CD11c+ dendritic cells mediate antigen-specific suppression in extracorporeal photopheresis.

Extracorporeal photopheresis (ECP) represents one of the most widespread and effective cell therapies for graft-versus-host disease and other T cell-mediated disorders. However, the key factors affecting the therapeutic efficacy of ECP remain unclear. We hypothesized that therapeutic effects are mediated by ECP-treated antigen-presenting dendritic cells (DC). To test this hypothesis, we used the experimental model of contact hypersensitivity (CHS). The ECP's therapeutic activity improved when the total cell dose of the ECP-treated cells was increased. We used different haptens during sensitization to demonstrate that the anti-inflammatory activity of ECP is antigen-specific. This confirmed the hypothesis that professional antigen-presenting cells are involved in the mode of action. Also, the ECP's therapeutic activity was abrogated by the depletion of CD11c+ DC, which represents fewer than 1% of all the ECP-exposed cells. Finally, we confirm the critical importance of CD11c+ DC for ECP activity by showing that only a few purified CD11c+ DC are sufficient to mediate its therapeutic effect. The finding that ECP-treated, physiological antigen-presenting DC alone mediate antigen-specific modulation of a pathological immune response may result in better-targeted interventions when treating patients.

Effectiveness and mediators of change of an online CBT intervention for students with adjustment disorder-study protocol for a randomized controlled trial.

BACKGROUND: Adjustment problems and disorders are highly prevalent among university students worldwide. These problems can cause significant interference in academic and social functioning and increase vulnerability to other mental health disorders. Unfortunately, only half of students in need receive psychological help. Furthermore, few studies have evaluated psychological interventions for adjustment disorders in students. New, more scalable forms of treatment for students with an adjustment disorder need to be developed, evaluated, and implemented. The study aims to determine the effectiveness of an online transdiagnostic cognitive behavioural intervention for students experiencing adjustment disorder and to assess mediators of change. METHOD/DESIGN: In this three-arm randomized controlled trial, we plan to recruit 214 Polish students diagnosed with an adjustment disorder. Participants who meet initial eligibility criteria will be randomly assigned to one of three 6-week conditions: (1) online cognitive behavioural therapy intervention based on an existing, empirically supported transdiagnostic protocol, the unified protocol; (2) online progressive muscle relaxation training as an active control group; or (3) waiting-list control group. Both interventions are asynchronous, interactive, and include minimal amount of therapist support. Assessments will consist of self-report questionnaires, daily diary measures, and neurocognitive tasks for evaluating cognitive functioning. These will be conducted at baseline, post-treatment, and 1-month follow-up. Daily diary measures will be taken during the first and last week of treatment (or waitlist period). Primary outcome measures will include adjustment disorder severity; secondary outcome measures will consist of other negative (psychopathology: depression, anxiety, and stress) and positive (life satisfaction) indexes of mental health as well as process measures (e.g. mindfulness, experiential avoidance, cognitive fusion). DISCUSSION: To our knowledge, the current study is the first to evaluate the effectiveness of a psychological intervention for students with adjustment disorder. Therefore, it may have important practical implications for students with this disorder. It can potentially guide the development of a scalable, validated treatment option. TRIAL REGISTRATION: Clinical Trials, NCT05768308, registered 14 March 2023, https://www. CLINICALTRIALS: gov/ct2/show/NCT05768308.

Magnetic resonance imaging techniques for indirect assessment of myelin content in the brain using standard T1w and T2w MRI sequences and postprocessing analysis.

