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There is generally a lack of knowledge on how marine organic carbon accumulation is linked to vertical export and primary productivity patterns in the Arctic Ocean. Despite the fact that annual primary production in the Arctic has increased as a consequence of shrinking sea ice, its effect on flux, preservation, and accumulation of organic carbon is still not well understood. In this study, a multi-proxy geochemical and organic-sedimentological approach is coupled with organic facies modelling, focusing on regional calculations of carbon cycling and carbon burial on the western Barents Shelf between northern Scandinavia and Svalbard. OF-Mod 3-D, an organic facies modelling software tool, is used to reconstruct and quantify the marine and terrestrial organic carbon fractions and to make inferences about marine primary productivity changes across the marginal ice zone (MIZ). By calibrating the model against an extensive set of sediment surface samples, we improve the Holocene organic carbon budget for ice-free and seasonally ice-covered areas in the western Barents Sea. The results show that higher organic carbon accumulation rates in the MIZ are best explained by enhanced surface water productivity compared to ice-free regions, implying that shrinking sea ice may reveal a significant effect on the overall organic carbon storage capacity of the western Barents Sea shelf [ABSTRACT FROM AUTHOR]

There is generally a lack of knowledge on how marine organic carbon accumulation is linked to vertical export and primary productivity patterns. In this study, a multi-proxy geochemical and organic-sedimentological approach is coupled with organic facies modelling focusing on regional calculations of carbon cycling and carbon burial on the western Barents shelf between northern Scandinavia and Svalbard. OF-Mod 3D, an organic facies modelling software tool, is used to reconstruct the marine and terrestrial organic carbon fractions and to make inferences about marine primary productivity in this region. The model is calibrated with an extensive sample dataset and reproduces the present-day regional distribution of the organic carbon fractions well. Based on this new organic facies model, we present regional carbon mass accumulation rate calculations for the western Barents Sea. [ABSTRACT FROM AUTHOR]

In this paper, we discuss the relationship between the organic matter, sulphur and phosphate contents of Upper Cretaceous marine carbonates (Karabogaz Formation) in the Adiyaman Petroleum Province of SE Turkey. The results of organic geochemical analyses of core samples obtained from the Karabogaz Formation suggest that phosphate deposition occurred in settings where the water column was oxic to sub-oxic. However, the preservation of organic matter was favoured in anoxic environments. Moreover, the presence of sulphur (especially sulphur incorporated into kerogen) in organic matter-rich layers led to early oil generation. The results of stepwise py-gc analyses are consistent with a model in which, with increasing maturity, S-S and C-S bonds are the first to be eliminated from the macromolecular kerogen structure. Study of the maturity evolution of S-rich kerogen by laboratory pyrolysis implies that marginally mature and/or mature kerogen in the Karabogaz Formation, which may be classified as classic 'Type II' kerogen, was most probably Type II/S at lower maturity stages. This enabled oil generation to occur at relatively shallow burial depths and relatively early stages of maturation. It is reasonable to conclude that Type II/S kerogen, overlooked in previous studies, was abundant in TOC-rich intervals in the Karabogaz Formation. Early generation (and expulsion) from Type II/S kerogen may have sourced the sulphur-rich oils in the Adiyaman area oilfields. [ABSTRACT FROM AUTHOR]

α2-Macroglobulin (A2M) is a proteinase inhibitor found in association with senile plaques (SP) in Alzheimer's disease (AD). A2M has been implicated biochemically in binding and degradation of the amyloid β(Aβ) protein which accumulates in SP. We studied the relationship between Alzheimer's disease and a common A2M polymorphism, Val1000 (GTC)/lle1000 (ATC), which occurs near the thiolester active site of the molecule. In an initial exploratory data set (90 controls and 171 Alzheimer's disease) we noted an increased frequency of the G/G genotype from 0.07 to 0.12. We therefore tested the hypothesis that the G/G genotype is over-represented in Alzheimer's disease in an additional independent data set: a group of 359 controls and 566 Alzheimer's disease patients. In the hypothesis testing cohort, the G/G genotype increased from 0.07 in controls to 0.12 in Alzheimer's disease (P < 0.05, Fisher's exact test). The odds ratio for Alzheimer's disease associated with the G/G genotype was 1.77 (1.16–2.70, P < 0.01) and in combination with APOE4 was 9.68 (95% CI 3.91–24.0, P < 0.001). The presence of the G allele was associated with an increase in Aβ burden in a small series. The A2M receptor, A2M-r/LRP, is a multifunctional receptor whose ligands include apolipoprotein E and the amyloid precursor protein. These four proteins have each been genetically linked to Alzheimer's disease, suggesting that they may participate in a common disease pathway. [ABSTRACT FROM AUTHOR]

