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It is believed that fetal hemoglobin (HbF) expression in adults is largely genetically regulated. The increased expression of HbF in pregnancy has been reported in a small number of articles. Different mechanisms have been proposed, but the description of HbF expression during pregnancy remains unclear. The objectives of this study were to document HbF expression during peri and postpartum periods, confirm its maternal origin, and assess clinical and biochemical parameters potentially associated with HbF modulation. In this observational prospective study, 345 pregnant women were followed. At baseline, 169 had HbF expression (≥1% of total hemoglobin) and 176 did not have HbF expression. Women were followed at the obstetric clinic during their pregnancy. Clinical and biochemical parameters were measured at each visit. Analyses were made to determine which parameters had a significant correlation to HbF expression. Results show that HbF expression of ≥1% during peri and postpartum periods in pregnant women without influencing comorbidities is at its highest peak during the first trimester. In all women, it was proven that HbF was of maternal origin. A significant positive correlation between HbF expression, βeta-human chorionic gonadotropin (β-HCG), and glycosylated hemoglobin (HbA1c) was present. A significant negative association between HbF expression and total hemoglobin was found. HbF expression induction during pregnancy is probably associated with an increase in β-HCG and HbA1C, and a decrease in total hemoglobin, which could temporarily reactivate the fetal erythropoietic system.

Inflammatory abdominal aortic aneurysms (iAAA) are a form of noninfectious aortitis in patients with abdominal aortic aneurysms (AAA). Ultrasound could help to detect iAAA early. This retrospective observational study assessed the potential of using ultrasound to detect iAAA in a case series of iAAA patients, and the diagnostic value of ultrasound to detect iAAA in consecutive patients in a follow-up for AAA, referred to as a feasibility study. In both studies, diagnosis of iAAA was based on a cuff surrounding the aneurysm using CT (golden standard). The case series included 13 patients (age 64 (61; 72) years; 100% male). The feasibility study included 157 patients (age 75 (67; 80) years; 84% male). In the case series, all iAAA patients showed a cuff surrounding the aortic wall on ultrasound. In the feasibility study with AAA patients, ultrasound yielded no cuff in 147 (93.6%; CT negative in all cases), a typic cuff in 8 (5.1%; CT positive in all cases), and an inconclusive cuff in 2 (1.3%; CT negative in both cases) patients. Sensitivity and specificity were 100% and 98.7%, respectively. This study indicates that iAAA can be identified with ultrasound, and safely ruled out. In positive ultrasound cases, additional CT imaging might still be warranted.

Surgical ciliated cysts occur primarily in the maxilla after radical maxillary sinus surgery. We report the first case of a surgical ciliated cyst that developed in the infratemporal fossa 25 years after the patient sustained severe facial trauma. The patient complained of mandibular pain and limited mouth opening. The patient’s condition was completely resolved 5 months after marsupialization via Le Fort I osteotomy. Surgical morbidities can be minimized by proper diagnosis and less invasive surgery.

Improvements in the treatment of childhood cancer have considerably enhanced survival rates over the last decades, to over 80% as per today. However, this great achievement has been accompanied by the occurrence of several early and long-term treatment-related complications major of which is the cardiotoxicity. The chemotherapeutic agents that have been implicated as a cause of cardiotoxicity, are mostly anthracyclines and mitoxantrone, alkylating agents, proteasome inhibitors and to a lesser extent anti-microtubule agents, cisplatin, monoclonal antibodies, small molecular tyrosine kinase inhibitors, and nucleotide synthesis inhibitors. Routine diagnosis and monitoring of cardiotoxicity rely on electrocardiography and echocardiography. For the early detection of cardiotoxicity, in recent years, major studies have been conducted using biomarkers such as troponin, N-terminal pro b-natriuretic peptide, etc. Despite refinements in diagnostics still severe limitations exist, due to the increase of the above-mentioned biomarkers, only after significant cardiac damage has occurred. Lately, research has been expanded by introducing new technologies and finding new markers by omics approach. These new markers could be used not only for early detection, but also for early prevention of cardiotoxicity. The omics science, which includes genomics, transcriptomics, proteomics, and metabolomics, offers new opportunities for biomarker discovery in cardiotoxicity and may provide understanding of mechanisms of cardiotoxicity, beyond traditional technologies. This article reviews the contemporary definition of cardiotoxicity, older and newer chemotherapeutic agents mainly involved in cardiotoxicity and the methods of early and preventive diagnosis, using omics technology.

Raynaud’s Phenomenon (RP) leading to repetitive ischemia and reperfusion (IR) stress, is the first recognizable sign of systemic sclerosis (SSc) leading to increased oxidative stress. High-mobility group box-1 (HMGB1) is a nuclear factor released by apoptotic and necrotic cells after oxidative stress. Since HMGB1 can signal through the receptor for advanced glycation end products (RAGE), we investigated whether an RP attack promotes the release of HMGB1, leading to fibroblast activation and the upregulation of interferon (IFN)-inducible genes. A cold challenge was performed to simulate an RP attack in patients with SSc, primary RP (PRP), and healthy controls. We measured levels of HMGB1 and IFN gamma-induced Protein 10 (IP-10) at different time points in the serum. Digital perfusion was assessed by photoplethysmography. In vitro, HMGB1 or transforming growth factor (TGF-β1) (as control) was used to stimulate healthy human dermal fibroblasts. Inflammatory, profibrotic, and IFN-inducible genes, were measured by RT-qPCR. In an independent cohort, sera were obtained from 20 patients with SSc and 20 age- and sex-matched healthy controls to determine HMGB1 and IP-10 levels. We found that HMGB1 levels increased significantly 30 min after the cold challenge in SSc compared to healthy controls. In vitro stimulation with HMGB1 resulted in increased mRNA expression of IP-10, and interleukin-6 (IL-6) while TGF-β1 stimulation promoted IL-6 and Connective Tissue Growth Factor (CTGF). In serum, both HMGB1 and IP-10 levels were significantly higher in patients with SSc compared to healthy controls. We show that cold challenge leads to the release of HMGB1 in SSc patients. HMGB1 induces IP-10 expression in dermal fibroblasts partly through the soluble RAGE (sRAGE) axis suggesting a link between RP attacks, the release of HMGB1 and IFN-induced proteins as a putative early pathogenetic mechanism in SSc.

Hepatocellular carcinoma is the most common primary malignant hepatic tumor and occurs most often in the setting of chronic liver disease. Liver transplantation is a curative treatment option and is an ideal solution because it solves the chronic underlying liver disorder while removing the malignant lesion. However, due to organ shortages, this treatment can only be applied to carefully selected patients according to clinical guidelines. Artificial intelligence is an emerging technology with multiple applications in medicine with a predilection for domains that work with medical imaging, like radiology. With the help of these technologies, laborious tasks can be automated, and new lesion imaging criteria can be developed based on pixel-level analysis. Our objectives are to review the developing AI applications that could be implemented to better stratify liver transplant candidates. The papers analysed applied AI for liver segmentation, evaluation of steatosis, sarcopenia assessment, lesion detection, segmentation, and characterization. A liver transplant is an optimal treatment for patients with hepatocellular carcinoma in the setting of chronic liver disease. Furthermore, AI could provide solutions for improving the management of liver transplant candidates to improve survival.

