O-glycosylation of IgA1 and the pathogenesis of an autoimmune disease IgA nephropathy.

IgA nephropathy is a kidney disease characterized by deposition of immune complexes containing abnormally O-glycosylated IgA1 in the glomeruli. Specifically, some O-glycans are missing galactose that is normally ß1,3-linked to N-acetylgalactosamine of the core 1 glycans. These galactose-deficient IgA1 glycoforms are produced by IgA1-secreting cells due to a dysregulated expression and activity of several glycosyltransferases. Galactose-deficient IgA1 in the circulation of patients with IgA nephropathy is bound by IgG autoantibodies and the resultant immune complexes can contain additional proteins, such as complement C3. These complexes, if not removed from the circulation, can enter the glomerular mesangium, activate the resident mesangial cells, and induce glomerular injury. In this review, we briefly summarize clinical and pathological features of IgA nephropathy, review normal and aberrant IgA1 O-glycosylation pathways, and discuss the origins and potential significance of natural anti-glycan antibodies, namely those recognizing N-acetylgalactosamine. We also discuss the features of autoantibodies specific for galactose-deficient IgA1 and the characteristics of pathogenic immune complexes containing IgA1 and IgG. In IgA nephropathy, kidneys are injured by IgA1-containing immune complexes as innocent bystanders. Most patients with IgA nephropathy progress to kidney failure and require dialysis or transplantation. Moreover, most patients after transplantation experience a recurrent disease. Thus, a better understanding of the pathogenetic mechanisms is needed to develop new disease-specific treatments.

IgA Nephropathy: Significance of IgA1-Containing Immune Complexes in Clinical Settings.

IgA nephropathy (IgAN) is considered to be an autoimmune disease characterized by the formation of IgA1-containing immune complexes in the circulation and glomerular immunodeposits. Extensive research has identified multiple genetic, immunological, and environmental factors contributing to disease development and progression. The pathogenesis of IgAN is considered a multifactorial process involving the formation of immune complexes wherein aberrantly O-glycosylated IgA1 is recognized as an autoantigen. Consequently, the clinical presentation of IgAN is highly variable, with a wide spectrum of manifestations ranging from isolated microscopic hematuria or episodic macroscopic hematuria to nephrotic-range proteinuria. Whereas some patients may exhibit a slowly progressive form of IgAN, others may present with a rapidly progressive glomerulonephritis leading to kidney failure. Development of the treatment for IgAN requires an understanding of the characteristics of the pathogenic IgA1-containing immune complexes that enter the glomerular mesangium and induce kidney injury. However, not all details of the mechanisms involved in the production of galactose-deficient IgA1 and immune-complex formation are fully understood. Here, we review what we have learned about the characteristics of nephritogenic IgA1 in the half-century since the first description of IgAN in 1968.

Fungal infection frequency in newly diagnosed acute myeloid leukaemia patients treated with venetoclax plus azacitidine with or without antifungal prophylaxis.

Our observational study analysed fungal infection frequency within cohorts with versus without antifungal prophylaxis (AFP) among newly diagnosed first-line venetoclax and azacitidine (VEN + AZA)-treated acute myeloid leukaemias in Czech, Austrian and Slovak haematology centres. Among 186 patients, 85 (46%) received antifungal prophylaxis, while 101 (54%) received no prophylaxis. Fungal infections occurred in 1/85 patients with prophylaxis (1%) and 5/101 patients without prophylaxis (5%) (p = 0.222). No significant difference was recorded between cohorts with and without AFP in terms of death rate (p = 0.296) and overall survival (p = 0.844). In conclusion, most infections were not severe, developing during the first treatment-cycle and did not affect patients' overall outcome.

