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Profile of Luspatercept in the Treatment of Anemia in Adults with Non-Transfusion-Dependent β-Thalassemia (NTDT): Design, Development and Potential Place in Therapy
Get PDFOver the past decade, evidence has been mounting on the detrimental clinical sequelae of untreated anemia in patients with non-transfusion-dependent β-thalassemia (NTDT). There are no pharmacologic agents that are specifically approved for the management of anemia in NTDT, and available options such as splenectomy, transfusion therapy, and hydroxyurea each come with their own shortcomings, especially for long-term use. Luspatercept is an erythroid maturation agent that has been evaluated in a Phase 2, randomized trial and showed a significant benefit in raising hemoglobin level by at least 1 g/dL in adults with NTDT and a baseline hemoglobin level ≤10 g/dL. These data led to luspatercept’s approval by the European Commission for the treatment of anemia in adults with NTDT and presents the first evidence-based approach for a novel agent that is able to ameliorate anemia in this patient population. © 2023 Musallam et al
Fallopian tube lesions as potential precursors of early ovarian cancer: a comprehensive proteomic analysis
Get PDFOvarian cancer is the leading cause of death from gynecologic cancer worldwide. High-grade serous carcinoma (HGSC) is the most common and deadliest subtype of ovarian cancer. While the origin of ovarian tumors is still debated, it has been suggested that HGSC originates from cells in the fallopian tube epithelium (FTE), specifically the epithelial cells in the region of the tubal-peritoneal junction. Three main lesions, p53 signatures, STILs, and STICs, have been defined based on the immunohistochemistry (IHC) pattern of p53 and Ki67 markers and the architectural alterations of the cells, using the Sectioning and Extensively Examining the Fimbriated End Protocol. In this study, we performed an in-depth proteomic analysis of these pre-neoplastic epithelial lesions guided by mass spectrometry imaging and IHC. We evaluated specific markers related to each preneoplastic lesion. The study identified specific lesion markers, such as CAVIN1, Emilin2, and FBLN5. We also used SpiderMass technology to perform a lipidomic analysis and identified the specific presence of specific lipids signature including dietary Fatty acids precursors in lesions. Our study provides new insights into the molecular mechanisms underlying the progression of ovarian cancer and confirms the fimbria origin of HGSC. © 2023, The Author(s)
The Absent Leviathan: The Fate of Power Sharing in Lebanon
Get PDFThis thesis critically examines the underlying reasons behind the failure of Lebanon's political system in regulating internal conflicts and assesses if the current political framework is salvageable. Furthermore, it examines the possibility of a new power-sharing agreement to effectively address internal conflicts, requiring the alignment of both internal and external interests. This study finds that Lebanon grapples with a costly sectarian governance system that breeds persistent internal conflict and deadlocks, necessitating external intervention for stability and the preservation of power sharing. The system has also facilitated elite capture of state institutions and widespread corruption. This, combined with the presence of an armed non-state actor within the political system, has significantly weakened the state. Furthermore, the elites' lack of political will to implement reforms and their persistence in maintaining the dysfunctional status quo have pushed the existing political structure to an irreparable state
Manufactured regional crises: The Middle East and North Africa under global food regimes
Get PDFThe current agrarian and food crisis in the Middle East and North Africa (MENA) has been interpreted through a number of tropes. Within the dominant mainstream discourse, the MENA region is often depicted as a homogenous geographical area characterized by dryness, infertile lands and poor water resources. How did imperialism, colonialism and the Cold War influence the MENA food systems? What were the effects of trade liberalization and neoliberalism on the agricultural systems in the region? These are some questions that this paper will try to answer using a geographical and historical-comparative analysis, through a food regimes lens. Understanding contemporary social relations dynamics cannot be limited to the recent period. Agriculture and food in the MENA region are anchored in the history of power relations ruled by flows of capital and the shaping of ecological transformations during the longue durée of capitalism and its corresponding modes of control and regulation. © 2023 John Wiley & Sons Ltd
Assessing the knowledge, attitudes, and practices of graduating medical students towards sexual health in Lebanon
