ABSTRACT
INTRODUCTION: ß-lactam antibiotics are promising treatments for Mycobacterium avium complex (MAC) lung disease. We hypothesized that benzylpenicillin has efficacy against MAC. METHODS: Benzylpenicillin lung concentration-time profiles of seven doses in three dosing schedules were administered for 28 days using the hollow fiber system model of intracellular MAC (HFS-MAC). Data were analyzed using the inhibitory sigmoid maximal effect (Emax) model for each sampling day, while two ordinary differential equations (ODEs) were used for the wild-type and penicillin-resistant mutants. RESULTS: Benzylpenicillin killed >2.1 log10 colony-forming unit (CFU)/mL below Day 0, better than azithromycin, ethambutol, and rifabutin. Efficacy was terminated by acquired resistance. Sigmoid Emax parameter estimates significantly differed between sampling days and were a poor fit. However, ODE model parameter estimates vs. exposure were a better fit. The exposure mediating Emax was 84.6% (95% CI 76.91-82.98) of time concentration exceeded the minimum inhibitory concentration (MIC). In Monte Carlo experiments, 24 million international units of benzylpenicillin continuous infusion achieved the target exposure in lungs of >90% of 10,000 subjects until an MIC of 64 mg/L, designated the susceptibility breakpoint. CONCLUSIONS: Benzylpenicillin demonstrated a better bactericidal effect against MAC than guideline-recommended drugs before the development of resistance. Its role in combination therapy with other drugs with better efficacy than guideline-recommended drugs should be explored.
INTRODUCTION: Les ß-lactamines représentent des options thérapeutiques prometteuses pour le traitement de la maladie pulmonaire à complexe Mycobacterium avium (MAC). Notre hypothèse suggère que la benzylpénicilline pourrait être efficace contre cette maladie pulmonaire causée par M. avium. MÉTHODES: Les concentrations pulmonaires de benzylpénicilline ont été mesurées à différents moments après l'administration de sept doses selon trois schémas différents pendant 28 jours dans le modèle de MAC intracellulaire du système de fibres creuses (HFS-MAC). Les données ont été analysées en utilisant un modèle sigmoïde inhibiteur à effet maximal (Emax) pour chaque jour d'échantillonnage, et deux équations différentielles ordinaires (ODE) ont été appliquées pour les souches sauvages et les mutants résistants à la pénicilline. RÉSULTATS: La benzylpénicilline a provoqué une réduction de >2,1 log10 CFU/mL en dessous du jour 0, surpassant ainsi l'azithromycine, l'éthambutol et la rifabutine. Cependant, son efficacité a été compromise par l'émergence d'une résistance. Les estimations des paramètres de l'Emax sigmoïde ont montré des différences significatives entre les jours d'échantillonnage et étaient mal ajustées. En revanche, les estimations des paramètres du modèle ODE en fonction de l'exposition étaient plus précises. L'exposition médiane de l'Emax était de 84,6% (IC à 95% 76,9182,98) du temps où la concentration dépassait la concentration minimale inhibitrice (MIC, pour l'anglais « minimum inhibitory concentration ¼). Dans les simulations de Monte Carlo, une perfusion continue de 24 millions d'unités internationales de benzylpénicilline a permis d'atteindre l'exposition cible dans les poumons de plus de 90% des 10 000 sujets, jusqu'à ce qu'une MIC de 64 mg/L soit atteinte, indiquant ainsi le point de rupture de la sensibilité. CONCLUSIONS: La benzylpénicilline a montré une efficacité bactéricide supérieure contre le MAC par rapport aux médicaments recommandés par les lignes directrices avant l'émergence de la résistance. Il convient d'explorer son utilisation dans une thérapie combinée avec des médicaments plus performants que ceux recommandés par les lignes directrices.
