The paper deals with the solution of problems that concern fractional time derivatives. Specifically the author's interest lies in solving circuit problems with so called fractional capacitors and ...fractional inductors. A numerical method is proposed that involves polynomial interpolation and the division of the entire time interval (for which computations are performed) into subintervals. Analytical formulae are derived for the integro-differentiation according to the Caputo fractional derivative. The rules that concern the subinterval dynamics throughout the computation are also presented in the paper. For exemplary linear circuit problems (AC and transient) involving fractional order elements the solutions have been obtained. These solutions are compared with ones obtained by means of traditional methods
Purpose
Dysthyroid optic neuropathy (DON) is a rare sight-threatening complication of Graves’ disease. First-line treatment for DON consists of high-dose intravenous methylprednisolone (ivMP), ...followed by immediate orbital decompression (OD) if the response is poor or absent as recommended by the 2021 European Group on Graves’ orbitopathy guidelines. The safety and efficacy of the proposed therapy have been proven. However, consensus regarding possible therapeutic options for patients with contraindications to ivMP/OD or resistant form of disease is missing. This paper aims to provide and summarize all available data regarding possible alternative treatment strategies for DON.
Methods
A comprehensive literature search within an electronic database was performed including data published until December 2022.
Results
Overall, 52 articles describing use of emerging therapeutic strategies for DON were identified. Collected evidence indicates that biologics, including teprotumumab and tocilizumab, may be considered as an important possible treatment option for DON patients. Rituximab should be avoided in DON due to conflicting data and risk of adverse events. Orbital radiotherapy could be beneficial for patients with restricted ocular motility classified as poor surgical candidates.
Conclusion
Only a limited number of studies have been dedicated to the therapy of DON, mostly retrospective with a small sample size. Clear criteria regarding diagnosis and resolution of DON do not exist, which restricts comparison of therapeutic outcomes. Randomized clinical trials and comparison studies with long-term follow-ups are necessary to verify the safety and efficacy of each therapeutic option for DON.
Summary
Cytoadhesion of infected red blood cells (iRBC) is mediated through parasite‐encoded, clonally variant surface antigens (VSA) and is a central process in the pathogenesis of Plasmodium ...falciparum malaria. Pregnancy‐associated malaria (PAM) has been linked to VSA‐mediated adhesion of iRBC to the glycosaminoglycan chondroitin sulphate A (CSA) in the placental intervillous space. Several studies have pointed to members of the PfEMP1 VSA family as mediators of CSA‐specific iRBC sequestration in the placenta. Here, we report marked upregulation of a single var gene in several P. falciparum parasite isolates after selection for adhesion to CSA in vitro. The gene belongs to a highly conserved and common var gene subfamily (var2csa). The var2csa genes are structurally distinct from all other var genes in the parasite genome in lacking both CIDR and DBL‐γ domains. These domains have previously been implicated in PfEMP1‐mediated adhesion to CD36 and CSA. We also show that var2csa was transcribed at higher levels in three placental parasite isolates compared with transcription in parasites from peripheral blood of two children with P. falciparum malaria. This var gene thus has the properties expected of a gene encoding the parasite adhesion molecule that initiates the pathology associated with PAM.
The relationship between the prevalence of multiple sclerosis (MS) and sunlight's ultraviolet radiation was proved. Oxidative stress plays a role in the pathogenic traits of MS. Melatonin possesses ...antioxidative properties and regulates circadian rhythms. Several studies have reported that the quality of life is worse in patients with MS than in healthy controls, with a higher prevalence of sleep disturbances, depression and fatigue. The aim of study was to evaluate 5 mg daily melatonin supplementation over 90 days on serum malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity and its' influence on impact of the quality of life of MS patients. A case-control prospective study was performed on 102 MS patients and 20 controls matched for age and sex. The EDSS, MRI examinations and Multiple Sclerosis Impact Scale (MSIS-29) questionnaire was completed. Marked increase in serum MDA concentration in all MS patients groups was observed and after melatonin treatment decreased significantly in interferons-beta and glatiramer acetate-treated groups, but not in mitoxantrone-treated group. A significant increase in SOD activity compared to controls only in glatiramer acetate-treated group was observed. After 3 months melatonin supplementation the SOD activity increased compared to initial values in interferons beta-treated groups. A significant increase in both MSIS-29-PHYS and MSIS-29-PSYCH items mean scores only in the MX group as compared to other groups was observed. There were no significant differences in mean MSIS-29-PHYS was observed before and after melatonin therapy. Melatonin supplementation caused a decrease in mean MSIS-29-PSYCH scores compared to initial values in interferons beta-treated groups. Finding from our study suggest that melatonin can act as an antioxidant and improves reduced quality in MS patients.
