Evaluation of the usefulness of insertion-null markers in critical skeletal remains.

Forensic DNA analysis in compromised skeletal remains may pose challenges due to DNA degradation, often resulting in partial or negative autosomal STRs profiles. To address this issue, alternative approaches such as mitochondrial DNA or SNPs typing may be employed; however, they are labour-intensive and costly. Insertion-null alleles (INNULs), short interspersed nuclear elements, have been suggested as a valuable tool for human identification in challenging samples due to their small amplicon size. A commercial kit including 20 INNULs markers along with amelogenin (InnoTyper® 21) has been developed. This study assesses its utility using degraded skeletal remains, comparing the results obtained (the number of detected alleles, RFU values, PHR, and the number of reportable markers) to those obtained using GlobalFiler™. Subsequently, the random match probability of the two profiles for each sample was determined using Familias version 3 to evaluate the power of discrimination of the results obtained from each kit. In every sample, InnoTyper® 21 yielded more alleles, higher RFU values, and a greater number of reportable loci. However, in most cases, both profiles were similarly informative. In conclusion, InnoTyper® 21 serves as a valuable complement to the analysis of challenging samples in cases where a poor or negative profile was obtained.

Drug-induced orthostatic hypotension: Cluster analysis of co-prescription patterns in older people in UK primary care.

PURPOSE: Over 250 medications are reported to cause orthostatic hypotension, associated with serious adverse outcomes in older adults. Studies suggest a harmful cumulative risk of orthostatic hypotension with multiple medication use. However, there is limited evidence on the potential for harm in practice, particularly which drugs is co-prescribed and may increase risk of orthostatic hypotension. METHODS: Retrospective cohort study and cluster analysis using general practice data from IQVIA Medical Research Data (IMRD) in patients aged ≥50 contributing data between 1 January 2018 and 31 December 2018. Thirteen drug groups known to be associated with orthostatic hypotension by mechanism, were analyzed and clusters generated by sex and age-band. RESULTS: A total of 602 713 individuals aged ≥50 with 283 912 (47%) men and 318 801 (53%) women were included. The most prevalent prescriptions that might contribute to orthostatic hypotension were ACE inhibitors, calcium-channel blockers, beta-blockers, selective serotonin reuptake inhibitors and uroselective alpha-blockers. We identified distinct clusters of cardiovascular system (cardiovascular system) drugs in men and women at all ages. cardiovascular system plus psychoactive drug clusters were common in women at all ages, and in men aged ≤70. cardiovascular system plus uroselective alpha-blockers were identified in men aged ≥70. CONCLUSIONS: Distinct clusters of drugs associated with orthostatic hypotension exist in practice, which change over the life course. Our findings highlight potentially harmful drug combinations that may cause cumulative risk of orthostatic hypotension in older people. This may guide clinicians about the potential of synergistic harm and to monitor for orthostatic hypotension if using combinations of cardiovascular system drugs, cardiovascular system plus psychoactive drugs and/or alpha-blockers-particularly in patients aged ≥70 or at high-risk due to comorbidity. Future research should consider quantifying the risk of drug-induced orthostatic hypotension with such drug combinations.

Understanding the association between pain and delirium in older hospital inpatients: systematic review and meta-analysis.

OBJECTIVE: Delirium and pain are common in older adults admitted to hospital. The relationship between these is unclear, but clinically important. We aimed to systematically review the association between pain (at rest, movement, pain severity) and delirium in this population. METHODS: PubMed, EMBASE, CINAHL, PsycINFO, Cochrane and Web of Science were searched (January 1982-November 2022) for Medical Subject Heading terms and synonyms ('Pain', 'Analgesic', 'Delirium'). Study eligibility: (1) validated pain measure as exposure, (2) validated delirium tool as an outcome; participant eligibility: (1) medical or surgical (planned/unplanned) inpatients, (2) admission length ≥ 48 h and (3) median cohort age over 65 years. Study quality was assessed with the Newcastle Ottawa Scale. We collected/calculated odds ratios (ORs) for categorical data and standard mean differences (SMDs) for continuous data and conducted multi-level random-intercepts meta-regression models. This review was prospectively registered with PROSPERO [18/5/2020] (CRD42020181346). RESULTS: Thirty studies were selected: 14 reported categorical data; 16 reported continuous data. Delirium prevalence ranged from 2.2 to 55%. In the multi-level analysis, pain at rest (OR 2.14; 95% confidence interval [CI] 1.39-3.30), movement (OR 1.30; 95% CI 0.66-2.56), pain categorised as 'severe' (OR 3.42; 95% CI 2.09-5.59) and increased pain severity when measured continuously (SMD 0.33; 95% CI 0.08-0.59) were associated with an increased delirium risk. There was substantial heterogeneity in both categorical (I2 = 0%-77%) and continuous analyses (I2 = 85%). CONCLUSION: An increase in pain was associated with a higher risk of developing delirium. Adequate pain management with appropriate analgesia may reduce incidence and severity of delirium.

