Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis.

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis.

Th17-associated cytokines IL-17 and IL-23 in inflamed skin of Darier disease patients as potential therapeutic targets.

Darier disease (DD) is a rare, inherited multi-organ disorder associated with mutations in the ATP2A2 gene. DD patients often have skin involvement characterized by malodorous, inflamed skin and recurrent, severe infections. Therapeutic options are limited and inadequate for the long-term management of this chronic disease. The aim of this study was to characterize the cutaneous immune infiltrate in DD skin lesions in detail and to identify new therapeutic targets. Using gene and protein expression profiling assays including scRNA sequencing, we demonstrate enhanced expression of Th17-related genes and cytokines and increased numbers of Th17 cells in six DD patients. We provide evidence that targeting the IL-17/IL-23 axis in a case series of three DD patients with monoclonal antibodies is efficacious with significant clinical improvement. As DD is a chronic, relapsing disease, our findings might pave the way toward additional options for the long-term management of skin inflammation in patients with DD.

Rohitukine content across the geographical distribution of Dysoxylum binectariferum Hook F. and its natural derivatives as potential sources of CDK inhibitors.

Dysoxylum binectariferum is an important medicinal plant distributed in the Western Ghats of India. The species has gained international importance for its anticancer component, rohitukine, a chromone alkaloid. Flavopiridol, P-276-00 and IIIM-290 are the derivatives of rohitukine in clinical trials against a wide range of cancers. Flavopiridol was recently approved as an orphan drug for chronic lymphocytic leukemia treatment. In this study, we report the isolation and characterization of rohitukine from the bark of D. binectariferum. Further, rohitukine was estimated across the Western-Ghats and the North-East regions of India. Additionally, D. binectariferum is also reported (∼45 compounds) to produce many natural derivatives of rohitukine and terpenoids, which were investigated in-silico to reveal promising CDK inhibitors. The metabolite fingerprinting of tissues of D. binectariferum was studied using HPTLC and FTIR. The distribution of major chromone alkaloid rohitukine was estimated by HPLC. Further, the pharmacological potential of D. binectariferum compounds was evaluated in-silico by discovering the potential protein targets, molecular docking, ADMET analysis and MD simulation. The isolation of rohitukine has yielded 0.6% from the bark of D. binectariferum. A higher percent of rohitukine was found in the Jog populations (0.58% & 1.28%: leaf & bark), whereas least was observed in the Phasighat population (∼0.06%: both leaf & bark). Across the geographic regions, a higher percent of rohitukine was found in the Central-southern Western Ghats, whereas lower in the northern parts of the Western Ghats and Northeast regions. The leaves produce a considerably higher percent of rohitukine and could be used as a sustainable source of rohitukine. The rohitukine analogues, along with other chromone alkaloids of D. binecatariferum were found to be more interactive with the "kinases" family of proteins, majorly "Serine/threonine-protein kinase PFTAIRE-2" (CDK15) with high confidence level (0.94-0.98). The molecular docking of these chromone alkaloids found a strong binding energy with six CDKs (-3.1 to -10.6 kcal/mol) along with a promising ADMET profile. In addition, molecular dynamic simulation found that the rohitukine complexes are virtually constant with CDK-1, 2, 9 and 15, which is substantiated with MM-PBSA free energy calculations. The chromone alkaloids, majorly rohitukine and its analogues were closely clustered with flavopiridol, P-276-00 and IIIM-290 along with other chrotacumines in the chemical phylogeny. In conclusion, D. binectariferum is a rich source of chromone alkaloids, which could lead to the discovery of more potential scaffolding for CDK inhibitors as anticancer drugs.

Recent advances in nanoparticles towards sustainability and their application in organic transformations in aqueous media.

Nanoparticles (NPs) play a crucial role in organic transformation and are becoming increasingly attractive in the field of catalysis as they show good catalytic activity in organic as well as aqueous media. Numerous NPs have been utilized for several organic transformations in aqueous media, which have led to dedicated efforts for the complete coverage of the application of metal, metal oxide, bimetallic and supported NPs in water-mediated organic transformations in the last decades. This review aims to provide current highlights on the application of various types of metal NPs for organic transformations in aqueous media. The remarkable benefits associated with the catalytic application of NPs in water allows for various transformations to be performed under very mild and green conditions. Lastly, the author's perspectives are briefly considered, including future developments and crucial challenges in the ever-growing field of nanocatalysis.

