Open-source, cost-effective system for low-light in vivo fiber photometry

ABSTRACTBackgroundIntracranial photometry through chronically implanted optical fibers is a widely adopted technique for measuring signals from fluorescent probes in deep-brain structures. The recent proliferation of bright, photo-stable, and specific genetically-encoded fluorescent reporters for calcium and for other neuromodulators has greatly increased the utility and popularity of this technique.New MethodHere we describe an open-source, cost-effective, microcontroller-based solution for controlling optical components in an intracranial photometry system and processing the resulting signal.ResultsWe show proof-of-principle that this system supports high quality intracranial photometry recordings from dorsal striatum in freely moving mice. A single system supports simultaneous fluorescence measurements in two independent color channels, but multiple systems can be integrated together if additional fluorescence channels are required. This system is designed to work in combination with either commercially available or custom-built optical components. Parts can be purchased for less than one tenth the cost of commercially available alternatives and complete assembly takes less than one day for an inexperienced user.Comparison with Existing Method(s)Currently available hardware draws on a variety of commercial, custom-built, or hybrid elements for both optical and electronic components. Many of these hardware systems are either specialized and inflexible, or over-engineered and expensive.ConclusionsThis open-source system increases experimental flexibility while reducing cost relative to current commercially available components. All software and firmware are open-source and customizable, affording a degree of experimental flexibility that is not available in current commercial systems.

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From hardware store to hospital: a COVID-19-inspired, cost-effective, open-source, in vivo-validated ventilator for use in resource-scarce regions

Bio-Design and Manufacturing ◽

10.1007/s42242-021-00164-1 ◽

2021 ◽

Author(s):

Matthew H. Park ◽

Yuanjia Zhu ◽

Hanjay Wang ◽

Nicholas A. Tran ◽

Jinsuh Jung ◽

...

Keyword(s):

Open Source ◽

Peak Inspiratory Pressure ◽

Cost Effective ◽

Global Scale ◽

Large Animal ◽

Life Saving ◽

Economic Barriers ◽

Care Guidelines ◽

Large Animals

AbstractResource-scarce regions with serious COVID-19 outbreaks do not have enough ventilators to support critically ill patients, and these shortages are especially devastating in developing countries. To help alleviate this strain, we have designed and tested the accessible low-barrier in vivo-validated economical ventilator (ALIVE Vent), a COVID-19-inspired, cost-effective, open-source, in vivo-validated solution made from commercially available components. The ALIVE Vent operates using compressed oxygen and air to drive inspiration, while two solenoid valves ensure one-way flow and precise cycle timing. The device was functionally tested and profiled using a variable resistance and compliance artificial lung and validated in anesthetized large animals. Our functional test results revealed its effective operation under a wide variety of ventilation conditions defined by the American Association of Respiratory Care guidelines for ventilator stockpiling. The large animal test showed that our ventilator performed similarly if not better than a standard ventilator in maintaining optimal ventilation status. The FiO2, respiratory rate, inspiratory to expiratory time ratio, positive-end expiratory pressure, and peak inspiratory pressure were successfully maintained within normal, clinically validated ranges, and the animals were recovered without any complications. In regions with limited access to ventilators, the ALIVE Vent can help alleviate shortages, and we have ensured that all used materials are publicly available. While this pandemic has elucidated enormous global inequalities in healthcare, innovative, cost-effective solutions aimed at reducing socio-economic barriers, such as the ALIVE Vent, can help enable access to prompt healthcare and life saving technology on a global scale and beyond COVID-19.

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The CSF p-tau181/Aβ42 Ratio Offers a Good Accuracy “In Vivo” in the Differential Diagnosis of Alzheimer’s Dementia

Current Alzheimer Research ◽

10.2174/1567205016666190725150836 ◽

2019 ◽

Vol 16 (7) ◽

pp. 587-595 ◽

Cited By ~ 7

Author(s):

Roberto Santangelo ◽

Alessandro Dell'Edera ◽

Arianna Sala ◽

Giordano Cecchetti ◽

Federico Masserini ◽

...

Keyword(s):

