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African Americans,hypertension and the renin angiotensin system

World Journal of Cardiology 2014年第9期6卷 878-889页

作者： Sandra F Williams susanne b nicholas Nosratola D Vaziri Keith C Norris Department of Endocrinology Cleveland Clinic Department of Clinical biomedical Science Charles E Schmidt College of MedicineFlorida Atlantic University Division of Nephrology and Division of Endocrinology Diabetes and HypertensionDepartment of Medicine David Geffen School of MedicineUniversity of California Division of Nephrology and Hypertension Departments of MedicinePhysiology and BiophysicsUniversity of California Division of General Internal Medicine and Health Services Research Los AngelesCA 90024United States Department of Medicine David Geffen School of Medicine University of California

African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system(RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans.

关键词： African American blood pressure Ethnicity Hypertension Renin Angiotensin

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beyond Membranes:The Evolution of Plant Lipid Signaling

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Molecular Plant 2020年第7期13卷 952-954页

作者： susanne Hoffmann-benning Department of biochemistry and Molecular biology Michigan State UniversityEast LansingMIUSA

Lipids have many essential functions in plants:They are membrane components and as such play an important role in compartmentation of the cell,membrane curvature,and formation of lipid rafts/microdomains;they participate in vesicle formation and trafficking,and act as a barrier to unrestricted trafficking of *** are also important intermediates in the biosynthesis of secondary metabolites and storage *** more interesting is their role in signaling.

关键词： Lipid Plant curvature

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Pesticides and trace elements in cannabis:Analytical and environmental challenges and opportunities

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Journal of Environmental Sciences 2019年第11期31卷 82-93页

作者： Caley b.Craven nicholas Wawryk Ping Jiang Zhongshan Liu Xing-Fang Li Department of Chemistry Faculty of Science University of Alberta Edmonton AB T6G 2G2 Canada Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and Pathology Faculty of Medicine and DentistryUniversity of Alberta Edmonton AB T6G 2G3 Canada

Cannabis is increasingly used for both medicinal and recreational purposes with an estimate of over 180 million users *** has recently legalized cannabis use in October 2018,joining several states,in the United States of America (e.g.,Colorado,California,and Oregon) and a few other countries.A variety of cannabis products including dry flowers,edibles,and oil products are widely *** high demand for cannabis products worldwide,the quality of cannabis and its related products has become a major concern for consumer *** guidelines have been set by different countries to ensure the quality,safety,and efficacy of cannabis *** general,these guidelines require control of contaminants including pesticides,toxic elements,mycotoxins,and pathogens,as well as residual solvents in regard to cannabis ***,appropriate analytical methods are required to determine these contaminants in cannabis products for quality *** this review,we focus on the current analytical challenges and method development for detection of pesticides and toxic elements in cannabis to meet various guidelines.

关键词： Cannabis QA/QC Contaminants Analytical testing Pesticides Heavy metals Regulations

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Combined risk modelling approach to identify the optimal carotid revascularisation approach

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Stroke & Vascular Neurology 2021年第3期6卷 476-482,I0080-I0084页

作者： James Francis burke Lewis b Morgenstern nicholas H Osborne Rodney A Hayward Neurology University of Michigan Michigan MedicineAnn ArborMichiganUSA Vascular Surgery Univerity of Michigan MedicineAnn ArborMichiganUSA Internal Medicine University of Michigan Michigan MedicineAnn ArborMichiganUSA

background Carotid endarterectomy(CEA)results in fewer perioperative strokes,but more myocardial infarctions(MI)than carotid artery stenting(CAS).We explored a combined modelling approach that stratifies patients by baseline stroke and *** baseline registry-based risk models for perioperative stroke and MI were identified via literature *** then selected treatment risk models in the Carotid Revascularisation Stenting versus Endarterectomy(CREST)trial by serially adding covariates(baseline risk,treatment(CEA vs CAS),treatment-risk interaction and age-treatment interaction terms).Treatment risk models were externally validated using data from the Society for Vascular Surgery(SVS)Vascular Quality Initiative(VQI)CEA and carotid stenting registries and treatment models were recalibrated to the SVS-VQI *** net benefit was estimated by summing the predicted stroke and MI risk differences with CEA versus *** Perioperative treatment models had moderate predictiveness(c-statistic 0.69 for stroke and 0.68 for MI)and reasonable calibration across the risk spectrum for both stroke and MI within *** external validation in SVS-VQI,predictiveness was substantially reduced(c-statistic 0.61 for stroke and 0.54 for MI)and models substantially overpredicted *** patients(86.7%)were predicted to have net benefit from CEA in CREST(97.0%of symptomatic patients vs 75%of asymptomatic patients).Discussion A combined modelling approach that separates risk elements has potential to inform optimal ***,our current approach is not ready for clinical *** data support guidelines that suggest that CEA should be the preferred revascularisation modality in most patients with symptomatic carotid stenosis.

