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Establishing a Pertinent In vitro Model of the Blood Brain Barrier to Elucidate the Mechanisms of Invasion and Drug Permeability to the Brain
Get PDFThe maintenance of homeostasis in the brain relies on the restrictive permeability of the blood brain barrier (BBB). Neurological disorders, neurodegeneration, infectious insults, and tumor metastasis to the brain are all consequences of the loss of structural integrity of the BBB. Specific to Lebanon, 80% of the Lebanese population is thought to be infected with Toxoplasma gondii (T. gondii). Chronic toxoplasmosis (CT) is established after the parasite crosses the BBB to form cysts in the brain. The latter is associated with primary neuropathies, neuropsychiatric and behavioral disorders as well as brain cancers. Furthermore, 1 in 8 women will develop breast cancer in their lifetime. One of the most devastating consequences of breast cancer development and progression is secondary metastasis to the brain. Hence, it is imperative to find a relevant way to study the BBB to curb the deleterious side effects of it being breached. Current models fail to recapitulate the fundamental properties required to mirror the pathophysiological features of the BBB, leaving a gap in the application and translation of the research for medical application. Therefore, there is a need for effective modeling of the BBB to elucidate mechanisms of a variety of diseases including parasitic infection, metastasis of cancer to the brain, and to assess current drugs for BBB permeability and for novel drug screening. In this study, we developed a three-dimensional (3D) model that recapitulates the physiological and molecular properties of the BBB in vitro. This was achieved using a trans-well, cell-cell and cell-matrix interaction model. This model uniquely uses primary human endothelial cells and astrocytes, as well as subendothelial basement membrane to faithfully mimic the cyto-architecture of the BBB. Barrier permeability was then assessed using trans epithelial/ endothelial electrical resistance (TEER) and a variety of permeability tracers. We used this model as a platform to assess the invasion of Toxoplasma gondii (T. gondii) to the brain and breast cancer metastasis. This novel BBB model will contribute to the assessment of known drugs that are BBB permeable as well as discovering novel drugs that can be delivered to the brain. In doing so, we hope to extricate the molecular mechanisms of these breaches of the BBB to contribute to the amelioration of the outcomes of diagnoses of T. gondii infection or metastatic breast cancer
Anxiety, depression and post-traumatic stress disorder in patients on hemodialysis in the setting of the pandemic, inflation, and the Beirut blast: a cross-sectional study
Get PDFBackground: In 2020, Lebanon has witnessed its worst economic crisis, exacerbated by the COVID-19 pandemic and a massive explosion of its capital. Amidst these stressors, this study aims at assessing the prevalence of depression, anxiety, suicidality, post-traumatic stress disorder (PTSD) and cognitive impairment in patients undergoing hemodialysis in an academic hospital destroyed by the explosion. Methods: This cross-sectional study conducted 6 months after the blast included adults on hemodialysis, with no previous diagnoses of dementia or intellectual disability. It explores prevalence rates of psychiatric disorders, in addition to other medical and psychosocial variables such as frailty, malnutrition, sarcopenia, quality of life and religiosity. Results: Forty two patients (mean age 66.1; SD: 11.2 years) undergoing hemodialysis for 6.12 years (SD:7.22 years) were included. Anxiety and depression rates reached 54.8% and 57.1% using cut-offs of 6 and 7 respectively on the Hospital Anxiety and Depression rating Scale. 9.5% of the patients reported being in the hospital at the time of the blast and 7.1% reported being injured. 33.3% screened positively for PTSD using a cut-off of 23 on the PCL-5. 26.2% had passive death wishes and 7.1% had suicide plans, however no one had attempted it. 23.8% were found cognitively impaired as shown by the Mini-Cog (<3). Around two-third of participants were moderately to severely malnourished per the GLIM criteria. One third suffered from frailty, according to the FRAIL screening tool. Around 60% suffered from sarcopenia, based on handgrip strength measures. These findings contrast with “acceptable to good” quality of life subjectively reported by participants on the Short Form 36 (SF-36) Health Survey. While one-third of participants participated in organizational religious activities, 88% reported significant subjective meaning of religion in their heart. Conclusions: Rates of depression, anxiety, PTSD, suicidality, and cognitive impairment were found to be alarming in the setting of an urban dialysis unit following a major explosion. Psychiatric disorders were found to be compounded with increased prevalence of malnutrition, frailty, and sarcopenia. These findings urge healthcare providers to implement early diagnostic and intervention strategies to improve both mental and physical wellbeing of this vulnerable population, in similar settings. © 2023, The Author(s)
The effect of workplace bullying on fatigue in school teachers: the moderating roles of gender and spirituality
