Detection Of Hypoxia Research Articles

Evaluation of 18F-EF5 for detection of hypoxia in localized adenocarcinoma of the prostate

Background A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of 18F-labeled hypoxia reporters. Although the 2-nitroimidazole 18F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using 18F-EF5 to detect hypoxia in clinical prostate tumours. Material and methods Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment 18F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. Results We found low tumour-to-muscle ratios of 18F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. Conclusion Our data do not support the use of 18F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.

FETAL QRS-COMPLEXES DETECTECTIONS IN ABDOMINAL SIGNAL BY USING WAVELET-BISPECTRUM

Fetal hypoxia or distress is a physical stress experienced by a fetus due to a lack of oxygen. Intrauterine hypoxia and the resultant perinatal brain damages may lead to extraordinary effects, including continuous lifelong treatments. One of the ways for detecting symptoms of hypoxia is monitoring of the fetus heart activity. At present, the basic method of monitoring the condition of unborn baby is the ultrasound cardiotocography (CTG). Considerably more information for early detection of the fetal hypoxia may be obtained by analyzing fetal electrocardiogram (FECG).

Fluorescence-Based Quantitative and Spatial Analysis of Tumour Spheroids: A Proposed Tool to Predict Patient-Specific Therapy Response.

Tumour spheroids are widely used to pre-clinically assess anti-cancer treatments. They are an excellent compromise between the lack of microenvironment encountered in adherent cell culture conditions and the great complexity of in vivo animal models. Spheroids recapitulate intra-tumour microenvironment-driven heterogeneity, a pivotal aspect for therapy outcome that is, however, often overlooked. Likely due to their ease, most assays measure overall spheroid size and/or cell death as a readout. However, as different tumour cell subpopulations may show a different biology and therapy response, it is paramount to obtain information from these distinct regions within the spheroid. We describe here a methodology to quantitatively and spatially assess fluorescence-based microscopy spheroid images by semi-automated software-based analysis. This provides a fast assay that accounts for spatial biological differences that are driven by the tumour microenvironment. We outline the methodology using detection of hypoxia, cell death and PBMC infiltration as examples, and we propose this procedure as an exploratory approach to assist therapy response prediction for personalised medicine.

Adoption of Color Doppler Ultrasound in the Measurement of Fetal Hypoxia in Late Pregnancy

Objective: In order to improve the detection rate of fetal hypoxia in the third trimester and reduce the probability of adverse pregnancy outcome, color doppler ultrasound (CDU), and contractions were used to assess the severity of fetal hypoxia. Methods: The 61 pregnant women diagnosed with intrauterine hypoxia in South District of The Affiliated Hospital of Chengde Medical College from October 2017 to September 2019 were classified as the sick group. Meanwhile, the 61 normal pregnant women were selected as the control group. CDU was used to detect the relevant indexes of umbilical artery (UA) and middle cerebral artery (MCA) in the two groups, including pulse index (PI), resistance index (RI), systolic peak blood flow velocity (S) and diastolic peak blood flow velocity (D). The Apgar scale was used to score neonatal status. According to the score results, newborns were divided into Apgar ≤ 7 group and Apgar > 7 group. The indexes of UA and MCA were compared between the two groups. The amniotic fluid status of pregnant women was assessed using the contractile stimulation test (CST). The rate of amniotic fluid pollution in pregnant women and the incidence of neonatal asphyxia were calculated. Pregnant women were grouped according to the CST score. The correlation between CST score and amniotic fluid pollution and neonatal asphyxia in pregnant women was analyzed. Results: First, the index of fetal UA was obviously higher than that of the control group, while the index of MCA was obviously lower than that of the control group (P < 0.05). Second, the indexes of fetal UA in Apgar ≤ 7 group were obviously higher than those in Apgar > 7 group, while those in MCA were obviously lower than those in Apgar > 7 group (P < 0.05). Third, the incidence of amniotic fluid pollution and neonatal asphyxia in low and middle groups of pregnant women was obviously higher than that in high groups (P < 0.01). Conclusion: This indicates that the CDU technology combined with uterine contraction stimulation experiment can assess the degree of intrauterine hypoxia in the late stage of pregnancy, which provides a feasible scheme for clinical detection of intrauterine hypoxia.

