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Abstract Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with a high risk of psychiatric and neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack of effective treatments underscore the urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as a crucial bidirectional pathway connecting the brain and the gastrointestinal (GI) system through an intricate network of neuronal, hormonal, and immunological pathways. Four main pathways are primarily implicated in this crosstalk, including the systemic immune system, autonomic and enteric nervous systems, neuroendocrine system, and microbiome. TBI induces profound changes in the gut, initiating an unrestrained vicious cycle that exacerbates brain injury through the brain-gut axis. Alterations in the gut include mucosal damage associated with the malabsorption of nutrients/electrolytes, disintegration of the intestinal barrier, increased infiltration of systemic immune cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction and disruption in the enteric nervous system (ENS) and autonomic nervous system (ANS). Collectively, these changes further contribute to brain neuroinflammation and neurodegeneration via the gut-brain axis. In this review article, we elucidate the roles of various anti-inflammatory pharmacotherapies capable of attenuating the dysregulated inflammatory response along the brain-gut axis in TBI. These agents include hormones such as serotonin, ghrelin, and progesterone, ANS regulators such as beta-blockers, lipid-lowering drugs like statins, and intestinal flora modulators such as probiotics and antibiotics. They attenuate neuroinflammation by targeting distinct inflammatory pathways in both the brain and the gut post-TBI. These therapeutic agents exhibit promising potential in mitigating inflammation along the brain-gut axis and enhancing neurocognitive outcomes for TBI patients.

Background & Aims: The abdominal discomfort experienced by patients with colitis may be attributable in part to the presence of small intestinal dysmotility, yet mechanisms linking colonic inflammation with small-bowel motility remain largely unexplored. We hypothesize that colitis results in small intestinal hypomotility owing to a loss of enteroendocrine cells (EECs) within the small intestine that can be rescued using serotonergic-modulating agents. Methods: Male C57BL/6J mice, as well as mice that overexpress (EECOVER) or lack (EECDEL) NeuroD1+ enteroendocrine cells, were exposed to dextran sulfate sodium (DSS) colitis (2.5% or 5% for 7 days) and small intestinal motility was assessed by 70-kilodalton fluorescein isothiocyanate–dextran fluorescence transit. EEC number and differentiation were evaluated by immunohistochemistry, terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling staining, and quantitative reverse-transcriptase polymerase chain reaction. Mice were treated with the 5-hydroxytryptamine receptor 4 agonist prucalopride (5 mg/kg orally, daily) to restore serotonin signaling. Results: DSS-induced colitis was associated with a significant small-bowel hypomotility that developed in the absence of significant inflammation in the small intestine and was associated with a significant reduction in EEC density. EEC loss occurred in conjunction with alterations in the expression of key serotonin synthesis and transporter genes, including Tph1, Ddc, and Slc6a4. Importantly, mice overexpressing EECs revealed improved small intestinal motility, whereas mice lacking EECs had worse intestinal motility when exposed to DSS. Finally, treatment of DSS-exposed mice with the 5-hydroxytryptamine receptor 4 agonist prucalopride restored small intestinal motility and attenuated colitis. Conclusions: Experimental DSS colitis induces significant small-bowel dysmotility in mice owing to enteroendocrine loss that can be reversed by genetic modulation of EEC or administering serotonin analogs, suggesting novel therapeutic approaches for patients with symptomatic colitis.

Summary: Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder resulting from a balanced translocation leading to BCR::ABL1 oncogene with increased tyrosine kinase activity. Despite the advancements in the development of tyrosine kinase inhibitors (TKIs), the T315I gatekeeper point mutation in the BCR::ABL1 gene remains a challenge. We have previously reported in a Drosophila CML model an increased hemocyte count and disruption in sessile hemocyte patterns upon expression of BCR::ABL1p210 and BCR::ABL1T315I in the hemolymph. In this study, we performed RNA sequencing to determine if there is a distinct gene expression that distinguishes BCR::ABL1p210 and BCR::ABL1T315I. We identified six genes that were consistently upregulated in the fly CML model and validated in adult and pediatric CML patients and in a mouse cell line expressing BCR::ABL1T315I. This study provides a comprehensive analysis of gene signatures in BCR::ABL1p210 and BCR::ABL1T315I, laying the groundwork for targeted investigations into the role of these genes in CML pathogenesis.

