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The floral industry grapples with challenges like changing climatic scenarios, differences in market trends, rising costs, and severe losses posed by insect pests. The management of dipteran pests encompassing diverse species, such as leaf miners, midges, flies, and mosquitoes, has emerged as an obligate adversary, inflicting substantial economic losses in the cut and loose flower industry. Through a comprehensive analysis of existing literature, this paper delves into the diverse array of dipteran species of leaf miners and midges, their life cycles, distribution, host range, damaging symptoms, insecticide resistance, and the management strategies practised to date. Furthermore, this critique underscores the urgent need for innovative approaches and integrated pest management techniques to mitigate the escalating menace of dipteran pests. By elucidating the multifaceted challenges and proposing strategic interventions, this critique aims to foster dialogue and inspire concerted action among researchers, stakeholders, and scholars to safeguard the sustainability and profitability of the floral industry.

Abstract There are genetic and environmental risk factors that contribute to the development of cognitive decline in Alzheimer’s disease (AD). Some of these include the genetic predisposition of the apolipoprotein E4 genotype, consuming a high-fat diet (HFD), and the female sex. Brain insulin receptor resistance and deficiency have also been shown to be associated with AD and cognitive impairment. Intranasal (INL) insulin enhances cognition in AD, but the response varies due to genotype, diet, and sex. We investigated here the combination of these risk factors in a humanized mouse model, expressing E3 or E4, following a HFD in males and females on cognitive performance and the brain distribution of insulin following INL delivery. The HFD had a negative effect on survival in male mice only, requiring sex to be collapsed. We found many genotype, diet, and genotype x diet effects in anxiety-related tasks. We further found beneficial effects of INL insulin in our memory tests, with the most important findings showing a beneficial effect of INL insulin in mice on a HFD. We found insulin distribution throughout the brain after INL delivery was largely unaffected by diet and genotype, indicating these susceptible groups can still receive adequate levels of insulin following INL delivery. Our findings support the involvement of brain insulin signaling in cognition and highlight continuing efforts investigating mechanisms resulting from treatment with INL insulin.

Introduction: Haemoglobin (Hb) and packed cell volume (PCV) are tests used in the assessment of anaemia. The Veri-Q haemoglobin meter is a new device in the point-of-care market used for the quantitative measurement of haemoglobin and packed cell volume. This study aimed to evaluate the performance of the Veri-Q haemoglobin meter for the assessment of haemoglobin and packed cell volume. Materials and Methods: Haemoglobin and packed cell volume estimations of one hundred and eleven participants were determined using the Veri-Q Red haemoglobin meter and statistically compared with those obtained from the conventional method (gold standard). Results: One hundred and eleven undergraduate students participated in this study, of whom 72 (64.9%) were females and 39 (35.1%) were males. The mean haemoglobin values calculated using the Veri-Q haemoglobin meter (11.97 ± 1.95 g/dl) were significantly lower than the values obtained with the conventional method (12.35 ± 1.66 g/dl) (t= 4.7549; p=0.0001). Similar results were obtained with packed cell volume estimation. The performance indices of the Veri-Q haemoglobin meter were as follows: sensitivity (75.41% for Hb and 77.05% for PCV), specificity (28.0% for Hb and PCV), positive predictive value (PPV) (56.1% for Hb and 56.63% for PCV), negative predictive value (48.28% for Hb and 50% for PCV). The prevalence of anemia in this study was 54.05%. Positive Likelihood Ratio (1.05 for Hb and 1.07 for PCV), Negative Likelihood Ratio (0.88 for Hb and 0.82 for PCV), Accuracy (54.05% for Hb and 54.95% for PCV). The Receiver Operative Characteristics (ROC) Area Under Curve (AUC) was 0.996 for Hb and 0.984 for PCV. A significant but weak positive correlation was found to exist between haemoglobin estimations using conventional and Veri-Q methods (r=0.3013, P =0.01); PCV (R=0.2512, P =0.07). The sensitivity of the device can be described as moderate while the specificity is low. The accuracy of the device is just average. Conclusion: The Veri-Q haemoglobin meter demonstrates an average level of accuracy and a high AUC, making it potentially useful for field epidemiological studies.

Abstract Artificial intelligence (AI) and machine learning (ML) pose a challenge for achieving science that is both reproducible and replicable. The challenge is compounded in supervised models that depend on manually labeled training data, as they introduce additional decision‐making and processes that require thorough documentation and reporting. We address these limitations by providing an approach to hand labeling training data for supervised ML that integrates quantitative content analysis (QCA)—a method from social science research. The QCA approach provides a rigorous and well‐documented hand labeling procedure to improve the replicability and reproducibility of supervised ML applications in Earth systems science (ESS), as well as the ability to evaluate them. Specifically, the approach requires (a) the articulation and documentation of the exact decision‐making process used for assigning hand labels in a “codebook” and (b) an empirical evaluation of the reliability” of the hand labelers. In this paper, we outline the contributions of QCA to the field, along with an overview of the general approach. We then provide a case study to further demonstrate how this framework has and can be applied when developing supervised ML models for applications in ESS. With this approach, we provide an actionable path forward for addressing ethical considerations and goals outlined by recent AGU work on ML ethics in ESS.

Background: Anterior cervical discectomy and fusions (ACDF) are among the most common cervical spine operations, with over 137,000 surgeries performed annually. Understanding reasons underlying malpractice pertaining to ACDF may inform physicians of practices to improve delivery of patient care and mitigate malpractice. The aim of our study was to analyze the causes and outcomes for lawsuits pertaining to ACDF. Methods: The Westlaw Edge and Verdict Search databases were queried for malpractice claims utilizing the keywords “anterior cervical discectomy and fusion” and “ACDF”. Inclusion criteria was based on relevance of case grievance(s) to ACDF. Data collected included date of case hearing, plaintiff demographics, defendant specialty, verdict ruling, location of filed claim, monetary award, and sustained injuries. Results: Fifty cases were included in this study after excluding 1933 cases. Of the 50 cases, 34 (68%) resulted in a defendant outcome, 8 (16%) resulted in a plaintiff outcome, and 8 (16%) resulted in settlement. Plaintiff verdicts resulted in an average monetary payment of $9.70 million, while settlements resulted in an average payment of $2.06 million. Reasons for litigation were divided into 10 categories, most commonly improper postoperative management (20%), hardware failure (18%), intraoperative error (14%), off-label use of implants (14%), and insufficient informed consent (12%). Conclusions: Malpractice claims due to ACDF are associated with higher frequencies of plaintiff verdicts and higher monetary costs compared to other spinal surgery procedures. There does not appear to be supporting evidence that spinal cord neuromonitoring is mandatory for ACDF procedures from a medicolegal standpoint.

