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A convenient and new synthetic approach has been developed for the oxidative cross-coupling of the C-N bond through the reaction between arylglyoxylic acids and tetraalkylthiuram disulfides. The reaction proceeds under ambient air at room temperature in the presence of visible light. This reaction offers a metal-, base-, photocatalyst-, and solvent-free synthesis of various α-ketoamides with moderate to excellent yields via the radical pathway. In addition, this protocol demonstrates the potential application of a gram-scale synthesis.
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We have introduced a sulfoximidation reaction initiated by visible light between α-phenyl vinyl azides and NH-sulfoximines. The cost-effective and readily accessible hypervalent iodine reagent (PIDA) easily promoted the oxidative sulfoximidation process to afford N-α-ketoacylated sulfoximines in good to high yields, involving the formation of two new C-O bonds and one C-N bond. Additionally, the protocol offers noteworthy advantages, including its metal-free and photocatalyst-free reaction and its broad substrate compatibility.
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BACKGROUND: Levamisole is less expensive and has a better toxicity profile compared to other steroid sparing agents used in nephrotic syndrome. It has a plasma half-life of 2.0 to 5.6 hours, but is conventionally administered on alternate days. We aimed to assess whether daily levamisole is safe and more effective than standard alternate-day therapy in maintaining remission in children with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). METHODS: An open-label randomized controlled trial was conducted in children with FR/SDNS. Group A received daily while Group B received alternate-day levamisole (2-3 mg/kg/dose) for 12 months. Prednisolone was tapered off by 3 months. Patients were monitored for relapses, further steroid requirement, and adverse effects. RESULTS: A total of 190 children with FR/SDNS (94 in Group A and 96 in Group B) were analyzed. Sustained remission for 12 months was observed in 36% of Group A and 27% of Group B patients (p = 0.18). Numbers completing 12 months in the study were 67% in Group A and 56% in Group B (p = 0.13). Time to first relapse, persistent FR/SDNS, and withdrawal due to poor compliance were statistically similar in both groups, while relapse rate and cumulative steroid dosage were significantly lower in Group A compared to Group B (p = 0.03 and p = 0.02, respectively). The incidence of adverse effects was comparable in both groups, with reversible leucopenia and hepatic transaminitis being the commonest. CONCLUSIONS: Daily levamisole therapy was not superior to alternate-day therapy in maintaining sustained remission over 12 months. Nevertheless, relapse rate and cumulative steroid dosage were significantly lower without increased adverse effects.
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Levamisol , Síndrome Nefrótica , Recidiva , Humanos , Levamisol/administração & dosagem , Levamisol/efeitos adversos , Síndrome Nefrótica/tratamento farmacológico , Masculino , Feminino , Criança , Pré-Escolar , Resultado do Tratamento , Esquema de Medicação , Indução de Remissão/métodos , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Adolescente , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversosRESUMO
BACKGROUND: Levamisole is a commonly used steroid-sparing agent (SSA), but the reported incidence of antineutrophil cytoplasmic antibody (ANCA) positivity has been concerning. METHODS: Observational cross-sectional study wherein children aged 2 to 18 years with frequently relapsing/steroid dependent nephrotic syndrome (FRNS/SDNS) on levamisole for ≥ 12 months were tested for ANCA. RESULTS: A total of 210 children (33% female), median age of 7.3 (IQR: 5.6-9.6) years, and a median duration of levamisole exposure of 21 (IQR: 15-30) months were tested. ANCA was positive in 18% (n = 37): 89% (n = 33) perinuclear ANCA (pANCA), 3% (n = 1) cytoplasmic ANCA (cANCA), and 8% (n = 3) both. Of ANCA-positive children, none had reduced eGFR or abnormal urinalysis. The majority of these children were asymptomatic (81%, n = 30). Rash was more common among ANCA-positive children [6/37 (16%) vs. 3/173 (2%), p = 0.0001]. On multivariate analysis, higher age (OR = 1.02, [95th CI: 1.01 to 1.03], p = 0.007) and longer duration of levamisole exposure (OR = 1.05, [95th CI: 1.02 to 1.08], p = 0.0007) were associated with ANCA positivity. Levamisole was stopped in ANCA-positive children with the resolution of any clinical manifestations if present. Repeat ANCA testing was performed in 54% (20/37), and all were ANCA negative by 18 months. CONCLUSIONS: Children with FRNS/SDNS on longer duration of levamisole were associated with increasing prevalence of ANCA positivity, but most of these children were clinically asymptomatic. Prospective studies are required to determine the chronology of ANCA positivity and its clinical implication.
