Dyslipidemia and Inflammation as Hallmarks of Oxidative Stress in COVID-19: A Follow-Up Study.

Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969-0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998-0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017-1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433-0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010-1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.

Endothelial Dysfunction and Neutrophil Degranulation as Central Events in Sepsis Physiopathology.

Sepsis is a major health problem worldwide. It is a time-dependent disease, with a high rate of morbidity and mortality. In this sense, an early diagnosis is essential to reduce these rates. The progressive increase of both the incidence and prevalence of sepsis has translated into a significant socioeconomic burden for health systems. Currently, it is the leading cause of noncoronary mortality worldwide and represents one of the most prevalent pathologies both in hospital emergency services and in intensive care units. In this article, we review the role of both endothelial dysfunction and neutrophil dysregulation in the physiopathology of this disease. The lack of a key symptom in sepsis makes it difficult to obtain a quick and accurate diagnosis of this condition. Thus, it is essential to have fast and reliable diagnostic tools. In this sense, the use of biomarkers can be a very important alternative when it comes to achieving these goals. Both new biomarkers and treatments related to endothelial dysfunction and neutrophil dysregulation deserve to be further investigated in order to open new venues for the diagnosis, treatment and prognosis of sepsis.

Cytokine and interleukin profile in patients with headache and COVID-19: A pilot, CASE-control, study on 104 patients.

BACKGROUND: The presence of headache during the acute phase of COVID-19 could be associated with the innate response and the cytokine release. We aim to compare the cytokine and interleukin profile in hospitalized COVID-19 patients at the moment of admission with and without headache during the course of the disease. METHODS: An observational analytic study with a case control design was performed. Hospitalized patients from a tertiary hospital with confirmed COVID-19 disease were included. Patients were classified into the headache or the control group depending on whether they presented headache not better accounted for by another headache disorder other than acute headache attributed to systemic viral infection. Several demographic and clinical variables were studies in both groups. We determined the plasmatic levels of 45 different cytokines and interleukins from the first hospitalization plasma extraction in both groups. RESULTS: One hundred and four patients were included in the study, aged 67.4 (12.8), 43.3% female. Among them, 29 (27.9%) had headache. Patients with headache were younger (61.8 vs. 69.5 years, p = 0.005) and had higher frequency of fever (96.6 vs. 78.7%, p = 0.036) and anosmia (48.3% vs. 22.7%, p = 0.016). In the comparison of the crude median values of cytokines, many cytokines were different between both groups. In the comparison of the central and dispersion parameters between the two groups, GROa, IL-10, IL1RA, IL-21, IL-22 remained statistically significant. After adjusting the values for age, sex, baseline situation and COVID-19 severity, IL-10 remained statistically significant (3.3 vs. 2.2 ng/dL, p = 0.042), with a trend towards significance in IL-23 (11.9 vs. 8.6 ng/dL, p = 0.082) and PIGF1 (1621.8 vs. 110.6 ng/dL, p = 0.071). CONCLUSIONS: The higher levels of IL-10 -an anti-inflammatory cytokine- found in our sample in patients with headache may be explained as a counteract of cytokine release, reflecting a more intense immune response in these patients.

Bisphenol A (BPA) modulates the expression of endocrine and stress response genes in the freshwater snail Physa acuta.

Bisphenol A (BPA), a known endocrine disrupting chemical (EDC) that can mimic the action of oestrogens by interacting with hormone receptors, is potentially able to influence reproductive functions in vertebrates and invertebrates. The freshwater pulmonate Physa acuta is a sensitive organism to xenobiotics appropriate for aquatic toxicity testing in environmental studies. This study was conducted to explore the effects of BPA on the Gastropoda endocrine system. The effects following a range of exposure times (5-96h) to BPA in P. acuta were evaluated at the molecular level by analysing changes in the transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), as well as in genes involved in the stress response, such as hsp70 and hsp90. Real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis showed that BPA induced a significant increase in the mRNA levels of ER, ERR, and RXR, suggesting that these receptors could be involved in similar pathways or regulation events in the endocrine disruptor activity of this chemical at the molecular level in Gastropoda. Additionally, the hsp70 expression was upregulated after 5 and 72h of BPA exposures, but hsp90 was only upregulated after 5h of BPA exposure. Finally, we assessed the glutathione-S-transferase (GST) activity after BPA treatment and found that it was affected after 48h. In conclusion, these data provide, for the first time, evidences of molecular effects produced by BPA in the endocrine system of Gastropoda, supporting the potential of ER, ERR and RXR as biomarkers to analyse putative EDCs in ecotoxicological studies. Moreover, our results suggest that P. acuta is an appropriate sentinel organism to evaluate the effect of EDCs in the freshwater environment.

