Reduced Oxygen Supply Research Articles

From oxygen shortage to neurocognitive challenges: behavioral patterns and imaging insights

Environmental hypoxia, resulting from reduced oxygen supply, poses a significant risk of dysfunctioning and damaging the neurocognitive system, particularly in relation to anxiety and stress. Inadequate oxygenation can lead to acute and chronic brain damage. Scholars used behavioral, hemodynamic, and electromagnetic neurofunctional techniques to investigate the effects of normobaric and hypobaric hypoxia on neurocognitive systems. They found a correlation between hypoxia, altered psychomotor responses, and changes in EEG alpha, theta, beta, and gamma rhythms, which affect spatial attention and memory. Hypoxia affects event related potential (ERP) components differently depending on latency. Perceptual responses N1 and P2 remain largely unaffected, while the amplitudes of preattentive MMN, vMMN, and P3a are significantly altered. Late latency components related to attention, particularly P3b, are also altered. These changes illustrate the spectrum from sensory detection to more complex cognitive processing, highlighting the brain's efficiency in managing information. Interestingly, the amplitudes of P3b, ADAN and CNV can increase with increased cognitive demands in hypoxia. This suggests a compensatory response. Prolonged exposure exacerbates these effects, resulting in compensatory delayed behavioral responses and alterations in behavioral monitoring and conflict inhibitory control, as reflected by reduced amplitudes in some attention related ERP components, including N2, N2pc, and ERN. Thus, neurocognitive function and integrity are under stress. ERP sources and hemodynamic images reveal that vulnerable brain regions include the frontal prefrontal cortices, hippocampus, basal ganglia, and parietal and visual cortices, which are essential for attention related processes like decision making and spatial memory. The auditory system appears less affected.

Daily snuff use during pregnancy, gestational length and birth weight; register-based study

BackgroundSnuff is a smokeless source of nicotine that is common in Scandinavia and increasingly used by women of fertile age. Persistent use of snuff during pregnancy has been associated with adverse pregnancy outcomes. Emerging data from the Medical Birth Registry of Norway distinguishes between occasional use and daily use. We provide preliminary estimates of associations between frequency of snuff and gestational length and birth weight.MethodsData on snuff use during pregnancies delivered in 2020 and 2021 were available for the west and central regions of Norway. Associations of snuff use with gestational length and birth weight at term (39–41 weeks) were estimated using quantile regression at the 25th, the 50th and the 75th percentiles, with adjustments for mother’s age, pre-pregnancy weight, and parity. We compared associations with the pregnancy outcomes according to maternal snuff and cigarette use.Results12.4% of 18 042 non-smoking women reported daily use of snuff before pregnancy, and 4.6% reported continuing use during pregnancy, with 1.2% still reporting daily use in the last trimester. Women with daily use through the last trimester delivered babies with a median gestational length reduced by 3.4 days (95% CI: -5.0 to -1.7 days) compared with women who never used snuff. The reduction was even stronger at the 25th percentile of gestational age. The median term birth weight was reduced by 44 g (95% CI: -134 to 46 g). These associations were much weaker for women who quit snuff at some point during pregnancy or used snuff only occasionally. Mothers who smoked daily through the last trimester had a median gestational length reduced by 2.1 days (95% CI: -2.7 to -1.4) and a median term birth weight reduced by 294 g (95% CI: -325 to -262) compared with never-smokers.ConclusionsDaily snuff use through the last trimester reduced the median gestational length by more than three days. Snuff reduced birth weight, but not as much as smoking, suggesting that the predominant effect of smoking on fetal growth is not through nicotine but through the additional toxic chemicals in cigarettes or by reduced oxygen supply to the fetus.

Maternal physical activity in healthy pregnancy: Effect on fetal oxygen supply.

We review evidence for effects of physical activity before and during gestation on the course of pregnancy and ask if there are circumstances where physical activity can stress the fetus due to competition for oxygen and energy substrates. We first summarize physiological responses to exercise in nonpregnant people and known physiological adaptations to pregnancy. Comparing the two, we conclude that physical activity prior to and continuing during gestation is beneficial to pregnancy outcome. The effect of starting an exercise regimen during pregnancy is less easy to assess as few studies have been undertaken. Results from animal models suggest that the effects of maternal exercise on the fetus are transient; the fetus can readily compensate for a short-term reduction in oxygen supply. In general, we conclude that physical activity before and during pregnancy is beneficial, and exercise started during pregnancy is unlikely to affect fetal development. We caution, however, that there are circumstances where this may not apply. They include the intensive exercise regimens of elite athletes and pregnancies at high altitudes where hypoxia occurs even in the resting state.