The purpose of this study was to investigate the alignment between the fourth-grade summative classroom assessments and the 'Matter and Energy' unit in the Lebanese science curriculum using: content and cognitive levels. Summative assessments were collected from a sample of 17 schools. The alignment between the classroom assessments and the Lebanese science curriculum were examined using three instruments: Curriculum Coding Sheet, Items Coding Sheet, and Item Analysis Sheet. The curricular learning objectives were used for matching the test items to the learning objectives in terms of content. Findings showed moderate content alignment; further analysis revealed that public schools had higher content alignment, and they covered a wider range of topics. In terms of cognitive level, there was a low alignment between the assessments collected and the curriculum; however, there were items that had higher cognitive level. Recommendations for curriculum developers and future research are discussed in light of these findings.

PURPOSE To assess the knowledge and intention for colorectal cancer (CRC) screening within the Lebanese community before and after a guided tour through an inflatable colon model. METHODS The Cancer Prevention and Control Program, Naef K. Basile Cancer Institute at the American University of Beirut Medical Center in collaboration with AMALOUNA educational nongovernmental organization launched awareness campaigns during which a walk-through inflatable colon was displayed. Pre- and post-surveys related to the age of screening, risk factors, symptoms, and CRC prevention were collected anonymously before and after touring the inflatable colon to assess the effectiveness of this educational tool. RESULTS Compiled data collected from 782 participants revealed that older age and higher education were predictors of favorable CRC screening knowledge and behaviors before entering the inflatable colon. Interestingly, touring the inflatable colon model significantly improved participants’ awareness and knowledge about CRC. Most importantly, it increased their willingness for screening and social engagement and comfort discussing and promoting CRC screening. CONCLUSION Overall, these results indicate that the interactive colon is an effective educational tool that can make a positive impact by improving the community CRC awareness and interest in CRC screening. They also highlight the importance of such educational efforts conducted in the community to create more awareness about CRC and emphasize the importance of its prevention.

Supine [18F]Fluorodeoxyglucose (FDG) positron emission technology/computed tomography (PET/CT) is a commonly used modality for the initial staging of breast cancer, and several previous studies have shown superior sensitivity and specificity of prone FDG PET/CT in comparison to its supine counterpart. This retrospective study included 25 females with breast cancer referred for staging. They underwent supine FDG PET/CT followed by prone FDG PET/CT. The outcomes were: number of primary breast lesions, anatomical site of FDG-avid lymph nodes (LNs), and number and type of bone lesions, with SUVmax of all corresponding parameters. Performance was superior in prone acquisition compared to supine acquisition, with the respective results: 29 vs. 22 breast tumor lesions detected, 62 vs. 27 FDG-avid axillary LNs detected, sensitivity of 68% vs. 57%, specificity of 64% vs. 53%. The detection rate of axillary LNs in the prone position was significantly higher (p = 0.001). SUVmax for breast tumor lesions (p = 0.000) and number of detected axillary LNs (p = 0.002) were significantly higher in prone acquisition. Five patients were upstaged after experts read the prone acquisition. Prone FDG PET/CT acquisition is a promising technique in detecting primary breast lesions and metastatic LNs possibly missed in supine acquisition, which may lead to change in patient staging and management.

Even if usually needed to achieve the gross total resection (GTR) of spinal benign nerve sheath tumors (NSTs), nerve root sacrifice remains controversial regarding the risk of neurological deficit. For foraminal NSTs, we hypothesize that the involved root is poorly functional and thus can be safely sacrificed. All spinal benign NSTs with foraminal extension that underwent surgery from 2013 to 2021 were reviewed. The impacts of preoperative clinical status and patient and tumor characteristics on long-term outcomes were analyzed. Twenty-six patients were included, with a mean follow-up (FU) of 22.4 months. Functional motor roots (C5-T1, L3-S1) were involved in 14 cases. The involved nerve root was routinely sacrificed during surgery and GTR was obtained in 84.6% of cases. In the functional root subgroup, for patients with a pre-existing deficit (n = 5/14), neurological aggravation persisted in one case at last FU (n = 1/5), whereas for those with no preop deficit (n = 9/14), a postoperative deficit persisted in one patient only (n = 1/9). Preoperative radicular pain was the only characteristic significantly associated with an immediate postoperative motor deficit (p = 0.03). The sacrifice of an involved nerve root in foraminal NSTs seems to represent a reasonable and relevant option to resect these tumors, permitting one to achieve tumor resection in an oncologic fashion with a high rate of GTR.

