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Abstract Background Lebanon, an Eastern Mediterranean country with a lower-middle income status, that once boasted a health care system that was functional despite its challenges and complexity. However, it has faced a series of crises—economic, an influx of refugees, political instability, and recent sanctions—that have significantly impacted its aim, principles and values that has impacted upon its ability to function. The objective of this study is to delve into the health service delivery within the Lebanese system and conduct a SWOT analysis (assessing strengths, weaknesses, opportunities, and threats). Methods We conducted a scoping review, examining literature related to the Lebanese health system and its performance in delivering healthcare services. We followed the Arksey and O’Malley framework, which involves six key phases: identifying the research question, identifying relevant studies, study selection, charting the data, collating, summarizing, and reporting the results, consultation. Results Despite Lebanon grappling with multiple crises in recent years—such as the COVID-19 pandemic and economic downturn—the health system has demonstrated resilience in service delivery. However, challenges persist. Healthcare providers, including physicians and nurses, must address these issues. Additionally, economic and political crises pose threats that have necessitated significant changes in healthcare service delivery. Conclusion In the system of healthcare in Lebanon, there have been remarkable achievements, but continuous attention by healthcare providers and the Ministry of Public Health (MoPH) is critical. Economic and political challenges exert constant pressure on service delivery and thus reveal a need for strategic changes, most importantly in health financing if Universal Health Coverage (UHC) is to be attained. Proper resources to strategic reform and system implementation in all parts of the country to ensure equitable access and quality care that is sustained are obligatory.

Abstract Background Rickettsial disease has been commonly associated with retinitis, retinal vasculitis, and optic nerve involvement, but the development of retinal neovascularization has been very rarely reported. We herein describe a case of rickettsial retinitis complicated with the development of sea-fan retinal neovascularization documented with multimodal imaging, including fundus photography, SS-OCT, fluorescein angiography, and SS-OCT angiography. Case presentation A 26-year-old female with a history of fever one week earlier presented with sudden decreased vision in the left eye. Best-corrected visual acuity (BCVA) was 20/2000 and the patient was diagnosed with rickettsial retinitis along the superotemporal retinal vascular arcade associated with serous retinal detachment and retinal hard exudates. The indirect immunofluorescence test was positive for Rickettsia conorii, and the patient was treated with oral doxycycline (200 mg/day) and oral prednisone (0.75 mg/kg/day, with gradual tapering). Four weeks after presentation, the retinal infiltrate and associated serous retinal detachment had resolved, but retinal hard exudates had increased. A large sea-fan preretinal fibrovascular neovascularization became apparent along the superotemporal retinal vascular arcade, but there was no associated retinal ischemia on fluorescein angiography. The patient received an adjunctive single intravitreal injection of 1.25 bevacizumab. Sequential follow-up examinations showed shrinking of sea-fan retinal neovascularization, a complete resolution of retinal hard exudates, and the development of a self-limited vitreous hemorrhage. On last follow-up, 30 months after intravitreal bevacizumab injection, BCVA was 20/25. Conclusion Patients with rickettsial retinitis may develop a sea-fan retinal neovascularization, with subsequent vitreous hemorrhage, putatively through inflammatory mechanisms. Multimodal imaging including OCT, fluorescein angiography, and OCT-angiography, is highly useful for accurate diagnosis and reliable monitoring of the evolution of retinitis, retinal neovascularization, and other retinal changes. The use of a combination therapy with oral doxycycline and corticosteroids and intravitreal anti-VEGF can improve outcomes.

Abstract The development of intelligent and programmable smart composite structure that can remember and restore their original shape after being extensively deformed is highly sought after for a wide variety of applications, such as deployable and morphing structures, soft robots, and smart infrastructure. Despite recent advancements, there remains a plethora of unexplored possibilities in the field of deployable structures utilizing shape programmable and intelligent composite materials. The aim of this research is to manufacture a deployable structure that is intelligent enough to monitor the deployment and programmable to be deployed in specific way. Here, a smart deployable auxetic structure is reported that not only possesses thermal and piezoresistive sensing properties but also acts as a thermally activated intelligent shape memory polymer composite (iSMPC). We have fabricated an intelligent fabric and embedded it as reinforcement within a polyurethane-based shape memory polymer matrix to make an intelligent auxetic (A-iSMPC) structure. It has been demonstrated that the intelligent fabric enhances the overall mechanical properties of the auxetic structure and allows monitoring the temperature variation and strain changes during shape programming and recovery. The A-iSMPC offered a negative Poisson’s ratio of − 0.44, shape recovery ratio of 96%, shape fixity ratio of 88% and compaction ratio of 62%. With its shape memory, auxetic, thermal and piezoresistive sensing capabilities, this iSMPC has the potential to be a multifunctional and multipurpose structure for a variety of applications.