Magnetic Resonance Imaging (MRI) has revolutionized our ability to non-invasively study the brain's structural and functional properties. However, detecting myelin, a crucial component of white matter, remains challenging due to its indirect visibility on conventional MRI scans. Myelin plays a vital role in neural signal transmission and is associated with various neurological conditions. Understanding myelin distribution and content is crucial for insights into brain development, aging, and neurological disorders. Although specialized MRI sequences can estimate myelin content, these are time-consuming. Also, many patients sent to specialized neurological centers have an MRI of the brain already scanned. In this study, we focused on techniques utilizing standard MRI T1-weighted (T1w) and T2 weighted (T2w) sequences commonly used in brain imaging protocols. We evaluated the applicability of the T1w/T2w ratio in assessing myelin content by comparing it to quantitative T1 mapping (qT1). Our study included 1 healthy adult control and 7 neurologic patients (comprising both pediatric and adult populations) with epilepsy originating from focal epileptogenic lesions visible on MRI structural scans. Following image acquisition on a 3T Siemens Vida scanner, datasets were co registered, and segmented into anatomical regions using the Fastsurfer toolbox, and T1w/T2w ratio maps were calculated in Matlab software. We further assessed interhemispheric differences in volumes of individual structures, their signal intensity, and the correlation of the T1w/T2w ratio to qT1. Our data demonstrate that in situations where a dedicated myelin-sensing sequence such as qT1 is not available, the T1w/T2w ratio provides significantly better information than T1w alone. By providing indirect information about myelin content, this technique offers a valuable tool for understanding the neurobiology of myelin-related conditions using basic brain scans.

Intravenous immunoglobulin up-regulates the expression of the inhibitory FcgammaIIB receptor on B cells.

Intravenous immunoglobulin (IVIg) preparations are known to modulate autoimmune/inflammatory diseases through several F(ab')(2)- and Fc-dependent mechanisms. In this study, we show that the in vitro and the in vivo exposure of B lymphocytes from lupus-prone and from healthy mice to IVIg results in an increased expression of their surface inhibitory FcgammaIIB receptors. Further, this exposure enhanced the ability of a chimeric antibody, cross-linking FcgammaRIIB and immunoglobulin receptors on DNA-specific B lymphocytes, to suppress IgG anti-DNA antibody production. F(ab')(2) fragments of IVIg had a similar activity as the intact preparation, whereas Fc fragments had no effect. This study describes a novel approach with clinical relevance for modulating B lymphocyte activity.

Rapidly growing, multifocal, benign choroid plexus tumor in an infant: case report.

Choroid plexus papillomas (CPPs) are rare, benign tumors that can arise in young children. Most pediatric patients present with signs of hydrocephalus and require immediate treatment. The natural history of choroid plexus tumors in children without hydrocephalus is poorly defined. In this report, the authors present the very rare case of a child without hydrocephalus but with two intraventricular choroid plexus tumors discovered shortly after birth. Initial imaging had been performed for seizures and showed agenesis of the corpus callosum and enhancing tumors in the third and left lateral ventricles. Sequential imaging demonstrated rapid growth of both tumors. The lateral tumor was removed when the child was 3 months of age. A histological examination of the specimen showed benign features with an elevated mitotic rate. Given the patient's age of under 3 years, the diagnosis was WHO grade I CPP. The third ventricle tumor grew rapidly. A second surgery was performed and this tumor was resected. Again, the pathological diagnosis was WHO grade I CPP. The authors present this rare case and discuss the current relevant literature.

Influence of disinfectants on domestic wastewater treatment plant performance.

The inhibition effect of the disinfectants was investigated under laboratory conditions. COD removal, nitrification process and oxygen uptake rate were the observed processes. Disinfectants can be divided into a few groups depending on the present biocides. The results of the experiments showed a significant influence of the disinfectants containing sodium hypochlorite on the activated sludge. Domestos and Savo caused the highest inhibition on the respiration, 99% and 100%, respectively; while Asanox and Clorox had the highest effect on COD removal, 97% and 100%, respectively. Bref duo active, which also contains sodium hypochlorite, caused the lowest inhibition for all observed processes. Disinfectants based on other biocides did not cause significant inhibitions.

EDDS and EDTA-enhanced zinc accumulation by Solanum nigrum inoculated with arbuscular mycorrhizal fungi grown in contaminated soil.