Advancements in risk stratification and management strategies in primary cardiovascular prevention.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for advancements in risk assessment and management strategies. Although significant progress has been made recently, identifying and managing apparently healthy individuals at a higher risk of developing atherosclerosis and those with subclinical atherosclerosis still poses significant challenges. Traditional risk assessment tools have limitations in accurately predicting future events and fail to encompass the complexity of the atherosclerosis trajectory. In this review, we describe novel approaches in biomarkers, genetics, advanced imaging techniques, and artificial intelligence that have emerged to address this gap. Moreover, polygenic risk scores and imaging modalities such as coronary artery calcium scoring, and coronary computed tomography angiography offer promising avenues for enhancing primary cardiovascular risk stratification and personalised intervention strategies. On the other hand, interventions aiming against atherosclerosis development or promoting plaque regression have gained attention in primary ASCVD prevention. Therefore, the potential role of drugs like statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, omega-3 fatty acids, antihypertensive agents, as well as glucose-lowering and anti-inflammatory drugs are also discussed. Since findings regarding the efficacy of these interventions vary, further research is still required to elucidate their mechanisms of action, optimize treatment regimens, and determine their long-term effects on ASCVD outcomes. In conclusion, advancements in strategies addressing atherosclerosis prevention and plaque regression present promising avenues for enhancing primary ASCVD prevention through personalised approaches tailored to individual risk profiles. Nevertheless, ongoing research efforts are imperative to refine these strategies further and maximise their effectiveness in safeguarding cardiovascular health.

Radiation Maculopathy in Patients with Malignant Melanoma of the Corpus Ciliare and Choroidea Following One-Day Session of Stereotactic Radiosurgery.

The aim of the thesis is to present the case of a patient in whom bilateral calcification of the hydrophilic intraocular lens (IOL) Lentis M+ LS-313 MF30 (Oculentis) has developed. Due to the negative effect on visual functions, explantation and replacement of the artificial lens was necessary in both eyes. Case Report: An overview of the available literature summarized the diagnostics, current examination methods and possibilities of the surgical solution of calcification of the bifocal hydrophilic lens Lentis M+ LS-313 MF30 (Oculentis). The specific solution is described in a case report of a patient in whom calcification of both lenses developed 6 years after implantation of the IOL. In 2015, the patient underwent uncomplicated cataract surgery of both eyes with the implantation of an artificial intraocular lens into the capsule. In September 2021, an 82-year-old man was examined at our outpatient clinic for deterioration of visual acuity and changes in the material of the artificial IOL which were perceptible during a clinical examination, on the recommendation of a local ophthalmologist. Blurred vision predominated. A diagnosis of intraocular lens opacification was confirmed and documented using a Scheimpflug camera (OCULUS Pentacam HR) and anterior OCT (Avanti RTVue XR Optovue,). The patient was indicated for explantation and replacement of the opacified intraocular lens in the left and subsequently in the right eye- The same type of IOL was used for reimplantation with good functional results. Conclusion: Since 2010, multifocal lens implantation has been on an upward trend worldwide. This type of MF IOL has also been used in thousands of implantations. A number of other explantations can be expected in the coming years. The optimal solution is the correct replacement of the calcified IOL with the same construction made of safer hydrophobic material.

Hot spring oases in the periglacial desert as the Last Glacial Maximum refugia for temperate trees in Central Europe.

Northern glacial refugia are a hotly debated concept. The idea that many temperate organisms survived the Last Glacial Maximum (LGM; ~26.5 to 19 thousand years) in several sites across central and northern Europe stems from phylogeographic analyses, yet direct fossil evidence has thus far been missing. Here, we present the first unequivocal proof that thermophilous trees such as oak (Quercus), linden (Tilia), and common ash (Fraxinus excelsior) survived the LGM in Central Europe. The persistence of the refugium was promoted by a steady influx of hydrothermal waters that locally maintained a humid and warm microclimate. We reconstructed the geological and palaeohydrological factors responsible for the emergence of hot springs during the LGM and argue that refugia of this type, allowing the long-term survival and rapid post-LGM dispersal of temperate elements, were not exceptional in the European periglacial zone.

Systematic analysis of mucosal-associated invariant T cells in haematological malignancies.

