The association of ABCB1 gene polymorphism with clinical response to carbamazepine monotherapy in patients with epilepsy.

BACKGROUND: Epilepsy is a common neurological disease but around 30% of patients fail to respond to antiepileptic drug (AED) treatment. Genetic variation of the ATP-binding cassette subfamily B, member 1 (ABCB1) gene, a drug efflux transporter may infer treatment resistance by decreasing gastrointestinal absorption and preventing AED entry into the brain. This study examined the impact of ABCB1 genetic variants on carbamazepine responsiveness. MATERIALS AND METHODS: Genomic DNA was extracted from whole blood of 104 epileptic patients. Genotyping of 3 ABCB1 variants (c.C3435T, c.G2677T/A and c.C1236T) was undertaken using validated TaqMan allelic discrimination assays. Plasma carbamazepine levels were measured at 3 and 6 months following the initial dose using high-performance liquid chromatography (HPLC) alongside clinical outcomes evaluation. RESULTS: Nonresponse to carbamazepine (CBZ) was associated significantly with the ABCB1 variants c.C3435T, c.G2677T/A, c.C1236T and TTT, TTC haplotypes (P < 0.05). There was no significant association between variants and plasma CBZ level (P > 0.05). CONCLUSIONS: Our results showed that variant alleles of the ABCB1 gene and TTT, TTC haplotypes were significantly associated with CBZ resistance without affecting the plasma level of carbamazepine. The findings of this study may help to predict patient's response to treatment ultimately it will improve the personalized and evidence based treatment choice of patients with epilepsy.

Density Functional Theory Calculations and Molecular Docking Analyses of Flavonoids for Their Possible Application against the Acetylcholinesterase and Triose-Phosphate Isomerase Proteins of Rhipicephalus microplus.

Ticks and tick-borne diseases constitute a substantial hazard to the livestock industry. The rising costs and lack of availability of synthetic chemical acaricides for farmers with limited resources, tick resistance to current acaricides, and residual issues in meat and milk consumed by humans further aggravate the situation. Developing innovative, eco-friendly tick management techniques, such as natural products and commodities, is vital. Similarly, searching for effective and feasible treatments for tick-borne diseases is essential. Flavonoids are a class of natural chemicals with multiple bioactivities, including the inhibition of enzymes. We selected eighty flavonoids having enzyme inhibitory, insecticide, and pesticide properties. Flavonoids' inhibitory effects on the acetylcholinesterase (AChE1) and triose-phosphate isomerase (TIM) proteins of Rhipicephalus microplus were examined utilizing a molecular docking approach. Our research demonstrated that flavonoids interact with the active areas of proteins. Seven flavonoids (methylenebisphloridzin, thearubigin, fortunellin, quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), quercetagetin-7-O-(6-O-p-coumaroyl-ß-glucopyranoside), rutin, and kaempferol 3-neohesperidoside) were the most potent AChE1 inhibitors, while the other three flavonoids (quercetagetin-7-O-(6-O-caffeoyl-ß-d-glucopyranoside), isorhamnetin, and liquiritin) were the potent inhibitors of TIM. These computationally-driven discoveries are beneficial and can be utilized in assessing drug bioavailability in both in vitro and in vivo settings. This knowledge can create new strategies for managing ticks and tick-borne diseases.

The Novel Interplay between Commensal Gut Bacteria and Metabolites in Diet-Induced Hyperlipidemic Rats Treated with Simvastatin.