The effect of two different chelating agents [EDTA and EDDS (S,S-ethylenediaminedissucinic acid)] on Zn tissue accumulation in Solanum nigrum L. grown in a naturally contaminated soil was assessed. Under those conditions, the response of the plant to the inoculation with two different isolates of arbuscular mycorrhizal fungi (AMF)--Glomus claroideum and Glomus intraradices--was also studied. Plants grown in the local contaminated soil (Zn levels of 433mg kg(-1)) accumulated up to 1191mg kg(-1) of Zn in the roots, 3747mg kg(-1) in the stems and 3409mg kg(-1) in the leaves. S. nigrum plants grown in the same soil spiked with extra Zn (Zn levels of 964mg kg(-1)) accumulated up to 4735, 8267 and 7948mg Zn kg(-1) in the leaves, stems and roots, respectively. The addition of EDTA promoted an increase in the concentration of Zn accumulated by S. nigrum of up to 231% in the leaves, 93% in the stems and 81% in the roots, while EDDS application enhanced the accumulation in leaves, stems and roots up to 140, 124 and 104%, respectively. In the stems, the presence of Zn was predominantly detected in the cortex collenchyma cells, the starch sheath and the internal phloem and xylem parenchyma, and the addition of chelating agents did not seem to have an effect on the localisation of accumulation sites. The devise of a chelate-enhanced phytoextraction strategy, using chelating agents and AMF, is discussed.

Solanum nigrum grown in contaminated soil: effect of arbuscular mycorrhizal fungi on zinc accumulation and histolocalisation.

Zn tissue accumulation in Solanum nigrum grown in a non-contaminated and a naturally contaminated Zn matrix and the effect of inoculation with different arbuscular mycorrhizal fungi (AMF) on metal uptake were assessed. S. nigrum grown in the contaminated soil always presented higher Zn accumulation in the tissues, accumulating up to 1622 mg Zn kg(-1). The presence of both Glomus claroideum and Glomus intraradices enhanced the uptake and accumulation of Zn by S. nigrum (up to 83 and 49% higher Zn accumulation, respectively). The main deposits of the metal were found in the intercellular spaces and in the cell walls of the root tissues, as revealed by autometallography, with the inoculation with different AMF species causing no differences in the location of Zn accumulation. These findings indicate that S. nigrum inoculated with selected heavy metal tolerant AMF presents extracting and accumulating capacities, constituting a potentially suitable remediation method for Zn polluted soils.

Anaerobic stabilisation of sludge produced during municipal wastewater treatment by electrocoagulation.

Anaerobic digestion of sludge from small electrocoagulation wastewater treatment plant (SEWWTP) is described. The sludge for digestion (SEWWTP sludge) was taken from pilot-scale SEWWTP with the capacity of about 200-population equivalent (25 m3 of municipal wastewater per day). Due to the technology of wastewater treatment, the characteristics of SEWWTP sludge was different from sludge produced in conventional mechanical-biological wastewater treatment plant. Therefore, experiments were focused on possibilities of anaerobic sludge digestion and determination of conditions and parameters (amount and quality of the sludge, biogas production, etc.). Average COD removal efficiency in the pilot-scale SEWWTP exceeded 80%. Organic content of excess sludge (volatile suspended solids (VSS)) was in the range of 52.1-59.2% (these values are much lower compared to VSS content in raw sludge from conventional municipal wastewater treatment plant, where VSS is about 75%). Biogas production from anaerobic digestion of SEWWTP sludge was approximately three times lower compared to standard production in conventional municipal wastewater treatment plant. Low pH (6.5-6.7), high concentration of iron (up to 1400 mg/L) and aluminium (up to 1300 mg/L) and very low (almost zero) concentration of dissolved phosphorus in sludge water were the main factors limiting the rate of anaerobic processes. Based on these results, anaerobic digestion of SEWWTP sludge was not recommended as an appropriate stabilisation method.

Histological and ultrastructural evidence for zinc sequestration in Solanum nigrum L.

