A glimpse into the past of Hansen's disease - Re-evaluation and comparative analysis of cases with leprosy from the Avar period of the Trans-Tisza region, Hungary.

Our knowledge of how society viewed leprosy and treated its victims in the past is still scarce, especially in geographical regions and archaeological periods from where no written sources are available. To fill in some research gaps, we provide the comparative analysis of five previously described, probable cases with leprosy from the Avar-period Trans-Tisza region (Hungary). The five skeletons were subject to a detailed macromorphological (re-)evaluation. Where possible, the biological and social consequences of having leprosy were reconstructed based on the observed bony changes and mortuary treatment, respectively. The retrospective, macromorphology-based diagnosis of leprosy could be established in three cases only. Based on the detected skeletal lesions, all of them suffered from near-lepromatous or lepromatous leprosy. The disease resulted in aesthetic repercussions and functional implications, which would have been disadvantageous for these individuals, and limited or changed their possibilities to participate in social situations. They could have even required heavy time investment from their respective communities. The analysis of the mortuary treatment of the confirmed leprosy cases revealed no evidence of a social stigma. These findings indicate that the afflicted have not been systematically expulsed or segregated, at least in death, in the Early Middle Ages of the Carpathian Basin.

Add-on Sacubitril/Valsartan Therapy Induces Left Ventricular Remodeling in Non-responders to Cardiac Resynchronization Therapy to a Similar Extent as in Heart Failure Patients Without Resynchronization.

INTRODUCTION: Non-responders to cardiac resynchronization therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcome of patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials with no data on the specific cohort of CRT-NRs. The aim of this study was to compare the echocardiographic and biomarker changes in CRT-NR patients treated with versus without SV, and in patients with HFrEF on SV therapy. METHODS: CRT-NR patients initiated on SV (group I), CRT-NR patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (group II), and patients with HFrEF (without CRT) initiated on SV (group III) were identified in our heart failure (HF) registry. CRT-NR was defined as < 10% improvement in left ventricular ejection fraction (LV EF) 6 months after the implantation. Echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at baseline and at the end of follow-up were compared. RESULTS: A total of 275 patients (group I, 70; group II, 70; and group III, 135) were included. After a follow-up of 7.54 ± 1.8 months (mean ± standard deviation [SD]), LV EF (%) increased in group I (25.2 ± 5.7 versus 29.4% ± 6.7; p < 0.001) and in group III (26.6 ± 6.4 versus 29.9 ± 6.7; p < 0.001). LV end-systolic diameters (mm) decreased in group I (56.6 ± 9.0 versus 54.3 ± 8.7; p = 0.004) and in group III (55.9 ± 9.9 versus 54.3 ± 11.2; p = 0.021). The levels of NT-proBNP (pg/mL) decreased in group I (2058.86 [1041.07-4502.51] versus 1121.55 [545-2541]; p < 0.001) and in group III (2223.35 [1233.03-4795.96] versus 1123.09 [500.38-2651.27]; p < 0.001). The extent of improvement was similar in groups I and III (p > 0.05). No significant changes were detected in group II. CONCLUSION: SV therapy induced similar improvements in echocardiographic parameters and in NT-proBNP levels in CRT-NR patients and in patients with HFrEF without resynchronization.

Assessing the Spontaneous Spread of Climate-Adapted Woody Plants in an Extensively Maintained Collection Garden.

Climate change may strongly modify the habitat conditions for many woody plant species. Some species could disappear from their natural habitats and become endangered, while others could adapt well to the changed environmental conditions and continue to survive successfully or even proliferate more easily. A similar process can occur within the artificial urban environment as the hitherto popularly planted urban trees may suffer from the extremities of the urban climate. However, among the planted taxa, there are species that spread spontaneously and appear as weeds in extensively managed gardens. In our study, we evaluated the native and non-native species involved in spontaneous spreading in the institutional garden of Buda Arboretum (Budapest) during the COVID-19 period in 2020-2021 when entry was prohibited, and maintenance went on in a restricted, minimal level. We investigated the correlation between spontaneously settling and planted individuals, and then performed multivariate analyses for native and non-native spreading plants for spatial and quantitative data. During our studies, we observed the spontaneous spreading of 114 woody species, of which 38 are native and 76 are non-native. Taking the total number of individuals into account, we found that, in addition to the 2653 woody species planted, a further 7087 spontaneously emerged weeds developed, which creates an additional task in the maintenance.

