Tungsten Disulfide-Interfacing Nickel-Porphyrin For Photo-Enhanced Electrocatalytic Water Oxidation.

Covalent functionalization of tungsten disulfide (WS2 ) with photo- and electro-active nickel-porphyrin (NiP) is reported. Exfoliated WS2 interfacing NiP moieties with 1,2-dithiolane linkages is assayed in the oxygen evolution reaction under both dark and illuminated conditions. The hybrid material presented, WS2 -NiP, is fully characterized with complementary spectroscopic, microscopic, and thermal techniques. Standard yet advanced electrochemical techniques, such as linear sweep voltammetry, electrochemical impedance spectroscopy, and calculation of the electrochemically active surface area, are used to delineate the catalytic profile of WS2 -NiP. In-depth study of thin films with transient photocurrent and photovoltage response assays uncovers photo-enhanced electrocatalytic behavior. The observed photo-enhanced electrocatalytic activity of WS2 -NiP is attributed to the presence of Ni centers coordinated and stabilized by the N4 motifs of tetrapyrrole rings at the tethered porphyrin derivative chains, which work as photoreceptors. This pioneering work opens wide routes for water oxidation, further contributing to the development of non-noble metal electrocatalysts.

Сomparative analysis of large diameter bearing ceramic monoblock acetabular components.

Introduction: The goal of total hip arthroplasty (THA) is to provide ease to patients with persistent and exhausting pain. Durability is the main challenge associated with any tribological pair, with the aim of minimizing wear and thus avoiding problems with aseptic loosening of components and osteolysis. When polyethylene inserts are used in young patients, we should always consider their disadvantages, e.g., increased wear of the interacting components. Proper selection of friction pairs allows prolonged implant life. Ceramic-on-ceramic (CoC) friction pairs should provide long-term wear of the friction components. Objectives: To evaluate the mid-term results of using the monoblock Maxera Cup (Zimmer Biomet) acetabular system in cementless THA. Methods: We operated on 151 patients using the monoblock Maxera Cup (Zimmer Biomet) acetabular system. The mean follow-up duration was 6 years (73.8 ± 11.7 months). Fifty-seven women and 94 men aged 19-64 years were surgically treated. All 170 THA cases in 151 patients were divided into 3 groups according to the diameters of the CoC friction pairs used (40, 44, and 48 mm). As a control group, we have taken 50 patients who received 50 THA using a standard 36 mm CoC friction pair. The achieved functional results were evaluated using the HHS scale, WOMAC scale, and SF36 scale. We also evaluated the mean duration of surgical intervention and blood loss. Results: When assessing long-term results, the average HHS significantly increased from 34.10 (before surgery) to 87.50 (postoperation) points in the 1st group, from 46.24 to 96.5 points in the 2nd group, and from 38.70 to 92.10 points in the 3rd group. From preoperative examination to 1 year after surgery, there was a 2.4-fold improvement in the functional results in group 1 and 1,8 and 2.9 -fold improvement in groups 2 and 3, indicating excellent treatment results. Inconsistent creaking in the implanted joint was noted in only 2.6% of cases in which a CoC friction pair with a diameter of 44 mm was used. We did not observe any complications associated with aseptic or septic loosening of the components either clinically or radiologically during the 7-year follow-up period after surgery in the entire patient population. Conclusions: 1Use of the CoC monoblock allowed us to expect an increase in the life cycle of the implant and provided good joint function and perception by the patient.2Monoblock cups provided good joint function and perception by the patient.3Acoustic effects, in the form of minor creaking, did not affect the functional results.

Non-immunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4·5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial.

