A case of renal cell carcinoma in the contralateral kidney withTFE3 gene translocation following successful treatment of nephroblastomaShunsuke Fujisawa1), Junya Furukawa1), Takuto Hara1), Keiske Okada1), Kouji Chiba1),Yuzo Nakano1), Toshiki Hyodo2), Yoji Nagashima3), Masato Fujisawa1)1)Department of Urology, Kobe University Graduate School of Medicine2) Department of Diagnostic Pathology, Kobe University Graduate School of Medicine3) Division of Surgical Pathology, Tokyo Women’s Medical University Hospital

MULTICENTRIC RETICULOHISTIOCYTOSIS- A RARE AND DISABLING DISEASEOmowunmi Ashaolu1, Selwyn Ng2, Shaun Smale3, Jenny Hughes11Clinical fellow, Department of Dermatology, Princess of Wales Hospital, Bridgend, UK, wunmi.ashaolu@wales.nhs.uk2Consultant, Department of Histopathology, Morriston Hospital, Swansea, UK, selwyn.ng@wales.nhs.uk3Consultant, Department of Rheumatology, Princess of Wales Hospital, Bridgend UK, shaun.smale@wales.nhs.uk1Consultant, Department of Dermatology, Princess of Wales Hospital, Bridgend, UK,jenny.hughes@wales.nhs.uk.A 39-year-old man presented with 5-week history of multiple discrete and skin-coloured lesions on his hands, forearms, and face. He also had severely painful, stiff, and swollen fingers. He was otherwise well with no relevant personal or family history. Skin examination showed multiple discrete and coalescing firm, reddish brown, tender papules of varying sizes distributed mainly over the dorsum of the hands and nail folds (Fig 1) with no mucosal involvement. There was bilateral swelling and stiffness of the joints, especially the distal interphalangeal joints.Baseline investigations, autoantibody, viral screen, and staging CT to rule out underlying malignancy were normal. Radiographs of both hands showed soft tissue swelling and subtle perierosions in the small joints of the hands. Histopathology of the skin biopsy showed infiltration of the dermis and subcutaneous fat by mononuclear and multinucleated histiocytes with granular eosinophilic cytoplasm that showed positivity for CD45, CD68 and factor 13a and negativity for S100- and CD1a (Fig 2). Based on these findings a diagnosis of multicentric reticulohistiocytosis was made.He was initially treated with non-steroidal anti-inflammatory, Morphine, Alendronate and Oral corticosteroids. With worsening disease activity, Denosumab, oral methotrexate, hydroxychloroquine, infliximab, tocilizumab and leflunomide were added sequentially, however there was no symptom improvement. He was then considered for Tofacitinib 5mg twice daily with improvement after 4 weeks of initiating this therapy evidenced by improved sleep, skin symptoms and joint pains.Multicentric reticulohistiocytosis is a rare, multisystem inflammatory disease with unknown aetiology. It was first reported by Weber and Freudenthal in 1937, however Goltz and Laymon coined the term multicentric reticulohistiocytosis in 1954. Approximately 300 cases have been reported in the literature with most from Europe and United States. It is slightly predominant in women1 and symptoms manifest from the fourth decade of life2. Associated involvement of the joints impacts significantly on patients’ quality of life due to limitations on activities of daily living which inadvertently increases the risk of increased anxiety and depression.The cause of MRH is not known but activated macrophages and increased levels of TNF-alpha, IL-12, IL-1, and IL-63 have been documented.Cutaneous manifestation of MRH includes firm, discrete clustered reddish brown to flesh-coloured papules or nodules that gradually enlarge in size. It typically occurs over the joints of fingers and wrists giving a characteristic coral bead appearance1 as seen in our patient. Other commonly affected include the face giving leonine facies. However any part of the body can be affected including nail4 , mucosal surfaces1, lungs and heart. Fever, weight loss and malaise have also been reported. In addition, symmetrical polyarthritis mainly affecting the hands can potentially progress to arthritis mutilans. Differential diagnosis includes rheumatoid arthritis and psoriatic arthritis.Although MRH is not a paraneoplastic disease, solid organ especially breast and stomach carcinomas and haematological malignancies have been reported in 31% of cases5 therefore underlying malignancy should always be ruled out in a patient with MRH.There is no laboratory test specific for MRH. Histological studies show multinucleated giant cells with pale, fine, granular eosinophilic cytoplasm in the dermis. Stains are negative for S100, CD34, factor XIIIa and alpha-1-antitrypsin but positive for PAS and histiocytes (vimentin, CD68, CD45 and MAC387)2. Langerhans granules are absent on electron microscopy.There are no established treatment guidelines owing to the rarity and lack of controlled studies of the disease. The disease can be self-limiting, however this may have caused severe joint destruction. Prednisolone, immunomodulatory and disease modifying antirheumatic drugs, TNF inhibitors either as monotherapies or combination therapies have shown varying response. Tofacitinib, a selective JAK inhibitor, licenced for the treatment of rheumatoid arthritis has also been reported to be of benefit in the treatment of MRH6.MRH is a rare disease that cause disfiguring skin lesions and disabling arthritis therefore early recognition, and treatment is important to prevent long term deformities. In conclusion, we present a patient with a very rare non-Langerhans cell histiocytosis with typical clinical, histopathological and immunohistochemical findings.aFig 1: Showing coral bead appearance of multicentric reticulohistiocytosis