Witnessing inter-parental violence in childhood and help-seeking behaviours in violence against women in Peru.

BACKGROUND: Violence against women (VAW) severely impacts their physical and mental health. In some cultures, women can normalize certain types of violence if they were linked to home models in childhood and, eventually, do not seek for help in adulthood. We aimed to determine, in Peruvian women, (1) the association between witnessing violence in their family of origin and VAW experienced in adulthood, (2) the extent to which women who have experienced VAW seek some help, and (3) identify VAW prevalence by Peruvian region. METHODS: Cross-sectional study of secondary data obtained from the 2019 National Demographic and Family Health Survey (ENDES). The outcome was VAW (psychological, physical and sexual violence), whereas the exposure was witnessing violence in the home of origin. Help-seeking behavior was a secondary outcome, for which VAW was the exposure. Prevalence ratios (PR) were estimated to assess both associations, unadjusted and adjusted for covariates (aPR). RESULTS: Data from 14,256 women aged 15 to 49 years were analysed. 51.5% reported having experienced VAW and 43.8% witnessed violence in the home of origin during childhood. Witnessing inter-parental violence in childhood was associated with psychological violence aPR = 1.25 (95% CI: 1.17-1.33), physical aPR = 1.52 (95% CI: 1.38-1.67), and sexual aPR = 1.99 (95% CI: 1.57-2.52). Women who have experienced both types of violence (physical and sexual) were more likely to help-seeking (aPR = 1.30, 95% CI: 1.14-1.50) than women suffering only one type of violence. CONCLUSION: Women who reported having witnessed home violence in their childhood are more likely to experience Violence Against Women (VAW) by their current partner. Physical and sexual violence with a current partner was more associated with witnessing inter-parental violence in childhood, and when physical and sexual violence jointly occurred women were more help-seeking. The southern region of Peru is identified as an area of high vulnerability for women. It is crucial to promote educative and community-based programs aimed at the prevention and early recognition of VAW.

Cultural adaptation to Bolivian Quechua and psychometric analysis of the Patient Health Questionnaire PHQ-9.

OBJECTIVE: Cultural adaptation of the Patient Health Questionnaire-PHQ-9 to Bolivian Quechua and analysis of the internal structure validity, reliability, and measurement invariance by sociodemographic variables. METHODS: The PHQ-9 was translated and back-translated (English-Quechua-English) to optimise translation. For the cultural adaptation, experts, and people from the target population (e.g., in focus groups) verified the suitability of the translated PHQ-9. For the psychometric analysis, we performed a Confirmatory Factor Analysis (CFA) to evaluate internal validity, calculated α and ω indices to assess reliability, and performed a Multiple Indicator, Multiple Cause (MIMIC) model for evaluating measurement invariance by sex, age, marital status, educational level and residence. We used standard goodness-of-fit indices to interpret both CFA results. RESULTS: The experts and focus groups improved the translated PHQ-9, making it clear and culturally equivalent. For the psychometric analysis, we included data from 397 participants, from which 73.3% were female, 33.0% were 18-30 years old, 56.7% reported primary school studies, 63.2% were single, and 62.0% resided in urban areas. In the CFA, the single-factor model showed adequate fit (Comparative Fit Index = 0.983; Tucker-Lewis Index = 0.977; Standardized Root Mean Squared Residual = 0.046; Root Mean Squared Error of Approximation = 0.069), while the reliability was optimal (α = 0.869-0.877; ω = 0.874-0.885). The invariance was confirmed across all sociodemographic variables (Change in Comparative Fit Index (delta) or Root Mean Square Error of Approximation (delta) < 0.01). CONCLUSIONS: The PHQ-9 adapted to Bolivian Quechua offers a valid, reliable and invariant unidimensional measurement across groups by sex, age, marital status, educational level and residence.

Highest oxygen consumption prediction: introducing variable theoretical proportional factors for different sports.