974 Non-invasive transabdominal assessment of In-Utero fetal oxygen saturation in a hypoxic lamb model

Fetal heart rate monitoring is a poor predictor of fetal hypoxia due to its high false-positive rate. Utilizing a novel transabdominal fetal pulse oximeter (TFO), this study aimed to demonstrate the feasibility of non-invasive and direct assessment of fetal arterial blood oxygen saturation in-utero (SaO2) in a hypoxic lamb model. Fetal hypoxia was induced in 3 gravid term ewes (137.3±3.2 days gestation) by placing an inflatable balloon catheter in the infrarenal aorta via the common femoral artery (Fig 1). A fetal carotid arterial line was placed for continuous hemodynamic monitoring and arterial blood gases (ABG). The uterus was closed around the right fetal forelimb, and the laparotomy was closed, leaving the limb exposed for conventional pulse oximetry. The fetus’s depth from the ewe’s skin was determined, and the TFO device was placed on the ewe’s abdomen. The aortic balloon catheter was inflated in a stepwise fashion to decrease the ewe’s distal mean arterial pressure (dMAP) in 5mmHg increments. At each step, dMAP was maintained for 10 min, and fetal ABGs were recorded at 2.5, 5, and 10-min marks. The balloon was fully deflated after two consecutive measurements of fetal SaO2 <15%. The fetus was recovered for 45 min, and the stepwise gradient was repeated for a second round. At each dMAP level, the average fetal oxygen saturation measured by the TFO (SpO2) was compared to the average fetal SaO2. TFO measurements of fetal SpO2 were compared to fetal SaO2 (Fig 2A) and were found to be highly correlative (R=0.64 and p<0.0001) (Fig 2B). The ex-utero conventional clinical pulse oximeter readings from the exposed forelimb had a weak correlation with fetal SaO2 (R=0.16 and p<0.0003). Fetal depth, composed of ewe’s abdominal wall and uterine wall thickness, was 15.0±4.3mm (SD). The novel TFO device can measure fetal SaO2 based on the high correlation of SpO2 and SaO2 despite intervening maternal anatomy. TFO can potentially improve the accuracy of fetal hypoxia detection. Future research will focus on intrapartum validation in lamb models and human pregnancies.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The evidence and feasibility of using pulse oximetry for the management of childhood pneumonia in low- and middle-income countries: a clinical review

The use of pulse oximetry (POx) for the diagnosis and management of childhood pneumonia has been of interest in recent years. In order to effectively employ POx to manage childhood pneumonia in LMICs, we aim to answer the following five questions through a literature review. These five questions are: 1) Which clinical signs are reliable to detect hypoxia? 2) What is the prevalence of hypoxia among those diagnosed with pneumonia? 3) Does the detection of hypoxia among clinical pneumonia patients improve survival? 4) How reliable are current POx devices in the field? and 5) What are the problems in introducing POx in the field?We searched three keywords-IMCI, childhood pneumonia and pulse oximetry, with the PubMed search engine and extracted 119 articles and book chapters. Each article was reviewed to answer above five questions. The literature review indicates that none of the clinical signs reliably detect hypoxia in children. The prevalence of hypoxia among pneumonia varied based on the study. 17-32% of patients without a diagnosis of pneumonia presented with hypoxia. There are currently no randomized trials available to demonstrate the benefit of pulse oximetry in childhood pneumonia survival. Various devices and probes are used in different studies and there are still technical and logistical issues related to POx device use in the field to manage childhood pneumonia in LMICs. There are numerous barriers to train healthcare workers in all levels. We need affordable, reliable, easy to use pulse oximetry for childhood pneumonia management.