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Anticorpos Anticitoplasma de Neutrófilos , Levamisol , Síndrome Nefrótica , Humanos , Levamisol/efeitos adversos , Criança , Feminino , Masculino , Estudos Transversais , Anticorpos Anticitoplasma de Neutrófilos/sangue , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/imunologia , Síndrome Nefrótica/sangue , Pré-Escolar , Adolescente , Estudos de CoortesRESUMO
Acute kidney injury (AKI) is a known independent risk factor for morbidity/mortality but there is scarcity of robust data on it among childhood nephrotic syndrome (NS). We assessed the incidence of AKI among hospitalized children with NS as well as looked for any significant risk factors. Prospective observational study conducted across two tertiary pediatric hospitals in Eastern India from September 2020 to August 2021. Children aged 1-18 years admitted with NS and without any nephritic features or pre-existing chronic kidney disease (CKD) were included. In 200 admissions (n = 176; 63% female, median age 4 years [IQR: 3-7]), AKI occurred in 36 (18%; 95% CI 13 to 36%). Two children required kidney replacement therapy and one death was recorded. In 27/36 (75%), AKI resolved within 48 h, 4 had persistent AKI, 3 acute kidney disease, and two progressed to CKD. On multivariate regression analysis: fractional excretion of sodium ≤ 0.2% (OR 12.77; 95% CI 3.5-46.4), male gender (OR 6.38; 95% CI 2.76-14.74), underlying infection (OR 5.44; 95% CI 2.4-11.86), nephrotoxic drugs (OR 4.83; 95% CI 2.21-10.54), and albumin ≤ 1.4 g/dl (OR 4.35; 95% CI 1.55-12.8) were associated with AKI. A predictive equation using these five variables on admission had high AUC (0.86) in correctly identifying 17 children who subsequently developed AKI. Conclusion: In a low resource setting, AKI is common among hospitalized children with NS. Larger multi-center prospective studies are needed to refine prediction equations and test its utility in preventing AKI development. What is Known: ⢠Acute Kidney Injury is a known independent risk factor for increased morbidity and mortality. ⢠There are few studies to assess the incidence of Acute kidney injury in hospitalised cases of childhood nephrotic syndrome.. What is New: ⢠This is the largest prospective cohort of children suffering from nephrotic syndrome, in India, proposing a novel algorithm for predicting the risk of AKI among hospitalised cases of childhood nephrotic syndrome.
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Injúria Renal Aguda , Síndrome Nefrótica , Insuficiência Renal Crônica , Criança , Humanos , Masculino , Feminino , Pré-Escolar , Incidência , Síndrome Nefrótica/complicações , Síndrome Nefrótica/epidemiologia , Estudos Prospectivos , Fatores de Risco , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Insuficiência Renal Crônica/complicações , Estudos RetrospectivosRESUMO
1-Butane sulfonic acid-3-methylimidazolium tosylate, [BSMIM]OTs, is a remarkable catalyst for the cascade synthesis of coumarin-functionalized indole derivatives via a tandem cyclization reaction of aniline and phenylglyoxal monohydrate. This reaction possibly proceeds through imine formation/nucleophilic addition/cyclization. In addition, this method shows lower E-factors. A clean reaction, easily accessible reactants, metal-free and environmentally friendly reaction conditions, and reusability of the catalyst are the notable advantages of this procedure. In addition, molecular docking studies show the theoretical possibility of binding these types of synthesized compounds to key proteins in tumorigenesis.
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4-Hidroxicumarinas , Líquidos Iônicos , Simulação de Acoplamento Molecular , Estrutura Molecular , Indóis/química , Ciclização , Catálise , ÁcidosRESUMO
The in vitro diagnostics of cancer are not represented well yet, but the need for early-stage detection is undeniable. In recent decades, surface-enhanced Raman spectroscopy (SERS) has emerged as an efficient, adaptable, and unique technique for the detection of cancer molecules in their early stages. Herein, we demonstrate an opto-plasmonic hybrid structure for sensitive detection of the prostate cancer biomarker sarcosine using silica nanospheres coated silver nano-islands as a facile and efficient SERS active substrate. The SERS active platform has been developed via thin (5-15 nm) deposition of silver islands using a simple and cost-effective Radio Frequency (RF) sputtering technique followed by the synthesis and decoration of silica nanospheres (~500 nm) synthesized via Stober's method. It is anticipated that the coupling of Whispering Gallery Modes and photonic nano-jets in SiO2 nanospheres induce Localized Surface Plasmon Resonance (LSPR) in Ag nano-islands, which is responsible for the SERS enhancement. The as-fabricated SERS active platform shows a linear response in the physiological range (10 nM to 100 µM) and an extremely low limit of detection (LOD) of 1.76 nM with a correlation coefficient of 0.98 and enhancement factor ~2 × 107. The findings suggest that our fabricated SERS platform could be potentially used for the rapid detection of bio-chemical traces with high sensitivity.