关键词： carotid Surgery optimal

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Thermal hypersensitivity in a subset of irritable bowel syndrome patients

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World Journal of Gastroenterology 2009年第26期15卷 3254-3260页

作者： QiQi Zhou Roger b Fillingim Joseph L Riley Ⅲ G nicholas Verne Department of Medicine OhioState University Columbus Ohio 43210 United States College of Dentistry University of Florida Gainesville Florida 32610 United States North Florida/South Georgia Veteran Health System Gainesville Florida 32610 United States Research Service Cincinnati VAMCCincinnati Ohio 45220 United States

AIM： To characterize thermal hypersensitivity in patients with constipation- and diarrhea-predominant irritable bowel syndrome （IbS）. METHODS： Thermal pain sensitivity was tested among patients with diarrhea-predominant IbS （D-IbS） and constipation-predominant IbS （C-IbS） compared to healthy subjects. A total of 42 patients （29 female and 13 male; mean age 27.0 ＋ 6.4 years） with D-IbS; 24 patients （16 female and eight male; mean age 32.5 ：1：8.8 years） with C-IbS; and 52 control subjects （34 female and 18 male; mean age 27.3 ± 8.0 years） participated in the study. Thermal stimuli were delivered using a Medoc Thermal Sensory Analyzer with a 3 cm × 3 cm surface area. Heat pain threshold （HPTh） and heat pain tolerance （HPTo） were assessed on the left ventral forearm and left calf using an ascending method of limits. The Functional bowel Disease Severity Index （FbDSI） was also obtained for all subjects. RESULTS： Controls were less sensitive than C-IbS and D-IbS （both at P 〈 0.001） with no differences between C-IbS and D-IbS for HPTh and HPTo. Thermal hyperalgesia was present in both groups of IbS patients relative to controls, with IbS patients reporting significantly lower pain threshold and pain tolerance at both test sites. Cluster analysis revealed the presence of subgroups of IbS patients based on thermal hyperalgesia. One cluster （17% of the sample） showed a profile of heat pain sensitivity very similar to that of healthy controls; a second cluster （47% of the sample） showed moderate heat pain sensitivity; and a third cluster （36% of the sample） showed a very high degree of thermal hyperalgesia. CONCLUSION： A subset of IbS patients had thermal hypersensitivity compared to controls, who reported significantly lower HPTh and HPTo. All IbS patients had a higher score on the FbDSI than controls. Interestingly, the subset of IbS patients with high thermal sensitivity （36%） had the highest FbDSI score compared to the other two groups of IbS patients.

关键词： Irritable bowel syndrome Visceral pain thermal hypersensitivity Heat pain threshold Heat pain tolerance

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Neural grafting for Parkinson's disease:challenges and prospects

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Neural Regeneration Research 2017年第3期12卷 389-392页

作者： Thomas b.Stoker nicholas F.blair Roger A.barker John van Geest Center for brain Repair Department of Clinical NeurosciencesUniversity of CambridgeCambridgeUK Wellcome Trust-Medical Research Council Stem Cell Institute University of CambridgeCambridgeUK

Parkinson＇s disease（PD） is a neurodegenerative condition which causes a characteristic movement disorder secondary to loss of dopaminergic neurons in the substanitia *** motor disorder responds well to dopamine-replacement therapies,though these result in significant adverse effects due to non-physiological release of dopamine in the striatum,and off-target ***-based regenerative treatments offer a potential means for targeted replacement of dopamine,in a physiological *** neurons for cell-based therapies can be obtained from several *** ventral mesencephalon tissue contains dopaminergic neuron progenitors,and has been transplanted into the striatum of PD patients with good results in a number of ***,the ethical implications and logistical challenges of using fetal tissue mean that fetal ventral mesencephalon is unlikely to be used in a widespread clinical *** pluripotent stem cells can be used to generate dopaminergic neurons for transplantation,providing a source of autologous tissue for *** approach means that challenges associated with allografts,such as the potential for immune rejection,can be ***,the associated cost and difficulty in producing a standardized product from different cell lines means that,at present,this approach is not commercially viable as a cell-based *** neurons derived from embryonic stem cells offer the most promising basis for a cell-based therapy for Parkinson＇s disease,with trials due to commence in the next few *** there are ethical considerations to take into account when using embryonic tissue,the possibility of producing a standardized,optimized cell product means that this approach can be both effective,and commercially viable.

