The role of multiple sclerosis subtype in microvascular decompression outcomes for patients with trigeminal neuralgia.

OBJECTIVES: While patients with concomitant trigeminal neuralgia (TN) and multiple sclerosis (MS) are understood to experience a more intractable pain phenotype, whether TN pain outcomes differ by the presenting MS subtype is not well characterized. This study's objective is to compare post-operative pain and numbness outcomes following microvascular decompression (MVD) in TN patients with either relapsing-remitting MS (RRMS) or progressive MS. METHODS: We retrospectively reviewed all TN patients who underwent MVDs at our institution from 2007 to 2020. Of the 1044 patients reviewed, 45 (4.3%) patients with MS were identified. Patient demographics, procedural characteristics, and post-operative pain and numbness scores were recorded and compared. Factors associated with pain recurrence were assessed using survival analyses and multivariate regressions. RESULTS: Of the resulting 45 MS patients, 34 (75.6%) patients presented with the RRMS subtype, whereas 11 (24.4%) patients exhibited progressive MS. Using an adjusted multivariate ordinal regression, the subtype of MS was not significantly associated with the Barrow Neurological Institute (BNI) pain score at final follow-up. Using a Kaplan-Meier survival analysis and a multivariate Cox proportional hazards regression, respectively, RRMS was significantly associated with a shorter post-operative pain-free interval (p = 0.04) as well as a greater risk for pain recurrence (p = 0.02). CONCLUSIONS: Although the degree of pain at final follow-up may not differ, RRMS patients are at increased risk for pain recurrence following MVD for TN. These results align with a growing understanding that neuroinflammation may play a significant role in TN pain.

Head and Neck Cystic Lesions: A Cytology Review of Common and Uncommon Entities.

BACKGROUND: Cystic lesions of the head and neck are a diagnostic challenge since they are seen in the clinical presentation of a wide variety of conditions. Herein, common and uncommon entities that present as cystic lesions in the head and neck are reviewed. SUMMARY: In this study, peer-reviewed articles were selected using the database PubMed, Google, Google Scholar, and Scopus. Emphasis was placed on peer-reviewed articles that discuss the cytomorphology and differential diagnosis of entities that present as cystic lesions of the head and neck. In the anterior neck, both benign and malignant neoplasms can present, including papillary thyroid carcinoma (PTC), thyroid adenomatoid nodule, parathyroid cysts, and thyroglossal cysts. In the lateral neck, branchial cleft cyst, PTC, ectopic thyroid cyst, and squamous cell carcinomas (human papilloma virus and non- human papilloma virus-related) are common. Age over 40 years raises the possibility of malignancy. In the deep neck, mostly benign cystic entities occur such as a pleomorphic adenoma, paraganglioma, schwannoma, branchial cyst, epidermal inclusion cyst, and lymphoepithelial cyst. Lesions with squamous cell features can pose diagnostic dilemmas. CONCLUSION: Cytologic examination of head and neck cysts can provide valuable information regarding the nature of the cystic lesions. Information about anatomic site and clinical history can assist with the differential diagnoses. Ancillary studies can improve the diagnosis in some cases. Each case should be evaluated very carefully since there are a wide variety of congenital conditions, infectious/inflammatory conditions, benign neoplasms, and primary and secondary malignancies presenting as a cystic mass in the head and neck.

Multi-Drug Resistant Coliform: Water Sanitary Standards and Health Hazards.

Water constitutes and sustains life; however, its pollution afflicts its necessity, further worsening its scarcity. Coliform is one of the largest groups of bacteria evident in fecally polluted water, a major public health concern. Coliform thrive as commensals in the gut of warm-blooded animals, and are indefinitely passed through their feces into the environment. They are also called as model organisms as their presence is indicative of the prevalence of other potential pathogens, thus coliform are and unanimously employed as adept indicators of fecal pollution. As only a limited accessible source of fresh water is available on the planet, its contamination severely affects its usability. Coliform densities vary geographically and seasonally which leads to the lack of universally uniform regulatory guidelines regarding water potability often leads to ineffective detection of these model organisms and the misinterpretation of water quality status. Remedial measures such as disinfection, reducing the nutrient concentration or re-population doesn't hold context in huge lotic ecosystems such as freshwater rivers. There is also an escalating concern regarding the prevalence of multi-drug resistance in coliforms which renders antibiotic therapy incompetent. Antimicrobials are increasingly used in household, clinical, veterinary, animal husbandry and agricultural settings. Sub-optimal concentrations of these antimicrobials are unintentionally but regularly dispensed into the environment through seepages, sewages or runoffs from clinical or agricultural settings substantially adding to the ever-increasing pool of antibiotic resistance genes. When present below their minimum inhibitory concentration (MIC), these antimicrobials trigger the transfer of antibiotic-resistant genes that the coliform readily assimilate and further propagate to pathogens, the severity of which is evidenced by the high Multiple Antibiotic Resistance (MAR) index shown by the bacterial isolates procured from the environmental. This review attempts to assiduously anthologize the use of coliforms as water quality standards, their existent methods of detection and the issue of arising multi-drug resistance in them.

