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Sexual dimorphism in acute myocardial infarction-induced acute kidney injury: cardiorenal deteriorating effects of ovariectomy in premenopausal female mice
Get PDFAcute kidney injury (AKI) is a common complication of cardiovascular diseases (CVDs) in both males and females, increasing mortality rate substantially. Premenopausal females appear to be more protected, suggesting a potential protective role of female sex hormones. Here, we tested the hypothesis that ovariectomy (OVX) eliminates the beneficial effect of female sex on renal protection following acute myocardial infarction (MI). Seven days post-MI, both sexes exhibited worsened kidney function and a substantial decrease in total kidney NAD levels. UnlikeMI femalemice, MI males showed exacerbated morphological alterations with increased proinflammatory, proapoptotic, and profibrotic biomarkers. The expression of NAD+ biosynthetic enzymes NAMPT and NMRK-1 was increased in MI females only, while males showed a substantial increase in NAD+ consuming enzyme PARP-1. OVX did not eliminate the female-sex protection of glomerular morphology but was associated with swelling of proximal convoluted tubules with MI as in males. With OVX, MI females had enhanced proinflammatory cytokine release, and a further decrease in creatinine clearance and urine output was observed. Our findings suggest that MI induced AKI in both sexes with pre-menopausal female mice being more protected. Ovariectomy worsens aspects of AKI in females after MI, which may portend increased risk for development of chronic kidney disease. ©2023 The Author(s)
How I treat non-transfusion-dependent β-thalassemia
Get PDFThe intricate interplay of anemia and iron overload under the pathophysiological umbrella of ineffective erythropoiesis in non-transfusion-dependent β-thalassemia (NTDT) results in a complex variety of clinical phenotypes that are challenging to diagnose and manage. In this article, we use a clinical framework rooted in pathophysiology to present 4 common scenarios of patients with NTDT. Starting from practical considerations in the diagnosis of NTDT, we delineate our strategy for the longitudinal care of patients who exhibit different constellations of symptoms and complications. We highlight the use of transfusion therapy and novel agents, such as luspatercept, in the patient with anemia-related complications. We also describe our approach to chelation therapy in the patient with iron overload. Although tackling every specific complication of NTDT is beyond the scope of this article, we touch on the management of the various morbidities and multisystem manifestations of the disease. © 2023 The American Society of Hematolog
Selective Colloid Transport across Planar Polymer Brushes
Get PDFPolymer brushes are attractive as surface coatings for a wide range of applications, from fundamental research to everyday life, and also play important roles in biological systems. How colloids (e.g., functional nanoparticles, proteins, viruses) bind and move across polymer brushes is an important yet under-studied problem. A mean-field theoretical approach is presented to analyze the binding and transport of colloids in planar polymer brushes. The theory explicitly considers the effect of solvent strength on brush conformation and of colloid-polymer affinity on colloid binding and transport. The position-dependent free energy of the colloid insertion into the polymer brush which controls the rate of colloid transport across the brush is derived. It is shown how the properties of the brush can be adjusted for brushes to be highly selective, effectively serving as tuneable gates with respect to colloid size and affinity to the brush-forming polymer. The most important parameter regime simultaneously allowing for high brush permeability and selectivity corresponds to a condition when the repulsive and attractive contributions to the colloid insertion free energy nearly cancel. This theory should be useful to design sensing and purification devices with enhanced selectivity and to better understand mechanisms underpinning the functions of biological polymer brushes. © 2023 Wiley-VCH GmbH
Low molecular weight heparin in COVID-19: benefits and concerns
Get PDFSince its emergence, the COVID-19 pandemic had a dramatic impact on the public health worldwide and it scarred the medical, economical, and social determinants of health. Even after the significant vaccination advances, the disease of SARS-CoV-2 can manifest in severe presentations with life-threatening thromboembolic and multi-organ complications leading to notable morbidity and mortality. Clinicians and researchers are on continuous pursuit of investigating different approaches in the attempt to prevent the infection and minimize its severity. Although the COVID-19’s pathophysiology remains relatively unclear, it is well established now that coagulopathy, systemic thrombotic propensity, and a robust immunoinflammatory response are some of the most important determinants of its morbidity and mortality. Accordingly, research efforts have focused on addressing the inflammatory and hematological cascades using available agents to avoid thromboembolic events. Several studies and investigators have emphasized the importance of Low molecular weight heparin (LMWH), namely, Lovenox, in addressing these sequelae of the COVID-19 disease, either prophylactically or therapeutically. This review explores the benefits and concerns of employing LMWH, a widely used anticoagulant, in COVID-19 disease. It delves into Enoxaparin as a molecule, along with its pharmacology, mechanism of action, and clinical uses. It also reviews the current high-quality clinical evidence that highlight the role of enoxaparin in SARS-CoV-2 infection. Copyright © 2023 Makarem, Zareef, Abourjeili, Nassar, Bitar and Arabi