The complex and dynamic interaction between cellular energy control and gene expression modulation is shown by the intersection between mitochondrial metabolism and epigenetics in hypoxic environments. Poor oxygen delivery to tissues, or hypoxia, is a basic physiological stressor that sets off a series of reactions in cells to adapt and endure oxygen-starved environments. Often called the “powerhouse of the cell,” mitochondria are essential to cellular metabolism, especially regarding producing energy through oxidative phosphorylation. The cellular response to hypoxia entails a change in mitochondrial metabolism to improve survival, including epigenetic modifications that control gene expression without altering the underlying genome. By altering the expression of genes involved in angiogenesis, cell survival, and metabolism, these epigenetic modifications help cells adapt to hypoxia. The sophisticated interplay between mitochondrial metabolism and epigenetics in hypoxia is highlighted by several important points, which have been summarized in the current article. Deciphering the relationship between mitochondrial metabolism and epigenetics during hypoxia is essential to understanding the molecular processes that regulate cellular adaptation to reduced oxygen concentrations.

In order to improve the pharmacological and therapeutic properties of drugs, researchers have attempted numerous novel approaches, such as stimuli-responsive systems, and targeted drug delivery systems. These systems can be attempted by nano-based drug delivery systems involving biocompatible polymers. One among which is chitosan, a linear polysaccharide, a promising potential polymer that gained interest in delivering challenging drugs. Chitosan can encapsulate and release the drugs in a controlled/sustained manner. Chitosan can be used to develop a variety of drug delivery carriers, including films, gels, nanoparticles, nanodispersions, nanomicelles, and patches. In this regimen, minimally invasive photodynamic therapy has recently gained much interest in treating vascular diseases, including cancer, ocular diseases, microbial infections, skin disorders, etc. Photodynamic therapy utilizes light excited at a specific wavelength, eliciting singlet oxygen production. Self-lighting photodynamic therapy and combination-based photodynamic therapy also offer synergistic effects. Photodynamic therapy is more selective and specific, which may offer treatment for deep-seated diseased tissues compared to conventional therapeutic modalities. Light-activated novel drug delivery formulations have been reported using various biocompatible polymers, including chitosan. Chitosan offers its effectiveness as mucoadhesiveness, tissue penetrability, antioxidant, antimicrobial properties, supports in singlet oxygen generation, and shown its benefits in photodynamic therapy. Therefore, this review presents numerous applications of chitosan-based light-activated drug delivery systems with particular emphasis on their patents and clinical trials. The literature has been collected and compiled using various search resources such as Science Direct, J-Gate, Google Scholar, PubMed, and research data.

Fibrosis is a prevalent and detrimental condition associated with various diseases with a high impact on global morbidity and mortality rates. Despite its diverse causes and affected organs, common underlying mechanisms drive the development and progression of the disease. These mechanisms include an exaggerated inflammatory response, excessive activation of fibroblasts, and abnormal tissue remodeling following severe or repetitive tissue injury. Although significant advancements have been achieved to enhance our understanding of fibrosis, there is still a gap between identifying potential antifibrotic targets and successfully translating them into effective clinical interventions. Novel approaches that target specific cellular and molecular processes involved in fibrosis hold promise for reducing the pathological consequences of the disease. Understanding the pathogenesis and clinical implications of fibrotic diseases is crucial for developing effective therapeutic strategies and improving patient outcomes. In this review, we introduce the concept of fibrosis, discuss the mechanisms by which it arises, and explore existing and emerging therapeutic approaches in development.

Background: A water extract (CAW) of the Ayurvedic plant Centella asiatica administered in drinking water has been shown to improve cognitive deficits in mouse models of aging and neurodegenerative diseases. Here the effects of CAW administered in drinking water or the diet on cognition, measures of anxiety and depression-like behavior in healthy aged mice are compared.Methods: Three- and eighteen-month-old male and female C57BL6 mice were administered rodent AIN-93M diet containing CAW (0, 0.2, 0.5 or 1% w/w) to provide 0, 200 mg/kg/d, 500 mg/kg/d or 1,000 mg/kg/d CAW for a total of 5 weeks. An additional group of eighteen-month-old mice were treated with CAW (10 mg/mL) in their drinking water CAW for a total of 5 weeks to deliver the same exposure of CAW as the highest dietary dose (1,000 mg/kg/d). CAW doses delivered were calculated based on food and water consumption measured in previous experiments. In the fourth and fifth weeks, mice underwent behavioral testing of cognition, anxiety and depression (n = 12 of each sex per treatment group in each test).Results: Aged mice of both sexes showed cognitive deficits relative to young mice while only female aged mice showed increased anxiety compared to the young female mice and no differences in depression were observed between the different ages. CAW (1,000 mg/kg/d) in the drinking water improved deficits in aged mice in learning, executive function and recognition memory in both sexes and attenuated the increased measures of anxiety observed in the aged female mice. However, CAW in the diet only improved executive function in aged mice at the highest dose (1,000 mg/kg/d) in both sexes and did so less robustly than when given in the water. There were no effects of CAW on depression-like behavior in aged animals regardless of whether it was administered in the diet or the water.Conclusions: These results suggest that CAW can ameliorate age-related changes in measures of anxiety and cognition and that the mode of administration is important for the effects of CAW on resilience to these age-related changes.

Abstract Background del Nido cardioplegia (DN) has been shown to be safe in adult patients undergoing isolated coronary artery bypass grafting with normal left ventricular ejection fraction. We sought to determine whether it was also safe in adult patients with diminished left ventricular function. Methods All patients with preoperative left ventricular ejection fraction ≤ 40% undergoing isolated coronary artery bypass grafting between 1/1/2019 and 7/10/2022 were retrospectively analyzed. Off-pump and beating heart cases were excluded. Patients were divided by surgeon preference between conventional cardioplegia (CCP) and DN. Baseline and intraoperative characteristics and short-term postoperative outcomes were compared. Results Six surgeons performed 829 isolated coronary artery bypass operations during the study. Two-hundred seventy-two met study criteria. Three surgeons used exclusively CCP for the duration of the study, two used exclusively DN and one switched from CCP to DN mid-way through. Group totals were: CCP n = 181 and DN n = 91. There were no significant differences in baseline characteristics including mean left ventricular ejection fraction (CCP 32.5 ± 7.4% vs. DN 33.4 ± 7.29%, p = 0.939). Other than a significant decrease in bypass time for DN (113.20 ± 37.2 vs. 122.43 ± 34.3 min, p = 0.043) there were no intergroup differences in urgency, number of grafts, ischemic time or incidence of blood transfusion. Postoperative outcomes between CCP and DN were similar including incidence of atrial fibrillation (12.2% vs. 8.8%, p = 0.403), intensive care length of stay (3.7 ± 2.3 vs. 4.3 ± 3.7 days, p = 0.886), total length of stay (5.7 ± 3.7 vs. 6.3 ± 4.4 days, p = 0.922) and 30-day mortality (3.85% vs. 1.10%, p = 0.205). Conclusion Compared to conventional cardioplegia, del Nido cardioplegia provides equivalent short-term outcomes in patients with low left ventricular ejection fraction undergoing isolated coronary artery bypass grafting.

