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.

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.

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.

Microbiological Changes and Caries-Preventive Effect of an Innovative Varnish Containing Chlorhexidine in Orthodontic Patients.

The aim of this study was to investigate the effects of Cervitec Plus® on the level of mutans streptococcus (SM) and lactobacillus (LB) colonies and the development of white spot lesions (WSLs) in patients with fixed orthodontic appliances. Informed consent was obtained from 32 volunteers (age 16.5 ± 2.75 years). At baseline, levels of the bacterial colonies were determined in saliva and plaque using a chairside test (CRT Bacteria, Ivoclar-Vivadent, Schaan, Liechtenstein), and the number of WSLs was registered. After placing the fixed appliance, Cervitec Plus® or placebo varnishes (Ivoclar-Vivadent, Schaan, Liechtenstein) were applied monthly around the brackets and tubes, randomly in the right or left (test and placebo) quadrants of the same dental arch. SM and LB colonies in saliva and the SM colonies in plaque were determined on 11-21, 13-23, 15-25, and 16-26 teeth monthly over a 6-month period. At the sixth month, the number of new WSLs was determined. By the end of the study, compared with baseline, the ratio of saliva samples belonging to the low-risk category was significantly higher (p ≤ 0.01) from the 2nd month regarding the SM (76 vs. 52%) and LB (69 vs. 52%); reduction of SM in plaque was significantly greater on the test than placebo sides (6.69 ± 1.71 and 4.45 ± 1.60, respectively; p ≤ 0.01). The mean number of new WSLs was significantly lower in the test (0.06 ± 1.60) than in the placebo quadrants (1.13 ± 1.50, p ≤ 0.01). CONCLUSION: Monthly use of Cervitec Plus® could result in a significant improvement in oral health of orthodontic patients.

[The probability of obstructive sleep apnea disorders emergence by odds ratio of main risk factors]. / Az alvási apnoe szindróma vezeto rizikótényezoinek esélyhányadosai.

INTRODUCTION: The quality of sleep plays a serious role in the individual's daytime performace and state of health, there by it has a strong influence on the society. AIM: The present study measures the probability developing and severity of obstructive sleep apnea syndrome, - which belongs to group of disorders of the respiratory - through odds ratio of leading risk factors. METHOD: 127 persons were examined in the test. The sleep structure test data were processed by polysomnographic screening device. RESULTS: The nutritional level of body in mass index (BMI), and the neck circumferences data were recorded in cm. On the basis of the examination the gender as a risk factor it can be said that the odds ratio for men compared to women, more than three times higher of emergence of disease. CONCLUSIONS: Men's chance of the emergence of serious disease is more than four times higher than women's chance. In the men's test group the most significant predictor of obstructive sleep apnea amongst the risk factors is the circumference according to odds ratio. In women's group the leader odds ratio is BMI. More than 50% of test goup don't report about daytime sleepiness, and this fact draws our attention to the role of risk factors' odds ratio in selection. Orv Hetil. 2017; 158(21): 823-828.

Increased IL-21 Expression Induces Granzyme B in Peripheral CD5(+) B Cells as a Potential Counter-Regulatory Effect in Primary Sjögren's Syndrome.

Recently, we reported elevated proportions of circulating follicular T helper cells and higher levels of interleukin- (IL-) 21 in primary Sjögren's syndrome (pSS). Interaction of invariant natural killer T (iNKT) cells with B cells and granzyme B (GrB) production may be also important in pSS. Thirty-two pSS patients and 24 healthy controls were enrolled in our study. We investigated the expression of intracellular GrB and IL-21 receptor (IL-21R) of CD19(+)CD5(+) and CD19(+)CD5(-) B cells; furthermore, we determined the IL-21 expression of iNKT cells as well. We also assessed the proportion of transitional (CD19(+)CD24(high)CD38(high)), mature (CD19(+)CD24(int)CD38(int)) and primarily memory (CD19(+)CD24(high)CD38(-)) B cells. CD5(+) but not CD5(-) B cells showed elevated GrB and IL-21R expression in pSS; additionally IL-21 expression of iNKT cells was also elevated. The ratios of transitional and mature B cells were elevated in pSS, while primarily memory B cell percentages were decreased, which correlated with GrB and IL-21R expression of CD19(+) B cells. Our results suggest that enhanced IL-21R expression of CD19(+)CD5(+) B cells and production of IL-21 by iNKT cells may play an important role in the pathogenesis of pSS by regulating CD19(+)CD5(+) B cell functions and increasing GrB production, presumably leading to a counter-regulatory effect in the disease.