A brief review on critical analytical aspects for quantification of ambroxol in biological samples.

Ambroxol (AMB) is a member of the expectorant class, widely used as a secreolytic agent in patients to break up secretions. AMB is rapidly and effectively distributed from blood to tissue. The lungs have the highest concentration of AMB; accumulation of AMB in human lung tissue was detected at concentrations 15- to 20-fold greater than those reported in the circulation. Because of its wide range of actions and therapeutic applications may be worth looking into, particularly for respiratory symptoms, antioxidant, anti-inflammatory, influenza, and rhinovirus infections. Though several analytical methodologies have been established and confirmed for the AMB analysis in matrices of pharmaceutical and biological origins, novel sustainable, and economical methods are still to be choice of protocol to increase its sensitivity, reliability, and repeatability. Therefore, the present review offers an overview of critical analytical aspects regarding the HPLC, LC-MS/MS, HPTLC, capillary electrophoresis, spectrophotometry, and electrochemical methods for quantifying AMB in pharmaceutical and biological samples. Furthermore, this review will thoroughly discuss the physicochemical properties, stability, extraction conditions, instrumentation, and operational parameters of the targeted analyte. As a result, for the first time, this review complies with vital background information and an up-to-date interpretation of research undertaken by anticipated methodologies examined and implemented for the pharmaceutical analysis AMB.

Parameter Identification of Cardiovascular System Model Used for Left Ventricular Assist Device Algorithms.

Advancement of implanted left ventricular assist device (LVAD) technology includes modern sensing and control methods to enable online diagnostics and monitoring of patients using on-board sensors. These methods often rely on a cardiovascular system (CVS) model, the parameters of which must be identified for the specific patient. Some of these, such as the systemic vascular resistance (SVR), can be estimated online while others must be identified separately. This paper describes a three-staged approach for designing a parameter identification algorithm (PIA) for this problem. The approach is demonstrated using a two-element Windkessel model of the systemic circulation (SC) with a time-varying elastance for the left ventricle (LV). A parameter identifiability stage is followed by identification using an unscented Kalman filter (UKF), which uses measurements of LV pressure (Plv), aortic pressure (Pao), aortic flow (Qa), and known input measurement of LVAD flowrate (Qvad). Both simulation and experimental data from animal experiments were used to evaluate the presented methods. By bounding the initial guess for left ventricular volume, the identified CVS model is able to reproduce signals of Plv, Pao, and Qa within a normalized root mean squared error (nRMSE) of 5.1%, 19%, and 11%, respectively, during simulations. Experimentally, the identified model is able to estimate SVR with an accuracy of 3.4% compared with values from invasive measurements. Diagnostics and physiological control algorithms on-board modern LVADs could use CVS models other than those shown here, and the presented approach is easily adaptable to them. The methods also demonstrate how to test the robustness and accuracy of the identification algorithm.

The Impact of "COVID-19" and "Webinar Pandemic" on Plastic Surgery Practice in Teaching Institutes and Resident Training-A Multicentric Perspective.

Introduction The study was carried out to quantify the changes induced by the pandemic in plastic surgery practice and training and to study the impact of the webinars on plastic surgery education from a residents' perspective. Methods In this multicentric study, the number and type of surgeries, cause of injuries, and their regional variation during the coronavirus disease 2019 (COVID-19) period (February-September 2020) were compared with pre-COVID-19 time. An online survey on the impact of webinars was conducted for plastic surgery trainees across the country. Results There was a significant reduction in total number of surgeries ( p = 0.003). The procedures for hand ( p = 0.156), faciomaxillary injuries ( p = 0.25), and replantations ( p = 0.46) were comparable; there was a significant reduction in combined orthopedic-plastic-surgical procedures ( p = 0.009) during the pandemic. There was a significant reduction in road accidents ( p = 0.007) and suicidal injuries ( p = 0.002) and increase in assault ( p = 0.03) and domestic accidents ( p = 0.01) during the COVID-19 period. A usefulness score of >8 was given for the webinars by 68.7% residents. There was no significant difference in perception of utility when correlated with the academic program at their institutes ( p = 0.109); 92% opined webinars should continue in post-COVID times. Conclusion There was a drastic reduction in number of elective and emergency procedures during the COVID-19 time, negatively affecting resident training program. Majority of residents felt that webinars could prove a useful adjunct to training in formal training program in post-COVID-19 scenario.