Abstract Current methods for recording large-scale neuronal activity from behaving mice at single-cell resolution require either fixing the mouse head under a microscope or attachment of a recording device to the animal’s skull. Both of these options significantly affect the animal behavior and hence also the recorded brain activity patterns. Here, we introduce a different method to acquire snapshots of single-cell cortical activity maps from freely-moving mice using a calcium sensor called CaMPARI. CaMPARI has a unique property of irreversibly changing its color from green to red inside active neurons when illuminated with 400 nm light. We capitalize on this property to demonstrate cortex-wide activity recording without any head fixation, tethering, or attachment of a miniaturized device to the mouse’s head. Multiple cortical regions were recorded while the mouse was performing a battery of behavioral and cognitive tests. We identified task-dependent activity patterns across motor and somatosensory cortices, with significant differences across sub-regions of the motor cortex and correlations across several activity patterns and task parameters. This CaMPARI-based recording method expands the capabilities of recording neuronal activity from freely-moving and behaving mice under minimally-restrictive experimental conditions and provides large-scale volumetric data that are currently not accessible otherwise.

Abstract Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a fatty acid oxidation disorder (FAOD) caused by a pathogenic variant, c.1528 G > C, in HADHA encoding the alpha subunit of trifunctional protein (TFPα). Individuals with LCHADD develop chorioretinopathy and peripheral neuropathy not observed in other FAODs in addition to the more ubiquitous symptoms of hypoketotic hypoglycemia, rhabdomyolysis and cardiomyopathy. We report a CRISPR/Cas9 generated knock-in murine model of G1528C in Hadha that recapitulates aspects of the human LCHADD phenotype. Homozygous pups are less numerous than expected from Mendelian probability, but survivors exhibit similar viability with wildtype (WT) littermates. Tissues of LCHADD homozygotes express TFPα protein, but LCHADD mice oxidize less fat and accumulate plasma 3-hydroxyacylcarnitines compared to WT mice. LCHADD mice exhibit lower ketones with fasting, exhaust earlier during treadmill exercise and develop a dilated cardiomyopathy compared to WT mice. In addition, LCHADD mice exhibit decreased visual performance, decreased cone function, and disruption of retinal pigment epithelium. Neurological function is affected, with impaired motor function during wire hang test and reduced open field activity. The G1528C knock-in mouse exhibits a phenotype similar to that observed in human patients; this model will be useful to explore pathophysiology and treatments for LCHADD in the future.

The response of the brain to radiation is important for cancer patients receiving whole or partial brain irradiation or total body irradiation, those exposed to irradiation as part of a nuclear accident or a nuclear war or terrorism event, and for astronauts during and following space missions. The mechanisms mediating the effects of irradiation on the hippocampus might be associated with alterations in hippocampal DNA methylation. Changes in cytosine methylation involving the addition of a methyl group to cytosine (5 mC) and especially those involving the addition of a hydroxy group to 5 mC (hydroxymethylcytosine or 5 hmC) play a key role in regulating the expression of genes required for hippocampal function. In this review article, we will discuss the effects of radiation on hippocampal DNA methylation and whether these effects are associated with hippocampus-dependent cognitive measures and molecular measures in the hippocampus involved in cognitive measures. We will also discuss whether the radiation-induced changes in hippocampal DNA methylation show an overlap across different doses of heavy ion irradiation and across irradiation with different ions. We will also discuss whether the DNA methylation changes show a tissue-dependent response.

DNA damage in the brain is influenced by endogenous processes and metabolism along with exogenous exposures. Accumulation of DNA damage in the brain can contribute to various neurological disorders, including neurodegenerative diseases and neuropsychiatric disorders. Traditional methods for assessing DNA damage in the brain, such as immunohistochemistry and mass spectrometry, have provided valuable insights but are limited by their inability to map specific DNA adducts and regional distributions within the brain or genome. Recent advancements in DNA damage detection methods offer new opportunities to address these limitations and further our understanding of DNA damage and repair in the brain. Here, we review emerging techniques offering more precise and sensitive ways to detect and quantify DNA lesions in the brain or neural cells. We highlight the advancements and applications of these techniques and discuss their potential for determining the role of DNA damage in neurological disease.

Serotonin syndrome is a toxidrome consisting of autonomic instability, altered mentation, hyperreflexia, clonus, and seizures. It is suspected to be due to either elevated serotonin concentrations or overstimulation of 5-hydroxytryptamine (5-HT) receptors. There are at least seven families of serotonin or 5-HT receptors along with multiple subtypes. The 5-HT1A and 5-HT2A serotonin receptor subtypes are heavily suspected to cause the broad spectrum of symptoms seen in serotonin syndrome. We present the case of a young woman treated with multiple psychotropic medications who developed serotonin syndrome (SS) after receiving electroconvulsive therapy (ECT). She had multiple psychiatric hospitalizations, and ECT was determined to be the appropriate course of treatment due to her treatment-resistant symptoms and catatonia. The case was unique as she tolerated multiple ECT treatments over a few weeks before the acute onset of serotonin syndrome following her eighth treatment, and she did not have any medication changes after the second ECT treatment. The patient’s acute presentation of rigidity, elevated temperature, hyperreflexia, diaphoresis, confusion, and psychomotor agitation led to a diagnosis of serotonin syndrome. ECT is a neuromodulatory procedure approved for treatment-resistant depression and schizophrenia that involves electrically stimulating the brain with electrodes on the scalp to induce a seizure. The mechanism by which ECT confers therapeutic benefit for patients with neuropsychiatric conditions is not entirely understood. We discuss some of the literature on SS and ECT to better understand the potential for a causal relationship.

Introduction: The space environment astronauts experience during space missions consists of multiple environmental challenges, including microgravity. In this study, we assessed the behavioral and cognitive performances of male Fisher rats 2 months after sham irradiation or total body irradiation with photons in the absence or presence of simulated microgravity. We analyzed the plasma collected 9 months after sham irradiation or total body irradiation for distinct alterations in metabolic pathways and to determine whether changes to metabolic measures were associated with specific behavioral and cognitive measures.Methods: A total of 344 male Fischer rats were irradiated with photons (6 MeV; 3, 8, or 10 Gy) in the absence or presence of simulated weightlessness achieved using hindlimb unloading (HU). To identify potential plasma biomarkers of photon radiation exposure or the HU condition for behavioral or cognitive performance, we performed regression analyses.Results: The behavioral effects of HU on activity levels in an open field, measures of anxiety in an elevated plus maze, and anhedonia in the M&M consumption test were more pronounced than those of photon irradiation. Phenylalanine, tyrosine, and tryptophan metabolism, and phenylalanine metabolism and biosynthesis showed very strong pathway changes, following photon irradiation and HU in animals irradiated with 3 Gy. Here, 29 out of 101 plasma metabolites were associated with 1 out of 13 behavioral measures. In the absence of HU, 22 metabolites were related to behavioral and cognitive measures. In HU animals that were sham-irradiated or irradiated with 8 Gy, one metabolite was related to behavioral and cognitive measures. In HU animals irradiated with 3 Gy, six metabolites were related to behavioral and cognitive measures.Discussion: These data suggest that it will be possible to develop stable plasma biomarkers of behavioral and cognitive performance, following environmental challenges like HU and radiation exposure.