Journal: Allergy

Chagas disease is a chronic infection caused by Trypanosoma cruzi. The first-line drugs approved for treatment have several limitations and are associated with toxicity. The recombinant TSA-1-C4 and Tc24-C4 proteins have been profiled as promising candidates for the formulation of therapeutic vaccines, leading us to propose them in combination as a bivalent recombinant protein strategy. In this study, we evaluated the immunomodulatory effect of TSA-1-C4 plus Tc24-C4 recombinant protein combination by in-vitro assays. Macrophages from naïve BALB/c mice were isolated and stimulated with TSA-1-C4+Tc24-C4 proteins, supernatants were recovered to measure NO, H 2O 2, and, TNF-α, IL-1β, IL-6 and IL-10 cytokines. Stimulated macrophages were co-cultured with CD8 + T cells from naïve mice, and inflammatory cytokine-profile was measured from supernatants. Additionally, by experimental T. cruzi acute infection model, cytotoxicity was evaluated in mice after the treatment with TSA-1-C4+Tc24-C4 proteins in presence of a TLR-4 agonist adjuvant, E6020-SE. We observed that the bivalent recombinant protein strategy activates macrophages by NO and H 2O 2 production, also induced a significant Th1 immune-response compared to either TSA-1-C4 or Tc24-C4 stimulated macrophages. Moreover, naïve CD8 + T cells in presence of TSA-1-C4+Tc24-C4 stimulated-macrophages similarly boosted Th1 profile by significant production of IFN-γ and TNF-α cytokines. These results support the synergistic effect of the bivalent recombinant protein strategy, which leads activation of peritoneal macrophages and CD8 + T cells eliciting the Th1 immune response. Although the administration of TSA-1-C4+Tc24-C4+E6020-SE showed cytotoxic activity in T. cruzi-infected mice, there was not a benefit compared to stimulate with TSA-1-C4 or Tc24-C4 antigens formulated with E6020-SE adjuvant.

Most of the first eight pilot regions in China have entered the long-period continuous operation stage, and the second batch of six power spot pilots have started their simulation trial runs; however, the construction of power markets in the hydropower-rich regions of China (i.e., Sichuan and Yunnan) still faces multiple problems, including poor reliability of medium- and long-term power supplies, inefficient hydropower resource utilization and consumption scales, and unstable market prices. In this study, we establish a multi-scale joint clearing model for different market models (considering both long- and short-term operation strategies) and perform simulations of different market models at different time scales, to compare and analyze their optimization results and electricity price fluctuations. The model can stabilize the market price and reasonably reflect the true value of hydropower; it can also promote the consumption of clean energy and ensure the reliability of power supplies in the medium and long term. Finally, suggestions are made regarding the selection of electricity market models, the security of energy supplies, and the design of sustainable development mechanisms for hydropower in hydropower-rich regions, with a view to providing useful references for the development of China’s electricity market.

Code smells are usually ignored as they are neither a bug, nor a vulnerability. Quality engineers and, specially, security architects ignore them. As some of the code smells may lead towards vulnerability which may further be exploited by the hackers, therefore, such vulnerable code smells must be considered and further mitigated by threat modelers. In order to provide a repository of such code smells to security designers, a process had been devised and experimented. During the execution, various web applications had been passed through SAST and resulting code smells had been extracted and then inserted into a new dataset via Python. Later on, the code smells deposited in the dataset had been classified into various categories. Finally, machine learning algorithms had been assessed through WEKA and the fastest as well the most accurate algorithm had been selected. Current security standards do not ensure mitigation of threats caused by leading-to-vulnerability code smells, till to date. Typically, threat modelers assess security of a system through modeling threats via CIA, STRIDE and LINDDUN standards on its DFD and various architectural / infrastructural diagrams. Unless, they do not know that exploitable vulnerability still exists even after performing all secure design principles, the system would still be open to attacks. Our hypothesis was that vulnerable code smells still exist even after complying with all threat modeling standards. In the end, descriptive and inferential statistics had been used to analyse the results as well as test our hypothesis.

Our previous study has shown that ferromagnetic gadolinium silicide (Gd5Si4) nanoparticles (NP) could be potentially efficient T2 CA for MRI with significantly reduced echo time (TE) compared to Superparamagnetic Iron Oxide Nanoparticles (SPION) [1]. T2 CA are defined by their relaxivity, r2, which is dependent on both the saturation magnetization (Ms) and size of the NPs [1,2,4]. In this study, effect of Gd5Si4 NPs of varying sizes and concentrations are investigated on T1, T2 and T2* (effective/observed T2) relaxations times. Gd5Si4 NPs categorized into three fractions (named S1, S2 and S3) based on average sizes of 586 nm, 287 nm and 135 nm respectively as analyzed from SEM images (Fig. 1). XRD analysis on the combined samples shows that Gd5Si4 is the major phase while GdSi and Gd5Si3 are present as the minor phases in all fractions (Fig. 1). Magnetic properties measured in VSM reveal that the Curie temperature (Tc) decreases for Gd5Si4 phase from 312 K for S1 to 304 K for S2 and is undetectable in S3. The M-H curves at 300 K exhibits ferromagnetic behavior descending to paramagnetic as we move from S1 to S3 fraction (Fig. 1). MR data were acquired on the 21.1 T (900 MHz) magnet. The results shown in Table 1 indicate that higher concentrations of NPs shorten the T2 and T2* relaxation times and the contrast disappears rapidly at higher dilutions. The S2 fraction at 1/20 dilution shows notably shortened T1 and T2 relaxation times compared to the other two fractions. Although S1 has higher Gd5Si4 phase volume fraction and larger average particle size compared to S2, further investigation is needed inorder to establish the reason for shortened relaxation times compared to the S1 fraction. Acknowledgements

