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A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+breast cancer cells

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Microsystems & Nanoengineering 2024年第1期10卷 287-299页

作者： Braulio Andrés Ortega Quesada Jonathan Cuccia Rachael Coates Blake Nassar Ethan Littlefield elizabeth C.Martin Adam t.Melvin Cain Department of Chemical Engineering Louisiana State UniversityBaton RougeLA 70803USA Department of Chemical and Biological Engineering Clemson UniversityClemsonSC 29634USA Biological and Agricultural Engineering Louisiana State UniversityBaton RougeLA 70803USA Department Medicine Section Hematology and Medical OncologyTulane UniversityNew OrleansLA 70118USA

Metastatic breast cancer leads to poor prognoses and worse outcomes in patients due to its invasive behavior and poor response to therapy.It is still unclear what biophysical and biochemical factors drive this more aggressive phenotype in metastatic cancer;however recent studies have suggested that exposure to fluid shear stress in the vasculature could cause this.In this study a modular microfluidic platform capable of mimicking the magnitude of fluid shear stress(FSS)found in human vasculature was designed and fabricated.this device provides a platform to evaluate the effects of FSS on MCF-7 cell line,an estrogen receptor positive(ER+)breast cancer cell line,during circulation in the vessels.Elucidation of the effects of FSS on MCF-7 cells was carried out utilizing two approaches:single cell analysis and bulk analysis.For single cell analysis,cells were trapped in a microarray after exiting the serpentine channel and followed by immunostaining on the device(on-chip).Bulk analysis was performed after cells were collected in a microtube at the outlet of the microfluidic serpentine channel for western blotting(off-chip).It was found that cells exposed to an FSS magnitude of 10 dyn/cm^(2) with a residence time of 60 s enhanced expression of the proliferation marker Ki67 in the MCF-7 cell line at a single cell level.to understand possible mechanisms for enhanced Ki67 expression,on-chip and off-chip analyses were performed for pro-growth and survival pathways ERK,AKt,and JAK/StAt.Results demonstrated that after shearing the cells phosphorylation of p-AKt,p-mtOR,and p-StAt3 were observed.However,there was no change in p-ERK1/2.AKt is a mediator of ER rapid signaling,analysis of phosphorylated ERαwas carried out and no significant differences between sheared and non-sheared populations were observed.taken together these results demonstrate that FSS can increase phosphorylation of proteins associated with a more aggressive phenotype in circulating cancer cells.these findings provide additional information that may help

关键词： fluid breast estrogen

Hepatic grooves:An observational study at laparoscopic surgery

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World Journal of Experimental Medicine 2024年第2期14卷 97-102页

作者： Shamir O Cawich Dexter A thomas Fawwaz Mohammed Michael t Gardner Marlene Craigie Shaneeta Johnson Ramnanand S Kedambady Department of Surgery University of the West IndiesSt Augustine 000000Trinidad and Tobago Department of Surgery Port of Spain General HospitalPort of Spain 000000Trinidad and Tobago Section of Anatomy Basic Medical SciencesUniversity of the West IndiesKingston 000000Jamaica Department of Radiology University of the West IndiesKingston 000000Jamaica Department of Surgery Morehouse School of MedicineAtlantaGA 30310United States Section of Anatomy Department of Basic Medical SciencesUniversity of the West IndiesKingston KIN7Jamaica

BACKGROUND In traditional descriptions,the upper surface of the liver is smooth and convex,but deep depressions are variants that are present in 5%-40%of patients.We sought to determine the relationship between surface depressions and the diaphragm.AIM to use exploratory laparoscopy to determine the relationship between surface depressions and the diaphragm.MEtHODS An observational study was performed in all patients undergoing laparoscopic upper gastro-intestinal operations between January 1,2023 and January 20,2024.A thirty-degree laparoscope was used to inspect the liver and diaphragm.When surface depressions were present,we recorded patient demographics,presence of diaphragmatic bands,rib protrusions and/or any other source of compression during inspection.RESULtS Of 394 patients,343 had normal surface anatomy,and 51(12.9%)had prominent surface depressions on the liver.there was no significant relationship between the presence of surface depressions and gender nor the presence of rib projections.However,there was significant association between the presence of surface depressions and diaphragmatic muscular bands(Pth these data,the diaphragmatic-band theory has gained increased importance over other theories for surface depressions.Further studies are warranted using cross sectional imaging to confirm relationships with intersectional planes as well as beta-catenin assays in the affected liver parenchyma.

