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The structures of three 3-methyl-1H-1,2,4-triazole-5-thione derivatives are reported. The structure of 4-amino-3-methyl-1H-1,2,4-triazole-5(4H)-thione, C3H6N4S, (I), has been redetermined with an improved model for the H atoms: the non-H atoms of (I) all lie on mirror planes in space group Pbcm, and the H atoms of the methyl group are disordered over two sets of reflection-related atomic sites having occupancy 0.5: two independent N—H...S hydrogen bonds link the molecules of compound (I) into complex sheets. The non-H atoms in the molecules of 4-[(E)-(3,4-dimethoxybenzylidene)amino]-3-methyl-1H-1,2,4-triazol-5(4H)-thione, C12H14N4O2S, (II), despite lying in general positions are close to planar, with a dihedral angle between the two rings of 6.31 (10)°: the molecules of compound (II) are linked by a three-centre N—H...(O)2 hydrogen bond into a C(10)C(11)[R12(5)] chain of rings. A second polymorph of 4-[(E)-(5-bromo-2-hydroxy-5-bromobenzylidene)amino]-3-methyl-1H-1,2,4-triazole-5(4H)-thione, C10H9BrN4OS, (III), has been identified; the non-H atoms are nearly co-planar with a dihedral angle between the two rings of 1.9 (4)°. There is an intramolecular O—H...N hydrogen bond and the molecules are linked by N—H...S hydrogen bonds, forming centrosymmetric R22(8) dimers. Comparisons are made with some related structures.

The title compound, C10H10N4OS, is nearly planar with the mean planes of the hydroxybenzyl and triazole rings inclined at an angle of only 3.2 (7)°. In the crystal, O—H...N hydrogen bonds between the hydroxy group and the triazole ring in concert with weak N—H...S intermolecular interactions between the triazole ring and thione group form chains along [-210] enclosing R22(8) graph-set motifs. A weak intramolecular C—H...S interaction and intermolecular π–π interactions [centroid–centroid distance = 3.5990 (15) Å] are also observed.

Introduction: There is varying impact of COVID19 on world population depending on ethnicity, age and underlying co-morbidities. However, the lack of data regarding the effect of COVID on patients with rheumatological disorders (RDs) from different nations adds to uncertainty on disease outcome. Across the world, many rheumatology associations have joined hands to collate-related information. A national database under Indian Rheumatology Associations (IRAs) was developed to understand the impact of underlying RD and immunosuppressants during the COVID pandemic on its severity and outcome in our country. Methods: All registered members of IRA were invited to participate in this registry and provide information of reverse transcription–polymerase chain reaction confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-infected RD patients using an online platform https://iradatabaseard.in/iracovid/index.php. The results of the data were analyzed using the appropriate statistics. Multivariate logistic regression was used to analyze the impact of different variables on mortality. Odds ratio and 95% confidence interval were used to define risk of death. Results: In this retrospective cross-sectional study, data for 447 RD patients who were infected with SARS-CoV2 data were available as of December 1, 2020. The mean age was 47.9 ± 14.4 years, including two children and 93 (20.8%) geriatric age group patients, male: female ratio was 0.4:1 and mean disease duration was 79.3 ± 77.1 months. Rheumatoid arthritis was the most common RD. Underlying disease was quiescent in 54.7% and active in 18.4% patients. Most common medications at the time of COVID diagnosis were steroids (57.76%) and hydroxychloroquine (67.34%). Fever and cough were the most common symptoms. More than half of the patients (54.4%) needed hospitalization. Oxygen requirement was noted in 18.8%, intensive care unit admission, and invasive ventilation was needed in 6.0%, and 2.9% patients, respectively. Complete recovery was seen in 95.5% of patients and 4.47% (n = 20) expired due to COVID. The presence of comorbidity, dyspnea, and a higher neutrophil count was statistically significantly associated with death (P < 0.05). None of the other factors affected COVID-19 outcome. Conclusion: This is the largest cohort from a single nation looking at the interface between RD and COVID. The results indicate that patients with RD do not show increased mortality despite current use of disease-modifying anti-rheumatic drugs/immunosuppressants.