Pediatric lipoblastomas: A case series
Get PDFIntroduction: Lipoblastoma is a rare benign tumor originating from embryonic fat cells that occurs mostly within the first 3 years of life. It predominantly involves the subcutaneous tissue of the trunk and the extremities. However, in rare cases it can occur in other sites and the presentation can be the result of mass effect exerted on adjacent structures. Case presentation: We present 2 cases of lipoblastoma, both occurring in uncommon locations (retroperitoneum, neck) and exerting life-threatening mass effect. Both patients underwent complete surgical excision of the mass with preservation of vital structures and the final diagnosis was made by histopathology. The two patients were alive and doing well on follow up after surgery. Conclusion: Variability in presentation, anatomic locations, and patient characteristics necessitate a comprehensive understanding of lipoblastoma along with other entities that can mimic its presentation. The 2 cases of lipoblastoma presented in this case series, highlight the complexities related to diagnosing and managing lipoblastoma especially when occurring at unusual places and exerting a critical mass effect on vital structures. © 2023 The Author
Efficacy of DNA Polymerase Inhibitors in Triple-Negative Breast Cancer Cells
No full textIntroduction: Breast cancer is the most common malignancy among women and the second leading cause of cancer-related mortality globally, posing a significant public health burden. Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with high associated metastasis and an overall poor prognosis. Due to the lack of long-established scarcity of specific effective therapies, TNBC is usually treated using conventional chemotherapy leading to drug resistance and relapse pressing the urge to develop novel and effective therapeutic strategies. DNA polymerase 1 and histone deacetylase 1, play a key role in cell proliferation, DNA synthesis, and replication, and regulation of epigenetic mechanisms, are significantly highly expressed in breast tumors compared to normal breast tissues. Therefore, these two enzymes present potential targets for drugs that block DNA synthesis suppressing tumor growth. We have shown that the adamantyl retinoid, ST1926, a potent cancer therapeutic compound, to be a POLA1 inhibitor. Sub-micromolar concentrations of ST1926 suppress the proliferation and induce cell death in human breast cancer cells while sparing normal ones. We have synthesized two ST1926 analogues, MIR002 and GEM144, with improved pharmacological properties and dual POLA1 and HDAC11 inhibitors activities forming a novel class of inhibitory compounds. In this study, we accessed the anti-tumor effects of ST1926, MIR002 and GEM144 and investigated cell death mechanism, and their mode of action on a panel of human TNBC cell lines and normal-like breast cells.
Methods: Basal POLA1 and HDAC11 levels were measured by immunoblotting technique in different types of human TNBC cell lines (HCC1806, MDA-MB-453, and MDA-MB-231) and normal-like MCF10A breast cells. The selected cell lines have lost or mutant p53 and represent different TNBC subtypes. The mechanism of action of the different treatments was studied on cell growth by sulforhodamine B (SRB). Cell cycle arrest was determined by using propidium iodide-based flow cytometric analysis of DNA content. DNA damage was assessed by immunoblotting techniques, and apoptotic cell death using the TUNEL assay and PARP cleavage.
Results: ST1926, MIR002, and GEM144 suppressed the growth of all tested TNBC cell lines at low micromolar concentrations while sparing normal-like breast cells as shown by SRB. The different treatments induced an early effect on HCC1806 and a more delayed one on MDA-MB-453 cells. Cell cycle analysis showed that ST1929, MIR002 and GEM144 induced cell death and a massive accumulation of treated cells in the sub-G1 phase. DNA damage and double strand break was detected by the increase in γ-H2AX in GEM144-treated TNBC cells. Apoptosis was confirmed by TUNEL positivity and PARP cleavage in HCC1806 suggesting a caspase-dependent cell death. On the other hand, apoptotic cell death identified by the TUNEL positivity in GEM144-treated MDA-MB-456 cells did not show PARP cleavage suggesting a caspase-independent mode cell death. Finally, the protein levels of POLA1 and HDAC11 were reduced in GEM144 treated TNBC cells.