Endocrine-related genes are altered by antibacterial agent triclosan in Chironomus riparius aquatic larvae.

Triclosan (TCS) is an antibacterial agent widely used in personal care and consumer products and commonly detected in aquatic ecosystems. In the present study, the effects of TCS on endocrine-related genes of Chironomus riparius aquatic larvae, a reference organism in aquatic toxicology, were evaluated. Twenty-four-hour in vivo exposures at 10µg/L, 100µg/L, and 1000µg/L TCS revealed that this xenobiotic was able to alter the transcriptional activity of ecdysone receptor gene (EcR), the ultraspiracle gene (usp), the estrogen-related receptor gene (ERR), and the E74 early ecdysone-inducible gene, as measured by real-time RT-PCR. Moreover, the hsp70 gene, a heat shock protein gene, was upregulated after exposure to TCS. The results of the present work provide the first evidence of the potential disruptive effects of TCS in endocrine-related genes suggesting a mode of action that mimics ecdysteroid hormones in insects.

Measuring conflicts in the management of anthropized ecosystems: Evidence from a choice experiment in a human-created Mediterranean wetland.

Economic valuation of ecosystem services provides valuable information for the management of anthropized environments, where individual preferences can be heterogeneous and even opposed. Here, we discuss how these ecosystem services were approached in the literature and we address the main issues in relation to their economic valuation. We consider that avoiding misspecifications in economic valuation surveys requires considering the linkages between anthropized ecosystems and human intervention. To illustrate, we analyse the case study of a human-created Mediterranean wetland (El Hondo, SE Spain) using a Choice Experiment. Our findings suggest that management strategies in El Hondo should be oriented to improve the water ecological status, to enhance biodiversity and to develop ecotourism, whereas hunting should be strictly limited and controlled. Our measures of conflict (trade-off between ecosystem services and willingness to pay values) can help to find the optimal allocation of public and private goods and services and for the implementation of compensation schemes in the area. According to public preferences, a conservationist management strategy would generate 331,100 €/year in terms of environmental benefits, whereas a tourism-based management strategy would benefit society with 805,200 €/year.

LPS-Induced Macrophage Activation and Plasma Membrane Fluidity Changes are Inhibited Under Oxidative Stress.

Macrophage activation is essential for a correct and efficient response of innate immunity. During oxidative stress membrane receptors and/or membrane lipid dynamics can be altered, leading to dysfunctional cell responses. Our aim is to analyze membrane fluidity modifications and cell function under oxidative stress in LPS-activated macrophages. Membrane fluidity of individual living THP-1 macrophages was evaluated by the technique two-photon microscopy. LPS-activated macrophage function was determined by TNFα secretion. It was shown that LPS activation causes fluidification of macrophage plasma membrane and production of TNFα. However, oxidative stress induces rigidification of macrophage plasma membrane and inhibition of cell activation, which is evidenced by a decrease of TNFα secretion. Thus, under oxidative conditions macrophage proinflammatory response might develop in an inefficient manner.

Percutaneous Closure of Massive Mitral Paravalvular Leak.

A 59-year-old male with a history of mitral valve replacement several years previously was admitted to the authors' institution with symptoms of advanced heart failure. Echocardiography showed a severe paravalvular dehiscence and surgery was discouraged due to high perioperative risk. A first transcatheter leak closure was unsuccessful despite the correct deployment of various occluding devices. A second percutaneous attempt was carried out with implantation of three Amplatzer Vascular Plug® III devices (five occluders were positioned in total within the oblong defect), leading to a mild residual leakage. Device embolism occurred twice during the procedure but was resolved using adequate catheter retrieval techniques.

Oxidative stress effect on progesterone-induced blocking factor (PIBF) binding to PIBF-receptor in lymphocytes.

Receptor-ligand binding is an essential interaction for biological function. Oxidative stress can modify receptors and/or membrane lipid dynamics, thus altering cell physiological functions. The aim of this study is to analyze how oxidative stress may alter receptor-ligand binding and lipid domain distribution in the case of progesterone-induced blocking factor/progesterone-induced blocking factor-receptor. For membrane fluidity regionalization analysis of MEC-1 lymphocytes, two-photon microscopy was used in individual living cells. Lymphocytes were also double stained with AlexaFluor647/progesterone-induced blocking factor and Laurdan to evaluate -induced blocking factor/progesterone-induced blocking factor-receptor distribution in the different membrane domains, under oxidative stress. A new procedure has been developed which quantitatively analyzes the regionalization of a membrane receptor among the lipid domains of different fluidity in the plasma membrane. We have been able to establish a new tool which detects and evaluates lipid raft clustering from two-photon microscopy images of individual living cells. We show that binding of progesterone-induced blocking factor to progesterone-induced blocking factor-receptor causes a rigidification of plasma membrane which is related to an increase of lipid raft clustering. However, this clustering is inhibited under oxidative stress conditions. In conclusion, oxidative stress decreases membrane fluidity, impairs receptor-ligand binding and reduces lipid raft clustering.