Abstract Background We conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs). Methods This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome. Results COVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5–20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p

Aim: The present study is intended to analyze the preliminary interim data to understand the burden of associated comorbidities in autoimmune rheumatic diseases (AIRDS) in the Indian population from the Indian Rheumatology Association database. Materials and Methods: The independent prospective, multicenter, observational study evaluated the preliminary data obtained from 5 centers across India. The data pertaining to comorbidities were collected, as per the definition of the new International Classification Diseases-10 version of the Charlson Comorbidity Index. The details such as socioeconomic status, impairment in the working capability, and their capacity to cope with their job after developing the disease were gathered for selected patients. The patients were broadly classified into five based on diagnosed AIRDS namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), seronegative spondyloarthropathy (SpA), psoriasis arthritis (PsA), and scleroderma. The prevalence of different comorbidities was compared between the groups using Chi-square or Fischer-exact test for nonparametric data and analysis of variance for continuous variables. Results: The study considered the data of 1885 for the analysis and 129 patients were excluded due to missing variables and data inconsistency. The socioeconomic distribution of AIRDS indicated that SLE was more prevalent among upper-middle-class followed by SpA (60.3% and 50.94%, respectively). RA and systemic sclerosis (SSc) were more common among the lower-income group, and PsA was common among the upper socioeconomic group. The most common comorbidity found in patients with RA and PsA was hypertension (20.97%, 17.14%), SLE and SSc was thyroid disease (21.49%, 17.78%), and SpA was diabetes (2.96%). Conclusion: AIRDs are associated with the significant burden of comorbidities. Further studies are needed to understand the pattern of prevalence of comorbidities across different age groups.

Introduction: Previous exposure to Rituximab affects the immunogenicity of vaccination including that against coronavirus disease (COVID-19). However, dynamics of the effect of rituximab on vaccination are not well understood. This study aims to assess the role of timing of vaccine dosing and B-cell repopulation on vaccine seroconversion. Methods: Autoimmune rheumatic disease (AIRD) patients treated with rituximab who had completed two doses of COVID-19 vaccination were enrolled. Peripheral B-cell counts were estimated along with the titer of immunoglobulin G antibody-directed against the receptor-binding domain of spike1 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Antibody titers of participants were compared against B-cell re-population. Results: Out of the 33 participants with available prevaccination B-cell counts, 11 did not have any detectable peripheral B cells before vaccination, and out of these patients, only 1 developed antibodies postvaccination, whereas, of the remaining 22, 18 (81.8%) had a positive seroconversion. Although all patients who had received the last dose of Rituximab at least 1 year before vaccination had antibodies, there was no direct correlation between time from the last dose and antibody positivity. B-cell re-population was strongly associated with seroconversion (P = 0.0001). Conclusion: In rituximab-treated patients, humoral responses to SARS-CoV-2 vaccination depend on peripheral B-cell re-population rather than the timing of the vaccination postrituximab infusion.

Drug-free remission is the ideal end point for any chronic disease. Although there are data on drug-free remission in rheumatoid arthritis and lupus, such data are limited for most vasculitis. Notably, there is less evidence for disease-modifying agents in large-vessel vasculitis (LVV). Thus, we explored the literature about sustained remission in LVV. MEDLINE and SCOPUS were searched for outcomes in LVV, and the results were manually screened for studies with at least 1-year follow-up. Isolated polymyalgia rheumatica was not included. In giant cell arteritis (GCA), histological and clinical remissions were discordant. Histology could not predict relapse rate. Various imaging techniques exhibit vessel wall inflammation in clinically quiescent disease. Relapse rate seems to correlate with the rate of steroid reduction. Relapse was rare when on higher steroid doses. Emerging evidence suggests that tocilizumab and methotrexate may prevent relapse. In Takayasu arteritis (TA), histology specimens are difficult to obtain. Remission on imaging does not mirror clinical remission. While magnetic resonance imaging and positron emission tomography are sensitive tools, these cannot differentiate smouldering disease from vascular repair. The best predictor of relapse is the extent of disease. Approximately half of the TA patients relapsed by 5 years. In patients undergoing intravascular procedures, restenosis occurred in around a third. Even for patients on anti- Tumour necrosis factor necrosis factor, sustained remission was in 20% only. LVV seems to be steroid dependent, and the efficacy of various steroid-sparing agents cannot be established unless the natural history of the disease is known. Both TA and GCA can have grumbling courses with relapse rates increasing over time.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a delayed form of severe cutaneous adverse reaction (SCAR) seen in association with certain drugs, especially anticonvulsants and allopurinol. Unlike other SCARs, DRESS is associated with significant systemic involvement such as fever, lymphadenopathy, eosinophilia, renal failure, transaminitis, and myocarditis. Because of delayed onset of symptoms and a persistent course even after discontinuation of culprit drug, DRESS can mimic a variety of rheumatological disorders. Even though glucocorticoids are the mainstay of treatment, unlike other SCARs, DRESS is associated with a high incidence of viral reactivation, especially with members of the human Herpesviridae family. Early identification of the viral activation and prompt therapy is critical in the management of DRESS.