BACKGROUND: Non-immunogenic staphylokinase is modified recombinant staphylokinase with low immunogenicity, high thrombolytic activity, and selectivity to fibrin. We aimed to assess the safety and efficacy of a single intravenous bolus of non-immunogenic staphylokinase compared with alteplase in patients with acute ischaemic stroke within 4·5 h after symptom onset. METHODS: We did a randomised, open-label, multicentre, parallel-group, non-inferiority trial in 18 clinical sites in Russia. We included patients aged 18 years and older with a diagnosis of acute ischaemic stroke (up to 25 points on the National Institutes of Health Stroke Scale). The study drug had to be administered within 4·5 h after the onset of symptoms. Patients were randomly assigned to receive either non-immunogenic staphylokinase (10 mg) or alteplase (0·9 mg/kg, maximum 90 mg), both administered intravenously. The randomisation sequence was created by an independent biostatistician using computer-generated random numbers. 84 blocks (block size of four) of opaque sealed envelopes were numbered sequentially from 1 to 336 and were opened in numerical order. Patients were unaware of their assigned treatment and were assessed by the study investigators who were also unaware of the treatment assignment on all trial days. Emergency department staff, who administered the assigned drug and opened the envelopes, were not masked to treatment. The primary efficacy endpoint was a favourable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. The margin of non-inferiority was established as 16% for the difference in mRS score of 0-1 on day 90. Non-inferiority was tested using Welch's t-test for the primary outcome only. Endpoints were analysed in the per-protocol population, which comprised all randomly assigned patients who completed treatment without any protocol violations; this population was identical to the intention-to-treat population. This trial is completed and registered at ClinicalTrials.gov, NCT03151993. FINDINGS: Of 385 patients recruited from March 18, 2017, to March 23, 2019, 336 (87%) were included in the trial. 168 (50%) patients were randomly assigned to receive non-immunogenic staphylokinase and 168 (50%) to receive alteplase. The median duration of follow-up was 89 days (IQR 89-89). 84 (50%) of 168 patients in the non-immunogenic staphylokinase group had a favourable outcome at day 90 compared with 68 (40%) of 168 patients in the alteplase group (odds ratio [OR] 1·47, 95% CI 0·93 to 2·32; p=0·10). The difference in the rate of favourable outcome at day 90 was 9·5% (95% CI -1·7 to 20·7) and the lower limit did not cross the margin of non-inferiority (pnon-inferiority <0·0001). Symptomatic intracranial haemorrhage occurred in five (3%) patients in the non-immunogenic staphylokinase group and in 13 (8%) patients in the alteplase group (p=0·087). On day 90, 17 (10%) patients in the non-immunogenic staphylokinase group and 24 (14%) patients in the alteplase group had died (p=0·32). 22 (13%) patients in the non-immunogenic staphylokinase group had serious adverse events, compared with 37 (22%) patients in the alteplase group (p=0·044). INTERPRETATION: Non-immunogenic staphylokinase was non-inferior to alteplase for patients with acute ischaemic stroke. Mortality, symptomatic intracranial haemorrhage, and serious adverse events did not differ significantly between groups. Future studies are needed to continue to assess the safety and efficacy of non-immunogenic staphylokinase in patients with acute ischaemic stroke within the 4·5 h time window, and to assess the drug in patients with acute ischaemic stroke outside this time window with reperfusion CT or magnetic resonance angiography followed by thrombectomy if necessary. FUNDING: The Russian Academy of Sciences.

Role of Hepcidin in Anemia of Chronic Disease in Rheumatoid Arthritis.

