area of superficial, dimple mucocytes and stroma of the dimples, and the number of dead mucocytes were calculated. To clarify the differentiation of epithelial cells, they were stained with alcian blue RESULTS: DAG was detected in all studied brain structures: amygdala, hippocampus, and hypothalamus. The highest concentration of DAG was noted in the hypothalamus (p 0.05), which may serve as an indirect confirmation of the data on the presence of ghrelin-containing neurons in the nuclei of the hypothalamus. After exposure to stress, a sharp decrease in the level of DAG was observed in all studied brain structures (812 times, p 0.01): amygdala, hippocampus, and hypothalamus. It has been established that the experience of the stress of the death of a partner is expressed by erosive inflammation of the gastric mucosa, the death of many mucous cells, and an increase in mucus production in viable epithelial cells. CONCLUSION: Psychoemotional stress completely suppresses the content of desacyl ghrelin of the brain in rats, which may be based on both a disturbance of the central mechanisms of limbic regulation and a violation of peripheral mechanisms, in particular, reactive changes in the gastric mucosa.

RGC-32 Acts as a Hub to Regulate the Transcriptomic Changes Associated With Astrocyte Development and Reactive Astrocytosis

Response Gene to Complement 32 (RGC-32) is an important mediator of the TGF-β signaling pathway, and an increasing amount of evidence implicates this protein in regulating astrocyte biology. We showed recently that spinal cord astrocytes in mice lacking RGC-32 display an immature phenotype reminiscent of progenitors and radial glia, with an overall elongated morphology, increased proliferative capacity, and increased expression of progenitor markers when compared to their wild-type (WT) counterparts that make them incapable of undergoing reactive changes during the acute phase of experimental autoimmune encephalomyelitis (EAE). Here, in order to decipher the molecular networks underlying RGC-32’s ability to regulate astrocytic maturation and reactivity, we performed next-generation sequencing of RNA from WT and RGC-32 knockout (KO) neonatal mouse brain astrocytes, either unstimulated or stimulated with the pleiotropic cytokine TGF-β. Pathway enrichment analysis showed that RGC-32 is critical for the TGF-β-induced up-regulation of transcripts encoding proteins involved in brain development and tissue remodeling, such as axonal guidance molecules, transcription factors, extracellular matrix (ECM)-related proteins, and proteoglycans. Our next-generation sequencing of RNA analysis also demonstrated that a lack of RGC-32 results in a significant induction of WD repeat and FYVE domain-containing protein 1 (Wdfy1) and stanniocalcin-1 (Stc1). Immunohistochemical analysis of spinal cords isolated from normal adult mice and mice with EAE at the peak of disease showed that RGC-32 is necessary for the in vivo expression of ephrin receptor type A7 in reactive astrocytes, and that the lack of RGC-32 results in a higher number of homeodomain-only protein homeobox (HOPX)+ and CD133+ radial glia cells. Collectively, these findings suggest that RGC-32 plays a major role in modulating the transcriptomic changes in astrocytes that ultimately lead to molecular programs involved in astrocytic differentiation and reactive changes during neuroinflammation.

Reactivity in measuring depression

If a human subject knows they are being measured, this knowledge may affect their attitudes and behaviour to such an extent that it affects the measurement results as well. This broad range of effects is shared under the term ‘reactivity’. Although reactivity is often seen by methodologists as a problem to overcome, in this paper I argue that some quite extreme reactive changes may be legitimate, as long as we are measuring phenomena that are not simple biological regularities. Legitimate reactivity is reactivity which does not undermine the accuracy of a measure; I show that if such reactivity were corrected for, this would unjustifiably ignore the authority of the research subject. Applying this argument to the measurement of depression, I show that under the most commonly accepted models of depression there is room for legitimate reactivity. In the first part of the paper, I provide an inventory of the different types of reactivity that exist in the literature, as well as the different types of phenomena that one could measure. In the second part, I apply my argument to the measurement of depression with the PHQ-9 survey. I argue that depending on what kind of phenomenon we consider depression to be (a disease, a social construction, a harmful dysfunction, or a practical kind), we will accept different kinds of reactivity. I show that both under the harmful dysfunction model and the practical kinds model, certain reactive changes in measuring depression are best seen as legitimate recharacterizations of the underlying phenomenon, and define what legitimate means in this context. I conclude that in both models, biological aspects constrain characterization, but the models are not so strict that only one concept is acceptable, leaving room for reactivity.