In an attempt to define possible subgroups of Alzheimer's disease, 21 patients satisfying current clinical diagnostic criteria for this disorder were divided on the basis of progression rates of symptoms. Thirteen patients with relatively rapid intellectual deterioration did not differ from eight patients showing slow progression with respect to global intellectual performance, sex, or age at onset of symptoms. Neuropsychological testing revealed that although the two groups were indistinguishable in verbal or visuospatial functions associated with the parietotemporal cortex, the more rapidly deteriorating group had significantly greater impairment in executive functions attributed to the frontal lobe. PET scans showed equivalent reductions in glucose metabolism in the parietotemporal cortex, but patients with relatively fast progression had significantly greater hypometabolism frontally. These results suggest an association between relatively severe frontal lobe involvement and a rapid clinical course that might have important implications for the development of treatment strategies for patients with Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: In Southern Europe Olea europaea leafs are known as a folk remedy for hypertension. Cardiovascular diseases are still the leading causes of morbidity and mortality in industrialized countries with hypertension being one of the main risk factors. Aim of the study: We investigated effects of a commercial Olea europaea leaf extract (OLE) on isolated hearts and cultured cardiomyocytes. Materials and methods: Isolated rabbit hearts were perfused according to the Langendorff technique and connected to a 256-channel epicardial mapping system. Voltage clamp experiments were performed in cultured neonatal rat cardiomyocytes using a perforated-patch technique. Results: OLE caused a concentration-depended decrease in systolic left ventricular pressure and heart rate as well as an increase in relative coronary flow and a slight, but not significant prolongation of PQ-time. There were no significant changes between the groups in the activation-recovery interval and its dispersion, total activation time, peak-to-peak amplitude, percentage of identical breakthrough-points and similar vectors of local activation. Voltage clamp experiments in cultured neonatal rat cardiomyocytes showed a significant decrease in maximum I Ca,L by OLE which was reversible upon wash-out. Conclusions: OLE suppresses the L-type calcium channel directly and reversibly. Our findings might help to understand the traditional use of OLE in the treatment of cardiovascular disease. [Copyright &y& Elsevier]

Chapter 2 of the book "Advances in Parasitology" is presented. It explores the structure and content of the Entamoeba histolytica genome. It discusses that the intestinal parasite Entamoeba histolytica is one of the most widespread and clinically important parasites, as well as one of the first protists for which a draft genome sequence has been published.