Objective Anemia of chronic disease is a frequent consequence in rheumatoid arthritis and is associated with major clinical and patient outcomes. The present cross-sectional study explored the role of hepcidin (HEP) in anemia of chronic disease in rheumatoid arthritis by studying its relationships with markers of anemia, iron metabolism, inflammation, and erythropoiesis. Methods Blood samples from anemic ( n = 43) and nonanemic ( n = 43) rheumatoid arthritis patients were analyzed for markers of anemia (hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red cells distribution width, and reticulocyte hemoglobin), iron metabolism (iron, total iron binding capacity, ferritin, transferrin saturation, soluble transferrin receptor), inflammation (erythrocyte sedimentation rate, C-reactive protein, and interleukin 6), and erythropoiesis (erythropoietin and HEP). Correlation analysis was used to identify relationships between HEP and all other variables. Principal component analysis was used to identify common underlying dimensions representing linear combinations of all variables. Results HEP had statistically significant mostly moderate-to-large correlations with markers of anemia (0.30-0.70, all p < 0.01), small correlation with markers of iron metabolism and markers of inflammation ( r = 0.20-0.40, all p < 0.01), and moderate correlations with markers of erythropoiesis. Principal component analysis revealed two underlying components (factors) capturing approximately 50% of total variability. Factor 1 comprised mainly of markers of anemia, iron metabolism, and erythropoiesis and was related to "erythrocyte health status," while factor 2 comprised mainly markers of inflammation and iron metabolism and was related to "acute phase reactants." HEP was the only variable demonstrating substantial loadings on both factors. Conclusions HEP is related to markers of anemia, iron metabolism, inflammation, and erythropoiesis. In addition, when all variables are "reduced" to a minimum number of two "latent" factors, HEP is loaded on both, thus underlying its pivotal role in the complex interaction of the erythropoietic response in inflammation-induced anemia and/or functional iron deficiency.

Clinical, Serological and Immunological Characteristics in Greek Patients with Psoriatic Arthritis: The Role of IL-17, IL-23, and Sclerostin.

Psoriatic arthritis (PsA) is an inflammatory form of arthritis that belongs to the family of spondyloarthritis (SpA) and is related to skin psoriasis. The incidence and prevalence of the disease vary considerably between countries. PsA is classified into axial PsA and peripheral PsA, with a wide range of other extra-articular manifestations. Although the aetiology of the disease is unknown, genetic, environmental, and immunologic factors appear to affect its appearance. In recent years, the role of the immune system in the pathogenesis of PsA has been increasingly investigated. Specific cytokines such as tumour necrosis factor (TNF), interleukin (IL-) 17 and IL-23, play an essential role affecting joint structures. This observation led to the emergence of tumour necrosis factor inhibitors (TNFi) that offer considerable therapeutic benefit to PsA patients. However, chronic inflammation causes bone loss, while new bone formation may also occur in both peripheral and axial skeleton. The molecular mechanisms underlying these processes have not yet been fully understood. So far, the role of the Wnt/ß-catenin pathway and its inhibitors (Dickkopf and sclerostin) has been evaluated in ankylosing spondylitis (AS), but in PsA has not been studied sufficiently. The present study aims to investigate the epidemiological characteristics and clinical features (articular and extra-articular manifestations) as well as the treatment of PsA patients in the region of northwestern (NW) Greece. It also aims to evaluate the role of specific cytokines and sclerostin in patients with PsA, giving evidence to possible future biomarkers or even therapeutic targets for the disease.

Sjögren Syndrome Associated with Inflammatory Muscle Diseases.

OBJECTIVES: Sjögren's syndrome (SS) is a chronic autoimmune inflammatory disorder characterized by diminished lacrimal and salivary gland function that may affect multiple organ systems. The association of SS with inflammatory myopathies (IM), a group of diseases characterized by chronic inflammation of striated muscle and skin has been infrequently described. METHODS: We present two cases diagnosed with SS who developed IM. We have also conducted a review of the English literature to depict all available clinical evidence on the clinical association of SS with IM. RESULTS: Two female patients diagnosed with SS developed polymyositis (PM) and inclusion body myositis (IBM) respectively. The literature review identified 24 cases with coexistence of the two autoimmune conditions (SS and IM). Twenty-two patients were females and two males. Eight patients were diagnosed with IBM, 15 were diagnosed with PM and 1 with dermatomyositis. All patients had biopsy proven IM. CONCLUSIONS: There is evidence of clinical association of primary SS and IM especially with IBM and PM. Patients with SS and symptoms of muscle weakness should be investigated for associated IM.

Counting Costs under Severe Financial Constraints: A Cost-of-Illness Analysis of Spondyloarthropathies in a Tertiary Hospital in Greece.