PurposeTo examine body weight change in women undergoing in vitro fertilization and embryo transfer (IVF-ET) using antagonist protocol after up to three treatment cycles.MethodsA prospective cohort study among IVF patients treated between 2018 and 2019. Each patient underwent weight measurement three times during the treatment cycle: before treatment, at the beginning of the hormonal stimulation, and at the completion of the cycle, on the day of the pregnancy test. Data were also analyzed according to the body mass index (BMI) groups for normal weight, overweight, and obese patients. Finally, weight changes were recorded following altogether 519 treatment cycles, 240, 131, and 148 cycles, for normal weight, overweight, and obese patients, respectively.ResultsThe change in the patient's weight was clinically non-significant either during the waiting period or during gonadotropin administration, and overall, during the first, second, or third treatment cycles. The recorded mean total weight change of 0.26 ± 1.85, 0.4 ± 1.81, and 0.17 ± 1.7, after the first, second, or third treatment cycles, represent a change of 0.36%, 0.56%, and 0.23% of their initial weights, respectively. This change of less than 1% of the body weight falls short of the clinically significant weight gain of 5%–7%. Analyzing the data for the various BMI groups, the changes observed in body weight were under 1%, hence with no clinical significance.ConclusionThe findings of the study reject the myth that hormone therapy involves clinically significant weight gain, and this can lower the concerns of many patients who are candidates for treatment of assisted reproductive technology.

According to the World Health Organization, hundreds of individuals commence wheelchair use daily, often due to an injury such as spinal cord injury or through a condition such as a stroke. However, manual wheelchair users typically experience reductions in individual community mobility and participation. In this review, articles from 2017 to 2023 were reviewed to identify means of measuring community mobility and participation of manual wheelchair users, factors that can impact these aspects, and current rehabilitation techniques for improving them. The selected articles document current best practices utilizing self-surveys, in-clinic assessments, and remote tracking through GPS and accelerometer data, which rehabilitation specialists can apply to track their patients’ community mobility and participation accurately. Furthermore, rehabilitation methods such as wheelchair training programs, brain-computer interface triggered functional electric stimulation therapy, and community-based rehabilitation programs show potential to improve the community mobility and participation of manual wheelchair users. Recommendations were made to highlight potential avenues for future research.

IntroductionThe COVID-19 pandemic has highlighted the need to identify mechanisms of antiviral host defense against SARS-CoV-2. One such mediator is interferon-g (IFN-γ), which, when administered to infected patients, is reported to result in viral clearance and resolution of pulmonary symptoms. IFN-γ treatment of a human lung epithelial cell line triggered an antiviral activity against SARS-CoV-2, yet the mechanism for this antiviral response was not identified.MethodsGiven that IFN-γ has been shown to trigger antiviral activity via the generation of nitric oxide (NO), we investigated whether IFN-γ induction of antiviral activity against SARS-CoV-2 infection is dependent upon the generation of NO in human pulmonary epithelial cells. We treated the simian epithelial cell line Vero E6 and human pulmonary epithelial cell lines, including A549-ACE2, and Calu-3, with IFN-γ and observed the resulting induction of NO and its effects on SARS-CoV-2 replication. Pharmacological inhibition of inducible nitric oxide synthase (iNOS) was employed to assess the dependency on NO production. Additionally, the study examined the effect of interleukin-1b (IL-1β) on the IFN-g-induced NO production and its antiviral efficacy.ResultsTreatment of Vero E6 cells with IFN-γ resulted in a dose-responsive induction of NO and an inhibitory effect on SARS-CoV-2 replication. This antiviral activity was blocked by pharmacologic inhibition of iNOS. IFN-γ also triggered a NO-mediated antiviral activity in SARS-CoV-2 infected human lung epithelial cell lines A549-ACE2 and Calu-3. IL-1β enhanced IFN-γ induction of NO, but it had little effect on antiviral activity.DiscussionGiven that IFN-g has been shown to be produced by CD8+ T cells in the early response to SARS-CoV-2, our findings in human lung epithelial cell lines, of an IFN-γ-triggered, NO-dependent, links the adaptive immune response to an innate antiviral pathway in host defense against SARS-CoV-2. These results underscore the importance of IFN-γ and NO in the antiviral response and provide insights into potential therapeutic strategies for COVID-19.

Thrombus formation is highly dependent upon the physico-chemical environment in which it is triggered. Our ability to understand how thrombus formation is initiated, regulated, and resolved in the human body is dependent upon our ability to replicate the mechanical and biological properties of the arterial wall. Current in vitro thrombosis models principally use reductionist approaches to model the complex biochemical and cellular milieu present in the arterial wall, and so researcher have favored the use of in vivo models. The field of vascular tissue engineering has developed a range of techniques for culturing artificial human arteries for use as vascular grafts. These techniques therefore provide a basis for developing more sophisticated 3D replicas of the arterial wall that can be used in in vitro thrombosis models. In this review, we consider how tissue engineering approaches can be used to generate 3D models of the arterial wall that improve upon current in vivo and in vitro approaches. We consider the current benefits and limitations of reported 3D tissue engineered models and consider what additional evidence is required to validate them as alternatives to current in vivo models.

Objective: Dimethylsulfoxide-cryopreserved platelets are being evaluated for treatment of acute hemorrhage in patients with thrombocytopenia or platelet dysfunction when liquid stored platelets are unavailable. Patients undergoing cardiac surgery with cardiopulmonary bypass with risk factors for significant bleeding represent a population for which determining efficacy and safety of cryopreserved platelets is ideal in the clinical trial setting. The primary objective is to compare blood loss in cardiopulmonary bypass patients receiving cryopreserved platelets or liquid stored platelets. Methods: In patients undergoing cardiac surgery utilizing cardiopulmonary bypass, a standardized algorithm with transfusion triggers will be used to guide the intra- and postoperative administration of study platelets, either cryopreserved platelets or liquid stored platelets, based on the clinical presentation. The primary efficacy end point was the volume of blood loss from completion of chest closure (time 0) until the time chest tubes were removed or 24 hours after chest closure, whichever is earlier. Results: This design article describes an ongoing multicenter, randomized, blinded trial to evaluate noninferiority or superiority of cryopreserved platelets with liquid stored platelets in controlling blood loss in patients undergoing cardiopulmonary bypass surgery. Conclusions: Frozen storage could substantially safely extend the shelf life of stored platelets. If efficacy and safety were demonstrated in this trial, current constraints on platelet use in low resource military and civilian settings would be relieved.

The CD47 “don’t eat me” marker is upregulated following exposure to DNA damaging agents, including irradiation, a process that is dependent on Mre11, a key player in the DNA damage response pathway.

