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We describe the case of a previously healthy 9-year-old girl hospitalised due to hypoxaemic pneumonia. Two months after discharge, she maintained low oxygen saturations and persistent dry cough without dyspnoea, haemoptysis, migraine or palpitations. Cardiac and pulmonary auscultation was normal

Diabetic wound (DW) is one of the leading complications of diabetes patients with a long history. It also puts an economic burden on people recovering from injuries to manage medication. The critical factors in the treatment of DW are infection, inflammation, and low oxygen level. Since these non-healing injuries are linked to the extended recovery process, current treatments are studied only for a short period. The areas covered in this article are an overview of DM, Pathophysiology of DW, stages of wound healing (Hemostasis, Inflammation, Proliferation, Maturation), the role of growth factor in diabetic wound healing, advantages of micro and nanoparticles over other drug delivery systems and micro and nanoparticles for the delivery of growth factors with different studies.

Different infections have been presenting danger to mankind every once in a while and in 2019 a serious respiratory illness (COVID-19) reported in Wuhan, Hubei province of China, became a threat to general wellbeing not only in China but all the nations throughout the world. COVID-19 disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is found to be associated with a wide range of opportunistic fungal and bacterial infections. Candidial and aspergillus infections leading to mucormycosis and orbital compartment syndrome have been reported to be the main co-infections in COVID-19 patients, which must be recognized and treated promptly to avoid any morbidity and mortality. Low oxygen environment, acidic medium, high glucose, decreased phagocytic activity and increased ferritin levels in addition to prolonged hospitalization with or without mechanical ventilators are considered as the main risk factors. Thus, the main aim of the article is to briefly survey and discuss about the types, causes, methods to prevent and treatment modalities of main co-morbidity of COVID 19 i.e. mucormycosis.

Happy Hypoxia is one of the symptoms of Covid-19 that is often not known by society. This condition is often found in cases of Covid-19 with very low oxygen levels in the blood. Happy Hypoxia can be fatal with the failure of several organs of the body. The purpose of this study was to determine the relationship between the incidences of happy hypoxia in suspected Covid-19 patients with a history of cardiovascular disease at the ER Panti Waluya Hospital, Malang. The design of this study was cross sectional with a total sample of 18 Covid-19 patients selected using the Total Sampling technique. Data about Happy Hypoxia and history of cardiovascular disease were taken based on secondary data from Medical Records in the ER Panti Waluya Hospital, Malang. Based on the results of the Fisher Exact Test, it was found that p = (0.0477) (0.050) so H1 was rejected, meaning that there was no relationship between the incidence of happy hypoxia in suspected Covid-19 patients with a history of cardiovascular disease in the ER Panti Waluyo Hospital, Malang City. This means that the incidence of happy hypoxia in Covid-19 patients is not only related to cardiovascular disease Keywords: cardiovascular desease, covid-19, happy hypoxia ABSTRAK Salah satu gejala Covid-19 yang sering tidak diketahui oleh masyarakat umum adalah happy hypoxia. Kondisi ini sering ditemukan kasus Covid-19 dengan kadar oksigen dalam darah sangat rendah sehingga bisa berdampak pada terjadinya pingsan atau bisa berakibat fatal juga dengan adanya kekagalan beberapa organ organ tubuh. Tujuan dari penelitian ini adalah untuk mengetahui Hubungan Kejadian Happy Hypoxia Pada Pasien Suspek Covid-19 Dengan Riwayat Penyakit Cardiovaskuler Di UGD Rs Panti Waluya Malang. Desain penelitian ini menggunakan cross sectional dengan jumlah sampel sebanyak 18 pasien Covid-19 yang dipilih dengan tekhnik Total Sampling. Data tentang Happy Hypoxia dan riwayat penyakit kardiovaskuler diambil berdasarkan data sekunder dari Rekam Medik di UGD RS Panti Waluya Malang. Berdasarkan hasil uji Fisher Exact Test didapatkan p = (0,477)(0,050) sehingga H1 ditolak, artinya tidak ada Hubungan Kejadian Happy Hypoxia Pada Pasien Suspek Covid-19 Dengan Riwayat Penyakit Kardivaskuler Di UGD RS Panti waluyo Kota Malang.. Hal ini memberikan makna bahwa kejadian happy hypoxia pada pasien Covid-19 tidak hanya berkaitan dengan penyakit kardiovaskuler. Kata kunci: Covid-19, Happy hypoxia, Penyakit Kardiovaskuler

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 adenocar...

Respiratory failure (apnea) often occurs in premature babies, this should be avoided because it causes low oxygen concentrations in the blood so that it can damage brain function and lead to death. Apnea is characterized by a decrease in oxygen saturation (SpO2). The purpose of this study was to design an apnea monitor that was detected with SpO2 parameters, alarms, and vibrating stimulation. This study uses infrared and red LEDs that emit light through the surface of the finger and is detected by a photodiode sensor, this light signal will be converted into an electrical signal and calculated by Arduino to determine the patient's SpO2 and BPM values. If the SpO2 value drops 5% within 5 seconds from the baseline, the device will indicate apnea has occurred and the vibrating motor is working. SpO2 signals and alarms are sent to the nurse station computer via Bluetooth HC-05. The instrument was calibrated with an SpO2 calibrator and the measurement results were compared with a BION pulse oximetry brand. The results of the instrument measurement on two subjects on the SpO2 parameter showed an error value of 2% and the BPM parameter obtained an error value of 4.54%. Testing the BPM parameter using a calibrator at the 30 and 60 BPM settings shows an error value of 0% and at the 120 BPM setting the error value is 0.01%. The vibrating motor to stimulate the baby's body when apnea occurs is functioning properly. The results showed that measurements using subjects tended to have high error values ​​due to several factors. This research can be implemented on patient monitors to improve patient safety and reduce the workload of nurses or doctors

Major advances in the field of genomic technologies have led to an improvement in cancer diagnosis, classification and prognostication. However, many cancers remain incurable due to the development of drug resistance, minimal residual disease (MRD) and disease relapse, highlighting an incomplete understanding of the mechanisms underlying these processes. In recent years, the impact of non‐genetic factors on neoplastic transformations has increasingly been acknowledged, and growing evidence suggests that low oxygen (O2) levels (ie hypoxia) in the tumour microenvironment play a critical role in the development and treatment of cancer. As a result, there is a growing need to develop research tools capable of reproducing physiologically relevant O2 conditions encountered by cancer cells in their natural environments in order to gain in‐depth insight into tumour cell metabolism and function. In this review, the authors highlight the importance of hypoxia in the pathogenesis of malignant diseases and provide an overview of novel engineering tools that have the potential to further drive this evolving, yet technically challenging, field of cancer research.