PURPOSE: The use of a fixed theoretical-proportional-factor (TPF15) is one of the indirect highest-oxygen-consumptions (HOC) assessment methods, but it may not accurately reflect the physiological differences across various sports (cycling-triathlon-running-football-multisport). The aim of this study is to evaluate the variability of TPF across different sports, proposing a series of sport-specific new TPF values for more accurate HOC estimation. METHODS: A sample of 340 adults (26.01 ± 7.18 years) performed a maximal-incremental-test using sport-specific-ergometers. HOC was considered for cycling  V ˙ O 2peak , whereas for the other investigated sports it was considered V ˙ O 2max . HOC was directly measured using a gas-analyzer, and TPF values were calculated using heart rate (HR): the ratio of HRmax/HRrest multiplied for the measured values of HOC. A one-way ANOVA was used to measure differences and Bland-Altman plots were constructed to compare predicted and actual  V ˙ O 2max / V ˙ O 2peak . RESULTS: Actual HOC was significantly greater than those predicted by the fixed TPF15 (P < 0.001). Sport-specific new TPF values ranged from 16.55 in multisport to 20.15 in cycling, consistently exceeding the old fixed TPF15, and predicting therefore better HOC. The new TPF exhibited a closer agreement with the directly measured V ˙ O 2max / V ˙ O 2peak  compared to the TPF15. Furthermore, the new TPF reduced the typical-measurement-error (14.94-17.78%) compared to TPF15 (15.63-24.13%). CONCLUSION: This study suggests that new TPF values predict V ˙ O 2max / V ˙ O 2peak  with higher accuracy compared to the traditional method. The use of HRmax and HRrest values allows to customize training programs for different athletes. Future research should focus on validating these findings across larger populations of athletes.

PICC tip dislodgement causing massive pleural effusion and atelectasis with acute respiratory failure: a case report.

Peripheral intravenous central catheter (PICC) is a common tool for intravenous infusion for children who need central venous access. Although it is safe for physicians and nurses to place, complications like infection, occlusion, phlebitis, and bleeding can occur. We report a 5-month-old infant who suffered respiratory failure caused by catheter malposition resulting in massive fluid infusion into the thoracic cavity. Point-of-care ultrasound (POCUS) was utilized to identify a massive pleural effusion that prompted urgent drainage. Complications related to PICC in pediatric patients are not common but difficult to immediately identify sometimes. Therefore, careful attention should be paid by physicians to identify and reduce the risk of complications associated with PICC. Thus, visual tools are strongly advised to enhance the safety of invasive procedures.

Brodalumab for moderate-severe hidradenitis suppurativa: An open-label multicentric cohort study in real clinical practice.

INTRODUCTION: The use of biological therapy is becoming increasingly common in patients with hidradenitis suppurativa (HS). Levels of serum TNF-alfa and IL17 support the role of an immune system dysregulation in the pathogenesis of HS. Brodalumab targets the receptor A of IL-17, thus having a promising role in the treatment of HS. MATERIAL AND METHODS: A multicenter retrospective observational open-label study was conducted in two tertiary hospitals. Adults with moderate to severe HS under treatment with brodalumab 210 mg at week 0, 1, 2 and then every 2 weeks were included and assessed at weeks 0 and 16 which was the median follow-up time. Demographic and disease-related variables as well as response parameters (HiSCR and IHS4) and safety data were recorded and analysed. RESULTS: A total of 16 patients (75% males) were included in our study. 50% of patients presented an inflammatory phenotype and mean BMI was 28.37. HiSCR was achieved in 50% of patients and mean IHS4 decreased from 24.13 to 16.81 (p = 0.002). No differences were found between those who achieved HiSCR and those who did not. Grade 2 adverse events were reported in three patients with no fatal outcomes and treatment discontinuation was advised in four patients. CONCLUSIONS: Brodalumab seems to be effective and safe in patients with moderate to severe HS, even in those that did not respond to adalimumab, which, at the moment, is the only widely approved biologic for this indication. Thus, it stands as an interesting option for the treatment of HS.

Study of the Diagnostic Accuracy Between the Position of the Articular Disc According to Magnetic Resonance Imaging and Arthroscopy Findings for Temporomandibular Disorders.