HUBUNGAN ANTARA ANEMIA DAN INDEKS MASA TUBUH IBU HAMIL TERHADAP KEJADIAN STUNTING PADA ANAK: LITERATURE REVIEW

There are many factors that cause stunting, including anemia. Pregnant women who experience anemia have a reduced oxygen supply to their body cells and brain. In general, anemia in pregnant women is caused by a lack of nutrition, a lack of iron in the food consumed, poor absorption, and chronic diseases (such as tuberculosis, lung, intestinal worms, and malaria). The body mass index of pregnant women is another cause of stunting. Mothers who are short (height <150 cm) and thin (body mass index <18.5 kg/m2) have a greater risk of birthing stunting babies than mothers who have good nutritional status. In addition to macronutrient problems, micronutrient deficiencies in pregnant women need attention. The objective of this study is to determine the relationship between anaemia and body mass index of pregnant women on the incidence of stunting in children, through a literature review. We used the literature review method with 15 journals, 10 international journals, and 5 national journals. The literature review analysis revealed a correlation between anaemia and body mass index in pregnant women and the incidence of stunting. The condition of anaemia in the mother during pregnancy will affect the metabolism of the foetus to be not optimal because there is a lack of haemoglobin levels to bind oxygen so that the adequacy of nutritional intake while in the womb is low and has an impact on foetal growth, which results in low birth weight and length. There is a relationship between anemia and pregnant women's body mass index in terms of stunting incidence.

Perlecan: An Islet Basement Membrane Protein with Protective Anti-Inflammatory Characteristics.

Throughout the isolation process, human islets are subjected to destruction of the islet basement membrane (BM) and reduced oxygen supply. Reconstruction of the BM represents an option to improve islet function and survival post-transplant and may particularly be relevant for islet encapsulation devices and scaffolds. In the present study, we assessed whether Perlecan, used alone or combined with the BM proteins (BMPs) Collagen-IV and Laminin-521, has the ability to protect isolated human islets from hypoxia-induced damage. Islets isolated from the pancreas of seven different organ donors were cultured for 4-5 days at 2% oxygen in plain CMRL (sham-treated controls) or in CMRL supplemented with BMPs used either alone or in combination. Postculture, islets were characterized regarding survival, in vitro function and production of chemokines and reactive oxygen species (ROS). Individually added BMPs significantly doubled islet survival and increased in vitro function. Combining BMPs did not provide a synergistic effect. Among the tested BMPs, Perlecan demonstrated the significantly strongest inhibitory effect on chemokine and ROS production when compared with sham-treatment (p < 0.001). Perlecan may be useful to improve islet survival prior to and after transplantation. Its anti-inflammatory potency should be considered to optimise encapsulation and scaffolds to protect isolated human islets post-transplant.

Determinants of birth weight and length: an analysis of the 2020 mothers' cohort register data

A woman's nutritional status significantly impacts the qualities of the baby she delivers, as assessed by the baby's weight and length at birth. This study aimed to identify factors influencing birth weight and length using a retrospective case-control design with secondary data collected from the mothers' cohort register at the Community Health Center in 2020-2021. The study included 100 samples, comprising 25 cases and 75 controls. Several determinants of birth weight and length were examined: the mother's age (OR=4.1, 95% CI 1.41-12.0), weight gain during pregnancy (OR=3.6, 95% CI 1.051-12.553), mid-upper arm circumference (OR=2.9, 95% CI 1.061-8.220), hemoglobin level (OR=4.711, 95% CI 1.57-14.11), and iron supplement intake (OR=1.837, 95% CI 0.600-5.624), with hemoglobin level identified as the most influential factor on birth qualities. Mothers with less than normal hemoglobin levels have a 4.7 times higher risk of delivering babies of lower weight and length than mothers with normal hemoglobin levels. The impact of low hemoglobin in pregnant women includes reduced oxygen supply for both the mother and fetus, resulting in low birth weight, child anemia, premature birth, and child mortality. Given these significant effects, it is crucial to establish standards for health services in Indonesia, ensuring that pregnant women with low hemoglobin receive comprehensive care aligned with Indonesia's Sustainable Development Goals (SDGs) standards.

