QCD Crossover at Finite Chemical Potential from Lattice Simulations.

We provide the most accurate results for the QCD transition line so far. We optimize the definition of the crossover temperature T_{c}, allowing for its very precise determination, and extrapolate from imaginary chemical potential up to real µ_{B}≈300 MeV. The definition of T_{c} adopted in this work is based on the observation that the chiral susceptibility as a function of the condensate is an almost universal curve at zero and imaginary µ_{B}. We obtain the parameters κ_{2}=0.0153(18) and κ_{4}=0.00032(67) as a continuum extrapolation based on N_{t}=10, 12, 16 lattices with physical quark masses. We also extrapolate the peak value of the chiral susceptibility and the width of the chiral transition along the crossover line. In fact, both of these are consistent with a constant function of µ_{B}. We see no sign of criticality in the explored range.

Under inflammatory stimuli mesenteric mesothelial cells transdifferentiate into macrophages and produce pro-inflammatory cytokine IL-6.

OBJECTIVE: Inflammatory stimuli inducing epithelial-to-mesenchymal transition (EMT) can transdifferentiate mesenteric mesothelial cells into macrophages. METHODS: Sprague Dawley rat mesenteric mesothelial cells were used as a model. 1 ml Freund adjuvant was injected into the peritoneal cavity of rat and GM-CSF treatment was used to induce inflammation. IL-10 and IL-6 expression were studied by immunocytochemistry and Western blot analysis both in vivo and in vitro. RESULTS: Control mesothelial cell express anti-inflammatory IL-10, but no pro-inflammatory IL-6 expression could be detected in them. By the time of inflammation, IL-6 expression increased (reached the maximum level at the fifth day of inflammation), parallel to this the IL-10 entirely disappeared from these cells. In vitro GM-CSF treatment resulted in similar changes. As the mesothelial cells started to recover (at the eighth day of inflammation) IL-6 expression decreased and IL-10 level started to increase again. CONCLUSION: These data show that under inflammatory stimuli mesothelial cells-like macrophages-can produce pro-inflammatory cytokines.

Autophagy is the key process in the re-establishment of the epitheloid phenotype during mesenchymal-epithelial transition (MET).

In previous studies we showed that during Freund's adjuvant induced inflammation rat mesenteric mesothelial cells undergo epithelial-mesenchymal transition type II (EMT). This process was characterized by a dramatic increase of the number of cell organelles and volume of mesothelial cells. After the inflammation reached its maximum, the mesenchymal-like cells gradually regained their epithelial phenotype (mesenchymal-epithelial transition, MET). During the recovery process, the decrease of the number of cell organelles was accompanied by an increasing number of autophagic structures in the cytoplasm, indicating that autophagy might play crucial role in MET. Morphometric data of this study showed that the number of the autophagic organelles increased by the time of inflammation and was the highest at day 7-8, when regeneration started. These morphological observations were supported by immunocytochemistry and Western blot analyses with various markers, directly or indirectly involved in this process. Endocytic markers were expressed at high level during both EMT and MET, while the expression of factors regulating autophagy simultaneously changed with the morphology: p-Akt and p-mTOR level was high at day 3-5 and significantly decreased when autophagy speeded up. The Beclin-1, which is the key factor of initiating autophagy, was expressed at the early time of inflammation. These results strongly suggest that autophagy plays important role in regeneration (MET), and it is regulated and synchronized by various signalling events during inflammation.

GM-CSF and GM-CSF receptor have regulatory role in transforming rat mesenteric mesothelial cells into macrophage-like cells.

OBJECTIVE AND DESIGN: During peritonitis, mesothelial cells assume macrophage characteristics, expressing macrophage markers, indicating that they might differentiate into macrophage-like cells. MATERIALS AND SUBJECTS: Twenty-five male rats were used for in vivo experiments. For in vitro experiments, a primary mesentery culture model was developed. The mesothelial cell to macrophage-like cell transition was followed by studying ED1 expression. TREATMENTS: In vitro primary mesenteric culture was treated with granulocyte-macrophage colony-stimulating factor (GM-CSF, 1 ng/ml). Blocking internalization of receptor-ligand complex, Dynasore (80 µM) was used. Acute peritonitis was induced by Freund's adjuvant's (1 ml) intraperitoneal injection. RESULTS: Immunohistochemistry: GM-CSF in vitro treatment resulted in a prominent ED1 expression in transformed mesothelial cells. Blocking the internalization, ED1 expression could not be detected. GM-CSF receptor (both α and ß) was expressed in mesothelial cells in vitro (even if the GM-CSF was not present) and in vivo. Inflammation resulted in an increasing GM-CSF and GM-CSF-receptor level in the lysate of mesothelial cells. CONCLUSIONS: Mesothelial cells can differentiate into macrophage-like cells, and GM-CSF, produced by the mesothelial cells, has probably an autocrine regulatory role in this transition. Our results provide new data about the plasticity of mesothelial cell and support the idea that during inflammation macrophages can derive from non-hematopoietic sources as well.