Clinical Practice ◽

Clinical Diagnosis ◽

Fdg Pet ◽

Amyloid Β ◽

Cost Effective ◽

Daily Clinical Practice ◽

Different Types ◽

Experimental Trials ◽

Csf Findings

Background: The incoming disease-modifying therapies against Alzheimer’s disease (AD) require reliable diagnostic markers to correctly enroll patients all over the world. CSF AD biomarkers, namely amyloid-β 42 (Aβ42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau181), showed good diagnostic accuracy in detecting AD pathology, but their real usefulness in daily clinical practice is still a matter of debate. Therefore, further validation in complex clinical settings, that is patients with different types of dementia, is needed to uphold their future worldwide adoption. Methods: We measured CSF AD biomarkers’ concentrations in a sample of 526 patients with a clinical diagnosis of dementia (277 with AD and 249 with Other Type of Dementia, OTD). Brain FDG-PET was also considered in a subsample of 54 patients with a mismatch between the clinical diagnosis and the CSF findings. Results: A p-tau181/Aβ42 ratio higher than 0.13 showed the best diagnostic performance in differentiating AD from OTD (86% accuracy index, 74% sensitivity, 81% specificity). In cases with a mismatch between clinical diagnosis and CSF findings, brain FDG-PET partially agreed with the p-tau181/Aβ42 ratio, thus determining an increase in CSF accuracy. Conclusions: The p-tau181/Aβ42 ratio alone might reliably detect AD pathology in heterogeneous samples of patients suffering from different types of dementia. It might constitute a simple, cost-effective and reproducible in vivo proxy of AD suitable to be adopted worldwide not only in daily clinical practice but also in future experimental trials, to avoid the enrolment of misdiagnosed AD patients.

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Polyamines and Related Nitrogen Compounds in the Chemotherapy of Neglected Diseases Caused by Kinetoplastids

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180427151338 ◽

2018 ◽

Vol 18 (5) ◽

pp. 321-368 ◽

Cited By ~ 2

Author(s):

Juan A. Bisceglia ◽

Maria C. Mollo ◽

Nadia Gruber ◽

Liliana R. Orelli

Keyword(s):

Drug Targets ◽

Redox Homeostasis ◽

Cost Effective ◽

Structural Features ◽

Mammalian Host ◽

Neglected Diseases ◽

Nitrogen Compounds ◽

Chemical Structures

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.

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Extended Routine Follow-up of Primary Uncomplicated Hip and Knee Arthroplasty is not Necessary

The Open Orthopaedics Journal ◽

10.2174/1874325001913010266 ◽

2019 ◽

Vol 13 (1) ◽

pp. 266-271

Author(s):

Georgina Kakra Wartemberg ◽

Thomas Goff ◽

Simon Jones ◽

James Newman

Keyword(s):

Aseptic Loosening ◽

Revision Surgery ◽

Revision Arthroplasty ◽

Cost Effective ◽

Face To Face ◽

Primary Surgery ◽

Effective System ◽

Knee Revision Surgery ◽

Knee Revision

Aims: To create a more effective system to identify patients in need of revision surgery. Background: There are over 160,000 total hip and knee replacements performed per year in England and Wales. Currently, most trusts review patients for up to 10 years or more. When we consider the cost of prolonged reviews, we cannot justify the expenditure within a limited budget. Study Design & Methods: We reviewed all patients' notes that underwent primary hip and knee revision surgery at our institution, noting age, gender, symptoms at presentation, referral source, details of the surgery, reason for revision and follow up history from primary surgery. Results: There were 145 revision arthroplasties (60 THR and 85 TKR) that met our inclusion criteria. Within the hip arthroplasty group, indications for revision included aseptic loosening (37), dislocation (10), and infection (3), periprosthetic fracture, acetabular liner wear and implant failure. All thirty-seven patients with aseptic loosening presented with pain. Twenty-five were referred from general practice with new symptoms. The remaining were clinic follow-ups. The most common reason for knee revision was aseptic loosening (37), followed by infection (21) and then progressive osteoarthritis (8). Most were referred from GP as a new referral or were clinic follow-ups. All patients were symptomatic. Conclusion: All the patients that underwent revision arthroplasty were symptomatic. Rather than yearly follow up, we recommend a cost-effective system. We are implementing a 'non face-to-face' system. Patients would be directly sent a questionnaire and x-ray form. The radiographs and forms will be reviewed by an experienced arthroplasty surgeon. The concerning cases will be seen urgently in a face-to-face clinic.

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Facile sonochemical-assisted synthesis of orthorhombic phase black phosphorus/rGO hybrids for effective photothermal therapy

Nanophotonics ◽

10.1515/nanoph-2019-0476 ◽

2020 ◽

Vol 9 (9) ◽

pp. 3023-3034

Author(s):

Weiyuan Liang ◽

Dou Wang ◽

Xiaohui Ren ◽

Chenchen Ge ◽

Hanyue Wang ◽

...

Keyword(s):

Electrode Materials ◽

Orthorhombic Phase ◽

Cost Effective ◽

Black Phosphorus ◽

Antitumor Effects ◽

Covalent Bonds ◽

Preparation Conditions ◽

Reduced Graphene

AbstractTwo-dimensional black phosphorus (BP) has been demonstrated to be promising in photoelectronic devices, electrode materials, and biomedicine owing to its outstanding properties. However, the application of BP has been hindered by harsh preparation conditions, high costs, and easy degradation in ambient condition. Herein, we report a facile and cost-effective strategy for synthesis of orthorhombic phase BP and a kind of BP-reduced graphene oxide (BP/rGO) hybrids in which BP remains stable for more than 4 weeks ascribed to the formation of phosphorus-carbon covalent bonds between BP and rGO as well as the protection effect of the unique wrinkle morphology of rGO nanosheets. Surface modification BP/rGO hybrids (PEGylated BP/rGO) exhibit excellent photothermal performance with photothermal conversion efficiency as high as 57.79% at 808 nm. The BP/rGO hybrids exhibit enhanced antitumor effects both in vitro and in vivo, showing promising perspectives in biomedicine.