The Effect of Aerobic Exercise and Low-Impact Pilates Workout on the Adaptive Immune System.

Growing evidence indicates the pronounced effects of physical activity on immune functions, which may largely depend on the type of exercise, intensity, and duration. However, limited information is available regarding the effects of low-impact exercises, especially on the level of adaptive immune system. Our study aimed to investigate and compare the changes in a broad spectrum of lymphocyte subtypes after 14 weeks of aerobic-type total-body-shaping workouts (TBSW) and Pilates workouts (PW) among healthy individuals. We determined the percentages of peripheral natural killer cells and different T and B lymphocyte subtypes with flow cytometry. At the end of the exercise program, significant changes in naïve and memory lymphocyte ratios were observed in TBSW group. Percentages of naïve cytotoxic T (Tc) cells elevated, frequencies of memory Tc and T-helper cell subsets decreased, and distribution of naïve and memory B cells rearranged. Proportions of activated T cells also showed significant changes. Nonetheless, percentages of anti-inflammatory interleukin (IL)-10-producing regulatory type 1 cells and immunosuppressive CD4+CD127lo/-CD25bright T regulative cells decreased not only after TBSW but also after PW. Although weekly performed aerobic workouts may have a more pronounced impact on the adaptive immune system than low-impact exercises, both still affect immune regulation in healthy individuals.

Altered Circulating Follicular T Helper Cell Subsets and Follicular T Regulatory Cells Are Indicators of a Derailed B Cell Response in Lupus, Which Could Be Modified by Targeting IL-21R.

Systemic lupus erythematosus (SLE) is characterized by the breakdown of self-tolerance, the production of high-affinity pathogenic autoantibodies and derailed B cell responses, which indicates the importance of central players, such as follicular T helper (TFH) subsets and follicular T regulatory (TFR) cells, in the pathomechanism of the disease. In this study, we aimed to analyze the distribution of the circulating counterparts of these cells and their association with disease characteristics and B cell disproportions in SLE. We found that the increased percentage of activated circulating TFH (cTFH) and cTFR cells was more pronounced in cutaneous lupus; however, among cTFH subsets, the frequency of cTFH17 cells was decreased in patients with lupus nephritis. Furthermore, the decreased proportion of cTFH17 cells was associated with low complement C4 levels and high disease activity scores. We also investigated whether the blocking of the IL-21 receptor (IL-21R) with an anti-IL-21R monoclonal antibody inhibits the B cell response, since IL-21 primarily produced by TFH cells potentially promotes humoral immunity. We observed that anti-IL-21R inhibited plasmablast generation and immunoglobulin production. Our study demonstrated that, besides cTFR/cTFH imbalance, cTFH17 cells play a crucial role in SLE pathogenesis, and modulating cTFH-B cell interaction through the IL-21/IL-21R pathway may be a promising therapeutic strategy to suppress the pathological B cell response.

The long-term effect of removing the UV-protectant usnic acid from the thalli of the lichen Cladonia foliacea.

Terricolous lichens are abundant in semi-arid areas, where they are exposed to high irradiation. Photoprotection is essential for the algae as the photobiont provides the primer carbon source for both symbionts. The UV-protectant lichen metabolites and different quenching procedures of the alga ensure adequate photoprotection. Since the long-term effect of diminishing UV-protectant lichen metabolites is unknown, a major part of lichen secondary metabolites was removed from Cladonia foliacea thalli by acetone rinsing, and the lichens were then maintained under field conditions to investigate the effect on both symbionts for 3 years. Our aim was to determine if the decreased level of UV-protectant metabolites caused an elevated photoprotection in the algae and to reveal the dynamics of production of the metabolites. Photosynthetic activity and light protection were checked by chlorophyll a fluorescence kinetics measurements every 6 months. The concentrations of fumarprotocetraric and usnic acids were monitored by chromatographic methods. Our results proved that seasonality had a more pronounced effect than that of acetone treatment on the function of lichens over a long-term scale. Even after 3 years, the acetone-treated thalli contained half as much usnic acid as the control thalli, and the level of photoprotection remained unchanged in the algae. However, the amount of available humidity was a more critical limiting environmental factor than the amount of incoming irradiation affecting usnic acid production. The lichenicolous fungus Didymocyrtis cladoniicola became relatively more abundant in the acetone-treated samples than in the control samples, indicating a slight change caused by the treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s11557-022-01831-y.