Lifestyle and behavioural changes in older adults during the Covid-19 pandemic are associated with subjective cognitive complaints.

Subjective cognitive complaints (SCC) is a self-reported experience of persistently impaired cognitive functions which could be the earliest red flag of neurocognitive disorders. The COVID-19 pandemic and related restriction measures changed the lifestyle and behaviour of older adults. The aim of this study was to assess the relation of these changes and SCC status in Hungary. This cross-sectional study analysed the data of 359 elderly Hungarians who filled out the WW-FINGERS-SARS-CoV2 survey. A quarter of the respondents (n:88) reported SCC in connection with the pandemic. We compared sociodemographic features, health status, lifestyle, and social life parameters between subjects with reported SCC and without. To eliminate the potential interrelation across group differences, stepwise logistic regression was applied. Participants with SCC showed the following characteristics, compared to individuals without: (1) they were older; (2) they were more likely to be women; (3) they had a higher number of chronic disorders; (4) showed more prominent impairment in physical mobility; (5) had worse sleep quality; (6) spent less time with family; and (7) used internet more frequently during the pandemic (all p's < 0.001). Logistic regression highlighted that only two parameters were related to SCC status independently, the physical mobility (ability to walk 500 m without difficulties; OR = 1.186; p < 0.001; 95%CI = 1.101, 1.270) and changes in time spent with grandchildren (OR = 1.04; p = 0.015; 95%CI = 1.008, 1.073). Our study draws attention to the importance of physical mobility and quality time with family as key factors in the cognitive well-being of elderly people.

Is there a flavor hierarchy in the deconfinement transition of QCD?

We present possible indications for flavor separation during the QCD crossover transition based on continuum extrapolated lattice QCD calculations of higher order susceptibilities. We base our findings on flavor-specific quantities in the light and strange quark sector. We propose a possible experimental verification of our prediction, based on the measurement of higher order moments of identified particle multiplicities. Since all our calculations are performed at zero baryochemical potential, these results are of particular relevance for the heavy-ion program at the LHC.

[Care of dementia in the general practice]. / A dementia ellátása a háziorvosi gyakorlatban.

Treating and caring for people with dementia is a complex task, which can be achieved through cooperation between primary and specialist healthcare, social care and specialist care services. General practitioners are key players in the prevention, screening, treatment and care of dementia. Our aim was to present the general practitioner's aspects of modern dementia care through different levels of prevention. Educating patients to lead a healthy lifestyle and optimising their cardiovascular status reduces the risk of developing dementia. Emphasis was placed on early screening and referral to a specialist, and the importance of timely, individualised therapy for modern care. General practitioner's care of patients with dementia includes monitoring the progression of the disease as well as co-morbidities so that the quality of life of both the patients and their family can be improved by reducing complications. Family doctors also have an important role to support family members who care for the patient. In addition to presenting the current possibilities in Hungary, we reviewed the international literature and national guidelines, which must be followed continuously to ensure quality patient care. Orv Hetil. 2023; 164(32): 1263-1270.

Impact of the third wave of the COVID-19 pandemic on the lifestyle, mental and physical health of the Hungarian population over 60 / A COVID-19-pandémia harmadik hullámának hatása a 60 év feletti magyar lakosság életmódjára, mentális és fizikai egészségére