Abstract Background Pituitary apoplexy is acute infarction with or without hemorrhage of the pituitary gland. It is a rare but potentially life-threatening emergency that most commonly occurs in the setting of pituitary adenoma. The mechanisms underlying pituitary apoplexy are not well understood, but are proposed to include factors of both hemodynamic supply and adenoma demand. In the case of patients with known pituitary macroadenomas undergoing major surgery for other indications, there is a theoretically increased risk of apoplexy in the setting of “surgical stress.” However, risk stratification of patients with nonfunctioning pituitary adenomas prior to major surgery is challenging because the precipitating factors for pituitary apoplexy are not completely understood. Here we present a case in which intraoperative hypovolemia is a possible mechanistic precipitating factor for pituitary apoplexy. Case presentation A 76-year-old patient with a known hypofunctioning pituitary macroadenoma underwent nephrectomy for renal cell carcinoma, during which there was significant intraoperative blood loss. He became symptomatic with ophthalmoplegia on the second postoperative day, and was diagnosed with pituitary apoplexy. He was managed conservatively with cortisol replacement therapy, and underwent therapeutic anticoagulation 2 months after pituitary apoplexy for deep vein thrombosis. His ophthalmoplegia slowly resolved over months of follow-up. Pituitary apoplexy did not recur with therapeutic anticoagulation. Conclusions When considering the risk of surgery in patients with a known pituitary macroadenoma, an operation with possible high-volume intraoperative blood loss may have increased risk of pituitary apoplexy because intraoperative hypovolemia may precipitate ischemia, infarction, and subsequent hemorrhage. This may be particularly relevant in the cases of elective surgery. Additionally, we found that we were able to therapeutically anticoagulate a patient 2 months after pituitary apoplexy for the management of deep vein thrombosis without recurrence of pituitary apoplexy.

Background and Purpose: The interprofessional gap between neurosurgeons and neuroradiologists has been increasing steadily since the implementation of electronic health record systems and remote radiology readings. Our aim was to survey and report the current practices employed by neurosurgeons in utilizing neuroradiology reports for management of patients with lumbar spinal stenosis. Materials and Methods: A voluntary survey was distributed among a group of neurosurgeons affiliated with the United States Veterans Affairs Health System. Survey questions were aimed at assessing the trends and the subsequent practice patterns in neurosurgical utilization of neuroradiology reports in patients with LSS. Results: 20 out of 43 respondents across all surveyed VAHS centers completed the survey, achieving a 46.5% response rate. 95% (19/20) of respondents had an on-site radiologist, while 80% (16/20) had access to a neuroradiologist. 95% (19/20) of respondents report having imaging routinely read by a neuroradiologist. 40% (8/20) of the neurosurgeons read the ordered radiology reports less than 50% of the time. Only 20% of respondents always read the neuroradiology report. 60% (12/20) of the surveyed neurosurgeons frequently reported major discrepancies between imaging interpretation among neuroradiologists and the surveyed neurosurgeons, with only 45% (9/20) neurosurgeons contacting the neuroradiologist to discuss discrepancies. Furthermore, a majority of neurosurgeons do not routinely participate in conferences where imaging is discussed. Conclusions: Our results suggest that the increase in teleradiology and remote readings may cause neurosurgeons to largely ignore radiology reports and major discrepancies in imaging interpretation when treating suspected LSS. Whether such practices lead to altered surgical outcomes and affect healthcare costs warrants further investigation.

Gingival abscess is a localized, acute inflammatory lesion which is caused by various factors that include microbial plaque infection, foreign body impaction, and trauma. Management includes a simple incision and draining of the purulent exudate along with systemic antibiotics in most of the cases. This article reports a case of a 16-year-old female patient, with a chief complaint of painful and swollen gums in her lower right front tooth region of the jaw along with fever for the past 5 days. Emergency treatment of abscess drainage was done on day 1. On 5th day of review, the case presented with persistent signs of gingival inflammation in relation to 43 to 41. Considering the provisional diagnosis as dentigerous cyst with persistent gingival abscess, definitive treatment was performed by transalveolar extraction of the impacted canine and debridement of the osseous lesion. The histologic analysis of the lesion exhibited foci of eosinophilic coagulum-like areas with epicentric and radiating filamentous appearance at the periphery, which is suggestive of an inflamed dentigerous cyst with actinomycosis infection of periodontium.

Abstract Plasma apolipoprotein E levels were previously associated with the risk of developing Alzheimer’s disease (AD), levels of cerebrospinal fluid AD biomarkers, cognition and imaging brain measures. Outside the brain, the liver is the primary source of apoE and liver transplantation studies have demonstrated that liver-derived apoE does not cross the blood–brain-barrier. How hepatic apoE may be implicated in behavioral and cognitive performance is not clear. In the current study, we behaviorally tested FRGN mice with humanized liver harboring the ε3/ε3 genotype (E3-human liver (HL)) and compared their behavioral and cognitive performance with that of age-matched ε3/ε3 targeted replacement (E3-TR) mice, the latter produces human apoE3 throughout the body whereas the E3-HL mice endogenously produce human apoE3 only in the liver. We also compared the liver weights and plasma apoE levels, and assessed whether plasma apoE levels were correlated with behavioral or cognitive measures in both models. E3-HL were more active but performed cognitively worse than E3-TR mice. E3-HL mice moved more in the open field containing objects, showed higher activity levels in the Y maze, showed higher activity levels during the baseline period in the fear conditioning test than E3-TR mice, and swam faster than E3-TR mice during training to locate the visible platform in the water maze. However, E3-HL mice showed reduced spatial memory retention in the water maze and reduced fear learning and contextual and cued fear memory than E3-TR mice. Liver weights were greater in E3-HL than E3-TR mice and sex-dependent only in the latter model. Plasma apoE3 levels were similar to those found in humans and comparable in female and male E3-TR mice but higher in female E3-HL mice. Finally, we found correlations between plasma apoE levels and behavioral and cognitive measures which were predominantly model-dependent. Our study demonstrates mouse-model dependent associations between plasma apoE levels, behavior and cognition in an ‘AD-neutral’ setting and suggests that a humanized liver might be sufficient to induce mouse behavioral and cognitive phenotypes.

Introduction: The response of the brain to space radiation is an important concern for astronauts during space missions. Therefore, we assessed the response of the brain to 28Si ion irradiation (600 MeV/n), a heavy ion present in the space environment, on cognitive performance and whether the response is associated with altered DNA methylation in the hippocampus, a brain area important for cognitive performance.Methods: We determined the effects of 28Si ion irradiation on object recognition, 6-month-old mice irradiated with 28Si ions (600 MeV/n, 0.3, 0.6, and 0.9 Gy) and cognitively tested two weeks later. In addition, we determined if those effects were associated with alterations in hippocampal networks and/or hippocampal DNA methylation.Results: At 0.3 Gy, but not at 0.6 Gy or 0.9 Gy, 28Si ion irradiation impaired cognition that correlated with altered gene expression and 5 hmC profiles that mapped to specific gene ontology pathways. Comparing hippocampal DNA hydroxymethylation following proton, 56Fe ion, and 28Si ion irradiation revealed a general space radiation synaptic signature with 45 genes that are associated with profound phenotypes. The most significant categories were glutamatergic synapse and postsynaptic density.Discussion: The brain’s response to space irradiation involves novel excitatory synapse and postsynaptic remodeling.