A Comprehensive Investigation into the Distribution of Circulating B Cell Subsets in the Third Trimester of Pregnancy.

Maternal B cells play a crucial role in the development and maintenance of pregnancy, due to their humoral activities and regulatory functions. In the study, we investigated the alterations in the distributions of naïve and memory B cell subsets, as well as regulatory B (Breg) cells, in the third trimester of pregnancy. Peripheral blood from 14 healthy pregnant women in the third trimester and 7 healthy non-pregnant women was collected and examined for the frequencies of B cell subsets, including IgD+CD27- naïve, IgD+CD27+ un-switched memory, IgD-CD27+ switched memory, CD38intCD24int mature-naïve, CD38-CD24hi primarily memory and CD38hiCD24hi transitional B cells by flow cytometry. Breg cell subsets were also characterized based on the expression of CD5, CD1d and IL-10. In pregnant women, the proportions of un-switched memory and transitional B cells were significantly decreased. Additionally, the frequencies of both CD5+CD1d+ Breg and IL-10-producing B10 cells were decreased in pregnancy. Changes in the distribution of transitional B cells as well as Breg cells may be crucial contributors for the development of altered maternal immune responses and tolerance needed for the maintenance of normal pregnancy in the third trimester.

Usage of high-flow oxygen therapy outside the intensive care unit: a possibility to delay or prevent the need for mechanical ventilation among COVID-19 patients / Nagy áramlású oxigénnel végzett terápia az intenzív osztály keretein kívül alkalmazva: lehetoség a gépi lélegeztetés késleltetésére vagy elkerülésére COVID­19-ben

Összefoglaló. Bevezetés és célkituzés: Szakirodalmi adatok a súlyos lefolyású COVID-19 terápiájában a noninvazív megoldások elonyét jelezték a prompt invazív megoldásokhoz képest. A COVID-19-pandémia drámai helyzetében felmerült a nagy áramlású oxigénnel (HFO) végzett terápia alkalmazásának létjogosultsága az intenzív terápiás osztály (ITO) keretein kívül. A szerzok a súlyos hypoxiával érkezo páciensek számára a "high-flow" kezelés legjobb orvosi gyakorlatát keresték. Módszer: Áttekintették a COVID-19-pandémia elso három hullámában a Somogy Megyei Kaposi Mór Oktató Kórház Infektológiai Osztályán HFO-val kezelt páciensek dokumentációját (n = 193). Nemparaméteres statisztikai módszerekkel elemezték a HFO-kezelés elott és alatt mért oxigénszaturáció-értékeket, a HFO-kezeléssel töltött napok számát és az egyes páciensek kórlefolyásának kimenetelét: a hazabocsátást, az ITO-ra áthelyezést vagy a halálozást mint három lehetséges végpontot megjelölve. Külön értékelték a harmadik hullám idoszakát (a standard terápia ekkorra kialakult). Eredmények: A járvány elorehaladtával a MET- (Medical Emergency Team) rendszer igénybevétele 811%-ra emelkedett, a HFO-készülékek száma 567%-kal nott. A COVID-19-protokoll szerinti kezelés mellett HFO-terápiára szoruló páciensek 18,7%-a invazív megoldást elkerülve, gyógyultan távozhatott, optimális terhelés és szakmai tapasztalat mellett ez az arány elérte a 36%-ot is. A hazabocsátható páciensek csoportjában a kezdeti szaturációk medián értéke 78%, a teljes HFO-kezelés ideje 8,5 nap volt. A páciensek 1%-ában pneumothoraxot, pneumomediastinumot észleltek. A végül közvetlenül hazabocsátható, illetve ITO-ra került páciensek kezdeti oxigénszaturáció-értékének különbsége nem bizonyult szignifikánsnak. Következtetés: A jelen közlemény is alátámasztja, hogy a kezdeti alacsony szaturációérték önmagában nem jelenti az invazív beavatkozás létjogosultságát ebben a kórképben. "High-flow" kezeléseket az intenzíves kezelés eloszobájaként nem intenzíves szakemberek is végezhetnek COVID-19-betegekben, rendszeres intenzíves konzultáció mellett, hogy a HFO-kezelés melletti rosszabbodás minél inkább felfedezheto legyen. Orv Hetil. 2022; 163(7): 254-266. INTRODUCTION AND OBJECTIVES: Previous studies have shown the advantage of non-invasive over prompt invasive approaches in the treatment of patients with severe COVID-19. The dramatic situation of the pandemic raised the legitimacy of using high-flow oxygen therapy (HFO) outside the intensive care unit (ICU). The authors investigated ways of its best practice. METHOD: They retrospectively analysed documentation of patients receiving HFO in the first three waves of the pandemic on the Infectious Diseases' Ward (n = 193), to record oxygen saturation levels before and during HFO, number of treatment days. Discharge at home, transfer to intensive care unit and death were chosen as the three possible endpoints. The period of the third wave (standard therapy established) was analysed separately. RESULTS: As the pandemic progressed, the usage of MET (Medical Emergency Team) grew to 811%, the number of HFO devices grew by 567%. With concomitant standard COVID-19 therapy, 18.7% of the patients requiring HFO could be discharged home, avoiding invasive solutions. With optimal workload and experience, this ratio reached 36%. Among patients later discharged home, the median oxygen saturation before HFO was 78%, the total time with HFO was 8,5 days. The occurrence of pneumothorax or pneumomediastinum was 1%. The difference in oxygen saturation before HFO between the patients later discharged home and those transferred to ICU was not significant. CONCLUSION: The results support the assumption that low oxygen saturation at admission does not inevitably require invasive intervention in COVID-19 patients, high-flow oxygen therapy can also be performed by non-ICU professionals as ante-room to the ICU, under regular supervision by ICU experts, so that the deterioriation of the patients' condition is discovered appropriately. Orv Hetil. 2022; 163(7): 254-266.