Effect of water supply on growth and polyphenols of lemon balm (Melissa officinalis L.) and thyme (Thymus vulgaris L.).

A pot experiment was carried out with lemon balm (Melissa officinalis L.) and thyme (Thymus vulgaris L.). Different water supply was applied: 25%, 40% and 70% saturation of soil water capacity (SWC). Morphological traits, biomass and phenolic type active ingredients were investigated. Among the two species, main differences were registered in biomass and TPC. Lower SWC resulted in reduced biomass production of lemon balm, while the applied stress treatments did not effect the biomass of thyme. In lemon balm, highest TPC contents were measured in control plants both in shoots and roots but in thyme, the shoots showed a significantly increased TPC at the 25% SWC conditions. Neither the content of total flavonoids nor that of the rosmarinic acid was affected by the treatments. The antioxidant capacity proved to be in tight connection with the TPC in both species (r = 0.766-0.883). The rosmarinic acid content of lemon balm plants contributed to the antioxidant capacity, as well (r = 0.679-0.869).

Membrane Assays to Characterize Interaction of Drugs with ABCB1.

ATP-binding cassette sub-family B member 1 (ABCB1) [P-glycoprotein (P-gp), multidrug resistance protein 1 (MDR1)] can affect the pharmacokinetics, safety, and efficacy of drugs making it important to identify compounds that interact with ABCB1. The ATPase assay and vesicular transport (VT) assay are membrane based assays that can be used to measure the interaction of compounds with ABCB1 at a lower cost and higher throughput compared to cellular-based assays and therefore can be used earlier in the drug development process. To that end, we tested compounds previously identified as ABCB1 substrates and inhibitors for interaction with ABCB1 using the ATPase and VT assays. All compounds tested interacted with ABCB1 in both the ATPase and VT assays. All compounds previously identified as ABCB1 substrates activated ABCB1-mediated ATPase activity in the ATPase assay. All compounds previously identified as ABCB1 inhibitors inhibited the ABCB1-mediated transport in the VT assay. Interestingly, six of the ten compounds previously identified as ABCB1 inhibitors activated the basal ATPase activity in activation assays suggesting that the compounds are substrates of ABCB1 but can inhibit ABCB1 in inhibition assays. Importantly, for ATPase activators the EC50 of activation correlated with the IC50 values from the VT assay showing that interactions of compounds with ABCB1 can be measured with similar levels of potency in either assay. For ATPase nonactivators the IC50 values from the ATPase inhibition and VT inhibition assay showed correlation. These results demonstrate the utility of membrane assays as tools to detect and rank order drug-transporter interactions.

The histopathology of labial salivary glands in primary Sjögren's syndrome: focusing on follicular helper T cells in the inflammatory infiltrates.

Recently, we revealed the importance of follicular helper T cells (T(FH)) in the pathogenesis of primary Sjögren's syndrome (pSS). In the present study, we focused on the site of the inflammation and determined the composition of lymphocyte infiltration in labial salivary gland (LSG) biopsies with special emphasis on T(FH) and germinal center B cells. We selected tissue blocks obtained from ten patients at the time of disease onset. Detection of cell specific markers was performed with immunohistochemical and immunofluorescence stainings. We evaluated patients' clinical and laboratory features retrospectively and assessed the relation between disease course and early histopathological findings. LSG biopsies were graded based on the extension and arrangement level of periductal inflammatory cell infiltrates. T(FH) cell markers (CD84, PD-1, and Bcl-6) occurred predominantly in more organized structures with higher focus scores. The coexpression of CD3 and Bcl-6 markers clearly identified T(FH) cells close to Bcl-6(+) B cells with the typical formation of germinal centers. Systemic features were developed later in the disease course only in patients with highly structured infiltrates and the presence of T(FH) cells. Our observations suggest that the presence of T(FH) cells in LSGs at the disease onset may predict a more pronounced clinical course of pSS.

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.

Follicular helper T cells may play an important role in the severity of primary Sjögren's syndrome.