Magnetic Resonance Imaging (MRI) T2-weighted white matter hyperintensity (WMH) is a marker of small vessel cerebrovascular pathology and is of ischemic origin. The prevalence and severity of WMH is associated with cardiovascular risk factors, aging, and cognitive injury in mild cognitive impairment (MCI), vascular dementia, and Alzheimer’s disease (AD). WMH especially affects executive function, with additional effects on memory and global cognition. Apolipoprotein E (apoE) plays a role in cholesterol metabolism and neuronal repair after injury. Human and animal studies support a role for apoE in maintaining white matter integrity. In humans, there are three major human apoE isoforms, E2, E3, and E4. Human apoE isoforms differ in risk to develop AD and in association with WMH. In this Mini Review, we propose an increased focus on the role of WMH in cognitive health and cognitive injury and the likely role of apoE and apoE isoform in modulating these effects. We hypothesize that apoE and apoE isoforms play a role in modulating WMH via apoE isoform-dependent effects on oxylipins and 7-ketocholesterol, as well as amyloid related vascular injury, as seen in cerebral amyloid angiopathy.

Abstract Tight regulation of immediate early gene (IEG) expression is important for synaptic plasticity, learning, and memory. Recent work has suggested that DNA double strand breaks (DSBs) may have an adaptive role in post-mitotic cells to induce IEG expression. Physiological activity in cultured neurons as well as behavioral training leads to increased DSBs and subsequent IEG expression. Additionally, infusion of etoposide—a common cancer treatment that induces DSBs—impairs trace fear memory. Here, we assessed the effects of hippocampal infusion of 60 ng of etoposide on IEG expression, learning, and memory in 3–4 month-old C57Bl/6J mice. Etoposide altered expression of the immediate early genes cFos and Arc in the hippocampus and impaired hippocampus-dependent contextual fear memory. These data add to the growing evidence that DSBs play an important role in IEG expression, learning, and memory, opening avenues for developing novel treatment strategies for memory-related disorders.

Abstract To combat the various DNA lesions and their harmful effects, cells have evolved different strategies, collectively referred as DNA damage response (DDR). The DDR largely relies on intranuclear protein networks, which sense DNA lesions, recruit DNA repair enzymes, and coordinates several aspects of the cellular response, including a temporary cell cycle arrest. In addition, external cues mediated by the surface EGF receptor (EGFR) through downstream signaling pathways contribute to the cellular DNA repair capacity. However, cell cycle progression driven by EGFR activation should be reconciled with cell cycle arrest necessary for effective DNA repair. Here, we show that in damaged cells, the expression of Mig-6 (mitogen-inducible gene 6), a known regulator of EGFR signaling, is reduced resulting in heightened EGFR phosphorylation and downstream signaling. These changes in Mig-6 expression and EGFR signaling do not occur in cells deficient of Mre-11, a component of the MRN complex, playing a central role in double-strand break (DSB) repair or when cells are treated with the MRN inhibitor, mirin. RNAseq and functional analysis reveal that DNA damage induces a shift in cell response to EGFR triggering that potentiates DDR-induced p53 pathway and cell cycle arrest. These data demonstrate that the cellular response to EGFR triggering is skewed by components of the DDR, thus providing a plausible explanation for the paradox of the known role played by a growth factor such as EGFR in the DNA damage repair.

Abstract Post-Traumatic Stress Disorder (PTSD) is a highly prevalent mental health disorder. Due to the high level of variability in susceptibility and severity, PTSD therapies are still insufficient. In addition to environmental exposures, genetic risks play a prominent role and one such factor is apolipoprotein E. The protein (apoE) is functionally involved in cholesterol transport and metabolism and exists as 3 major isoforms in humans: E2, E3, and E4. To model the role of apolipoprotein E isoform in stress-related changes in behavior and cognition, female and male mice (3–5 months of age) expressing E2, E3, or E4 were used. Mice were either placed into control groups or exposed to chronic variable stress (CVS), which has been shown to induce PTSD-like behavioral and neuroendocrine changes. E2 mice showed a unique response to CVS compared to E3 and E4 mice that included impaired spatial learning and memory, increased adrenal gland weight, and no increase in glucocorticoid receptor protein levels (normalized to apoE levels). In addition, the cholesterol metabolite 7-ketocholesterol was elevated in the cortex after CVS in E3 and E4, but not E2 female mice. E2 confers unique changes in behavioral, cognitive, and biomarker profiles after stress exposure and identify 7-ketocholesterol as a possible novel biomarker of the traumatic stress response. We further explored the relationship between E2 and PTSD in an understudied population by genotyping 102 patients of Cambodian and Vietnamese ethnicity. E2 carriers demonstrated a higher odds ratio of having a PTSD diagnosis compared to E3/E3 carriers, supporting that the E2 genotype is associated with PTSD diagnosis after trauma exposure in this population.

We assessed the effects of conventional and ultra-high dose rate (UHDR) electron irradiation on behavioral and cognitive performance one month following exposure and assessed whether these effects were associated with alterations in the number of immune cells in the hippocampus using flow cytometry. Two-month-old female and male C57BL/6J mice received whole-brain conventional or UHDR irradiation. UHDR mice were irradiated with 9 MeV electrons, delivered by the Linac-based/modified beam control. The mice were irradiated or sham-irradiated at Dartmouth, the following week shipped to OHSU, and behaviorally and cognitively tested between 27 and 41 days after exposure. Conventional- and UHDR-irradiated mice showed impaired novel object recognition. During fear learning, conventional- and UHDR-irradiated mice moved less during the inter-stimulus interval (ISI) and UHDR-irradiated mice also moved less during the baseline period (prior to the first tone). In irradiated mice, reduced activity levels were also seen in the home cage: conventional- and UHDR-irradiated mice moved less during the light period and UHDR-irradiated mice moved less during the dark period. Following behavioral and cognitive testing, infiltrating immune cells in the hippocampus were analyzed by flow cytometry. The percentage of Ly6G+ CD45+ cells in the hippocampus was lower in conventional- and UHDR-irradiated than sham-irradiated mice, suggesting that neutrophils might be particularly sensitive to radiation. The percentage of Ly6G+ CD45+ cells in the hippocampus was positively correlated with the time spent exploring the novel object in the object recognition test. Under the experimental conditions used, cognitive injury was comparable in conventional and UHDR mice. However, the percentage of CD45+ CD11b+ Ly6+ and CD45+ CD11b+ Ly6G- cells in the hippocampus cells in the hippocampus was altered in conventional- but not UHDR-irradiated mice and the reduced percentage of Ly6G+ CD45+ cells in the hippocampus might mediate some of the detrimental radiation-induced cognitive effects.

While solar energy has been an emerging source of renewable energy for many years now with various studies delving into building more robust and compact solar cells, their use as a power source for mobile and small machinery such as Wireless Sensor Networks (WSN) is less discussed. However, with increasing global efforts in subsidizing more sustainable technology and energy, many studies have emerged in the past decade on building solar power based wireless sensor networks. The combination of novel harvesting circuits, mechanisms to obtain maximum possible power, smart power management algorithms and improving energy technology has provided the necessary framework for self-powered WSN nodes that have much longer lifetime. This paper reviews the newer proposed technology that aids the development of Solar Energy Harvesting Wireless Sensor Networks.