Abstract Background The past few decades have witnessed a tremendous development in the field of genetics. The implementation of next generation sequencing (NGS) technologies revolutionized the field of molecular biology and made the genetic information accessible at a large scale. However, connecting a rare genetic variation to a complex phenotype remains challenging. Indeed, identifying the cause of a genetic disease requires a multidisciplinary approach, starting with the establishment of a clear phenotype with a detailed family history and ending, in some cases, with functional assays that are crucial for the validation of the pathogenicity of a mutation. Methods Two hundred Lebanese patients, presenting a wide spectrum of genetic disorders (neurodevelopmental, neuromuscular or metabolic disorders, etc.), sporadic or inherited, dominant or recessive, were referred, over the last three and a half years, to the Medical Genetics Unit (UGM) of Saint Joseph University (USJ). In order to identify the genetic basis of these diseases, Whole Exome Sequencing (WES), followed by a targeted analysis, was performed for each case. In order to improve the genetic diagnostic yield, WES data, generated during the first 2 years of this study, were reanalyzed for all patients who were left undiagnosed at the genetic level. Reanalysis was based on updated bioinformatics tools and novel gene discoveries. Results Our initial analysis allowed us to identify the specific genetic mutation causing the disease in 49.5% of the cases, in line with other international studies. Repeated WES analysis enabled us to increase the diagnostics yield to 56%. Conclusion The present article reports the detailed results of both analysis and pinpoints the contribution of WES data reanalysis to an efficient genetic diagnosis. Lessons learned from WES reanalysis and interpretation are also shared.

Polydimethylsiloxane (PDMS), a silicone elastomer, is increasingly being used in health and biomedical fields due to its excellent optical and mechanical properties. Its biocompatibility and resistance to biodegradation led to various applications (e.g., lung on a chip replicating blood flow, medical interventions, and diagnostics). The many advantages of PDMS are, however, partially offset by its inherent hydrophobicity, which makes it unsuitable for applications needing wetting, thus requiring the hydrophilization of its surface by exposure to UV or O2 plasma. Yet, the elastomeric state of PDMS translates in a slow, hours to days, process of reducing its surface hydrophilicity—a process denominated as hydrophobic recovery. Using Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM), the present study details the dynamics of hydrophobic recovery of PDMS, on flat bare surfaces and on surfaces embedded with hydrophilic beads. It was found that a thin, stiff, hydrophilic, silica film formed on top of the PDMS material, following its hydrophilization by UV radiation. The hydrophobic recovery of bare PDMS material is the result of an overlap of various nano-mechanical, and diffusional processes, each with its own dynamics rate, which were analyzed in parallel. The hydrophobic recovery presents a hysteresis, with surface hydrophobicity recovering only partially due to a thin, but resilient top silica layer. The monitoring of hydrophobic recovery of PDMS embedded with hydrophilic beads revealed that this is delayed, and then totally stalled in the few-micrometer vicinity of the embedded hydrophilic beads. This region where the hydrophobic recovery stalls can be used as a good approximation of the depth of the resilient, moderately hydrophilic top layer on the PDMS material. The complex processes of hydrophilization and subsequent hydrophobic recovery impact the design, fabrication, and operation of PDMS materials and devices used for diagnostics and medical procedures. Consequently, especially considering the emergence of new surgical procedures using elastomers, the impact of hydrophobic recovery on the surface of PDMS warrants more comprehensive studies.

Burn wound healing is a very intricate and complex process that conventionally includes three interrelated and overlapping stages of hemostasis/inflammation, proliferation and remodeling. This review aims to explore the molecular interactions of NGF with the most prominent cell types in the skin and their respective secretory products during wound healing, particularly burn wound healing. Different types of cells such as, nerve cells, endothelial cells, mast cells, macrophages, neutrophils, keratinocytes and fibroblasts all come into play through a plethora of cytokines and growth factors including nerve growth factor (NGF). NGF is a pleiotropic molecule that exerts its effects on all the aforementioned cells using two types of receptors (TrkA and p75) and affects wound healing by decreasing healing time and improving the quality of the scar. Both receptors mediate cellular proliferation, survival and apoptosis through complex signaling molecules. During the inflammatory phase, macrophages and mast cells secrete ample cytokines and growth factors, including NGF, which participate in the inflammatory reaction and induction of other cells targeting a homeostatic state. The proliferative phase follows, and NGF promotes angiogenesis through VEGF and FGF expression in endothelial cells. NGF also stimulates keratinocyte proliferation and neurite extension through the TrkA-PI3K/Akt pathway. Other molecules such as TGF-β1, IL-1β and TNF-α increase NGF expression in fibroblasts through dynamic interactions with Smads and MAPK molecules. Stimulated fibroblasts induce new collagen production to form the granulation tissue. In the remodeling phase, NGF regulates fibroblasts and induces their differentiation into myofibroblasts ultimately leading to wound contracture. In addition, NGF stimulates melanocytes and enhances hair growth and pigmentation. Such data depict the mechanisms of action of NGF implicated in the various stages of the healing process and support its applicability as a new targeted therapeutic molecule effective in burn wound healing but with some limitations. [ABSTRACT FROM AUTHOR]