Despite the growing importance of oxygen-delivery devices worldwide, there are only a few reports of physiological data on various oxygen masks in children. The possibility of carbon dioxide (CO2) rebreathing has been a prevalent concern with the use of oxygen-delivery devices. OxyMask KidTM (Southmedic Inc. Canada; hereafter OxyMask) is expected to reduce CO2 rebreathing even at low oxygen flow rates because of its structural features. Biological data using OxyMask in children have not been well investigated. Measured respiratory parameters of OxyMask with those of a simple oxygen mask in healthy children were compared. Ten subjects were enrolled, with a median age of 5.4 years. All subjects used both OxyMask and a simple oxygen mask. The fraction of inspiratory oxygen (FIO2), partial pressure of inspiratory CO2 (PICO2), and partial pressure of end-tidal CO2 were measured using a sidestream gas-sampling monitor in all subjects. The oxygen flow rate was set at 1, 3, 5, and 10 L/min. FIO2 levels were higher with OxyMask than those with the simple oxygen mask at 3 L/min of oxygen. PICO2 levels were significantly lower with OxyMask than those with the simple oxygen mask (1.5 mmHg vs. 3.7 mmHg at 1 L/min, P = 0.005; 1.0 mmHg vs. 2.7 mmHg at 3 L/min, P = 0.005, respectively), whereas PICO2 levels were higher at low oxygen flow rates with both masks.Conclusion: Our results showed that higher FIO2 and less CO2 rebreathing were achieved with OxyMask than those with a simple oxygen mask at low flow rates of oxygen in healthy children. What is Known: • OxyMask is expected to reduce carbon dioxide rebreathing even at low oxygen flow rates because of its structural features. • Efficacy has been demonstrated in experimental models and adult data, but clinical data on the use of the OxyMask in children are limited. What is New: • Higher fraction of inspiratory oxygen and lesser carbon dioxide rebreathing were achieved with OxyMask than with a simple oxygen mask at low flow rates of oxygen in healthy children.

Tumors exhibit areas of decreased oxygenation due to malformed blood vessels. This low oxygen concentration decreases the effectiveness of radiation therapy, and the resulting poor perfusion can prevent drugs from reaching areas of the tumor. Tumor hypoxia is associated with poorer prognosis and disease progression, and is therefore of interest to preclinical researchers. Although there are multiple different ways to measure tumor hypoxia and related factors, there is no standard for quantifying spatial and temporal tumor hypoxia distributions in preclinical research or in the clinic. This review compares imaging methods utilized for the purpose of assessing spatio-temporal patterns of hypoxia in the preclinical setting. Imaging methods provide varying levels of spatial and temporal resolution regarding different aspects of hypoxia, and with varying advantages and disadvantages. The choice of modality requires consideration of the specific experimental model, the nature of the required characterization and the availability of complementary modalities as well as immunohistochemistry.

Introduction Efficient evaluation with an early surrogate endpoint, taking into account the process of disease evolution, may not only clarify inconsistent or underpowered results but also provide a new insight into the exploration of a new antiviral therapy for treating COVID-19 patients. Methods We assessed the dynamics of COVID-19 disease spectrum, commencing from low-risk (no or low oxygen supplement), medium-risk (non-invasive ventilator or high oxygen supplement), and high-risk (extracorporeal membrane oxygenation or invasive ventilator) risk state on enrollment, and then the subsequent progression and regression of risk states until discharge or death. The efficacy of antiviral therapy in altering the dynamics was assessed by using the high-risk state as a surrogate endpoint based on the data retrieved from the two-arm Adaptive Covid-19 Treatment Trial. Results Using the high-risk state as a surrogate endpoint, remdesivir treatment led to a decrease in the high-risk COVID-19 state by 34.8% (95% CI 26.7–42.0%) for a 14-day period and 29.3% (95% CI 28.8–29.8%) up to 28 days, which were consistent with a statistically significant reduction of death by 30.5% (95% CI 6.6, 50.9%) up to a 28-day period. The estimates of numbers needed to be treated were 100.9 (95% CI 88.1, 115.7) for using the high-risk COVID-19 state as a surrogate endpoint for a 14-day period and 133.3 (95% CI 112.5, 158.0) were required for averting one death from COVID-19 up to 28 days. Conclusions We demonstrate the expedient use of the high-risk COVID-19 disease status as a surrogate endpoint for evaluating the primary outcome of the earliest death. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00431-9.

Purpose To evaluate the effect of a one-time dose of insulin or insulin-like growth factor 1 (IGF-1) on cellular proliferation and migration of subacromial bursa tissue (SBT) over time. Methods SBT was harvested from over the rotator cuff tendon in 4 consecutive patients undergoing primary arthroscopic rotator cuff repair. SBT was cultured for 3 weeks in complete media until reaching confluence. The culture dishes were stored in a humidified, low oxygen tension (5% CO2) incubator at 37°C. SBT of each patient underwent treatment with a one-time dose of insulin or IGF-1, whereas nontreated SBT served as a negative control. Cellular proliferation and migration were evaluated after 24, 48, 72, and 96 hours of incubation. SBT-derived cells migrated in the detection field were visualized using fluorescent microscopy. Results Cellular proliferation at 24, 48, 72, and 96 hours was 1.40 ± 0.27, 1.00 ± 0.20, 1.47 ± 0.31, and 1.68 ± 0.28 for IGF-1; 1.44 ± 0.24, 1.15 ± 0.27, 1.60 ± 0.36, and 1.61 ± 0.32 for insulin; and 1.51 ± 0.35, 1.29 ± 0.33, 1.53 ± 0.35, and 1.57 ± 0.38 for nontreated SBT. Untreated SBT demonstrated a significantly greater proliferation when compared with IGF-1 and insulin within the first 48 hours, although this effect was found to subside by 96 hours. Cellular migration at 24, 48, 72, and 96 hours was 575.7 ± 45.0, 641.6 ± 77.7, 728.3 ± 122.9, and 752.3 ± 114.5 for IGF-1; 528.4 ± 31.3, 592.5 ± 69.8, 664.2 ± 115.2, and 695.6 ± 148.2 for insulin; and 524.4 ± 41.9, 564.4 ± 49.8, 653.2 ± 81.5, and 685.7 ± 115.5 for nontreated SBT. Insulin showed no difference in migration at each timepoint compared to nontreated SBT (P > .05, respectively). Conclusions Insulin and IGF-1 initially inhibit cellular proliferation of human SBT, although this effect was found to subside by 96 hours. Further, neither insulin nor IGF-1 changed the slope of cellular migration over time. However, each treatment group demonstrated a significant increase in cellular proliferation and migration. Clinical Relevance In the setting of biologic augmentation of rotator cuff repair, the compatibility and synergistic effect of insulin on human SBT is highly limited.

