Synthesis of New Iminosugar Derivatives Based on (S)-(1,2,3,6-Tetrahydropyridazin-3-yl)methanol

(S)-(1,2,3,6-Tetrahydropyridazin-3-yl)methanol was synthesized in two steps by the Diels-Alder reaction of penta-2,4-dien-1-ol with diethyl azodicarboxylate in the presence of (S)-BINOL as chiral catalyst. The subsequent Boc-protection of the 2-position of the pyridazine ring, ring-closing carbonylation of the hydroxy group, and deprotection afforded a bicyclic iminosugar analog. The structure of the isolated compounds was proved by NMR, IR, and mass spectra and elemental analyses

Antimony-Doped Tin(II) Sulfide Thin Films

Thin-film solar cells made from earth-abundant, inexpensive, and nontoxic materials are needed to replace the current technologies whose widespread use is limited by their use of scarce, costly, and toxic elements. Tin monosulfide (SnS) is a promising candidate for making absorber layers in scalable, inexpensive, and nontoxic solar cells. SnS has always been observed to be a p-type semiconductor. Doping SnS to form an n-type semiconductor would permit the construction of solar cells with p-n homojunctions. This paper reports doping SnS films with antimony, a potential n-type dopant. Small amounts of antimony (1%) were found to greatly increase the electrical resistance of the SnS. The resulting intrinsic SnS(Sb) films could be used for the insulating layer in a p-i-n design for solar cells. Higher concentrations (5%) of antimony did not convert the SnS(Sb) to low-resistivity n-type conductivity, but instead the films retain such a high resistance that the conductivity type could not be determined. Extended X-ray absorption fine structure analysis reveals that the highly doped films contain precipitates of a secondary phase that has chemical bonds characteristic of metallic antimony, rather than the antimony–sulfur bonds found in films with lower concentrations of antimony.United States. Dept. of Energy. Sunshot Initiative (Contract DE-EE0005329)National Science Foundation (U.S.) (Grant CBET-1032955

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Anti-remodeling efficacy of eprosartan in patients with essential hypertension, and gene polymorphism of angiotensin II type 1 receptors

Aim. To study the effects of long-term eprosartan treatment efficacy on myocardial structure and function in patients with essential arterial hypertension (EAH), and the association of these effects with structural polymorphism of angiotensin II type 1 receptors (AT2RI). Material and methods. The study included 121 males with Stage II-III EAH (WHO/ISH, 1999), mean age 49.09±8.34 years, with disease duration of 2-15 years. Central hemodynamics parameters and left ventricular myocardial mass (LVMM) were assessed by echocardiography (EchoCG) method. Left ventricular hypertrophy (LVH) was identified, according to the values of LVMM and LVMM index (LVMMI). LVH was diagnosed in LVMMI &gt;134 g/m2. LV diastolic filling was assessed with Doppler EchoCG, by peak rates of early and late filling, and their ratio. Endothelial function was investigated with Doppler ultrasound. Prevalence of alleles and genotypes of polymorphic fragments (A1166C) of angiotensin II type 1 receptor gene was studied. The association of A/C polymorphism with hemodynamic parameters, LVH markers, endothelial function (EF), and eprosartan monotherapy efficacy, was also investigated. Results. A significant prevalence of A-allele and AA-genotype of AT1RII gene A1166C-polymorphic marker was observed. AC+CC genotypes were associated with more severe LVH, LV diastolic dysfunction, and EF disturbances. With equally high antihypertensive efficacy of 3-month eprosartan therapy, only AA-genotype patients demonstrated substantial LVH regression and complete normalization of vasoregulatory EF. Conclusion. Eprosartan demonstrated high antihypertensive efficacy in all participants. But only among AA-genotype patients, substantial LVH regression and complete normalization of vasoregulatory EF was observed during 3-month eprosartan therapy