Computational modelling of the therapeutic outputs of photodynamic therapy on spheroid-on-chip models

Photodynamic therapy (PDT) is a medical radio chemotherapeutic method that uses light, photosensitizing agents, and oxygen to produce cytotoxic compounds, which eliminate malignant cells. Recently, Microfluidic systems have been used to analyse photosensitizers (PSs) due to their potential to replicate in vivo environments. While prior studies have established a strong correlation between reacted singlet oxygen concentration and PDT-induced cellular death, the effects that the ambient fluid flow might have on the concentration of oxygen and PS have been disregarded in many, which limits the reliability of the results. Herein, we coupled the transport of oxygen and PS throughout the ambient medium and within the spheroidal multicellular aggregate to initially study the profiles of oxygen and PS concentration alongside PDT-induced cellular death throughout the spheroid before and after radiation. The attained results indicate that the PDT-induced cellular death initiates on the surface of the spheroids and subsequently spreads to the neighbouring regions, which is in great accordance with experimental results. Afterward, the effects that drug-light interval (DLI), fluence rate, PS composition, microchannel height, and inlet flow rate have on the therapeutic outcomes are studied. The findings show that adequate DLI is critical to ensure uniform distribution of PS throughout the medium, and a value of 5 h was found to be sufficient. The composition of PS is critical, as ALA-PpIX induces earlier cell death but accelerates oxygen consumption, especially in the outer layers, depriving the inner layers of oxygen necessary for PDT, which in turn disrupts and prolongs the exposure time compared to mTHPC and Photofrin. Despite the fluence rate directly influencing the singlet oxygen generation rate, increasing the fluence rate by 189 mW/cm2 would not significantly benefit us. Microwell height and inlet flow rate involve competing phenomena—increasing height or decreasing flow reduces oxygen supply and increases PS “washout” and its concentration.

A deep learning method for locating fetal heart rate decelerations during labour using crowd-sourced data

Monitoring the heart rate of a fetus is the only method for continuously monitoring fetal well-being during labour. Decelerations in the fetal heart rate, usually corresponding with contractions, provide information regarding the ability of the fetus to cope with a reduced oxygen supply caused by contractions. For this reason, visual and computer-based assessments of fetal well-being depend upon the correct identification of decelerations. Agreement between clinical professionals when identifying these features is poor. Automated methods offer a more consistent alternative, but must perform at a level comparable to a trained human observer. Collecting data to train these systems can be difficult due to time restraints on experts in fetal medicine. In this study, we designed a website to crowd-source data from clinical professionals at their convenience. This data was combined with that from other publicly available sources to produce a dataset that was used to train a convolutional auto-encoder to locate decelerations. Crowd-sourcing was found to be an effective method for collecting data that was suitable to successfully train a deep learning model to locate decelerations. The model trained using this data provided a comparable level of accuracy to users of the website and other models used for the same purpose.

Evaluation of the Effects of Epidural Labour Analgesia on Mode of Delivery in 250 Bedded District Hospital, Bagerhat, Bangladesh

Background: Labor pain is intensely severe, often leading to hyperventilation and hormonal releases that can harm the fetus by reducing oxygen supply and causing metabolic acidosis. Effective pain management during childbirth is crucial for both physical and mental health. Various pharmacologic and non-pharmacologic methods are available, with epidural analgesia being a prominent choice. It is widely used in high-income countries, provides substantial pain relief, and benefits uterine contractions and placental perfusion. Epidural analgesia has potential side effects and controversies, such as delayed labor and higher intervention rates. Aim of the Study: The study aimed to examine the impact of epidural analgesia on the mode of delivery. Methods: This observational study, conducted from July 2021 to June 2022 at the Department of Gynecology and Obstetrics in a 250-bed District Hospital in Bagerhat, Bangladesh, included 50 participants divided into two groups of 25 each: Group A (with epidural analgesia) and Group B (without epidural analgesia). Approved by the Ethical Committee, the study included women aged 18-35 years, 37-41 weeks gestation, in labor with regular contractions, at least 4 cm cervical dilatation, and a regular fetal heart rate pattern. Excluded were women with medical or obstetrical complications, uterine scars, or spinal deformities. Data were collected via interviews, observations, and clinical examinations. Result: In this study of 50 participants (25 per group), most women were under 30 years old, with mean ages of 22.4±4.5 and 22.9±5.2 years in groups A and B, respectively. Gestational ages ranged from 37 to 40 weeks, and BMIs were 18.5-24.9 kg/m². Both groups had similar parity distributions. Normal vaginal births occurred in 84% (Group A) and 88% (Group B), with LSCS rates at 4%. Group A had 60% male neonates with average birth weights of 2.86±0.27 kg, and Group B had 56% males with weights of 2.88±0.26 kg. APGAR scores were high in both groups. Conclusion: Epidural labor analgesia is safe and does not increase instrumental deliveries or affect neonatal outcomes, making it a viable pain management option. Obstetric care providers can use this information to counsel women.