Oxidative stress plays a pivotal role in cardiovascular (CV) disease, but current biomarkers used to predict CV events are still insufficient. In this study, we comparatively assessed the utility of redox-related biomarkers in predicting the risk of CV events and all-cause mortality in male and female subjects from the general population. Subjects (n = 5955) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) population-based cohort study were included. Blood homocysteine, gamma-GT, HDL cholesterol, bilirubin and protein-adjusted free thiol (R-SH, sulfhydryl groups) levels were quantified at baseline and were prospectively analyzed in association with the risk of CV events and all-cause mortality. After adjustment for potentially confounding factors, protein-adjusted R-SH and homocysteine levels were significantly associated with the risk of CV events in men (HR 0.63 [0.40–0.99], p = 0.045 and HR 1.58 [1.20–2.08], p = 0.001, respectively). Protein-adjusted R-SH and HDL cholesterol levels were significantly associated with the risk of all-cause mortality in men (HR 0.52 [0.32–0.85], p = 0.009 and HR 0.90 [0.85–0.94], p < 0.001, respectively), while the same was observed for bilirubin and homocysteine levels in women (HR 0.68 [0.48–0.98], p = 0.040 and HR 2.30 [1.14–3.76], p < 0.001, respectively). Lower levels of protein-adjusted R-SH were robustly associated with an increased risk of CV events and all-cause mortality in men. Our results highlight the value of R-SH levels in cardiovascular risk assessment and their potential significance as being amenable to therapeutic intervention, while reaffirming the importance of other oxidative stress-related biomarkers, such as homocysteine, HDL cholesterol and bilirubin.

Recurrent pregnancy loss is a distressing condition affecting 1–2% of couples. Traditionally investigations have focused on the female, however more recently researchers have started to explore the potential contribution of the male partner. Seminal reactive oxygen species have a physiological function in male reproduction but in excess are suspected to generate structural and functional damage to the sperm. Evidence is mounting to support an association between elevated seminal reaction oxygen species and recurrent pregnancy loss. Studies suggest that the rates of sperm DNA damage are higher in the male partners of women affected by recurrent pregnancy loss compared with unaffected men. However, the available pool of data is conflicting, and interpretation is limited by the recent change in nomenclature and the heterogeneity of study methodologies. Furthermore, investigation into the effects of oxidative stress on the epigenome show promise. The value of antioxidant therapy in the management of recurrent pregnancy loss currently remains unclear.

One of the richest tissues in lipid content and diversity of the human body is the brain. The human brain is constitutively highly vulnerable to oxidative stress. This oxidative stress is a determinant in brain aging, as well as in the onset and progression of sporadic (late-onset) Alzheimer’s disease (sAD). Glycerophospholipids are the main lipid category widely distributed in neural cell membranes, with a very significant presence for the ether lipid subclass. Ether lipids have played a key role in the evolution of the human brain compositional specificity and functionality. Ether lipids determine the neural membrane structural and functional properties, membrane trafficking, cell signaling and antioxidant defense mechanisms. Here, we explore the idea that ether lipids actively participate in the pathogenesis of sAD. Firstly, we evaluate the quantitative relevance of ether lipids in the human brain composition, as well as their role in the human brain evolution. Then, we analyze the implications of ether lipids in neural cell physiology, highlighting their inherent antioxidant properties. Finally, we discuss changes in ether lipid content associated with sAD and their physiopathological implications, and propose a mechanism that, as a vicious cycle, explains the potential significance of ether lipids in sAD.

Peer reviewed: True, Plasma membrane mimetics can potentially play a vital role in drug discovery and immunotherapy owing to the versatility to assemble facilely cellular membranes on surfaces and/or nanoparticles, allowing for direct assessment of drug/membrane interactions. Recently, bacterial membranes (BMs) have found widespread applications in biomedical research as antibiotic resistance is on the rise, and bacteria-associated infections have become one of the major causes of death worldwide. Over the last decade, BM research has greatly benefited from parallel advancements in nanotechnology and bioelectronics, resulting in multifaceted systems for a variety of sensing and drug discovery applications. As such, BMs coated on electroactive surfaces are a particularly promising label-free platform to investigate interfacial phenomena, as well as interactions with drugs at the first point of contact: the bacterial membrane. Another common approach suggests the use of lipid-coated nanoparticles as a drug carrier system for therapies for infectious diseases and cancer. Herein, we discuss emerging platforms that make use of BMs for biosensing, bioimaging, drug delivery/discovery, and immunotherapy, focusing on bacterial infections and cancer. Further, we detail the synthesis and characteristics of BMs, followed by various models for utilizing them in biomedical applications. The key research areas required to augment the characteristics of bacterial membranes to facilitate wider applicability are also touched upon. Overall, this review provides an interdisciplinary approach to exploit the potential of BMs and current emerging technologies to generate novel solutions to unmet clinical needs.

Pregnancy-associated breast cancer (PABC) is commonly defined as a breast cancer occurring during pregnancy, throughout 1 year postpartum, or during lactation. Despite being a rare circumstance, PABC is one of the most common types of malignancies occurring during pregnancy and lactation, with growing incidence in developed countries, due both to decreasing age at onset of breast cancer and to increasing maternal age. Diagnosis and management of malignancy in the prenatal and postnatal settings are challenging for practitioners, as the structural and functional changes that the breast undergoes may be misleading for both the radiologist and the clinician. Furthermore, safety concerns for the mother and child, as well as psychological aspects in this unique and delicate condition, need to be constantly considered. In this comprehensive review, clinical, diagnostic, and therapeutic aspects of PABC (including surgery, chemotherapy and other systemic treatments, and radiotherapy) are presented and fully discussed, based on medical literature, current international clinical guidelines, and systematic practice.

Parkinson’s disease is the second most common neurodegenerative disorder, affecting 2–3% of the population of patients >65 years. Although the standard diagnosis of PD is clinical, neuroimaging plays a key role in the evaluation of patients who present symptoms related to neurodegenerative disorders. MRI, DAT-SPECT, and PET with [18F]-FDG are routinely used in the diagnosis and focus on the investigation of morphological changes, nigrostriatal degeneration or shifts in glucose metabolism in patients with parkinsonian syndromes. The aim of this study is to review the current PET radiotracers targeting TSPO, a transmembrane protein that is overexpressed by microglia in another pathophysiological process associated with neurodegenerative disorders known as neuroinflammation. To the best of our knowledge, neuroinflammation is present not only in PD but in many other neurodegenerative disorders, including AD, DLB, and MSA, as well as atypical parkinsonian syndromes. Therefore, in this study, specific patterns of microglial activation in PD and the differences in distribution volumes of these radiotracers in patients with PD as compared to other neurodegenerative disorders are reviewed.