Hybrid Mock Circulatory Loop Simulation of Extreme Cardiac Events.

OBJECTIVE: This paper presents preliminary methods of incorporating the pathological conditions of cardiac arrhythmias and valvular stenosis in hybrid mock circulation loop (hMCL) operation for the enhanced verification and validation of mechanical circulatory support devices such as VADs. METHODS: The MGH/MF Waveform datasets from PhysioNet database (including both nominal and clinically diagnosed arrhythmic ECG measurements) as well as cardiovascular system model updates are used to recreate arrhythmic events and valvular stenosis in vitro. RESULTS: Preliminary results show the hMCL can recreate each tested cardiac event within 2% and 4% mean error for reference pressure tracking in the aortic and left ventricular pressure chambers, respectively. Further, frequency spectrum analysis comparisons using the magnitude-squared coherence analysis shows close alignment between measured arrhythmic and hMCL realized pressure frequency content. CONCLUSION: The generation of cardiac arrhythmias and valvular stenosis around a VAD via both model and acute measurement based methods was achieved. SIGNIFICANCE: Pathological conditions such as cardiac arrhythmias and valvular stenosis are limited in documentation despite the large percentage of patients who experience these events. This paper provides a means to begin incorporating these events into hardware-in-the-loop mock circulatory systems for next generation VAD validation and verification.

HPLC-PDA identification and resolution of rufinamide forced degradation impurities: A congregated chemometric expedite optimization coupled with factorials and desirability.

Rufinamide is used presently to treat Lenaux-Gastaut syndrome. A full factorial design and desirability approach was investigated for the optimization of hydrolytic stress via response surface curves (RSCs). The degradation impurities were identified and resolved using reversed-phase high-performance liquid chromatography (RP-HPLC) on the Qualisil® BDS C8 column. Acetonitrile-water (29:71, v/v) was optimized for the mobile phase and used at a flow rate of 1.0 ml/min with detection at a wavelength of 230 nm. Rufinamide showed appreciable susceptibility to hydrolysis under acidic and alkaline stress, and substantial degradation in the neutral condition. It degraded much less under oxidative stress. Exposure towards thermal and photolytic stress conditions indicated appreciable stability. The developed method was subjected to validation as per the recommendations of the International Conference on Harmonization. The proposed method showed no influence from the excipients and the degradation products. As well as good precision and accuracy in determination, the method showed a linear response between 2 and 12 µg ml-1 . The method was extended for determination in a human plasma sample, which resulted in excellent recovery without interference from matrix effects. The combined use of desirability and design for the optimization of acidic and alkaline hydrolytic stress led to simple and rapid analysis.

A Brief Review on Determination of Acenocoumarol in Biological and Pharmaceutical Specimens: Analytical Methodologies.

Acenocoumarol is an oral anticoagulant medicinal agent is frequently prescribed for the prophylaxis and the management of thromboembolic events. Acenocoumarol is prescribed in the form of racemic mixture and S- form is a more influential isomer. Acenocoumarol starts quickly with action and absorption, and the effect lasts for 15-20 h. In most patients, the therapeutic prothrombin range is caused 36 h after the primary dose. This review offers a detailed overview of the various analytical methodologies published in the literature from 1976 to uptil now for evaluation acenocoumarol and its combinations in specimens. The present review also stated the chiral analytical methods for the quantification of its enantiomers. A detailed study of the work revealed several analytical methodologies are routinely used for estimation of acenocoumarol includes UV/Vis-Spectrophotometry, liquid chromatography-mass spectrophotometry, high-performance liquid-chromatography, gas chromatography, high-performance thin-layer chromatography, capillary electrophoresis, Fourier-transform infrared spectroscopy and many miscellaneous techniques. Pharmaceutical analysis carried out the prominent task to understand the knowledge of the physicochemical properties of the medicinal agent; since the establishment of a new analytical method is still a challenging task for a research scientist. Thus, the present review will help to research scientist for the development of new analytical methods for the acenocoumarol.

