An elegant, atom efficient protocol via a one-pot four-component cyclocondensation reaction of aromatic aldehydes, malononitrile, acetylenedicarboxylates and arylamines catalyzed by copper(i) iodide ...in aqueous medium under ultrasound irradiation has been developed for the synthesis of a series of novel pharmacologically interesting polysubstituted 1,4-dihydropyridines. In comparison with the reported methods, our approach is expedient and offers several advantages such as: a shorter reaction time, excellent yields, milder conditions, convenience and environmental benignity. We have herein successfully demonstrated the utility of sonication in a multicomponent reaction (MCR), which exhibits a better functional group tolerance, and straightforward product isolation and purification by precipitation.
Variations of the sciatic nerve have been extensively studied in the past including its relationship with the piriformis muscle and associated clinical conditions like piriformis syndrome and ...sciatica. In the present study we noticed some interesting variations of the sciatic nerve, which were slightly different from the cases described earlier. In the previous studies most of the authors described the higher division of sciatic nerve and none of them discussed its formation. In this study we tried to look its formation from the sacral plexus and its divisions in the thigh. We noticed that in one cadaver the two components of the sciatic nerve originated directly from the sacral plexus and coursed down without merging in the thigh. Should this be called a higher division or non formation of the sciatic nerve? On the other hand in two other cadavers, the two divisions after emerging separately from the sacral plexus, united in the gluteal region and in the thigh respectively. Should we call this as higher division or low formation of the sciatic nerve? In two other cadavers the sciatic nerve emerged from the greater sciatic foramen below the piriformis and divided in the gluteal region itself. Ideally this should be called as higher division of sciatic nerve.
The structure–activity relationship study of a diphenylpropanamide series of ROR-γ selective modulators is reported. Compounds were screened using chimeric receptor Gal4 DNA-binding domain (DBD)-NR ...ligand binding domain cotransfection assay in a two-step format. Three different regions of the scaffold were modified to assess the effects on repression of ROR-γ transcriptional activity and potency. The lead compound 1 exhibits modest mouse pharmacokinetics and an acceptable in vitro profile which makes it a suitable in vivo probe to interrogate the functions of ROR-γ in animal models of disease.
This article considers the reception and genre of the Shāhnāmah in India. It takes as its starting-point comments made by the poet Mirza Asad Allah Khan Ghalib in 1866, moving on to look at a Mughal ...Shāhnāmah adaptation, the Tarikh-i dil-gusha-i Shamsher-Khani, and its Urdu translations, as well as other Persian, Urdu and Arabic texts. It investigates the (mis)identification of the Shāhnāmah’s genre, looking at cases in which it was understood as historiographical rather than as a romance, and seeking an explanation for this ‘contamination’ of the sincere genre of history by the mendacious romance genre. A methodological split in the historiographical corpus is proposed, between a rationalist (‘aqli) and transmission-based (naqli) method. The contest between these two methods is considered, and the prevalence of transmission-based history and its similarity to romance is brought forward as a possible reason for the porousness of the border between these ostensibly opposing genres.
Traumatic brain injury (TBI) proves to be an obstacle for Bangladeshi patients due to the lack of facilities and specialist doctors in regional sections of the country. This study aimed to record ...different attributes of Bangladeshi TBI patients over a year i.e., their injury characteristics, treatments received and understand their impacts on the severity of TBI.OBJECTIVETraumatic brain injury (TBI) proves to be an obstacle for Bangladeshi patients due to the lack of facilities and specialist doctors in regional sections of the country. This study aimed to record different attributes of Bangladeshi TBI patients over a year i.e., their injury characteristics, treatments received and understand their impacts on the severity of TBI.This cross-sectional study was carried out among 280 TBI patients treated in a tertiary care hospital in Dhaka. The physicians determined TBI's severity and prognosis as per the Glasgow Coma Scale (GCS) and Glasgow Outcome Score (GOS) respectively.METHODThis cross-sectional study was carried out among 280 TBI patients treated in a tertiary care hospital in Dhaka. The physicians determined TBI's severity and prognosis as per the Glasgow Coma Scale (GCS) and Glasgow Outcome Score (GOS) respectively.Most TBI patients were male (76.1%) and aged between 18 and 50 years (52.2%), as in previous studies in South Asian countries. However, the prevalence of TBI due to road traffic accidents (RTAs) was much higher (67.9%) than in the earlier studies in South Asia. Additionally, more patients suffered from severe TBI (29.3%) and moderate TBI (35.7%), and a higher percentage of patients went through surgery (56.8%) compared to previous studies. A significant association of demographic (residence) and clinical characteristics (consciousness after injury, CT scan findings and treatment type) with the severity of TBI was found in bivariate analysis. It also revealed the significant dependence of clinical characteristics (TBI etiology, post-injury consciousness, treatment type and TBI severity) on TBI prognosis. Multivariate analysis showed that patients who were unconscious after TBI and with evident brain injury observed in CT scans have a substantially higher risk of having moderate or severe TBI than mild TBI. Moreover, patients with TBI due to RTAs or falls, evident brain injury in CT scans, post-surgical seizure, and moderate or severe TBI have a significantly higher risk of getting a more unfavorable TBI prognosis than moderate disability.RESULTSMost TBI patients were male (76.1%) and aged between 18 and 50 years (52.2%), as in previous studies in South Asian countries. However, the prevalence of TBI due to road traffic accidents (RTAs) was much higher (67.9%) than in the earlier studies in South Asia. Additionally, more patients suffered from severe TBI (29.3%) and moderate TBI (35.7%), and a higher percentage of patients went through surgery (56.8%) compared to previous studies. A significant association of demographic (residence) and clinical characteristics (consciousness after injury, CT scan findings and treatment type) with the severity of TBI was found in bivariate analysis. It also revealed the significant dependence of clinical characteristics (TBI etiology, post-injury consciousness, treatment type and TBI severity) on TBI prognosis. Multivariate analysis showed that patients who were unconscious after TBI and with evident brain injury observed in CT scans have a substantially higher risk of having moderate or severe TBI than mild TBI. Moreover, patients with TBI due to RTAs or falls, evident brain injury in CT scans, post-surgical seizure, and moderate or severe TBI have a significantly higher risk of getting a more unfavorable TBI prognosis than moderate disability.In this study, RTAs were found to be the major cause of TBI. Additionally, some variables were identified as possible determinants of TBI severity and prognosis among Bangladeshi patients. The correlation of these variables with TBI should be further studied with the hopes that steps will be taken to reduce TBI incidents and improve its management to reduce the overall burden.CONCLUSIONSIn this study, RTAs were found to be the major cause of TBI. Additionally, some variables were identified as possible determinants of TBI severity and prognosis among Bangladeshi patients. The correlation of these variables with TBI should be further studied with the hopes that steps will be taken to reduce TBI incidents and improve its management to reduce the overall burden.