关键词： Liver Variant Vein Hepatic Surgery

EZH2 inhibitors promote β-like cell regeneration in young and adult type 1 diabetes donors

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Signal transduction and targeted therapy 2024年第2期9卷 679-692页

作者： Keith Al-Hasani Safiya Naina Marikar Harikrishnan Kaipananickal Scott Maxwell Jun Okabe Ishant Khurana thomas Karagiannis Julia J.Liang Lina Mariana thomas Loudovaris thomas Kay Assam El-Osta Epigenetics in Human Health and Disease Program Baker Heart and Diabetes Institute75 Commercial RoadMelbourne 3004 VICAustralia Department of Diabetes Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia Epigenetics in Human Health and Disease Laboratory Central Clinical SchoolMonash UniversityMelbourne 3004 VICAustralia School of Science STEM CollegeRMIT UniversityMelbourne 3001 VICAustralia Immunology and Diabetes Unit St Vincent’s Institute of Medical ResearchFitzroy 3065 VICAustralia Department of Medicine and therapeutics The Chinese University of Hong KongSha TinHong Kong SAR Hong Kong Institute of Diabetes and Obesity Prince of Wales HospitalThe Chinese University of Hong Kong3/F Lui Che Woo Clinical Sciences Building30-32-Ngan Shing StreetSha TinHong Kong SAR Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongSha TinHong Kong SAR Biomedical Laboratory Science Department of TechnologyFaculty of HealthUniversity College CopenhagenCopenhagenDenmark

β-cells are a type of endocrine cell found in pancreatic islets that synthesize,store and release insulin.In type 1 diabetes(t1D),t-cells of the immune system selectively destroy the insulin-producingβ-cells.Destruction of these cells leads to a lifelong dependence on exogenous insulin administration for survival.Consequently,there is an urgent need to identify novel therapies that stimulateβ-cell growth and induceβ-cell function.We and others have shown that pancreatic ductal progenitor cells are a promising source for regeneratingβ-cells for t1D owing to their inherent differentiation capacity.Default transcriptional suppression is refractory to exocrine reaction and tightly controls the regenerative potential by the EZH2 methyltransferase.In the present study,we show that transient stimulation of exocrine cells,derived from juvenile and adult t1D donors to the FDAapproved EZH2 inhibitors GSK126 and tazemetostat(taz)influence a phenotypic shift towards aβ-like cell identity.the transition from repressed to permissive chromatin states are dependent on bivalent H3K27me3 and H3K4me3 chromatin modification.targeting EZH2 is fundamental toβ-cell regenerative potential.Reprogrammed pancreatic ductal cells exhibit insulin production and secretion in response to a physiological glucose challenge ex vivo.these pre-clinical studies underscore the potential of small molecule inhibitors as novel modulators of ductal progenitor differentiation and a promising new approach for the restoration ofβ-like cell function.

关键词： EZH2 struction inhibitors

Development of a Proof-of-Concept Multi-Method Computer Simulation to Support Rural Healthcare Disaster Preparedness Planning

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International Journal of Disaster Risk Science 2024年第3期15卷 346-358页

作者： thomas A.Berg Kristina W.Kintziger Julie Suzuki Crumly Scott A.Lawson Carole R.Myers tracey t.Stansberry College of Nursing University of Tennessee Knoxville Department of Environmental Agricultural and Occupational Health University of Nebraska Medical Center Public Health and Healthcare Oak Ridge Associated Universities

Due to a lack of resources, rural communities often face challenges when planning catastrophic events. this project involved applying systems thinking and model-based systems engineering to develop a proof-of-concept, multi-method computer simulation and then determining whether the simulation could be used to assess the efficacy of disaster planning approaches on health outcomes in rural communities, as a function of primary healthcare. the project focus was a rural or non-urban healthcare system experiencing a natural hazard. Both system dynamics and discrete event models were incorporated to represent subsystem operations, crucial disaster responses, as well as three key response systems: public health, emergency management, and healthcare. the subsystem models included several components: policies/procedures, communications,resources, exercises/drills/training, healthcare space and staff, and the flow of affected people into and through the system.the combined simulation can serve as a first step to a more comprehensive approach to helping rural communities achieve more efficient and effective healthcare planning for disaster responses.