Get PDFWorkplace bullying is quite prevalent and has been linked to many health complaints. The relationship between workplace bullying and fatigue was documented in previous studies. However, knowledge on how this relationship develops with the interplaying factors of spirituality and gender was not investigated before especially among schoolteachers. The aim of this study is to explore the relationship between workplace bullying and fatigue as moderated by spirituality and gender among schoolteachers in Lebanon. This is a cross-sectional study, where 215 schoolteachers aged 18 till 64 and employed for a minimum of 6 months were recruited through systematic sampling. Six private and six public schools in Beirut participated in the study. Online questionnaires using validated scales were used. Both simple and multiple ordinal logistic regression were performed for the statistical analysis. Results showed that workplace bullying is a predictor of fatigue with an odds ratio of 2.74 and p-value 0.008. Gender was found to be an effect modifier for this relationship, mainly among females (OR 2.66, p-value 0.047) but not among males. Anxiety and depression also predicted higher levels of fatigue (OR 5.75, p-value 0.017). Spirituality did not moderate this relationship. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
Vision Impairment and Patient Activation among Medicare Beneficiaries
Get PDFPurpose: Low patient activation is associated with poor patient outcomes. People with vision impairment may have low patient activation as a result of communication and access barriers. We examined the association of patient activation with vision impairment. Methods: Cross-sectional study using the 2016 Medicare Current Beneficiary Survey. Older Medicare beneficiaries, without dementia, who completed the topical patient activation questionnaire were included. The primary exposure was self-reported vision impairment (no vision impairment, a little vision impairment, a lot of vision impairment), and the secondary exposure was dual sensory impairment (no sensory impairment, vision impairment only, hearing impairment only, dual sensory impairment). Patient activation scores were categorized as low, moderate, or high based on their distribution around the mean. Multivariable-adjusted ordinal regression models examined the association of patient activation with vision impairment, and then with dual sensory impairment. Results: In total, 6,683 participants were included. Those with a little vision impairment had 20% lower odds of higher patient activation (odds ratio [OR] = 0.80, 95% confidence interval [CI] = 0.71–0.90), and those with a lot of vision impairment had 26% lower odds of higher patient activation (OR = 0.74, 95% CI = 0.55–0.98). In the second model, having vision or hearing impairment only was associated with lower odds of higher activation than having no sensory impairment. Having dual sensory impairment was associated with even lower odds of higher activation. Conclusion: Older Medicare beneficiaries with sensory impairment may be a group to target to improve patient activation levels, which could potentially improve health outcomes and health care utilization patterns in this population. © 2022 Taylor & Francis Group, LLC
Consensus on the management of platinum-sensitive high-grade serous epithelial ovarian cancer in Lebanon
Get PDFOvarian cancer is the most lethal gynecologic cancer. The high grade serous epithelial (HGSE) subtype is the most aggressive and it often presents at advanced stages, while screening programs have not proven beneficial. Management of the advanced stages (FIGO III and IV), which constitute the majority of diagnoses, usually consists of platinum-based chemotherapy and cytoreductive surgery (primary or interval) followed by maintenance therapy. Currently, the standard-of-care for advanced newly diagnosed HGSE ovarian cancer, as per international medical societies, starts with upfront cytoreductive surgery, followed by platinum-based chemotherapy (mostly carboplatin and paclitaxel) and/or anti-angiogenic agent bevacizumab, then maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor with/without/or bevacizumab (continued). PARP inhibitor use depends on the patient's genetic signature, mainly the breast cancer gene (BRCA) mutation and the homologous recombination deficiency (HRD) status. Therefore, genetic testing is recommended at diagnosis to inform treatment and prognosis. In line with the evolving standard-of-care for ovarian cancer, a panel of experts in treating advanced ovarian cancer convened to lay down practical recommendations on the management of advanced ovarian cancer in Lebanon; since the currently applicable guidelines by the Lebanese Ministry of Public Health for cancer treatment have not been updated yet to reflect the treatment paradigm shift brought upon by the development and approval of PARP inhibitors. The current work reviews the leading clinical trials on PARP inhibitors (as maintenance for newly diagnosed advanced and platinum-sensitive relapsed ovarian cancer), presents international recommendations, and proposes treatment algorithms for optimal local practice. © 2023 The Author(s
Annular Lichenoid Dermatitis of Youth: Its Pathogenesis, Diagnosis, and Management
No full textAnnular lichenoid dermatitis of youth (ALDY) is a newly described controversial benign lichenoid inflammatory cutaneous disorder often characterized by annular patches with hypopigmented center and surrounding erythematous border. Primarily, it affects the trunk and groin of young patients. Since its first description in 2003, additional patients have been reported, leading to better characterization of the entity; nevertheless, the pathogenesis is still unclear, and several hypotheses have been provided about possible triggering or causative factors. It tends to follow a chronic course, with some lesions spontaneously remitting, while others may be persistent or recur post-treatment. No standard validated treatment has been indicated so far for this disorder. Commonly prescribed topical treatment includes corticosteroids and calcineurin inhibitors with variable response
