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Background and Aims. The aim of this study was to evaluate changes in vascular density in the macula after pars plana vitrectomy for idiopathic macular hole (IMD) with macular peeling and flap. Methods. A prospective study of 35 eyes in 34 patients who had undergone standard surgery. Evaluated parameters were best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CRT), macular volume (TMV) and vascular density of the superficial and deep capillary plexus. The follow-up period was one year. Results. We divided the total group into two: temporal and circular flap and total group. We compared the values after surgery with the preoperative values. In the total group, BCVA increased from 48.38 to 71.44 letters (P≤0.05). IOP changed from 15.24 to 14.76 mmHg (P>0.05). CRT decreased from 432.27 to 323.64 µm (P≤0.05). TMV changed from 0.26 to 0.25 mm3 (P>0.05). The vascular density of the superficial plexus decreased from 32 to 28% (P≤0.05). The intercapillary space of the superficial plexus increased from 68 to 72% (P≤0.05). The vascular density of the deep plexus increased from 17 to 23%. The intercapillary space of the deep vascular plexus decreased from 83 to 77%. Changes in vascular density and intercapillary space of the deep plexus were statistically significant for certain months after operations (P≤0.05). There were no significant differences between subgroups. Conclusion. The superficial plexus vascular density is almost the same in the temporal flap and in the foveal-sparing flap is decreased, and the deep plexus vascular density increased statistically significantly during the follow-up period after surgery.

IntroductionThis paper investigates the links between deforestation and key economic, social, environmental, and geographical variables. We focus on per capita GDP, total forest cover, and the population across a diverse sample of countries from five continents for the last three decades.MethodsThis study utilizes a regression model using panel data to show the impact of key economic, and social variables on deforestation. Also, set of dummy variables is introduced in the paper. To enable the investigation, we use a set of dummies to capture their influence. The random effect specifications are used in this investigation. The research focuses on a period ranging from 1990 to 2020.ResultsResults show how different socio-economic variables influence deforestation. For example, disruptive events like the COVID-19 pandemic and the financial crisis had a negative effect on forest area development across all models. GDP per capita has different impact depending on the size of a country. Former colonies seem to have more deforestation.ConclusionsThe global environmental challenges posed by human activities and their impact on the state of forest have become increasingly evident. It is necessary to undertake policy and governance reforms to establish a solid legal framework, strengthen enforcement mechanisms, and foster transparency and accountability. The promotion of sustainable agriculture and agroforestry practices can substantially alleviate pressure on forests. Furthermore, it is necessary to mitigate disruptive events like pandemics by establishing specific strategies and creating contingency plans.

Aim. The objective of this study was to evaluate the efficacy of diabetic macular edema (DME) therapy using subthreshold micropulse laser (SMPL) with a wavelength of 577 nm during a long-term monitoring period of 5 years. Methods. The cohort included the total number of 52 eyes of 34 patients with DME. All underwent the standard laser treatment for the diabetic retinopathy outside the macula and DME treatment with SMPL. Subsequent check-ups were followed every 3 months in the first year of treatment, and every 4 to 6 months in the following years. The treatment was combined neither with focal macular laser nor with anti-VEGF therapy. Results. The mean central retinal thickness (CRT) was 345.9 µm SD 122.6 µm at the beginning of the monitoring. At the end of the follow-up period five years after treatment it was 256.4 µm SD 98.4 µm. The mean CRT decreased by 89.5 µm SD 153.6 µm during 5 years. At the beginning of the monitoring, before treatment with SMPL, the best corrected visual acuity (BCVA) was 70.0, SD 10.1 ETDRS letters. One year after therapy, BCVA was 72, SD 10.0 letters, two years later it was 71.4, SD 10.4 letters and decreased to 66.9, SD 12.1 letters after 5 years. The mean BCVA decreased by merely 3.1, SD 10.9 letters during 5 years. Conclusion. Based on our long-term observations, the DME treatment with SMPL appears to be an effective method for reducing DME and protecting BCVA against rapid worsening.

Abstract Psoriasis is a chronic, immune-mediated, inflammatory disease primarily affecting the skin. It is currently coming to light that patients with psoriasis have disrupted intestinal barrier and often suffer from comorbidities associated with the gastrointestinal tract. Moreover, there is growing evidence of both cutaneous and intestinal paradoxical reactions during biologic treatment in patients with psoriasis. This review focuses on barrier defects and changes in immune responses in patients with psoriasis, which play an important role in the development of the disease but are also influenced by modern biological treatments targeting IL-17 and TNFα cytokines. Here, we highlight the relationship between the gut–skin axis, microbiota, psoriasis treatment, and the incidence of paradoxical reactions, such as inflammatory bowel disease in patients with psoriasis. A better understanding of the interconnection of these mechanisms could lead to a more personalized therapy and lower the incidence of treatment side effects, thereby improving the quality of life of the affected patients.