The way in which biological motion is processed, globally or locally, may depend upon the observer’s perceptual skill or experience with the stimulus. Skilled athletes with extensive perceptual experience observing sport-specific movements use globally distributed motion information across an opponent’s body to anticipate actions, while less skilled athletes focus on single-reliable kinematic cues. Published reports have demonstrated that attention can be primed globally or locally before perceptual tasks, and such an intervention could highlight motion processing mechanisms used by skilled and less skilled observers. In this study, we investigate skill-differences in biological motion processing using attentional priming. Skilled (N = 16) and less skilled (N = 16) players anticipated temporally occluded videos of beach volleyball attacks while being primed using a Navon matching task. EEG at parietal regions was measured to index global or local attention. Skilled players were more accurate than less skilled players across occlusion intervals and priming conditions. Global priming resulted in better performance for both skill groups. Skilled players showed significantly reduced alpha and beta power in the right compared to left parietal region, but brain activity was not affected by priming interventions. Our findings highlight the importance of right parietal dominance for skilled performers, which may be functional for inhibiting left hemispheric local processing or enhancing visual spatial attention for dynamic visual scenes. Further work is needed to systematically determine the function of this pattern of brain activity during skilled anticipation in other contexts.

Abstract Aim: We aim to compare nephrotoxic spectrum of IOCM and that of LOCM in a more intensive and comprehensive perspective using the real-world database. Methos: This is an observational, retrospective, pharmacovigilance study based on Vigibase. 7 products (iodixanol, iohexol, iopamidol, iopromide, iobitridol, ioversol and iomeprol) of ICM were included. Variable matching method was used for deduplication procedure. Two data mining method, reporting odds ratio (ROR) and bayesian confidence propagation neural networks of information components (IC) were used to detect signals for the full database, gender stratums (male and female), age stratum (0 to 64 years, 65 to 74 years and 75 or more years) and pooled analysis of total renal adverse events (AEs). Package ‘base’, ‘utils’ and ‘pheatmap’ of R language (version 4.1.2) were used to perform analysis and plot figures. Results: We got 2703 ICSRs and 3155 renal AE reports. The five most frequently reported were acute kidney injury, renal failure, renal impairment azotaemia and anuria. All ICM had highest signal value detected in age ≥75 years. Iodaxinal and iohexol had most signals detected. In pooled analysis of renal AEs, no signals detected for iopamidol, iomeprol and iopromide in the full database stratum. Conclusion: No evidence approved IOCM has safer nephrotoxicity than LOCM. CIN spectrum varies a lot within LOCM. Regarding to the whole population, not all products of ICM, such as iopamidol, iomeprol and iopromide, is likely to cause CIN.

Potato peel waste (PPW), a zero-value byproduct generated from potato processing, is a promising fermentation substrate due to its large quantity of starch, non-starch polysaccharide, lignin, protein, and lipid. Rhizopus oryzae is a filamentous fungus that is mainly known as a lactic acid producer and can ferment various agro-wastes. This study aimed to use R. oryzae for the fermentation of PPW. A series of batch fermentations were conducted to investigate the effects of different PPW loading rates (2 – 8%) and particle sizes (0 – 4mm). Under an initial PPW loading rate of 8% and particle size of 1 – 2mm, the maximum ethanol (23.9 mL/L) and lactic acid (2.60 mL/L) concentrations, the highest ethanol (11.93 mL/L•day) and lactic acid (1.56 mL/L•day) maximum production rates were obtained. Under these conditions, the yield of ethanol and lactic acid were 298 mL/mgPPW and 33 mL/mgPPW, respectively. R. oryzae was shown to utilize PPW as a substrate to produce value-added bioproducts such as ethanol (major product) and lactic acid.