Mesenchymal stromal cells (MSCs) present the capacity to secrete multiple immunomodulatory factors in response to their microenvironment. This property grants them a golden status among the novel alternatives to treat multiple diseases in which there is an unneeded or exaggerated immune response. However, important challenges still make difficult the clinical implementation of MSC-based therapies, being one of the most remarkable the lack of efficacy due to their transient immunomodulatory effects. To overcome this issue and boost the regulatory potential of MSCs, multiple strategies are currently being explored. Some of them consist of ex vivo pre-conditioning MSCs prior to their administration, including exposure to pro-inflammatory cytokines or to low oxygen concentrations. However, currently, alternative strategies that do not require such ex vivo manipulation are gaining special attention. Among them, the recreation of a three dimensional (3D) environment is remarkable. This approach has been reported to not only boost the immunomodulatory potential of MSCs but also increase their in vivo persistence and viability. The present work revises the therapeutic potential of MSCs, highlighting their immunomodulatory activity as a potential treatment for diseases caused by an exacerbated or unnecessary immune response. Moreover, it offers an updated vision of the most widely employed pre-conditioning strategies and 3D systems intended to enhance MSC-mediated immunomodulation, to conclude discussing the major challenges still to overcome in the field.

Introduction: Sickle Cell Disease (SCD) is the most prevalent genetic disease in the world predominantly in the African population with Sickle Cell Anaemia (SCA) being its dominant form. One of the most frequent complications of SCD is osteomyelitis. SCA is due to a point mutation in the beta globin chain of haemoglobin. This is responsible for the sickled shape of RBCs under low oxygen tension conditions leading to obstruction in the microcirculation. This leads to vaso-occlusive crises (VOC) which has a similar clinical presentation to that of osteomyelitis, another complication of SCD. Case Presentation: We present the case of a three-year-old girl with SCA who presented with an inability to bear weight in a febrile context. A diagnosis of VOC was initially made, which was later on changed to both a left chronic tibial and right distal femoral osteomyelitis following a series of biological, and imaging investigations. Surgical debridement and drainage were performed, resulting 9 weeks later in the involution of fever and leg pain. Conclusion: Osteomyelitis when associated with SCD is a dreadful and deathly disease in low income countries as it also presents like VOC therefore higher suspicion index is recommended. It is therefore important to take this into consideration at an early stage in patients with homozygous sickle cell disease so as to rapidly initiate multidisciplinary care. Appropriate investigations, appropriate antibiotic therapy, and timely surgical intervention would help to greatly reduce morbidity and mortality.

Summary HIF is a transcription factor that plays an essential role in the cellular response to low oxygen, orchestrating a metabolic switch that allows cells to survive in this environment. In immunity, infected and inflamed tissues are often hypoxic, and HIF helps immune cells adapt. HIF-α stabilization can also occur under normoxia during immunity and inflammation, where it regulates metabolism but in addition can directly regulate expression of immune genes. Here we review the role of HIF in immunity, including its role in macrophages, dendritic cells, neutrophils, T cells, and B cells. Its role in immunity is as essential for cellular responses as it is in its original role in hypoxia, with HIF being implicated in multiple inflammatory diseases and in immunosuppression in tumors.

Background Based on “gut-brain axis” theory, we employed a rat 6-OHDA lesion model to examine the impact of gut-acupuncture on motor symptoms, the abundance of DA neurons in the SN, the hemodynamic characteristics of the carotid artery and SNH. Methods 6-OHDA-induced PD rats were treated with gut-acupuncture daily, starting day 15 after surgery. Mobility of the limbs was evaluated, abundance of TH + DA neurons in the SN detected, The diameter of carotid arteries and hemodynamic parameters measured by cervical vascular ultrasound CVUS, and TCS utilized to examine SNH. Results Our data show that gut-acupuncture correlates with significantly increased abundance of TH, a marker of DA neurons compared to untreated rats. Furthermore the area of SNH in the injured side of the acupuncture group was significantly reduced. PSV of LCCA, LICA, RICA showed that were significantly improved i.e. decreased in the acupuncture group, while the diameter of LICA and RCCA in acupuncture group was narrower. We also found that the PSV was significantly increased and the vascular diameter narrowed in LCCA and LICA during treatment, whereas after removing the acupuncture needle the PSV decreased and the vascular diameter widened. Conclusions Gut-acupuncture can reduce SNH and influence TH abundance in the SN which correlated with changes of hemodynamic characteristics of the lesioned side. We suggest a regulatory mechanism which may affect the vagus nerve through the ENS and cause the change of cervical hemodynamics. It further induces low oxygen tension microenvironment conducive to the proliferation of neural stem cells, which leads to the enrichment of TH in PD model rats of acupuncture group.

By generating a periodic impulse-like pressure (2.0–4.4 kPa, 84 s) to actively exchange the gas in synthesis furnace, pure AlN powder of low oxygen content was synthesized via additive free carbothermal reduction and nitridation (CRN) of Al2O3 powder. Compared with the conventional CRN method, the proposed extra gas exhaust process can more effectively remove the side-produced CO from the reaction sites to accelerate nitridation process and decrease the residual oxygen content in the obtained AlN powder. For example, with 39 wt% activated carbon loaded in the raw material at 1650 °C for 4 h, the prepared AlN powder by the proposed synthesis scheme has only 0.68 wt% residual oxygen. The effects of carbon content, synthesis temperature and holding time on the residual oxygen content in AlN powder by the proposed synthesis scheme were also studied. The ball-milled as-prepared AlN powder was pressureless sintered at 1880 °C for 2.5 h to obtain a translucent AlN ceramics (37.6% at ~5700 nm), which demonstrates the excellent sinterability of the as-prepared AlN powder.

Objective: Obesity, which is one of the most important health problems of today's people, remains current due to the risks of illness it brings due to the increase rate in the world. Material and Methods: Male Sprague Dawley rats were used in our study of obesity. Rats were divided into four groups as standard diet/ normal oxygen, standard diet/low oxygen, high-fat diet/normal oxygen and high-fat diet / low oxygen. For the study, a special cage with a low oxygen level of 17-18% was made in a closed system. After achieving the desired 25% weight increase in obese group rats, blood, liver, lung, white adipose tissue and brown adipose tissue were obtained from the rats. In these tissues, adrenomedullin, hypoxic inducible factor 1-α (HIF1-α) and matrix metalloproteinase-II (MMP-II) levels were measured by ELISA. Results: According to our results, there was a significant increase in adrenomedullin, HIF1-α and MMP-II in white adipose tissue, and adrenomedullin and MMP-II in brown adipose tissue. It was found that the amount of HIF1-α increased significantly in liver and lung tissues. Conclusion: According to the metabolic status of adipose tissue, it is thought that the effect of adrenomedullin, HIF1-α and MMP-II can increase vascularization of brown adipose tissue and provide energy consumption.