Aims. We present a familial hereditary macular dystrophy, resembling North Carolina Macular Dystrophy. In members of a family, we describe the development of diagnostic-therapeutic approaches and their impact on the prognosis of those whose vision was affected. Methods. The macular dystrophy of varying degrees of severity was diagnosed in 3 consecutive generations in different family members, both men and women. Modern therapeutic tools were used for the diagnostics. In one patient of the youngest generation, the development of secondary choroidal neovascularization (CNV) was identified and treated with an anti-VEGF (vascular endothelial growth factor) agent. DNA was isolated from venous blood and genome sequencing was performed in a proband. Results. We analysed the data of 13 members of one family of three consecutive generations. Six of them had macular dystrophy. The first were two of three siblings, a woman (73 years old) and a man (67). The offspring of the afflicted man, a female (36) and a male (80), had maculopathy. The first daughter of the woman (12) revealed findings of maculopathy but with normal electrical activity of the retina. The second girl (18), developed secondary CNV which responded well to intravitreal anti-VEGF treatment. Genetic analysis excluded mutations previously reported to be pathogenic for NCMD. Conclusion. If there is a maculopathy of unclear etiology in younger patients or in patients with unclear development or appearance, it is advisable to focus carefully on the family history and trace the occurrence of impaired vision in other family members.

CT protocols that diagnose COVID-19 vary in regard to the associated radiation exposure and the desired image quality (IQ). This study aims to evaluate CT protocols of hospitals participating in the RACOON (Radiological Cooperative Network) project, consolidating CT protocols to provide recommendations and strategies for future pandemics. In this retrospective study, CT acquisitions of COVID-19 patients scanned between March 2020 and October 2020 (RACOON phase 1) were included, and all non-contrast protocols were evaluated. For this purpose, CT protocol parameters, IQ ratings, radiation exposure (CTDIvol), and central patient diameters were sampled. Eventually, the data from 14 sites and 534 CT acquisitions were analyzed. IQ was rated good for 81% of the evaluated examinations. Motion, beam-hardening artefacts, or image noise were reasons for a suboptimal IQ. The tube potential ranged between 80 and 140 kVp, with the majority between 100 and 120 kVp. CTDIvol was 3.7 ± 3.4 mGy. Most healthcare facilities included did not have a specific non-contrast CT protocol. Furthermore, CT protocols for chest imaging varied in their settings and radiation exposure. In future, it will be necessary to make recommendations regarding the required IQ and protocol parameters for the majority of CT scanners to enable comparable IQ as well as radiation exposure for different sites but identical diagnostic questions.

Background. Tumor necrosis factor-alpha (TNF-α) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation. Methods. We analyzed the power of serum biomarkers to predict the failure of anti-TNF-α. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-α, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-β1 (TGF-β1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1). Results. We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-β1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-β1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment. Conclusions. The TGF-β1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-β) are not markedly influenced by the treatment and that anti-TNF-α therapy decreases MMP-9 without influencing the treatment outcome.

Crohn’s disease (CD) and ulcerative colitis (UC) are two forms of inflammatory bowel disease (IBD), where the role of gut but not skin dysbiosis is well recognized. Inhibitors of TNF have been successful in IBD treatment, but up to a quarter of patients suffer from unpredictable skin adverse events (SkAE). For this purpose, we analyzed temporal dynamics of skin microbiota and serum markers of inflammation and epithelial barrier integrity during anti-TNF therapy and SkAE manifestation in IBD patients. We observed that the skin microbiota signature of IBD patients differs markedly from healthy subjects. In particular, the skin microbiota of CD patients differs significantly from that of UC patients and healthy subjects, mainly in the retroauricular crease. In addition, we showed that anti-TNF-related SkAE are associated with specific shifts in skin microbiota profile and with a decrease in serum levels of L-FABP and I-FABP in IBD patients. For the first time, we showed that shifts in microbial composition in IBD patients are not limited to the gut and that skin microbiota and serum markers of the epithelium barrier may be suitable markers of SkAE during anti-TNF therapy.