•Anodic treatment has been used to modify the Zn-Ni alloy coatings on steel.•Alcoholic solutions were used for the first time for anodizing of Zn-Ni coatings.•The obtained passive films were ...nanometric in thickness which results in colorizing.•The coatings had mixed oxide-alkoxide character.•Terminal voltage of 20 V was the best for improving the corrosion resistance.
The subject of this investigation is the anodic treatment of galvanic Zn-Ni alloy coatings in alkaline solutions of selected alcohols and their characterization. The process was carried out galvanostatically at an anodic current density in the range 0.06–6.25 A/dm2 for 2–60 minutes. The characterization of the formed coatings was based on the morphological studies (OM), determination of the chemical and phase composition (XPS and GIXD), as well as film thickness (UV–vis spectroscopic ellipsometry) and corrosion investigations (EIS). It was found that the coatings have a mixed oxide-alkoxide passive character with the alkoxide-rich layer on the top. The anodic oxidation led to the coloration of the alloy; various colors (beige, blue, and violet) could be obtained depending on the process parameters. The colors were strongly related to the thickness of the films, which is similar to the passive layers found on valve metals (e.g. titanium). The thickest of the conversion coatings had ca. 250 nm. The EIS investigations showed the improvement of corrosion resistance of the substrate after the anodic treatment.
The multistep character of cancer progression makes it difficult to define a unique biomarker of the disease. Interdisciplinary approaches, combining various complementary techniques, especially ...those operating at a nanoscale level, potentially accelerate characterization of cancer cells or tissue properties. Here, we study a relation between the surface and biomechanical properties of melanoma cells, measured by mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). In total, seven cell lines have been studied. Six of them were melanoma cells derived from various stages of tumor progression: (1) WM115 cells derived from a 55 year old female skin melanoma at a vertical growth phase (VGP) in the primary melanoma site, (2) WM793 cells established from the vertical growth phase (VGP) of a primary skin melanoma lesion, (3) WM266-4 cells established from a cutaneous skin metastasis detected in the same patient as WM115 cells, (4) WM239 cells derived from a cutaneous skin metastasis, (5) 1205Lu cells originated from a lung metastasis diagnosed in the same patient as WM793 cells, and (6) A375P-cells were derived from a solid malignant tumor located in the lung. As a reference cell line, human epidermal melanocytes from adult skin (primary cell line HEMa-LP) were used. Results reveal low, medium, and large deformability of melanoma cells originating from vertical growth phase (VGP), and skin and lung metastasis, respectively. These changes were accompanied by distinct outcome from principal component analysis (PCA). In relation to VGP melanoma cells, cells from skin and lung metastasis reveal similar or significantly different surface properties. The largest deformability difference observed for cells from VGP and lung metastasis was accompanied by the largest separation of unspecific changes in their surface properties. In this way, we show the evidence that biomechanical and surface biochemical properties of cells change in parallel, indicating a potential of being used as nanobiophysical fingerprints of melanoma progression.