Hyperlipidemia is one kind of metabolic syndrome for which the treatment commonly includes simvastatin (SV). Individuals vary widely in statin responses, and growing evidence implicates gut microbiome involvement in this variability. However, the associated molecular mechanisms between metabolic improvement and microbiota composition following SV treatment are still not fully understood. In this study, combinatory approaches using ultrahigh-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF MS/MS)-based metabolomic profiling, PCR-denaturing gradient gel electrophoresis (PCR-DGGE), quantitative PCR (qPCR), and 16S rRNA gene sequencing-based gut microbiota profiling were performed to investigate the interplay of endogenous metabolites and the gut microbiota related to SV treatment. A total of 6 key differential endogenous metabolites were identified that affect the metabolism of amino acids (phenylalanine and tyrosine), unsaturated fatty acids (linoleic acid and 9-hydroxyoctadecadienoic acid (9-HODE)), and the functions of gut microbial metabolism. Moreover, a total of 22 differentially abundant taxa were obtained following SV treatment. Three bacterial taxa were identified to be involved in SV treatment, namely, Bacteroidaceae, Prevotellaceae, and Porphyromonadaceae. These findings suggested that the phenylalanine and tyrosine-associated amino acid metabolism pathways, as well as the linoleic acid and 9-HODE-associated unsaturated fatty acid metabolism pathways, which are involved in gut flora interactions, might be potential therapeutic targets for improvement in SV hypolipidemic efficacy. The mass spectrometric data have been deposited to MassIVE (https://massive.ucsd.edu/ProteoSAFe/static/massive.jsp). Username: MSV000087842_reviewer. Password: hardworkingzsr.

Updates on the Role of Probiotics against Different Health Issues: Focus on Lactobacillus.

This review article is built on the beneficial effects of Lactobacillus against different diseases, and a special focus has been made on its effects against neurological disorders, such as depression, multiple sclerosis, Alzheimer's, and Parkinson's disease. Probiotics are live microbes, which are found in fermented foods, beverages, and cultured milk and, when administered in an adequate dose, confer health benefits to the host. They are known as "health-friendly bacteria", normally residing in the human gut and involved in maintaining homeostatic conditions. Imbalance in gut microbiota results in the pathophysiology of several diseases entailing the GIT tract, skin, immune system, inflammation, and gut-brain axis. Recently, the use of probiotics has gained tremendous interest, because of their profound effects on the management of these disease conditions. Recent findings suggest that probiotics enrichment in different human and mouse disease models showed promising beneficial effects and results in the amelioration of disease symptoms. Thus, this review focuses on the current probiotics-based products, different disease models, variable markers measured during trials, and evidence obtained from past studies on the use of probiotics in the prevention and treatment of different diseases, covering the skin to the central nervous system diseases.

A Comprehensive Open-Source Simulation Framework for LiFi Communication.

Light Fidelity (LiFi) is a new candidate for wireless networking that utilizes the visible light spectrum and exploits the existing lighting infrastructure in the form of light-emitting diodes (LEDs). It provides point-to-point and point-to-multipoint communication on a bidirectional channel at very high data rates. However, the LiFi has small coverage, and its optical gain is closely related to the receiver's directionality vis-à-vis the transmitter, therefore it can experience frequent service outages. To provide reliable coverage, the LiFi is integrated with other networking technologies such as wireless fidelity (WiFi) thus forming a hybrid system. The hybrid LiFi/WiFi system faces many challenges including but not limited to seamless integration with the WiFi, support for mobility, handover management, resource sharing, and load balancing. The existing literature has addressed one or the other aspect of the issues facing LiFi systems. There are limited free source tools available to holistically address these challenges in a scalable manner. To this end, we have developed an open-source simulation framework based on the network simulator 3 (ns-3), which realizes critical aspects of the LiFi wireless network. Our developed ns-3 LiFi framework provides a fully functional AP equipped with the physical layer and medium access control (MAC), a mobility model for the user device, and integration between LiFi and WiFi with a handover facility. Simulation results are produced to demonstrate the mobility and handover capabilities, and the performance gains from the LiFi-WiFi hybrid system in terms of packet delay, throughput, packet drop ratio (PDR), and fairness between users. The source code of the framework is made available for the use of the research community.

Gut microbial dysbiosis and its association with esophageal cancer.