Systematically review the comparison of anterior and posterior framed walker in terms of biomechanical analysis and energy expenditure and to discuss the implications for clinical practice. A systematic literature search was performed to identify studies that evaluated the gait pattern, upper extremity (UE) kinetics and kinematics and energy consumption. Outcome measures and treatment results for them were identified. 6 studies met the criteria and were included in this systematic review. Gait analysis, UE kinetics and kinematics and energy consumption were all assessed in 4 different papers. Gait parameters were comparable between walkers but declined torso tilt was found in the posterior walker group. In UE joints, two groups showed no significant difference but adaptive therapeutic posterior walker helped decrease UE burden. Most of papers prefer posterior walkers because of low oxygen cost. For better gait pattern, less UE burden and energy consumption, the adaptive therapeutic posterior walker is relatively the proper choice among all. For future studies, crossover studies or randomized controlled trails (RCTs) with larger sample size and more accurate measurement equipment may provide more persuasive evidence. Long term effects of walker users can also be investigated.

Background Although low oxygen saturations are generally regarded as deleterious, recent studies in ICU patients have shown that a liberal oxygen strategy increases mortality. However, the optimal oxygen saturation target remains unclear. The goal of this study was to determine the optimal range by using real-world data. Methods Replicate retrospective analyses were conducted of two electronic medical record databases: the eICU Collaborative Research Database (eICU-CRD) and the Medical Information Mart for Intensive Care III database (MIMIC). Only patients with at least 48 h of oxygen therapy were included. Nonlinear regression was used to analyze the association between median pulse oximetry-derived oxygen saturation (Spo2) and hospital mortality. We derived an optimal range of Spo2 and analyzed the association between the percentage of time within the optimal range of Spo2 and hospital mortality. All models adjusted for age, BMI, sex, and Sequential Organ Failure Assessment score. Subgroup analyses included ICU types, main diagnosis, and comorbidities. Results The analysis identified 26,723 patients from eICU-CRD and 8,564 patients from MIMIC. The optimal range of Spo2 was 94% to 98% in both databases. The percentage of time patients were within the optimal range of Spo2 was associated with decreased hospital mortality (OR of 80% vs 40% of the measurements within the optimal range, 0.42 [95% CI, 0.40-0.43] for eICU-CRD and 0.53 [95% CI, 0.50-0.55] for MIMIC). This association was consistent across subgroup analyses. Conclusions The optimal range of Spo2 was 94% to 98% and should inform future trials of oxygen therapy.

Cyclooxygenase (COX) is proposed to regulate cerebral blood flow (CBF); however, accurate regional contributions of COX are relatively unknown at baseline and particularly during hypoxia. We hypothesized that COX contributes to both basal and hypoxic cerebral vasodilation, but COX-mediated vasodilation is greater in the posterior versus anterior cerebral circulation. CBF was measured in 9 healthy adults (28 ± 4 yr) during normoxia and isocapnic hypoxia (fraction of inspired oxygen = 0.11), with COX inhibition (oral indomethacin, 100mg) or placebo. Four-dimensional flow magnetic resonance imaging measured cross-sectional area (CSA) and blood velocity to quantify CBF in 11 cerebral arteries. Cerebrovascular conductance (CVC) was calculated (CVC = CBF × 100/mean arterial blood pressure) and hypoxic reactivity was expressed as absolute and relative change in CVC [ΔCVC/Δ pulse oximetry oxygen saturation ([Formula: see text])]. At normoxic baseline, indomethacin reduced CVC by 44 ± 5% ( P < 0.001) and artery CSA ( P < 0.001), which was similar across arteries. Hypoxia ([Formula: see text] 80%–83%) increased CVC ( P < 0.01), reflected as a similar relative increase in reactivity (% ΔCVC/−Δ[Formula: see text]) across arteries ( P < 0.05), in part because of increases in CSA ( P < 0.05). Indomethacin did not alter ΔCVC or ΔCVC/Δ[Formula: see text] to hypoxia. These findings indicate that 1) COX contributes, in a largely uniform fashion, to cerebrovascular tone during normoxia and 2) COX is not obligatory for hypoxic vasodilation in any regions supplied by large extracranial or intracranial arteries.

We report two highly fluorinated Cu-based imaging agents, CuL1 and CuL2, for detecting cellular hypoxia as nanoemulsion formulations. Both complexes retained their initial quenched 19F MR signals due to paramagnetic Cu2+; however, both complexes displayed a large signal increase when the complex was reduced. DLS studies showed that the CuL1 nanoemulsion (NECuL1) had a hydrodiameter of approximately 100 nm and that it was stable for four weeks post-preparation. Hypoxic cells incubated with NECuL1 showed that 40% of the Cu2+ taken up was reduced in low oxygen environments.

Here, we show that metal oxide surfaces catalyze the formation of intermediate defluorinated tetrafluoroethylene (TFE) radicals, resulting in enhanced binding on the corresponding metal oxide surfaces. We attribute the preferential adsorption and radical formation of TFE on Cr2O3(0001) relative to TiO2(110) to the low oxygen coordination of Cr surface atoms. This hints at a possible dependence of the TFE binding strength to the surface stoichiometry of metal-oxide surfaces.

Purpose: Hypoxia (low oxygen) is a common feature of solid tumours that has been intensely studied for more than six decades. Here we review the importance of hypoxia to radiotherapy with a particular focus on the contribution of hypoxia to immune responses, metastatic potential and FLASH radiotherapy, active areas of research by leading women in the field. Conclusion: Although hypoxia-driven metastasis and immunosuppression can negatively impact clinical outcome, understanding these processes can also provide tumour-specific vulnerabilities that may be therapeutically exploited. The different oxygen tensions present in tumours and normal tissues may underpin the beneficial FLASH sparing effect seen in normal tissue and represents a perfect example of advances in the field that can leverage tumour hypoxia to improve future radiotherapy treatments.

Tumour hypoxia is significantly correlated with patient survival and treatment outcomes. At the molecular level, hypoxia is a major driving factor for tumour progression and aggressiveness. Despite the accumulative scientific and clinical efforts to target hypoxia, there is still a need to find specific treatments for tumour hypoxia. In this review, we discuss a variety of approaches to alter the low oxygen tumour microenvironment or hypoxia pathways including carbogen breathing, hyperthermia, hypoxia-activated prodrugs, tumour metabolism and hypoxia-inducible factor (HIF) inhibitors. The recent advances in technology and biological understanding reveal the importance of revisiting old therapeutic regimens and repurposing their uses clinically.