ABSTRACT
Antimicrobial resistance (AMR) is a global health crisis and there is an urgent need to better understand AMR mechanisms. Antibiotic treatment alters several aspects of bacterial physiology, including increased ATP utilization, carbon metabolism, and reactive oxygen species (ROS) formation. However, how the "bioenergetic stress" induced by increased ATP utilization affects treatment outcomes is unknown. Here we utilized a synthetic biology approach to study the direct effects of bioenergetic stress on antibiotic efficacy. We engineered a genetic system that constitutively hydrolyzes ATP or NADH in Escherichia coli. We found that bioenergetic stress potentiates AMR evolution via enhanced ROS production, mutagenic break repair, and transcription-coupled repair. We also find that bioenergetic stress potentiates antimicrobial persistence via potentiated stringent response activation. We propose a unifying model that antibiotic-induced antimicrobial resistance and persistence is caused by antibiotic-induced. This has important implications for preventing or curbing the spread of AMR infections.
ABSTRACT
The design of surface plasmon resonance (SPR) sensors has been greatly enhanced in recent years by the advancements in the production and integration of nanostructures, leading to more compact and efficient devices. There have been reports of novel SPR sensors having distinct nanostructures, either as signal amplification tags like gold nanoparticles (AuNPs) or as sensing substrate-like two-dimensional (2D) materials including graphene, transition metal dichalcogenides (TMDCs), MXene, black phosphorus (BP), metal-organic frameworks (MOFs), and antimonene. Such 2D-based SPR biosensors offer advantages over conventional sensors due to significant increases in their sensitivity with a good figure of merit and limit of detection (LOD). Due to their atomically thin structure, improved sensitivity, and sophisticated functionalization capabilities, 2D materials can open up new possibilities in the field of healthcare, particularly in point-of-care diagnostics, environmental and food monitoring, homeland security protection, clinical diagnosis and treatment, and flexible or transient bioelectronics. The present study articulates an in-depth analysis of the most recent developments in 2D material-based SPR sensor technology. Moreover, in-depth research of 2D materials, their integration with optoelectronic technology for a new sensing platform, and the predicted and experimental outcomes of various excitation approaches are highlighted, along with the principles of SPR biosensors. Furthermore, the review projects the potential prospects and future trends of these emerging materials-based SPR biosensors to advance in clinical diagnosis, healthcare biochemical, and biological applications.
Subject(s)
Surface Plasmon Resonance , Biosensing Techniques/methods , Gold/chemistry , Graphite/chemistry , Limit of Detection , Metal Nanoparticles/chemistry , Metal-Organic Frameworks/chemistry , Nanostructures/chemistry , Phosphorus/chemistry , Surface Plasmon Resonance/methodsABSTRACT
BACKGROUND: Antioxidants minimise oxidative stress and enhance sperm quality in the process of cryopreservation. OBJECTIVE: To assess the impact of Cinnamomum zeylanicum extract as an additive during the post-dilution and post-thaw stages of Murrah buffalo semen cryopreservation. MATERIALS AND METHODS: The semen sample was diluted using Tris-Egg-Yolk-Citric-Acid-Fructose-Glycerol extender and subsequently divided into three groups: Group 1, TEYCAFG without any additives or controls (C); Group 2, TEYCAFG fortified with a 50 ug/mL aqueous extract of cinnamon (T1); and Group 3, TEYCAFG fortified with a 50 ug/mL ethanolic extract of cinnamon (T2). The evaluation included an assessment of progressive motility, live spermatozoa, sperm abnormalities, HOST, CMPT, and enzyme leakage (GOT and GPT) at both the post-dilution and post-thaw stages. RESULTS: The groups that received cinnamon supplementation demonstrated statistically significant improvements (p<0.05) in various parameters, including an increase in the progressive motility, live spermatozoa, and HOS-positive spermatozoa, as well as greater distance traveled by vanguard spermatozoa compared to the control group. Furthermore, the cinnamon-added groups exhibited a significant decrease (p<0.05) in the percentage of sperm abnormalities and lower enzyme leakage (GOT and GPT) in post-thawed semen. CONCLUSION: Aqueous extract of C. zeylanicum at a concentration of 50 µg/mL provides superior protection of sperm structures and functions as compared to both the ethanolic extract of C. zeylanicum at the same concentration and the control group. Doi.org/10.54680/fr24310110712.
