Menstrual health and period poverty in Lebanon during economic crisis: A qualitative analysis of the challenges and recommendations.

Objective: Recently, severe period poverty has had a dramatic spread throughout Lebanon as a result of several crises: the COVID-19 pandemic, the Beirut explosion, and the economic collapse. Period poverty is the lack of access to menstrual hygiene materials, comfortable environments, and adequate education about menstrual health. Due to the great implications of period poverty on Lebanese women's health, our study aims to explore stakeholder's perspective on the Lebanese public health policy regarding menstrual health, the evolving challenges it faces in the context of the current economic collapse, and to suggest recommendations for solutions. Methods: Our study is qualitative in nature, where data collection was done via online semi-structured interviews with stakeholders from the public and private sectors of the Lebanese healthcare system in addition to non-governmental organizations (NGOs) and physicians. Data were then analyzed based on themes and subthemes that emerged from the interviews. Results: Nine stakeholders were interviewed: five from NGOs, two obstetrics and gynecology physicians, and two public sector representatives. The challenges to menstrual health were subcategorized into previously existing and new ones. The consequences of poor menstrual health were tackled on the mental, physical, and social levels. Stakeholders suggested both short-term and long-term recommendations. Short-term recommendations included decreasing the monetary burden by subsidizing menstrual products or via a coupon system. Long-term recommendations included proper education on multiple levels, cooperation between key players in the private and public sectors, and encouragement of local production to ensure future sustainability. Conclusion: Menstrual health is a neglected public health issue in Lebanon, causing detrimental effects on girls and women residing in the country. Proper planning and collaboration between the private and public sectors are required to address this human rights issue.

SMPDL3b modulates radiation-induced DNA damage response in renal podocytes.

The kidneys are radiosensitive and dose-limiting organs for radiotherapy (RT) targeting abdominal and paraspinal tumors. Excessive radiation doses to the kidneys ultimately lead to radiation nephropathy. Our prior work unmasked a novel role for the lipid-modifying enzyme, sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b), in regulating the response of renal podocytes to radiation injury. In this study, we investigated the role of SMPDL3b in DNA double-strand breaks (DSBs) repair in vitro and in vivo. We assessed the kinetics of DSBs recognition and repair along with the ATM pathway and nuclear sphingolipid metabolism in wild-type (WT) and SMPDL3b overexpressing (OE) human podocytes. We also assessed the extent of DNA damage repair in SMPDL3b knock-down (KD) human podocytes, and C57BL6 WT and podocyte-specific SMPDL3b-knock out (KO) mice after radiation injury. We found that SMPDL3b overexpression enhanced DSBs recognition and repair through modulating ATM nuclear shuttling. OE podocytes were protected against radiation-induced apoptosis by increasing the phosphorylation of p53 at serine 15 and attenuating subsequent caspase-3 cleavage. SMPDL3b overexpression prevented radiation-induced alterations in nuclear ceramide-1-phosphate (C1P) and ceramide levels. Interestingly, exogenous C1P pretreatment radiosensitized OE podocytes by delaying ATM nuclear foci formation and DSBs repair. On the other hand, SMPDL3b knock-down, in vitro and in vivo, induced a significant delay in DSBs repair. Additionally, increased activation of apoptosis was induced in podocytes of SMPDL3b-KO mice compared to WT mice at 24 h post-irradiation. Together, our results unravel a novel role for SMPDL3b in radiation-induced DNA damage response. The current work suggests that SMPDL3b modulates nuclear sphingolipid metabolism, ATM nuclear shuttling, and DSBs repair.

Translational Aspects of the Mammalian Target of Rapamycin Complexes in Diabetic Nephropathy.

Significance: Despite the many efforts put into understanding diabetic nephropathy (DN), direct treatments for DN have yet to be discovered. Understanding the mechanisms behind DN is an essential step in the development of novel therapeutic regimens. The mammalian target of rapamycin (mTOR) pathway has emerged as an important candidate in the quest for drug discovery because of its role in regulating growth, proliferation, as well as protein and lipid metabolism. Recent Advances: Kidney cells have been found to rely on basal autophagy for survival and for conserving kidney integrity. Recent studies have shown that diabetes induces renal autophagy deregulation, leading to kidney injury. Hyper-activation of the mTOR pathway and oxidative stress have been suggested to play a role in diabetes-induced autophagy imbalance. Critical Issues: A detailed understanding of the role of mTOR signaling in diabetes-associated complications is of major importance in the search for a cure. In this review, we provide evidence that mTOR is heavily implicated in diabetes-induced kidney injury. We suggest possible mechanisms through which mTOR exerts its negative effects by increasing insulin resistance, upregulating oxidative stress, and inhibiting autophagy. Future Directions: Both increased oxidative stress and autophagy deregulation are deeply embedded in DN. However, the mechanisms controlling oxidative stress and autophagy are not well understood. Although Akt/mTOR signaling seems to play an important role in oxidative stress and autophagy, further investigation is required to uncover the details of this signaling pathway. Antioxid. Redox Signal. 37, 802-819.