The aim of this study was to prospectively evaluate the diagnostic accuracy between the position of the disc in the temporomandibular joint (TMJ) according to findings on magnetic resonance (MRI) imaging and the position of the disc depending on the "roofing" in arthroscopic evaluation in patients who underwent arthroscopy for a temporomandibular disorder (TMD). This relationship was analyzed in 298 patients diagnosed with internal derangements. The concordance between the 2 methods was evaluated using the κ coefficient. A significant agreement was observed between the findings in MRI and roofing in arthroscopy with an excellent concordance between the variables (κ=0.83, P<0.05). This indicates that both diagnostic methods are equally valid in the precise description and evaluation of the disc position for patients with a TMD undergoing arthroscopy.

Design and Characterization of a Wearable Inertial Measurement Unit.

The utilization of inertial measurement units as wearable sensors is proliferating across various domains, such as health care, sports, and rehabilitation. This expansion has produced a market of devices tailored to accommodate very specific ranges of operational demands. Simultaneously, this growth is creating opportunities for the development of a new class of devices more oriented towards general-purpose use and capable of capturing both high-frequency signals for short-term, event-driven motion analysis and low-frequency signals for extended monitoring. For such a design, which combines flexibility and low cost, a rigorous evaluation of the device in terms of deviation, noise levels, and precision is essential. This evaluation is crucial for identifying potential improvements and refining the design accordingly, yet it is rarely addressed in the literature. This paper presents the development process of such a device. The results of the design process demonstrate acceptable performance in optimizing energy consumption and storage capacity while highlighting the most critical optimizations needed to advance the device towards the goal of a smart, general-purpose unit for human motion monitoring.

Multipurpose Modular Wireless Sensor for Remote Monitoring and IoT Applications.

Today, maintaining an Internet connection is indispensable; as an example, we can refer to IoT applications that can be found in fields such as environmental monitoring, smart manufacturing, healthcare, smart buildings, smart homes, transportation, energy, and others. The critical elements in IoT applications are both the Wireless Sensor Nodes (WSn) and the Wireless Sensor Networks. It is essential to state that designing an application demands a particular design of a WSn, which represents an important time consumption during the process. In line with this observation, our work describes the development of a modular WSn (MWSn) built with digital processing, wireless communication, and power supply subsystems. Then, we reduce the WSn-implementing process into the design of its modular sensing subsystem. This would allow the development and launching processes of IoT applications across different fields to become faster and easier. Our proposal presents a versatile communication between the sensing modules and the MWSn using one- or two-wired communication protocols, such as I2C. To validate the efficiency and versatility of our proposal, we present two IoT-based remote monitoring applications.

Altered Plasma Membrane Lipid Composition in Hypertensive Neutrophils Impacts Epithelial Sodium Channel (ENaC) Endocytosis.

Biological membranes are composed of a lipid bilayer with embedded proteins, including ion channels like the epithelial sodium channel (ENaC), which are critical for sodium homeostasis and implicated in arterial hypertension (HTN). Changes in the lipid composition of the plasma membrane can significantly impact cellular processes related to physiological functions. We hypothesized that the observed overexpression of ENaC in neutrophils from HTN patients might result from alterations in the structuring domains within the plasma membrane, disrupting the endocytic processes responsible for ENaC retrieval. This study assessed the structural lipid composition of neutrophil plasma membranes from HTN patients along with the expression patterns of key elements regulating ENaC at the plasma membrane. Our findings suggest alterations in microdomain structure and SGK1 kinase activity, which could prolong ENaC presence on the plasma membrane. Additionally, we propose that the proteasomal and lysosomal degradation pathways are insufficient to diminish ENaC presence at the plasma membrane in HTN. These results highlight the importance of understanding ENaC retrieval mechanisms and suggest that targeting these mechanisms could provide insights for developing drugs to prevent and treat HTN.

Recently Reported Biological Activities and Action Targets of Pt(II)- and Cu(II)-Based Complexes.

Most diseases that affect human beings across the world are now treated with drugs of organic origin. However, some of these are associated with side effects, toxicity, and resistance phenomena. For the treatment of many illnesses, the development of new molecules with pharmacological potential is now an urgent matter. The biological activities of metal complexes have been reported to have antitumor, antimicrobial, anti-inflammatory, anti-infective and antiparasitic effects, amongst others. Metal complexes are effective because they possess unique properties. For example, the complex entity possesses the effective biological activity, then the formation of coordination bonds between the metal ions and ligands is controlled, metal ions provide it with extraordinary mechanisms of action because of characteristics such as d-orbitals, oxidation states, and specific orientations; metal complexes also exhibit good stability and good physicochemical properties such as water solubility. Platinum is a transition metal widely used in the design of drugs with antineoplastic activities; however, platinum is associated with side effects which have made it necessary to search for, and design, novel complexes based on other metals. Copper is a biometal which is found in living systems; it is now used in the design of metal complexes with biological activities that have demonstrated antitumoral, antimicrobial and anti-inflammatory effects, amongst others. In this review, we consider the open horizons of Cu(II)- and Pt(II)-based complexes, new trends in their design, their synthesis, their biological activities and their targets of action.