Subject(s)
Antioxidants , Buffaloes , Cryopreservation , Plant Extracts , Semen , Male , Animals , Semen/cytology , Semen/metabolism , Cryopreservation/veterinary , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Trehalose/pharmacology , Antioxidants/pharmacology , Fertility Preservation/veterinaryABSTRACT
The emergence of computationally powerful smartphones, relatively affordable high-resolution camera, drones, and robotic sensors have ushered in a new age of advanced sensible monitoring tools. The present review article investigates the burgeoning smartphone-based sensing paradigms, including surface plasmon resonance (SPR) biosensors, electrochemical biosensors, colorimetric biosensors, and other innovations for modern healthcare. Despite the significant advancements, there are still scarcity of commercially available smart biosensors and hence need to accelerate the rates of technology transfer, application, and user acceptability. The application/necessity of smartphone-based biosensors for Point of Care (POC) testing, such as prognosis, self-diagnosis, monitoring, and treatment selection, have brought remarkable innovations which eventually eliminate sample transportation, sample processing time, and result in rapid findings. Additionally, it articulates recent advances in various smartphone-based multiplexed bio sensors as affordable and portable sensing platforms for point-of-care devices, together with statistics for point-of-care health monitoring and their prospective commercial viability.
Subject(s)
Biosensing Techniques , Environmental Monitoring , Food Safety , Smartphone , Humans , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Environmental Monitoring/methods , Environmental Monitoring/instrumentation , Food Analysis/methods , Food Analysis/instrumentation , Point-of-Care Systems , Colorimetry/methods , Colorimetry/instrumentationABSTRACT
To determine the efficacy of the probiotic Bifidobacterium longum CECT 7347 (ES1) and postbiotic heat-treated Bifidobacterium longum CECT 7347 (HT-ES1) in improving symptom severity in adults with diarrhea-predominant irritable bowel syndrome (IBS-D), a randomised, double-blind, placebo-controlled trial with 200 participants split into three groups was carried out. Two capsules of either ES1, HT-ES1 or placebo were administered orally, once daily, for 84 days (12 weeks). The primary outcome was change in total IBS-Symptom Severity Scale (IBS-SSS) score from baseline, compared to placebo. Secondary outcome measures were stool consistency, quality of life, abdominal pain severity and anxiety scores. Safety parameters and adverse events were also monitored. The change in IBS-SSS scores from baseline compared to placebo, reached significance in the ES1 and HT-ES1 group, on Days 28, 56 and 84. The decrease in mean IBS-SSS score from baseline to Day 84 was: ES1 (-173.70 [±75.60]) vs placebo (-60.44 [±65.5]) (p < .0001) and HT-ES1 (-177.60 [±79.32]) vs placebo (-60.44 [±65.5]) (p < .0001). Secondary outcomes included changes in IBS-QoL, APS-NRS, stool consistency and STAI-S and STAI-T scores, with changes from baseline to Day 84 being significant in ES1 and HT-ES1 groups, compared to the placebo group. Both ES1 and HT-ES1 were effective in reducing IBS-D symptom severity, as evaluated by measures such as IBS-SSS, IBS-QoL, APS-NRS, stool consistency, and STAI, in comparison to the placebo. These results are both statistically significant and clinically meaningful, representing, to the best of the authors' knowledge, the first positive results observed for either a probiotic or postbiotic from the same strain, in this particular population.