Abdominal apoplexy: A rare case of spontaneous middle colic artery rupture with transverse colectomy.

INTRODUCTION AND IMPORTANCE: Idiopathic spontaneous intraperitoneal hemorrhage (ISIH) is a rare but potentially fatal entity. The majority of the reported cases of ISIH due to middle colic artery rupture are associated with pseudoaneurysm. Our case is unique in that no pathology could be identified. To our knowledge, this is the third case report in the literature of a spontaneous middle colic artery rupture with no underlying pathology. CASE PRESENTATION: In our report, we present the case of a 27-years old male presenting with a hemoperitoneum due to ruptured middle colic artery with no evidence of pseudoaneurysm or any other pathology. The patient's hemodynamic status deteriorated abruptly requiring a damage control exploratory laparotomy for evacuation of the hemoperitoneum, ligation of the middle colic artery and transverse colectomy. The post-operative course was uneventful afterwards and the patient was discharged a week after presentation with full recovery. DISCUSSION: Patients with ISIH might exhibit the "double rupture" phenomenon, compromising their hemodynamic stability and necessitating urgent surgical interventions. CTA can be of paramount importance to guide such interventions if the patient's clinical status permits. Angiographic embolization is an acceptable alternative approach in specific situations. CONCLUSION: ISIH should be on the differential diagnosis of any young patient presenting to the ED with an acute abdomen, regardless of the identifiable risk factors.

Modulation of DNA Damage Response by Sphingolipid Signaling: An Interplay that Shapes Cell Fate.

Although once considered as structural components of eukaryotic biological membranes, research in the past few decades hints at a major role of bioactive sphingolipids in mediating an array of physiological processes including cell survival, proliferation, inflammation, senescence, and death. A large body of evidence points to a fundamental role for the sphingolipid metabolic pathway in modulating the DNA damage response (DDR). The interplay between these two elements of cell signaling determines cell fate when cells are exposed to metabolic stress or ionizing radiation among other genotoxic agents. In this review, we aim to dissect the mediators of the DDR and how these interact with the different sphingolipid metabolites to mount various cellular responses.

Modulation of radiation-induced damage of human glomerular endothelial cells by SMPDL3B.

The intracellular molecular pathways involved in radiation-induced nephropathy are still poorly understood. Glomerular endothelial cells are key components of the structure and function of the glomerular filtration barrier but little is known about the mechanisms implicated in their injury and repair. The current study establishes the response of immortalized human glomerular endothelial cells (GEnC) to ionizing radiation (IR). We investigated the role of sphingolipids and the lipid-modifying enzyme sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) in radiation-induced GEnC damage. After delivering a single dose of radiation, long and very-long-chain ceramide species, and the expression levels of SMPDL3b were elevated. In contrast, levels of ceramide-1-phosphate (C1P) dropped in a time-dependent manner although mRNA and protein levels of ceramide kinase (CERK) remained stable. Treatment with C1P or knocking down SMPDL3b partially restored cell survival and conferred radioprotection. We also report a novel role for the NADPH oxidase enzymes (NOXs), namely NOX1, and NOX-derived reactive oxygen species (ROS) in radiation-induced GEnC damage. Subjecting cultured endothelial cells to radiation was associated with increased NOX activity and superoxide anion generation. Silencing NOX1 using NOX1-specific siRNA mitigated radiation-induced oxidative stress and cellular injury. In addition, we report a novel connection between NOX and SMPDL3b. Treatment with the NOX inhibitor, GKT, decreased radiation-induced cellular injury and restored SMPDL3b basal levels of expression. Our findings indicate the importance of SMPDL3b as a potential therapeutic target in radiation-induced kidney damage.

Translational Aspects of Sphingolipid Metabolism in Renal Disorders.

Sphingolipids, long thought to be passive components of biological membranes with merely a structural role, have proved throughout the past decade to be major players in the pathogenesis of many human diseases. The study and characterization of several genetic disorders like Fabry's and Tay Sachs, where sphingolipid metabolism is disrupted, leading to a systemic array of clinical symptoms, have indeed helped elucidate and appreciate the importance of sphingolipids and their metabolites as active signaling molecules. In addition to being involved in dynamic cellular processes like apoptosis, senescence and differentiation, sphingolipids are implicated in critical physiological functions such as immune responses and pathophysiological conditions like inflammation and insulin resistance. Interestingly, the kidneys are among the most sensitive organ systems to sphingolipid alterations, rendering these molecules and the enzymes involved in their metabolism, promising therapeutic targets for numerous nephropathic complications that stand behind podocyte injury and renal failure.