Hypoxia is evident in several bone diseases which are characterized by excessive bone resorption by osteoclasts, the bone-resorbing cells. The effects of hypoxia on osteoclast formation and activities are widely studied but remain inconclusive. This systematic review discusses the studies reporting the effect of hypoxia on osteoclast differentiation and activity. A literature search for relevant studies was conducted through SCOPUS and PUBMED MEDLINE search engines. The inclusion criteria were original research articles presenting data demonstrating the effect of hypoxia or low oxygen on osteoclast formation and activity. A total of 286 studies were identified from the search, whereby 20 studies were included in this review, consisting of four in vivo studies and 16 in vitro studies. In total, 12 out of 14 studies reporting the effect of hypoxia on osteoclast activity indicated higher bone resorption under hypoxic conditions, 14 studies reported that hypoxia resulted in more osteoclasts, one study found that the number remained unchanged, and five studies indicated that the number decreased. In summary, examination of the relevant literature suggests differences in findings between studies, hence the impact of hypoxia on osteoclasts remains debatable, even though there is more evidence to suggest it promotes osteoclast differentiation and activity.

Epilepsy is a neurological disease which is non transmissible and affects across all ages. It is signalized by observing repetitions of seizures. Main causes of epilepsy are head injuries, low oxygen during birth, brain tumors, genetic conditions and infections like meningitis or encephalitis. A seizure came out whenever explosion of electrical impulses in brain elude their normal restricts. Traditional diagnosis techniques may take time to diagnose and it may differ in perfection as compared to automated system due to lack of expertization in each case. So this is a serious issue that disorder must be diagnose prior to the manifestation of behavioral symptoms. The main motive of this study is bestow expert model for recognizing disorders on basis of Electroencephalogram (EEG) data using Deep learning methodology. In this paper to detect epileptic seizures, author presented long short-term memory (LSTM) model on Bonn’s EEG dataset. Metrics calculated to check the efficacy of the technique are accuracy, specificity and sensitivity. Proposed model has achieved 98.5% accuracy, 99% sensitivity and 98% specificity only in 30 epochs.

Cellular therapy is a promising tool of human medicine to successfully treat complex and challenging pathologies such as cardiovascular diseases or chronic inflammatory conditions. Bone marrow-derived mesenchymal stromal cells (BMSCs) are in the limelight of these efforts, initially, trying to exploit their natural properties by direct transplantation. Extensive research on the therapeutic use of BMSCs shed light on a number of key aspects of BMSC physiology including the importance of oxygen in the control of BMSC phenotype. These efforts also led to a growing number of evidence indicating that the beneficial therapeutic effects of BMSCs can be mediated by BMSC-secreted agents. Further investigations revealed that BMSC-excreted extracellular vesicles could mediate the potentially therapeutic effects of BMSCs. Here, we review our current understanding of the relationship between low oxygen conditions and the effects of BMSC-secreted extracellular vesicles focusing on the possible medical relevance of this interplay.

Background Cardiorespiratory fitness (CRF) is the core element of health-related physical fitness evaluation. High pressure and low oxygen in Tibet (over 3,500 m above sea level) may negatively impact the residents’ CRF. The 20-m shuttle run test (20mSRT) is the most popular field-based assessment and estimate of CRF in children and adolescents worldwide. However, normative CRF data for the children and adolescents residing in China’s plateau region are unavailable, which prevents comparability among those living at high-altitudes around the world. Purpose To measure the CRF of Chinese children and adolescents aged 9–18 years living in Tibet at altitudes exceeding 3,500 m, and to identify correlations between this metric and demographic characteristics (age, sex, and ethnicity). These data were then compared with those generated in the lowland (Shanghai, China) and various global regions. Methods 20mSRT performance (number of completed laps) and predicted peak oxygen consumption (VO2peak) were used as indicators of CRF. We measured the CRF of 1,717 healthy children and adolescents aged 9–18 years living in Tibet. The CRF data from school-age subjects in Shanghai (2,437 boys and 2,396 girls) and worldwide (1,142,026 students from 50 countries/regions in Africa, Asia, Europe, Latin America, North America, and Oceania) were collated from published papers. Results The average CRF of the participants from Tibet was 39.8 mL/kg/min. The male subjects (n = 876; 41.1 ± 4.42 mL/kg/min) had a higher average CRF than their female counterparts (n = 841; 37.8 ± 5.40 mL/kg/min). CRF decreased with age in both sexes at statistical significance (F = 1249.9, p for trend 0.05). The indigenous Tibetans (n = 1289; 40.1 ± 3.71 mL/kg/min) had a significant higher average CRF than those of Han descent (n = 394; 38.9 ± 4.70 mL/kg/min) (p < 0.05). Conclusions Children and adolescents aged 7–18 years residing above 3,500 m in Tibet displayed lower CRF traits compared with their counterparts from the plains area and other high altitude places. CRF varied according to age, sex, and ethnic group. Given the importance of CRF in children and adolescents, effective intervention strategies should be implemented to improve CRF in children and adolescents on the plateau.