The Negative Impact of Vaping and Electric Cigarettes for Healing of Acute Wounds: A Literature Review

Emerging evidence suggests that vaping can significantly impede wound healing, with prevalence rates of current e-cigarette use varying between 3.3% and 11.8%. This study aims to investigate the impact of vaping on wound healing, particularly in acute wounds encountered in plastic surgery settings. Electronic cigarettes (e-cigarettes), comprising a rechargeable battery and an atomizer or heating element, typically contain flavored liquids with or without nicotine as humectants. Skin wounds heal through overlapping inflammatory, proliferative, and remodeling phases. Chemical constituents of e-cigarettes, including propylene glycol (PG), vegetable glycerin (VG), nicotine, flavoring agents, and contaminants, hinder wound healing by inducing osmotic effects, cellular toxicity, vasoconstriction, reduced oxygen supply, impaired angiogenesis, cytotoxicity, and modulation of inflammatory responses. Similar to conventional cigarettes, e-cigarettes may compromise wound healing through a multifaceted mechanism, although they may offer a comparatively less harmful alternative.

Association Between Corneal Changes and Retinal Oximetry in Diabetes Mellitus.

Diabetes mellitus (DM) causes different corneal changes that are associated with the severity of diabetic retinopathy. To identify the pathophysiological reasons for this, corneal tomography and optical densitometry (COD) were combined with retinal oximetry. Patients with DM and healthy subjects were included in this pilot study. Spatially resolved corneal thickness and COD were assessed using the Pentacam HR (Oculus). The pachymetry difference (PACDiff) was calculated as an indicator of an increase in the peripheral corneal thickness. Oxygen saturation (SO2) of the retinal vessels was measured using the Retinal Vessel Analyzer (Imedos Systems UG). Subsequently, the associations between corneal and retinal parameters were analyzed. Data from 30 patients with DM were compared with those from 30 age-matched healthy subjects. In DM, arterial (P = 0.048) and venous (P < 0.001) SO2 levels were increased, and arteriovenous SO2 difference was decreased (P < 0.001). In patients, PACDiff was higher than that in healthy subjects (P < 0.05), indicating a stronger increase in peripheral corneal thickness. The COD was reduced in DM (P = 0.004). The PACDiff of concentric rings with a diameter of 4 mm (r = -0.404; P = 0.033) to 8 mm (r = -0.522; P = 0.004) was inversely correlated with the arteriovenous SO2 difference. Furthermore, PACDiff 4 mm was negatively associated with arterial SO2 (r = -0.389; P = 0.041), and the COD of the peripheral corneal areas correlated positive with arterial SO2 (COD total 10-12 mm: r = 0.408; P = 0.025). These associations might indicate a common pathogenesis of corneal and retinal changes in DM, which could be caused by reduced oxygen supply, mitochondrial dysfunction, oxidative stress, and cytokine effects.

Cross-Oxygen Gradients Transcriptomic Comparison Revealed the Central Role of MAPK and Hippo in Hypoxia-Mediated Mammary Proliferation Inhibition.

