Nairobi Eye: A Clinico-epidemiological Study from A Tertiary Care Center of Central Nepal

Introduction: Periocular paederus dermatitis (Nairobi eye) is characterized by erythematous vesiculobullouslinear plaque with stinging sensation. It commonly occurs during rainy season. It has been describedin people living near agricultural fields due to the potential toxin pederin. This study aims to evaluate thedemographic profile and clinical presentation of patients with periocular paederus dermatitis in a tertiary carecenter. Methods: This was a descriptive, cross-sectional study evaluating patients attending dermatologyand/or ophthalmology department with features consistent with paederus dermatitis involving perioculararea from June to August, 2019. Relevant demographic and clinical data were obtained; clinical photographswere taken and histopathology performed among selected patients. Results: A total of 24 (14.8%) patients hadfeatures of Nairobi eye among 162 patients of paederus dermatitis. Majority of the patients were males (1.4:1)with mean age 29.08±13.38 years. The peak time of presentation was the first week of July (37.5%). Meantime period between onset of symptoms and presentation was 3.41±2.01 days. The lesions were unilateral inall cases, with predominant involvement of the right eye (62%). Burning sensation (80%) and itching (60%)were the predominant symptoms while conjunctival hyperemia (41.6%), seropurulent discharge (20.8%)and chemosis (16.6%) were the ocular findings. Most of the patients (n=17, 70.8%) noticed the lesion whilewaking up in the morning. Conclusion: The finding of the present study has shown that Nairobi eye isa common presentation during rainy season. Periocular findings with significant intraocular signs weredocumented to be presenting features among patients with periocular paederus dermatitis

Asymmetric Synthesis of -Borylated Amines via Rhodium-Catalyzed Hydroboration of Allylamine Derivatives

The Takacs group has explored different dimensions of Catalytic Asymmetric Hydroboration (CAHB) reaction mainly focusing on variety of amide, oxime ether and phosphonate directing groups. Inspired by the results obtained with BINOL- and TADDOL- derived chiral catalysts along with pinacolborane, we explored the potential of acyclic N-acyl allylamines as substrates for direct-hydroboration to prepare chiral amine derivatives bearing g-boronic ester functionality, yields up to 90% with 98:2 enantioselectivity. The major enantiomer obtained is independent of starting alkene geometry, revealing that rhodium-catalyzed cis/trans-alkene isomerization occurs prior to hydroboration. In this poster, we will discuss the generation of active catalysts starting from different pre-catalysts. We find that the counterion (e.g., BF4-, BArF-) plays an important role in the reaction. Furthermore, we find that the addition of an external fluoride source (e.g., tetrabutylammonium difluorotriphenylsilicate (TBAT)) significantly impacts the reaction rate. These and other observations lead us to consider a novel catalytic cycle initiated by a rhodium(I)-hydride complex. Finally, the stereospecific transformations of the newly generated C–B bond to access drug candidates will be highlighted to demonstrate the utility of these chiral synthons

Pharmacological Evaluation of the Long-Term Effects of Xanomeline on the M1 Muscarinic Acetylcholine Receptor

Xanomeline is a unique agonist of muscarinic receptors that possesses functional selectivity at the M1 and M4 receptor subtypes. It also exhibits wash-resistant binding to and activation of the receptor. In the present work we investigated the consequences of this type of binding of xanomeline on the binding characteristics and function of the M1 muscarinic receptor. Pretreatment of CHO cells that stably express the M1 receptor for 1 hr with increasing concentrations of xanomeline followed by washing and waiting for an additional 23 hr in control culture media transformed xanomeline-induced inhibition of [3H]NMS binding from monophasic to biphasic. The high-affinity xanomeline binding site exhibited three orders of magnitude higher affinity than in the case of xanomeline added directly to the binding assay medium containing control cells. These effects were associated with a marked decrease in maximal radioligand binding and attenuation of agonist-induced increase in PI hydrolysis and were qualitatively similar to those caused by continuous incubation of cells with xanomeline for 24 hr. Attenuation of agonist-induced PI hydrolysis by persistently-bound xanomeline developed with a time course that parallels the return of receptor activation by prebound xanomeline towards basal levels. Additional data indicated that blockade of the receptor orthosteric site or the use of a non-functional receptor mutant reversed the long-term effects of xanomeline, but not its persistent binding at an allosteric site. Furthermore, the long-term effects of xanomeline on the receptor are mainly due to receptor down-regulation rather than internalization

Dermatological Practice in Nepal during COVID-19 Crisis: Recommendations of National Panel of Experts