关键词： Computer simulation Disaster preparedness Model-based systems engineering Rural healthcare System dynamics model Systems thinking

B-cell and antibody responses to SARS-CoV-2:infection,vaccination,and hybrid immunity

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Cellular & Molecular Immunology 2024年第2期21卷 144-158页

作者： Dennis Lapuente thomas H.Winkler Matthias tenbusch Institut für klinische und molekulare Virologie Universitätsklinikum Erlangen und Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergSchlossgarten 491054 ErlangenGermany Department of Biology Division of GeneticsNikolaus-Fiebiger-Center for Molecular MedicineFriedrich-Alexander-Universität Erlangen-Nürnberg(FAU)ErlangenGermany Medical Immunology Campus Erlangen Friedrich-Alexander-Universität(FAU)Erlangen-NürnbergSchlossplatz 191054 ErlangenGermany

the emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in 2019 prompted scientific,medical,and biotech communities to investigate infection-and vaccine-induced immune responses in the context of this pathogen.B-cell and antibody responses are at the center of these investigations,as neutralizing antibodies(nAbs)are an important correlate of protection(COP)from infection and the primary target of SARS-CoV-2 vaccine modalities.In addition to absolute levels,nAb longevity,neutralization breadth,immunoglobulin isotype and subtype composition,and presence at mucosal sites have become important topics for scientists and health policy makers.the recent pandemic was and still is a unique setting in which to study de novo and memory B-cell(MBC)and antibody responses in the dynamic interplay of infection-and vaccine-induced immunity.It also provided an opportunity to explore new vaccine platforms,such as mRNA or adenoviral vector vaccines,in unprecedented cohort sizes.Combined with the technological advances of recent years,this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings.In this review,we summarize the key findings of the last 2.5 years regarding infection-and vaccine-induced B-cell immunity,which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.

关键词： SARS-CoV-2 neutralizing antibodies memory responses vaccines IgG4

Does topical vancomycin prevent fracture-related infections in closed fractures undergoing open reduction and internal fixation?A randomised controlled trial

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Chinese Journal of traumatology 2024年第2期27卷 71-76页

作者： Mohit Gandhi Gopisankar Balaji Jagdish Menon Ruben Raj thomas Department of Orthopaedics Jawaharlal Institute of Postgraduate Medical Education and ResearchPondicherryIndia Department of Preventive and Social Medicine Jawaharlal Institute of Postgraduate Medical Education and ResearchPondicherryIndia

Purpose:the role of topical vancomycin in fracture-related infection(FRI)is debatable.Very few studies have reported their efficacy in open and high-risk extremity fractures.this study aimed to assess topical vancomycin's role in reducing FRI in closed fractures undergoing open surgical intervention with an implant.Methods:this prospective randomized cohort study was carried out between February 2021 to January 2022.Patients with isolated closed fractures,who were planned for open reduction and internal fixation within 2 weeks from the time of injury were included for this study.the data collected included age,gender,socioeconomic status,mechanism of injury,diagnosis,tscherne classification,and time interval to take up for surgery.Patients were randomized into the intervention and control groups using the block randomization technique.the control group received only systemic antibiotic prophylaxis,whereas the intervention group received topical application of vancomycin powder in the surgical wound alongside systemic antibiotic prophylaxis.the primary outcome measure was the incidence of FRI among these individuals.Clinical and radiological findings and culture reports(in cases with infection)were recorded during the post-operative period and at 6 weeks of follow-up.All relevant statistical calculations were done using StAtA statistical/data analysis-parallel edition version 16.0(StataCorp LLC).the quantitative variables like age and duration of the surgery were assessed for normalcy by Shapiro-Wilk W test.An independent samples t-test with equal variances was applied to the age data.Fisher's exact test was used for the analysis of the primary outcome measure(presence of FRI following surgery),and"Risk of FRI"and"Risk difference"between the 2 groups was calculated.the strength of the association between qualitative variables was assessed using the Fisher's exact and Chi-square tests,respectively.Results:there were 88 patients included in this study.No statistical significance was found about FRI between both grou

关键词： Infections Antibiotics Vancomycin Fractures

the timing of Primary Neurosurgical Repair and Wound-Site Infection in Children with Myelomeningocele

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Open Journal of Modern Neurosurgery 2024年第2期14卷 137-148页

作者： Joseph O. Obande Paul t. Bitrus elizabeth I. Obande Division of Neurosurgery Department of Surgery University of Abuja Teaching Hospital Abuja Nigeria Post-Basic School of Critical Care Nursing University of Abuja Teaching Hospital Abuja Nigeria