A Concise Analytical Profile of Efavirenz: Analytical Methodologies.

Non-nucleoside reverse transcriptase inhibitors are the prime members of antiretroviral therapy that are presently employed for the management of the human immunodeficiency virus. It uses an enzyme i.e., reverse transcriptase to convert its ribonucleic acid into reverse transcription; these agents impede the function of reverse transcriptase and reverse transcription counter human immunodeficiency virus from replicating. Efavirenz is the first-generation non-nucleoside reverse transcriptase inhibitor agent. Similar to the other non-nucleoside reverse transcriptase inhibitor agents; it is prescribed with other inhibitors in combination for regimens antiretroviral therapy. To enhance survival and avoid aggressive infections in patients affected with human immunodeficiency virus infection, adequate antiretroviral therapy is the most significant treatment. Accordingly, the development and validation of such therapeutic agents are challenging work for the analysts. Therefore, the proposed review integrally addresses the analytical reports of efavirenz recorded in the literature databases like Scopus, Web of Science, Google Scholar, Pub-Med, and through many other sources. It has been remarked that for the development of efavirenz many analytical techniques were used for addressing the qualitative and quantitative estimation of efavirenz from various pharmaceutical and biological matrices. This review plan to review the stereochemistry, mechanism of action, resistance, pharmacokinetics, pharmacodynamics, safety and adverse reaction, and various analytical approaches assessed for the same. The hyphenated and chromatographic techniques are frequently used for analysis of cited drug.

Exploring an experimental combination of analytical quality by design and green analytical chemistry approaches for development of HPTLC densitometric protocol for the analysis of barnidipine hydrochloride.

An experimental combination of analytical quality by design and green analytical chemistry approaches is introduced to develop an high-performance thin-layer chromatography (HPTLC) approach to quantify barnidipine hydrochloride in the pharmaceutical matrix. The analytical quality by design approach was introduced to green analytical chemistry to enhance protocol knowledge while ensuring efficiency and reducing environmental impacts, energy consumption and analyst visibility. This analytical approach was systematically addressed by exploring failure mode effect analysis, risk assessment and optimization design. Subsequently, a screening of primary variables was performed to select the aptest proportion of solvents in the mobile phase resulting from the principles of green analytical chemistry. Failure mode effect analysis and a risk assessment study were attempted to estimate the critical method parameters (CMPs). The influence of the CMPs on critical analytical attributes, i.e. retention factor and peak area, was assessed through a screening design. A response surface methodology was then executed for the critical analytical attributes as a concern of the determined CMPs, and the conditions for excellent resolution were determined using a desirability procedure. The established protocol was validated in compliance with the International Conference on Harmonization guideline Q2(R1) and showed excellent specificity and sensitivity.

Functional and regulatory aspects of oxidative stress response in X monosomy.

The partial/complete loss of one X chromosome in a human female leads to Turner syndrome (TS). TS individuals display a range of phenotypes including short stature, osteoporosis, ovarian malfunction, diabetes, and thyroid dysfunction. Epigenetic factors and regulatory networks are distinctly different in X monosomy (45, X). In a lifetime, an individual is exposed to a variety of stress conditions. To study whether X monosomy cells display a differential response upon exposure to mild stress as compared to normal 46, XX cells and whether this may contribute to various co-morbidities in aneuploid individuals, we have carried out a transcriptomic analysis of human fibroblasts 45, X and 46, XX after exposure to mild oxidative stress. Under these conditions, over 350 transcripts were seen to be differentially expressed in 45, X and 46, XX cells. Pathways associated with oxidative stress were differentially expressed highlighting the differential regulation of genes and associated phenotypes. It could be seen that X monosomy cells are more susceptible to oxidative stress as compared to normal cells and have altered molecular pathways both in normal conditions and also upon exposure to mild oxidative stress. To explore this aspect in detail, we have mapped the expressions of transcription factors (TFs) in 45, X and 46, XX cells. The network of transcription activating factors is differentially regulated in 45, X and 46, XX cells under stress exposure. It is tempting to speculate that the altered ability of 45, X (Turner) cells to respond to stress may play a significant role in the physiological function and altered phenotypes in Turner syndrome.