Mucosal-associated invariant T-cells (MAIT) are unconventional T-cells with cytotoxic and pro-inflammatory properties. Previous research has reported contradictory findings on their role in cancerogenesis with data being even scarcer in haematological malignancies. Here, we report the results of a systematic analysis of MAIT cells in treatment-naïve patients with a broad range of haematological malignancies. We analysed peripheral blood of 204 patients and 50 healthy subjects. The pool of haematological patients had a statistically significant lower both the absolute value (median values, 0.01 × 109/L vs. 0.05 × 109/L) of MAIT cells and their percentage (median values 0.94% vs. 2.56%) among T-cells compared to the control group. Separate analysis showed that the decrease in the absolute number of MAIT cells is significant in patients with acute myeloid leukaemia, myeloproliferative neoplasms, plasma cell myeloma, B-cell non-Hodgkin lymphomas, otherwise not specified, diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma compared to the control population. Furthermore, in haematological malignancies, MAIT cells overexpress PD-1 (average values, 51.7% vs. 6.7%), HLA-DR (average values, 40.2% vs. 7%), CD38 (average values, 25.9% vs. 4.9%) and CD69 (average values, 40.2% vs. 9.2%). Similar results were obtained when comparing patients with individual malignancies to the control population. Our data show that the depletion of circulating MAIT cells is a common observation in a broad spectrum of haematological malignancies. In addition to their reduced numbers, MAIT cells acquire an activated/exhausted phenotype.

Participatory development of an mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED).

BACKGROUND: The escalating global prevalence of type 2 diabetes and prediabetes presents a major public health challenge. Physical activity plays a critical role in managing (pre)diabetes; however, adherence to physical activity recommendations remains low. The ENERGISED trial was designed to address these challenges by integrating mHealth tools into the routine practice of general practitioners, aiming for a significant, scalable impact in (pre)diabetes patient care through increased physical activity and reduced sedentary behaviour. METHODS: The mHealth intervention for the ENERGISED trial was developed according to the mHealth development and evaluation framework, which includes the active participation of (pre)diabetes patients. This iterative process encompasses four sequential phases: (a) conceptualisation to identify key aspects of the intervention; (b) formative research including two focus groups with (pre)diabetes patients (n = 14) to tailor the intervention to the needs and preferences of the target population; (c) pre-testing using think-aloud patient interviews (n = 7) to optimise the intervention components; and (d) piloting (n = 10) to refine the intervention to its final form. RESULTS: The final intervention comprises six types of text messages, each embodying different behaviour change techniques. Some of the messages, such as those providing interim reviews of the patients' weekly step goal or feedback on their weekly performance, are delivered at fixed times of the week. Others are triggered just in time by specific physical behaviour events as detected by the Fitbit activity tracker: for example, prompts to increase walking pace are triggered after 5 min of continuous walking; and prompts to interrupt sitting following 30 min of uninterrupted sitting. For patients without a smartphone or reliable internet connection, the intervention is adapted to ensure inclusivity. Patients receive on average three to six messages per week for 12 months. During the first six months, the text messaging is supplemented with monthly phone counselling to enable personalisation of the intervention, assistance with technical issues, and enhancement of adherence. CONCLUSIONS: The participatory development of the ENERGISED mHealth intervention, incorporating just-in-time prompts, has the potential to significantly enhance the capacity of general practitioners for personalised behavioural counselling on physical activity in (pre)diabetes patients, with implications for broader applications in primary care.

Sarcopenia and adipose tissue evaluation by artificial intelligence predicts the overall survival after TAVI.