关键词： Parkinson's disease neural grafting embryonic stem cells induced pluripotent stem cells induced neurons cell-based therapies

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H pylori and gastric cancer: Shifting the global burden

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World Journal of Gastroenterology 2006年第34期12卷 5458-5464页

作者： Christian Prinz susanne Schwendy Petra Voland II. MedicalDepartment Technical University of Munich D-81675 MunichGermany

Infection with H pylori leads to a persistent chronic inflammation of the gastric mucosa, thereby increasing the risk of distal gastric adenocarcinoma. Numerous studies have determined a clear correlation between Hpylori infection and the risk of gastric cancer; however, general eradication is not recommended as cancer prophylaxis and time points for treatment remain controversial in different areas of the world. Prevalence rates in Western countries are decreasing, especially in younger people （〈 10%）; and a decline in distal gastric adenocarcinoma has been observed. Risk groups in Western countries still show considerably higher risk of developing cancer, especially in patients infected with cagA^＋ strains and in persons harboring genetic polymorphism of the IL-1b promoter （-511T/T） and the corresponding IL-1 receptor antagonist （IL-1RN^＊2）. Thus, general eradication of all infected persons in Western countries not recommended and is limited to risk groups in order to achieve a risk reduction. In contrast, infection rates and cancer prevalence are still high in East Asian countries. A prevention strategy to treat infected persons may avoid the development of gastric cancer to a large extent and with enormous clinical importance. However, studies in China and Japan indicate that prevention of gastric cancer is effective only in those patients that do not display severe histological changes such as atrophy and intestinal metaplasia. Thus, prophylactic strategies to prevent gastric cancer in high risk populations such as China should therefore especially aim at individuals now at younger age when the histological alterations caused by the bacterial infection was still reversible. In countries with a low prevalence of gastric cancer, risk groups carrying cagA^＋ strains and IL-1 genetic polymorphisms should be identified and treated.

关键词： H pylori Gastric cancer

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Four-wheel-drive immune protection

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3637-3638页

作者： Fabian Heinrich susanne Krasemann Institute of Legal Medicine University Medical Center Hamburg Eppendorf20251 HamburgGermany Institute of Neuropathology University Medical Center Hamburg Eppendorf20251 HamburgGermany

In a recent study published in Cell,Zhang and colleagues provide the first longitudinal study comparing four different COVID-19 vaccines head-to-head for binding and neutralizing antibodies,spike-specific CD4+or CD8+T... 详细信息

关键词： antibodies immune vaccines

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New methods for identification of disinfection byproducts of toxicological relevance: Progress and future directions

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Journal of Environmental Sciences 2021年第1期33卷 151-159页

作者： nicholas J.P.Wawryk Caley b.Craven Lindsay K.Jmaiff blackstock Xing-Fang Li Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and PathologyFaculty of Medicine and DentistryUniversity of AlbertaEdmontonABT6G 2G3Canada

Disinfection byproducts(DbPs)represent a ubiquitous source of chemical exposure in disinfected *** over 700 DbPs have been identified,the drivers of toxicity remain poorly ***,ever evolving water treatment practices have led to a continually growing list of *** of analytical technologies have enabled the identification of new classes of DbPs and the quantification of these chemically diverse sets of *** we summarize advances in new workflows for DbP analysis,including sample preparation,chromatographic separation with mass spectrometry(MS)detection,and data *** aid in the selection of techniques for future studies,we discuss necessary considerations for each step in the *** review focuses on how each step of a workflow can be optimized to capture diverse classes of DbPs within a single ***,we highlight new MS-based approaches that can be powerful for identifying novel DbPs of toxicological *** discuss current challenges and provide perspectives on future research directions with respect to studying new DbPs of toxicological *** analytical technologies continue to advance,new strategies will be increasingly used to analyze complex DbPs produced in different treatment processes with the aim to identify potential drivers of toxicity.

关键词： Water disinfection byproducts(DbPs) Emerging contaminants Mass spectrometry Chromatography Nontargeted analysis Toxicity drivers

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Ultrafast imaging of terahertz electric waveforms using quantum dots

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Light(Science & Applications) 2022年第1期11卷 63-68页

作者： Moritz b.Heindl nicholas Kirkwood Tobias Lauster Julia A.Lang Markus Retsch Paul Mulvaney Georg Herink Experimental Physics VIII-Ultrafast Dynamics University of BayreuthBayreuthGermany ARC Centre of Excellence in Exciton Science School of ChemistryUniversity of MelbourneMelbourneAustralia Physical Chemistry I University of BayreuthBayreuthGermany

Microscopic electric fields govern the majority of elementary excitations in condensed matter and drive electronics at frequencies approaching the Terahertz(THz)***,only few imaging schemes are able to resolve sub-wavelength fields in the THz range,such as scanning-probe techniques,electro-optic sampling,and ultrafast electron ***,intrinsic constraints on sample geometry,acquisition speed and field strength limit their ***,we harness the quantum-confined Stark-effect to encode ultrafast electric near-fields into colloidal quantum dot *** approach,termed Quantum-probe Field Microscopy(QFIM),combines far-field imaging of visible photons with phase-resolved sampling of electric *** capturing ultrafast movies,we spatio-temporally resolve a Terahertz resonance inside a bowtie antenna and unveil the propagation of a Terahertz waveguide excitation deeply in the sub-wavelength *** demonstrated QFIM approach is compatible with strong-field excitation and sub-micrometer resolution—introducing a direct route towards ultrafast field imaging of complex nanodevices inoperando.

关键词： antenna waveguide quantum

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