Abstract: Hematopoietic stem cells (HSCs) are characterized by the ability to self-renew and to replenish the hematopoietic system. The cell-cycle kinase cyclin-dependent kinase 6 (CDK6) regulates transcription, whereby it has both kinase-dependent and kinase-independent functions. Herein, we describe the complex role of CDK6, balancing quiescence, proliferation, self-renewal, and differentiation in activated HSCs. Mouse HSCs expressing kinase-inactivated CDK6 show enhanced long-term repopulation and homing, whereas HSCs lacking CDK6 have impaired functionality. The transcriptomes of basal and serially transplanted HSCs expressing kinase-inactivated CDK6 exhibit an expression pattern dominated by HSC quiescence and self-renewal, supporting a concept, in which myc-associated zinc finger protein (MAZ) and nuclear transcription factor Y subunit alpha (NFY-A) are critical CDK6 interactors. Pharmacologic kinase inhibition with a clinically used CDK4/6 inhibitor in murine and human HSCs validated our findings and resulted in increased repopulation capability and enhanced stemness. Our findings highlight a kinase-independent role of CDK6 in long-term HSC functionality. CDK6 kinase inhibition represents a possible strategy to improve HSC fitness., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: The relationship between erectile dysfunction (ED) and cardiovascular (CV) events has been postulated, with ED being characterized as a potential harbinger of CV disease. Location of residence is another important consideration, as the impact of rural residence has been associated with worse health outcomes., Aim: To investigate whether men from rural settings with ED are associated with a higher risk of major adverse CV events (MACEs)., Methods: A propensity-weighted retrospective cohort study was conducted with provincial health administrative databases. ED was defined as having at least 2 ED prescriptions filled within 1 year. MACE was defined as the first hospitalization for an episode of acute myocardial infarction, heart failure, or stroke that resulted in a hospital visit >24 hours. We classified study groups into ED urban, ED rural, no ED urban, and no ED rural. A multiple logistic regression model was used to determine the propensity score. Stabilized inverse propensity treatment weighting was then applied to the propensity score., Outcomes: A Cox proportional hazard model was used to examine our primary outcome of time to a MACE., Results: The median time to a MACE was 2731, 2635, 2441, and 2508 days for ED urban (n = 32 341), ED rural (n = 18 025), no ED rural (n = 146 358), and no ED urban (n = 233 897), respectively. The cohort with ED had a higher proportion of a MACE at 8.94% (n = 4503), as opposed to 4.58% (n = 17 416) for the group without ED. As compared with no ED urban, no ED rural was associated with higher risks of a MACE in stabilized time-varying comodels based on inverse probability treatment weighting (hazard ratio, 1.06-1.08). ED rural was associated with significantly higher risks of a MACE vs no ED rural, with the strength of the effect estimates increasing over time (hazard ratio, 1.10-1.74)., Clinical Implications: Findings highlight the need for physicians treating patients with ED to address CV risk factors for primary and secondary prevention of CV diseases., Strengths and Limitations: This is the most extensive retrospective study demonstrating that ED is an independent risk factor for MACE. Due to limitations in data, we were unable to assess certain comorbidities, including obesity and smoking., Conclusions: Our study confirms that ED is an independent risk factor for MACE. Rural men had a higher risk of MACE, with an even higher risk among those who reside rurally and are diagnosed with ED., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Immune cells need to sustain a state of constant alertness over a lifetime. Yet, little is known about the regulatory processes that control the fluent and fragile balance that is called homeostasis. Here we demonstrate that JAK-STAT signaling, beyond its role in immune responses, is a major regulator of immune cell homeostasis. We investigated JAK-STAT-mediated transcription and chromatin accessibility across 12 mouse models, including knockouts of all STAT transcription factors and of the TYK2 kinase. Baseline JAK-STAT signaling was detected in CD8 + T cells and macrophages of unperturbed mice-but abrogated in the knockouts and in unstimulated immune cells deprived of their normal tissue context. We observed diverse gene-regulatory programs, including effects of STAT2 and IRF9 that were independent of STAT1. In summary, our large-scale dataset and integrative analysis of JAK-STAT mutant and wild-type mice uncovered a crucial role of JAK-STAT signaling in unstimulated immune cells, where it contributes to a poised epigenetic and transcriptional state and helps prepare these cells for rapid response to immune stimuli., (© 2024. The Author(s).)