Due to its aggressive nature and low survival rate, esophageal cancer is one of the deadliest cancer. While the intestinal microbiome significantly influences human health and disease. This research aimed to investigate and characterize the relative abundance of intestinal bacterial composition in esophageal cancer patients. The fecal samples were collected from esophageal cancer patients (n = 15) and healthy volunteers (n = 10). The PCR-DGGE was carried out by focusing on the V3 region of the 16S rRNA gene, and qPCR was performed for Bacteroides vulgatus, Escherichia coli, Bifidobacterium, Clostridium leptum and Lactobacillus. High-throughput sequencing of the 16S rRNA gene targeting the V3+V4 region was performed on 20 randomly selected samples. PCR-DGGE and High-throughput diversity results showed a significant alteration of gut bacterial composition between the experimental and control groups, which indicates the gut microbial dysbiosis in esophageal cancer patients. At the phylum level, there was significant enrichment of Bacteroidetes, while a non-significant decrease of Firmicutes in the experimental group. At family statistics, a significantly higher level of Bacteroidaceae and Enterobacteriaceae, while a significantly lower abundance of Prevotellaceae and Veillonellaceae were observed. There was a significantly high prevalence of genera Bacteroides, Escherichia-Shigella, while a significantly lower abundance of Prevotella_9 and Dialister in the experimental group as compared to the control group. Furthermore, the species analysis also showed significantly raised level of Bacteroides vulgatus and Escherichia coli in the experimental group. These findings revealed a significant gut microbial dysbiosis in esophageal cancer patients. So, the current study can be used for the understanding of esophageal cancer treatment, disease pathway, mechanism, and probiotic development.

Moxifloxacin and gemifloxacin mediates its antispasmodic profile via ATP-sensitive potassium channels: An in-vitro bioassay study.

Moxifloxacin and gemifloxacin were tested on isolated rabbits' jejunal preparations as little is known about its effects on gastrointestinal tissues. Moxifloxacin and gemifloxacin were tested in concentrations 0.01-10µg/mL for possible effect(s) on isolated rabbits' jejunal preparations. The drugs were applied on spontaneous, on low K+ (20mM)-induced contractions and on high K+ (80mM)-induced contractions. Response was plotted as % of its respective controls. EC50 for Moxifloxacin and Gemifloxacin on spontaneous (without Glibenclamide) contractions are 2.83±0.5µg/mL and 1.11±0.2µg/mL, respectively. Moxifloxacin and Gemifloxacin relaxed the low K+ (20mM) -induced contractions, which were inhibited in presence of Glibenclamide (3µM). Our result indicates that the relaxant activity of Moxifloxacin and Gemifloxacin is mediated possibly through activation of ATP-sensitive potassium channels (KATP). The relaxant effect of Moxifloxacin and Gemifloxacin is predominantly mediated by activation of ATP-Sensitive potassium channels (KATP), which could be cause of one of relaxing mechanisms.

Molecular characterization of gut microbial shift in SD rats after death for 30 days.

To observe the temporal shifts of the intestinal microbial community structure and diversity in rats for 30 days after death. Rectal swabs were collected from rats before death (BD) and on day 1, 5, 10, 15, 20, 25, and 30 after death (AD). Bacteria genomic DNA was extracted and V3 + V4 regions of 16S rRNA gene were amplified by PCR. The amplicons were sequenced at Illumina MiSeq sequencing platform. The bacterial diversity and richness showed similar results from day 1 to 5 and day 10 to 25 all presenting downtrend, while from day 5 to 10 showed slightly increased. The relative abundance of Firmicutes and Proteobacteria displayed inverse variation in day 1, 5, 10 and that was the former decreased, the latter increased. Bacteroidetes, Spirochaete and TM7 in day 15, 20, 25, 30 was significantly decline comparing with BD. Enterococcus and Proteus displayed reduced trend over day 1, 5, 10 and day 10, 15, 20, 25, respectively, while Sporosarcina showed obvious elevation during day 15, 20, 25. Accordingly, there was a certain correlation between intestinal flora succession and the time of death. The results suggested that intestinal flora may be potential indicator to aid estimation of post-mortem interval (PMI).

Bipartite Gaussian quantum steering, entanglement, and discord and their interconnection via a parametric down-converter.