Background: the optimal time to closure of a newborn with a myelomeningocele has been the focus of a number of evaluations. the timing of primary surgery has received significant attention due to its relationship to repair-site infection that can lead to increased morbidity and prolonged hospital stays. It is on this basis that recommendations have utilized 48 - 72 hours post birth as ideal time of closure. this is not only prevent infection at the site but also prevent ventriculitis and neural structure damage. We therefore, hypothesized an increase in wound infection rates in those patients with delays in myelomeningocele repair. Methods: We retrospectively reviewed the records of 103 children with myelomeningocele treated between 2016 and 2023. At discharge the patients were followed up at the post-operative clinic visit 2 weeks later. Children were assigned to 1 of 2 groups, those who underwent primary neurosurgical repair within 72 hours of delivery (Group 1) and those undergoing repair after 72 hours (Group 2). We compared the infection rates. Results: 103 children who underwent myelomeningocele repair were identified, with a median time from birth to treatment of 1 day. Eight (7.8 %) patients were noted to have post-repair surgical site complications. there was no significant difference in rates of infection between Group 1 and Group 2 repair times. the presence of infection was associated increased length of stay when compared to neonates without infection. Conclusion: In children with myelomeningocele, the timing of primary neurosurgical repair appears not to have a significant impact on surgical site infection. Closure of the spinal lesion within the first 72 hours of life may be more favorable for neural damage prevention. these results suggest that early myelomeningocele repair may not impart significantly on the rate of wound-site infection.

关键词： Spina Bifida Surgical timing Excision and Repair Surgical Site Infection Myelomeningocele

Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy

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Asian Journal of Urology 2024年第2期11卷 316-323页

作者： Ryan A.Dornbier Chirag P.Doshi Shalin C.Desai Petar Bajic Michelle Van Kuiken Mark Khemmani Ahmer V.Farooq Larissa Bresler thomas M.t.turk Alan J.Wolfe Kristin G.Baldea Loyola University Medical Center Department of UrologyMaywoodILUSA Loyola University Chicago Department of Microbiology and ImmunologyMaywoodILUSA

Objective:to identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).the association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains unknown.Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk.Methods:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without MetS.Both sample types were subjected to expanded quantitative urine culture(EQUC)and 16 S ribosomal RNA gene sequencing.Results:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS comorbidities.No controls had uric acid stone composition.By EQUC,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to controls.to validate our EQUC results,we performed 16 S ribosomal RNA gene sequencing.In 12/16(75.0%)sequence-positive stones,EQUC reliably isolated at least one species of the sequenced genera.Bacteria were detected in both“infectious”and“non-infectious”stone compositions.Conclusion:Bacteria are more common and more abundant in MetS stones than control stones.Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

关键词： Nephrolithiasis Urolithiasis Metabolic syndrome Urinary microbiome Percutaneous nephrolithotomy

Bacterial plant pathogens affect the locomotor behavior of the insect vector:a case study of Citrus volkameriana-triozae erytreae-Candidatus Liberibacter asiaticus system

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Insect Science 2024年第3期31卷 901-910页

作者： Arnaud Ameline Alain Karkach thomas Denoirjean Martial Grondin Florencia Molinari Patrick turpin Helene Delatte Bernard Reynaud UMR CNRS 7058 EDYSAN(Ecologie et Dynamique des Systemes Anthropises) Universite de Picardie Jules VerneAmiensCedexFrance UMR PVBMt(Peuplements végétaux et bioagresseurs en milieu tropical) Universitéde la RéunionSaint PierreLa RéunionFrance

Plant pathogens can alter the behavior of their insect vectors as well as their survival and reproduction.the African psyllid,trioza erytreae,is one of the vectors of Huanglongbing,a citrus disease caused mainly by"Candidatus Liberibacter asiaticus"(CLas).the purpose of this study was to characterize the effects of CLas on the psyllid,t.erytreae using Citrus volkamerina plants as the study system.the study focused more specifically on the CLas effects prior to and after its acquisition by the psyllid t.erytreae.Our results did not support the hypothesis that CLas effects psyllid probing behavior prior to acquisition;few differences were observed between uninfected t.erytrea feeding on CLas-infected versus control plants.On the other hand,compared to psyllids that had completed their development on control plants,the ones that had completed their development on a CLas-infected plant exhibited changes in their behavior(greater velocity),physiology(smaller mass)and biochemistry(lower water and lipid content).Altogether,our results confirm the existence of a marked postacquisition effect on the vector locomotor behavior and a minor preacquisition effect of CLas on the vector behavior,which can be partially explained by physiological and biochemical changes.

关键词： electrical penetration graph Huanglongbing locomotory behavior lipid biomass probing behavior vector manipulation