Conclusion: These results demonstrate the effectiveness of ST1926, MIR002, and GEM144 in inhibiting TNBC cell growth and inducing apoptosis independently of p53 signaling pathways. This research may shed the light on a new potential therapeutic approach for TNBC management. Future in vivo studies using the intra-ductal breast cancer mouse model may be used to further validate this new therapeutic approach
Deliveries in Lebanon, the Country with the Highest Refugee Density in the World: A Descriptive Review
No full textPurpose: The aim of this study is to analyze obstetrical and reproductive health parameters in Lebanon from 2015 until 2018 in the setting of the Syrian refugee influx in order to evaluate potential risks and provide a management plan to improve outcomes. Description: Data from the Lebanese Ministry of Public Health (LMPH) on all obstetrical deliveries that occurred in Lebanon between 2015 and 2018 was screened and analyzed. Number and mode of delivery as well as maternal and neonatal outcomes were included. Joinpoint regression analysis was used for trends of selected parameters. Independent two-sample t-tests were used for comparisons. Assessment: Women of non-Lebanese nationality residing in Lebanon had a significantly greater number of total deliveries (p-value < 0.001), vaginal deliveries (p-value = 0.002), cesarean sections (p-value = 0.02). When looking at delivery trends from 2015 to 2018, Lebanese women had a significant decrease in total number of deliveries (p-value < 0.001) and vaginal deliveries (p-value < 0.001). Conclusion: Total number of deliveries and cesarean sections is on the rise in Lebanon. Cesarean section practice should be audited by the LMPH and the Lebanese Order of Physicians (LOP). Local and international agencies should prioritize the implementation and management of family planning facilities in refugee hosting countries. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature
Role of pro-inflammatory interleukins in osteoarthritis: a narrative review
No full textPurpose: This manuscript will summarize the role of pro-inflammatory cytokines and tackle newly discussed ones within the scope of OA pathogenesis as mentioned in the recent literature. This will allow for a better understanding of the mechanisms behind such a complicated disease. Material and methods: Relevant articles were obtained by searching key terms including “pro-inflammatory cytokines,” “inflammation,” “pathophysiology,” “cartilage damage,” and “OA” in PubMed and Google Scholar databases. The year ranges set for the selection of the articles was between 2015 -2021. Inclusion criteria was based on the relevance and contribution to the field of the study. Results: Osteoarthritis (OA) has a complex multifactorial pathophysiology which is attributed to molecular and biomechanical changes that disrupt the normal balance of synthesis and degradation of articular cartilage and subchondral bone. Pro-inflammatory cytokines, with their wide range of action and intricate signaling pathways, are the constant subject of new discoveries revolving around this inflammatory disease. The available literature indicates that some of these cytokines such as IL-33, IL-17, IL-6, and IL-22 have a direct relation to cartilage degradation, while others like IL-15, IL-1, IL-7, and IL-34 have an indirect one. Conclusions: Inflammation has an essential role in the manifestation of osteoarthritis clinical events. Specifically, certain cytokines exhibit pro-inflammatory properties that are markedly activated during the course of the disease and notably alter the homeostasis of the joint environment. However, clinical trials and observational studies remain insufficient to navigate the varying nature of this disease in humans. © 2022 Informa UK Limited, trading as Taylor & Francis Group
Bilingual Cigarette Warning Labels: Effects on Young People's Recall and Attention in Lebanon
No full textThe goal was to determine the effects of bilingual cigarette warning labels on the recall performance and attention of young bilingual Lebanese college students. Forty-eight students were shown English-only, Arabic-only, or bilingual cigarette warning labels in 2020. Participants recalled as many of the labels as they could after the experiment and then two weeks later. Eye tracking was used to determine attention to the label and subjective data were collected. Results showed that bilingual labels did not lead to better recall; participants needed more time to extract data from bilingual labels and first looked at them later in time, although bilingual labels were revisited more. However, participants believed that bilingual labels were better. It appeared that bilingual labels led to clutter rather than helped recall. © The Author(s) 2023
Impact of Evapotranspiration and Biomass Model Selection on Irrigation Economics: WaPOR, HSEB, And GYMEE. Insights From the Litani River Basin
No full textUsing Economic Irrigation Water Productivity (EIWP) as an indicator for on-farm irrigation decision-making is of utmost importance in addressing the challenges posed by poor policies in managing agricultural water use, particularly in water-scarce basins. Various modeling systems are available for quantifying crop actual evapotranspiration (ETa) and biomass needed for measuring the economic output obtained from each unit of irrigation water utilized. The difference in ETa and biomass estimates between the modeling systems could translate into a difference in EIWP outcomes, which influences the basin-wide irrigation water management. In this paper we examine the influence of selecting different ETa and biomass models, particularly the hybrid single-source energy balance HSEB, the Global Field-Scale Crop Yield and ET Mapper in Google Earth Engine GYMEE, and FAO’s WaPOR V2, on evaluating EIWP on a basin-wide level. The method includes combining remote sensing and economic data to compare variability in ETa, biomass, and EIWP values derived from HSEB, GYMEE, and WaPOR. The approach is demonstrated with field survey data from the upper hydrologic unit of Lebanon’s largest catchment, the Litani River Basin, in its three productive districts Baalbak, Zahleh, and West Bekaa for the year 2021. Field-scale mean monthly ETa and biomass estimates for all crops, obtained from both models, are very comparable. On a district level, the results reveal a reasonable model agreement for the four crops in the estimation of ETa with moderate to strong correlation (0.75 0.9). Contrary to the ETa results, the GYMEE model consistently estimates slightly higher mean biomass values for all crops compared to WaPOR. The EIWP values produced by both models consistently indicate that potato holds the highest EIWP across all districts, followed by onion, table grapes, and wheat. The mean district HSEB-GYMEE model derived EIWPs are slightly higher than those derived from the WaPOR model for most crops. For EIWP obtained from HSEB-GYMEE, mean EIWP for potato is 12 times higher than that of wheat. As for that obtained from WaPOR, mean EIWP for potato is 10 times higher than that of wheat. The paper establishes a basis for future research on the application of remote sensing models in addressing water-stressed and socioeconomically challenged basins, with the potential to inform strategic irrigation management decisions based on model selection