In this study, we quantify quantum steering, quantum entanglement, and quantum discord and their interconnection using the technique of parametric down-conversion. Initially, two single-mode Gaussian states together with a non-linear crystal in a cavity are considered. The behavior of the three kinds of quantum correlations depend on the phase of the coherent pump field, purity, and non-classicality of the input states, and the damping rates of the cavity. The amount and time evolution of the quantum correlations enhances with the difference between the non-classicality of the initial states. In presence of the damping rates, the quantum steering and quantum entanglement (quantum discord) increase (decreases) with the purity of the input cavity field. We note that the amount and survival time of the quantum correlations can be controlled by varying the relative phase associated to the coherent pump field. The boundaries of the three kinds of quantum correlations are defined and explained with respect to each other, which form a hierarchy.

State, religion and the marginalisation of traditional healing in Gwadar, Pakistan.

This ethnographic encounter explores suppression and domination faced by traditional health seekers in Gwadar, Pakistan. The study aimed to provide an insight into the ways in which practicing traditional healthcare becomes a challenge when it conflicts with the assimilationist project of the state. Qualitative research methods, including in-depth interviews and participant observation, were used to collect data on the encounters of traditional health seekers with the state and dominant religion. The findings show that traditional health seeking behaviour was stereotyped as non-civilised and archaic by medical staff, and labelled as non-religious, and thus, suppressed by radical Islamist groups and other state apparatuses. This situation has further negative effects on the health of traditional health seekers as the national healthcare system does not efficiently provide the services required by this population. State laws, a general environment of fear, and threats have led this population to legal consciousness and contextual awareness; they have further adopted multiple resistance strategies to navigate and circumvent oppressive laws and domination in order to follow their traditional healthcare practices. This study suggests that national cosmopolitan healthcare services provided to the fishing community should be tailored to and not suppress the culturally specific health needs of that population. Members of the fishing community should not be compelled to abstain from their traditional healthcare and health-seeking behaviours; traditional healthcare practices should be merged with cosmopolitan ones in order to address the sociocultural issues and meet the health needs of this marginalised population.

Relaxant activity of different fractions of fruits of Rosa moschata J.

The current work is an attempt to know that in which fraction(s) the relaxant constituents of Rosa moschata concentrate. Crude methanolic extract of Rosa moschata was prepared as per our reported procedure. Sub fractions of methanol extract were extracted with different solvents in increasing order of polarity i.e. n-hexane > chloroform > ethyl acetate > n-butanol > residual aqueous fractions. Different concentrations (0.01, 0.03, 0.1, 0.3, 1, 3, 5 and 10 mg/ml) of the fractions were tested on spontaneous contractions and KCl induced contractions on rabbits' jejunal preparations. Calcium Concentration Response Curves (CCRCs) in the presence and absence of the test fractions using verapamil were constructed to understand its mechanisms. EtOA fraction was more relaxant with EC50 values 0.812±0.149 mg/ml on spontaneous and 2.01±0.08 mg/ml on KCl induced contractions. we also found right shift in its EC50 values expressed as log [Ca++]M values. In presence of 0.3 mg/ml EtOA fraction, its EC50 value was -2.22±0.035 vs control EC50 -2.71±0.21. For n-BuOH fraction, EC50 value was -1.82±0.00 vs control with EC50 -2.28±0.049 at concentration of 0.3 mg/ml. Ethyl acetate fraction of Rosa moschata was more potent and is therefore can be a target for activity guided isolation of calcium channel antagonists.

Hierarchy of temporal quantum correlations using a correlated spontaneous emission laser.

As an active quantum system, the correlated spontaneous emission laser has many valuable applications in quantum information processing. Here, we report on temporal evolution of the quantum correlations such as quantum discord, entanglement, steering, and Bell non-locality for the field retrieved in the form of two-mode Gaussian state using a system of correlated spontaneous emission laser. We consider the initial modes of the cavity field as two independent arbitrary single-mode Gaussian states inside the cavity. The density matrix for the resulting cavity field is evaluated both analytically and numerically with respect to the time evolution of the laser system. The influences of the non-classicality and purity of the initial cavity modes, the Rabi frequency of the classical coupling field, and the cavity damping rates are studied thoroughly. We show explicitly that the boundaries for the four kinds of the temporal quantum correlations of the cavity field retrieved satisfy a strict hierarchy.

Effect of Exercise Interventions on Kainate Induced Status Epilepticus and Associated Co-morbidities; A Systematic Review and Meta-Analysis.