Introduction: Novel Coronavirus disease has caused a substantial halt to the ongoing world in every aspect. There are medical and social implications of the disease. Cutaneous manifestations have been reported to be a part of the disease as well. Dermatologists globally are in dilemma with the clinical practice because of the fear of acquiring the disease. Objectives: This article aims to recommend best practice measures that can be followed in local scenario for re-opening up of dermatological services in the context of Nepal. Materials and Methods: A preliminary draft for guidance on Dermatological services based on recommendations of American Academy of Dermatology, International league of Dermatological societies, National recommendations from Ministry of Health, Nepal was sent to a panel of national experts to determine the level of consensus in first week of April, 2020.  A preliminary survey was sent to all the members of Society of Dermatologists, Venereologists, and leprologists of Nepal on first week of June and a second draft was subsequently formed which was sent again to experts and revised based on the opinions of national experts. Results: A total of 19 experts participated in the preparation of draft and reached a national consensus after a series of revisions in preliminary draft. Conclusion: Agreements regarding the opening of practice in dermatology discipline have been summarized. Recommendations have been made for opening of dermatological services – opening of outpatient department, performing dermatosurgical and cosmetic procedures as well as strategies on triage of patients and use of masks

DNA-Sequence Variation Among Schistosoma mekongi Populations and Related Taxa; Phylogeography and the Current Distribution of Asian Schistosomiasis

Schistosomiasis is a disease caused by parasitic worms of the genus Schistosoma. In the lower Mekong river, schistosomiasis in humans is called Mekong schistosomiasis and is caused by Schistosoma mekongi. In the past, Mekong schistosomiasis was known only from the lower Mekong river. Here DNA-sequence variation is used to study the relationships and history of populations of S. mekongi. Populations from other rivers are compared and shown to be S. mekongi, thus confirming that this species is not restricted to only a small section of one river. The dates of divergence among populations are also estimated. Prior to this study it was assumed that S. mekongi originated in Yunnan, China, migrated southwards across Laos and into Cambodia, later becoming extinct in Laos (due to conditions unsuitable for transmission). In contrast, the dates estimated here indicate that S. mekongi entered Cambodia from Vietnam, 2.5–1 Ma. The pattern of genetic variation fits better with a more recent, and ongoing, northwards migration from Cambodia into Laos. The implications are that Mekong schistosomiasis is more widespread than once thought and that the human population at risk is up to 10 times greater than originally estimated. There is also an increased possibility of the spread of Mekong schistosomiasis across Laos

Convergent functional genomics of anxiety disorders: translational identification of genes, biomarkers, pathways and mechanisms

Anxiety disorders are prevalent and disabling yet understudied from a genetic standpoint, compared with other major psychiatric disorders such as bipolar disorder and schizophrenia. The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers. Human studies, particularly genetic ones, are susceptible to the issue of being underpowered, because of genetic heterogeneity, the effect of variable environmental exposure on gene expression, and difficulty of accrual of large, well phenotyped cohorts. Animal model gene expression studies, in a genetically homogeneous and experimentally tractable setting, can avoid artifacts and provide sensitivity of detection. Subsequent translational integration of the animal model datasets with human genetic and gene expression datasets can ensure cross-validatory power and specificity for illness. We have used a pharmacogenomic mouse model (involving treatments with an anxiogenic drug—yohimbine, and an anti-anxiety drug—diazepam) as a discovery engine for identification of anxiety candidate genes as well as potential blood biomarkers. Gene expression changes in key brain regions for anxiety (prefrontal cortex, amygdala and hippocampus) and blood were analyzed using a convergent functional genomics (CFG) approach, which integrates our new data with published human and animal model data, as a translational strategy of cross-matching and prioritizing findings. Our work identifies top candidate genes (such as FOS, GABBR1, NR4A2, DRD1, ADORA2A, QKI, RGS2, PTGDS, HSPA1B, DYNLL2, CCKBR and DBP), brain–blood biomarkers (such as FOS, QKI and HSPA1B), pathways (such as cAMP signaling) and mechanisms for anxiety disorders—notably signal transduction and reactivity to environment, with a prominent role for the hippocampus. Overall, this work complements our previous similar work (on bipolar mood disorders and schizophrenia) conducted over the last decade. It concludes our programmatic first pass mapping of the genomic landscape of the triad of major psychiatric disorder domains using CFG, and permitted us to uncover the significant genetic overlap between anxiety and these other major psychiatric disorders, notably the under-appreciated overlap with schizophrenia. PDE10A, TAC1 and other genes uncovered by our work provide a molecular basis for the frequently observed clinical co-morbidity and interdependence between anxiety and other major psychiatric disorders, and suggest schizo-anxiety as a possible new nosological domain