Laryngeal adenoid cystic carcinoma (LACC) is a sporadic neoplasm, especially if supraglottic. The COVID-19 pandemic worsened the presenting stage of many cancers and impacted their prognosis negatively. Here, a case of a patient with adenoid cystic carcinoma (ACC) with delayed diagnosis and a rapid deterioration with distant metastasis due to the COVID-19 pandemic is illustrated. Next, we present a literature review of this rare glottic ACC. The COVID-19 pandemic worsened the stage of presentation of many cancers and adversely affected their prognosis. The present case had a rapidly lethal course, undoubtedly due to the diagnosis delay caused by the COVID-19 pandemic, which impacted the prognosis of this rare glottic ACC. Strict follow-up is recommended for any suspicious clinical findings, as an early diagnosis will improve the disease prognosis, and to consider the influence of the COVID-19 pandemic, especially on the timing of common diagnostic and therapeutic procedures for oncological diseases. In the post-COVID-19 era, it is important to generate new diagnostic scenarios to achieve an increasingly rapid diagnosis of oncological diseases, especially the rare ones, through screening or similar procedures.

Extracellular vesicles are a diverse group of particles that include exosomes, microvesicles, and apoptotic bodies and are defined by size, composition, site of origin, and density. They incorporate various bioactive molecules from their cell of origin during formation, such as soluble proteins, membrane receptors, nucleic acids (mRNAs and miRNAs), and lipids, which can then be transferred to target cells. Extracellular vesicles/exosomes have been extensively studied as a critical factor in pathophysiological processes of human diseases. Urinary extracellular vesicles could be a promising liquid biopsy for determining the pattern and/or severity of kidney histologic injury. The signature of urinary extracellular vesicles may pave the way for noninvasive methods to supplement existing testing methods for diagnosing kidney diseases. We discuss the potential role of urinary extracellular vesicles in various chronic kidney diseases in this review, highlighting open questions and discussing the potential for future research.

The aim of this study was to compare the effect of using depth of invasion (DOI) versus tumor thickness (TT) as a prognostic factor for early-stage oral squamous cell carcinoma (OSCC). A total of 57 patients with early-stage OSCC treated surgically from 2009 to 2014 at our institution were reviewed retrospectively. Histopathological measurement of DOI and TT was performed. The validation of DOI and TT as prognostic factors was conducted using a Kaplan–Meier survival analysis. TT had no association with disease-specific survival (DSS) or progression-free survival (PFS) in this cohort; however, increased DOI was significantly associated with decreased DSS but not correlated to decreased PFS. The T category of the 7th edition of AJCC was statistically associated with both DSS and PFS; however, the T category of the 8th edition of the AJCC was only associated with DSS. In this study group, TT could not be used as a prognostic factor, and DOI was not by itself sufficient to predict prognosis for early-stage OSCC. The T category in AJCC 8th Edition cannot be considered the sole prognostic factor for early OSCC, so additional prognostic factors may need to be considered.

Community-acquired pneumonia caused by Mycoplasma pneumoniae or Chlamydia pneumoniae is usually mild. Mycoplasma pneumoniae-related and C. pneumoniae-related acute respiratory distress syndromes (ARDSs) are rare. Moreover, to our knowledge, there are no published reports on ARDS caused by M. pneumoniae and C. pneumoniae coinfection. Here, we report a case of an immunocompetent young woman who was co-infected with M. pneumoniae and C. pneumoniae and was started on treatment with piperacillin and clarithromycin. Two days later, she developed ARDS. She recovered rapidly following a change of antibiotic treatment to levofloxacin and was discharged on day 12. We conducted exome sequencing followed by alternative filtering to search for candidate ARDS-related genes. We identified an intronic variant of unknown significance within leucine-rich repeat-containing 16A (LRRC16A), a gene previously identified as a significant locus for platelet count with a possible role in ARDS. This is a rare case of ARDS in a young adult caused by M. pneumoniae and C. pneumoniae coinfection. This case suggests that ARDS in young adults may be correlated with variants in LRRC16A. This requires confirmation by further case reports.

Misaligned teeth have a tremendous impact on oral and dental health, and the most efficient method of correcting the problem is orthodontic treatment with orthodontic appliances. The study was conducted to investigate the metal composition of selected orthodontic alloys, the release of metal ions, and the oxidative consequences that the metal ions may cause in the cell. Different sets of archwires, stainless steel brackets, and molar bands were incubated in artificial saliva for 90 days. The composition of each orthodontic material and quantification of the concentration of metal ions released were evaluated. Metal ion mixtures were prepared to determine the occurrence of oxidative stress, antioxidant enzyme defense system, and oxidative damage to proteins. The beta titanium alloy released the fewest metal ions and did not cause oxidative stress or protein damage. The metal ions from stainless steel and the cobalt-chromium alloy can cause oxidative stress and protein damage only at high concentrations. All metal ions from orthodontic alloys alter the activity of antioxidant enzymes in some way. The determined amounts of metal ions released from orthodontic appliances in a simulated oral environment are still below the maximum tolerated dose, and the concentrations of released metal ions are not capable of inducing oxidative stress, although some changes in antioxidant enzyme activity were observed at these concentrations.

Infectious diarrhea is a global pediatric health concern; therefore, rapid and accurate detection of enteropathogens is vital. We evaluated the BioFire® FilmArray® Gastrointestinal (GI) Panel with that of comparator laboratory tests. Stool samples of pediatric patients with diarrhea were prospectively collected and tested. As a comparator method for bacteria, culture, conventional PCR for diarrheagenic E. coli, and Allplex GI-Bacteria(I) Assay were tested. For discrepancy analysis, BD MAX Enteric Bacterial Panel was used. As a comparator method for virus, BD MAX Enteric Virus Panel and immunochromatography was used and Allplex GI-Virus Assay was used for discrepancy analysis. The “true positive” was defined as culture-positive and/or positive results from more than two molecular tests. Of the 184 stool samples tested, 93 (50.5%) were true positive for 128 pathogens, and 31 (16.9%) were positive for multiple pathogens. The BioFire GI Panel detected 123 pathogens in 90 of samples. The BioFire GI Panel demonstrated a sensitivity of 100% for 12 targets and a specificity of >95% for 16 targets. The overall positive rate and multiple pathogen rate among patients in the group without underlying diseases were significantly higher than those in the group with hematologic disease (57.0% vs. 28.6% (p = 0.001) and 20.4% vs. 4.8% (p = 0.02), respectively). The BioFire GI Panel provides comprehensive results within 2 h and may be useful for the rapid identification of enteropathogens.