Sarcopenia is a serious systemic disease that reduces overall survival. TAVI is selectively performed in patients with severe aortic stenosis who are not indicated for open cardiac surgery due to severe polymorbidity. Artificial intelligence-assisted body composition assessment from available CT scans appears to be a simple tool to stratify these patients into low and high risk based on future estimates of all-cause mortality. Within our study, the segmentation of preprocedural CT scans at the level of the lumbar third vertebra in patients undergoing TAVI was performed using a neural network (AutoMATiCA). The obtained parameters (area and density of skeletal muscles and intramuscular, visceral, and subcutaneous adipose tissue) were analyzed using Cox univariate and multivariable models for continuous and categorical variables to assess the relation of selected variables with all-cause mortality. 866 patients were included (median(interquartile range)): age 79.7 (74.9-83.3) years; BMI 28.9 (25.9-32.6) kg/m2. Survival analysis was performed on all automatically obtained parameters of muscle and fat density and area. Skeletal muscle index (SMI in cm2/m2), visceral (VAT in HU) and subcutaneous adipose tissue (SAT in HU) density predicted the all-cause mortality in patients after TAVI expressed as hazard ratio (HR) with 95% confidence interval (CI): SMI HR 0.986, 95% CI (0.975-0.996); VAT 1.015 (1.002-1.028) and SAT 1.014 (1.004-1.023), all p < 0.05. Automatic body composition assessment can estimate higher all-cause mortality risk in patients after TAVI, which may be useful in preoperative clinical reasoning and stratification of patients.

In vitro Testing of Trichomonas vaginalis Drug Susceptibility: Evaluation of Minimal Lethal Concentration for Secnidazole that Correlates with Treatment Success.

ABSTRACT: We determined the in vitro minimum lethal concentration (MLC) of secnidazole (SEC) and assessed correlation with clinical susceptibility among T. vaginalis isolates obtained from 71 women, of whom 66 were successfully treated with this medication. An MLC ≤12.5 µg/ml correlated with clinical susceptibility in this study.

Identification of Plasmatic MicroRNA-206 as New Predictor of Early Recurrence of Atrial Fibrillation After Catheter Ablation Using Next-generation Sequencing.

BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) is indicated in patients with recurrent and symptomatic AF episodes. Despite the strict inclusion/exclusion criteria, AF recurrence after CA remains high. Identification of a novel biomarker that would predict AF recurrence would help to stratify the patients. The aim of the study was to seek novel biomarkers among the plasmatic microRNAs (miRNAs, miRs). METHODS: A prospective monocentric study was conducted. A total of 49 consecutive AF patients indicated for CA were included. Blood sampling was performed prior to CA. RNA was isolated from plasma using commercial kits. In the exploration phase, small RNA sequencing was performed in ten AF patients (five with and five without AF recurrence) using Illumina instrument. In the validation phase, levels of selected miRNAs were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in all participants. RESULTS: Altogether, 22 miRNAs were identified as altered between the groups by next-generation sequencing (using the DESeq2 algorithm). Using qRT-PCR, levels of the five most altered miRNAs (miR-190b/206/326/505-5p/1296-5p) were verified in the whole cohort. Plasma levels of hsa-miR-206 were significantly higher in patients with early (within 6 months) AF recurrence and showed an increase of risk recurrence,2.65 times by every increase in its level by 1 unit in the binary logistic regression. CONCLUSION: We have identified a set of 22 plasmatic miRNAs that differ between the patients with and without AF recurrence after CA and confirmed hsa-miR-206 as a novel miRNA associated with early AF recurrence. Results shall be verified in a larger independent cohort.

The neurotropic schistosome vs experimental autoimmune encephalomyelitis: are there any winners?

The incidences of multiple sclerosis have risen worldwide, yet neither the trigger nor efficient treatment is known. Some research is dedicated to looking for treatment by parasites, mainly by helminths. However, little is known about the effect of helminths that infect the nervous system. Therefore, we chose the neurotropic avian schistosome Trichobilharzia regenti, which strongly promotes M2 polarization and tissue repair in the central nervous system, and we tested its effect on the course of experimental autoimmune encephalomyelitis (EAE) in mice. Surprisingly, the symptoms of EAE tended to worsen after the infection with T. regenti. The infection did not stimulate tissue repair, as indicated by the similar level of demyelination. Eosinophils heavily infiltrated the infected tissue, and the microglia number increased as well. Furthermore, splenocytes from T. regenti-infected EAE mice produced more interferon (IFN)-γ than splenocytes from EAE mice after stimulation with myelin oligodendrocyte glycoprotein. Our research indicates that the combination of increased eosinophil numbers and production of IFN-γ tends to worsen the EAE symptoms. Moreover, the data highlight the importance of considering the direct effect of the parasite on the tissue, as the migrating parasite may further tissue damage and make tissue repair even more difficult.