Abstract Background Dogs are considered the main domestic animals that may be a reservoir for Leishmania infantum, the agent of zoonotic visceral leishmaniasis (ZVL) in several countries of the world. The dog may host other Leishmania species, but its epidemiological role in the maintenance and spreading of these parasites is not completely elucidated. Zoonotic cutaneous leishmaniasis (ZCL), caused by Leishmania major, affects thousands of people every year and is particularly diffused in many countries of North Africa and Middle East Asia. In ZCL endemic countries, few reports of L. major-positive dogs have been reported, probably because most human cases occur in poor rural areas where the social role of the dog and its medical management is not well considered. The aim of the present study is to better understand the possible involvement of domestic dogs in the epidemiology of ZCL. Methods Our research focused on a well-established endemic focus of ZCL, in the area of Echrarda, Kairouan Governorate, central Tunisia. A total of 51 dogs with no or mild clinical signs of vector borne diseases were selected in small villages where human cases of ZCL are yearly present. All dogs were sampled for the Leishmania spp. diagnosis, by using the following procedures: blood sample for serology and buffy coat quantitative polymerase chain reaction (qPCR), popliteal fine needle aspiration, and cutaneous biopsy punch for lymph node and skin qPCR. Results The results demonstrated a high percentage (21.6%) of dogs positive at least at one or more test; the most sensitive technique was the lymph node qPCR that detected 8/11 positive dogs. Nine, out of the eleven positive dogs, resulted as infected by Leishmania infantum; ITS1-PCR-sequencing allowed Leishmania major identification in the remaining two cases, both from the popliteal lymph node samples, which can suggest a possible visceral spread of a cutaneous Leishmania species in the dog. Interestingly, one of the two L. major-positive dogs was living in the same house where 6-year-old children showed cutaneous lesions referred to as ZCL. Conclusions To our knowledge, this is the first report of L. major-positive dogs in Tunisia, the epidemiological role of which remains under investigation. Graphical Abstract

BACKGROUND: Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration. METHODS: This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (

Introduction: The pathophysiology of idiopathic intracranial hypertension (IIH) is not fully characterized, and less is known about its development in transgender patients. Several cases of IIH in transgender patients have been reported, but fewer cases have been published that identify a cerebrospinal fluid (CSF) leak as a complication of IIH in this population. These patients can serve as an important study population, as an association between exogenous testosterone use in karyotypical females and development of IIH may support a hormonally mediated mechanism of development of this disease. Case Presentation: We describe the case of a 33-year-old obese (BMI: 30.58 kg/m2) female-to-male transgender patient on exogenous testosterone for 15 years who presented with 1 month of acute or chronic headache with profuse rhinorrhea. Fundoscopic exam revealed disk pallor and edema consistent with a Frisen grade 3 papilledema. Nasal secretion was positive for beta-2 transferrin, consistent with CSF. Computed tomography head demonstrated a 5-mm defect in the medial left middle cranial fossa, bilateral optic nerve prominence and tortuosity, and abnormal arachnoid granulations concerning for IIH. After a successful endoscopic endonasal repair of the left lateral sphenoid recess leak, our patient continued to report headaches, was started on acetazolamide, and noted improvement in symptoms. Conclusion: The case described herein further supports the growing body of evidence that implicates a hormonal mechanism of action in the development of IIH. Importantly, it also addresses the need for increased study and conversation about rare neurologic diseases in transgender patients.

Abstract Background In humanitarian settings, brief screening instruments for child psychological distress have potential to assist in assessing prevalence, monitoring outcomes, and identifying children and adolescents in most need of scarce resources, given few mental health professionals for diagnostic services. Yet, there are few validated screening tools available, particularly in Arabic. Methods We translated and adapted the Child Psychosocial Distress Screener (CPDS) and the Pediatric Symptom Checklist (PSC) and conducted a validation study with 85 adolescents (aged 10–15) in Lebanon. We assessed internal consistency; test-retest reliability; convergent validity between adolescent- and caregiver-report and between the two measures; ability to distinguish between clinical and non-clinical samples; and concurrent validity against psychiatrist interview using the Kiddie Schedule for Affective Disorders and Schizophrenia. Results The translated and adapted child-reported PSC-17 and PSC-35, and caregiver-reported PSC-35 all showed adequate internal consistency and test-retest reliability and high concurrent validity with psychiatrist interview and were able to distinguish between clinical and non-clinical samples. However, the caregiver-reported PSC-17 did not demonstrate adequate performance in this setting. Child-reported versions of the PSC outperformed caregiver-reported versions and the 35-item PSC scales showed stronger performance than 17-item scales. The CPDS showed adequate convergent validity with the PSC, ability to distinguish between clinical and non-clinical samples, and concurrent validity with psychiatrist interview. Internal consistency was low for the CPDS, likely due to the nature of the brief risk-screening tool. There were discrepancies between caregiver and child-reports, worthy of future investigation. For indication of any diagnosis requiring treatment, we recommend cut-offs of 5 for CPDS, 12 for child-reported PSC-17, 21 for child-reported PSC-35, and 26 for caregiver-reported PSC-35. Conclusions The Arabic PSC and CPDS are reliable and valid instruments for use as primary screening tools in Lebanon. Further research is needed to understand discrepancies between adolescent and caregiver reports, and optimal methods of using multiple informants.