In prenatal diagnostics, NIPT screening utilizing read coverage-based profiles obtained from shallow WGS data is routinely used to detect fetal CNVs. From this same data, fragment size distributions of fetal and maternal DNA fragments can be derived, which are known to be different, and often used to infer fetal fractions. We argue that the fragment size has the potential to aid in the detection of CNVs. By integrating, in parallel, fragment size and read coverage in a within-sample normalization approach, it is possible to construct a reference set encompassing both data types. This reference then allows the detection of CNVs within queried samples, utilizing both data sources. We present a new methodology, WisecondorFF, which improves sensitivity, while maintaining specificity, relative to existing approaches. WisecondorFF increases robustness of detected CNVs, and can reliably detect even at lower fetal fractions (

L-kynurenine (L-KYN) is an endogenous metabolite, that has been used as a neuroprotective strategy in experimental models. The protective effects of L-KYN have been attributed mainly to kynurenic acid (KYNA). However, considering that L-KYN is prone to oxidation, this redox property may play a substantial role in its protective effects. The aim of this work was to characterize the potential impact of the redox properties of L-KYN, in both synthetic and biological systems. First, we determined whether L-KYN scavenges reactive oxygen species (ROS) and prevents DNA and protein oxidative degradation in synthetic systems. The effect of L-KYN and KYNA (0.1–100 µM) on redox markers (ROS production, lipoperoxidation and cellular function) was compared in rat brain homogenates when exposed to FeSO4 (10 µM). Then, the effect of L-KYN administration (75 mg/kg/day for 5 days) on the GSH content and the enzymatic activity of glutathione reductase (GR) and glutathione peroxidase (GPx) was determined in rat brain tissue. Finally, brain homogenates from rats pretreated with L-KYN were exposed to pro-oxidants and oxidative markers were evaluated. The results show that L-KYN is an efficient scavenger of ●OH and ONOO−, but not O2●– or H2O2 and that it prevents DNA and protein oxidative degradation in synthetic systems. L-KYN diminishes the oxidative effect induced by FeSO4 on brain homogenates at lower concentrations (1 µM) when compared to KYNA (100 µM). Furthermore, the sub-chronic administration of L-KYN increased the GSH content and the activity of both GR and GPx, and also prevented the oxidative damage induced by the ex vivo exposure to pro-oxidants. Altogether, these findings strongly suggest that L-KYN can be considered as a potential endogenous antioxidant.

Essential metals such as copper, iron, and zinc are cofactors in various biological processes including oxygen utilisation, cell growth, and biomolecular synthesis. The homeostasis of these essential metals is carefully controlled through a system of protein transporters involved in the uptake, storage, and secretion. Some metal ions can be transformed by processes including reduction/oxidation (redox) reactions, and correspondingly, the breakdown of metal ion homeostasis can lead to formation of reactive oxygen and nitrogen species. We have previously demonstrated rapid biochemical responses to stress involving alterations in the redox state to generate free radicals and the resultant oxidative stress. However, the effects of stress on redox-active metals including iron and copper and redox-inert zinc have not been well characterised. Therefore, this study aims to examine the changes in these essential metals following exposure to short-term repeated stress, and to further elucidate the alterations in metal homeostasis through expression analysis of different metal transporters. Outbred male Wistar rats were exposed to unrestrained (control), 1 day, or 3 days of 6 h restraint stress (n = 8 per group). After the respective stress treatment, blood and liver samples were collected for the analysis of biometal concentrations and relative gene expression of metal transporter and binding proteins. Exposure to repeated restraint stress was highly effective in causing hepatic redox imbalance. Stress was also shown to induce hepatic metal redistribution, while modulating the mRNA levels of key metal transporters. Overall, this study is the first to characterise the gene expression profile of metal homeostasis following stress and provide insight into the changes occurring prior to the onset of chronic stress conditions.

Oxygen (O2) quantification is essential for assessing cell metabolism, and its consumption in cell culture is an important indicator of cell viability. Recent advances in microfluidics have made O2 sensing a crucial feature for organ-on-chip (OOC) devices for various biomedical applications. OOC O2 sensors can be categorized, based on their transducer type, into two main groups, optical and electrochemical. In this review, we provide an overview of on-chip O2 sensors integrated with the OOC devices and evaluate their advantages and disadvantages. Recent innovations in optical O2 sensors integrated with OOCs are discussed in four main categories: (i) basic luminescence-based sensors; (ii) microparticle-based sensors; (iii) nano-enabled sensors; and (iv) commercial probes and portable devices. Furthermore, we discuss recent advancements in electrochemical sensors in five main categories: (i) novel configurations in Clark-type sensors; (ii) novel materials (e.g., polymers, O2 scavenging and passivation materials); (iii) nano-enabled electrochemical sensors; (iv) novel designs and fabrication techniques; and (v) commercial and portable electrochemical readouts. Together, this review provides a comprehensive overview of the current advances in the design, fabrication and application of optical and electrochemical O2 sensors.

Small bowel malignancies are rare and usually asymptomatic or symptoms are nonspecific. Therefore, small bowel tumors are difficult to diagnose. In patients with iron deficiency anemia (IDA) who have negative bidirectional endoscopy results, the small bowel may be considered the source of bleeding. However, in asymptomatic IDA patients with negative bidirectional endoscopy results, evidence supporting the routine use of capsule endoscopy (CE) is insufficient. CE can be considered in selected patients with recurrent or persistent IDA. The frequency of small bowel malignancies is low in patients undergoing CE for IDA, but the usefulness of CE for the diagnosis of small bowel malignancies in younger age groups with IDA has been reported. For patients with risk factors for small bowel malignancy, investigation of the small bowel should be considered. Efforts should be made to prevent adverse events, such as capsule retention or capsule aspiration, through meticulous history taking and endoscopic capsule delivery as necessary.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as a chronic bladder disorder with suprapubic pain (pelvic pain) and pressure and/or discomfort related to bladder filling accompanied by lower urinary tract symptoms, such as urinary frequency and urgency without urinary tract infection (UTI) lasting for at least 6 weeks. IC/BPS presents significant bladder pain and frequency urgency symptoms with unknown etiology, and it is without a widely accepted standard in diagnosis. Patients’ pathological features through cystoscopy and histologic features of bladder biopsy determine the presence or absence of Hunner lesions. IC/PBS is categorized into Hunner (ulcerative) type IC/BPS (HIC/BPS) or non-Hunner (nonulcerative) type IC/BPS (NHIC/BPS). The pathophysiology of IC/BPS is composed of multiple possible factors, such as chronic inflammation, autoimmune disorders, neurogenic hyperactivity, urothelial defects, abnormal angiogenesis, oxidative stress, and exogenous urine substances, which play a crucial role in the pathophysiology of IC/BPS. Abnormal expressions of several urine and serum specimens, including growth factor, methylhistamine, glycoprotein, chemokine and cytokines, might be useful as biomarkers for IC/BPS diagnosis. Further studies to identify the key molecules in IC/BPS will help to improve the efficacy of treatment and identify biomarkers of the disease. In this review, we discuss the potential medical therapy and assessment of therapeutic outcome with urinary biomarkers for IC/BPS.