No full textObjective: To assess the knowledge, attitudes, and practices of graduating medical students in Lebanon regarding sexual health, as well as their readiness to learn about it, and to determine the demographic and educational factors that influence our findings. Methods: Cross-sectional study. A self-designed questionnaire exploring various components of sexual health was sent to 578 graduating medical students in Lebanon. Knowledge, attitude, and practice scores were computed and analyzed. Results: The overall mean knowledge score was relatively low (2.61, range −13 to 10). A statistically significant difference was found in the mean knowledge score across religion (P = 0.028) and religiosity (P < 0.001) categories. The mean practice score also differed significantly across income groups (P = 0.010). No other significant associations were found between gender, sexuality, environment, primary source of sexual health education, or language and the mean knowledge, attitude, and practice scores. Conclusion: Additional standardized assessment of medical students' competences in sexual health matters through diverse research models is needed. Re-examination of existing medical curricula and inclusion of more extensive sexual health education is necessary to improve patient care. © 2022 International Federation of Gynecology and Obstetrics
Impact of Obstructive Sleep Apnea Syndrome on Time to Complete Recovery of Continence after Robot-Assisted Radical Prostatectomy: A Propensity Score Matching Analysis
No full textBackground: Postoperative urinary incontinence after robot-assisted radical prostatectomy (RARP) represents a bothersome side effect, which may permanently affect patient's quality of life. Several studies have demonstrated that obstructive sleep apnea syndrome (OSAS) is associated with urinary symptoms such as urge incontinence, overactive bladder, and nocturia. In this study, we sought to further explore the effect of OSAS on urinary continence after RARP. Methods: We queried our prospectively collected institutional RARP database and identified 82 patients with OSAS and 131 controls, which were matched for age and body mass index (BMI), with available follow-up data for continence. To minimize selection bias, we conducted a propensity score-matched analysis. Patient's characteristics and urinary continence outcomes were compared between the two groups before and after propensity-score matching. Kaplan-Meier curves were constructed to assess the difference in continence between the two groups. Results are presented as means with standard deviations and percentages with 95% confidence intervals (CIs). Results: A total of 213 patients were included in the analysis, of whom 82 with OSAS and 131 with non-OSAS (control group). The mean age of the total cohort was 61.7 ± 6.96 years, the mean BMI was 30.4 ± 5.36, and 52% of the cohort were classified as obese (BMI ≥30). In post-propensity score-matched analyses, there was no significant difference in baseline demographics and tumor characteristics between the two groups (included 82 cases in each group). The median time to continence was 6.6 months for the control group as compared with 13.0 months for the OSAS group (p < 0.001). At 12 months the continence rate for the OSAS group was 41.2% (95% CI: 28.9%-51.4%) as compared with 61.7% (95% CI: 28.5%-71.5%) for the control group. At 24 months the continence rate for the OSAS group was 68.7% (95% CI: 56%-77.7%) as compared with 90.8% (95% CI: 79%-96%) for the control group. Conclusion: On matched analysis, we found that patients with OSAS tended to demonstrate worse urinary continence recovery as compared with patients without OSAS. Additional investigation will be necessary to confirm these initial findings. © Copyright 2023, Mary Ann Liebert, Inc., publishers 2023
OPTIMIZATION OF A SOLAR PHOTOVOLTAIC MICRO GRID FOR ELECTRICITY AND DESALINATED WATER SUPPLY
No full textRenewable energy is promising to become a major resource for future communities,
while water scarcity is becoming a major threat. The use of solar photovoltaic (PV) to power
reverse osmosis (RO) plants and produce water will enhance the sustainability of water supplies
in several dry coastal areas. Varying the operating power level of the RO plant has been
proposed in the literature as a solution to accommodate intermittent PV power sources. Such
variable operation is intended to match the RO load to the available PV power. Nevertheless,
such operation has not been used outside research laboratories and small pilot plants. In this
work, different case studies to evaluate the benefit of using variable operation and its effects
on system design, system operation and levelized cost of water (LCOW) were investigated. A
simulation model for the optimal operation of the system is developed using three-dimensional
dynamic programming (DP) to determine the power levels of the PV generators, battery, diesel
generator, and RO plant while optimal sizing of these plants and associated water tanks was
solved using an ordinal optimization (OO) approach. Simulations are performed under a
MATLAB environment. The use of OO permitted the examination of a large design search
space quickly but exhaustively using a simple model. The different designs were then ranked
in increasing cost order and assessed a reduced number of these using an accurate model to
simulate the system operation on an hourly basis for all the days of the year. This approach
relies on the fundamental tenet of OO: “order is robust to the noise introduced by the simple
model”. Different power modulation strategies are investigated, and their implications on the
hydraulic operating parameters are presented. The operation of the RO system at varying power
levels and different sizes of backup systems (battery and diesel generator) was investigated.