Markers of human endometrial hypoxia can be detected in vivo and ex vivo during physiological menstruation.

STUDY QUESTIONCan markers of human endometrial hypoxia be detected at menstruation in vivo?SUMMARY ANSWEROur in vivo data support the presence of hypoxia in menstrual endometrium of women during physiological menstruation.WHAT IS KNOWN ALREADYCurrent evidence from animal models and human in vitro studies suggests endometrial hypoxia is present at menstruation and drives endometrial repair post menses. However, detection of human endometrial hypoxia in vivo remains elusive.STUDY DESIGN, SIZE, DURATIONWe performed a prospective case study of 16 women with normal menstrual bleeding.PARTICIPANTS/MATERIALS, SETTING, METHODSReproductively aged female participants with a regular menstrual cycle underwent objective measurement of their menstrual blood loss using the alkaline haematin method to confirm a loss of <80 ml per cycle. Exclusion criteria were exogenous hormone use, an intrauterine device, endometriosis or fibroids >3 cm. Participants attended for two MRI scans; during days 1–3 of menstruation and the early/mid-secretory phase of their cycle. The MRI protocol included dynamic contrast-enhanced MRI and T2* quantification. At each visit, an endometrial sample was also collected and hypoxia-regulated repair factor mRNA levels (ADM, VEGFA, CXCR4) were quantified by RT-qPCR.MAIN RESULTS AND THE ROLE OF CHANCEWomen had reduced T2* during menstrual scans versus non-menstrual scans (P = 0.005), consistent with menstrual hypoxia. Plasma flow (Fp) was increased at menstruation compared to the non-menstrual phase (P = 0.0005). Laboratory findings revealed increased ADM, VEGF-A and CXCR4 at menstruation on examination of paired endometrial biopsies from the menstrual and non-menstrual phase (P = 0.008; P = 0.03; P = 0.009). There was a significant correlation between T2* and these ex vivo hypoxic markers (P < 0.05).LIMITATIONS, REASONS FOR CAUTIONThis study examined the in vivo detection of endometrial hypoxic markers at specific timepoints in the menstrual cycle in women with a menstrual blood loss <80 ml/cycle and without significant uterine structural abnormalities. Further research is required to determine the presence of endometrial hypoxia in those experiencing abnormal uterine bleeding with and without fibroids/adenomyosis.WIDER IMPLICATIONS OF THE FINDINGSHeavy menstrual bleeding (HMB) is a common, debilitating condition. Understanding menstrual physiology may improve therapeutics. To our knowledge, this is the first in vivo data supporting the presence of menstrual hypoxia in the endometrium of women with normal menstrual bleeding. If aberrant in those with HMB, these non-invasive tests may aid diagnosis and facilitate personalized treatments for HMB.STUDY FUNDING/COMPETING INTEREST(S)This work was funded by Wellbeing of Women grant RG1820, Wellcome Trust Fellowship 209589/Z/17/Z and undertaken in the MRC Centre for Reproductive Health, funded by grants G1002033 and MR/N022556/1. H.O.D.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (but with no personal remuneration) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc; Myovant Sciences GmbH. H.O.D.C. receives royalties from UpToDate for articles on abnormal uterine bleeding.TRIAL REGISTRATION NUMBERN/A.