Labor and delivery entail a complex and sequential metabolic and physiologic cascade, culminating in most circumstances in successful childbirth, although delivery can be a risky episode if oxygen supply is interrupted, resulting in perinatal asphyxia (PA). PA causes an energy failure, leading to cell dysfunction and death if re-oxygenation is not promptly restored. PA is associated with long-term effects, challenging the ability of the brain to cope with stressors occurring along with life. We review here relevant targets responsible for metabolic cascades linked to neurodevelopmental impairments, that we have identified with a model of global PA in rats. Severe PA induces a sustained effect on redox homeostasis, increasing oxidative stress, decreasing metabolic and tissue antioxidant capacity in vulnerable brain regions, which remains weeks after the insult. Catalase activity is decreased in mesencephalon and hippocampus from PA-exposed (AS), compared to control neonates (CS), in parallel with increased cleaved caspase-3 levels, associated with decreased glutathione reductase and glutathione peroxidase activity, a shift towards the TIGAR-dependent pentose phosphate pathway, and delayed calpain-dependent cell death. The brain damage continues long after the re-oxygenation period, extending for weeks after PA, affecting neurons and glial cells, including myelination in grey and white matter. The resulting vulnerability was investigated with organotypic cultures built from AS and CS rat newborns, showing that substantia nigra TH-dopamine-positive cells from AS were more vulnerable to 1 mM of H2O2 than those from CS animals. Several therapeutic strategies are discussed, including hypothermia; N-acetylcysteine; memantine; nicotinamide, and intranasally administered mesenchymal stem cell secretomes, promising clinical translation.

12 páginas, 3 figuras, 1 tabla, A rapid and high throughput protocol to measure the catalase activity in vitro has been designed. Catalase is an enzyme with unusual kinetic properties because it does not follow the standard Michaelis–Menten model and is inactivated by H2O2. This makes the analysis of the two rate equations of the second‐ordered reactions of the kinetic model rather complex. A two‐degree polynomial fitting of the experimental data is proposed after transforming the exponential form of the integrated rate equation of the [H2O2] into a polynomial using the Taylor series. The fitting is validated by establishing an experimental linear relationship between the initial rate of the H2O2 decomposition and the protein concentration, regardless of the suicide inactivation that catalase might undergo beyond t > 0. In addition, experimental considerations are taken into account to avoid statistical bias in the analysis of the catalase activity. ANOVA analyses show that the proposed protocol can be utilized to measure the initial rate of the H2O2 decomposition by catalase in 32 samples in triplicates if kept below 8 mM min−1 in the microplate wells. These kinetic and statistical analyses can pave the way for other antioxidant enzyme activity assays in microplate readers at small scale and low cost., This research was funded by the Spanish national plan for Scientific and Technical Research and Innovation, grant number AGL2016-79589-R, and the regional government of Castilla y León, grant number CSI260P20. The Project “CLU-2019-05—IRNASA/CSIC Unit of Excellence” funded by the Junta de Castilla y León and co-financed by the European Union (ERDF “Europe drives our growth”) is also acknowledged

One of the most dangerous diseases that threaten people is cancer. If diagnosed in earlier stages, cancer, with its life-threatening consequences, has the possibility of eradication. In addition, accuracy in prediction plays a significant role. Hence, developing a reliable model that contributes much towards the medical community in the early diagnosis of biopsy images with perfect accuracy comes to the forefront. This article aims to develop better predictive models using multivariate data and high-resolution diagnostic tools in clinical cancer research. This paper proposes the social spider optimisation (SSO) algorithm-tuned neural network to classify microscopic biopsy images of cancer. The significance of the proposed model relies on the effective tuning of the weights of the neural network classifier by the SSO algorithm. The performance of the proposed strategy is analysed with performance metrics such as accuracy, sensitivity, specificity, and MCC measures, and the attained results are 95.9181%, 94.2515%, 97.125%, and 97.68%, respectively, which shows the effectiveness of the proposed method for cancer disease diagnosis.

In this work, eight different types of optical oxygen sensing films were prepared by impregnating indicator and matrix solution on the surface of a polypropylene microporous filter membrane. The polymer matrix of the sensing films was ethyl cellulose (EC), polymethyl methacrylate (PMMA), and their blends with different mixing ratios. Scanning electron microscopy (SEM), laser confocal microscopy, and fluorescence spectrometer were used to investigate the morphologies and optical properties of the sensing films. Phase delay measurements under different oxygen partial pressures (PO2) and temperatures were applied to investigate the analytical performances of the sensing film for gaseous O2 monitoring. Results show that the response time of all the sensing films was extremely fast. The sensitivities and dynamic ranges of the sensing films with the blended polymer matrix were separately decreased and increased as the EC/PMMA ratio decreased, and the S-V curve of the sensing films blended with equal content of EC and PMMA exhibited good linearity under different temperatures, showing a promising prospect in practical application.

Conventional sample preparation techniques require bulky and expensive instruments and are not compatible with next-generation point-of-care diagnostic testing. Here, we report a manually operated syringe-tip inertial microfluidic centrifuge (named i-centrifuge) for high-flow-rate (up to 16 mL/min) cell concentration and experimentally demonstrate its working mechanism and performance. Low-cost polymer films and double-sided tape were used through a rapid nonclean-room process of laser cutting and lamination bonding to construct the key components of the i-centrifuge, which consists of a syringe-tip flow stabilizer and a four-channel paralleled inertial microfluidic concentrator. The unstable liquid flow generated by the manual syringe was regulated and stabilized with the flow stabilizer to power inertial focusing in a four-channel paralleled concentrator. Finally, we successfully used our i-centrifuge for manually operated cell concentration. This i-centrifuge offers the advantages of low device cost, simple hand-powered operation, high-flow-rate processing, and portable device volume. Therefore, it holds potential as a low-cost, portable sample preparation tool for point-of-care diagnostic testing.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition causing bladder pressure and pain. The condition is of unknown etiology and is often accompanied by other symptoms, including chronic pelvic pain, increased urinary urgency, and frequency. There is no definitive diagnosis for IC/BPS, and treatment options are currently limited to physical therapy and medications to help alleviate symptoms. The endogenous cannabinoid system (ECS) is an important regulator of numerous physiological systems, including the urinary system. Modulations of the ECS have been shown to be beneficial for IC/BPS-associated pain and inflammation in rodents. As an attempt to identify potential biomarkers for IC/BPS, we reviewed experimental studies where the components of the ECS have been quantified in experimental models of IC/BPS. Further investigations using well-defined animal models and patients’ data are required to obtain stronger evidence regarding the potential for ECS components to be definitive biomarkers for IC/BPS.