Introduction: Elderly population is the most vulnerable group of the COVID-19 pandemic, since they often live with chronic diseases. Objective: The goal of our research is to analyze the direct and indirect effects of the pandemic on the Hungarian population over 60 years of age. Method: We collected data using the authentic Hungarian translation of the,World-Wide FINGERS SARS-CoV-2 Survey between 1st of February and 1st of June 2021. Results: Our study included 431 people with a low rate of COVID infection (6%). The most marked changes were the increase in the use of digital services in 71%, increased feeling of loneliness in 46%, decrease in subjective sleep quality in 47%, and reduced contact with friends and relatives in 80% of the respondents. Eight-six percent of participants had at least one chronic illness and 23% missed an illness-related medical visit during the pandemic. In 45%, the subjective quality of life deteriorated and 25% reported impairment of memory functions. Discussion: Participants became socially isolated during the pandemic having a significant negative impact on their way of life. The changes in physical and mental health are likely to be reflected in an increased incidence and accelerated progression of age-related diseases in the elderly. Conclusion: In order to reduce the direct and indirect harmful effects of the COVID-19 pandemic, it is of paramount importance to know how the pandemic and the following restrictions affect the behavior and lifestyle of the elderly as well as the care of patients living with chronic diseases.

Endocytosis of GM-CSF receptor ß is essential for signal transduction regulating mesothelial-macrophage transition.

During Freund's adjuvant induced inflammation rat mesenteric mesothelial cells transdifferentiate into mesenchymal cell. They express macrophage markers, inflammatory cytokines (TGF-ß, TNFα, IL-6), and specific receptors. When primary mesenteric cultures were treated with GM-CSF and/or TGF-ß (in vitro), similar phenotypic and biological changes were induced. It seemed likely that GM-CSF receptor-ligand complex should be internalized to initiate mesothelial-macrophage transition. To follow the intracellular route of GM-CSF receptor ß, we co-localized this receptor with various endocytic markers (Cav-1, EEA1, Rab7, and Rab11a), and carried out detailed immunocytochemical, statistical and biochemical analyses. Since STAT5 is one of the downstream element of GM-CSF signaling, we followed the expression and phosphorylation level of this transcription factor. Our results showed that in mesenteric mesothelial cells GM-CSF receptor ß is internalized by caveolae, delivered into early endosomes where the signaling events occur, STAT5A is phosphorylated by JAK2, and then translocated into the nucleus. When dynamin-dependent endocytosis of GM-CSFR ß is inhibited by dynasore, phosphorylation of STAT5A is not occurred, confirming, that the internalization of receptor ß is indispensable for signal transduction. At the early time of inflammation a significant receptor recycling can be found to the plasma membrane. Later (day 8) the receptor is delivered into late endosomes, indicating that its degradation has already started, and the regeneration of mesothelial cells can start. All of these data strongly support that the internalization of GM-CSF receptor ß is required and essential for signal transduction.

Inflammation-Induced Epithelial-to-Mesenchymal Transition and GM-CSF Treatment Stimulate Mesenteric Mesothelial Cells to Transdifferentiate into Macrophages.

In our previous work, we showed that during inflammation-induced epithelial-to-mesenchymal transition (EMT), mesenteric mesothelial cells express ED1 (pan-macrophage marker), indicating that they are transformed into macrophage-like cells. In this paper, we provide additional evidences about this transition by following the phagocytic activity and the TNFα production of mesenteric mesothelial cells during inflammation. Upon injection of India ink particles or fluorescent-labeled bioparticles (pHrodo) into the peritoneal cavity of rats pretreated with Freund's adjuvant, we found that mesothelial cells efficiently engulfed these particles. A similar increase of internalization could be observed by mesothelial cells in GM-CSF pretreated primary mesenteric culture. Since macrophages are the major producers of tumor necrosis factor, TNFα, we investigated expression level of TNFα during inflammation-induced EMT and found that TNFα was indeed expressed in these cells, reaching the highest level at the 5th day of inflammation. Since TNFα is one of the target genes of early growth response (EGR1) transcription factor, playing important role in monocyte-macrophage differentiation, expression of EGR1 in mesothelial cells was also investigated by Western blot and immunocytochemistry. While mesothelial cells did not express EGR1, a marked increase was observed in mesothelial cells by the time of inflammation. Parallel to this, nuclear translocation of EGR1 was shown by immunocytochemistry at the day 5 of inflammation. Caveolin-1 level was high and ERK1/2 became phosphorylated as the inflammation proceeded showing a slight decrease when the regeneration started. Our present data support the idea that under special stimuli, mesenteric mesothelial cells are able to transdifferentiate into macrophages, and this transition is regulated by the caveolin-1/ERK1/2/EGR1 signaling pathway.

Estrogen receptor alpha is expressed in mesenteric mesothelial cells and is internalized in caveolae upon Freund's adjuvant treatment.