Biophysical experiments reveal a protective role of protein phosphatase Z1 against oxidative damage of the cell membrane in Candida albicans.

Protein phosphatase Z1 (Ppz1) has been shown to take part in important physiological functions in fungi including a contribution to virulence of Candida albicans. Although its involvement in the oxidative stress response has also been documented, the exact mechanism of action of its protective effect against oxidative damage remains unknown. By developing a pipeline to analyze the biophysical properties of the cell membrane in fungi, we demonstrate that the plasma membrane of Ppz1-KO Candida albicans displays increased sensitivity to tert-butyl-hydroperoxide-induced oxidative damage. In particular, the response to the oxidizing agent, characterized by increased lipid peroxidation, reduced lipid order, and inhibited lateral mobility of plasma membrane components, is significantly more pronounced in the Ppz1-KO C. albicans strain than in the wild-type counterpart. Remarkably, membrane constituents became almost completely immobile in the phosphatase deletion mutant exposed to oxidative stress. Furthermore, moderately elevated membrane lipid peroxidation accompanied by the aforementioned changes in the biophysical characteristics of the plasma membrane are already detectable in untreated Ppz1-KO cells indicating latent membrane damage even in the absence of oxidative stress. In conclusion, the hypersensitivity of cells lacking Ppz1 to oxidative damage establishes that potential Ppz1 inhibitors may synergize with oxidizing agents in prospective anti-fungal combination therapies.

The Negative Effect of Protein Phosphatase Z1 Deletion on the Oxidative Stress Tolerance of Candida albicans Is Synergistic with Betamethasone Exposure.

The glucocorticoid betamethasone (BM) has potent anti-inflammatory and immunosuppressive effects; however, it increases the susceptibility of patients to superficial Candida infections. Previously we found that this disadvantageous side effect can be counteracted by menadione sodium bisulfite (MSB) induced oxidative stress treatment. The fungus specific protein phosphatase Z1 (CaPpz1) has a pivotal role in oxidative stress response of Candida albicans and was proposed as a potential antifungal drug target. The aim of this study was to investigate the combined effects of CaPPZ1 gene deletion and MSB treatment in BM pre-treated C. albicans cultures. We found that the combined treatment increased redox imbalance, enhanced the specific activities of antioxidant enzymes, and reduced the growth in cappz1 mutant (KO) strain. RNASeq data demonstrated that the presence of BM markedly elevated the number of differentially expressed genes in the MSB treated KO cultures. Accumulation of reactive oxygen species, increased iron content and fatty acid oxidation, as well as the inhibiting ergosterol biosynthesis and RNA metabolic processes explain, at least in part, the fungistatic effect caused by the combined stress exposure. We suggest that the synergism between MSB treatment and CaPpz1 inhibition could be considered in developing of a novel combinatorial antifungal strategy accompanying steroid therapy.