AimsGestation is linked to changes in gut microbiota composition and function. Since gestational diabetes mellitus (GDM) can develop at any time of the pregnancy, we stratified the women into four groups according to the time and test used for the diagnosis. We focused on the gut microbiota pattern in early pregnancy to detect changes which could be linked to later GDM development.MethodsWe collected stool samples from 104 pregnant women including obese individuals (first trimester body mass index median was 26.73). We divided the women into four groups according to routine screening of fasting plasma glucose (FPG) levels and oral glucose tolerance test (oGTT) in the first and third trimesters, respectively. We processed the stool samples for bacterial 16S rRNA and fungal ITS1 genes sequencing by Illumina MiSeq approach and correlated the gut microbiota composition with plasma short-chain fatty acid levels (SCFA).ResultsWe found that gut bacterial microbiota in the first trimester significantly differs among groups with different GDM onset based on unweighted UniFrac distances (p=0.003). Normoglycemic women had gut microbiota associated with higher abundance of family Prevotellaceae, and order Fusobacteriales, and genus Sutterella. Women diagnosed later during pregnancy either by FGP levels or by oGTT had higher abundances of genera Enterococcus, or Erysipelotrichaceae UCG-003, respectively. We observed significant enrichment of fungal genus Mucor in healthy pregnant women whereas Candida was more abundant in the group of pregnant women with impaired oGTT. Using correlation analysis, we found that Holdemanella negatively correlated with Blautia and Candida abundances and that Escherichia/Shigella abundance positively correlated and Subdoligranulum negatively correlated with plasma lipid levels. Coprococcus, Akkermansia, Methanobrevibacter, Phascolarctobacterium and Alistipes positively correlated with acetate, valerate, 2-hydroxybutyrate and 2-methylbutyrate levels, respectively, in women with GDM.ConclusionsWe conclude that there are significant differences in the gut microbiota composition between pregnant women with and without GDM already at the early stage of pregnancy in our cohort that included also overweight and obese individuals. Specific microbial pattern associated with GDM development during early pregnancy and its correlation to plasma lipid or SCFA levels could help to identify women in higher risk of GDM development.

Background and Aims. The aim of this study was to evaluate changes in vascular density in the macula after pars plana vitrectomy for idiopathic macular hole (IMD) with macular peeling and flap. Methods. A prospective study of 35 eyes in 34 patients who had undergone standard surgery. Evaluated parameters were best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CRT), macular volume (TMV) and vascular density of the superficial and deep capillary plexus. The follow-up period was one year. Results. We divided the total group into two: temporal and circular flap and total group. We compared the values after surgery with the preoperative values. In the total group, BCVA increased from 48.38 to 71.44 letters (P≤0.05). IOP changed from 15.24 to 14.76 mmHg (P>0.05). CRT decreased from 432.27 to 323.64 µm (P≤0.05). TMV changed from 0.26 to 0.25 mm3 (P>0.05). The vascular density of the superficial plexus decreased from 32 to 28% (P≤0.05). The intercapillary space of the superficial plexus increased from 68 to 72% (P≤0.05). The vascular density of the deep plexus increased from 17 to 23%. The intercapillary space of the deep vascular plexus decreased from 83 to 77%. Changes in vascular density and intercapillary space of the deep plexus were statistically significant for certain months after operations (P≤0.05). There were no significant differences between subgroups. Conclusion. The superficial plexus vascular density is almost the same in the temporal flap and in the foveal-sparing flap is decreased, and the deep plexus vascular density increased statistically significantly during the follow-up period after surgery. [ABSTRACT FROM AUTHOR]

Abstract Choroidal neovascularization (CNV) is a rare complication of the Multiple Evanescent White Dot Syndrome (MEWDS). It can develop after resolving of the disease when there is already no evident inflammatory activity. Therefore, a long‐term follow‐up of such patients is important.

Present investigations are focused on synthesis of magnetite/cerium dioxide reactive sorbents in various weight ratios of components and their characterization of chemical and magnetic properties. The morphology and changes in magnetic transformations in dependence on composition are followed by electron microscopy, X-ray diffraction, Mössbauer spectroscopy and magnetic measurements at room and low temperatures. Degradation efficiency is evaluated from a decomposition of the organophosphorus pesticide parathion methyl using prepared reactive sorbents. The experimental results reveal that the degradation efficiency, expressed by rate constant (mol/h) in dependence on amount of cerium dioxide content (vol.%), is independent on kind of iron oxide but increases with cerium dioxide content. On the contrary, saturation and remanent magnetizations are highly sensitive to relative ratio of iron oxides; magnetite, maghemite and hematite, originating from the initial magnetite transformations in dependence on sample composition.