The accumulation of contaminants in the environment due to anthropogenic activities is a matter of global concern. Solanum nigrum L. plants, able to accumulate zinc and hyperaccumulate cadmium, were challenged with 0.025 g Zn L(-1) during 35 days. The localization of Zn in roots, stems and leaves of S. nigrum plants was evaluated by autometallography (AMG) in order to determine the specific tissue, cell and subcellular compartments of Zn sequestration. This Zn concentration resulted in stunted plant growth but no other symptoms of Zn toxicity. Zinc concentration in the plants was highest in the roots, 666 mg Zn kg(-1) fresh weight (f.w.), and lower in the stems, 318 mg Zn kg(-1) f.w., and leaves, 101 mg Zn kg(-1) f.w. Roots of Zn-treated plants showed an underdeveloped structure but additional layers of proliferating cortical parenchyma cells. AMG of S. nigrum roots, stems and leaves revealed a generalized Zn distribution associated with the cell walls in all tissues. In the vasculature (xylem and phloem), Zn was observed at the plasma membrane-cell wall complex of vascular parenchyma cells and conducting elements. Conspicuous Zn deposits were detected in the vacuoles of cortical parenchyma and starch sheath, as well as in the tonoplast of the mesophyll cells. Our results suggest that Zn flux through the plant occurs via the xylem and phloem and associated parenchyma until it is conducted to permanent storage sites, namely, the apoplast and vacuoles of cortical parenchyma cells of the root, stem and the leaf mesophyll.

Zinc Accumulation and Tolerance in Solanum nigrum are Plant Growth Dependent.

Zinc tolerance, accumulation, and organic acid production by Solanum nigrum, a known Zn accumulator, was studied during pre- and post-flowering stages of development. The plants, when challenged with Zn concentrations lethal to plantlets, showed an increase in tolerance from pre-flowering to post-flowering, which was accompanied by a reduction of Zn translocation to the aerial plant parts. Treatment with Zn induced a differential response in organic acids according to the plant organ and developmental stage. In the roots, where Zn concentrations were similar in pre- and post-flowering plants, a general decrease in organic acid in pre-flowering roots contrasted with the increase observed in post-flowering plants. In the stems, Zn induced a generalized increase in organic acids at both growth stages while in the leaves, a slight increase in malic and shikimic was observed in pre-flowering plants and only shikimic acid levels were significantly increased in post-flowering plants. This work shows that Zn accumulation and tolerance in S. nigrum vary during plant development--an observation that may be important to improve the efficiency of phytoremediation approaches. Furthermore, the data suggest the involvement of specific organic acids in this response.

Frequency of the R3500Q mutation of the apolipoprotein B-100 gene in a sample screened clinically for familial hypercholesterolemia in Hungary.

Familial hypercholesterolemia (FH) and familial defective apolipoprotein B-100 (FDB) cause early onset of coronary heart diseases (CHD). According to the recommendations of the international MEDPED program, we tried to find FH cases. We analyzed 73 FH probands and their 304 first-degree relatives. A total of 39 probands were found from the 21000 subjects screened (1:538) from family doctors' registers recording all citizens, while the remaining 34 were derived from screened patients from lipid clinics. In our FH probands, four cases of FDB (R3500Q mutation) were diagnosed with allele-specific PCR, and the mutation was also detectable in five cases out of seven living family members. In the remaining 69 FH families, 156 people were diagnosed clinically with FH, and 31.8% of the males (against 13% of the not clinically diagnosed FH males, P<0.01), and 32.4% of the females (against 13.5% of the not clinically diagnosed FH females, P<0.01) suffered from early onset CHD. The plasma total cholesterol level of the FDB patients, especially in the younger patients, was very close to normal values. Therefore, the FDB patients seem to be under-represented in this type of survey. Because FDB is one of the independent causes of early onset CHD, the R3500Q mutation should be considered in families with a high frequency of cardiovascular diseases.

Euphenic prevention of coronary artery disease.