What is already known on this topicIBS is a chronic functional gastrointestinal disorder characterized by abdominal pain, bloating and abnormalities in stool frequency or form. The gut microbiota of people living with IBS differs markedly to the microbiota of healthy individuals. Gut microbiota may play a key role in IBS aetiology and IBS symptoms may be alleviated by modulating the gut microbiota. Several proposed ways to modulate gut health include normalizing the gut microbiota, preventing the overgrowth of pathogenic bacteria, modulating visceral afferent pathways, and enhancing intestinal barrier function. However, significant heterogeneity between studies, study quality and population, study design and concerns about sample size have limited national and supranational bodies from recommending probiotics for IBS. Further well-powered, randomized, repeatable and controlled trials are warranted.What this study addsThe results of this study substantially contribute to the IBS research field, firstly by providing clinically meaningful and statistically significant results from a rigorous, well designed randomized, placebo-controlled trial and secondly, by exploring the use of postbiotics in IBS, an area of research still in its infancy. Probiotic (ES1) and postbiotic (HT-ES1) supplementation significantly reduced IBS symptom severity scores compared to placebo. This study met primary and secondary outcomes and strongly suggest that ES1 and HT-ES1 could be beneficial in the management of IBS.How this study might affect research, practice, or policyThis study adds to the current evidence base, supporting the use of probiotic/postbiotics for IBS. This research could be used to inform health professionals about using probiotics in IBS and help improve the quality of life and wellbeing for people living with the condition.
Subject(s)
Bifidobacterium longum , Gastrointestinal Microbiome , Irritable Bowel Syndrome , Peptides, Cyclic , Adult , Humans , Irritable Bowel Syndrome/therapy , Quality of Life , Hot Temperature , DiarrheaABSTRACT
Lanthanide-doped core-shell nanomaterials have illustrated budding potential as luminescent materials, but their biological applications have still been very limited due to their aqueous solubility and biocompatibility. Here, we report a simple and cost-effective approach to construct a water-stable chitosan-functionalized lanthanoid-based core shell (Ca-Eu:Y2O3@SiO2) nanophosphor. The as-synthesized Ca-Eu:Y2O3@SiO2-chitosan (CEY@SiO2-CH) nanophosphor has been characterized for its structural, morphological, and optical properties, by employing different analytical tools. This sensing platform is suitable for dsDNA probing by tracing the "turn on" fluorescence signal generated by CEY@SiO2-CH nanophosphor with the addition of dsDNA. The ratio of fluorescence intensity enhancement is proportional to the concentration of dsDNA in the range 0.1-90 nM, with the limit of detection at â16.1 pM under optimal experimental conditions. The enhancement in fluorescence response of functionalized core-shell phosphor with dsDNA is due to the antenna effect. Additionally, response of probe has been studied for the real samples displaying percent recovery in between 101 and 105, maximum RSD% upto 5.23 (n = 3). This outcome can be applied to the selective sensing of dsDNA through optical response. These findings establish the CEY@SiO2-CH a simple, portable, and potential candidate as a sensor for rapid and analytical detection of dsDNA.
Subject(s)
Biosensing Techniques , Chitosan , Europium/chemistry , Silicon Dioxide/chemistry , Coloring Agents , Water , DNAABSTRACT
Epidemiological evidence shows that residential proximity to greenspaces is associated with lower risk of all-cause and cardiovascular mortality; however, the mechanism(s) underlying this link remains unclear. Plants emit biogenic volatile organic compounds such as α-pinene that could elicit beneficial cardiovascular effects. To explore the role of α-pinene more directly, we studied the metabolism and the vascular effects of α-pinene. We found that exposure of mice to α-pinene (1 ppm, 6 h) generated two phase I oxidation metabolites, cis- and trans-verbenol [(1R,2R,5R)-verbenol and (1 R,2S,5R)-verbenol)] and myrtenol [(1S,5R)-(+)-myrtenol] that were identified in urine by GC-MS. Precontracted naïve murine male and female aorta and superior mesenteric artery (SMA) were relaxed robustly (60% tension reduction) by increasing concentrations of α-pinene, myrtenol, and verbenol to 0.3 mM, whereas 1 mM α-pinene was vasotoxic. The SMA was six times more sensitive than the aorta to α-pinene. Both myrtenol and verbenol were equally potent and efficacious as parent α-pinene in male and female SMA. The sensitive portion of the α-pinene-, myrtenol-, and verbenol-induced relaxations in male SMA was mediated by 1) endothelium, 2) eNOS-derived NO, and 3) guanylyl cyclase (GC) activity. Moreover, α-pinene activated the transient receptor potential ankyrin-1 (TRPA1) channel whereas the metabolites did not. Endothelial-derived NO regulates blood flow, blood pressure, and thrombosis, and it is plausible that inhaled (and ingested) α-pinene (or its metabolites) augments NO release to mediate the cardiovascular benefits of exposure to greenness.NEW & NOTEWORTHY A common plant-derived biogenic volatile organic compound, α-pinene, and two of its metabolites, myrtenol and verbenol, stimulate vasorelaxation in murine superior mesenteric artery. Both α-pinene- and its metabolites induce vasorelaxation by activation of the endothelium, nitric oxide, and guanylyl cyclase. α-Pinene also activates the transient receptor potential ankyrin-1. Positive associations between greenness exposure and human cardiovascular health may be a result of the vascular action of α-pinene and its metabolites, a novel consideration.