This ability to vary the RO operating level helped in a better matching of the system load to
the available, yet variable, PV power, even when the backup and storage systems were at a
minimum. Operating an RO plant with PV and backup systems is found to be far more cost
effective than operating it without backup systems, reducing costs by 37-57% for the case
studies considered
Central and Peripheral Hemodynamics in Young Adults Who Use Water Pipes and the Acute Effects of Water-Pipe Use
No full textBackground: Tobacco use via water pipe (commonly referred to as water-pipe smoking [WPS]) is popular among young adults globally and exposes those who smoke to toxicants. Research Question: Is WPS associated with impaired measures of arterial function and does WPS acutely impair these measures in young adults? Study Design and Methods: We assessed heart rate (HR), brachial and aortic BP, HR-adjusted augmentation index (AI), and carotid-femoral pulse wave velocity (CFPWV) in 62 individuals who use water pipes and 34 individuals who have never used a water pipe recruited from the community (mean age, 22.5 ± 3.0 years; 48% female). Measurements were obtained before and after an outdoor session of WPS among participants who use water pipes and among the control group of participants who have never used a water pipe. Measurements were compared after vs before exposure and between those who use and those who do not use water pipes, adjusting for possible confounders using linear regression. Results: Participants who use water pipes and control participants had similar demographic characteristics. BP and HR increased acutely after WPS (brachial systolic BP by 4.13 mm Hg [95% CI, 1.91-6.36 mm Hg]; aortic systolic BP by 2.31 mm Hg [95% CI, 0.28-4.33 mm Hg]; brachial diastolic BP by 3.69 mm Hg [95% CI, 1.62-5.77 mm Hg]; aortic diastolic BP by 3.03 mm Hg [95% CI, 0.74-5.33 mm Hg]; and HR by 7.75 beats/min [95% CI, 5.46-10.04 beats/min]), but not in the control group. AI was significantly higher in participants who use water pipes compared with those who do not (9.02% vs 3.06%; P = .03), including after adjusting for BMI and family history of cardiovascular disease (β = 6.12; 95% CI, 0.55-11.69; P = .03) and when assessing habitual tobacco use via water-pipe extent (water pipes used/day × water-pipe use duration) in water-pipe-years (β = 2.51/water-pipe-year; 95% CI, 0.10-4.92/water-pipe-year; P = .04). However, CFPWV was similar in those who use water pipes and those who do not, and AI and CFPWV did not change acutely after WPS. Interpretation: In apparently healthy young individuals from the community, habitual WPS was associated with increased AI, a predictor of cardiovascular risk, and one WPS session acutely increased HR and brachial and aortic BP. © 2023 American College of Chest Physician
Polycystic Ovary Syndrome: Pathophysiology and Controversies in Diagnosis
Get PDFPolycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder that commonly affects women in the reproductive age group. The disorder has features that propose a blend of functional reproductive disorders, such as anovulation and hyperandrogenism, and metabolic disorders, such as hyperglycemia, hypertension, and obesity in women. Until today, the three implemented groups of criteria for the diagnosis of PCOS are from the National Institutes of Health (NIH) in the 1990s, Rotterdam 2003, and the Androgen Excess Polycystic Ovary Syndrome 2009 criteria. Currently, the most widely utilized criteria are the 2003 Rotterdam criteria, which validate the diagnosis of PCOS with the incidence of two out of the three criteria: hyperandrogenism (clinical and/or biochemical), irregular cycles, and polycystic ovary morphology. Currently, the anti-Müllerian hormone in serum is introduced as a substitute for the follicular count and is controversially emerging as an official polycystic ovarian morphology/PCOS marker. In adolescents, the two crucial factors for PCOS diagnosis are hyperandrogenism and irregular cycles. Recently, artificial intelligence, specifically machine learning, is being introduced as a promising diagnostic and predictive tool for PCOS with minimal to zero error that would help in clinical decisions regarding early management and treatment. Throughout this review, we focused on the pathophysiology, clinical features, and diagnostic challenges in females with PCOS. © 2023 by the authors
Characteristics of Self-Rated Oral Health among Syrian Refugee Parents in Ontario
Get PDFBackground. Canada has been hosting Syrian refugees since early 2015. Almost half of the Syrian refugee population lives in Ontario, with dental health being at the top of the list of important immediate needs. The objective of the study was to evaluate self-rated oral health and its associated factors among Syrian refugee parents residing in Ontario. Methods. This was a cross-sectional study where 540 Syrian refugee parents, residing in Ontario and with at least one child less than 18 years of age, were interviewed. Information about self-rated oral health was collected based on the question In general, how would you rate the health of your teeth and mouth?with answers ranging from 1 representing excellentand 5 representing very poor.Multiple linear regression analysis was performed to assess the independent relationship between each of the sociodemographic-, migration-, health-, dental-related factors, and self-rated oral health. Results. The overall prevalence of poor and very poor self-rated oral health was 43.5%. The results showed that the presence of dental health insurance, private sponsorship, improved physical and mental health, and regular visits to the dentist were factors related to improved oral health. Discussion. To achieve better oral health outcomes among refugee populations, including Syrian refugees, efforts should be focused on improving dental care and dental insurance for vulnerable populations. © 2023 Aseel Alzaghoul et al