OBJECTIVE: To investigate the total annual direct cost of patients with spondyloarthritis (SpA) in Greece. METHODS: Retrospective study with 156 patients diagnosed and followed up in the rheumatology clinic of the University Hospital of Ioannina. Sixty-four had ankylosing spondylitis (AS) and 92 had psoriatic arthritis (PsA). Health resource use for each patient was elicited through a retrospective chart review that documented the use of monitoring visits, medications, laboratory/diagnostic tests, and inpatient stays for the previous year from the date that the review took place. Costs were calculated from a third-party payer perspective and are reported in 2014 euros. RESULTS: The mean ± SD annual direct cost for the patients with SpA reached €8680 ± 6627. For the patients with PsA and AS, the cost was estimated to be €8097 ± 6802 and €9531 ± 6322, respectively. The major cost was medication, which represented 88.9%, 88.2%, and 89.3% of the mean total direct cost for SpA, AS, and PsA, respectively. The annual amount of the scheduled tests for all patients corresponded to 7.5%, and for those performed on an emergency basis, 1.1%. Further, the cost for scheduled and emergency hospitalization, as well as the cost of scheduled visits to an outpatient clinic, corresponded to 2.5% of the mean total annual direct cost for the patients with SpA. CONCLUSION: SpA carries substantial financial cost, especially in the era of new treatment options. Adequate access and treatment for patients with SpA remains a necessity, even in times of fiscal constraint. Thus, the recommendations of the international scientific organizations should be considered when administering high-cost drugs such as biological treatments.

Effect of hydroxychloroquine on the lipid profile of patients with Sjögren syndrome.

OBJECTIVE: Many studies have highlighted the hypolipidemic action of hydroxychloroquine (HCQ). We investigated the effect of HCQ on the lipid profile of patients with Sjögren syndrome (SS). METHODS: The present retrospective observational study included 71 female patients with SS treated with HCQ. The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol, triglycerides (TG), and atherogenic index (TC/HDL) were measured at baseline, after 6 months, and 1, 3, and 5 years after initiation of HCQ treatment. Analysis to investigate changes over time was performed in the entire patient group and in the separate subgroups: those receiving (21 patients) and those not receiving (50 patients) hypolipidemic treatment. RESULTS: For the entire group of patients a statistically significant decrease in TC was noted (levels before treatment 220 ± 41 mg/dl, and at 5 yrs 206 ± 32 mg/dl, p = 0.006). A statistically significant difference was observed in the levels of HDL (57 ± 14 mg/dl vs 67 ± 17 mg/dl, p < 0.001) and in atherogenic index (4.0 ± 1.3 vs 3.3 ± 0.9, p < 0.001). Patients not receiving a hypolipidemic agent during the same period demonstrated a decrease in TC (214 ± 40 mg/dl vs 208 ± 34 mg/dl, p = 0.049), an increase in HDL levels (55 ± 15 mg/dl vs 67 ± 18 mg/dl, p < 0.001), and a decrease in atherogenic index (4.0 ± 1.4 vs 3.3 ± 0.9, p < 0.001). In the subgroup of patients receiving hypolipidemic treatment, the respective changes in their lipid profile were not significant in the first years but became significant in the long term. CONCLUSION: Use of HCQ in patients with SS was related to a statistically significant decrease in TC, an increase in HDL, and improvement in the atherogenic index.

Cell attachment on poly(3-hydroxybutyrate)-poly(ethylene glycol) copolymer produced by Azotobacter chroococcum 7B.