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Coagulation factors used in prophylactic treatment of patients with clotting disorders are associated with significant costs to health care systems. These products have complex pharmacokinetic profiles subject to large inter-individual variation making their efficient use challenging. Prior to this project, pharmacists were not involved as part of the Hemophilia care teams across Canada. The purpose of this pilot project was to determine whether employment of a pharmacist with expertise and a focus on plasma protein and related products including hemophilia treatments, would be an effective strategy to reduce costs associated with clotting factor prophylaxis regimens and identify the pharmacist’s activities associated with this new role. A cost-minimization analysis was conducted to compare the addition of a pharmacist to the care team of the Hemophilia Treatment Centre (HTC) at a pediatric hospital serving 500,000 children and youth. The analysis was performed from the perspective of the formulary manager, Canadian Blood Services, over a 1-year period including 9 months of interventions. The pharmacist performed 18 therapeutic optimizations on 14 patients with moderate to severe hemophilia A or B, and 1 von Willebrand patient, aged 3 to 18 years old. As a result of the pharmacist’s intervention, clotting factor treatment costs extrapolated over one year were reduced by 20.5% for these patients. This represents a net savings of $225K CAD/year, or $12.5K CAD/optimization/year. The addition of a pharmacist to the HTC to manage recombinant and plasma-derived coagulation factors can optimise the treatment plan and significantly reduce the costs of managing patients with hemophilia.

Static features of the executive control network (ECN), dorsal attention network (DAN), default mode network (DMN), and salience network (SN) have displayed dysfunction in people with autism spectrum disorder (ASD). However, research on the dynamic brain function of these networks in ASD is rare. In this study, co-activation pattern (CAP) analysis was performed on the whole cortex to study dynamic dysfunction in ASD using a large multisite resting-state fMRI dataset (295 ASDs, 446 healthy controls). Eight transient network states (TNSs) were defined, the dwell time, persistence, and transitions of each TNS were calculated to evaluate dynamic brain function. Using hierarchical clustering, the eight TNSs were divided into three clusters: ‘DMN activating’, ‘SN activating’, and ‘ECN and DAN activating’. We found ‘ASD-biased’ DMN and SN TNSs, which showed larger dwell time and longer persistence in ASD group than healthy control (CON) group. More transition within ‘ASD-biased’ TNSs were found in ASD group. Dwell time of the ‘ASD-biased’ ‘SN activating’ TNS was significantly correlated with social deficits only in the ASD group. Our results imply the dynamic dysfunction of ASD does not come from the occurrence of DMN, ECN, or SN, but comes from the atypical co-activation patterns within them. Our results also indicate people with ASD have stronger negative connectivity between DMN and ECN in childhood. This connection dosen’t change significantly with age in ASD group, but is supposed to increase with age until adulthood as the growth trajectory in healthy inviduals, which implies the early overgrowth of ASD children.