Introduction: In universal healthcare systems, patients may still encounter financial obstacles from cancer treatments, potentially influencing treatment decision-making. We investigated the relationship between socioeconomic status and treatment decision-making as it pertains to patient values, preferences, and perceived barriers to care for localized prostate cancer., Methods: We conducted a prospective study of patients undergoing a prostate biopsy for the initial detection of prostate cancer. Sociodemographic variables were collected, with validated instruments used to determine health literacy levels. Patients were divided into two groups using self-reported income; those with a positive identification of prostate cancer underwent additional surveys to ascertain their knowledge of their diagnosis, treatment-related preferences, and socioeconomic barriers to care. Descriptive statistics were used., Results: Of 160 patients, approximately one-third were classified as having low health literacy. Within the low-income group, education levels were lower (34.6% had less than high school education vs. 10.2% in the high-income group) and unemployment rates higher (75.0% unemployed vs. 38.9% in the high-income group). Low-income patients with prostate cancer placed greater importance on indirect out-of-pocket expenses related to treatment (78.3% vs. 33.3%, p=0.001), higher emphasis on treatment-related travel time (50% vs. 15.1%, p=0.004), and more often had difficulty paying for healthcare services in the past (30.9% vs. 9.1%, p=0.02)., Conclusions: Patients with lower household incomes have unique treatment values and decision-making preferences. They may experience additional challenges and barriers to obtaining cancer care, at least partly related to indirect costs. These findings should be considered when framing prostate cancer treatment discussions and designing patient-facing health information.

Background: The presence of contrast enhancement (CE) on magnetic resonance imaging (MRI) is one of the principal criteria for diagnosis and disease activity of multiple sclerosis (MS). Therefore, MS patients are frequently exposed to contrast agents, which may cause deposition in the brain, restricting its use in repeat examinations. Thus, serum biomarkers may be valuable as surrogate parameters to evaluate MS activity., Methods: REDUCE-GAD was a prospective, multicentric, biobanking study to determine whether established serum markers (neurofilament light chain [NfL], glial fibrillary acidic protein [GFAP], tau protein, ubiquitin-carboxyl-terminal-hydrolase (UCH-L1), S100B and matrix-metalloproteinase 9 [MMP9]) are predictive of CE-positive MRI lesions. Blood samples were obtained from patients undergoing MRI 5 days before or after collection., Results: Patients (N = 102) from four different centers with confirmed MS or related disorders were included; n = 57 (55.9%) showed CE on MRI versus n = 45 (44.1%) without CE. Only higher NfL values indicated CE (odds ratio [OR] 1.05; 95% CI 1.0-1.09) and were correlated with number (ρ = 0.47; p < 0.001) and diameter of CE lesions (ρ = 0.58; p < 0.001). Nfl Z-scores improved diagnostic accuracy (OR 1.52; 95% CI 1.06-2.18). Receiver operator characteristic analysis revealed a reasonable cut-off value for NfL at 14.1 pg/mL (sensitivity 49.1%; specificity 82.2%; positive predictive value 77.8%; negative predictive value 56.0%). NfL ≥59.2 pg/mL was exclusively observed in patients with CE., Conclusions: Evaluation of several possible serum biomarkers for CE in MS patients provided the most robust results for NfL, particularly as Z-scores. Following further evaluation, biomarkers may help stratify the application of contrast agents for brain imaging in MS patients., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Intratesticular testosterone is vital for spermatogenesis, male fertility, and virility. Currently the only method to assess levels of intratesticular testosterone is to perform testicular biopsy which is invasive and can lead to several complications. Approaches to assess intratesticular testosterone have been understudied but hold promise as future male contraceptive agents and may grant the ability to monitor patients undergoing hormonal changes from therapeutic and diagnostic perspectives. Previous studies have sought to assess the utility of 17-hydroxyprogesterone (17-OHP) and insulin-like factor 3 (INSL3) as accurate surrogate biomarkers of intratesticular testosterone. The aim of this review is thus to highlight the importance of intratesticular testosterone and the consequent advances that have been made to elucidate the potential of biomarkers for intratesticular testosterone in the context of male infertility., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Intralesional Collagenase Clostridium histolyticum (CCh) was the first non-surgical therapy approved for Peyronie's disease (PD). However, CCh's cost and poor market uptake has led to its discontinuation in Europe and Canada. In Canada, Xiaflex® is the trade name for CCh and it is produced by Paladin Labs Inc, an operating company of Endo International. The paper aims to better understand Canadian CCh providers' perspectives regarding its treatment efficacy and the potential impact of its discontinuation. All Xiaflex®-approved Canadian providers were asked to complete an anonymous 21-question survey using an online platform. Analysis consisted of descriptive statistics. Outcomes of interest included previous experience with CCh, protocols utilized, experience with insurance coverage, clinical and patient-reported outcomes, and provider perspectives on the discontinuation of CCh. Overall response rate was 48.3% (29/60). A total of 89% of respondents were male, 61% were in practice more than 10 years, 32% were in an academic practice, and 46% had completed an Andrology/Sexual Medicine fellowship. A total of 93% of respondents felt that CCh was superior to other intralesional therapies for PD. In all, 86% reported a patient satisfaction rate of at least 50%, and the majority (75%) saw a clinically meaningful response. Only 7% expressed difficulty obtaining insurance coverage, with many providers (71%) achieving an insurance approval rate between 75 and 100%. Only 54% of respondents reported that they would continue treating PD in light of CCh's discontinuation, and 96% felt that CCh's discontinuation represents a loss to Canadian patients. In light of CCh's discontinuation, most (79%) are now more likely to offer surgical treatment. In conclusion, most CCh providers found CCh to be effective and were dismayed by its discontinuation. The survey demonstrated that due to the withdrawal of CCh from Canada, physicians' abilities to offer effective medical therapy may become limited, with more providers offering surgical options for PD., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