Subject(s)
Ankyrins , Monoterpenes , Humans , Animals , Mice , Monoterpenes/pharmacology , Monoterpenes/metabolism , Endothelium/metabolism , Guanylate CyclaseABSTRACT
BACKGROUND: Observational real-world studies on therapeutic drug monitoring (TDM) in relation to pharmacokinetic (PK) target values are lacking. This study aims to describe the PK of rifampicin (RIF) and isoniazid (INH) in a real-world setting of patients with drug-susceptible TB in relation to frequently used threshold values.METHODS: A total of 116 patients with TB using standard doses of RIF and INH and who had TDM as part of clinical care were included. Maximum plasma concentration (Cmax) and 24 h area under the concentration time curve (AUC24) at standard and revised doses were described in relation to the threshold values (Cmax ≥8 mg/L for RIF and ≥3 mg/L for INH).RESULTS: For RIF (100 patients), median Cmax and median AUC24 were respectively 7.9 mg/L (IQR 6.0-11.0) and 35.8 mg*h/L (IQR 27.4-57.3) at the first TDM measurement after a standard dose of 600 mg. For INH (90 patients), median Cmax and median AUC24 were respectively 2.9 mg/L (IQR 1.3-2.5) and 12.5 mg*h/L (IQR 8.7-18.9) at the first TDM after a standard dose 300 mg. Overall, more than 50% of study participants had drug exposure below threshold values at the first TDM.CONCLUSION: Our study shows that the measured Cmax values for both RIF and INH were frequently below the pre-specified targets, emphasising the need for better justification of drug exposure targets. These TDM results highlight the need for validating PK targets of anti-TB drugs associated with clinically relevant outcomes.
Subject(s)
Isoniazid , Tuberculosis , Humans , Isoniazid/therapeutic use , Rifampin/therapeutic use , Tuberculosis/drug therapyABSTRACT
Many countries are using health insurance to advance progress towards universal health coverage (UHC). India launched the Pradhan Mantri Jan Arogya Yojana (PM-JAY) health insurance scheme in 2018. We examine the political economy context around PM-JAY policy formulation, by examining the perspectives of policy stakeholders shaping decisions around the reform. More specifically, we focus on early policy design at the central (national) level. We use a framework on the politics of UHC reform proposed by Fox and Reich (The politics of universal health coverage in low- and middle-income countries: A framework for evaluation and action. J. Health Polit. Policy Law 2015;40:1023-1060), to categorize the reform into phases and examine the interactions between actors, institutions, interests, ideas and ideology which shaped reform decisions. We interviewed 15 respondents in Delhi between February and April 2019, who were either closely associated with the reform process or subject experts. The ruling centre-right government introduced PM-JAY shortly before national elections, drawing upon policy legacies from prior and state insurance schemes. Empowered policy entrepreneurs within the government focused discourse around ideas of UHC and strategic purchasing, and engaged in institution building leading to the creation of the National Health Authority and State Health Agencies through policy directives, thereby expanding state infrastructural and institutional power for insurance implementation. Indian state inputs were incorporated in scheme design features like mode of implementation, benefit package and provider network, while features like the coverage amount, portability of benefits and branding strategy were more centrally driven. These balanced negotiations opened up political space for a cohesive, central narrative of the reform and facilitated adoption. Our analysis shows that the PM-JAY reform focused on bureaucratic rather than ideological elements and that technical compromises and adjustments accommodating the interests of states enabled the political success of policy formulation. Appreciating these politics, power and structural issues shaping PM-JAY institutional design will be important to understand how PM-JAY is implemented and how it advances UHC in India.