Effects of Functional Training on Sarcopenia in Elderly Women in the Presence or Absence of ACE Inhibitors.

Sarcopenia, defined as loss of muscle mass and strength, develops gradually with aging or after chronic disease. Efforts are ongoing to identify the best interventions that can slow down or stop sarcopenia. Nutrition-based interventions and exercise therapy may be beneficial; however, pharmacotherapy also could play a role. The effect of ACE inhibitors on physical performance is controversial. The present study investigates the impact of functional training on sarcopenia in the presence or absence of ACEi in elderly females. A total of 35 women over 65 years of age were selected for two groups on the basis that they were taking ACEi (n = 18) or not (n = 17). All subjects conducted a training program two times a week for 6 months. We examined various factors related to sarcopenia. After completing the short physical performance battery (SPPB) test, we found a significant improvement after 6 months of functional training. SPPB values of the ACEi group were significantly lower at the beginning of the study; however, we observed no difference between the SPPB results of the two groups after the training period. We conducted further studies to measure posture and spine mobility. Our Schober and Cobra test results revealed significantly improved spine mobility (both flexor and extensor) in both groups after 6 months of training. Furthermore, the grip strength of the hands, studied by an electric dynamometer, was significantly improved in both groups at the end of the training period. Our results indicated that functional training may improve body composition and muscle strength in patients diagnosed with sarcopenia. Furthermore, ACEi may be a helpful additional therapy in older adult patients suffering from severe sarcopenia.

Regular Exercise May Restore Certain Age-Related Alterations of Adaptive Immunity and Rebalance Immune Regulation.

Age-related changes of the immune system lead to an increased morbidity and mortality due to enhanced vulnerability to infectious diseases and malignancies. Recent studies revealed the important effects of physical activity on immune functions, which may largely depend on the type of exercise, its intensity and duration. However, limited information is available regarding the immunological effects of sport activities in older ages. The aim of our study was to examine the changes in a wide spectrum of lymphocyte subtypes after regular workout among healthy elderly individuals. We enrolled 29 elderly women with sedentary lifestyle (mean age: 67.03 ± 3.74 years) to take part in a 6-week long functional conditioning gymnastic exercise program. The percentages of peripheral natural killer (NK), NKT cells, T and B lymphocyte subtypes (early-/late-activated T, naïve and memory T, cytotoxic T (Tc), T-helper (Th)1, Th2, Th17, T regulatory type 1 (Tr1), CD4+CD127lo/-CD25bright Treg, as well as naïve and memory B cells) were determined by flow cytometry. Evaluation of the changes in functional capability of Treg cells was based on in vitro functional assays. At the end of exercise program, in parallel with improvements in body composition and physical performance, significant changes in naïve and memory lymphocyte ratios were observed. Importantly, levels of naïve Tc cells elevated, ratios of effector memory Tc cells decreased and distribution of memory B cells rearranged as well. Additionally, proportions of late-activated HLA-DR+ T cells increased, while percentages of anti-inflammatory interleukin (IL)-10 producing Tr1 cells, as well as immunosuppressive CD4+CD127lo/-CD25bright Treg cells decreased following the exercise workout. Changes observed after the regular exercise program indicate an improvement in the age-related redistribution of certain naïve and memory cell proportions and a retuned immune regulation in older ages.

Effect of rapid response system on hospital mortality, implemented by Somogy County Kaposi Mór Teaching Hospital / A Somogy Megyei Kaposi Mór Oktató Kórház által bevezetett gyors reagálású rendszer hatása a kórházi mortalitásra.