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease characterized by progressive enlargement of fluid-filled cysts derived from renal tubular epithelial cells, which has become the fourth leading cause of end-stage renal diseases. Currently, treatment options for ADPKD remain limited. The purpose of this study was to discover an effective therapeutic drug for ADPKD. With virtual screening, Madin-Darby canine kidney (MDCK) cyst model, embryonic kidney cyst model and kidney-specific Pkd1 knockout mouse (PKD) model, we identified obacunone as a candidate compound for ADPKD drug discovery from a natural antioxidant compound library. In vitro experiments showed that obacunone significantly inhibited cyst formation and expansion of MDCK cysts and embryonic kidney cysts in a dose-dependent manner. In vivo, obacunone treatment significantly reduced the renal cyst development in PKD mice. Western blot and morphological analysis revealed that obacunone served as a NRF2 activator in ADPKD, which suppressed lipid peroxidation by up-regulating GPX4 and finally restrained excessive cell proliferation by down-regulating mTOR and MAPK signaling pathways. Experimental data demonstrated obacunone as an effective renal cyst inhibitor for ADPKD, indicating that obacunone might be developed into a therapeutic drug for ADPKD treatment.

Sustainability, circular economy and alternative production systems are urgent imperatives for humanity and animal husbandry. Unless wasted, agri-food by-products can offer a promising source of high value. We evaluated the effect of rice bran (RB), corncob (CC), potato peels (PP), solid biogas residues (BR), and olive-oil processing residuals (OR), as alternative substrates to wheat bran (WB as control), on the growth and nutritional value of Tenebrio molitor during its breeding for animal feeds and/or human consumption. Innovation-wise, we further investigated the substrate supplementation (0, 10, 20%) with post-distillation residues of Mediterranean aromatic-medicinal plants (MAPs: lavender, Greek oregano, rosemary, olive; 1:1:1:1 ratio). Tenebrio molitor larvae (TML) were reared in all the studied substrates, and TML and diets’ proximate and fatty acid compositions as well as total phenol and flavonoid content and antioxidant potential were assessed using standard procedures. After statistical analysis of correlations, we observed that CC promoted oviposition and progeny survival; larval weight and dry matter were positively affected mainly by dietary energy and fat content; number of TML and/or larval weight increased using 10% MAPs inclusion in WB, RB and OR or RB, OR, BR and PP, respectively, which did not affect protein content; TML fatty acid composition decreased the content of saturated ones and increased that of mono-unsaturated ones; MAPs residues had an apparent favorable impact on total phenolic content and antioxidant activity of each substrate, with RB displaying the highest capacity and content. These findings indicate that alternative substrates can be exploited and their enrichment with natural phenolics is able to influence T. molitor growth, offering highly beneficial and nutritional value.

Prunus cerasoides (PC) has been reported to have antimicrobial and anti-inflammatory properties, but its potential as a neuroprotective agent in a mouse model of cerebral ischemia has not been explored. Considering neuroglobin (Ngb), an endogenous neuroprotective factor, as a novel approach to neuroprotection, in this study, Ngb promoter activity, Ngb expression changes, and antioxidant protection by PC extract (PCE) and PC component compounds (PCCs) were analyzed in oxygen–glucose deprivation (OGD)-treated neurons. In vivo analysis involved transient middle cerebral artery occlusion (tMCAO) in mice with pre- and post-treatment exposure to PCE. Following ischemic stroke induction, neurological behavior scores were obtained, and cellular function-related signals were evaluated in the ischemic infarct areas. In addition to PCE, certain component compounds from PCE also significantly increased Ngb levels and attenuated the intracellular ROS production and cytotoxicity seen with OGD in primary neurons. Administration of PCE reduced the infarct volume and improved neurological deficit scores in ischemic stroke mice compared with the vehicle treatment. Increased Ngb levels in infarct penumbra with PCE treatment were also accompanied by decreased markers of apoptosis (activated p38 and cleaved caspase-3). Our findings point to the benefits of Ngb-mediated neuroprotection via PCE and its antioxidant activity in an ischemic stroke model.

Obesity-related dysmetabolic conditions are amongst the most common causes of death globally. Indicaxanthin, a bioavailable betalain pigment from Opuntia ficus-indica fruit, has been demonstrated to modulate redox-dependent signalling pathways, exerting significant anti-oxidative and anti-inflammatory effects in vitro and in vivo. In light of the strict interconnections between inflammation, oxidative stress and insulin resistance (IR), a nutritionally relevant dose of indicaxanthin has been evaluated in a high-fat diet (HFD) model of obesity-related IR. To this end, biochemical and histological analysis, oxidative stress and inflammation evaluations in liver and adipose tissue were carried out. Our results showed that indicaxanthin treatment significantly reduced body weight, daily food intake and visceral fat mass. Moreover, indicaxanthin administration induced remarkable, beneficial effects on HFD-induced glucose dysmetabolism, reducing fasting glycaemia and insulinaemia, improving glucose and insulin tolerance and restoring the HOMA index to physiological values. These effects were associated with a reduction in hepatic and adipose tissue oxidative stress and inflammation. A decrease in RONS, malondialdehyde and NO levels, in TNF-α, CCL-2 and F4-80 gene expression, in p65, p-JNK, COX-2 and i-NOS protein levels, in crown-like structures and hepatic inflammatory foci was, indeed, observed. The current findings encourage further clinical studies to confirm the effectiveness of indicaxanthin to prevent and treat obesity-related dysmetabolic conditions.

As the basic element of aerobic animal life, oxygen participates in most physiological activities of animals. Hypoxia stress is often the subject of aquatic animal research. Macrobrachium nipponense, an economically important aquatic animal in southern China, has been affected by hypoxia for many years and this has resulted in a large amount of economic loss due to its sensitivity to hypoxia; Metabolism and transcriptome data were combined in the analysis of the hepatopancreas of M. nipponense in different physiological states under hypoxia; A total of 108, 86, and 48 differentially expressed metabolites (DEMs) were found in three different comparisons (survived, moribund, and dead shrimps), respectively. Thirty-two common DEMs were found by comparing the different physiological states of M. nipponense with the control group in response to hypoxia. Twelve hypoxia-related genes were identified by screening and analyzing common DEMs. GTP phosphoenolpyruvate carboxykinase (PEPCK) was the only differentially expressed gene that ranked highly in transcriptome analysis combined with metabolome analysis. PEPCK ranked highly both in transcriptome analysis and in combination with metabolism analysis; therefore, it was considered to have an important role in hypoxic response. This manuscript fills the one-sidedness of the gap in hypoxia transcriptome analysis and reversely deduces several new genes related to hypoxia from metabolites. This study contributes to the clarification of the molecular process associated with M. nipponense under hypoxic stress.

Flavonoids constitute a group of polyphenolic compounds characterized by a common gamma-benzo- pyrone structure considered in numerous biological systems to possess antioxidant capacity. Among the different applications of flavonoids, its genoprotective capacity against damage induced by ionizing radiation stands out, which has been related to antioxidant activity and its chemical structure. In this study, we determined the frequency of appearance of micronucleus in vivo by means of the micronucleus assay. This was conducted in mice treated with different flavonoids before and after exposure to 470 mGy X-rays; thereafter, their bone marrow polychromatophilic erythrocytes were evaluated to establish the structural factors enhancing the observed genoprotective effect. Our results in vivo show that the presence of a monomeric flavan-3-ol type structure, with absence of carbonyl group in position C4 of ring C, absence of conjugation between the carbons bearing the C2 = C3 double bond and the said ring, presence of a catechol group in ring B and characteristic hydroxylation in positions 5 and 7 of ring A are the structural characteristics that determine the highest degree of genoprotection. Additionally, a certain degree of polymerization of this flavonoid monomer, but maintaining significant levels of monomers and dimers, contributes to increasing the degree of genoprotection in the animals studied at both times of their administration (before and after exposure to X-rays).