The role of hypoxia in terms of affecting mammary epithelial cells (MECs) proliferation is closely associated with the milk synthesis of lactating mammals. Primary bovine MECs were cultured at 1, 6, 11, 16, and 21% O2 for 24 h. The results showed that cell proliferation decreased linearly, and hypoxic inducible factor (HIF)-1α expression increased linearly along with the declining O2. The linear increase in oxidative stress resulted in the accumulation of malondialdehyde and reactive oxygen species and decreased antioxidant enzyme activities following the reduced O2. Concerning mitochondria, the dynamin-related protein 1 showed improved expression, and optin atrophy protein 1 decreased along with the decreasing O2 gradient, which led to decreased mitochondrial mass and mitophagy emerging under 1% O2. Oxygen concentration-trend RNA-seq analysis was conducted. Specifically, HIF-1-MAPK (1% O2), PI3K-Akt-MAPK (6% O2), and p53-Hippo (11 and 16% O2) were found to primarily regulate cell proliferation in response to hypoxia compared with normoxia (21%), respectively. In conclusion, our study suggests that bMEC proliferation is suppressed in low-oxygen conditions, and is exacerbated following the reduced oxygen supply. The cross-oxygen gradient comparisons suggest that MAPK and Hippo, which are core pathways of mammary cell proliferation, are repressed by hypoxia via oxidative-stress-dependent signals.

Sorafenib-Encapsulated Liposomes to Activate Hypoxia-Sensitive Tirapazamine for Synergistic Chemotherapy of Hepatocellular Carcinoma.

Combination therapy with the synergistic effect is an effective way in cancer chemotherapy. Herein, an antiangiogenic sorafenib (SOR) and hypoxia-activated prodrug tirapazamine (TPZ)-coencapsulated liposome (LipTPZ/SOR) is prepared for chemotherapy of hepatocellular carcinoma (HCC). SOR is a multi-target tyrosine kinase inhibitor that can inhibit tumor cell proliferation and angiogenesis. The antiangiogenesis effect of SOR can reduce oxygen supply and aggravate tumor hypoxia, which is able to activate hypoxia-sensitive prodrug TPZ, exhibiting the synergistic antitumor effect. LipTPZ/SOR at different molar ratios of TPZ and SOR can significantly inhibit the proliferation of hepatocellular carcinoma cells. The mole ratio of TPZ and SOR was optimized to 2:1, which exhibited the best synergetic antitumor effect. The synergistic antitumor mechanism of SOR and TPZ was also investigated in vivo. After treated with SOR, the number of vessels was decreased, and the degree of hypoxia was aggravated in tumor tissues. What is more, in the presence of SOR, TPZ could be activated to inhibit tumor growth. The combination of TPZ and SOR exhibited an excellent synergistic antitumor effect. This research not only provides an innovative strategy to aggravate tumor hypoxia to promote TPZ activation but also paints a blueprint about a new nanochemotherapy regimen for the synergistic chemotherapy of HCC, which has excellent biosafety and bright clinical application prospects.

Squalene production under oxygen limitation by Schizochytrium sp. S31 in different cultivation systems

The triterpene squalene is widely used in the food, cosmetics and pharmaceutical industries due to its antioxidant, antistatic and anti-carcinogenic properties. It is usually obtained from the liver of deep sea sharks, which are facing extinction. Alternative production organisms are marine protists from the family Thraustochytriaceae, which produce and store large quantities of various lipids. Squalene accumulation in thraustochytrids is complex, as it is an intermediate in sterol biosynthesis. Its conversion to squalene 2,3-epoxide is the first step in sterol synthesis and is heavily oxygen dependent. Hence, the oxygen supply during cultivation was investigated in our study. In shake flask cultivations, a reduced oxygen supply led to increased squalene and decreased sterol contents and yields. Oxygen-limited conditions were applied to bioreactor scale, where squalene accumulation and growth of Schizochytrium sp. S31 was determined in batch, fed-batch and continuous cultivation. The highest dry matter (32.03 g/L) was obtained during fed-batch cultivation, whereas batch cultivation yielded the highest biomass productivity (0.2 g/L*h−1). Squalene accumulation benefited from keeping the microorganisms in the growth phase. Therefore, the highest squalene content of 39.67 ± 1.34 mg/g was achieved by continuous cultivation (D = 0.025 h−1) and the highest squalene yield of 1131 mg/L during fed-batch cultivation. Volumetric and specific squalene productivity both reached maxima in the continuous cultivation at D = 0.025 h−1 (6.94 ± 0.27 mg/L*h−1 and 1.00 ± 0.03 mg/g*h−1, respectively). Thus, the choice of a suitable cultivation method under oxygen-limiting conditions depends heavily on the process requirements.Key points• Measurements of respiratory activity and backscatter light of thraustochytrids• Oxygen limitation increased squalene accumulation in Schizochytrium sp. S31• Comparison of different cultivation methods under oxygen-limiting conditions

Pregnancy course and outcomes in patients with non-insulin dependent gestational diabetes mellitus: An observational cohort study