Wide application of minimally processed saliva on multiple RT-PCR kits for SARS-CoV-2 detection in Indonesia

Saliva as a sample matrix has been an attractive alternative for the detection of SARS-CoV-2. However, due to potential variability in collection and processing steps, evaluating a proposed workflow amongst the local population is recommended. Here, we aim to validate the collection and treatment of human saliva as a direct specimen for RT-qPCR-based detection of SARS-CoV-2 in Indonesia. We demonstrated that SARS-CoV-2 target genes were detected in saliva specimens and remained stable for five days refrigerated or room temperature storage. The method of processing saliva specimens described in this report bypasses the need for an RNA-extraction process, thereby reducing the cost, time, and manpower required for processing samples. The developed method was tested across nine commercial kits, including the benchmark, to demonstrate its wide applicability on multiple existing workflows. Our developed method achieved 86% overall agreement rate compared to paired nasopharyngeal and oropharyngeal swab specimens (NPOP). With the assistance of a saliva sampling device, the collection was found to be more convenient for individuals and improved the overall agreement rate to 97%.

An Investigative Review for Pharmaceutical Analysis of 1,4-Dihydropyridine-3,5-Dicarboxylic Acid Derivative: Cilnidipine.

Hypertension is commonly a quiet condition, and it expands the risk of heart diseases and stroke. Calcium delivers a substantial role in cardiovascular functions and hence is essential for cardiac automaticity and functioning. Calcium channel antagonists are the choice of drugs for the management of cardiovascular diseases; they precisely stop the introduction of calcium through L-type calcium channels are existing channels in the heart. Cilnidipine belongs to the class 4th generation calcium channel blockers as a foremost therapeutic agent used in the treatment of hypertension and heart diseases. This review article focuses on an inclusive account of crucial analytical methodologies used for the pharmaceutical analysis of cilnidipine in pure forms, biological samples and pharmaceuticals. According to literature reports several analytical techniques such as hyphenated techniques, high-performance thin-layer chromatography, high-performance liquid-chromatography, capillary electrophoresis, voltammetry, UV/Vis-spectrophotometry, and Fourier-transform infrared spectroscopy approaches have been used for determination of cilnidipine alone or in the combined dosage form. We have also discussed the pharmacopeial assay methods, physicochemical properties, and also depict the stacked column chart for year wise publication count for cilnidipine. From literature, concluded that the high-performance liquid-chromatography and UV/Vis-spectrophotometry methods are the most prevailing methods for the analysis of cilnidipine. The data presented in this review may provide a very significant base for further studies on cilnidipine in the area of drug analysis.

An appraisal of anti-mycobacterial activity with structure-activity relationship of piperazine and its analogues: A review.

Piperazine, is privileged six membered nitrogen containing heterocyclic ring also known as 1,4-Diazacyclohexane. Consequently, piperazine is a versatile medicinally important scaffold and is an essential core in numerous marketed drugs with diverse pharmacological activities. In recent years several potent molecules containing piperazine as an essential subunit of the structural frame have been reported, especially against Mycobacterium tuberculosis (MTB). Remarkably, a good number of these reported molecules also displayed potential activity against multidrug-resistant (MDR), and extremely drug-resistant (XDR) strains of MTB. In this review, we have made a concerted effort to retrace anti-mycobacterial compounds for the past five decades (1971-2019) specifically where piperazine has been used as a vital building block. This review will benefit medicinal chemists as it elaborates on the design, rationale and structure-activity relationship (SAR) of the reported potent piperazine based anti-TB molecules, which in turn will assist them in addressing the gaps, exploiting the reported strategies and developing safer, selective, and cost-effective anti-mycobacterial agents.

A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin.

Human skin contains a population of memory T cells that supports tissue homeostasis and provides protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tissue environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rγnull (NSG) mice that carried in vivo-generated engineered human skin (ES). ES was generated from human keratinocytes and fibroblasts and was initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC, this reductionist system allowed us to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69+ memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69- T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases.