The species flock of haplochromine cichlid fishes in Lake Victoria is one of the most extensive and recent radiations of vertebrates known. Over the past 15 years, however, many of the haplochromine cichlid species have vanished, and predation by the introduced Nile perch (Lates niloticus) is thought to be one of the most significant factors underlying this mass extinction. Information on the hypoxia tolerance of haplochromines from the Lake Victoria is valuable for predicting their response to the increasing anoxia within the lake and in evaluating their potential use of low oxygen regions as refugia from predation by introduced Nile perch. This study examines the response of nine cichlid species from Lake Victoria (eight indigenous, one introduced) and three cichlid species from Lake Tanganyika to different low-oxygen regimes under laboratory conditions. Fish were exposed to progressive and acute hypoxia, with and without access to the surface. All species used aquatic surface respiration at very low Po2. Buccal bubble holding and active swimming at the surface during aquatic surface respiration were used by many species and may serve to increase its efficiency. Lacustrine cichlids endemic to Lake Victoria were more tolerant of hypoxia than ecologically similar species from Lake Tanganyika. The two species examined that are widespread in variety of aquatic habitats exhibited a relatively high tolerance to hypoxia, with well-developed aquatic surface respiration and bubble-holding capabilities and no loss of equilibrium during progressive hypoxia. Species strongly affected by recent changes in Lake Victoria were not consistently poorer in their hypoxia tolerance than less-affected species. But, two of the less-affected species are inhabitants of shallow, rocky habitats, an environment that may be both rich in oxygen and well defended against the Nile perch because of the structural complexity of the rocky, littoral area. The generally high levels of hypoxia tolerance in the cichlid species examined from Lake Victoria suggest that these species potentially could use low-oxygen refugia to escape Nile perch predation. Some species that are thought to have disappeared may currently inhabit low-oxygen refugia that have not been adequately sampled. Tolerancia a la hipoxia en ciclidos del Africa oriental: Refugios con bajo contenido de oxigeno en el lago Victoria Resumen: El grupo de especies de peces ciclidos haplocrominidos del lago Victoria es una de las radiaciones de vertebrados mas recientes y extensivas de la que se tenga conocimiento. Sin embargo, a lo largo de los ultimos 15 anos, muchas de las especies de ciclidos haplocrominidos han desaparecido, y la predacion por una especie introducida, la perca del Nilo (Lates niloticus) es considerada como uno de los factores mas significativos que contribuyeron a esta extincion masiva. La informacion sobre la tolerancia a la hipoxia de los haplocrominidos del lago Victoria es valiosa para predecir sus respuestas a la anoxia en aumento dentro del lago y en la evaluacion del uso potencial de regiones con bajo contenido de oxigeno como refugios contra la predacion por parte de la perca del Nilo. Este estudio examina la respuesta de nueve especies de ciclidos del lago Victoria (ocho indigenas y una introducida) y tres especies de ciclidos del lago Tanganica bajo distintos regimenes de bajo contenido en oxigeno en condiciones de laboratorio. Los peces fueron expuestos a una hipoxia progresiva y aguda, con o sin acceso a la superficie. Todas las especies usaron respiracion de superficie cuando los niveles de Po2 eran muy bajos. Muchas especies usaron la retencion de burbujas en la boca y la naticion activa en la superficie durante la respiracion de superficie, las cuales podrian servir para aumentar su eficiencia. Los ciclidos lacustres endemicos al lago Victoria fueron mas tolerantes a la hipoxia que las especies ecologicamente similares del lago Tanganica. Las dos especies examinadas que tienen amplia distribucion en una variedad de habitats acuaticos exhibieron una tolerancia relativamente alta a la hipoxia, con respiracion de superficie y capacidad para la retencion de burbujas bien desarrolladas y sin ninguna perdida en el equilibrio durante la hipoxia progresiva. Las especies fuertemente afectadas por cambios recientes en el lago Victoria no fueron consistentemente mas pobres en su tolerancia a la hipoxia que las especies menos afectadas. Sin embargo dos de las especies menos afectadas son residentes de habitats rocosos someros, un ambiente que podria ser rico en oxigeno y podria estar resguardado de la perca del Nilo debido a la complejidad estructural del area litoral rocosa. Los niveles generalmente altos de tolerancia a la hipoxia en las especies de ciclidos del lago Victoria examinadas sugiere que estas especies podrian usar en forma potencial los refugios con bajo contenido de oxigeno para escapar de la predacion por parte de la perca del Nilo. Alguna de las especies que se piensa han desaparecido podrian, en la actualidad, residir en refugios con bajo contenido de oxigeno que no han sido muestreados adecuadamente.

An 89-year-old woman was admitted to hospital with a fall, general malaise and low oxygen saturations. She tested positive for SARS-CoV-2 and commenced on standard therapy for COVID-19 pneumonia. She improved initially but reported ongoing dyspnoea exacerbated by position. Following investigations to rule out other causes, she was given a diagnosis of platypnoea-orthodeoxia syndrome (POS). She was treated with gradual verticalization therapy with supplemental oxygen and subsequently discharged to an intermediate care bed (ICB).

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

Background We present a case of Hemoglobin (Hgb) Louisville in a 6-y old girl presenting with hypoxia and mild hemolytic anemia. Methods Hgb Louisville is a rare, unstable hemoglobin variant with low oxygen affinity, but initial workup of this case using widely-available hemoglobin fractionation methods was unable to differentiate this variant from normal hemoglobins. Results This resulted in a delayed diagnosis. Conclusion This case highlights the limitations of routine hemoglobin fractionation methods for correct diagnosis of hemoglobin variants, and subsequent impact on patient care and management.

This paper presents a theoretical elaboration aimed to explain the correlation found between a new rs-fMRI modality and electrophysiology and nuclear medicine neuroimaging, performed to localize epileptogenic brain areas. We present in detail the clinical history, and electrophysiological and neuroimaging results of one child with intractable epilepsy, who was submitted for Phase-1 work-up as candidate for epilepsy surgery. The patient underwent a thorough workup including video-telemetry, ictal and interictal nuclear medicine imaging, resting-state fMRI, EEG-fMRI, intracranial electroencephalography (ECoG), deep electrode implantation, and resective surgery. Electrophysiology and neuroimaging findings were concordant with findings provided by the resting-state mean signal. The patient became seizure-free after the resection of the target area. A theoretical discussion is provided that considers the presence of a stable BOLD effect explaining the findings of the observed resting-state mean signal. This stable BOLD is linked to low regional metabolism usually present in the epileptogenic area during interictal periods, coupled with low oxygen extraction. Low oxygen extraction leaves more oxygen for the draining venule and consequently increases the BOLD signal.

Increasing attention is given to the finding that macrophages under hypoxia are capable of controlling infection by the intracellular protozoan parasite Leishmania amazonensis. The hypoxia-inducible factor (HIF)-1α has been shown to play an essential role in this enhanced innate immune response. Our study aimed to explore the HIF-1α-dependent mechanisms leading to reduced survival of the parasites residing in macrophages under low oxygen conditions. Hypoxia triggered (P 0.01) NADPH oxidase 2 (Nox2) expression and reactive oxygen species (ROS) production in J774 macrophages upon 24-h infection with L. amazonensis. Furthermore, increased (P 0.01) expression levels of HIF-1α and macrophage migration inhibitory factor (MIF) were detected in the infected cells grown at 3% oxygen tension. We found that either HIF-1α silencing, Nox2 inhibition or MIF antagonism caused a significant (P 0.05) reversal of the improved leishmanicidal activity displayed by the hypoxic phagocytes. Taken together, our current results suggest that, under conditions of limited availability of oxygen, activation of the HIF-1α/MIF axis via Nox2/ROS induction promotes killing of L. amazonensis amastigotes by macrophages. Such protective mechanism might operate in L. amazonensis-infected tissues where low oxygen levels prevail.

The highlands evoke both fascination and awe. Regardless of the reason to live in the highlands, symptoms related to altitude sickness are unbearable because of low atmospheric pressure, low oxygen concentration, strong ultraviolet radiation, cold, and psychological factors. Food and herbal medicines and/or health-care foods have protected highland dwellers owing to their multisystem regulation. These versatile products combine health-care properties with medical values by enhancing immunity, relieving physical fatigue, improving sleep, and augmenting hypoxia tolerance, with rare side effects. We therefore aimed to provide a more comprehensive analysis of these nutraceuticals, which can be used to prevent and treat symptoms of altitude hypoxia in the Chinese market. Finally, we dissect a new perspective for their promotion and development from molecular aspects.