Background. Gestational diabetes mellitus is the most frequent metabolic disorder during pregnancy. Its prevalence is steadily increasing worldwide. In the setting of hyperinsulinism, this pathology may cause various structural and functional changes in the placenta, as well as a reduction in oxygen supply to the fetus. This may result in fetal hypoxia and increased risk of fetal growth restriction. Therefore, research into the specific features of gestation course in patients with gestational diabetes mellitus in order to prevent its complications appears relevant. Objective. To study the specific features of gestation, delivery, and perinatal outcomes in patients with non-insulin dependent gestational diabetes mellitus. Methods. We conducted an observational cohort study of the case histories of 120 women with singleton pregnancies of the second and third trimesters with diagnosed non-insulin dependent gestational diabetes mellitus, their labor and delivery records, and the medical records of the newborns. All the patients were managed at the Ural Research Institute of Maternity and Child Care during 2021–2023. The main group comprised 70 patients whose pregnancy was complicated by sub- and decompensated forms of placental insufficiency. The comparison group comprised 50 pregnant women without pathologies of the fetoplacental complex. The obstetric history, gestation course of the present pregnancy and its outcomes, as well as the condition of the newborns, were analyzed. The obtained data were processed by the methods of variation statistics using Microsoft Excel spreadsheets (Microsoft, USA) and Statistica 13 (DellInc., USA) and MedCalc 15.8 (MedCalcSoftware, Belgium) applications. The null hypothesis was rejected at p &gt; 0.05. Results. Gestational diabetes mellitus in previous pregnancies was statistically significantly less frequent in the main group (2.9% (n = 2)) than in the comparison group (18.0% (n = 9)) ( p &gt; 0.05). Placental insufficiency in the main group was characterized by fetal growth restriction, which was associated with impaired uteroplacental blood flow in 58.6% (n = 41) of the cases. In the main group, the pregnancy ended in preterm delivery in 21.4% (n = 15) of the cases; in 78.6% (n = 55) of the cases, the delivery was at term. There were no preterm births in the comparison group, p &gt; 0.05. Cesarean section was performed in 62.9% (n = 44) of patients in the main group, compared to 20.0% (n = 10) in the comparison group ( p &gt; 0.05). Newborns of the main group required respiratory support more often (p &gt; 0.05). Conclusion. The mechanism of placental insufficiency in patients with non-insulin dependent gestational disorders of carbohydrate metabolism remains to be elucidated. Further research should investigate the predictors of fetoplacental complex pathologies in this group of patients in order to reduce the number of perinatal complications.

Retinal oxygen extraction and hyperemic response in patients with Type II diabetes at different stages of non‐proliferative diabetic retinopathy

Purpose: Diabetic retinopathy (DR) is a worldwide cause of irreversible vision loss. Vascular factors such as reduced oxygen supply and impaired neurovascular coupling play a major role in the development of DR. We therefore investigated retinal oxygen metabolism and functional hyperemia in patients with Type II diabetes at different stages of non‐proliferative DR and healthy controls.Methods: To study retinal oxygen metabolism, a total of 67 patients with Type II diabetes (34 patients with no, 15 with mild and 18 with moderate‐to‐severe DR) and 20 healthy controls were recruited. We used the oxygen module of a Retinal Vessel Analyzer to measure retinal oxygen saturation in arteries and veins, and a custom‐built Doppler optical coherence tomography (DOCT) system to assess total retinal blood flow (TRBF). Values of retinal oxygen saturation and TRBF were then used to calculate retinal oxygen extraction. To measure the hyperaemic response, 29 patients with no, 12 with mild, 15 with moderate‐to‐severe DR and 20 healthy controls were included. Retinal blood flow was assessed before and during visual stimulation by combined measurement of retinal vessel calibres and blood velocity using the Dynamic Vessel Analyzer (Imedos, Germany) and DOCT.Results: Retinal oxygen extraction was lowest in patients with moderate‐to‐severe DR (1.78 ± 0.57 μL O2/min, p = 0.040 vs. healthy controls), followed by mild DR (1.90 ± 0.77 μL O2/min), no DR (2.14 ± 0.6 μL O2/min) and healthy controls (2.24 ± 0.57 μL O2/min). Compared to healthy controls (40.4 ± 27.2%), flicker responses were significantly decreased in patients with DR depending on the stage of DR (no DR 37.7 ± 26.0%, mild DR 26.2 ± 28.2%, moderate‐to‐severe DR 22.3 ± 13.9%; p = 0.035, ANOVA).Conclusions: Our results indicate that retinal oxygen extraction as well as hyperaemic response decreases with increasing severity of DR. Further studies are needed to assess whether these retinal functional changes can be used to identify high‐risk patients.