PURPOSE: To conduct a systematic review and meta-analysis of studies testing the effect of exercise in Kainic-acid (KA) induced status-epilepticus (SE) and to quantify the efficacy of exercise strategies in the prognosis of SE and co-morbidities. METHODS: Two authors searched online databases (Pubmed and Web of Science) independently for studies testing the efficacy of exercise programs in KA-induced SE models. Reviewers autonomously extracted data on models used, exercise interventions and prognosis in all reported outcomes (behavioral, histological, biochemical and cognitive outcomes). All studies were summarized and relevant outcomes' data were pooled by means of a meta-analysis. RESULTS: Among 14 selected studies; Quantitative analysis of studies with pre-SE exercise interventions showed significant reduction in mortality rate among 76 animals of four studies (RR = 0.57, [95% CI 0.34, 0.95], p = 0.03, I2 = 57%) and seizure rating score among three studies (n = 56) with MD = - 1.04, [95% CI - 2.07, - 0.00], p = 0.05, I2 = 71%. Three studies (n = 62) presented with improved anti-oxidant enzymes' profile (SMD = 0.75, [95% CI 0.55, 2.31], p = 0.0008, I2 = 44%) as a result of exercise intervention. Same intervention failed to show any significant measure for BDNF level and neuroprotection assessed through neuronal number in different brain areas with MD = - 1.22, [95% CI - 136.66, 134.22], p = 0.99, I2 = 0% and SMD = - 0.05, [95% CI - 0.62, 0.52], p = 0.86, I2 = 61% respectively. Qualitative review concluded in the reduction of median seizure score, depression and anxiety-like behaviors with improved cognitive performances in pre-SE exercised animals while improved memory and learning capabilities with increased neurogenesis were observed in post-SE exercised models. CONCLUSIONS: Exercise before SE reduces behavioral seizures and oxidative stress with improvements in cognitive abilities. Post-SE exercise enhances learning and memory with neurogenesis in KA models. More extensive research on morphological and biochemical profiles is needed to explore underlying mechanisms.

Quantum steering of a two-mode Gaussian state using a quantum beat laser.

We study the quantum steering of a two-mode Gaussian state evolved by a simple quantum beat laser with the cavity field being initially in arbitrary two single-mode Gaussian states and the lasing medium being driven by a strong classical field. In presence of the cavity damping, the quantum steering time of the two-mode Gaussian state increases with the relative intensity of the coupling fields, whereas the relative phase switches the steerable states into the non-steerable and vice versa. We further show that the higher the non-classicality of the initial cavity modes, the longer the time of steerability in the two-mode Gaussian state. Nonetheless, the quantum steering is irrespective of the influence from the purity of the initial cavity modes of the laser system.

Coherence control of entanglement dynamics of two-mode Gaussian state via Raman driven quantum beat laser using Simon's criterion.

We study the entanglement dynamics of two-mode Gaussian state (TMGS) in a quantum beat laser driven by two classical fields in Raman configuration using Simon's criterion of quantum state separability. The two modes of the cavity field are considered initially in general single-mode Gaussian states. The effect of the non-classicality, purity, and relative phase of the cavity modes on the entanglement phenomenon is studied thoroughly. We show that in the presence of cavity decay rates, the higher the non-classicality of the initial states, the higher is the inseparability of the evolved TMGS of the cavity field. The inseparability, on the other side, is independent of the purity of the initial states. Moreover, the time scale of the entangled state increases with the relative intensity of the driving fields, whereas the relative phase switches the entangled state into the disentangled state of the cavity field and vice versa. The quantum statistics of the mean photons number of the cavity field is analyzed.

Visible Light Communication: A System Perspective-Overview and Challenges.

Visible light communication (VLC) is a new paradigm that could revolutionise the future of wireless communication. In VLC, information is transmitted through modulating the visible light spectrum (400⁻700 nm) that is used for illumination. Analytical and experimental work has shown the potential of VLC to provide high-speed data communication with the added advantage of improved energy efficiency and communication security/privacy. VLC is still in the early phase of research. There are fewer review articles published on this topic mostly addressing the physical layer research. Unlike other reviews, this article gives a system prespective of VLC along with the survey on existing literature and potential challenges toward the implementation and integration of VLC.