Dermatology and rheumatology are two specialties that deal with significant overlap. In this context, it is important that the dermatologists acquaint themselves with conditions presenting with arthropathy. As the first step, it is essential to know whether the origin of musculoskeletal symptom is articular or extra-articular; inflammatory or noninflammatory; acute or chronic; oligo- or poly-articular. This will help in narrowing down the differential diagnoses as well as in better correlation with the cutaneous symptoms. In this review, we discuss the skin and articular manifestations of common inflammatory and noninflammatory arthropathies including rheumatoid arthritis, spondyloarthropathies, connective tissue disorders, vasculitis, crystal arthropathies, infective arthritis, arthritis associated with degenerative, endocrine and metabolic conditions, etc. We have also added a section on the common cutaneous features associated with the treatment of rheumatologic diseases. A basic understanding of the joint pathologies and associated skin changes will help a long way in the better management of these conditions.

Pulmonary edema is a rare mechanism of death that develops after partial hanging, a potential complication that physicians should consider early in the management of these patients. This case series discusses the presentation, evaluation, and treatment course of three patients who had attempted suicide by hanging and were admitted to the hospital. These patients were admitted to the intensive care unit after being stabilized and supportive treatment was provided. In all the cases, a radiological scan of the chest revealed diffuse infiltrates consistent with pulmonary edema on both sides, features of which were also noted during a diagnostic bronchoscopy. After providing the best intensive care in the hospital, two patients clinically improved, and one patient succumbed to cardiac arrest. As most patients will be brought dead to the hospital following hanging, negative pressure pulmonary edema remains underdiagnosed. Thus, this case series enumerates the possible etiologies of negative pressure pulmonary edema and its contribution to death following suicidal hanging., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Athish et al.)

Adenoid cystic carcinoma (ACC) is a rare type of tumor that usually originates from minor salivary glands in the oral cavity. ACC of the larynx is even rare. This case study describes a 36-year-old non-smoking male farmer who initially presented with dyspnea and was misdiagnosed with bronchial asthma. Spirometry revealed fixed airway obstruction. Further evaluation revealed a pedunculated mass obstructing the airway, which was diagnosed as ACC by histopathological examination of the biopsy specimen. The patient was treated with radiation therapy, resulting in clinical improvement after six weeks. ACC is highly invasive and slow-growing, with perineural extension and a higher risk of recurrence. Metastasis in the lungs is common. Adequate preoperative staging, including imaging with computed tomography (CT) and magnetic resonance imaging, is important for planning treatment. The role of radiation therapy with concurrent chemotherapy is still under trial., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Athish et al.)

Efficient and dynamic light manipulation at small scale is highly desirable for many photonics applications. Active optical metasurfaces represent a useful way of achieving this due to their creative design potential, compact footprint, and low power consumption, paving the way toward the realization of chip-scale photonic devices with tunable optical functionality on demand. Here, we demonstrate a dynamically tunable, dual-function metasurface based on dielectric resonances in vanadium dioxide that is capable of independent active amplitude and phase control without the use of mechanical parts. Significant developments in the nanofabrication of vanadium dioxide have been shown to enable this metasurface. Gradual thermal control of the metasurface yields a computationally predicted continuously tuned amplitude modulation of 19 dB with negligible phase modulation and a continuously tuned phase modulation of 228° with negligible amplitude modulation, both at near-infrared wavelengths. Experimentally, a maximum continuously tuned amplitude modulation of 9.6 dB and phase modulation of 120° are shown, along with demonstration of stable intermediate states and repeated modulation without degradation. Reprogrammable optical functionality can thus be achieved in precisely engineered nanoantenna arrays for adaptive modulation of amplitude and phase of light for applications such as tunable holograms, lenses, and beam deflectors.