Summary Endothelial cells (ECs) from the small intestine, colon, liver, and heart have distinct phenotypes and functional adaptations that are dependent on their physiological environment. Gut ECs adapt to low oxygen, heart ECs to contractile forces, and liver ECs to low flow rates. Isolating high-purity ECs in sufficient quantities is crucial to study their functions. Here, we describe protocols combining magnetic and fluorescent activated cell sorting for rapid and reproducible EC purification from four adult murine tissues. For complete details on the use and execution of these protocols, please refer to Kalucka et al. (2020)., Graphical abstract, Highlights • Protocols allowing for simultaneous isolation of murine ECs from different tissue • Rapid and efficient isolation of ECs from the small intestine, colon, heart, and liver • Combination of magnetic and fluorescent activated cell sorting • High purity and quality of isolated murine endothelial cells evident from scRNA-seq, Endothelial cells (ECs) from the small intestine, colon, liver, and heart have distinct phenotypes and functional adaptations that are dependent on their physiological environment. Gut ECs adapt to low oxygen, heart ECs to contractile forces, and liver ECs to low flow rates. Isolating high-purity ECs in sufficient quantities is crucial to study their functions. Here, we describe protocols combining magnetic and fluorescent activated cell sorting for rapid and reproducible EC purification from four adult murine tissues.

Although the use of porous scaffolds in tissue engineering has been relatively successful, there are still many limitations that need to be addressed, such as low vascularization, low oxygen and nutrient levels, and immune-induced inflammation. As a result, the current porous scaffolds are insufficient when treating large defects. This paper analyzed scientific research pertaining to the effects of macro-/micro-channels on the cell recruitment, vascularization, and immune response of tissue engineering scaffolds. Most of the studies contained either cell culturing experimentation or experimentation on small animals such as rats and mice. The sacrificial template method, template casting method, and 3D printing method were the most common methods in the fabrication of channeled scaffolds. Some studies combine the sacrificial and 3D printing methods to design and create their scaffold with channels. The overall results from these studies showed that the incorporation of channels within scaffolds greatly increased vascularization, reduced immune response, and was much more beneficial for cell and growth factor recruitment compared with control groups that contained no channels. More research on the effect of micro-/macro-channels on vascularization or immune response in animal models is necessary in the future in order to achieve clinical translation.

Sickle cell disease is a type of anemia distinguish by irregular erythrocytes that cause blood stream blocking, it is a severe hematological condition that causes people to be treated regularly during their lives and may also result in death. Standard RBC have a spherical form and are compact and resilient, allowing them to travel across narrow capillaries with ease. Irregular RBC’s, on the other hand, have a sickle appearance and are rigid and blunt, allowing them to get trapped in thin blood vessels. Patients will experience discomfort as a result of this, and low oxygen and exhaustion will result. In this research a Deep CNN model, to classy sickle cell disease and data augmentation technique such as flipping, zooming, height and width shift done to get much better accuracy, in this research Idb1 erythrocytes microscopic photographs of blood smears obtained from patients infected with sickle cell, and the dataset is divided into test and train for each classis which are circular, elongated and others. For the classification task five pre trained model are used which are VGG16, VVG19, ResNet50, ResNet101 and Inception V3. Proposed models’ efficiency is shown by the results of the work, which offers better accuracy of the classification.

OBJECTIVES Older patients have a higher cardiac surgery-associated acute kidney injury (CSA-AKI) related mortality. Low oxygen delivery (DO2) during cardiopulmonary bypass (CPB) is a risk factor for CSA-AKI, but critical DO2 thresholds for older patients are unknown. This study investigated critical DO2 thresholds for CSA-AKI in patients ≥70 years undergoing on-pump cardiac surgery. METHODS Patients were enrolled from July 2015 until August 2017. CPB data from 432 patients were collected, and DO2 values were calculated per minute. The primary outcome was CSA-AKI. The association between DO2 and CSA-AKI was analysed with multivariable regression analysis. Multiple DO2 thresholds were analysed. The association between CSA-AKI and the area below the DO2 thresholds (DO2 deficit) was evaluated, as was the association between frailty and CSA-AKI. RESULTS CSA-AKI occurred in 63 (14.6%) patients. Mean and nadir (lowest) DO2 values were lower in patients with CSA-AKI (283 vs 312 ml/min/m2; P-value CONCLUSIONS Low DO2 increased the risk for CSA-AKI in older patients who had cardiac surgery. A critical DO2 threshold of 270 ml/min/m2 was applicable for frail and non-frail patients. The efficacy of a DO2 >270 ml/min/m2 to reduce CSA-AKI in older patients needs further evaluation.

Various microorganisms present in beverages as contaminants, yet few can develop in the presence of acidic and low oxygen conditions. Notably, yeast is the dominant microbe group present in the fruit juices and drinks in the fruit juices and drinks. Due to the microbe development and secondary metabolite production, such as polluting compounds, carbon dioxide, and spoilage, the beverages were identified. Yeast and molds are considered to be a vital microbe that causes deterioration. The primary reason for the deterioration in fruits and fruit juices is because of the contamination caused by fungi and yeast, and sometimes damage may cause by insects. Sugars and sugar concentrates are generally polluted with osmophilic yeasts, for instance, Z. rouxii. This review mainly focuses on the types of spoilages in soft drinks and beverages and their control measures.

Metal-based contrast agents for magnetic resonance imaging present a promising avenue to image hypoxia. EuII -based contrast agents have a unique biologically relevant redox couple, EuII/III , that distinguishes this metal for use in hypoxia imaging. To that end, we investigated a strategy to enhance the contrast-enhancing capabilities of EuII -based cryptates in magnetic resonance imaging by controlling the rotational dynamics. Two dimetallic, EuII -containing cryptates were synthesized to test the efficacy of rigid versus flexible coupling strategies. A flexible strategy to dimerization led to a modest (114 %) increase in contrast enhancement per Eu ion (60 MHz, 298 K), but a rigid linking strategy led to an excellent (186 %) increase in contrast enhancement despite this compound's having the smaller molecular mass of the two dimetallic complexes. We envision the rigid linking strategy to be useful in the future design of potent EuII -based contrast agents for magnetic resonance imaging.