Subject(s)
Health Care Reform , Universal Health Insurance , Humans , Insurance, Health , Policy , IndiaABSTRACT
The idea of strain based manipulation of spins in magnetic two-dimensional (2D) van der Waal (vdW) materials leads to the development of new generation spintronic devices. Magneto-strain arises in these materials due to the thermal fluctuations and magnetic interactions which influences both the lattice dynamics and the electronic bands. Here, we report the mechanism of magneto-strain effects in a vdW material CrGeTe[Formula: see text] across the ferromagnetic (FM) transition. We find an isostructural transition in CrGeTe[Formula: see text] across the FM ordering with first order type lattice modulation. Larger in-plane lattice contraction than out-of-plane give rise to magnetocrystalline anisotropy. The signature of magneto-strain effects in the electronic structure are shift of the bands away from the Fermi level, band broadening and the twinned bands in the FM phase. We find that the in-plane lattice contraction increases the on-site Coulomb correlation ([Formula: see text]) between Cr atoms resulting in the band shift. Out-of-plane lattice contraction enhances the [Formula: see text] hybridization between Cr-Ge and Cr-Te atoms which lead to band broadening and strong spin-orbit coupling (SOC) in FM phase. The interplay between [Formula: see text] and SOC out-of-plane gives rise to the twinned bands associated with the interlayer interactions while the in-plane interactions gives rise to the 2D spin polarized states in the FM phase.
ABSTRACT
Anti-Ro/SSA-antibody-mediated endocardial fibroelastosis (EFE) without atrioventricular (AV) block at presentation is a rare cardiac phenotype. We report on 11 fetuses with this rare type of anti-Ro/SSA-antibody-mediated cardiac involvement, presenting with a distinctive echocardiographic pattern of EFE. Eleven fetuses with isolated EFE at presentation were included from four cardiac centers, and experienced fetal cardiologists reached a consensus regarding EFE location on echocardiography at presentation. Interval changes to subsequent fetal and postnatal echocardiograms were assessed to evaluate response to therapy. Echocardiographic markers of cardiac performance, including diastolic function and AV conduction, were reviewed. Ten fetuses were found to have EFE of the aortic root, proximal aorta and/or left ventricular outflow tract. In the same 10 cases, EFE of the pulmonary root, pulmonary artery and/or right ventricular outflow tract was identified. Six cases had atrial EFE and six had EFE of the crux. Four cases were known to be positive for anti-Ro/SSA antibodies prior to diagnosis, whereas, in the remaining seven, echocardiographic findings prompted testing, which was positive in all cases. The AV interval at presentation was normal in all cases, but one fetus subsequently developed AV block. Nine patients were treated with transplacental dexamethasone, five of which also received intravenous immunoglobulin (IVIG), and one received IVIG only. Of the 10 treated cases, six had improvement in EFE as shown by serial imaging and, in four cases, the severity was unchanged. All patients were liveborn. In our cohort, EFE of the aortic and pulmonary arteries and outflow tracts was nearly universal, and involvement of the atria and the crux of the heart was also common. The high survival rate and low burden of AV block are also suggestive of a distinct phenotype of anti-Ro/SSA-antibody-mediated cardiac disease with a favorable prognosis. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Subject(s)
Atrioventricular Block , Endocardial Fibroelastosis , Pregnancy , Female , Humans , Immunoglobulins, Intravenous , Fetus , Endocardial Fibroelastosis/diagnostic imaging , Echocardiography/methodsABSTRACT