The aim of this study was to investigate the possible role of follicular helper T (TFH) cells in the pathogenesis of primary Sjögren's syndrome (pSS) by analyzing immune-competent cells and serological markers with special emphasis on clinical symptoms. We enrolled 50 pSS patients and 16 healthy individuals in the study. Patients had elevated ratio of peripheral TFH cells, however, when dividing patients into two groups defined by the presence of extraglandular manifestations (EGMs), only patients with EGMs differed from controls significantly. Moreover, TFH cell percentages correlated positively with both activated T cell and Tr1 cell values. On the contrary, TFH cell percentages showed negative correlation with both IgM and IgG memory B cell proportions. Elevated TFH percent\ages were observed in the anti-SSA/SSB positive patients, and also in patients with higher IL-12, IL-21 levels and focus score values. Increased TFH cell proportions seem to have an important role in disease development.

Variability in P-glycoprotein inhibitory potency (IC50) using various in vitro experimental systems: implications for universal digoxin drug-drug interaction risk assessment decision criteria.

A P-glycoprotein (P-gp) IC50 working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC50 determinations. Each laboratory followed its in-house protocol to determine in vitro IC50 values for 16 inhibitors using four different test systems: human colon adenocarcinoma cells (Caco-2; eleven laboratories), Madin-Darby canine kidney cells transfected with MDR1 cDNA (MDCKII-MDR1; six laboratories), and Lilly Laboratories Cells--Porcine Kidney Nr. 1 cells transfected with MDR1 cDNA (LLC-PK1-MDR1; four laboratories), and membrane vesicles containing human P-glycoprotein (P-gp; five laboratories). For cell models, various equations to calculate remaining transport activity (e.g., efflux ratio, unidirectional flux, net-secretory-flux) were also evaluated. The difference in IC50 values for each of the inhibitors across all test systems and equations ranged from a minimum of 20- and 24-fold between lowest and highest IC50 values for sertraline and isradipine, to a maximum of 407- and 796-fold for telmisartan and verapamil, respectively. For telmisartan and verapamil, variability was greatly influenced by data from one laboratory in each case. Excluding these two data sets brings the range in IC50 values for telmisartan and verapamil down to 69- and 159-fold. The efflux ratio-based equation generally resulted in severalfold lower IC50 values compared with unidirectional or net-secretory-flux equations. Statistical analysis indicated that variability in IC50 values was mainly due to interlaboratory variability, rather than an implicit systematic difference between test systems. Potential reasons for variability are discussed and the simplest, most robust experimental design for P-gp IC50 determination proposed. The impact of these findings on drug-drug interaction risk assessment is discussed in the companion article (Ellens et al., 2013) and recommendations are provided.

Application of receiver operating characteristic analysis to refine the prediction of potential digoxin drug interactions.

In the 2012 Food and Drug Administration (FDA) draft guidance on drug-drug interactions (DDIs), a new molecular entity that inhibits P-glycoprotein (P-gp) may need a clinical DDI study with a P-gp substrate such as digoxin when the maximum concentration of inhibitor at steady state divided by IC50 ([I1]/IC50) is ≥0.1 or concentration of inhibitor based on highest approved dose dissolved in 250 ml divide by IC50 ([I2]/IC50) is ≥10. In this article, refined criteria are presented, determined by receiver operating characteristic analysis, using IC50 values generated by 23 laboratories. P-gp probe substrates were digoxin for polarized cell-lines and N-methyl quinidine or vinblastine for P-gp overexpressed vesicles. Inhibition of probe substrate transport was evaluated using 15 known P-gp inhibitors. Importantly, the criteria derived in this article take into account variability in IC50 values. Moreover, they are statistically derived based on the highest degree of accuracy in predicting true positive and true negative digoxin DDI results. The refined criteria of [I1]/IC50 ≥ 0.03 and [I2]/IC50 ≥ 45 and FDA criteria were applied to a test set of 101 in vitro-in vivo digoxin DDI pairs collated from the literature. The number of false negatives (none predicted but DDI observed) were similar, 10 and 12%, whereas the number of false positives (DDI predicted but not observed) substantially decreased from 51 to 40%, relative to the FDA criteria. On the basis of estimated overall variability in IC50 values, a theoretical 95% confidence interval calculation was developed for single laboratory IC50 values, translating into a range of [I1]/IC50 and [I2]/IC50 values. The extent by which this range falls above the criteria is a measure of risk associated with the decision, attributable to variability in IC50 values.

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.

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.

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.

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.

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.

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.

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.