Sparsentan ameliorates glomerular hypercellularity and inflammatory-gene networks induced by IgA1-IgG immune complexes in a mouse model of IgA nephropathy.

IgA nephropathy (IgAN) is characterized by glomerular deposition of immune complexes (ICs) consisting of IgA1 with O-glycans deficient in galactose (Gd-IgA1) and Gd-IgA1-specific IgG autoantibodies. These ICs induce kidney injury, and in the absence of disease-specific therapy, up to 40% of patients with IgAN progress to kidney failure. IgA1 with its clustered O-glycans is unique to humans, which hampered development of small-animal models of IgAN. Here, we used a model wherein engineered ICs (EICs) formed from human Gd-IgA1 and recombinant human IgG autoantibody are injected into nude mice to induce glomerular injury mimicking human IgAN. In this model, we assessed the protective effects of sparsentan, a single-molecule dual endothelin angiotensin receptor antagonist (DEARA) versus vehicle on EIC-induced glomerular proliferation and dysregulation of gene expression in the kidney. Oral administration of sparsentan (60 or 120 mg/kg daily) to mice intravenously injected with EIC attenuated the EIC-induced glomerular hypercellularity. Furthermore, analysis of changes in the whole kidney transcriptome revealed that key inflammatory and proliferative biological genes and pathways that are upregulated in this EIC model of IgAN were markedly reduced by sparsentan, including complement genes, integrin components, members of the mitogen-activated protein kinase family, and Fc receptor elements. Partial overlap between mouse and human differentially expressed genes in IgAN further supported the translational aspect of the immune and inflammatory components from our transcriptional findings. In conclusion, our data indicate that in the mouse model of IgAN, sparsentan targets immune and inflammatory processes leading to protection from mesangial hypercellularity.NEW & NOTEWORTHY The mechanisms by which deposited IgA1 immune complexes cause kidney injury during early phases of IgA nephropathy are poorly understood. We used an animal model we recently developed that involves IgA1-IgG immune complex injections and determined pathways related to the induced mesangioproliferative changes. Treatment with sparsentan, a dual inhibitor of endothelin type A and angiotensin II type 1 receptors, ameliorated the induced mesangioproliferative changes and the associated alterations in the expression of inflammatory genes and networks.

LIF/JAK2/STAT1 Signaling Enhances Production of Galactose-Deficient IgA1 by IgA1-Producing Cell Lines Derived From Tonsils of Patients With IgA Nephropathy.

Introduction: Galactose-deficient IgA1 (Gd-IgA1) plays a key role in the pathogenesis of IgA nephropathy (IgAN). Tonsillectomy has been beneficial to some patients with IgAN, possibly due to the removal of tonsillar cytokine-activated cells producing Gd-IgA1. To test this hypothesis, we used immortalized IgA1-producing cell lines derived from tonsils of patients with IgAN or obstructive sleep apnea (OSA) and assessed the effect of leukemia inhibitory factor (LIF) or oncostatin M (OSM) on Gd-IgA1 production. Methods: Gd-IgA1 production was measured by lectin enzyme-linked immunosorbent assay; JAK-STAT signaling in cultured cells was assessed by immunoblotting of cell lysates; and validated by using small interfering RNA (siRNA) knock-down and small-molecule inhibitors. Results: IgAN-derived cells produced more Gd-IgA1 than the cells from patients with OSA, and exhibited elevated Gd-IgA1 production in response to LIF, but not OSM. This effect was associated with dysregulated STAT1 phosphorylation, as confirmed by STAT1 siRNA knock-down. JAK2 inhibitor, AZD1480 exhibited a dose-dependent inhibition of the LIF-induced Gd-IgA1 overproduction. Unexpectedly, high concentrations of AZD1480, but only in the presence of LIF, reduced Gd-IgA1 production in the cells derived from patients with IgAN to that of the control cells from patients with OSA. Based on modeling LIF-LIFR-gp130-JAK2 receptor complex, we postulate that LIF binding to LIFR may sequester gp130 and/or JAK2 from other pathways; and when combined with JAK2 inhibition, enables full blockade of the aberrant O-glycosylation pathways in IgAN. Conclusion: In summary, IgAN cells exhibit LIF-mediated overproduction of Gd-IgA1 due to abnormal signaling. JAK2 inhibitors can counter these LIF-induced effects and block Gd-IgA1 synthesis in IgAN.