26 pages, 7 figures, 2 tables, supplementary material https://doi.org/10.3389/fmars.2020.604878.-- Data Availability Statement: The datasets generated for this study can be found in the online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/, GSE153343; doi: 10.1594/PANGAEA.913696, The marine environment is predicted to become warmer and more hypoxic, and these conditions may become a challenge for marine fish species. Phenotypically plastic responses facilitating acclimatization to changing environments can be mediated by DNA methylation through the modulation of gene expression. To investigate whether temperature and hypoxia exposure induce DNA methylation changes, we challenged post-smolt Atlantic salmon (Salmo salar) to increasing temperatures (12 → 20°C, 1°C week–1) under normoxia or moderate hypoxia (∼70% air saturation) and compared responses in the liver after 3 days or 4 weeks at 20°C. DNA methylation was studied in six genes related to temperature stress (cirbp, serpinh1), oxidative stress (prdx6, ucp2), apoptosis (jund), and metabolism (pdk3). Here, we report that exposure to high temperature, alone or combined with hypoxia, affected the methylation of CpG sites within different genomic regulatory elements around the transcription start of these temperature/hypoxia biomarker genes. Yet, we uncovered distinct CpG methylation profiles for each treatment group, indicating that each environmental condition may induce different epigenetic signatures. These CpG methylation responses were strongly dependent on the duration of stress exposure, and we found reversible, but also persistent, CpG methylation changes after 4 weeks of exposure to 20°C. Further, several of these changes in CpG methylation correlated with transcriptional changes, and thus, can be considered as regulatory epigenetic marks (epimarkers). Our study provides insights into the dynamic associations between CpG methylation and transcript expression in Atlantic salmon, and suggests that this epigenetic mechanism may mediate physiological acclimation to short-term and long-term environmental changes, Funding for this research was provided to AKG by the Ocean Frontier Institute, through an award from the Canada First Research Excellence Fund (20181007) and was supported by the Spanish Ministry of Science Grants AGL2015-73864-JIN “Ambisex” and RYC2018-024017-I, and an “Interomics” Grant (202030E004) from the Spanish National Research Council (CSIC) to LR. This research was conducted on samples collected through the “Mitigating the Impact of Climate-Related Challenges on Salmon Aquaculture (MICCSA)” project. MICCSA funding was provided by the Atlantic Canada Opportunities Agency (781-9658-205222), Innovate NL (5404-1209-104), and Innovate PEI to AKG, With the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)

Simple Summary In chronic myeloid leukemia (CML), a neoplasm brilliantly taken care of by a molecularly targeted therapeutic approach, the achievement of cure is nevertheless prevented by the maintenance of a small subset of treatment-resistant leukemia stem cells (LSCs), sustaining the so-called minimal residual disease of CML. The phenotypical and functional characterization of this LSC subset is, therefore, crucial to aim at the eradication of disease. Such a characterization includes the acquisition of information relative to the metabolic profile of treatment-resistant LSCs, which is functional to their maintenance in bone marrow. A number of metabolic features of LSCs were shown to determine their sensitivity or resistance to therapy. Glutamine metabolism emerged from this study as a potential target to overcome the persistence of therapy-resistant LSCs. Abstract This study was directed to characterize the role of glutamine in the modulation of the response of chronic myeloid leukemia (CML) cells to low oxygen, a main condition of hematopoietic stem cell niches of bone marrow. Cells were incubated in atmosphere at 0.2% oxygen in the absence or the presence of glutamine. The absence of glutamine markedly delayed glucose consumption, which had previously been shown to drive the suppression of BCR/Abl oncoprotein (but not of the fusion oncogene BCR/abl) in low oxygen. Glutamine availability thus emerged as a key regulator of the balance between the pools of BCR/Abl protein-expressing and -negative CML cells endowed with stem/progenitor cell potential and capable to stand extremely low oxygen. These findings were confirmed by the effects of the inhibitors of glucose or glutamine metabolism. The BCR/Abl-negative cell phenotype is the best candidate to sustain the treatment-resistant minimal residual disease (MRD) of CML because these cells are devoid of the molecular target of the BCR/Abl-active tyrosine kinase inhibitors (TKi) used for CML therapy. Therefore, the treatments capable of interfering with glutamine action may result in the reduction in the BCR/Abl-negative cell subset sustaining MRD and in the concomitant rescue of the TKi sensitivity of CML stem cell potential. The data obtained with glutaminase inhibitors seem to confirm this perspective.

You have just arrived in Namibia on the west coast of Southern Africa. You are shown around the hospital and the ICU. In the ICU, you discovered that the only ICU ventilator is a Mark 10 Bird Respirator (Fig. 51.1). You are familiar with this ventilator but see that the driving gas is 100% oxygen and not compressed air. There has been concern that the prolonged administration of high concentration of inspired oxygen may produce pulmonary damage [1, 2]. The nurse in the ICU tells you that they have not seen any pulmonary problem. You know that the Bird ventilator oxygen levels vary from 51.5% to 96.8% when 100% oxygen is used as the driving gas [3]. There is one patient in the ICU being ventilated with the Bird, using low oxygen flows. You tell the nurse that the oxygen levels are highest at low flows and at high cycling pressures [3]. Hence, if the patient can be ventilated with high flows and low cycling pressure, it would be better. The nurse tells you that high-flow oxygen is out of the question, as the hospital doesn’t have much money and oxygen is expensive.

In sickle cell anemia patients, red blood cells (RBCs) are known to become sickle shaped and stiff under hypoxic conditions as a consequence of hemoglobin polymerization. While RBC shape can discriminate sickle blood from healthy, it has not been used until now as a sole biophysical marker to differentiate between homozygous (disease) and heterozygous (trait) sickle blood samples. Here, we establish a technique based on the differential response of disease and trait RBCs to chemically-induced hypoxia to distinguish between these samples for the first time. By comparing the RBC shape distributions in blood treated with high and low concentrations of the hypoxia-inducing agent, we correctly identify 35 unknown blood samples as healthy, sickle cell disease or trait. Finally, we demonstrate our image-based classification technique with a portable smartphone microscope and a disposable microfluidic chip as a prospective point-of-care device enabling fast and confirmed diagnosis of sickle cell anemia. Significance statement Red blood cells (RBCs) of individuals with sickle cell anemia exhibit characteristic shapes in low oxygen environments. The shape of a sickle RBC is determined by its hemoglobin content and how fast oxygen is removed from its surroundings. We report a technique to distinguish between sickle cell carriers and individuals with sickle cell anemia within an hour by treating whole blood with a chemical that removes oxygen, imaging the blood sample inside a microfluidic chamber using a smartphone microscope and finally comparing the shapes of the sickle cells using a classification scheme. We demonstrate the proof of concept of a biophysical test based on the analysis of RBC shapes for point-of-care diagnosis of sickle cell disease in low resource settings.

A 71-year-old man presented to the emergency department (ED) with low oxygen saturations and symptoms consistent with COVID-19 infection. Apart from a small left-sided ischaemic stroke 10 years prior with very minor residual deficit, he had been well and in full-time employment until development of symptoms. Within minutes of commencing non-invasive ventilation (NIV) in the ED, he developed a complete left-sided paralysis and hemineglect. This case highlights the significance of the prothrombotic complications associated with COVID-19 infection. It also raises the question whether pressure changes upon commencing NIV could lead to clot migration.

Coal and methane were mixed and burned in the moderate and intensive low oxygen dilution–oxy coal combustion (MILD–OCC) mode, flame temperature was measured at different flame locations wit...