What over the counter (OTC) products have been evaluated for anxiety in adults aged 18-60? A scoping review.

BACKGROUND: Anxiety symptoms and disorders are common in the UK. Whilst waiting for, or alongside, treatments such as anxiolytics or psychological therapies, people often self-manage anxiety symptoms with products purchased over-the-counter (OTC), such as herbal medicines or dietary supplements. However, the evidence for these products is often presented across different reviews and is not easy for patients or healthcare professionals to compare and understand. AIMS: To determine the nature and size of the evidence base available for these products. METHODS: A scoping review. CENTRAL, MEDLINE, EMBASE, PsycInfo, and AMED (inception-Dec 2022) were searched for RCTs assessing OTC products in people aged 18-60 with symptoms or a diagnosis of anxiety. RESULTS: In total 69 papers assessing a range of products were found, which mostly focussed on kava, lavender, saffron, probiotics, Galphimia glauca and valerian. Studies used varying dosages. Compared to herbal medicine studies, there were much fewer dietary supplement studies and homeopathic remedy studies, despite some of use of these by the general public. CONCLUSION: Future research needs to investigate commonly used but less evaluated products (e.g. chamomile, St John's Wort) and to evaluate products against or alongside conventional treatments to better reflect patient decision making.

Genetic evaluations of dairy goats with few pedigree data: different approaches to use molecular information.

One of the limitations of implementing animal breeding programs in small-scale or extensive production systems is the lack of production records and genealogical records. In this context, molecular markers could help to gain information for the breeding program. This study addresses the inclusion of molecular data into traditional genetic evaluation models as a random effect by molecular pedigree reconstruction and as a fixed effect by Bayesian clustering. The methods were tested for lactation curve traits in 14 dairy goat herds with incomplete phenotypic data and pedigree information. The results showed an increment of 37.3% of the relationships regarding the originals with MOLCOAN and clustering into five genetic groups. Data leads to estimating additive variance, error variance, and heritability with four different models, including pedigree and molecular information. Deviance Information Criterion (DIC) values demonstrate a greater fitting of the models that include molecular information either as fixed (genetic clusters) or as random (molecular matrix) effects. The molecular information of simple markers can complement genetic improvement strategies in populations with little information.

Expanding Diagnostic Workup for hypertensive Intracerebral hemorrhage: a retrospective LATAM cerebrovascular registry comparison.

Background: The leading cause of spontaneous intracerebral hemorrhage (ICH) is hypertensive arteriolopathy. In addition to age and hypertension history, patients usually present other comorbidities that potentially increase morbimortality. Ancillary studies other than non-contrast computerized tomography (NCCT) may help clarify the diagnosis and increase the detection of potentially modifiable vascular risk factors. Unfortunately, their use is not routinely performed. Objective: The study aimed to determine the frequency of ancillary studies performed in patients with hypertensive ICH. Methods: We performed a retrospective analysis of three Latin American cerebrovascular registries from academic medical centers, analyzing the results with descriptive statistics focusing on diagnosis and short-term outcomes. Results: We analyzed a total of 1,324 patients (mean age 64 years). Hypertension and obesity were the most prevalent risk factors. Only 14% underwent MRI, 10.3% extracranial ultrasonography, and 6.7% echocardiography. Among the three registries, the Latin America Stroke Registry performed more ancillary studies. Most of the patients presented a poor clinical outcome and in-hospital death. Conclusions: The use of ancillary studies in the diagnostic workup of ICH was poor in the three registries, and mortality was high. The lack of ancillary studies performed may negatively impact outcomes.

A comparison between petrous bone and tooth, femur and tibia DNA analysis from degraded skeletal remains.