Increased [18F]FMISO accumulation under hypoxia by multidrug-resistant protein 1 inhibitors

Background[18F]Fluoromisonidazole ([18F]FMISO) is a PET imaging probe widely used for the detection of hypoxia. We previously reported that [18F]FMISO is metabolized to the glutathione conjugate of the reduced form in hypoxic cells. In addition, we found that the [18F]FMISO uptake level varied depending on the cellular glutathione conjugation and excretion ability such as enzyme activity of glutathione-S-transferase and expression levels of multidrug resistance-associated protein 1 (MRP1, an efflux transporter), in addition to the cellular hypoxic state. In this study, we evaluated whether MRP1 activity affected [18F]FMISO PET imaging.MethodsFaDu human pharyngeal squamous cell carcinoma cells were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, incubated with [18F]FMISO for 4 h under hypoxia, and their radioactivity was then measured. FaDu tumor-bearing mice were intravenously injected with [18F]FMISO, and PET/CT images were acquired at 4 h post-injection (1st PET scan). Two days later, the same mice were pretreated with MRP1 inhibitors (cyclosporine A, lapatinib, or MK-571) for 1 h, and PET/CT images were acquired (2nd PET scan).ResultsFaDu cells pretreated with MRP1 inhibitors exhibited significantly higher radioactivity than those without inhibitor treatment (cyclosporine A: 6.91 ± 0.27, lapatinib: 10.03 ± 0.47, MK-571: 10.15 ± 0.44%dose/mg protein, p < 0.01). In the in vivo PET study, the SUVmean ratio in tumors [calculated as after treatment (2nd PET scan)/before treatment of MRP1 inhibitors (1st PET scan)] of the mice treated with MRP1 inhibitors was significantly higher than those of control mice (cyclosporine A: 2.6 ± 0.7, lapatinib: 2.2 ± 0.7, MK-571: 2.2 ± 0.7, control: 1.2 ± 0.2, p < 0.05).ConclusionIn this study, we revealed that MRP1 inhibitors increase [18F]FMISO accumulation in hypoxic cells. This suggests that [18F]FMISO-PET imaging is affected by MRP1 inhibitors independent of the hypoxic state.

Tumor Hypoxia Regulates Immune Escape/Invasion: Influence on Angiogenesis and Potential Impact of Hypoxic Biomarkers on Cancer Therapies.

The environmental and metabolic pressures in the tumor microenvironment (TME) play a key role in molding tumor development by impacting the stromal and immune cell fractions, TME composition and activation. Hypoxia triggers a cascade of events that promote tumor growth, enhance resistance to the anti-tumor immune response and instigate tumor angiogenesis. During growth, the developing angiogenesis is pathological and gives rise to a haphazardly shaped and leaky tumor vasculature with abnormal properties. Accordingly, aberrantly vascularized TME induces immunosuppression and maintains a continuous hypoxic state. Normalizing the tumor vasculature to restore its vascular integrity, should hence enhance tumor perfusion, relieving hypoxia, and reshaping anti-tumor immunity. Emerging vascular normalization strategies have a great potential in achieving a stable normalization, resulting in mature and functional blood vessels that alleviate tumor hypoxia. Biomarkers enabling the detection and monitoring of tumor hypoxia could be highly advantageous in aiding the translation of novel normalization strategies to clinical application, alone, or in combination with other treatment modalities, such as immunotherapy.

Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models.

Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.

Hypoxia-Triggered Self-Assembly of Ultrasmall Iron Oxide Nanoparticles to Amplify the Imaging Signal of a Tumor.

Hypoxia is a common phenomenon among most solid tumors that significantly influences tumor response toward chemo- and radiotherapy. Understanding the distribution and extent of tumor hypoxia in patients will be very important to provide personalized therapies in the clinic. Without sufficient vessels, however, traditional contrast agents for clinical imaging techniques will have difficulty in accumulating in the hypoxic region of solid tumors, thus challenging the detection of hypoxia in vivo. To overcome this problem, herein we develop a novel hypoxia imaging probe, consisting of a hypoxia-triggered self-assembling ultrasmall iron oxide (UIO) nanoparticle and assembly-responding fluorescence dyes (NBD), to provide dual-mode imaging in vivo. In this strategy, we have employed nitroimidazole derivatives as the hypoxia-sensitive moiety to construct intermolecular cross-linking of UIO nanoparticles under hypoxia, which irreversibly form larger nanoparticle assemblies. The hypoxia-triggered performance of UIO self-assembly not only amplifies its T2-weighted MRI signal but also promotes the fluorescence intensity of NBD through its emerging hydrophobic environment incorporated into self-assemblies. In vivo results further confirm that our hypoxic imaging probe can display a prompt MRI signal for the tumor interior region, and its signal enhancement performs a long-term effective feature and gradually reaches 3.69 times amplification. Simultaneously, this probe also exhibits obvious green fluorescence in the hypoxic region of tumor sections. Accordingly, we also have developed a MRI difference value method to visualize the 3D distribution and describe the extent of the hypoxic tumor region within the whole bodies of mice. Due to its notable efficiency of penetration and accumulation inside a hypoxic tumor, our hypoxia imaging probe could also be considered as a potential candidate as a versatile platform for hypoxia-targeted drug delivery, and meanwhile its hypoxia-related therapeutic efficacy can be monitored.