Transformation of epithelial cells into connective tissue cells (epithelial-mesenchymal transition, EMT) is a complex mechanism involved in tumor metastasis, and in normal embryogenesis, while type II EMT is mainly associated with inflammatory events and tissue regenaration. In this study we examined type II EMT at the ultrastructural and molecular level during the inflammatory process induced by Freund's adjuvant treatment in rat mesenteric mesothelial cells. We found that upon the inflammatory stimulus mesothelial cells lost contact with the basal lamina and with each other, and were transformed into spindle-shaped cells. These morphological changes were accompanied by release of interleukins IL-1alpha, -1beta and IL-6 and by secretion of transforming growth factor beta (TGF-ß) into the peritoneal cavity. Mesothelial cells also expressed estrogen receptor alpha (ER-α) as shown by immunolabeling at the light and electron microscopical levels, as well as by quantitative RT-PCR. The mRNA level of ER-α showed an inverse correlation with the secretion of TGF-ß. At the cellular and subcellular levels ER-α was colocalized with the coat protein caveolin-1 and was found in the plasma membrane of mesothelial cells, in caveolae close to multivesicular bodies (MVBs) or in the membrane of these organelles, suggesting that ER-α is internalized via caveola-mediated endocytosis during inflammation. We found asymmetric, thickened, electron dense areas on the limiting membrane of MVBs (MVB plaques) indicating that these sites may serve as platforms for collecting and organizing regulatory proteins. Our morphological observations and biochemical data can contribute to form a potential model whereby ER-α and its caveola-mediated endocytosis might play role in TGF-ß induced type II EMT in vivo.

Epithelial-to-mesenchymal transition induced by Freund's adjuvant treatment in rat mesothelial cells: a morphological and immunocytochemical study.

Intraperitoneal injection of Freund's adjuvant induces acute peritonitis. By the time of the Freund's adjuvant treatment the flat, simple squamous epithelial cells became rounded, cuboidal shaped, many of them have lost their connection with the neighbouring cells and detached from the basement membrane. The macrophage markers' (ED1, OX43 and CD68) expression also increased in the mesothelial cells and more mesothelin and anti-ED1 double-labelled cells were found freely present close to the surface. The cytokeratin expression of the mesothelial cells has gradually decreased. At the 5th day of the inflammation practically there was no cytokeratin labelling present in the mesothelial cells and the mesothelin expression has significantly decreased. Parallel to this mesothelial cells started to express vimentin, a characteristic mesenchymal intermediate filament protein indicating that they gradually lost their epithelial character and gained mesenchymal phenotype. These results strongly suggest that under the effect of Freund's adjuvant treatment (inflammation) mesothelial cells can undergo epithelial-to-mesenchymal transition and differentiate into phagocytotic (macrophage-like) cells. Studying the caveolae/caveolin-1 on the plasma membrane of mesothelial cells we found that the Freund's adjuvant treatment has changed the cellular distribution of caveolin-1: as the inflammation progressed strong caveolin-1 labelling was found inside of the cytoplasm (in perinuclear localization) indicating that inflammation induced the caveolae internalization. These results indicate that caveolae/caveolin-1 might play important regulatory role in signal transduction leading to trasdifferentiation.

Mesothelial cells can detach from the mesentery and differentiate into macrophage-like cells.

Peritoneal cell suspension is composed of heterogeneous cell population. Macrophages are the most numerous cells among them. They can originate from different sources and can be resident, exudate and elicited. When we used Freund's adjuvant to elicit peritoneal macrophages, cells having large amount of caveolae on their plasma membrane appeared in the peritoneal wash. The number of these caveolae-rich cells increased by the time of the Freund's adjuvant treatment. Although their morphology was different form from the common macrophages, they were labelled with pan-macrophage antibodies. As the origin of these cells is unknown in this work, we tried to find out where they can originate from. Our interest turned towards the mesothelial cells. We found that the adjuvant treatment resulted in significant morphological changes in these cells and stimulate them to leave the surface of the mesentery. By the time of the adjuvant treatment, the macrophage markers expression increased in the mesothelial cells and more cells were found to detach from the mesentery. These results strongly suggest that under special stimuli mesothelial cells can leave the mesentery and differentiate into phagocytotic (macrophage-like) cells. These data raises the idea that mesothelial cells might not entirely differentiated and represent a multipotential cell lineage. To study whether this is the case we used anti-nestin antibody, which is a specific marker for multifunctional, multi-lineage progenitor cells. Mesothelial cells showed strong labelling with this antibody indicating that these cells really represent a 'young', not entirely differentiated cell population.