Many members of the Oomycota genus Phytophthora cause economic and environmental impact diseases in nurseries, horticulture, forest, and natural ecosystems and many are of regulatory concern around the world. At present, there are 223 described species, including eight unculturable and three lost species. Twenty-eight species need to be redescribed or validated. A lectotype, epitype or neotype was selected for 20 species, and a redescription based on the morphological/molecular characters and phylogenetic placement is provided. In addition, the names of five species are validated: P. cajani, P. honggalleglyana (Synonym: P. hydropathica), P. megakarya, P. pisi and P. pseudopolonica for which morphology and phylogeny are given. Two species, P. ×multiformis and P. uniformis are presented as new combinations. Phytophthora palmivora is treated with a representative strain as both lecto- and epitypification are pending. This manuscript provides the updated multigene phylogeny and molecular toolbox with seven genes (ITS rDNA, ß-tub, COI, EF1α, HSP90, L10, and YPT1) generated from the type specimens of 212 validly published, and culturable species (including nine hybrid taxa). The genome information of 23 types published to date is also included. Several aspects of the taxonomic revision and phylogenetic re-evaluation of the genus including species concepts, concept and position of the phylogenetic clades recognized within Phytophthora are discussed. Some of the contents of this manuscript, including factsheets for the 212 species, are associated with the "IDphy: molecular and morphological identification of Phytophthora based on the types" online resource (https://idtools.org/tools/1056/index.cfm). The first version of the IDphy online resource released to the public in September 2019 contained 161 species. In conjunction with this publication, we are updating the IDphy online resource to version 2 to include the 51 species recently described. The current status of the 223 described species is provided along with information on type specimens with details of the host (substrate), location, year of collection and publications. Additional information is provided regarding the ex-type culture(s) for the 212 valid culturable species and the diagnostic molecular toolbox with seven genes that includes the two metabarcoding genes (ITS and COI) that are important for Sanger sequencing and also very valuable Molecular Operational Taxonomic Units (MOTU) for second and third generation metabarcoding High-throughput sequencing (HTS) technologies. The IDphy online resource will continue to be updated annually to include new descriptions. This manuscript in conjunction with IDphy represents a monographic study and the most updated revision of the taxonomy and phylogeny of Phytophthora, widely considered one of the most important genera of plant pathogens. Taxonomic novelties: New species: Phytophthora cajani K.S. Amin, Baldev & F.J. Williams ex Abad, Phytophthora honggalleglyana Abad, Phytophthora megakarya Brasier & M.J. Griffin ex Abad, Phytophthora pisi Heyman ex Abad, Phytophthora pseudopolonica W.W. Li, W.X. Huai & W.X. Zhao ex Abad & Kasiborski; New combinations: Phytophthora ×multiformis (Brasier & S.A. Kirk) Abad, Phytophthora uniformis (Brasier & S.A. Kirk) Abad; Epitypifications (basionyms): Peronospora cactorum Lebert & Cohn, Pythiacystis citrophthora R.E. Sm. & E.H. Sm., Phytophthora colocasiae Racib., Phytophthora drechsleri Tucker, Phytophthora erythroseptica Pethybr., Phytophthora fragariae Hickman, Phytophthora hibernalis Carne, Phytophthora ilicis Buddenh. & Roy A. Young, Phytophthora inundata Brasier et al., Phytophthora megasperma Drechsler, Phytophthora mexicana Hotson & Hartge, Phytophthora nicotianae Breda de Haan, Phytophthora phaseoli Thaxt., Phytophthora porri Foister, Phytophthora primulae J.A. Toml., Phytophthora sojae Kaufm. & Gerd., Phytophthora vignae Purss, Pythiomorpha gonapodyides H.E. Petersen; Lectotypifications (basionym): Peronospora cactorum Lebert & Cohn, Pythiacystis citrophthora R.E. Sm. & E.H. Sm., Phytophthora colocasiae Racib., Phytophthora drechsleri Tucker, Phytophthora erythroseptica Pethybr., Phytophthora fragariae Hickman, Phytophthora hibernalis Carne, Phytophthora ilicis Buddenh. & Roy A. Young, Phytophthora megasperma Drechsler, Phytophthora mexicana Hotson & Hartge, Phytophthora nicotianae Breda de Haan, Phytophthora phaseoli Thaxt., Phytophthora porri Foister, Phytophthora primulae J.A. Toml., Phytophthora sojae Kaufm. & Gerd., Phytophthora vignae Purss, Pythiomorpha gonapodyides H.E. Petersen; Neotypifications (basionym): Phloeophthora syringae Kleb., Phytophthora meadii McRae Citation: Abad ZG, Burgess TI, Bourret T, Bensch K, Cacciola S, Scanu B, Mathew R, Kasiborski B, Srivastava S, Kageyama K, Bienapfl JC, Verkleij G, Broders K, Schena L, Redford AJ (2023). Phytophthora: taxonomic and phylogenetic revision of the genus. Studies in Mycology 106: 259-348. doi: 10.3114/sim.2023.106.05.