Hypoxic-ischaemic encephalopathy based on clinical signs and symptoms and associated factors among neonates, Southern Ethiopian public hospitals: a case-control study.

Hypoxic-ischaemic encephalopathy (HIE) is a severe condition that results from reduced oxygen supply and blood flow to the brain, leading to brain injury and potential long-term neurodevelopmental impairments. This study aimed to identify the maternal and neonatal factors associated with hypoxic-ischaemic encephalopathy among Neonates. The authors conducted a case-control study in 15 public hospitals with 515 neonates and mothers (175 cases and 340 controls). The authors used a questionnaire and clinical records created and managed by Kobo software to collect data. The authors diagnosed hypoxic-ischaemic encephalopathy (HIE) by clinical signs and symptoms. The authors used logistic regression to identify HIE factors. Hypoxic-ischaemic encephalopathy (HIE) was associated with maternal education, ultrasound checkup, gestational age, delivery mode, and labour duration. Illiterate mothers [adjusted odds ratio (AOR)= 1.913, 95% CI: 1.177, 3.109], no ultrasound checkup (AOR= 1.859, 95% CI: 1.073, 3.221), preterm (AOR= 4.467, 95% CI: 1.993, 10.012) or post-term birth (AOR= 2.903, 95% CI: 1.325, 2.903), caesarean section (AOR= 7.569, 95% CI: 4.169, 13.741), and prolonged labour (AOR= 3.591, 95% CI: 2.067, 6.238) increased the incidence of HIE. This study reveals the factors for hypoxic-ischaemic encephalopathy among neonates in Ethiopia. The authors found that neonates born to illiterate women, those who experienced prolonged labour, those whose mothers did not have ultrasound checkups during pregnancy, those delivered by caesarean section, and those born preterm, or post-term were more likely to develop hypoxic-ischaemic encephalopathy. These findings indicate that enhancing maternal education and healthcare services during pregnancy and delivery may positively reduce hypoxic-ischaemic encephalopathy among neonates.

Endovascular therapy for cerebral vasospasm after aneurysmal subarachnoid hemorrhage: Single-center experience in a high-volume neurovascular unit

IntroductionDespite targeted standard therapy, aneurysmal subarachnoid hemorrhage (aSAH) frequently leads to cerebral vasospasms (CVS) of large cerebral arteries, reduced oxygen supply of brain tissue, known as delayed cerebral ischemia (DCI), subsequent development of manifest cerebral infarction and poor neurological outcome. Research questionThe primary aim was to evaluate the efficacy of endovascular spasmolysis (eSL) as a rescue therapy for delayed ischemic neurological deficits (DIND) occurring despite maximum conservative treatment, with the potential benefit of preventing permanent ischemic deficits, and thus, improving overall neurological outcomes. Material and methodsIn our retrospective, monocentric study, we included 310 patients developing CVS during hospitalization and evaluated their clinical and radiographic outcomes. Severe vasospasm was defined by a mean velocity of >200 cm/s in transcranial Doppler ultrasound and/or occurrence of new neurological deficits, and/or decrease of at least 2 points on the Glasgow Coma Scale (GCS), respectively. Results92 patients (29.7%) underwent eSL due to persistent symptoms despite conservative therapy. Among endovascularly treated patients, 86% (n = 79) improved angiographically, 71% (n = 44) of 62 patients who underwent eSL due to symptomatic deterioration improved clinically. Clinical worsening due to progressive CVS occurred in 18% of cases (n = 11). Periprocedural complications were observed in 4% (n = 4). Discussion and conclusioneSL emerges as a safe and effective therapy for individuals experiencing DIND triggered by large-artery vasospasm following aSAH. The implementation of a standardized, multi-step process for detection and management, coupled with criteria for endovascular interventions, proves to be an efficient preventative approach to enhance neurological outcomes after aSAH.