Abstract Background Breast cancer (BC) is the most commonly diagnosed cancer in women. Treatment approaches that differ between estrogen-positive (ER+) and triple-negative BC cells (TNBCs) and may subsequently affect cancer biomarkers, such as H19 and telomerase, are an emanating delight in BC research. For instance, all-trans-Retinoic acid (ATRA) could represent a potent regulator of these oncogenes, regulating microRNAs, mostly let-7a microRNA (miR-let-7a), which targets the glycolysis pathway, mainly pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA) enzymes. Here, we investigated the potential role of ATRA in H19, telomerase, miR-let-7a, and glycolytic enzymes modulation in ER + and TNBC cells. Methods MCF-7 and MDA-MB-231 cells were treated with 5 µM ATRA and/or 100 nM fulvestrant. Then, ATRA-treated or control MCF-7 cells were transfected with either H19 or hTERT siRNA. Afterward, ATRA-treated or untreated MDA-MB-231 cells were transfected with estrogen receptor alpha ER(α) or beta ER(β) expression plasmids. RNA expression was evaluated by RT‒qPCR, and proteins were assessed by Western blot. PKM2 activity was measured using an NADH/LDH coupled enzymatic assay, and telomerase activity was evaluated with a quantitative telomeric repeat amplification protocol assay. Student’s t-test or one-way ANOVA was used to analyze data from replicates. Results Our results showed that MCF-7 cells were more responsive to ATRA than MDA-MB-231 cells. In MCF-7 cells, ATRA and/or fulvestrant decreased ER(α), H19, telomerase, PKM2, and LDHA, whereas ER(β) and miR-let-7a increased. H19 or hTERT knockdown with or without ATRA treatment showed similar results to those obtained after ATRA treatment, and a potential interconnection between H19 and hTERT was found. However, in MDA-MB-231 cells, RNA expression of the aforementioned genes was modulated after ATRA and/or fulvestrant, with no significant effect on protein and activity levels. Overexpression of ER(α) or ER(β) in MDA-MB-231 cells induced telomerase activity, PKM2 and LDHA expression, in which ATRA treatment combined with plasmid transfection decreased glycolytic enzyme expression. Conclusions To the best of our knowledge, our study is the first to elucidate a new potential interaction between the estrogen receptor and glycolytic enzymes in ER + BC cells through miR-let-7a.

Abstract Despite recent developments on the design of dynamic catalysts, none of them have been exploited for the in-situ control of multiple stereogenic centers in a single molecular scaffold. We report herein that it is possible to obtain in majority any amongst the four possible stereoisomers of an amino alcohol by means of a switchable asymmetric catalyst built on supramolecular helices. Hydrogen-bonded assemblies between a benzene-1,3,5-tricarboxamide (BTA) achiral phosphine ligand coordinated to copper and a chiral BTA comonomer are engaged in a copper-hydride catalyzed hydrosilylation and hydroamination cascade process. The nature of the product stereoisomer is related to the handedness of the helices and can thus be directed in a predictable way by changing the nature of the major enantiomer of the BTA comonomer present in the assemblies. The strategy allows all stereoisomers to be obtained one-pot with similar selectivities by conducting the cascade reaction in a concomitant manner, i.e. without inverting the handedness of the helices, or sequentially, i.e. by switching the handedness of the supramolecular helices between the hydrosilylation and hydroamination steps. Supramolecular helical catalysts appear as a unique and versatile platform to control the configuration of molecules or polymers embedding several stereogenic centers.

Fasting triggers diverse physiological adaptations including increases in circulating fatty acids and mitochondrial respiration to facilitate organismal survival. The mechanisms driving mitochondrial adaptations and respiratory sufficiency during fasting remain incompletely understood. Here we show that fasting or lipid availability stimulates mTORC2 activity. Activation of mTORC2 and phosphorylation of its downstream target NDRG1 at serine 336 sustains mitochondrial fission and respiratory sufficiency. Time-lapse imaging shows that NDRG1, but not the phosphorylation-deficient NDRG1Ser336Ala mutant, engages with mitochondria to facilitate fission in control cells, as well as in those lacking DRP1. Using proteomics, a small interfering RNA screen, and epistasis experiments, we show that mTORC2-phosphorylated NDRG1 cooperates with small GTPase CDC42 and effectors and regulators of CDC42 to orchestrate fission. Accordingly, RictorKO, NDRG1Ser336Ala mutants and Cdc42-deficient cells each display mitochondrial phenotypes reminiscent of fission failure. During nutrient surplus, mTOR complexes perform anabolic functions; however, paradoxical reactivation of mTORC2 during fasting unexpectedly drives mitochondrial fission and respiration.