Immunohistochemical analysis of microglial changes in the experimental acute hepatic encephalopathy

Hepatic encephalopathy (HE) is a syndrome of impaired brain function in patients with advanced liver failure and it manifests in form of psychometric tests alterations up to decreased consciousness and coma. The current knowledge about HE mainly focused on the theory of ammonia neurotoxicity and neuroinflammation. Microglia being resident innate immune cells of the brain when activated are responsible for the neuroinflammatory reactions. The aim – immunohistochemical study of the microglial changes in different rat brain regions in conditions of experimental acute HE (AHE). Materials and methods. We used acetaminophen induced liver failure model in Wistar rats. Four from 10 animals that survived up to 24 h after acetaminophen injection constituted “compensated group”; 6 animals which died within 24 h – “decompensated group”. Microglial reactive changes were analysed by the evaluation of the relative area (S rel., %) of CD68+ expression in the brain cells not associated with meninges and vessels, as well as the changing in shape and number of these cells. Results. Acetaminophen-induced AHE in rats was characterized by the regional- and time-dependent dynamic increase in CD68 expression level in the rat brain in form of significant (relatively to control) increase of CD68+ S rel. in brain cells and the number of such cells. The medians of CD68+ S rel. and their numbers in significantly changed regions of non-survived rats were, respectively: subcortical white matter – 0.24 (0.20; 0.26) and 11.00 (8.00; 13.00); thalamus – 0.13 (0.90; 0.18) and 6.00 (3.00; 7.00); caudate/putamen – 0.13 (0.12; 0.18) and 7.00 (4.00; 11.00) – all indicators were statistically significant compared to control. In the survived animals, indicators were, respectively: subcortical white matter – 0.24 (0.16; 0,26) and 10.00 (8.00; 12.00); caudate/putamen – 0.12 (0.10; 0.15) and 6.00 (4.00; 10.00) – the differences were significant compared to control. Conclusions. The highest and significant indicators were revealed at 24 h (compared to earlier time points) of the experiment in the white matter, thalamus and caudate/putamen. This fact reflects time-dependent dynamic boosting of reactive changes in microglia and presumably may indicate the regions of the most active neuroinflammatory response within the brain parenchyma in the conditions of AHE. The appearing of a small percentage of cells with amoeboid transformation among CD68+-cells may mean partial functional insufficiency of such cells due to probable suppressive impact of ammonia or other influencing factors, as well as insignificance of the material that needs to be phagocytosed under established conditions.

The cytological component of cervical cancer screening: causes of false negative and false positive results, and ways to avoid them

Cervical cancer (CC) screening is a major component of secondary prevention of CC and involves screening all women at risk of developing this disease, most of whom are asymptomatic. Cytology remains an important component of CC screening in the era of primary screening by genotyping the human papillomavirus. Papanikolaou staining is the method of choice for CC screening. This review highlights the causes of false negative results for various methods of Pap tests and how they can be prevented. A detailed analysis of conditions accompanied by a high probability of false positive abnormal results of the Pap test, an explanation of the pathophysiological basis of this phenomenon, clinical and cytological criteria for differential diagnosis is also presented.Pap test is a screening test. The aim of the cytological examination in CC screening is to assign the patient to a group with absent neoplastic changes in the cervical epithelium, a group with neoplastic changes in the cervical epithelium present, or a group when it is impossible to make an accurate differential diagnosis between benign reactive changes and neoplasia. The Bethesda Cytology Reporting System is used to unify and standardize these categories in most countries of the world. Benign conditions are a common cause of false positive reports of cellular atypia on cervical screening, as evidenced by a large number of studies. This fact should be taken into account both in the interpretation of the results and, if possible, in the planning of cervical screening. The most common conditions that are accompanied by reactive changes in the cervical epithelium, which can be incorrectly assessed as atypia, are: reactive and reparative inflammatory changes, atrophy, metaplasia, reactive changes caused by intrauterine devices. In this regard, when working with the cytological component of cervical screening, it is important for the clinician to understand the basic principles of assessing the cervical epithelium, which will allow using the descriptive part of the report to determine tactics if a false negative or false positive screening result is suspected.Thus, understanding the impact of common benign conditions on the cervical epithelium makes it possible to rationally plan cytological cervical screening and correctly interpret its results in order to achieve the best clinical results that are not limited to the detection of precancerous conditions.

Cervical cytology and associated factors among tribal women of Karnataka, India

Background Reproductive well-being is a crucial element of women’s health. Due to the asymptomatic nature of gynaecological morbidities, women rarely seek medical advice in the initial period leading to delayed diagnosis and poor prognosis of subsequent disease. The present study aimed to explore the cervical cytology and its associated risk factors among women from tribal communities of the southern part of coastal Karnataka, India. Methods Papanicolaou (Pap) smear test was performed among 1140 women from three tribal populations, to detect cervical lesions, infections and reactive changes. A semi-structured questionnaire was administered to collect data on socio-demographic and reproductive characteristics of the study population. Results The most predominant gynaecological complaint among the participants was severe lower back ache (77.6%), followed by white discharge per vagina (29.0%) and menstrual irregularities (25.9%). Of the 1140 women screened, 12.4% showed cervical microbial infections, 23.6% were reported to have reactive changes, and 0.2% had epithelial cell abnormalities in the cervix. Cervical microbial infections were found to be associated with younger age group, low socio-economic status and younger age at sexual debut. Conclusion Most of the symptoms suggestive of gynaecological morbidities reported in this study are preventable or treatable. Strengthening ongoing cervical cancer screening programme and implementation of health education programmes among tribal population would be the right policy approach to prevent, detect and treat these symptoms at an early stage and to achieve acceptable health outcomes among tribal women.