Subject(s)
Physicians , Supreme Court Decisions , Infant, Newborn , United States , Female , Humans , Critical Illness , Women's Health , FetusABSTRACT
BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.
Subject(s)
Antitubercular Agents , Drug Monitoring , Tuberculosis , Humans , Patient Care , Reference Standards , Tuberculosis/drug therapy , Antitubercular Agents/administration & dosageABSTRACT
BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.
Subject(s)
Tuberculosis, Pulmonary , Adult , Child , Humans , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiologyABSTRACT
NASA's Jet Propulsion Laboratory (JPL) is advancing research capabilities for data science with two of the National Cancer Institute's major research programs, the Early Detection Research Network (EDRN) and the Molecular and Cellular Characterization of Screen-Detected Lesions (MCL), by enabling data-driven discovery for cancer biomarker research. The research team pioneered a national data science ecosystem for cancer biomarker research to capture, process, manage, share, and analyze data across multiple research centers. By collaborating on software and data-driven methods developed for space and earth science research, the biomarker research community is heavily leveraging similar capabilities to support the data and computational demands to analyze research data. This includes linking diverse data from clinical phenotypes to imaging to genomics. The data science infrastructure captures and links data from over 1600 annotations of cancer biomarkers to terabytes of analysis results on the cloud in a biomarker data commons known as "LabCAS". As the data increases in size, it is critical that automated approaches be developed to "plug" laboratories and instruments into a data science infrastructure to systematically capture and analyze data directly. This includes the application of artificial intelligence and machine learning to automate annotation and scale science analysis.
Subject(s)
Artificial Intelligence , Data Science , Biomarkers, Tumor , Ecosystem , Humans , SoftwareABSTRACT
In this study, compacted hematite (Fe2O3) preforms were made and sintered at various temperatures, such as 1250 °C and 1300 °C, using both conventional and microwave sintering methods. The density, porosity, microhardness, cold crushing strength, microphotographs, and X-ray diffraction (XRD) analysis of the sintered preforms were used to evaluate the performance of the two sintering methods. It was found that microwave sintered preforms possessed lesser porosity and higher density than conventionally sintered preforms owing to uniform heating of the powdered ore in microwave sintering method. Furthermore, it was also observed that microwave sintered preforms exhibited relatively higher cold crushing strength and hardness than conventionally sintered preforms. Thus, the overall results revealed that microwave sintering yielded better properties considered in the present study.
ABSTRACT
Background: Helicobacter pylori infection has been known to be associated with dyspepsia for more than two decades; however, studies on this topic in India are limited. This study was carried out to estimate the Helicobacter pylori infection rates in non-ulcer dyspepsia. Methods: Helicobacter pylori infection rates detected by rapid urease test (RUT) positivity were analyzed in 235 patients presenting to a tertiary care center with dyspepsia having no evidence of peptic ulcer disease on esophagogastroduodenoscopy. Results: In this study, the prevalence of Helicobacter pylori infection diagnosed by the RUT was found to be 40.85%. Gender-based prevalence was found to be 40.14% and 41.93% for men and women, respectively. The highest prevalence was found in the age group of 30-39 years. The most common area of involvement was the isolated antrum of the stomach as seen in 93 patients. Conclusion: This study shows a modest RUT positivity rate for Helicobacter pylori infection with the commonest site of involvement being the antrum of the stomach. Further studies will be needed to assess the prevalence of Helicobacter pylori in the community to analyze the extent of infection.