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Pyrrole is one of the most important azaheterocycles, due to its wide range of applications in pharmaceuticals and optoelectronic materials, coupled with its utility as an intermediate in natural products.

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Background Information on the course of SARS-CoV-2 infection in children with chronic kidney disease (CKD) is limited. Methods We retrospectively reviewed the presentation and outcomes of SARS-CoV-2 infection in patients with CKD followed at any of the four pediatric nephrology centers in New Delhi from April 2020 to June 2021. Outcomes, including cardiopulmonary and renal complications, were reported in relation to underlying disease category and illness severity at presentation. Results Underlying illness in 88 patients included nephrotic syndrome (50%), other CKD stages 1–4 (18.2%), CKD 5D (17%), and CKD 5T (14.8%). Thirty-two of 61 patients with symptomatic COVID-19 and 9/27 asymptomatic patients were admitted for median 10 (interquartile range 7–15) days. Seventeen (19.3%) patients developed moderate or severe COVID-19. Systemic complications, observed in 30 (34.1%), included acute kidney injury (AKI, 34.2%), COVID-19 pneumonia (15.9%), unrelated pulmonary disease (2.3%), and shock (4.5%). Nineteen (21.6%) had severe complications (AKI stage 2–3, encephalopathy, respiratory failure, shock). Eight (11%) of twelve (16.4%) patients with severe AKI required dialysis. Three (3.4%) patients, two with steroid-resistant nephrotic syndrome in relapse and one with CKD 1–4, died due to respiratory failure. Univariate logistic regression indicated that patients presenting with nephrotic syndrome in relapse or moderate to severe COVID-19 were at risk of AKI (respective odds ratio, 95%CI: 3.62, 1.01–12.99; 4.58, 1.06–19.86) and/or severe complications (respective odds ratio, 95%CI: 5.92, 1.99–17.66; 61.2, 6.99–536.01). Conclusions Children with CKD presenting with moderate-to-severe COVID-19 or in nephrotic syndrome relapse are at risk of severe complications, including severe AKI and mortality. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05218-1.

A new class of potent PI3Kα inhibitors is identified based on aryl substituted morpholino-triazine scaffold. The identified compounds showed not only a high level of enzymatic and cellular potency in nanomolar range but also high oral bioavailability. The three lead molecules (based on their in vitro potency) when evaluated further for in vitro metabolic stability as well as pharmacokinetic profile led to the identification of 26, as a candidate for further development. The IC50 and EC50 value of 26 is 60 and 500 nM, respectively, for PI3Kα enzyme inhibitory activity and ovarian cancer (A2780) cell line. The identified lead also showed a high level of microsomal stability and minimal inhibition activity for CYP3A4, CYP2C19, and CYP2D6 at 10 μM concentrations. The lead compound 26, demonstrated excellent oral bioavailability with an AUC of 5.2 μM at a dose of 3 mpk in mice and found to be well tolerated in mice when dosed at 30 mpk BID for 5 days.

Endogenous endophthalmitis is a rare but potentially blinding complication of neonatal sepsis. Early diagnosis and aggressive treatment are essential to avoid vision loss. Therapeutic options include systemic and intravitreal antibiotics, as well as vitrectomy in selected cases. We report a series of 6 premature very low birth weight neonates who developed endogenous endophthalmitis in our NICU over the past 3 years. Endophthalmitis was part of early-onset sepsis in 2 newborns, both of whom died, and late-onset sepsis in 4 newborns, of which 1 infant died. None of the neonates had any history of previous trauma or intervention to the eye. Maternal screening for congenital infections, including HIV, was negative in all. Causative organisms included Klebsiella pneumoniae (2 cases), Pseudomonas aeruginosa (2 cases), Methicillin-resistant Staphylococcus aureus (1 case), and Candida albicans (1 case). All bacterial isolates showed resistance to first-line antibiotics. Of the 3 survivors, 2 infants had normal vision in the affected eye, and 1 developed phthisis bulbi after corneal perforation and required enucleation. This report draws attention to the emergence of endophthalmitis as a complication of neonatal sepsis in places where, although survival of very low birth weight newborns has increased significantly due to improved care, the burden of infection continues to be high. We emphasize the importance of daily examination of eyes as a part of routine clinical care in septic newborns for early diagnosis of endophthalmitis and prompt intervention in consultation with an ophthalmologist to optimize the outcome.

Patients with carcinoid syndrome diarrhea that is not controlled with long‐acting somatostatin analogs can benefit from the addition of the tryptophan hydroxylase inhibitor, telotristat ethyl. This article evaluates the real‐world effectiveness of telotristat ethyl using patient‐reported data.

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