Phase Morphology and Mechanical Properties of Super-Tough PLLA/TPE/EMA-GMA Ternary Blends.

The inherent brittleness of poly(lactic acid) (PLA) limits its use in a wider range of applications that require plastic deformation at higher stress levels. To overcome this, a series of poly(l-lactic acid) (PLLA)/biodegradable thermoplastic polyester elastomer (TPE) blends and their ternary blends with an ethylene-methyl acrylate-glycidyl methacrylate (EMA-GMA) copolymer as a compatibilizer were prepared via melt blending to improve the poor impact strength and low ductility of PLAs. The thermal behavior, crystallinity, and miscibility of the binary and ternary blends were analyzed by differential scanning calorimetry (DSC). Tensile tests revealed a brittle-ductile transition when the binary PLLA/20TPE blend was compatibilized by 8.6 wt. % EMA-GMA, and the elongation at break increased from 10.9% to 227%. The "super tough" behavior of the PLLA/30TPE/12.9EMA-GMA ternary blend with the incomplete break and notched impact strength of 89.2 kJ∙m-2 was observed at an ambient temperature (23 °C). In addition, unnotched PLLA/40TPE samples showed a tremendous improvement in crack initiation resistance at sub-zero test conditions (-40 °C) with an impact strength of 178.1 kJ∙m-2. Morphological observation by scanning electron microscopy (SEM) indicates that EMA-GMA is preferentially located at the PLLA/TPE interphase, where it is partially incorporated into the matrix and partially encapsulates the TPE. The excellent combination of good interfacial adhesion, debonding cavitation, and subsequent matrix shear yielding worked synergistically with the phase transition from sea-island to co-continuous morphology to form an interesting super-toughening mechanism.

Centre of pressure changes during stance but not during gait in young women after alcohol intoxication.

Background: Women are underrepresented in research focused on alcohol (e.g., Brighton, Moxham & Traynor, 2016; DOI 10.1097/JAN.0000000000000136) despite the changing patterns of alcohol consumption, which has been increasing in women in recent decades. The purpose of this study was to analyse the relationship between habitual alcohol consumption and centre of pressure (CoP) parameters during stance and gait while intoxicated by alcohol. Methods: Thirty women (24.39 ± 2.93 years) participated in this study. All participants were asked to answer the AUDIT questionnaire. Stance and gait analysis were repeated under two conditions on a Zebris platform (FDM GmbH; Munich, Germany): when the participants were sober (0.00% breath alcohol concentration, BrAC) and when they were in an intoxicated state (0.11% BrAC). Participants were divided by their AUDIT score into a low-risk alcohol consumption group (n = 15; AUDIT score: 3 to 6) and a hazardous alcohol consumption group (n = 15; AUDIT score: 7 to 13). Results: No statistical difference was observed in stance and gait parameters when comparing the low-risk and hazardous groups under 0.00% BrAC and 0.11% BrAC conditions. A statistically significant difference was observed when comparing 0.00% BrAC and 0.11% BrAC conditions within each group. This significant difference was found in CoP path length and CoP average velocity during quiet stance. However, no statistically significant differences were observed in CoP parameters during gait. An alcohol intoxication of 0.11% BrAC was not sufficient to cause statistically significant impairments in butterfly parameters of gait.