The purpose of this feasibility study was to incorporate the primary prevention of coronary artery disease (CAD) into periconception care. The first task was the preconceptional screening for CAD. The family and case histories and risk status of prospective mothers and fathers were obtained. Serum total cholesterol was measured in 3,530 female and 3,127 male participants. The mean serum nonfasting cholesterol was 192 +/- 40 mg/dl in women and 204 +/- 49 mg/dl in men. The levels of total cholesterol exceeded the upper limit of desirable total cholesterol (200 mg/dl) in 37% of women and in 49% of men. Only 7% of women and 5% of men had previous knowledge about their high total cholesterol. The second task was risk assessment for CAD in prospective parents and their planned baby and the identification of couples at high risk. The third step was the education of couples at high risk: how to reduce risk factors and how to enhance protective factors. Three months later, the short-term follow-up study indicated a 49 mg/dl (18%) and 43 mg/dl (16%) (range 250 to 300) reduction in total cholesterol in female and male participants, respectively, mainly due to an education program including change in diet, cessation of smoking, and so forth. The long-term follow-up will include both parents and children 3 years after the birth. Periconception care is appropriate for both a general and selective approach to population screening for total cholesterol and for primary prevention of CAD.

Measurements of nitrogen dioxide and sulphur dioxide concentrations in urban and rural areas of Poland using a passive sampling method.

Measurements of 1-month concentrations of NO(2) and SO(2) were carried out in the period from May 1993 to April 1994 in 147 points in 30 major cities of Poland and in 31 points in rural areas. The measurement points were divided into five classes representing: centres of cities, residential areas, industrial areas, traffic locations and rural areas. Passive samplers were prepared in one laboratory, mailed to local laboratories for sampling and then returned for analysis. The same samplers were used for collecting both NO(2) and SO(2). Analyses for NO(2) absorbed as nitrite were made spectrophotometrically after reaction with Saltzman reagent. Sulphur dioxide was determined as sulphate with ion chromatography. The consistency of data allowed comparison of levels of air pollution in different cities and the production of maps of spatial distribution of NO(2) and SO(2) in rural areas of Poland.

[Detection of tandem repeats in the genome of Citellus genus using restrictases]. / Obnaruzhenie tandemnykh povtorakh v genomakh suslikov roda Citellus s pomoshch'iu restriktaz.

DNA from ground squirrels of the Citellus genus (Rodentia, Sciuridae) were analysed by centrifugation in the presence of CsCl followed by digestion by restriction endonucleases. Digestion of DNA of two species C. undulatus and C. fulvus by 10 of the 16 restriction endonucleases used led to formation of electrophoretically discrete fragments that are multiple to 330 b.p. in length which points out the tandem organization of repetitive sequences similar to the satellite DNA of many mammal species. However, upon centrifugation we failed to reveal a satellite band in these species; hence the tandem repeats refer to the class of cryptic satellites in the ground squirrels and do not differ in base composition from the remaining part of DNA. The main fraction of the genome was revealed in the form of discrete fragments by cleavage with HindIII and AluI. Both of these restriction endonucleases were used for comparative analysis of DNA of 12 Citellus species. It has been shown that DNA of all species can be digested by HindIII and yields a series of fragments that are multiple to 330-30 b.p. in length and the total content of which varies from species to species within 4-22%. The fraction of the tandem repeats does not correlate with the systematic position of species nor with the amount of heterochromatin in the chromosomes. AluI cuts the DNA of 11 species yielding 110 and 220 b.p. fragments compared to only 60 and 280 b.p. in the DNA of C. dauricus. Under HindIII digestion we can also reveal the tandem repeats in marmot, which is phylogenetically close to the Citellus of the Marmota genus, but they have another periodicity--180 b.p. We propose that the age of ground squirrels repeats is 2-3 million years and they are significantly younger than the marmot repeats.

[Cholesterol levels in young men and women planning conception]. / Gyermeket akaró, fiatal, egészséges nök és férfiak összkoleszterin-értéke.