MRI diagnosis of cortical dysplasia in the immature brain

Introduction. Cortical dysplasias (CDs) encompass a wide variety of disorders that in most cases lead to epilepsy, especially in infants and young children. MRI diagnosis of CDs is a major part of presurgical examination of pediatric patients with resistant focal epilepsy.Aim. To identify MR markers of CD in the immature brain and develop an MRI protocol for early diagnosis of CDs.Materials and methods. Children aged &lt;2 y.o. (total 128) diagnosed with focal epilepsy were examined over 2017-2019. All MRI scans were performed using the GE 3 T system (General Electric, USA) in the standard MR sequences including T2WI FSE, T1 SE, FLAIR, DWI, SWAN, and FSPGR BRAVO supported with anesthesiological assistance. Аll patients were divided into 3 groups according to the degree of brain maturity; of those, 28 patients had MR signs of CD.Results. The rate of detection of small-size cortical malformations, such as nodular heterotopies or focal cortical dysplasias was significantly higher in groups of patients whose brains (according to MR images) were at the infantile or adult phases of myelination. In children with the isointensive phase myelination, only large cortical dysplasias could be identified. In the first phase, the focal malformations had low amplitude signals in T2-weighted images and high amplitude signals in T1, unlike those in adult patients. In the isointensive phase, the quality of visualization was significantly reduced and provided poor diagnostic information.Conclusion. The results confirm the diagnostic significance of early (before age of 5 months) MRI testing in cases with suspected CD-associated focal epilepsy. However, at the period between 5 and 12 months of age, MR imaging was ineffective for CD diagnosing. Later, in the period from 12 to 15 months, the MRI ability to identify the CDs gradually increased. We consider the standard T2 weighted images with high TR values, the most effective MR modality for diagnosing CDs in young children

Early diagnosis of myopia in children using the apparatus "Plusoptix-A-09"