Colocalization of IgG and IgA Heavy Chains with Kappa and Lambda Light Chains in Glomerular Deposits of IgA Nephropathy Patients Using High-Resolution Confocal Microscopy and Correlation with Oxford MEST-C Scores.

Routine immunofluorescence microscopy of glomerular immunodeposits in IgA nephropathy shows IgA, C3, and lambda light chains, and sometimes IgG, IgM, and kappa light chains. However, a previous study using high-resolution confocal microscopy showed IgG in all IgA nephropathy cases, likely representing autoantibodies specific for galactose-deficient IgA1. Here, we used high-resolution confocal microscopy to examine the composition of glomerular immunodeposits and colocalization of kappa and lambda light chains with IgA or IgG heavy chains in kidney-biopsy samples from twenty patients with IgA nephropathy, seventeen without IgG, and nine with no or trace kappa light chains by routine immunofluorescence microscopy. IgG was detected in all biopsies by high-resolution confocal microscopy. Single-optical-plane images showed similar colocalization of IgG heavy chains with kappa and lambda light chains. Colocalization of IgA heavy chains was greater with lambda light chains than with kappa light chains. Colocalization of IgG heavy chain with kappa light chains was higher than with lambda light chains in biopsies with endocapillary hypercellularity and crescents, i.e., biopsies with active lesions. We confirmed the utility of high-resolution confocal microscopy to detect components of glomerular immunodeposits not apparent on routine immunofluorescence microscopy and for colocalization of different components, potentially clarifying the pathogenesis of IgA nephropathy.

Changes in Segmental Impedances and Selected Body Composition Parameters Assessed by Multi-Frequency Bioimpedance Analysis after Fluid Consumption in Healthy Young Population.

Objectives: Body composition (BC) analysis is a routine part of comprehensive public health care. Assessment of BC is more important source of information than BMI. Adherence to the standard measurement conditions is essential for the correct results. Our study aimed to examine the effect of acute fluid consumption on measures of body mass (BM), percentage of body fat (%BF), visceral fat (VF), percentage of body water (%BW), and impedance at 100 kHz (I100) and 20 kHz (I20) using segmental multi-frequency bioelectrical impedance analysis (SMF-BIA) in a general healthy population. Methods: 95 consecutive healthy normal-weight adults (42 men; 53 women) were involved in the study (mean ± s.d.; age 23.9±1.6 years; body mass 68.3±14.1 kg). All subjects underwent two separate series of body composition (BC) measurements at 0 (BASELINE), 30, 60, 90 min (POST): the first series after drinking 600 ml of isotonic carbohydrate/electrolyte drink (IST) and the second after no fluid administration (CON). Individual measurements were performed in the morning on two consecutive days. Results: In the IST group, BM, VF (both P<0.001), and %BF (P<0.05) increased significantly at 30 min POST compared to BASELINE. BM and VF remained elevated at 90 min POST (both P<0.001). %BW decreased significantly at 30 min POST (P<0.01) then increased at 60 min (P<0.001) and 90 min (P<0.01) POST. There were no significant changes in I100. I20 increased significantly at 30 min POST (P<0.001) then decreased at 60 min (P<0.001) and 90 min POST (P<0.01) compared to BASELINE. In the CON group, BM and VF decreased below BASELINE at 90 min POST (P<0.001), %BF, %BW and I100 did not change significantly. The difference between IST and CON was statistically significant for all POST measurement times only in BM and VF (both P<0.001). The VF results are also underlined by the detected impedance changes in the trunk area at 20 kHz (B20) and 100 kHz (B100) at 60 min and 90 min (both P<0.001). Conclusions: Our study suggests that segmental impedances and BC measurement in healthy young normal-weight adults requires strict adherence to fluid restriction at least 90 min before the measurement to avoid false impedance values and overestimation of BM and VF.