The smart grid model is developed with some changes to help in implementing a demand response program which was initially developed for a Pecan Street project. Correspondingly, the real-time solar and load data are collected from the data port for the city of Austin. A single day is selected for our analysis of all four seasons of the year. The flat rate, and real-time and day-ahead pricing information are collected from ComEd. The key challenge for addressing business problems is the flexibility of consumption. However, without considering the properties of loss aversion, the system would not be a practical solution. So, in this article, a dynamic demand response program based on price elasticity that integrates loss aversion characteristics is proposed. The proposed system is compared for all pricing schemes and all seasons. Four scenarios are created for peak time rebate with different combinations of loss aversion factor values and all the possible combinations of rebates. This article directs how these combinations could change the demand curve and how the utility can make a decision about the specific importance of the criteria, such as the total demand carrying capacity, peak demand reduction, and in obtaining optimum profit for utility and the consumer.

Abstract Background The combination of multi-parametric MRI to locate and define suspected lesions together with their being targeted by an MRI-guided prostate biopsy has succeeded in increasing the detection rate of clinically significant disease and lowering the detection rate of non-significant prostate cancer. In this work we investigate the urologist’s learning curve of in-bore MRI-guided prostate biopsy which is considered to be a superior biopsy technique. Materials and methods Following Helsinki approval by The Chaim Sheba Medical Center ethics committee in accordance with The Sheba Medical Center institutional guidelines (5366-28-SMC) we retrospectively reviewed 110 IB-MRGpBs performed from 6/2016 to 1/2019 in a single tertiary center. All patients had a prostate multi-parametric MRI finding of at least 1 target lesion (prostate imaging reporting and data system [PI-RADS] score ≥ 3). We analyzed biopsy duration and clinically significant prostate cancer detection of targeted sampling in 2 groups of 55 patients each, once by a urologist highly trained in IB-MRGpBs and again by a urologist untrained in IB-MRGpBs. These two parameters were compared according to operating urologist and chronologic order. Results The patients’ median age was 68 years (interquartile range 62–72). The mean prostate-specific antigen level and prostate size were 8.6 ± 9.1 ng/d and 53 ± 27 cc, respectively. The mean number of target lesions was 1.47 ± 0.6. Baseline parameters did not differ significantly between the 2 urologists’ cohorts. Overall detection rates of clinically significant prostate cancer were 19%, 55%, and 69% for PI-RADS 3, 4 and 5, respectively. Clinically significant cancer detection rates did not differ significantly along the timeline or between the 2 urologists. The average duration of IB-MRGpB targeted sampling was 28 ± 15.8 min, correlating with the number of target lesions (p

Abstract In the brain, apolipoprotein E (apoE) plays an important role in lipid transport and response to environmental and age-related challenges, including neuronal repair following injury. While much has been learned from radiation studies in rodents, a gap in our knowledge is how radiation might affect the brain in primates. This is important for assessing risk to the brain following radiotherapy as part of cancer treatment or environmental radiation exposure as part of a nuclear accident, bioterrorism, or a nuclear attack. In this study, we investigated the effects of ionizing radiation on brain volumes and apoE levels in the prefrontal cortex, amygdala, and hippocampus of Rhesus macaques that were part of the Nonhuman Primate Radiation Survivor Cohort at the Wake Forest University. This unique cohort is composed of Rhesus macaques that had previously received single total body doses of 6.5–8.05 Gy of ionizing radiation. Regional apoE levels predicted regional volume in the amygdala and the prefrontal cortex. In addition, apoE levels in the amygdala, but not the hippocampus, strongly predicted relative hippocampal volume. Finally, radiation dose negatively affected relative hippocampal volume when apoE levels in the amygdala were controlled for, suggesting a protective compensatory role of regional apoE levels following radiation exposure. In a supplementary analysis, there also was a robust positive relationship between the neuroprotective protein α-klotho and apoE levels in the amygdala, further supporting the potentially protective role of apoE. Increased understanding of the effects of IR in the primate brain and the role of apoE in the irradiated brain could inform future therapies to mitigate the adverse effects of IR on the CNS.

Increasing frequencies of severe heat waves and drought are expected to influence the composition and functioning of ecosystems globally. Our ability to predict and mitigate these impacts depends on our understanding of species- and age-specific responses to these stressors. To assess the adaptive capacity of balsam fir to climate change, a cold-adapted boreal tree species, we conducted a climate-controlled greenhouse experiment with four provenances originating from across the species biogeographic range, 12 temperature treatments ensuring a minimum of +11°C warming, and five drought treatment intensities. We found considerable acclimation to temperature and drought treatments across all provenances, with steady gains in biomass under temperatures well-beyond the “worst-case” (RCP 8.5) climate forcing scenario within the species natural range. Acclimation was supported by high phenotypic plasticity in root:shoot ratio (RSR) and photosynthesis, which were greatly increased with warming, but were not affected by drought. Our results suggest that regardless of the observed provenance variation, drought and heat are not limiting factors of the current-year balsam fir seedling growth, instead, these factors may be more impactful on later stages of regeneration or previously stressed individuals, thus highlighting the necessity of incorporating the factors of ontogeny and provenance origin in future research regarding plant and climate interactions.

Abstract Age, apolipoprotein E (apoE) isoform, sex, and diet can independently affect the risk for the development of Alzheimer’s disease (AD). Additionally, synergy between some of these risk factors have been observed. However, the relation between the latter three risk factors has not been investigated. Central nervous system (CNS) insulin resistance is commonly involved in each of these risk factors. CNS insulin is primarily derived from the periphery in which insulin must be transported across the blood–brain barrier (BBB). Additionally, insulin can bind the brain endothelial cell to affect intracellular signaling. Therefore, we hypothesized CNS access to insulin could be affected by the combination of apoE isoform, sex, and diet. We analyzed insulin BBB pharmacokinetics in aged apoE targeted replacement (E3 and E4) male and female mice on a low-fat and high-fat diet. There were differences within males and females due to apoE genotype and diet in insulin interactions at the BBB. These sex-, diet-, and apoE isoform-dependent differences could contribute to the cognitive changes observed due to altered CNS insulin signaling.