Abstract Objective The TLR3/cGAS‐STING‐IFN signaling has recently been reported to be disturbed in colorectal cancer due to deregulated expression of the genes involved. Our study aimed to investigate the influence of potential regulatory variants in these genes on the risk of sporadic colorectal cancer (CRC) in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Methods The variants in the TLR3, CGAS, TMEM173, IKBKE, and TBK1 genes were selected using various online bioinformatic tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, SIFT, PolyPhen2, and miRNA prediction tools. Results Logistic regression analysis adjusted for age and sex detected a nominal association between CRC risk and three variants, CGAS rs72960018 (OR: 1.68, 95% CI: 1.11‐2.53, P‐value = .01), CGAS rs9352000 (OR: 2.02, 95% CI: 1.07‐3.84, P‐value = .03) and TMEM173 rs13153461 (OR: 1.53, 95% CI: 1.03‐2.27, P‐value = .03). Their cumulative effect revealed a threefold increased CRC risk in carriers of 5‐6 risk alleles compared to those with 0‐2 risk alleles. Epistatic interactions between these genes and the previously genotyped IFNAR1, IFNAR2, IFNA, IFNB, IFNK, IFNW, IRF3, and IRF7 genes, were computed to test their effect on CRC risk. Overall, we obtained nine pair‐wise interactions within and between the CGAS, TMEM173, IKBKE, and TBK1 genes. Two of them remained statistically significant after Bonferroni correction. Additional 52 interactions were observed when IFN variants were added to the analysis. Conclusions Our data suggest that epistatic interactions and a high number of risk alleles may play an important role in CRC carcinogenesis, offering novel biological understanding for the CRC management.

BackgroundUstekinumab, is a new therapy for patients with IBD, especially for patients suffering from Crohn's disease (CD) who did not respond to anti-TNF treatment. To shed light on the longitudinal effect of ustekinumab on the immune system, we investigated the effect on skin and gut microbiota composition, specific immune response to commensals, and various serum biomarkers.Methodology/principal findingsWe recruited 11 patients with IBD who were monitored over 40 weeks of ustekinumab therapy and 39 healthy controls (HC). We found differences in the concentrations of serum levels of osteoprotegerin, TGF-β1, IL-33, and serum IgM antibodies against Lactobacillus plantarum between patients with IBD and HC. The levels of these biomarkers did not change in response to ustekinumab treatment or with disease improvement during the 40 weeks of observation. Additionally, we identified differences in stool abundance of uncultured Subdoligranulum, Faecalibacterium, and Bacteroides between patients with IBD and HC.Conclusion/significanceIn this preliminary study, we provide a unique overview of the longitudinal monitoring of fecal and skin microbial profiles as well as various serum biomarkers and humoral and cellular response to gut commensals in a small cohort of patients with IBD on ustekinumab therapy.

Transient receptor potential melastatin 7 (TRPM7) represents melastatin TRP channel with two significant functions, cation permeability and kinase activity. TRPM7 is widely expressed among tissues and is therefore involved in a variety of cellular functions representing mainly Mg2+ homeostasis, cellular Ca2+ flickering, and the regulation of DNA transcription by a cleaved kinase domain translocated to the nucleus. TRPM7 participates in several important biological processes in the nervous and cardiovascular systems. Together with the necessary function of the TRPM7 in these tissues and its recently analyzed overall structure, this channel requires further studies leading to the development of potential therapeutic targets. Here we present the first study investigating the N-termini of TRPM7 with binding regions for important intracellular modulators calmodulin (CaM) and calcium-binding protein S1 (S100A1) using in vitro and in silico approaches. Molecular simulations of the discovered complexes reveal their potential binding interfaces with common interaction patterns and the important role of basic residues present in the N-terminal binding region of TRPM.

Complexes of IL-2 and JES6-1 mAb (IL-2/JES6) provide strong sustained IL-2 signal selective for CD25+ cells and thus they potently expand Treg cells. IL-2/JES6 are effective in the treatment of autoimmune diseases and in protecting against rejection of pancreatic islet allografts. However, we found that IL-2/JES6 also dramatically increase sensitivity to LPS-mediated shock in C57BL/6 mice. We demonstrate here that this phenomenon is dependent on endogenous IFN-γ and T cells, as it is not manifested in IFN-γ deficient and nude mice, respectively. Administration of IL-2/JES6 leads to the emergence of CD25+Foxp3-CD4+ and CD25+Foxp3-CD8+ T cells producing IFN-γ in various organs, particularly in the liver. IL-2/JES6 also increase counts of CD11b+CD14+ cells in the blood and the spleen with higher sensitivity to LPS in terms of TNF-α production and induce expression of CD25 in these cells. These findings indicate safety issue for potential use of IL-2/JES6 or similar IL-2-like immunotherapeutics.