Systemic-Onset Juvenile Idiopathic Arthritis with unusual Cutaneous Manifestation and peripheral eosinophilia: Case ReportAuthor details:Albraa Babiker Mohammed Alameen, MBBS, Omdurman Islamic University, Faculty of Medicine. (Author) Anas Babiker Mohammed Elamin, MBBS, University of Khartoum, Faculty of Medicine. (Co-Author) AbstractIntroduction: Systemic-onset juvenile idiopathic arthritis (SoJIA) is unique subtype of juvenile idiopathic arthritis (JIA) with very special clinical manifestations, complications and management options. The simultaneous presentation of tinea capitis has not been reported in the context of Systemic-Onset Juvenile Idiopathic Arthritis before.The case: in march 2021 a 5-years old Sudanese male presented to Ahmed Gasim Hospital with fever and bilateral ankle arthritis in a background of extensive scalp lesions which were scaly, itchy and associated with hair loss. On examination: his weight was 15 kg (on the 5thcentile). There was cervical lymphadenopathy, hepatomegaly and swelling and tenderness in both ankle joints with restriction of movements. Complete blood counts revealed leucocytosis, thrombocytosis, mild eosinophilia and microcytic hypochromic anaemia. Anti-dsDNA antibody was 45 IU/ml (positive), ANA profile was 0,8 Ratio (Equivocal), CRP was 34.4 mg/l, HDL was very high, these results support the diagnosis of SoJIA in a background of a kerion. Patient received: antibiotic, systemic antifungal, Corticosteroids, Hydroxychloroquine, Calcium and Vitamin D to which he achieved good results.Consent:Witten informed consent was obtained from patient’s parent to publish this report in accordance with the journal’s patient consent policy.Keywords: Systemic-onset juvenile idiopathic arthritis; Systemic juvenile idiopathic arthritis; Tinea capitis; eosinophilia; case report.IntroductionJuvenile idiopathic arthritis is a group of arthritis that occur before 16 years and last more than 6 weeks after exclusion of other aetiologies which is classified according to the International league of Associations for Rheumatology (ILAR) into 3 subtypes according to the clinical manifestations, complications and therapeutic options.(1–3) Systemic-onset juvenile idiopathic arthritis (SoJIA) is a very special subtype of juvenile idiopathic arthritis (JIA) that is characterized by fever which has a characteristic one or two spikes (>39°C) per day.(4) Also more than 80% of patients of this disease has a transient salmon-coloured macular or maculopapular rash that that accompanies the fever. They may have also myalgias and tenosynovitis and arthritis which may be oligoarticular to polyarticular.(3) The widely affected joints include wrists, knee, and ankles; but any joint can be affected, even the temporomandibular joints(5), cervical spine(6), hips(7), and the small joints of the hand and feet. SoJIA may present as painless lymphadenopathy (25%) hepatomegaly, splenomegaly or pericarditis which may be complicated by cardiac tamponade (3,4) There is no specific laboratory features that distinguishes SoJIA from other conditions, but the pattern of laboratory abnormalities may support the diagnosis, for examples; microcytic hypochromic anaemia, neutrophilic leucocytosis, thrombocytosis, high ESR, high CRP, high serum ferritin, low serum albumin, mildly elevated AST, high D-dimer and negative autoantibodies.(3) The treatment of JIA as whole focuses on suppressing inflammation, preserving functions, and preventing deformity and blindness.(8) the currently available drugs include nonsteroidal anti-inflammatory drugs (NSAID), Systemic corticosteroids and Disease-modifying anti-rheumatic drugs (DMARDs).(3,9,10) Eosinophil cells were associated with allergic bronchopulmonary aspergillosis and asthma exacerbation due to fungal antigens.(11) Moreover, a case report of kerion associated eosinophilia was described in which a dermatophytid reaction was thought to be the cause which responded to corticosteroid and antifungal.(12) 2 Case reports of 2 patients with systemic lupus erythromatosis in which tinea capitis was disseminated, one of them was using steroid the other was not.(13,14) and this is the first report related to juvenile idiopathic arthritis.Case reportHistory In March 2021; a 5-years old Sudanese male from Algazira, center of Sudan presented with bilateral ankle swelling, bilateral knee and hip pain and fever which started 1 month prior to presentation. His mother was also concerned about scales and hair loss all over the scalp which started 2 months prior to presentation. His symptoms started insidiously with the fever mainly at night and relieved by antipyretics. He had anorexia and weight loss but neither abdominal pain, vomiting, diarrhea, cough, upper respiratory tract symptoms, headache nor history of trauma. He had a past history of right knee swelling which was resolved spontaneously. He had no family history of autoimmune disease or malignancy and not exposed to any medications.ExaminationOn examination the patient was ill but not pale, jaundiced or cyanosed. His weight was 15 Kg (along the 5th centile) (fig. 1). The scalp had white-yellow scales with some swelling, hair loss and dried pus over some areas of the scalp (Fig. 2). There were Bilateral cervical lymphadenopathy which were non-tender, discrete and maximum diameter was 1×1 cm. Both ankle joints were Swollen (fig. 3),and tender to palpation and there was restriction of movements. Other joint examinations were normal. Abdominal examination revealed palpable liver which was 4 cm below the costal margin and palpable paraaortic lymph nodes.InvestigationsComplete blood count and peripheral blood picture revealed leucocytosis (WBCS=13.4*\(10^{3}\) which is high), neutrophil% = 49%, lymphocyte% = 38%, monocyte% = 5% and eosinophil% = 8% (mild eosinophilia) Thrombocytosis (614*\(10^{3}\)) and mild hypochromia (Hb=10.3 g/dl, MCV=71.8 fl, MCH=22.3 pg, MCHC=31.1 g/dl) were also present. Anti-dsDNA antibody was 45 IU/ml (positive). ANA profile was 0.8 Ratio (Equivocal). CRP was 34.4 mg/l (high) and ESR = 49 mm/hr. LDH was very high. Patient was treated with: Methylprednisolone 30mg/kg/day for 3 days. Followed by oral prednisone 1mg/kg/day. Hydroxychloroquine tabs 5mg/kg/day. Griseofulvin syrup 7.3mg/kg/day. Antibiotic Calcium and vitamin D. After 1 month of treatment follow-up the patient was improved and we refer him to the ophthalmologist for slit lamp examination.Discussion In this case the full detailed history and proper clinical examination in addition to laboratory findings are in favour of the diagnosis of systemic-onset juvenile idiopathic arthritis. This case may show that, musculoskeletal manifestations may be present earlier than any other symptoms. Also, we noticed that in the lipid profile the HDL was very high but serum ferritin and ESR was normal, a complicating macrophage activation syndrome was putted in mind and then excluded.(15,16) Does tinea capitis occur more extensively in this patient due to the disease itself we don’t know fully but in a previous case report to a patient with systemic lupus erythromatosis in which disseminated infection occurred simultaneously at the time of the diagnosis before even the use of corticosteroid.(13) in that case the causative agent was Microsporum gypseum but unfortunately in our case the diagnosis was made clinically only and microbiological consultation was not ordered due to financial problems but what make our case unique is its association with systemic-onset juvenile idiopathic arthritis and not Systemic lupus erythromatosis even before the start of immunosuppressive therapy.(13,14) Mild peripheral eosinophilia explanation in our case was challenging; whether it is related to a dermatophytid reaction with no obvious morbilliform or lichenoid lesions or due to other causes that are not typical with the present history such as drug tubulointerstitial nephritis or any other occult helminthic infection. But according to the other laboratory and history points the later causes were excluded and we left with the occult dermatophytid reaction which was consistent with the same observation from another case report of kerion due to T. tonsurans with 21% eosinophil in the complete which was reduced to 6% one month later after oral griseofulvin and corticosteroid were used.(12) but unlike that case in which the patient was 45 year old female with a clear medical background unlike our case. But this may point to the fact that complete blood count is not routinely ordered in tinea capitis and eosinophilia may be underreported if we associate this to the fact that eosinophil recognizes ß-glucan of the fungal cell wall and react to it by releasing its granules and this area is an area of investigation in the future.(11)Conclusion:Physicians should be alert to the presentation of systemic-onset JIA in our country in order to make prompt diagnosis and treatment decisions as early as possible. Careful follow-up of prolonged febrile patients with arthritis of unknown origin is important to reaching the diagnosis early and initiating treatment.Conflict of interest:NO conflict of interest.Recommendations:Further studies about the eosinophil count and its role in tinea capitis and systemic-onset juvenile idiopathic arthritis.Further studies about the immune response against fungi in the setting of juvenile idiopathic arthritis.Multidisciplinary team consultation (rheumatologist, ophthalmologist, orthopaedics and paediatrician) in case of SoJIA.Educate the patients about the disease and its complications, which are important to monitor the disease and long-term morbidity and mortality.References:1. Ravelli A MA. Juvenile idiopathic arthritis. Lancet. 2007;369:767–78.2. Petty RE, Southwood TR MP. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis second revision, Edmonton, 2001. J Rheumatol. 2004;31((2)):390–2.3. Lee, Jennifer JY and RS. “Systemic juvenile idiopathic arthritis.” Pediatr Clin. 2018;(65.4):691–709.4. Calabro JJ, Holgerson WB SG. Juvenile rheumatoid arthritis: a general review and report of 100 patients observed for 15 years. Semin Arthritis Rheum. 1976;5(3):257–98.5. Ringold S CR. The temporomandibular joint in juvenile idiopathic arthritis: frequently used and frequently arthritic. Pediatr Rheumatol Online J. 2009;7(1):11.6. Ornilla E, Ansell BM SA. Cervical spine involvement in patients with chronic arthritis undergoing orthopaedic surgery. Ann Rheum Dis. 1972;31:364–8.7. Modesto C, Woo P, García-Consuegra J, Merino R, García-Granero M, Arnal C, et al. Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis. Clin Exp Rheumatol. 2001;19(2):211–7.8. Nelson essentials of pediatrics, 7th edition.9. Guzman J, Oen K, Tucker LB, Huber AM, Shiff N, Boire G, et al. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis. 2015 Oct;74(10):1854–60.10. Horneff G, Schulz AC, Klotsche J, Hospach A, Minden K, Foeldvari I, et al. Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther. 2017 Nov;19(1):256.11. Manuscript A. NIH Public Access. 2009;181(4):2907–15.12. Martin ES, Elewski BE. bacterial pyoderma. 2003;177–9.13. Sanusi T, Gong J, Wang X, Zhao M, Zhao Y, An X, et al. Disseminated Favus Caused by Microsporum gypseum in a Patient with Systemic Lupus Erythematosus. 2016;(c):270–1.14. Feng J, Liu F, Wu F, Deng Q De. Tinea Infection with Scutula-like Lesions Caused by Microsporum Gypseum in a SLE Patient : Case Report and Literature Review. 2013;255–8.15. Cortis E, Insalaco A. Macrophage activation syndrome in juvenile idiopathic arthritis. Acta Paediatr Suppl. 2006 Jul;95(452):38–41.16. Ravelli, A., Magni-Manzoni, S., Pistorio, A. et al. Preliminary diagnostic guidelines for macrophage acti- vation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr. 2004;12.016(146):598–604.17. Colella, M. , Buttaro, G. , Masi, L. , Palma, E. , Amelio, R. and Vallone A. The difficult management of systemic-onset juvenile rheumatoid arthritis. Level of serum ferritin as aspecific diagnostic finding. Open J Pediatr. 2012;2:53–5.18. Jandus, P., Wang, W., Seitz, M. et al. High serum ferritin in adult-onset still’s disease. International Journal of Clinical Medicine. 2010;1:81–3.19. Meijvis, H., Endeman, A.B.M., Geers, E.J. and Borg EJ. Extremely high serum ferritin levels as diagnostic tool in adult-onset still’s disease. Netherl J Med. 2007;65:212–4.