Були обстежені 28 дітей (56 очей) з короткозорістю різного ступеня увіці від 1 до 10 років з використанням бінокулярного рефрактометра "Plusoptix А09" і методом скіаскопії. Скіаскопію проводили на широкій зіниці після закапування 1% розчину. При проведенні авторефрактометрії на приладі «Plusoptix А09» дослідження проводили на вузькій зіниці. Міопія слабкого ступеня була виявлена на 32 очах (57,1%) випадків, середнього ступеня - 20 очах (35,7%) і високого ступеня - 4 очах (21,4%). Косоокість на тлі міопії спостерігалася на 14 очах (25%) випадків кут по Гіршбергу становив 10-15 градусів. Встановлено, що у дітей у віці 4-6 років астигматизм діагностували частіше за даними авторефрактометрії в 23,2% в порівнянні з даними скіаскопії - 16,0%. При порівнянні результатів скіаскопії в умовах циклоплегії і авторефрактометрії у дітей з міопічною рефракцією найбільш точний збіг результатів в умовах циклоплегії було виявлено у дітей 1-4 років життя (sph -7,1% і cyl - 5,3%). Невідповідність результатів порівнюваних методів найбільш часто виявляло ослаблення клінічної рефракції за даними авторефрактометрії «Plusoptix А09» щодо скіаскопічних даних у дітей з міопією слабкого ступеня на 1,0D. Лише в разі міопії середнього ступеня спостерігалося деяке посилення рефракції за даними «Plusoptix А09» в порівнянні з скіаскопічними даними на 0,75 - 1,0D. Показники при міопії високого ступеня при використанні обох методів були однакові. Висновки. Метод авторефрактометрії на приладі «Plusoptix А09» дозволив проводити авторефрактоме- трію у дітей будь-якої вікової категорії.Были обследованы 28 детей (56 глаз) с близорукостью различной степени в возрасте от 1 до 10 лет с использованием бинокулярного рефрактометра "Plusoptix А09” и методом скиаскопии. Скиаскопию проводили на широком зрачке после закапывания 1% раствора. При проведении авторефрактометрии на приборе "Plusoptix А09” исследование проводили на узком зрачке. Миопия слабой степени была выявлена на 32 глазах (57,1%) случаев, средней степени - 20 глазах (35,7%) и высокой степени — 4 глазах (21,4%). Косоглазие на фоне миопии наблюдалось на 14 глазах (25%) случаев угол по Гиршбергу составлял 10-15 градусов. Установлено, что у детей в возрасте 4-6 лет астигматизм диагностировался чаще по данным авторефрактометрии в 23,2% по сравнению с данными скиаскопии - 16,0%. При сравнении результатов скиаскопии в условиях циклоплегии и авторефрактометрии у детей с миопической рефракцией наиболее точное совпадение результатов в условиях циклоплегии было выявлено у детей 1-4 лет жизни (sph -7,1% и cyl - 5,3%). Несоответствие результатов сравниваемых методов наиболее часто выявляло ослабление клинической рефракции по данным авторефрактометрии "Plusoptix А09” относительно скиаскопических данных у детей с миопией слабой степени на 1,0D. Лишь в случае миопии средней степени наблюдалось некоторое усиление рефракции по данным "Plusoptix А09” по сравнению со скиаскопическими данными на 0,75 - 1,0D. Показатели при миопии высокой степени при использовании обоих методов были одинаковы. Выводы. Метод авторефрактометрии на приборе "Plusoptix А09” позволил проводить авторефрактометрию у детей любой возрастной категории.Goal. To conduct a comparative analysis of the method of skiascopy and autorefractometry and evaluate the effectiveness of the device “PLUSOPTIX-A09” identification of myopia in children of early age. Methods. Was examined 28 children (56 eyes) with myopia of various degrees aged from 1 to 10 years using a binocular Refractometer “Plusoptix A09” and the method of skiascopy at the National Center of Ophthalmology named. Acad. Z. Aliyeva. The skiascopy was performed on dilated pupils after instillation of 1% solution of Mydriacyl (firma Alcon) Express method 1 drop every 15 minutes 3 times and waited for the next 25-30 minutes, and then spent the skiascopy. When conducting autorefractometry on the device “Plusoptix A09” the study was conducted on a narrow pupil, how wide the pupil is an obstacle for examination of patients. The average age was 6.5±2 years. Were boys and 13 (46,4%) girls and 15 (53.5 per cent). Low degree of myopia were detected in 32 eyes (57.1 percent) of the cases, the average degree -20глазах (35.7%) and high degree - 4 eyes (21.4%) patients. Strabismus on the background of myopia was observed in 14 eyes (25 %) cases, the angle of Girshberg was 10-15 degrees. All patients underwent a comprehensive ophthalmic using standard techniques used in the examination of children of early age. Results. High myopia in children of early age were detected much less frequently in 12.5% of cases than school-age children from 5-8 years 50%. In respect of children aged 4-6 years, were more common spherical component at 16.0%, compared to children 7-10 years, dominated by astigmatism in 23.2% of cases. According to autorefractometry “Plusoptix A09” on the narrow pupil showed some changes in the parameters of clinical refraction of the eye. Found that children aged 4-6 years astigmatism was diagnosed more frequently according to autorefractometry at 23.2% compared to skiaskopia -16,0%. In addition, the indices of refraction in children 7-10 years showed some changes, in particular, a spherical component according to skiaskopia was 14.2 percent, astigmatic - 23,2%, the data autorefractometry showed respectively -16,0% and 21.4%. Comparing the results of skiascopy in terms of cycloplegia and autorefractometry in children with myopia. The most accurate matching results autorefractometry and skiascopy in terms of cycloplegia were identified in children 1 - 4 years of life (sph -7.1% and cyl - 5.3 percent). Inconsistency of the results of the compared methods, the most frequently identified weakening clinical refraction according to autorefractometry ’’Plusoptix A09” relatively skiaskopia data in children with myopia of 1.0 D. Only in the case of myopia of an average degree was observed some increase of the refraction according to the “Plusoptix A09” compared to skiascopic data 0,75 - 1,0 D. Indicators with high myopia when using both methods were identical. In most cases, the results autorefractometry with a narrow pupil in children of early age coincided with the results of skiascopy in terms of cycloplegia. The discrepancy between the results of autorefractometry and skiascopy was 0.5-1.0 D, depending on the degree of myopia