Biomarker detection and bulk refractive index sensing are important across multiple industries ranging from early medical diagnosis to chemical process quality control. The bulky size, high cost, and complex architecture of existing refractive index and biomarker sensing technologies limit their use to highly skilled environments like hospitals, large food processing plants, and research labs. Here, we demonstrate a compact and inexpensive refractive index sensor based on resonant dielectric photonic nanoantenna arrays or metasurfaces. These dielectric resonances support Mie dipole and asymmetric resonances that shift with changes in their external environment. A single-wavelength transmission measurement in a portable (<250 in. 3 ), low-cost (<$4000) sensor shows sensitivity to 1.9 × 10 -6 change in the fluid refractive index without the use of a spectrometer or other complex optics. Our sensor assembly allows for measurements using multiple metasurfaces with identical resonances or varying resonance types for enhanced diagnostics on the same chip. Furthermore, a 10 kDa culture filtrate peptide CFP-10, a marker for human tuberculosis, is detected with our sensor with 10 pM resolution. This system has the potential to enable facile, fast, and highly sensitive measurements with adequate limits of detection for personalized biomedical diagnoses., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: Loss of α-crystallin chaperone function results in the lens protein aggregation leading to cataract. In this study, we evaluated the efficacy of micellar lutein with different fatty acids in modulating α-crystallin chaperone function under selenite cataract conditions., Methods: Cataract was induced in rat pups by giving sodium selenite (25 μM/kg body weight) by IP. Lutein [(L), 1.3 μmol/kg body weight)] was given day before and five days after selenite injection as a micelle with 7.5 mM linoleic acid (LA), or 7.5 mM eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) or 7.5 mM oleic acid (OA). Lens α-crystallins was purified, and its chaperone function and integrity was assessed. Cholesterol, calcium, calpain-2, procaspase-3, and expression of α-A and β-B1 crystallin in the lens of cataract and micellar lutein administered rats were evaluated., Results: Cataract induction significantly (p < 0.05) decreased lens α-crystallin chaperone function. Cataract rats had increased cholesterol and calcium level, increased the expression of calpain-2, and α-A and β-B1 crystallin, and reduced the pro-caspase-3 level in the lens. However, micellar lutein administration significantly (p < 0.05) protected client proteins from aggregation via the modulation of calcium-dependent calpain-2 protease activity. The chaperone function of lens α-crystallins in rats administered micellar lutein with EPA + DHA was found to be highest when compared to OA and LA., Conclusions: Micellar lutein with unsaturated fatty acids beneficially modulates α-crystallin chaperone function. Among the fatty acids tested, micellar lutein with EPA + DHA exhibited superior effects, thereby offering a promising strategy for cataract management., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Effects of lutein (L) and fatty acids [linoleic acid (LA), eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) and oleic acid (OA)] on oxidative stress and inflammation in cataract were assessed., Methods: Cataract was induced in male Wistar rat pups (11 days old) by giving a single dose of sodium selenite (25 μM/kg body weight) by IP. Lutein (1.3 μmol/kg body weight) was given one day before and five days after selenite injection as a micelle with 7.5 mM LA, or 7.5 mM EPA + DHA or 7.5 mM OA. Serum and lens oxidative stress and inflammatory parameters having a bearing cataract were assessed., Results: Serum and lens nitric oxide, MDA and protein carbonyls were significantly (p < 0.05) increased in cataract compared to control and experimental groups. Catalase, SOD, glutathione peroxidase and glutathione transferase activity and glutathione level in serum and lens of cataract group were significantly (p < 0.05) decreased. Serum eicosanoids (PGE 2 , LTB 4 , and LTC 4 ) and cytokines (CRP, TNF-α, IL1-β, and MCP-1) were significantly (p < 0.05) increased in cataract. The activity of cPLA2 and Cox-2 in cataract lens was higher (p < 0.05) compared to other groups. EP-1, NOS-2 and NF-kB expression were higher (p < 0.05) in cataract. The ratio of water insoluble to water soluble protein was increased in cataract lens. Group administered with L + EPA + DHA exhibited highest cataract prevention compared to L + LA and L + OA. Pups given lutein with EPA + DHA had the highest amount of lutein in the lens., Conclusions: The anti-cataract activity of lutein was influenced by fatty acids and found to be highest with EPA + DHA compared to LA or OA., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The authors describe the case of a patient who initially presented with uterine leiomyosarcoma (LMS) that later metastasized to the spine. The patient was treated at another institution for her primary uterine LMS, undergoing resection followed by adjuvant chemotherapy. After several years of disease remission, the patient presented in January 2011 to the authors' institution with recurrent uterine LMS metastatic to the spine, which has been treated with multiple therapeutic modalities in a combination of surgery, radiosurgery, and chemotherapy. As a result of this approach, the patient has been progression free for 35 months since her presentation (April 2011 to March 2014). We herein describe our experience treating this patient with recurrent uterine LMS of the spine and suggest that patients with recurrent uterine LMSs should be considered for treatment using a multimodality approach with emphasis on enrollment into clinical trials.