Background and purpose: Myricetin (3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one) is a polyhydroxyfavonol compound widely found in nature has been shown to possess anticancer effects in various cancers. Despite its efficacy, poor water solubility and low oral bioavailability hinders its therapeutic application. To overcome these limitations, Nanoemulsion (NE) emerged as a promising approach that combines the advantages of NE into a single delivery system. The present study aimed to investigate the advantage of myricetin loaded NE over and above native Myricetin. Experimental Approach: The nano-emulsion was formulated using Capryol 90 as oil, Tween 20 as a surfactant, and Transcutol HP as a co-surfactant. Further comparative analysis of Myricetin and nano-emulsified Myricetin (Myr-NE) were carried out in triple negative breast cancer (MDA-MB-231) cells for anticancer activity. Key results: The optimized Myr-NE had a zeta potential of -6.35±0.3, an average particle size of 89.32±2.8 nm, PDI of 0.105±0.02, and a spherical shape as confirmed in transmission electron microscopy. Diffusion-dominant drug release was observed with 95.49±2.84 % Drug release for 24hrs, 2-fold higher than Myr-suspension. When nano-emulsified, Myricetin exhibited efficient inhibition of cell proliferation, clonogenicity, and increased apoptosis with IC50 of 37 µM, a dose ~2.5 fold lower than native Myricetin. Mechanistic insights reveal that Myr-NE induced more ROS generation and considerably inhibited AKT and mTOR activation, leading to enhanced anticancer activity. Conclusions & Implications: In conclusion, these findings suggest that the therapeutic efficacy of Myricetin significantly improved through a novel Myr-NE formulation which may be a promising therapeutic approach for treating TNBC.