New optically pure isoxazoline-2-oxide and furan analogs have been synthesized using Pd(0) catalyzed intramolecular cyclizations. Starting from a
meso-diol, optically pure compounds were prepared ...without utilizing chiral ligands at any stage of the synthesis. The stereochemical outcome of the product (>99% ee) was influenced by desymmetrization catalyzed by
Pseudomonas cepacia lipase and the stereoselective nature of the palladium catalyzed transformations.
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NOD1 (nucleotide-binding oligomerization domain 1) protein is a member of the NLR (NACHT and leucine rich repeat domain containing proteins) protein family, which plays a key role in innate immunity ...as a sensor of specific microbial components derived from bacterial peptidoglycans and induction of inflammatory responses. Mutations in NOD proteins have been associated with various inflammatory diseases that affect NF-κB (nuclear factor κB) activity, a major signaling pathway involved in apoptosis, inflammation, and immune response. A luciferase-based reporter gene assay was utilized in a high-throughput screening program conducted under the NIH-sponsored Molecular Libraries Probe Production Center Network program to identify the active scaffolds. Herein, we report the chemical synthesis, structure–activity relationship studies, downstream counterscreens, secondary assay data, and pharmacological profiling of the 2-aminobenzimidazole lead (compound 1c, ML130) as a potent and selective inhibitor of NOD1-induced NF-κB activation.
Sojourners visiting high-altitude (HA) (>2500
m) are susceptible to HA disorders; on the contrary, HA natives are well adapted to the extreme hypoxic environment. High aldosterone levels are believed ...to be involved in HA disorders, we, therefore, envisaged role of
CYP11B2 gene variants in HA adaptation and therefore investigated the –344T/C, intron-2 conversion (Iw/Ic), K173R, and A5160C polymorphisms. In addition, polymorphisms in
AGT,
AT1R,
ATP1A1,
ADRB2, and
GSTP1 genes were also investigated. The study comprised of 662 subjects, comprising of 426 Himalayan highlanders (HLs) and 236 lowlanders (LLs). The –344T/C and K173R polymorphisms were found to be in complete linkage disequilibrium. The wild-type allele –344T and combination of wild-type homozygous genotypes between –344T/C, Iw/Ic, and A5160C polymorphisms, containing all the six wild-type alleles were over-represented in the HLs (
p
<
0.0001, and
p
=
0.008, respectively). The wild-type haplotypes –344T-Iw, –344T-5160A, and –344T-Iw-5160A also showed over-representation in the HLs (
p
<
0.0001). Furthermore, greater the number of wild-type alleles, lower was the ARR (
p
<
0.05). The genotype distribution in remaining genes did not differ. To conclude, the over-representation of wild-type −344T allele, genotype combinations and haplotypes of
CYP11B2, and their correlation with lower aldosterone levels associate with HA adaptation in the HLs. Such an allelic presentation in sojourners may help them cope with adverse HA environment.
The genes of the renin—angiotensin system (RAS) play an important role in the regulation of pulmonary vascular tone. Although studies on individual genes polymorphisms have reported association with ...high-altitude pulmonary oedema (HAPE), studies on multiple genes or epistasis are lacking. We therefore investigated the association of the RAS polymorphisms with HAPE. In a case-control design, we screened 163 HAPE-resistant/controls (HAPE-r) and 160 HAPEpatients (HAPE-p) of Indian origin for eight polymorphisms of four RAS genes, ACE, AGT, AGTR1 and AGTR2. Significant difference in genotype and allele frequencies of the ACE I/D and AGT M235T polymorphisms was observed between HAPE-p and HAPE-r (p < 0.05). In three-locus haplotype analysis of AGT the haplotype GTM was significantly higher in HAPE-p (29%) and haplotype GTT in HAPE-r (27%) after Bonferroni correction (p < 0.006). The differences were insignificant for polymorphisms from AGTR1 and AGTR2. The MDR (multifactor dimensional reduction) approach for gene—gene interaction depicted individual polymorphism M235T as the best disease predicting model (cross validation consistency, CVC = 10/10). We found a significant association of D allele of ACE and M allele of AGT with HAPE. The findings are supported at the haplotypic level as well as through nested genetic interaction between the RAS gene polymorphisms using the MDR approach.
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