Skeletal remains are the only biological material that remains after long periods; however, environmental conditions such as temperature, humidity, and pH affect DNA preservation, turning skeletal remains into a challenging sample for DNA laboratories. Sample selection is a key factor, and femur and tooth have been traditionally recommended as the best substrate of genetic material. Recently, petrous bone (cochlear area) has been suggested as a better option due to its DNA yield. This research aims to evaluate the efficiency of petrous bone compared to other cranium samples (tooth) and postcranial long bones (femur and tibia). A total amount of 88 samples were selected from 38 different individuals. The samples were extracted by using an organic extraction protocol, DNA quantification by Quantifiler Trio kit and amplified with GlobalFiler kit. Results show that petrous bone outperforms other bone remains in quantification data, yielding 15-30 times more DNA than the others. DNA profile data presented likeness between petrous bone and tooth regarding detected alleles; however, the amount of DNA extracted in petrous bones allowed us to obtain more informative DNA profiles with superior quality. In conclusion, petrous bone or teeth sampling is recommended if DNA typing is going to be performed with environmentally degraded skeletal remains.

Improving Equitability and Inclusion for Testing and Detection of Lead Poisoning in US Children.

Policy Points Child lead poisoning is associated with socioeconomic inequity and perpetuates health inequality. Methods for testing and detection of child lead poisoning are ill suited to the current demographics and characteristics of the problem. A three-pronged revision of current testing approaches is suggested. Employing the suggested revisions can immediately increase our national capacity for equitable, inclusive testing and detection. ABSTRACT: Child lead poisoning, the longest-standing child public health epidemic in US history, is associated with socioeconomic inequity and perpetuates health inequality. Removing lead from children's environments ("primary prevention") is and must remain the definitive solution for ending child lead poisoning. Until that goal can be realized, protecting children's health necessarily depends on the adequacy of our methods for testing and detection. Current methods for testing and detection, however, are no longer suited to the demographics and magnitude of the problem. We discuss the potential deployment and feasibility of a three-pronged revision of current practices including: 1) acceptance of capillary samples for final determination of lead poisoning, with electronic documentation of "clean" collection methods submitted by workers who complete simple Centers for Disease Control and Prevention-endorsed online training and certification for capillary sample collection; 2) new guidance specifying the analysis of capillary samples by inductively coupled plasma mass spectrometry or graphite furnace atomic absorption spectrometry with documented limit of detection ≤0.2 µg/dL; and 3) adaptive "census tract-specific" universal testing and monitoring guidance for children from birth to 10 years of age. These testing modifications can bring child blood lead level (BLL) testing into homes and communities, immediately increasing our national capacity for inclusive and equitable detection and monitoring of dangerous lower-range BLLs in US children.

Emergence of qualitative states in synthetic circuits driven by ultrasensitive growth feedback.

The mutual interactions between the synthetic gene circuits and the host growth could cause unexpected outcomes in the dynamical behaviors of the circuits. However, how the steady states and the stabilities of the gene circuits are affected by host cell growth is not fully understood. Here, we developed a mathematical model for nonlinear growth feedback based on published experimental data. The model analysis predicts that growth feedback could significantly change the qualitative states of the system. Bistability could emerge in a circuit without positive feedback, and high-order multistability (three or more steady states) arises in the self-activation and toggle switch circuits. Our results provide insight into the potential effects of ultrasensitive growth feedback on the emergence of qualitative states in synthetic circuits and the corresponding underlying mechanism.

Synergistic effect of elevated glucose levels with SARS-CoV-2 spike protein induced NOX-dependent ROS production in endothelial cells.

BACKGROUND: Diabetic patients infected with coronavirus disease 2019 (COVID-19) often have a higher probability of organ failure and mortality. The potential cellular mechanisms through which blood glucose exacerbates tissue damage due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. METHODS AND RESULTS: We cultured endothelial cells within differing glucose mediums with an increasing concentration gradient of SARS-CoV-2 Spike protein (S protein). S protein can cause the reduction of ACE2 and TMPRSS2, and activation of NOX2 and NOX4. A high glucose medium was shown to aggravate the decrease of ACE2 and activation of NOX2 and NOX4 in cultured cells, but had no effect on TMPRSS2. S protein mediated activation of the ACE2-NOX axis induced oxidative stress and apoptosis within endothelial cells, leading to cellular dysfunction via the reduction of NO and tight junction proteins which may collectively be exacerbated by elevated glucose. In addition, the glucose variability model demonstrated activation of the ACE2-NOX axis in a similar manner observed in the high glucose model in vitro. CONCLUSIONS: Our present study provides evidence for a mechanism through which hyperglycemia aggravates endothelial cell injury resulting from S protein mediated activation of the ACE2-NOX axis. Our research thus highlights the importance of strict monitoring and control of blood glucose levels within the context of COVID-19 treatment to potentially improve clinical outcomes.