Nootropic effects of synthetic flavonoid derivatives on scopolamine induced memory impairment in mice via cholinesterase inhibition and antioxidant system.

The synthesized flavonoid derivatives (flavonols and flavones) were subjected for in-vitro anticholinesterase evaluation followed by assessment of in-vivo memory enhancing effects using animal models. The ex-vivo analysis of brain was carried out and portions were subjected foe estimation of biochemical parameters that includes AChE, ACh, SOD and CAT level. Among tested flavonoids, the para substituted chloro containing flavonol (OF2) and flavone (F2) revealed a considerable in-vitro AChE and BuChE % inhibition with an IC50 values. It was observed from the in-vivo results that OF1-OF3 at 12.5 mg/kg b.w has significance over F1-F3 in ameliorating the memory in scopolamine induced amnesic mice in passive avoidance step through and novel object recognitions test. Scopolamine elevated significantly the AChE level, decreased the contents of ACh, SOD and CAT in the brain in amnesic model. The flavonoid derivatives showed significant effects on these changes by decreasing the ex-vivo AChE contents, enhancing the level of ACh, SOD and CAT suggesting their possible role as cholinesterase and antioxidant. These findings suggest that synthetic flavonols and flavones may serve as potential candidates for developing safer and effective nootropic agents.

Antidiabetic potential of flavonoids from Artemisia macrocephalla Jaquem in streptozotocin-induced diabetic rats: Pharmacological and biochemical approach.

Plants belongs to Asteraceae family are reported to be rich in major phytochemical including flavonoids and are documented to acquire antidiabetic response. Antidiabetic effects of salvigenin, eupatilin and cirsilineol were screened on in-vitro enzyme inhibition and in-vivo streptozotocin animal models. Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) produced antidiabteic responses in streptozotocin model for diabetes. All natural flavonoids reduces the blood glucose level to a significant level (*P<0.05, **P<0.01, ***P<0.001, n=8) but promising results were observed in eupatilin at dose of 7.5mk/kg (364.12±4.3 to 128.41±4.2mg/dL, n=8) and at dose of 7.5mk/kg 363.65±4.8 to 126.14±5.1mg/dL, n=8). Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) for 28 days showed a substantial fall (*P<0.05, **P<0.01, ***P<0.001, n=8) in total cholesterol, LDL and triglcerides (TGs) in comparison to diabetic model. The isolated flavonoids reduced considerably the serum ALP, SGPT and SGOT in rats intoxicated with streptozotocin. The results indicate that the flavonoids may be useful in the development of new antidiabetic drugs.

Total Endoscopic or Endoscope-Assisted Excision of Non-embolized Advanced Juvenile Nasopharyngeal Angiofibroma: A Clinical Case Series.

Background Surgical excision is the primary treatment for juvenile nasopharyngeal angiofibroma (JNA), but this procedure is challenging due to its high vascularity and local aggressiveness. Moreover, preoperative embolization is a subject of debate. Objective The objective of this study is to assess the efficacy, safety, and feasibility of endoscope-assisted excision as a surgical intervention for non-embolized advanced JNA. Materials and methods This case series involved six male patients (mean age: 16 years) with JNA, classified as stages Ⅱc to Ⅲb according to the Radkowski classification. None underwent preoperative embolization. Results Two stage Ⅱc cases underwent total endoscopic endonasal excision. One patient with stage Ⅲa and another with stage Ⅲb underwent surgery via an endoscope-assisted sublabial approach. Two patients, one with stage Ⅱc JNA and another with Ⅲb, underwent a two-stage procedure. Postoperative CT scans showed no residual disease at the six-month mark. On average, each procedure required 1.5 units of blood transfusion. One patient experienced intraoperative bleeding, whereas the remaining patients were free of any major complications. The mean operation duration was 175 minutes per procedure. The mean length of stay at the hospital was 3.75 days per procedure. Conclusion Endoscope-assisted or purely endoscopic approaches can be safely and effectively employed for the complete excision of non-embolized advanced JNAs.