Ecological or reproductive barriers can maintain species by preventing introgression in closely related taxa when their distributions overlap. In sympatry, sister-taxa may have greater genetic divergence than comparing the sister-taxa in allopatric parts of their range. When analyzing populations within a species, this may translate to greater genetic divergence between sympatry and allopatry. This genetic differentiation can be caused by either genetic drift or natural selection, depending on the evolutionary history of secondary contact. To identify a selective process, it is critical to find genes responsible for maintaining species barriers in sympatry. Here, we examined the role of natural selection in genetic differentiation within two recently diverged rockfish species, Sebastes diaconus and Sebastes mystinus. These species overlap along over 400 km of coastline in the eastern Pacific, with no evidence of hybridization. We found evidence of geographic genetic differentiation across a large span of the S. diaconus range, but not within S. mystinus. For both species, we identified outlier loci associated with regions of the genome under directional selection in allopatric versus sympatric populations. We also found signals of directional selection in shared genomic regions of both species, suggesting the evolutionary process of reinforcement maintained species boundaries once the two species were in secondary contact.

Nowadays, vehicle industrialization has realized several connectivity protocols to enable in-vehicle network communication. These protocols have been collectively standardized in a de facto standard for the in-vehicle network viz controller area network (CAN). Merely, CAN protocol shortages several security features that make vehicular communications susceptible to diverse message injection attacks that may mislead original electronic control units (ECUs) or cause failures. Therefore, defending the in-vehicle network from cyber-attacks is an essential concern. This paper proposes a fast anomalous traffic detection system for secure vehicular communications. The proposed system differentiates the performance of four different machine-learning approaches: Adaboost trees (ABT), Coarse decision trees (CDT), naïve Bayes classifier (NBC), and support vector machine (SVM). The models were evaluated on a recent dataset from a real-time vehicular communications environment, the car-hacking-2018 dataset. Specifically, the system considers five balanced classes, including one normal traffic class and four classes for message injection attacks over the in-vehicle controller area network: fuzzy attack, DoS attack, RPM attack (spoofing), and gear attack (spoofing). Our best performance outcomes belong to the ABT model, which notched 99.8% classification accuracy and 6.67 µseconds of classification overhead. Such results have outweighed existing in-vehicle intrusion detection systems employing the same/similar dataset.

Background: The characteristics and incidence of patients with tricuspid valve (TV) prolapse after leadless pacemaker implantation are unknown. Methods and Results: We retrospectively identified 35 of 85 patients with sufficient echocardiographic TV imaging before and after Micra transcatheter pacing system (Micra TPS) implantation. The post-procedure incidence of TV prolapse was 8.6%, and the cause of prolapse was chordae tendineae rupture. Patients with TV prolapse had significantly longer procedure times and more deployments than patients without TV prolapse. Conclusions: TV prolapse after Micra TPS implantation is not a rare complication and is accompanied by frequent deployments and prolonged procedure times.

Introduction: Several therapeutic options are usually discussed for otosclerosis management. Patients seek medical advice from an ENT specialist but are also increasingly using the internet for medical issues. This study intends to assess readability and quality of websites with information on otosclerosis. Materials & Methods: This is a cross-sectionnal study performed in a tertiary care center. The results of the first 2 pages of a Google search with the keyword “otosclerosis” were reviewed by two independent investigators. Readability was assessed with the Flesch–Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES) and Gunning Fog Index. For quality and reliability assessment, the 16-items DISCERN instrument was used. Spearman’s coefficient was used for correlations, and multivariate analyses of variance were used to assess differences. Inter-rater agreement was evaluated with concordance correlation coefficient. Results: 18 websites were included. Two websites (11.0%) were authored by academic institutions, 5/18 (28%) by government agencies, 6/18 (33%) by professional organizations and 5/18 (28%) were medical information websites. The mean DISCERN score of the 18 websites was 40.2±8.4/80 (range, 23.5–54), corresponding to “fair” quality. The mean FRES score was 43.27 ± 10.6, and the the mean FKGL was 11.43±2.30, corresponding to “difficult to read”. The mean Gunning Fog index was 12.90±2.19 (range 9.81- 18.20), corresponding to a “college freshman” level. Conclusions: This study shows that internet information on otosclerosis has an overall low readability, while the quality is heterogeneous and varies from “poor” to “good”. Efforts should be made to improve the readability of otosclerosis websites.