Összefoglaló. Bevezetés: Általánosságban elmondható, hogy a fekvobeteg-ellátást nyújtó egészségügyi intézmények intenzív terápiás osztályain (ITO) jelennek meg a legsúlyosabb kórképekkel és a legmagasabb halálozási aránnyal bíró esetek, rendszerint megkésve. Eltéroen az ITO-tól, más betegellátó osztályokon elofordulhat, hogy nem észlelik megfeleloen és idoben a betegek olyan állapotváltozásait, melyek elore jelzik például a szívleállást vagy a keringési rendszer várható összeomlását. Ennek kiküszöbölésére jelenthet megoldást az úgynevezett gyors reagálású rendszer (RRS), melynek segítségével csökkentheto a kórházon belüli mortalitás. Célkituzés: A Somogy Megyei Kaposi Mór Oktató Kórház a teljes intézményre kiterjedoen a 2016. évtol alkalmazza az RRS-t. A jelen tanulmány célja a kórházi mortalitás csökkentésével kapcsolatos elso eredmények bemutatása. Módszer: Vizsgálatunkban az ITO-ra került betegek adatbázisán alapuló kereszttáblás, illetve nemparametrikus statisztikai módszereket alkalmaztuk. Eredmények: A statisztikai próbák eredményei alapján megállapítottuk, hogy az intenzív ellátás felvételi diagnózisai (légzési elégtelenség, neurológiai ok, reanimáció, szepszis, szív/keringési, egyéb ok) között statisztikailag igazolható eltérés tapasztalható (p = 3,815e-14) RRS alkalmazásával és a nélkül. Az RRS-sel felvettek között magasabb arányt képviseltek a légzési elégtelenséggel és szepszissel érkezo, súlyosabb betegek, ugyanakkor kisebbnek bizonyult a reszuszcitáltak száma. Megbeszélés: Az RRS nélküli idoszak 2,983%-os intézményi mortalitása az RRS-idoszakban 2,932%-ra csökkent, azonban a beküldo osztályonkénti adatokban jelentos különbségeket tapasztaltunk. 21 fekvobeteg-osztály közül 19 osztály esetén csökkent a mortalitás az RRS bevezetését követoen. Következtetés: Arra a megállapításra jutottunk, hogy a nemzetközi szakirodalom alapján bevezetett RRS növelte az egészségügyi ellátás hatékonyságát, és ezáltal sikerült csökkenteni az intézményi szintu mortalitást. Orv Hetil. 2021; 162(20): 782-789. INTRODUCTION: In general, the cases with the most severe diseases and highest mortality rate are admitted to the intensive care units (ICU) usually late. Contrary to ICU, in other in-patient units it can happen that those changes in patients' condition, which pre-indicate, e.g., cardiac arrest or collapse of circulatory system, are not noticed properly and in time. To eliminate this, the so-called rapid response system (RRS) can be the solution, by the help of which hospital mortality can be reduced. Objectve: The RRS has been used all institution-wide in Somogy County Kaposi Mór Teaching Hospital from 2016. The aim of this study is to demonstrate the results concerning hospital mortality cutdown. METHOD: Our analysis was based on ICU patients' database and we applied cross-tabulation and non-parametric statistical methods. RESULTS: We appointed, that among admission diagnosises to ICU (respiration insufficiency, neurological reason, reanimation, sepsis, cardiac/circulatory condition, other), statistically verifiable discrepancy can be experienced (p = 3.815e-14) with using RRS or without it. Among those admitted via RRS, more severe patients with respiration insufficiency and septic conditions were represented in higher rate, while the number of the admitted ones after resuscitation has decreased. DISCUSSION: Hospital mortality rate of 2.983% without using RRS decreased into 2.932% in the period of using RRS, though we observed remarkable differences in data of non-ICU in-patient departments. Mortality has reduced in 19 in-patient departments out of 21, after implementing RRS. CONCLUSION: To sum it up, we identified that RRS implemented on the basis of international references has increased the efficiency of healthcare and owing to it, institution-level mortality has successfully decreased. Orv Hetil. 2021; 162(20): 782-789.

MSC-like cells increase ability of monocyte-derived dendritic cells to polarize IL-17-/IL-10-producing T cells via CTLA-4.