Multiple sclerosis (MS) prevalence is higher in geographic regions with less sunlight exposure. Melatonin participates in the effects of sunlight in healthy individuals and could play a role in MS ...pathophysiology. Melatonin crosses the blood-brain barrier and exerts antioxidative, immunomodulatory, and anti-inflammatory effects. Chronic fatigue syndrome concerns 80 - 90% MS patients. The pathophysiology of chronic fatigue syndrome is unknown, however activation of immune, inflammatory, oxidative and nitrosative stress mechanisms and plasma lipid peroxide elevation was reported. Homocysteine increases plasma lipid hydroperoxides levels. The aim was to determine the effect of melatonin supplementation on chronic fatigue syndrome in MS patients and evaluate plasma lipid hydroxyperoxides (LHP) and homocysteine concentrations as a potential biochemical fatigue biomarkers. Into a case-control prospective study 102 MS patients divided according receiving immunomodifying MS treatment into groups: RRMS-pretreated, RRMS-INF-beta, SP/PPMS-mitoxantrone, RRMS-relapse were enrolled. Patients were supplemented with melatonin over 90 days. Plasma LHP, homocysteine concentration, brain MRI and fatigue score were examined. Results show that LHP concentrations were significantly higher in all studied MS groups vs.
In all MS patient groups melatonin application resulted in significant decrease in plasma LHP concentrations. Plasma homocysteine concentration was similar in healthy people, RRMS-pretreated, RRMS-INF-beta and SP/PP-MS-mitoxantrone groups. However, in the RRMS-relapse group plasma levels of homocysteine were significantly higher compared to the RRMS-pretreated group. There were no significant differences in plasma homocysteine concentration in the studied groups before and after melatonin application. The fatigue score was significantly lower in RRMS pretreated group compared to RRMS-INF-beta and SP/PP MS-mitoxantrone treated patients. Plasma lipid hydroxyperoxides could be potential biochemical chronic fatigue syndrome biomarker in MS patients and homocysteine could be a potential marker of acute phase of MS. Melatonin exerts beneficial effects in MS patients based on its' proved antioxidative properties.
Ethylmalonic encephalopathy (EE) is a devastating neurodegenerative disease caused by mutations in the ETHE1 gene critical for hydrogen sulfide (H2S) detoxification. Patients present in infancy with ...hypotonia, developmental delay, diarrhea, orthostatic acrocyanosis and petechiae. Biochemical findings include elevated C4, C5 acylcarnitines and lactic and ethylmalonic acid (EMA) in body fluids. Current treatment modalities include metronidazole and N-acetylcysteine (NAC) to lower the production and promote detoxification of toxic H2S. Patients are typically identified after the onset of clinical symptoms and there is limited information about long term response to treatment.
We report the findings of two unrelated patients with EE, identified through newborn screening, who were managed with conventional treatment (NAC, metronidazole alternated with neomycin) and in patient 2, a novel dietary treatment restricting sulfur containing amino acids. Pathogenic mutations were confirmed in the ETHE1 gene (homozygous splice site mutation in patient 1, c.505 + 1G > A; compound heterozygous mutations in patient 2, c.131_132delAG + c.566delG).
Both patients were started on metronidazole and NAC by 10 weeks of age and treated for 23 months. Patient 1 did not accept the metabolic formula due to palatability and parental refusal for gastrostomy tube placement. She demonstrated improved biomarkers (EMA, lactic acid and thiosulfate) and an attenuated clinical course.
Patient 2 was started on a low methionine and cysteine diet at 8 months of age utilizing SOD Anamix® Early Years, (Nutricia). Baseline EMA levels were (642 mg/g Cr; n = 2) and decreased with medical treatment by 38% to a mean of 399 (n = 4, SD = 71, p 0.0013). With dietary treatment EMA levels were further reduced by 42% to a mean of 233 (n = 8, SD = 52, p 0.0030). Lactic acid, thiosulfates and clinical outcomes were also improved. Our long-term follow-up confirms previous reports of clinical improvement with NAC and metronidazole treatment. Additionally, our studies suggest that a diet restricted in sulfur-containing amino acids results in further improvement in clinical outcomes and biochemical markers.
•Clinical, biochemical and molecular findings of 2 patients with EE, detected by newborn screening•Confirmed previous reports of improvement with N-acetylcysteine and metronidazole•Further improvement documented with a new dietary treatment restricting sulfur-containing aminoacids
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