Abstract: Outcomes of hematopoietic stem cell transplantation (HSCT) have markedly improved over the past 2 decades, underscoring a need to better understand the long-term health effects of this intensive treatment modality. We describe the burden of chronic medical conditions and frail health among St. Jude Lifetime Cohort Study participants treated for childhood hematologic malignancies with HSCT (n = 112) or with conventional therapy (n = 1106). Chronic conditions and frail health were ascertained clinically and classified according to a modified version of the Common Terminology Criteria for Adverse Events (version 4.03) and the Fried Frailty Criteria. Seventy-nine transplants were allogeneic (41 from a sibling donor, 34 unrelated, and 4 others from related donor). Twenty-five allogeneic donor recipients had a history of chronic graft-versus-host disease. Compared to those treated with conventional therapy, a higher percentage of HSCT survivors had severe, disabling, or life threatening (grade 3-4) chronic conditions (81.3% vs 69.2%, P= .007). By age 25 years, HSCT survivors experienced 148 grade 3-4 events/100 compared to 60 among conventional therapy survivors (P≮ .001). Percentages of survivors with second neoplasms (17.0% vs 7.9%, P= .003), grade 3-4 cardiovascular (19.6% vs 10.2%, P= .004) and pulmonary (16.1% vs 4.6%, P≮ .001) conditions, and frail health (7.1% vs 1.6%, P≮ .001) were higher after HSCT than conventional therapy. These results underscore the need for clinical follow-up and provide data to guide the development of prevention and/or intervention strategies for this vulnerable population.

Objectives. The aim of this study is to demonstrate the various imaging appearances of stromal fibrosis on mammography, ultrasound, and magnetic resonance imaging (MRI). Material and Methods. This study included 75 female patients who presented to the American University of Beirut Medical Center between January 2010 and October 2015 for breast imaging. 66 (88%) patients obtained a mammogram, 71 (95%) had an ultrasound, and 6 (8%) had an MRI. Patients included had stromal fibrosis proven on biopsy. Results. The most common finding on mammogram was calcifications which was present in 14 (21%) patients, while on ultrasound it was a mass which was present in 61 (86%) patients. A mass was detected on MRI in 2 (33.5%) patients. Most lesions detected had benign findings such as masses with circumscribed margins. We had a follow-up for 53 (71%) patients with an average follow-up interval of 28.5 months (range: 5 – 70). Increase in size of the index lesion was noted in only 2 patients; upon rebiopsy, pathology results read stromal fibrosis for one lesion and fibroadenoma for the other. The remaining lesions were either stable or decreased in size. The higher detection rate of a mass on ultrasound was statistically significant (p

Colorectal cancer (CRC) is one of the most common cancers worldwide, with a high mortality rate, especially in those that are diagnosed in late stages of the disease. The current screening blood-based markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), have low sensitivity and specificity. Meanwhile, other modalities are either expensive or invasive. Therefore, recent research has shifted towards a minimally invasive test, namely, liquid biopsy. Exosomes are favorable molecules sought in blood samples, since they are abundant, stable in circulation, and harbor genetic information and other biomolecules that could serve as biomarkers or even therapeutic targets. Furthermore, exosomal noncoding RNAs, such as miRNAs, lncRNAs, and circRNAs, have demonstrated the diagnostic potential to detect CRC at an early stage with a higher sensitivity and specificity than CEA and CA19-9 alone. Moreover, they have prognostic potential that is TNM stage specific and could serve as predictive biomarkers for the most common chemotherapeutic drug and combination regimen in CRC, which are 5-FU and FOLFOX, respectively. Therefore, in this review, we focus on the role of these exosomal noncoding RNAs as diagnostic, prognostic, and predictive biomarkers. In addition, we discuss the advantages and challenges of exosomes as a liquid biopsy target.