Effect of oxidative stress on plasma membrane fluidity of THP-1 induced macrophages.

Plasma membrane is one of the preferential targets of reactive oxygen species which cause lipid peroxidation. This process modifies membrane properties such as membrane fluidity, a very important physical feature known to modulate membrane protein localization and function. The aim of this study is to evaluate the effect of oxidative stress on plasma membrane fluidity regionalization of single living THP-1 macrophages. These cells were oxidized with H(2)O(2) at different concentrations, and plasma membrane fluidity was analyzed by two-photon microscopy in combination with the environment-sensitive probe Laurdan. Results show a significant H(2)O(2) concentration dependent increase in the frequency of rigid lipid regions, mainly attributable to lipid rafts, at the expense of the intermediate fluidity regions. A novel statistical analysis evaluated changes in size and number of lipid raft domains under oxidative stress conditions, as lipid rafts are platforms aiding cell signaling and are thought to have relevant roles in macrophage functions. It is shown that H(2)O(2) causes an increase in the number, but not the size, of raft domains. As macrophages are highly resistant to H(2)O(2), these new raft domains might be involved in cell survival pathways.

Folate and Vitamin B12 Levels in Chilean Women with PCOS and Their Association with Metabolic Outcomes.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet and deficiencies in essential nutrients. This study aimed to assess the levels of folate and vitamin B12 (B12) and their relationship with metabolic factors in women with PCOS. Anthropometric, clinical, and genetic analyses were conducted to evaluate markers related to one-carbon metabolism in women with PCOS and in a control group. The PCOS group had a higher BMI and HOMA-IR (1.7 vs. 3.1; p < 0.0001). HDL cholesterol levels were 23% lower and triglyceride levels were 74% higher in women with PCOS. Although there were no significant differences in folate and B12 levels between the PCOS and control groups, over 60% of women with PCOS had low B12 levels (<300 pg/mL) and high homocysteine levels. In addition, the MTHFR A1298C and C677T polymorphisms were not associated with PCOS. Moreover, erythrocyte folate levels were positively correlated with fasting glucose, triglycerides, and free androgen index, and negatively correlated with SHBG and LH levels. These results suggest that B vitamins may be associated with the metabolic phenotype in PCOS. This study emphasizes the potential link between folate, vitamin B12, and metabolic and hormonal outcomes in women with PCOS.

Toward the autonomous flushing of building plumbing: Characterizing oxidation-reduction potential and temperature sensor dynamics.

Manual flushing of building plumbing is commonly used to address water quality issues that arise from water stagnation. Autonomous flushing informed by sensors has the potential to aid in the management of building plumbing, but a number of knowledge gaps hinder its application. This study evaluates autonomous flushing of building plumbing with online sensor and actuator nodes deployed under kitchen sinks in five residential houses. Online oxidation-reduction potential (ORP) and temperature data were collected for nine weeks during the winter and summer in houses with both free chlorine and chloramine. ORP levels in houses with free chlorine residuals decreased after overnight stagnation. The overnight decrease in ORP was not observed when tap water was automatically flushed for five minutes at 6:00 h every morning. ORP levels in houses with chloramine residuals did not decrease consistently after overnight stagnation, and daily automated flushes did not have an observable effect on the ORP signals. Additional laboratory experiments were carried out to evaluate ORP signals during chlorine decay and after incremental changes in chlorine, as would be expected in building plumbing conditions. Results from the lab and field deployments suggest on-line ORP sensors may be used to detect free chlorine decay due to stagnating water, but are not as effective in detecting chloramine decay. However, field results also suggest ORP may not respond as expected on a timely manner after free chlorine or chloramine have been restored, hindering their applicability in developing control algorithms. In this paper we tested twice-daily five-minute automatic flushing and found that it counteracts water quality degradation associated with overnight stagnation in free chlorine systems. An automatic sensor-based flushing is proposed using online temperature sensor data to determine when flushing has reached water from the main. The results suggest that flushing informed by temperature sensors can reduce the flushing time by 46 % compared to the preset five-minute static flush.