The Ketogenic Diet in Colorectal Cancer: A Means to an End
Get PDFSome diets, such as high lipid and high glucose diets, are known to increase the risk of colorectal cancer. On the other hand, little is known about diets that prevent colonic carcinogenesis. The ketogenic diet, which is characterized by high fat and very low carbohydrate content, is one such diet. The ketogenic diet decreases the amount of available glucose for tumors and shifts to the production of ketone bodies as an alternative energy source for healthy cells. Cancer cells are unable to use the ketone bodies for energy thus depriving them of the energy needed for progression and survival. Many studies reported the beneficial effects of the ketogenic diet in several types of cancers. Recently, the ketone body β-hydroxybutyrate has been found to possess anti-tumor potential in colorectal cancer. Despite its beneficial effects, the ketogenic diet also has some drawbacks, some of which are related to gastrointestinal disorders and weight loss. Thus, studies are being directed at this time towards finding alternatives to following a strict ketogenic diet and supplementing patients with the ketone bodies responsible for its beneficial effects in the hope of overcoming some potential setbacks. This article discusses the mechanism by which a ketogenic diet influences growth and proliferation of tumor cells, it sheds the light on the most recent trials regarding its use as an adjunctive measure to chemotherapy in patients with metastatic colorectal cancer, and it explains the limitations of its usage in metastatic patients and the promising role of exogenous ketone supplementation in this setting. © 2023 by the authors
Coping strategies and personal growth: The case of Palestinian refugees in Shatila camp, Lebanon
Get PDFThis study investigated the relationship between coping strategies used by adolescent refugees in the Palestinian refugees’ Shatila camp in Lebanon and posttraumatic growth. Moreover, the study explored and predicted the impact of coping strategies utilized by adolescent Palestinians in Shatila camp, Lebanon on their personal growth and psychological well-being. Data were collected using two questionnaires and a checklist: (a) LEC-5 checklist as an assessment tool to make sure that all the participants have faced or experienced stressful events, (b) questionnaires including the Ways of Coping Questionnaire (WCQ) to find out the style of coping refugees used, and (c) Posttraumatic Growth Inventory (PTGI) to identify the factors of growth refugees developed as a result of using different coping strategies. Sixty adolescent refugees at one of the centers in the camp (31 females and 29 males) who benefited from counseling services participated in the study. Adolescent refugees’ performance on the checklist and questionnaires revealed the prevalence of stressors among the refugees. The coping strategies mostly utilized were problem-focused coping strategies, as there was a correlation between its factors and some coping strategies, and there were coping strategies used that predict the development of growth among. Finally, as for the counseling and training programs and services, interventions and guidance services seem to better prepare refugees to handle and cope with the stress that they encounter to develop personal growth. Copyright © 2023 Al Beainy and El Hassan
Does time to angiography affect the survival of trauma patients with embolization to the pelvis? A retrospective study across trauma centers in the United States
Get PDFIntroduction: Traumatic pelvic injuries can result in rapid exsanguination. Bleeding control interventions include stabilization, angiography, and possible embolization. Previous studies yielded conflicting results regarding the benefit of a shorter time to embolization. Objectives: The aim of this study is to examine the impact of the time to angioembolization on the survival of patients presenting with pelvic injuries using a national database. Materials and Methods: This was an observational retrospective study that used the National Trauma Data Bank 2017 dataset. Adult patients with pelvic injuries and who received angiography with embolization to the pelvis were included. Univariate and bivariate analyses (survival to hospital discharge yes/no) were done. This was followed by a multivariable logistic regression analysis to assess the impact of time to angiography on survival to hospital discharge after adjusting for potential confounders. Results: A total of 1,057 patients were included. They were predominantly of male gender (69.3 %) with a median age of 50 years (IQR = [31–64]). The mean time to pelvic angiography was 264.0 ± 204.4 min. The overall survival rate at hospital discharge was 72.0 %. Time to angiography was not significantly associated with survival to hospital discharge before and after adjusting for clinically and statistically significant confounders (aOR = 1.000; 95 %CI=[0.999 – 1.001]; p = 0.866). Conclusion: Time to angiography was not associated with survival to hospital discharge of patients with pelvic injuries who required embolization. Further research examining specific patterns of injuries and assessing the impact of early angioembolization is needed. © 2023 Elsevier Lt