BACKGROUND: The improvement of biomedical properties, e.g. biocompatibility, of poly(3-hydroxyalkanoates) (PHAs) by copolymerization is a promising trend in bioengineering. We used strain Azotobacter chroococcum 7B, an effective producer of PHAs, for biosynthesis of not only poly(3-hydroxybutyrate) (PHB) and its main copolymer, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV), but also alternative copolymer, poly(3-hydroxybutyrate)-poly(ethylene glycol) (PHB-PEG). RESULTS: In biosynthesis we used sucrose as the primary carbon source and valeric acid or poly(ethylene glycol) 300 (PEG 300) as additional carbon sources. The chemical structure of PHB-PEG and PHB-HV was confirmed by 1H nuclear-magnetic resonance (1H NMR) analysis. The physico-chemical properties (molecular weight, crystallinity, hydrophilicity, surface energy) and surface morphology of films from PHB copolymers were studied. To study copolymers biocompatibility in vitro the protein adsorption and COS-1 fibroblasts growth on biopolymer films by XTT assay were analyzed. Both copolymers had changed physico-chemical properties compared to PHB homopolymer: PHB-HV and PHB-PEG had less crystallinity than PHB; PHB-HV was more hydrophobic than PHB in contrast to PHB-PEG appeared to have greater hydrophilicity than PHB; whereas the morphology of polymer films did not differ significantly. The protein adsorption to PHB-PEG was greater and more uniform than to PHB and PHB-PEG copolymer promoted better growth of COS-1 fibroblasts compared with PHB homopolymer. CONCLUSIONS: Thus, despite low EG-monomers content in bacterial origin PHB-PEG copolymer, this polymer demonstrated significant improvement in biocompatibility in contrast to PHB and PHB-HV copolymers, which may be coupled with increased protein adsorption and hydrophilicity of PEG-containing copolymer.

Giant cell fibroma in children: report of two cases and literature review.

BACKGROUND: Giant cell fibroma is a type of fibrous tumour of the oral mucosa which rarely affects children under the age of 10. The purpose of this paper was to contribute two clinically and histologically documented cases of giant cell fibroma in the free gingiva of a 7 and 6 year old boys. METHODS: Both nodules were presented in the mandibular anterior region. In the differential diagnosis several fibrous hyperplastic lesions were considered such as traumatic fibroma, papilloma, peripheral ossifying fibroma, peripheral odontogenic fibroma, giant cell fibroma and odontogenic hamartoma. RESULTS: The lesions were removed and the histological examination revealed fibrocollagenous connective tissue with the presence of stellate giant cells which confirmed the diagnosis of giant cell fibroma. CONCLUSIONS: Dentists should be aware of the existence of giant cell fibroma in children, which must be included in the differential diagnosis of nodular lesions of the gingiva and adequately diagnosed and treated by removal and histopathological examination.

Thermodynamic and kinetic basis for recognition and repair of 8-oxoguanine in DNA by human 8-oxoguanine-DNA glycosylase.

We have used a stepwise increase in ligand complexity approach to estimate the relative contributions of the nucleotide units of DNA containing 7,8-dihydro-8-oxoguanine (oxoG) to its total affinity for human 8-oxoguanine DNA glycosylase (OGG1) and construct thermodynamic models of the enzyme interaction with cognate and non-cognate DNA. Non-specific OGG1 interactions with 10-13 nt pairs within its DNA-binding cleft provides approximately 5 orders of magnitude of its affinity for DNA (ΔG° approximately -6.7 kcal/mol). The relative contribution of the oxoG unit of DNA (ΔG° approximately -3.3 kcal/mol) together with other specific interactions (ΔG° approximately -0.7 kcal/mol) provide approximately 3 orders of magnitude of the affinity. Formation of the Michaelis complex of OGG1 with the cognate DNA cannot account for the major part of the enzyme specificity, which lies in the k(cat) term instead; the rate increases by 6-7 orders of magnitude for cognate DNA as compared with non-cognate one. The k(cat) values for substrates of different sequences correlate with the DNA twist, while the K(M) values correlate with ΔG° of the DNA fragments surrounding the lesion (position from -6 to +6). The functions for predicting the K(M) and k(cat) values for different sequences containing oxoG were found.

On the theory of the modulation instability in optical fiber amplifiers.

The modulation instability (MI) in optical fiber amplifiers and lasers with anomalous dispersion leads to cw radiation breakup. This can be both a detrimental effect limiting the performance of amplifiers and an underlying physical mechanism in the operation of MI-based devices. Here we revisit the analytical theory of MI in fiber optical amplifiers. The results of the exact theory are compared with the previously used adiabatic approximation model, and the range of applicability of the latter is determined.