Asymptomatic bacteriuria in critical-access hospitals: Prevalence and patient characteristics driving treatment.

We evaluated the prevalence and treatment of asymptomatic bacteriuria (ASB) in 17 critical-access hospitals. Among 891 patients with urine cultures from September 2021 to June 2022, 170 (35%) had ASB. Also, 76% of patients with ASB received antibiotics for a median duration of 7 days, demonstrating opportunities for antimicrobial stewardship.

Cost benefit analysis of diversified farming systems across Europe: Incorporating non-market benefits of ecosystem services.

Crop diversification can enhance farm economic sustainability while reducing the negative impact on the environment and ecosystem services related. Despite the market and non-market benefits of crop diversification, monocropping is a widely used dominant practice in Europe. In this context, this works aims to assess the overall economic impact of several crop diversification systems across Europe and compared it to the monocropping system. For this purpose, an economic valuation by integrating market and non-market values for eight case studies distributed across three different European pedoclimatic regions (Southern Mediterranean, Northern Mediterranean and Boreal) is proposed. The economic valuation was conducted both in the short and medium-long term. For the short-term we conducted a social gross margin analysis, while for the medium-long term a cost-benefit analysis is developed. The results show an improvement in social gross margins for most of the diversification scenarios assessed when environmental and socio-cultural benefits are considered in the short-term. In the medium and long-term the transformation of cropping towards a more diversified agriculture is encouraged by greater economic benefits. These results provide a first insight in global economic performance of diversified cropping systems, whose main contribution relies on the integration of market and non-market values of ecosystem services from crop diversification. They are expected to be useful for guiding policy makers to promote crop diversification practices as a key instrument for building resilience in farming systems for an adaptive management to climate change.

Investigating the suitability of online flow cytometry for monitoring full-scale drinking water ozone system disinfection effectiveness.

While online monitoring of physicochemical parameters has widely been incorporated into drinking water treatment systems, online microbial monitoring has lagged behind, resulting in the use of surrogate parameters (disinfectant residual, applied dose, concentration × time, CT) to assess disinfection system performance. Online flow cytometry (online FCM) allows for automated quantification of total and intact microbial cells. This study sought to investigate the feasibility of online FCM for full-scale drinking water ozone disinfection system performance monitoring. A water treatment plant with high lime solids turbidity in the ozone contactor influent was selected to evaluate the online FCM in challenging conditions. Total and intact cell counts were monitored for 40 days and compared to surrogate parameters (ozone residual, ozone dose, and CT) and grab sample assay results for cellular adenosine triphosphate (cATP), heterotrophic plate counts (HPC), impedance flow cytometry, and 16S rRNA gene sequencing. Online FCM provided insight into the dynamics of the full-scale ozone system, including offering early warning of increased contactor effluent cell concentrations, which was not observed using surrogate measures. Positive correlations were observed between online FCM intact cell counts and cATP levels (Kendall's tau=0.40), HPC (Kendall's tau=0.20), and impedance flow cytometry results (Kendall's tau=0.30). Though a strong correlation between log intact cell removal and CT was not observed, 16S rRNA gene sequencing results showed that passage through the ozone contactor significantly changed the microbial community (p < 0.05). Potential causes of the low overall cell inactivation in the contactor and the significant changes in the microbial community after ozonation include regrowth in the later chambers of the contactor and varied ozone resistance of drinking water microorganisms. This study demonstrates the suitability of direct, online microbial analysis for monitoring full-scale disinfection systems.

QuantiFERON-TB reversion in children and adolescents with tuberculosis.

We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with significant decreases in TB1 (-1.72 vs. -0.03 IU/ml, p=0.001) and TB2 (-1.65 vs. -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0% vs 11.9%, p=0.042), and those with TST induration <15mm (29% vs 13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.

Genotoxic effects of environmental endocrine disruptors on the aquatic insect Chironomus riparius evaluated using the comet assay.