The purpose of this study is to incorporate the primary prevention of coronary heart disease into a periconception care. Among others total cholesterol was determined in 2610 female and 2307 male participants. The mean (+/- S.D.) of total cholesterol was 4.93 +/- 1.04 in females and 5.20 +/- 1.24 mmol/l in males. Only 7.9% of females and 4.7% of males had previous knowledge about their high total cholesterol. Three month later 1.08 mmol/l (16%) and 1.18 mmol/l (18%) reduction was found in total cholesterol of participants with > 6.5 mmol/l due to education programme including change in diet, to stop smoking, etc.

[Incidence of familial defective apolipoprotein B-100 in cases of patients diagnosed with familial hypercholesterolemia]. / A familiáris defektív apolipoprotein B-100 elöfordulási gyakorisága klinikailag familiáris hypercholesterinaemiásnak tartott betegek között.

Familial Hypercholesterolemia (FH) and Familial Defective Apolipoprotein B-100 (FDB) are monogenic, autosome, dominantly inherited diseases appearing as type II/a primary hypercholesterolemia. The frequency of the heterozygositic forms is 1:700-1:500 in European population. Both forms of hypercholesterolemia causes early onset coronary heart diseases (CHD). According to the recommendations of the international MED-PED program (Make Early Diagnoses--Prevent Early Death), we found 73 FH cases and their 377 first relatives (parents, siblings, children) were also assessed. 156 patients were diagnosed clinically FH (131 alive and 25 deceased), and 31.8% of the males and 32.4% of females suffered from early onset CHD. One family with FH consists of 5.46 members on the average and there are 2.39 FH patients in one family. In our FH cohort four patients with FDB (R3500Q mutation) were diagnosed with allelspecific PCR, and the mutation was detectable also in 9 cases out of 11 living family members. The plasma total cholesterol level of the FDB patients--especially at younger age--was very close to the normal values, which is in contrast to the findings in FH patients. Nevertheless, FDB can be one of the independent causes of the early onset CHD. Therefore, in families with high frequency of cardiovascular diseases the R3500Q mutation has to be considered.

Insights into phytoremediation solutions for environmental recovery.

Our environment is contaminated with organic and inorganic compounds released by anthropogenic activities that cause negative impacts on biological productivity and ecosystem sustainability and place human health at risk. Within the available remediation technologies, phytoremediation has emerged with high potential due to its reduced environmental impacts and economic costs. The research into phytoremediation has developed through a wide array of approaches, which also pertains to its inherent interdisciplinary characteristics, towards enhancing the potential of the technology for application in the field. Numerous patents present molecular solutions through which plants can be engineered to display improvements in key characteristics, such as the tolerance, uptake and accumulation of contaminants. The manipulation of plant growth and of the physico-chemical characteristics of the contaminated environments in order to enhance the remediation potential has also been the focus of several issued patents. This review attempts to highlight the most relevant patented advances in phytoremediation and to emphasise recent research efforts through which this green technology might be expected to develop into a commercially competitive alternative to other remediation methods.

Selective silencing of autoreactive B lymphocytes-Following the Nature's way.

A novel approach for the selective silencing of targeted autoreactive B lymphocytes is reviewed that mimics the physiological mechanisms for suppressing B cell activity. It is based on the use of bi- or tri-specific chimeric antibodies that cross-link BCRs with a pre-selected antigen-binding specificity with one or more inhibitory types of receptors on the surface of the same disease-associated B lymphocyte. The effect of these engineered antibodies was proved to be specific as they only suppressed the production of the targeted pathological antibodies while sparing those with other specificities. The administration of the chimeric molecules to lupus-prone MRL/lpr mice resulted in decreased levels of disease-associated IgG autoantibodies and of proteinuria, in the prevention of cutaneous lesions, in decreased sizes of the lymphoid organs and in prolonged survival. These results prove that it is indeed possible to selectively silence unwanted B lymphocytes as well as to significantly delay the natural course of a spontaneous antibody-mediated autoimmune disease.