Role of RIPK1 kinase in neuronal-glial network adaptation under hypoxic conditions

Cerebral hypoxia is a condition characterized by a reduced oxygen supply to tissues that plays a crucial role in the pathogenesis of numerous neurodegenerative diseases. In hypoxia, intracellular signaling cascades are activated, ultimately leading to various forms of nerve cell death. The initiation of necroptosis under hypoxic conditions is governed by PIPK1 kinase, and its inhibition could potentially offer neuroprotection against hypoxic damage [1–3]. Studies investigating the effects of blocking RIPK1 kinase on the activity of neuronal-glial networks are currently lacking. Consequently, RIPK1 kinase constitutes a promising objective for further exploration. Thus, the aim of this work is to examine the part played by RIPK1 kinase in the adjustment of neuronal-glial networks amid hypoxia. The study focused on primary cultures of nerve cells in the hippocampus of mouse embryos belonging to the C57Bl/6 line. Hypoxia was induced in vitro on the 14th day of culturing the nerve cells. The RIPK1 kinase inhibitor was administered 20 minutes prior to, during, and after the hypoxia intervention. After 7 days of the stress induction, the calcium and bioelectrical activity of the neuron-glial networks were evaluated. Calcium activity was assessed via the Oregon Green 488 BAPTA-1, AM (Thermo Fisher Scientific, USA) using a Zeiss LSM 800 confocal laser scanning microscope (Carl Zeiss, Germany). The experiments assessed total percentage of oscillating cells in culture, the frequency, and duration of calcium events. The analysis of bioelectrical activity was conducted using the MEA 60 multi-electrode arrays from Multichannel Systems. The registered signal from the arrays was processed through the MEAMAN algorithms in MATLAB (Certificate of State Registration of Computer Program No. 2012611190). The average number of small network packages and spikes was estimated. Under physiological conditions, spontaneous calcium activity is observed by the 21st day of neuron-glial network development. The percentage of cells exhibiting calcium events is 60.64 ± 3.68%, the frequency of calcium oscillations is 1.52±0.22 osc/min, and the duration is 9.63±0.75 s. During hypoxia modeling, the percentage of cells exhibiting calcium events decreased to 34.77±4.08%, and the frequency of calcium oscillations decreased to 0.64±0.08 osc/min. The inhibition of RIPK1 kinase maintains the percentage of cells exhibiting calcium events at the level of intact cultures, which is 60.38±3.4%. By the 21st day of culturing primary nerve cell cultures under physiological conditions, spontaneous bioelectrical activity forms. This is indicated by parameters such as the average number of small network clusters and spikes. Hypoxia modeling has a negative impact on the development of spontaneous bioelectrical activity. In the “Intact” group, the average number of small network packs was 36.12±4.27 packs per 10 minutes, while in the cell culture with hypoxia, it was 15.87±3.03 packs per 10 minutes. Additionally, the “Intact” group had an average of 90.22±12.32 spikes, while the cell culture with hypoxia had only 11.58±4.7 spikes. However, blocking RIPK1 kinase during hypoxia preserved the average number of small network packs (23,49±2,14 packs/10 min). Thus, inhibiting RIPK1 kinase under hypoxic conditions preserves the proportion of cells that exhibit spontaneous calcium events and partially preserves spontaneous bioelectrical activity.

Enhanced fetal hematopoiesis in response to symptomatic SARS-CoV-2 infection during pregnancy

BackgroundPregnant women and their fetuses are particularly susceptible to respiratory pathogens. How they respond to SARS-CoV-2 infection is still under investigation.MethodsWe studied the transcriptome and phenotype of umbilical cord blood cells in pregnant women infected or not with SARS-CoV-2.ResultsHere we show that symptomatic maternal COVID-19 is associated with a transcriptional erythroid cell signature as compared with asymptomatic and uninfected mothers. We observe an expansion of fetal hematopoietic multipotent progenitors skewed towards erythroid differentiation that display increased clonogenicity. There was no difference in inflammatory cytokines levels in the cord blood upon maternal SARS-CoV-2 infection. Interestingly, we show an activation of hypoxia pathway in cord blood cells from symptomatic COVID-19 mothers, suggesting that maternal hypoxia may be triggering this fetal stress hematopoiesis.ConclusionsOverall, these results show a fetal hematopoietic response to symptomatic COVID-19 in pregnant mothers in the absence of vertically transmitted SARS-CoV-2 infection which is likely to be a mechanism of fetal adaptation to the maternal infection and reduced oxygen supply.