Genotoxicity is one of the most important toxic endpoints in chemical toxicity testing and environmental risk assessment. The aim of this study was to evaluate the genotoxic potential of various environmental pollutants frequently found in aquatic environments and characterized by their endocrine disrupting activity. Monitoring of DNA damage was undertaken after in vivo exposures of the aquatic larvae of the midge Chironomus riparius, a model organism that represents an abundant and ecologically relevant macroinvertebrate, widely used in freshwater toxicology. DNA-induced damage, resulting in DNA fragmentation, was quantified by the comet assay after short (24 h) and long (96 h) exposures to different concentrations of the selected toxicants: bisphenol A (BPA), nonylphenol (NP), pentachlorophenol (PCP), tributyltin (TBT) and triclosan (TCS). All five compounds were found to have genotoxic activity as demonstrated by significant increases in all the comet parameters (%DNA in tail, tail length, tail moment and Olive tail moment) at all tested concentrations. Persistent exposure did not increase the extent of DNA damage, except for TCS at the highest concentration, but generally there was a reduction in DNA damage thought to be associated with the induction of the detoxification processes and repairing mechanisms. Comparative analysis showed differences in the genotoxic potential between the chemicals, as well as significant time and concentration-dependent variations, which most likely reflect differences in the ability to repair DNA damage under the different treatments. The present report demonstrates the sensitivity of the benthic larvae of C. riparius to these environmental genotoxins suggesting its potential as biomonitor organism in freshwater ecosystems. The results obtained about the DNA-damaging potential of these environmental pollutants reinforce the need for additional studies on the genotoxicity of endocrine active substances that, by linking genotoxic activity to other biological responses, could provide further understanding of adverse effects in aquatic environments.

Adenomatoid odontogenic tumor associated to reactive fibro-osseous lesion: A case report.

An adenomatoid odontogenic tumor (AOT) is a benign epithelial lesion, being the fourth most common among all odontogenic tumors. Usually presents as slow painless growth that sometimes leads to facial asymmetry. Many cases are detected by radiographic studies, and the indication for biopsy and surgery is secondary to this finding. We report a case of a 17-year-old man with a history of left mandibular painless swelling since 4 months ago, associated with facial asymmetry and hard consistency. An imaging study showed an extensive unilocular radiolucent lesion to the basilar arch, with defined limits and with peripheral hyperdense areas located only vestibular to the lesion. The histopathology was composed of odontogenic epithelial cell proliferation, with epithelial nodular and duct-like structures, rosettes of spindled epithelial cells with eosinophilic material, calcifications, and fibro-osseous reaction. Surgical conservative excision including the affected tooth is the treatment of choice and recurrence is rare. The histologic findings of reactive fibro-osseous proliferation in AOT should be interpreted as a reactive change in the tumor capsule and not as an adnexal lesion. We present an atypical case of AOT with reactive fibro-osseous reaction. Despite clinical aggressive behavior, conservative surgical treatment could be the treatment of choice. Additionally, we emphasize the importance of histopathological examination together with the imaging study of radiolucent lesions of the maxillary bones. Key words:Adenomatoid Odontogenic Tumor, Odontogenic tumor, fibro-osseous lesion.

Effectiveness and Safety of Cannabinoids as an Add-On Therapy in the Treatment of Resistant Spasticity in Multiple Sclerosis: A Systematic Review.

Background: Spasticity continues to be a very prevalent, highly invalidating, and difficult-to-manage symptom in patients with multiple sclerosis (MS). The aim of this systematic review is to evaluate the effectiveness of the use of cannabis and cannabinoids in these patients, evaluating its use as an additional therapy. Methods: We performed a systematic review of the literature searching in the major scientific databases (PubMed, Scopus, EMBASE, WOS, and Cochrane Library) for articles from January 2017 to May 2022 containing information about the effectiveness of cannabis and cannabinoids in patients with insufficient response to first-line oral antispastic treatment. Results: A total of five medium high-quality articles were selected to be part of the study and all evaluated the effectiveness of the tetrahydrocannabinol (THC) and cannabidiol (CBD) spray. The effectiveness of this drug and the significant improvements are produced on the patient-related spasticity assessment scales, obtaining improvement up to 45%; and on quality of life, producing a decrease in the appearance of symptoms related to spasticity, as well as an increase in the development of basic activities of daily living. The average dose is 5-7 sprays/day. The discontinuation rate for these treatments is around 40% due to lack of effectiveness and adverse events. All reported adverse effects are mild to moderate in severity and their incidence is ∼17%, although this figure tends to decrease with drug use. Conclusions: Adding the THC:CBD sprays have been shown to be more effective in treating MS spasticity than optimizing the dose of first-line antispastic drugs in selected responders patients. The safety and tolerability profiles remain in line with those obtained in other trials. More patients would benefit from treatment if the initial response search period was extended.

Prevalence and treatment of asymptomatic bacteriuria at academic and critical-access hospitals-Opportunities for stewardship efforts.

Asymptomatic bacteriuria (ASB) is common among hospitalized patients and often leads to inappropriate antimicrobial use. Data from critical-access hospitals are underrepresented. To target antimicrobial stewardship efforts, we measured the point prevalence of ASB and detected a high frequency of ASB overtreatment across academic, community, and critical-access hospitals.