Molecular modeling and prediction of binding mode and relative binding affinity of Art-Qui-OH with P. falciparum Histo-Aspartic Protease (HAP).

The relative binding affinity in terms of ΔΔG (bind-cald) value of the antimalarial compound artemisinin-quinine hybrid is primarily derived and is discussed in this article with reference to the ΔG (bind-cald) values of two known inhibitors Pepstatin-A and KNI-10006 complexed with HAP enzyme. The ΔG (bind-cald) value for KNI-10006 and Pepstatin-A is -14.10 kcal/mol and -13.09 kcal/mol respectively. The MM-GB/SA scoring results in the relative binding energy (ΔΔG (bind-cald)) of the hybrid molecule with respect to Pepstatin-A as 2.43 kcal/mol and 3.44 kcal/mol against KNI-10006. The overall binding mode of Art-Qui-OH resembles that of Pepstatin-A binding in HAP active site. We suggest here that the ΔΔG (bind-cald) value & proposed binding mode of the Art-Qui-OH for HAP enzyme should be considered for further structure-based drug design effort.

Molecular modeling and evaluation of binding mode and affinity of artemisinin-quinine hybrid and its congeners with Fe-protoporphyrin-IX as a putative receptor.

A recent rational approach to anti-malarial drug design is characterized as "covalent biotherapy" involves linking of two molecules with individual intrinsic activity into a single agent, thus packaging dual activity into a single hybrid molecule. In view of this background and reported anti malaria synergism between artemisinin and quinine; we describe the computer-assisted docking to predict molecular interaction and binding affinity of Artemisinin-Quinine hybrid and its derivatives with the intraparasitic haeme group of human haemoglobin. Starting from a crystallographic structure of Fe-protoporphyrin-IX, binding modes, orientation of peroxide bridge (Fe-O distance), docking score and interaction energy are predicted using the docking molecular mechanics based on generalized Born/surface area (MM-GBSA) solvation model. Seven new ligands were identified with a favourable glide score (XP score) and binding free energy (ΔG) with reference to the experimental structure from a data set of thirty four hybrid derivatives. The result shows the conformational property of the drug-receptor interaction and may lead to rational design and synthesis of improved potent artemisinin based hybrid antimalarial that target haemozoin formation.

Computational identification of sweet wormwood (Artemisia annua) microRNA and their mRNA targets.

Despite its efficacy against malaria, the relatively low yield (0.01%-0.8%) of artemisinin in Artemisia annua is a serious limitation to the commercialization of the drug. A better understanding of the biosynthetic pathway of artemisinin and its regulation by both exogenous and endogenous factors is essential to improve artemisinin yield. Increasing evidence has shown that microRNAs (miRNAs) play multiple roles in various biological processes. In this study, we used previously known miRNAs from Arabidopsis and rice against expressed sequence tag (EST) database of A. annua to search for potential miRNAs and their targets in A. annua. A total of six potential miRNAs were predicted, which belong to the miR414 and miR1310 families. Furthermore, eight potential target genes were identified in this species. Among them, seven genes encode proteins that play important roles in artemisinin biosynthesis, including HMG-CoA reductase (HMGR), amorpha-4,11-diene synthase (ADS), farnesyl pyrophosphate synthase (FPS) and cytochrome P450. In addition, a gene coding for putative AINTEGUMENTA, which is involved in signal transduction and development, was also predicted as one of the targets. This is the first in silico study to indicate that miRNAs target genes encoding enzymes involved in artemisinin biosynthesis, which may help to understand the miRNA-mediated regulation of artemisinin biosynthesis in A. annua.