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Nanopartículas Metálicas , Nanosferas , Neoplasias , Humanos , Masculino , Nanosferas/química , Próstata , Dióxido de Silício/química , Biomarcadores Tumorais , Nanopartículas Metálicas/químicaRESUMO
BACKGROUND: Transplantation is the optimal modality for children with ESRD. High risk of disease recurrence and graft loss with FSGS, and its financial implications, may result in families refusing transplantation. Deceased donation is often preferred for FSGS, but access is limited in many low- and middle-income group countries (LMIC; per capita gross national income between $1026 and $3995). As FSGS secondary to an underlying genetic etiology has low recurrence risk, we hypothesized that in LMIC such as India, families with children in ESRD secondary to FSGS with proven pathogenic mutation are more likely to consent for transplantation than those with unknown etiology. METHODS: Prospective cross-sectional study with retrospective chart review was undertaken (March 2011 and February 2019) to identify children with ESRD from FSGS. The objective was to ascertain NGS uptake and findings, parental decision for transplantation, and transplant outcome. RESULTS: 28 children with FSGS started transplant workup, and 15 (54%) families agreed for NGS testing. Pathogenic mutation (NPHS1 x 2, WT1 x 2, COL4A3 x 2, CD2AP, CRB2, COL4A5, INF 2, ACTN4, NPHP4: 1 each) was identified in 12 (80%). 92% (11/12) agreed to proceed with transplantation in contrast to 13% (2/16) who either did not undergo NGS testing or had no pathogenic mutation identified (P = .001). No disease recurrences were noted in those with a known pathogenic mutation. CONCLUSION: In LMIC, NGS results are useful in transplant discussions with families for children with ESRD secondary to FSGS.
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Testes Genéticos/métodos , Glomerulosclerose Segmentar e Focal/genética , Sequenciamento de Nucleotídeos em Larga Escala , Falência Renal Crônica/cirurgia , Transplante de Rim/psicologia , Consentimento dos Pais/psicologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Tomada de Decisões , Países Desenvolvidos , Feminino , Seguimentos , Marcadores Genéticos , Glomerulosclerose Segmentar e Focal/fisiopatologia , Humanos , Índia , Lactente , Recém-Nascido , Falência Renal Crônica/etiologia , Masculino , Mutação , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Risco , Análise de Sequência de DNARESUMO
Acute kidney injury (AKI) is a well-known life-threatening systemic effect of snake envenomation which commonly happens secondary to snake bites from families of Viperidae and Elapidae. Enzymatic toxins in snake venom result in injuries to all kidney cell types including glomerular, tubulo-interstitial and kidney vasculature. Pathogenesis of kidney injury due to snake envenomation includes ischaemia secondary to decreased kidney blood flow caused by systemic bleeding and vascular leakage, proteolytic degradation of the glomerular basement membrane by snake venom metalloproteinases (SVMPs), deposition of microthrombi in the kidney microvasculature (thrombotic microangiopathy), direct cytotoxic action of venom, systemic myotoxicity (rhabdomyolysis) and accumulation of large amounts of myoglobin in kidney tubules. Clinical features of AKI include fatigue, loss of appetite, headache, nausea, vomiting, oliguria and anuria. Monitoring of blood pressure, fluid balance, serum creatinine, blood urea nitrogen and serum electrolytes is useful in managing AKI induced by snake envenomation. Early initiation of anti-snake venom and early diagnosis of AKI are always desirable. Biomarkers which will help in early prediction of AKI are being explored, and current studies suggest that urinary clusterin, urinary neutrophil gelatinase-associated lipocalin, and serum cystatin C may play an important clinical role in the future. Apart from fluid and electrolyte management, kidney support including early and prompt initiation of kidney replacement therapy when indicated forms the bedrock in managing snake bite-associated AKI. Long-term follow-up is important because of chances of progression towards CKD.