This study examined how a standard exercise test (SET) affected (1) thyroid hormones (THs) of horses and (2) the relationship between the V La4 of horses and TH responses to the exercise in trained Standardbred racehorses (V La4 is the velocity run at defined conditions at which a blood lactate concentration of 4 mmol/L is determined). Twelve trained Standardbred racehorses (six stallions and six mares) performed SETs until the horses' blood lactate concentration was at or above 4 mmol/L. The horses were divided into three age groups (2, 3, and 4 years old); each group consists of 4 horses respectively (two male and two female), to evaluate the effects of age and sex on hormonal responses to SET. During each SET, blood samples were taken at rest and after each interval and at the end of SET. Blood was analysed for total and free triiodothyronine (T3, fT3) as well as total and free thyroxine (T4, fT4). The statistical model included three fixed factors (SET, sex and age) and their main interactions. ANOVA analysis revealed that T3 and fT3 were significantly influenced by SETs. Plasma T3 and fT3 concentrations were higher in 4-year-old horses compared to the other age groups. All plasma THs concentrations were higher in mares than in stallions. Correlations revealed that a higher V La4 was negatively related to all THs responses in 2-year-old Standardbred mares only. The SET used to determine V La4 increased selected THs (T3, fT3); these increases were inversely related to V La4 and affected by age and sex of the horses. The correlation of V La4 with thyroid exercise' response might provide some additional information for performance evaluation of Standardbred racehorses, especially for evaluating training adaptation, according to sex, and age. Further studies are necessary to provide support on the value of measuring THs in Standardbred racehorses of different sex and age., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Patients diagnosed with septic stone are at significant risk of morbidity and mortality should source control through drainage be delayed, and they are often admitted to intensive care units (ICU) for hemodynamic support. The purpose of this study was to determine patient factors that may predict mortality in patients admitted to ICU with septic stone, particularly whether rural patients at a greater distance from a tertiary care center were at greater risk of mortality given the inherent delay in intervention., Methods: The Manitoba Intensive Care Unit prospective registry began in 1999 and includes all patients admitted to ICU across Manitoba. Baseline characteristics, such as age, gender, vital signs, creatinine, Charlson comorbidity index (CCI), mortality outcomes, and location of residency were obtained for those admitted to ICU for septic stone. Association between death and clinical/demographic variables was performed with adjusted multivariable logistical regression analysis., Results: A total of 342 patients admitted to the ICU were analyzed, with a mean age of 63.5±15.5 years. Baseline characteristics were similar between groups (p>0.05). On multivariable adjusted logistical regression, the presence of acute kidney injury (AKI) (p<0.001) and intubation (p<0.001) were associated with mortality. There was no difference in mortality attributable to location of residency, vital signs, or CCI., Conclusions: Among patients admitted to the ICU for septic stones in Manitoba, we demonstrate an association between AKI and intubation with mortality. Other factors, such as whether patients were from a rural region and baseline patient characteristics, were not predictive of mortality.