Multiplex nucleic acid amplification assays that simultaneously detect multiple respiratory pathogens in a single nasopharyngeal swab (NPS) specimen are widely used for rapid clinical diagnostics. We evaluated Allplex Respiratory Panel (RP) 1, 2, 3, and the BioFire FilmArray RP assay for detecting respiratory pathogens from NPS specimens. In all, 181 NPS specimens obtained from patients suspected of having respiratory infections during the non-influenza season (August–December 2019) were included. The Allplex RP 1, 2, and 3 detected 154 samples positive for respiratory viruses, whereas the BioFire FilmArray detected viruses in 98 samples. Co-infection with two or more viruses was detected in 41 and 17 NPS specimens by Allplex RP and the BioFire FilmArray RP, respectively. For adenoviruses, Allplex RP 1 detected 31 specimens, compared to 34 by the BioFire FilmArray. In all, 64 NPS specimens were positive for human enterovirus (HEV) and human rhinovirus (HRV) on the Allplex RP, in contrast to 39 HEV/HRV on the BioFire FilmArray. The parainfluenza virus (PIV-1–4) detection rate differed between the two systems. Most discrepant results were observed for NPS specimens with high cycle threshold values obtained by Allplex RP. This study showed concordant performance of the Allplex RP 1, 2, 3, and the BioFire FilmArray RP for the simultaneous detection of multiple respiratory viruses.

TAR DNA-binding protein 43 (TDP-43) is a member of an evolutionarily conserved family of heterogeneous nuclear ribonucleoproteins that modulate multiple steps in RNA metabolic processes. Cytoplasmic aggregation of TDP-43 in affected neurons is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Mislocalized and accumulated TDP-43 in the cytoplasm induces mitochondrial dysfunction and reactive oxidative species (ROS) production. Here, we show that TDP-43- and rotenone-induced neurotoxicity in the human neuronal cell line SH-SY5Y were attenuated by hydroxocobalamin (Hb, vitamin B12 analog) treatment. Although Hb did not affect the cytoplasmic accumulation of TDP-43, Hb attenuated TDP-43-induced toxicity by reducing oxidative stress and mitochondrial dysfunction. Moreover, a shortened lifespan and motility defects in TDP-43-expressing Drosophila were significantly mitigated by dietary treatment with hydroxocobalamin. Taken together, these findings suggest that oral intake of hydroxocobalamin may be a potential therapeutic intervention for TDP-43-associated proteinopathies.

Surface-enhanced Raman spectroscopy (SERS) is a powerful technique for biosensing. However, SERS analysis has several concerns: the signal is limited by a number of molecules and the area of the plasmonic substrate in the laser hotspot, and quantitative analysis in a low-volume droplet is confusing due to the change of concentration during quick drying. The usage of hollow-core microstructured optical fibers (HC-MOFs) is thought to be an effective way to improve SERS sensitivity and limit of detection through the effective irradiation of a small sample volume filling the fiber capillaries. In this paper, we used layer-by-layer assembly as a simple method for the functionalization of fiber capillaries by gold nanoparticles (seeds) with a mean diameter of 8 nm followed by UV-induced chloroauric acid reduction. We also demonstrated a simple and quick technique used for the analysis of the SERS platform formation at every stage through the detection of spectral shifts in the optical transmission of HC-MOFs. The enhancement of the Raman signal of a model analyte Rhodamine 6G was obtained using such type of SERS platform. Thus, a combination of nanostructured gold coating as a SERS-active surface and a hollow-core fiber as a microfluidic channel and a waveguide is perspective for point-of-care medical diagnosis based on liquid biopsy and exhaled air analysis.

Exosomes carry cellular proteins and contain molecules that can be potential biomarkers of diseases. This study used a Syrian golden hamster model of 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral squamous cell carcinoma with radiation therapy to exclude the confounding factors that may affect outcomes in clinical studies, and re-examine the role of exosomes during tumorigenesis. We used data-dependent acquisition-based quantitative proteomics and bioinformatics analyses and found unique proteins present (desmocollin-2) or absent (Glucagon-cAMP-PKA-CREB pathway-related proteins) in the salivary exosomes of the pre-radiation DMBA-treated group (PreD). Comparing our data to other studies, salivary exosomes in the PreD group were found carrying proteins that the tumor mass does not express and lacking the proteins needed during tumorigenesis. Immunohistochemistry staining showed p53 expression but a negative apoptotic signal in the PreD tumor tissue. We thus suggest that inhibition of desmocollin-2 expression in tumor tissue may impede the activation of cell apoptosis. However, both the origin of the salivary exosomes and main role of the salivary exosome proteins should be clarified in future studies.

Animal models for complex diseases are needed to position and analyze the function of interacting genes. Previous positional cloning identified Ncf1 and Clec4b to be major regulators of arthritis models in rats. Here, we investigate epistasis between Ncf1 and Clec4b, two major regulators of arthritis in rats. We find that Clec4b and Ncf1 exert an additive effect on arthritis given by their joint ability to regulate neutrophils. Both genes are highly expressed in neutrophils, together regulating neutrophil availability and their capacity to generate reactive oxygen species. Using a glycan array, we identify key ligands of Clec4b and demonstrate that Clec4b-specific stimulation triggers neutrophils into oxidative burst. Our observations highlight Clec4b as an important regulator of neutrophils and demonstrate how epistatic interactions affect the susceptibility to, and severity of, autoimmune arthritis.

Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers’ attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5low/miR-222high status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.

Acidophilic archaea thrive in anaerobic and aerobic low pH environments (pH < 5) rich in dissolved heavy metals that exacerbate stress caused by the production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), hydroxyl radical (·OH) and superoxide (O2−). ROS react with lipids, proteins and nucleic acids causing oxidative stress and damage that can lead to cell death. Herein, genes and mechanisms potentially involved in ROS mitigation are predicted in over 200 genomes of acidophilic archaea with sequenced genomes. These organisms are often be subjected to simultaneous multiple stresses such as high temperature, high salinity, low pH and high heavy metal loads. Some of the topics addressed include: (1) the phylogenomic distribution of these genes and what this can tell us about the evolution of these mechanisms in acidophilic archaea; (2) key differences in genes and mechanisms used by acidophilic versus non-acidophilic archaea and between acidophilic archaea and acidophilic bacteria and (3) how comparative genomic analysis predicts novel genes or pathways involved in oxidative stress responses in archaea and likely horizontal gene transfer (HGT) events.