Mesenchymal stromal cell-like (MSCl) cells generated from human embryonic stem cells are considered to be an eligible cell line to model the immunomodulatory behavior of mesenchymal stromal cells (MSCs) in vitro. Dendritic cells (DCs) are essential players in the maintenance and restoration of the sensitive balance between tolerance and immunity. Here, the effects of MSCl cells on the in vitro differentiation of human monocytes into DCs were investigated. MSCl cells promote the differentiation of CTLA-4 expressing DCs via the production of all-trans retinoic acid (ATRA) functioning as a ligand of RARα, a key nuclear receptor in DC development. These semi-matured DCs exhibit an ability to activate allogeneic, naive T cells and polarize them into IL-10 + IL-17 + double-positive T helper cells in a CTLA-4-dependent manner. Mapping the molecular mechanisms of MSC-mediated indirect modulation of DC differentiation may help to expand MSCs' clinical application in cell-free therapies.

The Imbalance of Circulating Follicular T Helper Cell Subsets in Primary Sjögren's Syndrome Associates With Serological Alterations and Abnormal B-Cell Distribution.

Since B-cell hyperactivity and pathologic antibody response are key features in the immunopathogenesis of primary Sjögren's syndrome (pSS), the role of follicular T helper (TFH) cells as efficient helpers in the survival and differentiation of B cells has emerged. Our aim was to investigate whether a change in the balance of circulating (c)TFH subsets and follicular regulatory T (TFR) cells could affect the distribution of B cells in pSS. Peripheral blood of 38 pSS patients and 27 healthy controls was assessed for the frequencies of cTFH cell subsets, TFR cells, and certain B cell subpopulations by multicolor flow cytometry. Serological parameters, including anti-SSA, anti-SSB autoantibodies, immunoglobulin, and immune complex titers were determined as part of the routine diagnostic evaluation. Patients with pSS showed a significant increase in activated cTFH cell proportions, which was associated with serological results. Frequencies of cTFH subsets were unchanged in pSS patients compared to healthy controls. The percentages and number of cTFR cells exhibited a significant increase in autoantibody positive patients compared to patients with seronegative pSS. The proportions of transitional and naïve B cells were significantly increased, whereas subsets of memory B cells were significantly decreased and correlated with autoantibody production. Functional analysis revealed that the simultaneous blockade of cTFH and B cell interaction with anti-IL-21 and anti-CD40 antibodies decreased the production of IgM and IgG. Imbalance in TFH subsets and TFR cells indicates an ongoing over-activated humoral immune response, which contributes to the characteristic serological manifestations and the pathogenesis of pSS.

Associations between fitness levels and self-perceived health-related quality of life in community - dwelling for a group of older females.

BACKGROUND: For older adults perceived quality of life has been linked to the ability to accomplish everyday tasks, a functional capacity which is thought to be based upon physical fitness. Although there is a relationship between physical activity and quality of life in older adults, the fitness of older adults and its relationship to quality of life needs more investigation. Therefore, the purpose of this study was to examine the associations between self-reported health-related quality of life and physical fitness in community-dwelling older females. METHODS: A cross-sectional study between four different age groups in retirement villages from two different places of the southern and western region of Hungary, among 173 women between the ages of 58 and 94 years old. We measured physical fitness using the Fullerton Test protocol and self-perceived health quality of life using the Short-Form Health Survey. RESULTS: Group means were different in six-minute walk distance, handgrip strength, and arm curls. The youngest group of females had higher scores of fitness in these categories as compared to the oldest grouping of women. Quality of Life were also difference across age groupings although not linear across the four age categories. Moderate level positive relationship was evident between perceived physical function and certain categories of physical fitness. CONCLUSIONS: Sociability and self-motivation has a leading role in quality of life in elder population. It is worth putting a lot more emphasis into continuous cultural, social and most importantly into physical activity programs for elderly.

Measuring Psychological Inflexibility in Children and Adolescents: Evaluating the Avoidance and Fusion Questionnaire for Youth.