Modulation instability in high power laser amplifiers.

The modulation instability (MI) is one of the main factors responsible for the degradation of beam quality in high-power laser systems. The so-called B-integral restriction is commonly used as the criteria for MI control in passive optics devices. For amplifiers the adiabatic model, assuming locally the Bespalov-Talanov expression for MI growth, is commonly used to estimate the destructive impact of the instability. We present here the exact solution of MI development in amplifiers. We determine the parameters which control the effect of MI in amplifiers and calculate the MI growth rate as a function of those parameters. The safety range of operational parameters is presented. The results of the exact calculations are compared with the adiabatic model, and the range of validity of the latest is determined. We demonstrate that for practical situations the adiabatic approximation noticeably overestimates MI. The additional margin of laser system design is quantified.

Spatial structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 presumably corresponding to the receptor active state.

Proper lateral dimerization of the transmembrane domains of receptor tyrosine kinases is required for biochemical signal transduction across the plasma membrane. The spatial structure of the dimeric transmembrane domain of the growth factor receptor ErbB2 embedded into lipid bicelles was obtained by solution NMR, followed by molecular dynamics relaxation in an explicit lipid bilayer. ErbB2 transmembrane segments associate in a right-handed alpha-helical bundle through the N-terminal tandem GG4-like motif Thr652-X3-Ser656-X3-Gly660, providing an explanation for the pathogenic power of some oncogenic mutations.

Acinic cell carcinoma of the parotid gland in children a case report and literature review / Carcinoma de células acinosas de la glándula parótida en niños reporte de un caso y revisión de la literatura

Parotid acinic cell carcinoma is a rare malignancy in childhood. We report the case of a 12-year old girl presenting with a palpable mass in the left maxillofacial area. The radiologic evaluation showed a parotid mass. Tumour resection revealed acinic cell carcinoma of the parotid gland. She underwent complementary total parotidectomy without any adjuvant treatment. The patient has been disease-free for the last five years. We review the literature on acinic cell carcinomas of parotid glands in childhood.

El carcinoma de células acinosas de la parótida es una malignidad rara en la niñez. Reportamos el caso de una niña de 12 años con una masa palpable en el área maxilofacial izquierda. La evaluación radiológica mostró una masa parótida. La resección del tumor reveló un carcinoma celular de la glándula parótida. Fue sometida a una parotidectomía total complementaria sin tratamiento adyuvante alguno. La paciente ha estado libre de enfermedad durante los últimos cinco años. Revisamos la literatura sobre carcinomas de células acinosas en las glándulas parótidas en niños.

Acinic cell carcinoma of the parotid gland in children: a case report and literature review.

Parotid acinic cell carcinoma is a rare malignancy in childhood. We report the case of a 12-year-old girl presenting with a palpable mass in the left maxillofacial area. The radiologic evaluation showed a parotid mass. Tumour resection revealed acinic cell carcinoma of the parotid gland. She underwent complementary total parotidectomy without any adjuvant treatment. The patient has been disease-free for the last five years. We review the literature on acinic cell carcinomas of parotid glands in childhood.

Myasthenia gravis accompanied by thymomas not related to foamy virus genome in Belarusian's patients.

The spectrum and features of neurological disorders have been changed due to the Chernobyl catastrophe in the Republic of Belarus. More recently neurologists in Belarus have noted a significant increase in the frequency of myasthenia gravis (MG) with concomitant rise in the thymomas. There is some evidence suggesting that retroviruses play a key role in the development and pathogenesis of autoimmune diseases. This study analyzed thymomas from 45 MG patients from the Republic of Belarus by using PCR and primers for two regions of FV--gag and bel-2 genes. The results showed that none of the varied thymuses from the 45 MG patients contained FV genome. No relationship can be confirmed between FV and this disease and the results suggest that no pathological link between FV and MG exists.