Silica-supported dual-dye nanoprobes for ratiometric hypoxia sensing

A covalently encapsulated dual-dye silica nanoprobe has been developed by a one-pot approach for sensitive ratiometric hypoxia detection with the Ksv value of 243.1 bar−1 and I0/I100 ratio of 153.

A Simple Aggregation-Induced Emission Nanoprobe with Deep Tumor Penetration for Hypoxia Detection and Imaging-Guided Surgery in Vivo

The pan-cancer detection and precise visualization of tiny tumors in surgery still face great challenges. As tumors grow aggressively, hypoxia is a common feature of solid tumors and has supplied a general way for detecting tumors. Herein, we report a simple aggregation-induced emission nanoprobe-TPE-4NE-O that can specifically switch on their fluorescence in the presence of cytochrome P450 reductase, a reductase which is overexpressed under hypoxia conditions. The probe can selectively light up the hypoxia cells and has shown enhanced deep tumor penetration via charge conversion both in vitro and in vivo. After being modified with FA-DSPE-PEG, higher tumor uptake can be seen and FA-DSPE/TPE-4NE-O showed specific visualization to the hypoxia cancer cells. Excitingly, much brighter fluorescence was accumulated at the tumors in the FA-DSPE/TPE-4NE-O group, even though the tumor was as small as 2.66 mm. The excellent performance of FA-DSPE/TPE-4NE-O in detecting tiny tumors has made it possible for imaging-guided tumor resection. More importantly, the probe exhibited good biocompatibility with negligible organ damage and eliminated a hemolysis risk. The simple but promising probe has supplied a new strategy for pan-cancer detection and tiny tumor visualization, which have shown great potential in clinical translation.

PET/CT in the Evaluation of Hypoxia for Radiotherapy Planning in Head and Neck Tumors: Systematic Literature Review.

PET/CT combines imaging at the molecular level along with imaging at the anatomic level, which, with the administration of a hypoxia-sensitive radiopharmaceutical, allows evaluation of tissue oxygenation. Methods: This work consisted of a systematic literature review that included websites, books, and articles dated from July 1997 to December 2019. The aim was to identify the PET radiopharmaceuticals best suited to the detection of cell hypoxia and to recognize the benefits for planning intensity-modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT). Results: Hypoxia affects the likelihood of cure for head and neck tumors, reducing the success rate. Radiopharmaceuticals such as 18F-fluoromisonidazole, 18F-fluoroerythronitromidazole, and 18F-HX4 (18F-3-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol) allow the delineation of hypoxic subvolumes within the target volume to optimize IMRT/VMAT. Conclusion: Identification of hypoxic areas with PET/CT imaging and use of subsequent IMRT/VMAT allows for possible escalation of radiation dose in radioresistant subvolumes, with a consequent decrease in relapses and an increased likelihood of disease-free survival.