The title compound, C10H10N4OS, is nearly planar with the mean planes of the hy-droxy-benzyl and triazole rings inclined at an angle of only 3.2 (7)°. In the crystal, O-H⋯N hydrogen bonds between the hy-droxy group and the triazole ring in concert with weak N-H⋯S inter-molecular inter-actions between the triazole ring and thione group form chains along [-210] enclosing R 2 (2)(8) graph-set motifs. A weak intra-molecular C-H⋯S inter-action and inter-molecular π-π inter-actions [centroid-centroid distance = 3.5990 (15) Å] are also observed.

αB-Crystallin is a chaperone and an anti-apoptotic protein that is strongly expressed in many tissues, including the lens, retina, heart, and kidney. In the human lens, several lysine residues in αB-crystallin are acetylated. We have previously shown that such acetylation is predominant at lysine 92 (K92) and lysine 166 (K166). We have investigated the effect of lysine acetylation on the structure and functions of αB-crystallin by the specific introduction of an N(ε)-acetyllysine (AcK) mimic at K92. The introduction of AcK slightly altered the secondary and tertiary structures of the protein. The introduction of AcK also resulted in an increase in the molar mass and hydrodynamic radius of the protein, and the protein became structurally more open and more stable than the native protein. The acetyl protein acquired higher surface hydrophobicity and exhibited 25-55% higher chaperone activity than the native protein. The acetyl protein had more client protein binding per subunit of the protein and higher binding affinity relative to that of the native protein. The acetyl protein was at least 20% more effective in inhibiting chemically induced apoptosis than the native protein. Molecular modeling suggests that acetylation of K92 makes the "α-crystallin domain" more hydrophobic. Together, our results reveal that the acetylation of a single lysine residue in αB-crystallin makes the protein structurally more stable and improves its chaperone and anti-apoptotic activities. Our findings suggest that lysine acetylation of αB-crystallin is an important chemical modification for enhancing αB-crystallin's protective functions in the eye.

α-Crystallin is a major protein in the human lens that is perceived to help to maintain the transparency of the lens through its chaperone function. In this study, we demonstrate that many lens proteins including αA-crystallin are acetylated in vivo. We found that K70 and K99 in αA-crystallin and, K92 and K166 in αB-crystallin are acetylated in the human lens. To determine the effect of acetylation on the chaperone function and structural changes, αA-crystallin was acetylated using acetic anhydride. The resulting protein showed strong immunoreactivity against a N(ε)-acetyllysine antibody, which was directly related to the degree of acetylation. When compared to the unmodified protein, the chaperone function of the in vitro acetylated αA-crystallin was higher against three of the four different client proteins tested. Because a lysine (residue 70; K70) in αA-crystallin is acetylated in vivo, we generated a protein with an acetylation mimic, replacing Lys70 with glutamine (K70Q). The K70Q mutant protein showed increased chaperone function against three client proteins compared to the Wt protein but decreased chaperone function against γ-crystallin. The acetylated protein displayed higher surface hydrophobicity and tryptophan fluorescence, had altered secondary and tertiary structures and displayed decreased thermodynamic stability. Together, our data suggest that acetylation of αA-crystallin occurs in the human lens and that it affects the chaperone function of the protein., (Copyright © 2011 Elsevier B.V. All rights reserved.)