Construction, analysis and validation of co-expression network to understand stress adaptation in Deinococcus radiodurans R1.

Systems biology based approaches have been effectively utilized to mine high throughput data. In the current study, we have performed system-level analysis for Deinococcus radiodurans R1 by constructing a gene co-expression network based on several microarray datasets available in the public domain. This condition-independent network was constructed by Weighted Gene Co-expression Network Analysis (WGCNA) with 61 microarray samples from 9 different experimental conditions. We identified 13 co-expressed modules, of which, 11 showed functional enrichments of one or more pathway/s or biological process. Comparative analysis of differentially expressed genes and proteins from radiation and desiccation stress studies with our co-expressed modules revealed the association of cyan with radiation response. Interestingly, two modules viz darkgreen and tan was associated with radiation as well as desiccation stress responses. The functional analysis of these modules showed enrichment of pathways important for adaptation of radiation or desiccation stress. To decipher the regulatory roles of these stress responsive modules, we identified transcription factors (TFs) and then calculated a Biweight mid correlation between modules hub gene and the identified TFs. We obtained 7 TFs for radiation and desiccation responsive modules. The expressions of 3 TFs were validated in response to gamma radiation using qRT-PCR. Along with the TFs, selected close neighbor genes of two important TFs, viz., DR_0997 (CRP) and DR_2287 (AsnC family transcriptional regulator) in the darkgreen module were also validated. In our network, among 13 hub genes associated with 13 modules, the functionality of 5 hub genes which are annotated as hypothetical proteins (hypothetical hub genes) in D. radiodurans genome has been revealed. Overall the study provided a better insight of pathways and regulators associated with relevant DNA damaging stress response in D. radiodurans.

Human CD4+CD103+ cutaneous resident memory T cells are found in the circulation of healthy individuals.

Tissue-resident memory T cells (TRM) persist locally in nonlymphoid tissues where they provide frontline defense against recurring insults. TRM at barrier surfaces express the markers CD103 and/or CD69, which function to retain them in epithelial tissues. In humans, neither the long-term migratory behavior of TRM nor their ability to reenter the circulation and potentially migrate to distant tissue sites has been investigated. Using tissue explant cultures, we found that CD4+CD69+CD103+ TRM in human skin can down-regulate CD69 and exit the tissue. In addition, we identified a skin-tropic CD4+CD69-CD103+ population in human lymph and blood that is transcriptionally, functionally, and clonally related to the CD4+CD69+CD103+ TRM population in the skin. Using a skin xenograft model, we confirmed that a fraction of the human cutaneous CD4+CD103+ TRM population can reenter circulation and migrate to secondary human skin sites where they reassume a TRM phenotype. Thus, our data challenge current concepts regarding the strict tissue compartmentalization of CD4+ T cell memory in humans.

A comparison of the efficacy of two commercial acaricides (fipronil and amitraz) with Azadirachta indica (neem) on the brown dog tick (Rhipicephalus sanguineus) from canines in Trinidad

Objective: Rhipicephalus sanguineus, the most common species of tick found on canines in Trinidad. It is a potential vector for potentially fatal zoonotic diseases such as borreliosis (Lyme disease), babesiosis, anaplasmosis and human granulocytic ehrlichiosis. Common acaricides used by pet owners such as fipronil and amitraz are often misused and abused as owners may fail to follow the manufacturers' instructions. The objectives of this study were to compare the efficacies of the commercial acaricides (fipronil and amitraz) to the herbal alternative, neem on brown dog ticks in Trinidad. Design and Methodology: The Larval Packet Test (LPT) was conducted in triplicate for each of three concentrations (high, recommended and low concentrations) of fipronil, amitraz, neem oil and neem leaf extract. STATA version 15 was used to perform a mixed effects Poisson regression analysis. Results: Both the commercial and herbal acaricides were effective in causing death of the larvae. Larvae were susceptible to amitraz and fipronil at all concentrations used, however they displayed variable resistance to the neem oil and neem leaf extract. Conclusions: The commercial preparations (amitraz and fipronil) proved to be more effective than neem oil and neem leaf extract, however the latter can be used as a herbal alternative to control R. sanguineus in Trinidad.