Consumption of a high fat diet (HFD) is linked to metabolic syndrome and cognitive impairments. This is exacerbated in age-related cognitive decline (ACD) and in individuals with a genetic risk for Alzheimer’s disease (AD). Apolipoprotein E (apoE) is involved in cholesterol metabolism. In humans, there are three major isoforms, E2, E3, and E4. Compared to E3, E4 increases ACD and AD risk and vulnerability to the deleterious cognitive effects of a HFD. The plant compound Xanthohumol (XN) had beneficial effects on cognition and metabolism in C57BL/6J wild-type (WT) male mice put on a HFD at 9 weeks of age for 13 weeks. As the effects of XN in the context of a HFD in older WT, E3, and E4 female and male mice are not known, in the current study male and female WT, E3, and E4 mice were fed a HFD alone or a HFD containing 0.07% XN for 10 or 19 weeks, starting at 6 months of age, prior to the beginning of behavioral and cognitive testing. XN showed sex- and ApoE isoform-dependent effects on cognitive performance. XN-treated E4 and WT, but not E3, mice had higher glucose transporter protein levels in the hippocampus and cortex than HFD-treated mice. E3 and E4 mice had higher glucose transporter protein levels in the hippocampus and lower glucose transporter protein levels in the cortex than WT mice. In the standard experiment, regardless of XN treatment, E4 mice had nearly double as high ceramide and sphingomyelin levels than E3 mice and male mice had higher level of glycosylated ceramide than female mice. When the differential effects of HFD in E3 and E4 males were assessed, the arginine and proline metabolism pathway was affected. In the extended exposure experiment, in E3 males XN treatment affected the arginine and proline metabolism and the glycine, serine, and threonine metabolism. Myristic acid levels were decreased in XN-treated E3 males but not E3 females. These data support the therapeutic potential for XN to ameliorate HFD-induced cognitive impairments and highlight the importance of considering sex and ApoE isoform in determining who might most benefit from this dietary supplement.

This review focuses on the effects of exercise on various health-related outcomes in cancer survivors, encompassing body composition, cognitive function (including sleep), and gut microbiome health. By analyzing multiple studies, we aimed to summarize the existing evidence and shed light on underlying mechanisms. The findings strongly suggest that exercise serves as a multifaceted non-pharmacological strategy, playing a significant role in improving the overall health of cancer survivors by effectively reducing inflammation and oxidative stress. Exercise plays a crucial role in preventing muscle wasting, diminishing the presence of reactive oxygen species and pro-inflammatory cytokines, and enhancing antioxidant systems. Furthermore, exercise displays notable benefits in terms of executive cognitive functioning and fatigue alleviation, largely attributed to its anti-inflammatory impact on the central nervous system and its ability to induce neurogenesis via growth factors. Additionally, exercise positively influences microbial diversity, reduces gut inflammation, and enhances neurogenesis through the gut–brain axis. Our key findings underscore the reduction of oxidative stress and inflammation as primary mechanisms by which exercise effectively enhances health outcomes in cancer survivors. By delving deeper into these candidate mechanisms, we aim to provide valuable guidance for future research and interventions targeting the symptoms experienced by cancer survivors.

Current in vitro thrombosis models utilise simplistic 2D surfaces coated with purified components of the subendothelial matrix. The lack of a realistic humanised model has led to greater study of thrombus formation in in vivo tests in animals. Here we aimed to develop 3D hydrogel-based replicas of the medial and adventitial layers of the human artery to produce a surface that can optimally support thrombus formation under physiological flow conditions. These tissue-engineered medial- (TEML) and adventitial-layer (TEAL) hydrogels were developed by culturing human coronary artery smooth muscle cells and human aortic adventitial fibroblasts within collagen hydrogels, both individually and in co-culture. Platelet aggregation upon these hydrogels was studied using a custom-made parallel flow chamber. When cultured in the presence of ascorbic acid, the medial-layer hydrogels were able to produce sufficient neo-collagen to support effective platelet aggregation under arterial flow conditions. Both TEML and TEAL hydrogels possessed measurable tissue factor activity and could trigger coagulation of platelet-poor plasma in a factor VII-dependent manner. Biomimetic hydrogel replicas of the subendothelial layers of the human artery are effective substrates for a humanised in vitro thrombosis model that could reduce animal experimentation by replacing current in vivo models.

Abstract The space radiation environment consists of multiple species of charged particles, including 28Si ions, that may impact brain function during and following missions. To develop biomarkers of the space radiation response, BALB/c and C3H female and male mice and their F2 hybrid progeny were irradiated with 28Si ions (350 MeV/n, 0.2 Gy) and tested for behavioral and cognitive performance 1, 6, and 12 months following irradiation. The plasma of the mice was collected for analysis of miRNA levels. Select pertinent brain regions were dissected for lipidomic analyses and analyses of levels of select biomarkers shown to be sensitive to effects of space radiation in previous studies. There were associations between lipids in select brain regions, plasma miRNA, and cognitive measures and behavioral following 28Si ion irradiation. Different but overlapping sets of miRNAs in plasma were found to be associated with cognitive measures and behavioral in sham and irradiated mice at the three time points. The radiation condition revealed pathways involved in neurodegenerative conditions and cancers. Levels of the dendritic marker MAP2 in the cortex were higher in irradiated than sham-irradiated mice at middle age, which might be part of a compensatory response. Relationships were also revealed with CD68 in miRNAs in an anatomical distinct fashion, suggesting that distinct miRNAs modulate neuroinflammation in different brain regions. The associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28Si ion irradiation could be used for the development of biomarker of the space radiation response.

Abstract Background Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome. Methods This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan–Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality. Results A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow–Pittsburgh Cerebral Performance Categories 1–2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow 6.8 and lactate 15 mmol/L (RR 1.16, 95% CI 1.16–1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52–0.76). Conclusions A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.

Vascular cognitive impairment (VCI) is the second most common cause of dementia. There is no treatment for VCI, in part due to a lack of understanding of the underlying mechanisms. The G-protein coupled receptor 39 (GPR39) is regulated by arachidonic acid (AA)-derived oxylipins that have been implicated in VCI. Furthermore, GPR39 is increased in microglia of post mortem human brains with VCI. Carriers of homozygous GPR39 SNPs have a higher burden of white matter hyperintensity, an MRI marker of VCI. We tested the hypothesis that GPR39 plays a protective role against high-fat diet (HFD)-induced cognitive impairment, in part mediated via oxylipins actions on cerebral blood flow (CBF) and neuroinflammation. Homozygous (KO) and heterozygous (Het) GPR39 knockout mice and wild-type (WT) littermates with and without HFD for 8 months were tested for cognitive performance using the novel object recognition (NOR) and the Morris water maze (MWM) tests, followed by CBF measurements using MRI. Brain tissue and plasma oxylipins were quantified with high-performance liquid chromatography coupled to mass spectrometry. Cytokines and chemokines were measured using a multiplex assay. KO mice, regardless of diet, swam further away from platform location in the MWM compared to WT and Het mice. In the NOR test, there were no effects of genotype or diet. Brain and plasma AA-derived oxylipins formed by 11- and 15-lipoxygenase (LOX), cyclooxygenase (COX) and non-enzymatically were increased by HFD and GPR39 deletion. Interleukin-10 (IL-10) was lower in KO mice on HFD than standard diet (STD), whereas IL-4, interferon γ-induced protein-10 (IP-10) and monocyte chemotactic protein-3 (MCP-3) were altered by diet in both WT and KO, but were not affected by genotype. Resting CBF was reduced in WT and KO mice on HFD, with no change in vasoreactivity. The deletion of GPR39 did not change CBF compared to WT mice on either STD or HFD. We conclude that GPR39 plays a role in spatial memory retention and protects against HFD-induced cognitive impairment in part by modulating inflammation and AA-derived oxylipins. The results indicate that GPR39 and oxylipin pathways play a role and may serve as therapeutic targets in VCI.