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Myocardial fibrosis reversion via rhACE2-electrospun fibrous patch for ventricular remodeling prevention

npj Regenerative Medicine ◽

10.1038/s41536-021-00154-y ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zeping Qiu ◽

Jingwen Zhao ◽

Fanyi Huang ◽

Luhan Bao ◽

Yanjia Chen ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Fibrosis ◽

Ventricular Remodeling ◽

Cardiac Fibroblasts ◽

Cost Effective ◽

Intramyocardial Injection ◽

Undesirable Consequence ◽

Adverse Remodeling

AbstractMyocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.

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Light and CO2 Modulate the Accumulation and Localization of Phenolic Compounds in Barley Leaves

Antioxidants ◽

10.3390/antiox10030385 ◽

2021 ◽

Vol 10 (3) ◽

pp. 385

Author(s):

Lena Hunt ◽

Karel Klem ◽

Zuzana Lhotáková ◽

Stanislav Vosolsobě ◽

Michal Oravec ◽

...

Keyword(s):

Oxidative Stress ◽

Phenolic Compounds ◽

Co2 Concentration ◽

Environmental Stressors ◽

Low Light ◽

Mesophyll Cells ◽

Stress Prevention ◽

Tolerant Variety ◽

Barley Leaves

Barley (Hordeum vulgare) accumulates phenolic compounds (PhCs), which play a key role in plant defense against environmental stressors as antioxidants or UV screening compounds. The influence of light and atmospheric CO2 concentration ([CO2]) on the accumulation and localization of PhCs in barley leaves was examined for two varieties with different tolerances to oxidative stress. PhC localization was visualized in vivo using fluorescence microscopy. Close relationships were found between fluorescence-determined localization of PhCs in barley leaves and PhC content estimated using liquid chromatography coupled with mass spectroscopy detection. Light intensity had the strongest effect on the accumulation of PhCs, but the total PhC content was similar at elevated [CO2], minimizing the differences between high and low light. PhCs localized preferentially near the surfaces of leaves, but under low light, an increasing allocation of PhCs in deeper mesophyll layers was observed. The PhC profile was significantly different between barley varieties. The relatively tolerant variety accumulated significantly more hydroxycinnamic acids, indicating that these PhCs may play a more prominent role in oxidative stress prevention. Our research presents novel evidence that [CO2] modulates the accumulation of PhCs in barley leaves. Mesophyll cells, rather than epidermal cells, were most responsive to environmental stimuli in terms of PhC accumulation.

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Compliance as a Cost-Effective System of Interaction Between Business and Government

Journal of Business Ethics ◽

10.1007/s10551-021-04890-5 ◽

2021 ◽

Author(s):

Nikolay I. Dorogov ◽

Ivan A. Kapitonov ◽

Nazygul T. Batyrova

Keyword(s):

Cost Effective ◽

Effective System

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Marine Fish Primary Hepatocyte Isolation and Culture: New Insights to Enzymatic Dissociation Pancreatin Digestion

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041380 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1380

Author(s):

Neusa Figueiredo ◽

Beatriz Matos ◽

Mário Diniz ◽

Vasco Branco ◽

Marta Martins

Keyword(s):

Cell Viability ◽

Cell Cultures ◽

Marine Fish ◽

Sparus Aurata ◽

Cost Effective ◽

Primary Hepatocyte ◽

Digestion Method ◽

Trypan Blue Exclusion ◽

And Function

Primary cell cultures from wild organisms have been gaining relevance in ecotoxicology as they are considered more sensitive than immortalized cell lines and retain the biochemical pathways found in vivo. In this study, the efficacy of two methods for primary hepatocyte cell isolation was compared using liver from two marine fish (Sparus aurata and Psetta maxima): (i) two-step collagenase perfusion and (ii) pancreatin digestion with modifications. Cell cultures were incubated in L-15 medium at 17 ± 1 °C and monitored for up to six days for cell viability and function using the trypan blue exclusion test, MTT test, lactate dehydrogenase (LDH) activity, and ethoxyresorufin O-deethylase (EROD) activity after Benzo[a]Pyrene exposure. The results showed significant differences between the number of viable cells (p < 0.05), the highest number being obtained for the pancreatin digestion method (average = 4.5 ± 1.9 × 107 cells). Moreover, the hepatocytes showed solid adherence to the culture plate and the rounded shape, changing into a triangular/polygonal shape. The cell viability and function obtained by pancreatin digestion were maintained for five days, and the EROD induction after exposure to the B[a]P showed that cells were metabolically active. This study shows that the optimized pancreatin digestion method is a valid, cost-effective, and simple alternative to the standard perfusion method for the isolation of primary hepatocytes from fish and is suitable for ecotoxicological studies involving marine pollutants, such as PAHs.

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