Objective: Hybrid cardiovascular mock circuits (HMC), designed for dynamic testing of Ventricular Assist Devices (VAD), offer physiologic accuracy by sequestering model complexity in silico and ease of construction by reducing number of model elements in vitro. Despite superior response time and precision, pneumatic actuation is avoided in HMCs due to nonlinear dynamics and noise. We tested the hypothesis that a HMC consisting of a variable elastance-driven numerical circuit coupled to a pneumo-hydraulic physical circuit can be controlled without linearizing system dynamics. Methods: Reference left ventricular and aortic pressures generated in silico were tracked, respectively, in in vitro preload and afterload reservoirs by controlling non-linear pneumatic dynamics using the Lyapunov stability criterion. A centrifugal pump, the speed (i.e. flow) of which was adjusted using PID control, was interposed between the reservoirs and mimicked the VAD under evaluation. The flow of a recirculating gear pump was controlled by the backstepping method to equalize reservoir fluid volumes by rejecting pressure and flow disturbances. Sensor noise was reduced with discrete-time Kalman filtering. Results: Our results showed that normal, failing and assisted cardiovascular physiologies were numerically simulated and tracked at physical VAD terminals with high accuracy. Reservoir volumes remained stable at various combinations of heart rate, pressure, and VAD flow. Conclusion: The HMC described here offers a stable performance testing platform for VAD prototypes. Significance : This is the first proof that hybrid systems using pneumatic actuation at hydraulic interfaces can optimally be regulated with nonlinear controllers to achieve precise reference tracking and robust disturbance rejection.

Cataracts are considered the underlying cause of blindness globally. When the average age of the earth’s population is on the rise, cataract-induced blindness and visual dysfunction will increase dramatically. (1) Currently, the only viable treatment for cataracts is surgery, including removing the opaque lens and replacing it with an artificial one which has a huge impact on improving the patient’s quality of life. Undoubtedly, cataracts have far-reaching repercussions for countries in terms of social and economic burdens, for example, the increasing rate of automobile accidents due to reduced visual acuity. (2) Nonetheless, due to the lack of facilities, ophthalmologists, and funds, surgery is not a choice in developing countries. (3) It should be noted that posterior capsular opacification is a common complication of cataracts, and sometimes, a second intervention is necessary. (4)This research has thrown up many questions in need of further investigation to find medications that restore full transparency of the lens.

This study is focused on the anisotropic fatigue crack growth (FCG) behaviour of an aluminium AA7050-T7451 plate. L-T and S-T orientations were studied in M(T) samples with W=50 mm, in mode I loading, with R-ratio of +0.05. A numerical approach was used, assuming that crack tip plastic strain is the crack driving force. A purely kinematic elastic-plastic model was calibrated using experimental data from low cycle fatigue tests of smooth specimens in L and S orientations. The predicted FCG rates agree well with experimental trends in the Paris’ regime, suggesting that cyclic plastic deformation is the main damage mechanism. The numerical model was used to estimate the stress ratio effect for both orientations, which was found to be linked with crack closure variations. However, the closure free predicted trends for both microstructural orientations at R=0.05 are not overlapped, suggesting an effect of microstructure not linked to crack closure.

The paper addresses the non-cooperative game leader-synchronization problem with time-delays and gain perturbations. In the non-cooperative game, a stochastic communication protocol (SCP) is implemented to prevent the data collisions among agents. Coping with time-delays, SCP and gain perturbation simultaneously makes it extremely hard to get the accurate payoff value. Then, we resort to an explicit upper bound of payoff value as an alternative optimization objective. By using the linear matrix inequality (LMI)-constrained method, the leader-synchronization strategies form the J ̵̄ -Nash Equilibrium ( J ̵̄ -NE) solution of non-cooperative game. Sufficient conditions are established in the infinite-horizon with hope to guarantee the stability behavior. Finally, a simulation example is used to illustrate the validity of the proposed methodology.

Background and Purpose: The Bazhen decoction is one of the most extensively used Traditional Chinese medicine (TCM) prescriptions for anti-aging. However, due to the complicity of the components, the pharmacological mechanism of Bazhen decoction is still limited. Experimental approach: We applied RNA sequencing and transcriptome analysis to get the full view of the signaling pathways regulated by Bazhen decoction in the wild type cell background. By using the progeroid cells derived from Werner syndrome mice, we applied Western blot, Immunofluorescence, flow cytometry and telomere FISH to verify the transcriptome data. Key Results: The transcriptome profile revealed that Bazhen decoction might systematically regulate multiple anti-aging pathways, including stem cell regulation, protein homeostasis, cardiovascular function, neuronal function, anti-inflammation, anti-DNA damage induced stress, DNA helicase activity and telomere lengthening. We found that multiple DNA helicases and telomere regulating proteins were up-regulated by Bazhen decoction, which promoted the resolving of G-quadruplex (G4) structure, and facilitated DNA replication and telomere elongation. These improvements also endowed the cellular resistance to DNA damages induced by replication stress. Together these data suggest that Bazhen decoction facilitate G4 resolving and telomere maintenance, which might contribute to the longevity sustaining properties revealed by transcriptome profile. Conclusions & Implications: Our data revealed a new strategy for recovering the pharmacological signature pathways for TCM, which could help the clinical precision medicine of TCM. By applying transcriptome in TCM-treated normal cell, we tried out a systematic analysis for dissecting the molecular mechanism of complicated TCM prescription in the normal genetic background.