Seventy-two-hour unscheduled return visits (URVs) by emergency department patients are a key clinical index for evaluating the quality of care in emergency departments (EDs). This study aimed to develop a machine learning model to predict 72 h URVs for ED patients with abdominal pain. Electronic health records data were collected from the Chang Gung Research Database (CGRD) for 25,151 ED visits by patients with abdominal pain and a total of 617 features were used for analysis. We used supervised machine learning models, namely logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGB), and voting classifier (VC), to predict URVs. The VC model achieved more favorable overall performance than other models (AUROC: 0.74; 95% confidence interval (CI), 0.69–0.76; sensitivity, 0.39; specificity, 0.89; F1 score, 0.25). The reduced VC model achieved comparable performance (AUROC: 0.72; 95% CI, 0.69–0.74) to the full models using all clinical features. The VC model exhibited the most favorable performance in predicting 72 h URVs for patients with abdominal pain, both for all-features and reduced-features models. Application of the VC model in the clinical setting after validation may help physicians to make accurate decisions and decrease URVs.

Optical coherence tomography (OCT) has become the leading diagnostic tool in modern ophthalmology. We are interested here in developing a support tool for the segmentation of retina layers. The proposed method relies on graph theory and geodesic distance. As each retina layer is characterised by different features, the proposed method interleaves various gradients during detection, such as horizontal and vertical gradients or open-closed gradients. The method was tested on a dataset of 750 OCT B-Scan Spectralis provided by the Ophthalmology Department of the County Emergency Hospital Cluj-Napoca. The method has smaller signed error on layers B1, B7 and B8, with the highest value of 0.43 pixels. The average value of signed error on all layers is −1.99 ± 1.14 px. The average value for mean absolute error is 2.60 ± 0.95 px. Since the target is a support tool for the human agent, the ophthalmologist can intervene after each automatic step. Human intervention includes validation or fine tuning of the automatic segmentation. In line with design criteria advocated by explainable artificial intelligence (XAI) and human-centered AI, this approach gives more control and transparency as well as more of a global perspective on the segmentation process.

This study aims to develop a generalizable method for designing a patient-specific reconstructive scaffold implant for a large distal lateral femur defect using finite element (FE) analysis and topology optimization. A 3D solid-core implant for the distal femur defect was designed to withhold the femur load. Data from FE analysis of the solid implant were use for topology optimization to obtain a ‘bone scaffold implant’ with light-weight internal cavity and surface lattice features to allow for filling with bone material. The bone scaffold implant weighed 69.6% less than the original solid-core implant. The results of FE simulation show that the bone repaired with the bone scaffold implant had lower total displacement (12%), bone plate von Mises stress (34%), bone maximum first principal stress (33%), and bone maximum first principal strain (32%) than did bone repaired with bone cement. The trend in experimental strain with increasing load on the composite femur was greater with bone cement than with the bone scaffold implant. This study presents a generalizable method for designing a patient-specific reconstructive scaffold implant for the distal lateral femur defect that has sufficient strength and space for filling with allograft bone.

(1) Background: Respiratory insufficiency with acute respiratory distress syndrome (ARDS) and multi-organ dysfunction leads to high mortality in COVID-19 patients. In times of limited intensive care unit (ICU) resources, chest CTs became an important tool for the assessment of lung involvement and for patient triage despite uncertainties about the predictive diagnostic value. This study evaluated chest CT-based imaging parameters for their potential to predict in-hospital mortality compared to clinical scores. (2) Methods: 89 COVID-19 ICU ARDS patients requiring mechanical ventilation or continuous positive airway pressure mask ventilation were included in this single center retrospective study. AI-based lung injury assessment and measurements indicating pulmonary hypertension (PA-to-AA ratio) on admission CT, oxygenation indices, lung compliance and sequential organ failure assessment (SOFA) scores on ICU admission were assessed for their diagnostic performance to predict in-hospital mortality. (3) Results: CT severity scores and PA-to-AA ratios were not significantly associated with in-hospital mortality, whereas the SOFA score showed a significant association (p < 0.001). In ROC analysis, the SOFA score resulted in an area under the curve (AUC) for in-hospital mortality of 0.74 (95%-CI 0.63–0.85), whereas CT severity scores (0.53, 95%-CI 0.40–0.67) and PA-to-AA ratios (0.46, 95%-CI 0.34–0.58) did not yield sufficient AUCs. These results were consistent for the subgroup of more critically ill patients with moderate and severe ARDS on admission (oxygenation index

The intactness of blood–brain barrier (BBB) is compromised in Alzheimer’s disease (AD). Importantly, evidence suggests that the perturbation and abnormalities appearing in BBB can manifest early in the progression of the disease. The disruption of BBB allows extravasation of the plasma protein, fibrinogen, to enter brain parenchyma, eliciting immune reactivity and response. The presence of amyloid-β (Aβ) peptide leads to the formation of abnormal aggregates of fibrin resistant to degradation. Furthermore, Aβ deposits act on the contact system of blood coagulation, altering levels of thrombin, fibrin clots and neuroinflammation. The neurovascular unit (NVU) comprises an ensemble of brain cells which interact with infiltrating fibrinogen. In particular, interaction of resident immune cell microglia with fibrinogen, fibrin and Aβ results in the production of reactive oxygen species (ROS), a neurotoxic effector in AD brain. Overall, fibrinogen infiltration through a leaky BBB in AD animal models and in human AD tissue is associated with manifold abnormalities including persistent fibrin aggregation and clots, microglial-mediated production of ROS and diminished viability of neurons and synaptic connectivity. An objective of this review is to better understand how processes associated with BBB leakiness to fibrinogen link vascular pathology with neuronal and synaptic damage in AD.

Chronic kidney disease (CKD) is the progressive loss of renal function and the leading cause of end-stage renal disease (ESRD). Despite optimal therapy, many patients progress to ESRD and require dialysis or transplantation. The pathogenesis of CKD involves inflammation, kidney fibrosis, and blunted renal cellular antioxidant capacity. In this review, we have focused on in vitro and in vivo experimental and clinical studies undertaken to investigate the mechanistic pathways by which these compounds exert their effects against the progression of CKD, particularly diabetic nephropathy and kidney fibrosis. The accumulated and collected data from preclinical and clinical studies revealed that these plants/bioactive compounds could activate autophagy, increase mitochondrial bioenergetics and prevent mitochondrial dysfunction, act as modulators of signaling pathways involved in inflammation, oxidative stress, and renal fibrosis. The main pathways targeted by these compounds include the canonical nuclear factor kappa B (NF-κB), canonical transforming growth factor-beta (TGF-β), autophagy, and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid factor 2-related factor 2 (Nrf2)/antioxidant response element (ARE). This review presented an updated overview of the potential benefits of these antioxidants and new strategies to treat or reduce CKD progression, although the limitations related to the traditional formulation, lack of standardization, side effects, and safety.