Study of admission cardiotocography screening of high risk obstetric cases and its correlation with perinatal outcome

Objective: To predict the neonatal outcome in high risk obstetric cases by performing admission cardiotocography (CTG) testing. Aims: To study role of admission CTG in early detection of fetal hypoxia. To do correlation of admission CTG results and immediate perinatal outcome in high risk obstetric cases. Materials and Methods: The study was conducted in department of Obstetrics & Gynecology N.S.C.B. Medical College, Jabalpur from 1st June 2009 to 31st Oct. 2010. A total of 106 high risk cases meeting the inclusion criteria were subjected to admission CTG testing in this prospective study. Result of admission CTG testing was correlated with perinatal outcome. Results: The admission test had sensitivity of 38.1%, specificity of 100% and positive predictive value of 100% for predicting an Apgar score

Nano versus Molecular: Optical Imaging Approaches to Detect and Monitor Tumor Hypoxia.

Hypoxia is a ubiquitous feature of solid tumors, which plays a key role in tumor angiogenesis and resistance development. Conventional hypoxia detection methods lack continuous functional detection and are generally less suitable for dynamic hypoxia measurement. Optical sensors hereby provide a unique opportunity to noninvasively image hypoxia with high spatiotemporal resolution and enable real-time detection. Therefore, these approaches can provide a valuable tool for personalized treatment planning against this hallmark of aggressive cancers. Many small optical molecular probes can enable analyte triggered response and their photophysical properties can also be fine-tuned through structural modification. On the other hand, optical nanoprobes can acquire unique intrinsic optical properties through nanoconfinement as well as enable simultaneous multimodal imaging and drug delivery. Furthermore, nanoprobes provide biological advantages such as improving bioavailability and systemic delivery of the sensor to enhance bioavailability. This review provides a comprehensive overview of the physical, chemical, and biological analytes for cancer hypoxia detection and focuses on discussing the latest nano- and molecular developments in various optical imaging approaches (fluorescence, phosphorescence, and photoacoustic) in vivo. Finally, this review concludes with a perspective toward the potentials of these optical imaging approaches in hypoxia detection and the challenges with molecular and nanotechnology design strategies.

Microbial nitroreductases: A versatile tool for biomedical and environmental applications.

Nitroreductases, enzymes found mostly in bacteria and also in few eukaryotes, use nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor for their activity and metabolize an enormous list of a diverse nitro group-containing compounds. Nitroreductases that are capable of metabolizing nitroaromatic and nitro heterocyclic compounds have drawn great attention in recent years owing to their biotechnological, biomedical, environmental, and human impact. These enzymes attracted medicinal chemists and pharmacologists because of their prodrug selectivity for activation/reduction of nitro compounds that wipe out pathogens/cancer cells, leaving the host/normal cells unharmed. It is applied in diverse fields of study like prodrug activation in treating cancer and leishmaniasis, designing fluorescent probes for hypoxia detection, cell imaging, ablation of specific cell types, biodegradation of nitro-pollutants, and interpretation of mutagenicity of nitro compounds. Keeping in view the immense prospects of these enzymes and a large number of research contributions in this area, the present review encompasses the enzymatic reaction mechanism, their role in antibiotic resistance, hypoxia sensing, cell imaging, cancer therapy, reduction of recalcitrant nitro chemicals, enzyme variants, and their specificity to substrates, reaction products, and their applications.

The impact of pulse oximetry and Integrated Management of Childhood Illness (IMCI) training on antibiotic prescribing practices in rural Malawi: A mixed-methods study.