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Injúria Renal Aguda , Mordeduras de Serpentes , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Eletrólitos/sangue , Humanos , Terapia de Substituição Renal , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/diagnóstico , Mordeduras de Serpentes/terapiaRESUMO
Plant-insect interactions play a crucial role in shaping terrestrial ecosystems, influencing abundance and distribution of plant species. In the present study, we investigated leaf-mining patterns on fossil leaves from Pliocene strata of the Mahuadanr Valley, Jharkhand, eastern India, deposited under a seasonal tropical climate, and reported complex interactions between plants and insects. We identified 11 distinct mining morphotypes. These morphotypes were mainly found on Dipterocarpaceae, Fabaceae, Lauraceae, and Moraceae; similar mining traces were also observed in the contemporary vegetation surrounding the fossil site. Although mining richness was relatively high, only 2.6% of all leaves in the fossil assemblage were mined. We compared mining richness and abundance values with previously reported values for galling. While richness was slightly lower for galling, almost 50% of all fossil leaves were galled. A literature survey on mining and galling patterns in modern vegetation suggests that there is no global explanation for richness of mining or gall-inducing insects. Thus, low nutrient availability in the ancient forest, dominance of semideciduous leaves with hard texture, and different habitats in the same forest ecosystem, such as well-drained forests and riparian stands, may all have favored different types of specialized plant-insect interactions.
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Here, we investigated the diversity of Sericini in the faunistically rather unknown Lower Gangetic plains in North India, based on material from the collection of the Zoological Survey of India. We discovered one new species from West Bengal, Maladerakolkataensis Bhunia, Gupta, Sarkar & Ahrens, and provide further records of an additional 23 species belonging to five genera from the lowlands of the states Bihar and West Bengal. Out of these, 21 species represent new state records: 12 for Bihar and nine for West Bengal. All recorded species are briefly documented by diagnostic illustrations.
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Besouros , Animais , Índia , ZoologiaRESUMO
Background: The subfamily Luciolinae Lacordaire, 1857, a group of flashing fireflies, is composed of approximately 400 described species in the world. Though the taxonomy of this group has been fairly well established in Southeast (SE) Asia and the Australopacific Region, there is scope of gathering further information regarding taxonomic knowledge on this group from India. Until now, 32 Luciolinae species from nine genera have been reported from India, which is only about 8% (32 out of 400) of the world Luciolinae fauna. With this in mind, several faunistic surveys were conducted in Odisha and West Bengal States of India to explore the firefly fauna of the two States. New information: The faunistic surveys conducted in the Odisha and West Bengal States of India have revealed six new distributional records of Luciolinae firefly species belonging to the genera Abscondita Ballantyne, Lambkin & Fu 2013, Asymmetricata Ballantyne 2009, Pteroptyx Olivier 1902 and Sclerotia Ballantyne 2016 in the two States, earlier which were recorded from other States of India. Of the already recorded species, Abs.perplexa is recorded for the first time from both the States, whereas Abs.chinensis, Asy.ovalis and Scl.aquatilis present new records for Odisha State and Pt.malaccae and Scl.substriata for West Bengal State. The newly-recorded taxa are presented with their examined materials, diagnoses and brief biological notes. Some more distinguishing characters were added for the male genitalia of Abs.perplexa and Asy.ovalis. Further, a checklist of Luciolinae firefly species already recorded from India is also presented.
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We report a new type of fossil margin galls arranged in a linear series on dicot leaf impressions from the latest Neogene (Pliocene) sediments of the Chotanagpur Plateau, Jharkhand, eastern India. We collected ca. 1500 impression and compression leaf fossils, of which 1080 samples bear arthropod damage referable to 37 different damage types (DT) in the 'Guide to Insect (and Other) Damage Types in Compressed Plant Fossils'. A few leaf samples identified as Ipomoea L. (Convolvulaceae) have specific margin galls that do not match any galling DT previously described. This type of galling is characterized by small, linearly arranged, irregular, sessile, sub-globose, solitary, indehiscent, solid pouch-galls with irregular ostioles. The probable damage inducers of the present galling of the foliar margin might be members of Eriophyidae (Acari). The new type of gall suggests that marginal gall-inducing mites on leaves of Ipomoea did not change their host preference at the genus level since the Pliocene. The development of marginal leaf galling in Ipomoea is linked to extrafloral nectaries that do not offer protection against arthropod galling but indirectly protect the plant against herbivory from large mammals.
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Ipomoea , Ácaros , Animais , Insetos , Plantas , Folhas de Planta , Tumores de Planta , MamíferosRESUMO
In recent years several important viral infections have emerged and antiviral chemotherapeutic agents are not sufficiently effective in clinic, leading to serious human diseases and mortality. Therefore, novel antiviral candidates are urgently desirable, which undoubtedly is essential for the therapy of various fatal and debilitating viral infections. Heterocyclic compounds are obtaining importance in the field of medicinal chemistry because of the broad spectrum of their physiological activities. Among N- and S-containing heterocycles, indole, imidazole, thiazole, pyridine, and quinaxoline derivatives are especially attractive. The present review highlights antiviral behavior of these heterocyclic compounds.