The Avoidance and Fusion Questionnaire for Youth (AFQ-Y8) was developed to measure psychological inflexibility. Although the questionnaire is a well-known tool in clinical practice, its psychometric properties have not been widely investigated in the target population of children and adolescents. The purpose of this study was to investigate the factor structure and validity of the AFQ-Y8 (N = 1,572, mean age 15.39 years, girls 51%) on a Hungarian sample. We also tested the invariance of the measurement model across two age groups (11-14 and 15-20 years old). Results confirmed the single-factor structure of the AFQ-Y8. Psychological inflexibility was also found to be positively related to emotional instability, externalizing, and internalizing problems. Furthermore, psychological inflexibility explained the variance of life satisfaction when personality dimensions, emotional, and behavioral problems were accounted for. Measurement invariance across age groups was partially supported. These results suggest that the AFQ-Y8 is a reliable and valid instrument for assessing psychological inflexibility in children and adolescents.

Deletion of the fungus specific protein phosphatase Z1 exaggerates the oxidative stress response in Candida albicans.

BACKGROUND: Candida albicans is an opportunistic pathogen which is responsible for widespread nosocomial infections. It encompasses a fungus specific serine/threonine protein phosphatase gene, CaPPZ1 that is involved in cation transport, cell wall integrity, oxidative stress response, morphological transition, and virulence according to the phenotypes of the cappz1 deletion mutant. RESULTS: We demonstrated that a short-term treatment with a sublethal concentration of tert-butyl hydroperoxide suppressed the growth of the fungal cells without affecting their viability, both in the cappz1 mutant and in the genetically matching QMY23 control strains. To reveal the gene expression changes behind the above observations we carried out a global transcriptome analysis. We used a pilot DNA microarray hybridization together with extensive RNA sequencing, and confirmed our results by quantitative RT-PCR. Novel functions of the CaPpz1 enzyme and oxidative stress mechanisms have been unraveled. The numbers of genes affected as well as the amplitudes of the transcript level changes indicated that the deletion of the phosphatase sensitized the response of C. albicans to oxidative stress conditions in important physiological functions like membrane transport, cell surface interactions, oxidation-reduction processes, translation and RNA metabolism. CONCLUSIONS: We conclude that in the wild type C. albicans CaPPZ1 has a protective role against oxidative damage. We suggest that the specific inhibition of this phosphatase combined with mild oxidative treatment could be a feasible approach to topical antifungal therapy.

[The effect of reduced oxygen saturation during sleep on depression]. / Az alvás alatt jelentkezo oxigénszaturáció-csökkenés hatása a depresszióra.

Introduction: Numerous data suggest that episodes of breathing disorder during sleep are closely related to chronic cardiovascular and mental illnesses. Aim: In this study, we sought to find out how the decrease in oxygen saturation level and its duration during sleep are affected by the degree of depression and its extent. Method: Data of 76 persons were processed in the study. The oxygen saturation measured during sleep was obtained from data from a polysomnographic filter device. Data collection for depression symptoms was done with a validated questionnaire. The decrease of night oxygen saturation on the effect of the disease was illustrated by the odds ratio calculation. Results: The value below 90% of the average oxygen saturation during sleep time will more than double the risk of developing depression. It is also a risk factor for the severity of depression. Examining the duration of sleep time at reduced saturation, it mainly increases the chance of severe depression. Conclusions: Hypoxia during sleep and duration of hypoxic periods are a risk factor for the development of depression with therapeutic and diagnostic consequences. Orv Hetil. 2019; 160(20): 780-783.

[The importance of microRNAs in the development of systemic autoimmune disorders]. / A mikro-RNS-ek jelentosége szisztémás autoimmun betegségek kialakulásában.

MicroRNAs (miRNAs) are 18-25 nucleotide long, single stranded, endogenous, non-coding small RNAs playing an important role in regulating gene expression at posttranscriptional level. miRNAs control approximately 90% of protein-coding genes, and play a central role in various biological processes including immune cell lineage commitment, differentiation, proliferation, apoptosis and maintenance of immune homeostasis. Changes in the expression of certain miRNAs may lead to the development of many diseases, including systemic autoimmune diseases. In this study, we summarize the biogenesis of miRNAs, their role in regulation of the immune system, and review the latest research findings in systemic lupus erythematosus, primary Sjögren's syndrome, rheumatoid arthritis and systemic sclerosis. In the future, miRNAs may help not only in establishing diagnosis and prognosis but potentially serve as targets for modern therapeutic approaches in autoimmune diseases. Orv Hetil. 2019; 160(15): 563-572.