The misdiagnosis of non-malarial fever in sub-Saharan Africa has contributed to the significant burden of pediatric pneumonia and the inappropriate use of antibiotics in this region. This study aims to assess the impact of 1) portable pulse oximeters and 2) Integrated Management of Childhood Illness (IMCI) continued education training on the diagnosis and treatment of non-malarial fever amongst pediatric patients being treated by the Global AIDS Interfaith Alliance (GAIA) in rural Malawi. This study involved a logbook review to compare treatment patterns between five GAIA mobile clinics in Mulanje, Malawi during April-June 2019. An intervention study design was employed with four study groups: 1) 2016 control, 2) 2019 control, 3) IMCI-only, and 4) IMCI and pulse oximeter. A total of 3,504 patient logbook records were included based on these inclusion criteria: age under five years, febrile, malaria-negative, and treated during the dry season. A qualitative questionnaire was distributed to the participating GAIA providers. Fisher's Exact Testing and odds ratios were calculated to compare the prescriptive practices between each study group and reported with 95% confidence intervals. The pre- and post-exam scores for the providers who participated in the IMCI training showed an increase in content knowledge and understanding (p<0.001). The antibiotic prescription rates in each study group were 75% (2016 control), 85% (2019 control), 84% (IMCI only), and 42% (IMCI + pulse oximeter) (p<0.001). An increase in pneumonia diagnoses was detected for patients who received pulse oximeter evaluation with an oxygen saturation <95% (p<0.001). No significant changes in antibiotic prescribing practices were detected in the IMCI-only group (p>0.001). However, provider responses to the qualitative questionnaires indicated alternative benefits of the training including improved illness classification and increased provider confidence. Clinics that implemented both the IMCI course and pulse oximeters exhibited a significant decrease in antibiotic prescription rates, thus highlighting the potential of this tool in combatting antibiotic overconsumption in low-resource settings. Enhanced detection of hypoxia in pediatric patients was regarded by clinicians as helpful for identifying pneumonia cases. GAIA staff appreciated the IMCI continued education training, however it did not appear to significantly impact antibiotic prescription rates and/or pneumonia diagnosis.

Monochromophore-Based Phosphorescence and Fluorescence from Pure Organic Assemblies for Ratiometric Hypoxia Detection.

Hypoxia is a parameter related to many diseases. Ratiometric hypoxia probes often rely on a combination of an O2 -insensitive fluorophore and an O2 -sensitive phosphor in a polymer matrix, which require high cost and multi-step synthesis of transition metal complexes. The two-chromophore hypoxia probes encounter unfavorable energy transfer processes and different stabilities of the chromophores. Reported herein is a pure organic ratiometric hypoxia nanoprobe, assembled by a monochromophore, naphthalimide ureidopyrimidinone (BrNpA-UPy), bridged by a bis-UPy-functionalized benzyl skeleton. The joint factors of quadruple hydrogen bonding, the rigid backbone of UPy, and bromine substitution of the naphthalimide derivative facilitate bright phosphorescence (ΦP =7.7 %, τP =3.2 ms) and fluorescence of the resultant nanoparticles (SNPs) at room temperature, which enable accurate, ratiometric, sensitive oxygen detection (Ksv =189.6 kPa-1 ) in aqueous solution as well as in living HeLa cells.

Monochromophore‐Based Phosphorescence and Fluorescence from Pure Organic Assemblies for Ratiometric Hypoxia Detection

AbstractHypoxia is a parameter related to many diseases. Ratiometric hypoxia probes often rely on a combination of an O2‐insensitive fluorophore and an O2‐sensitive phosphor in a polymer matrix, which require high cost and multi‐step synthesis of transition metal complexes. The two‐chromophore hypoxia probes encounter unfavorable energy transfer processes and different stabilities of the chromophores. Reported herein is a pure organic ratiometric hypoxia nanoprobe, assembled by a monochromophore, naphthalimide ureidopyrimidinone (BrNpA‐UPy), bridged by a bis‐UPy‐functionalized benzyl skeleton. The joint factors of quadruple hydrogen bonding, the rigid backbone of UPy, and bromine substitution of the naphthalimide derivative facilitate bright phosphorescence (ΦP=7.7 %, τP=3.2 ms) and fluorescence of the resultant nanoparticles (SNPs) at room temperature, which enable accurate, ratiometric, sensitive oxygen detection (Ksv=189.6 kPa−1) in aqueous solution as well as in living HeLa cells.