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The main objective of this study is to assess the effect of soft skills and emotional intelligence on burnout among health-care professionals in Lebanon.

Abstract Background The mechanism by which HIV-1 induces AIDS is still unknown. Previously, synthetic peptides corresponding to the conserved immunosuppressive (isu) domain in gp41 of HIV-1 had been shown to inhibit proliferation and to modulate cytokine expression of immune cells. The question is, whether the viral gp41 can do the same. Results We show for the first time that two trimeric forms of glycosylated gp41 released from transfected human cells modulated expression of cytokines and other genes in human PBMCs in the same manner, but at least seven hundred-fold stronger compared to that induced by the isu peptide. Single amino acid substitutions in the isu domain of gp41 introduced by site-directed mutagenesis abrogated this property. Furthermore, replication-competent HIV-1 with a mutation in the isu domain of gp41 did not modulate the cytokine expression, while wild-type virus did. Interestingly, most of the abrogating mutations were not reported in viral sequences derived from infected individuals, suggesting that mutated non-immunosuppressive viruses were eliminated by immune responses. Finally, immunisation of rats with gp41 mutated in the isu domain resulted in increased antibody responses compared with the non-mutated gp41. These results show that non-mutated gp41 is immunosuppressive in immunisation experiments, i.e. in vivo, and this has implications for the vaccine development. Conclusions These findings indicate that the isu domain of gp41 modulates cytokine expression in vitro and suppresses antibody response in vivo and therefore may contribute to the virus induced immunodeficiency.

Protein misfolding and mislocalization are common to both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Maintaining proteostasis through induction of heat shock proteins (HSP) to increase chaperoning capacity is a rational therapeutic strategy in the treatment of ALS. However, the threshold for upregulating stress-inducible HSPs remains high in neurons, presenting a therapeutic obstacle. This study used mouse models expressing the ALS variants FUS R521G or SOD1 G93A to follow up on previous work in cultured motor neurons showing varied effects of the HSP co-inducer, arimoclomol, and class I histone deacetylase (HDAC) inhibitors on HSP expression depending on the ALS variant being expressed. As in cultured neurons, neither expression of the transgene nor drug treatments induced expression of HSPs in cortex, spinal cord or muscle of FUS R521G mice, indicating suppression of the heat shock response. Nonetheless, arimoclomol, and RGFP963, restored performance on cognitive tests and improved cortical dendritic spine densities. In SOD1 G93A mice, multiple HSPs were upregulated in hindlimb skeletal muscle, but not in lumbar spinal cord with the exception of HSPB1 associated with astrocytosis. Drug treatments improved contractile force but reduced the increase in HSPs in muscle rather than facilitating their expression. The data point to mechanisms other than amplification of the heat shock response underlying recovery of cognitive function in ALS-FUS mice by arimoclomol and class I HDAC inhibition and suggest potential benefits in counteracting cognitive impairment in ALS, frontotemporal dementia and related disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Heather Durham reports financial support was provided by Merck, Sharpe & Dohme Corporation, McGill Faculty of Medicine. Heather Durham reports financial support was provided by Brain Canada Foundation and ALS Society of Canada. Heather Durham reports equipment, drugs, or supplies was provided by BioMarin Pharmaceutical Inc. Chantelle Septhton reports financial support was provided by Brain Canada Foundation and ALS Society of Canada and FRSQ. Mario Fernandez Comaduran reports financial support was provided by Fonds de Recherche du Québec Nature et Technologies and Mitacs Globalink Graduate Fellowship, Consejo Nacional de Ciencia y Tecnología. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A simple and robust cell culture system is essential for generating authentic SARS-CoV-2 stocks for evaluation of viral pathogenicity, screening of antiviral compounds, and preparation of inactivated vaccines. Evidence suggests that Vero E6, a cell line commonly used in the field to grow SARS-CoV-2, does not support efficient propagation of new viral variants and triggers rapid cell culture adaptation of the virus. We generated a panel of 17 human cell lines overexpressing SARS-CoV-2 entry factors and tested their ability to support viral infection. Two cell lines, Caco-2/AT and HuH-6/AT, demonstrated exceptional susceptibility, yielding highly concentrated virus stocks. Notably, these cell lines were more sensitive than Vero E6 cells in recovering SARS-CoV-2 from clinical specimens. Further, Caco-2/AT cells provided a robust platform for producing genetically reliable recombinant SARS-CoV-2 through a reverse genetics system. These cellular models are a valuable tool for the study of SARS-CoV-2 and its continuously emerging variants., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

OBJECTIVE There is no definitive or consensus classification system for the jugular bulb position that can be uniformly communicated between a radiologist, neurootologist, and neurosurgeon. A high-riding jugular bulb (HRJB) has been variably defined as a jugular bulb that rises to or above the level of the basal turn of the cochlea, within 2 mm of the internal auditory canal (IAC), or to the level of the superior tympanic annulus. Overall, there is a seeming lack of consensus, especially when MRI and/or CT are used for jugular bulb evaluation without a dedicated imaging study of the venous anatomy such as digital subtraction angiography or CT or MR venography. METHODS A PubMed analysis of "jugular bulb" comprised of 1264 relevant articles were selected and analyzed specifically for an HRJB. A novel classification system based on preliminary skull base imaging using CT is proposed by the authors for conveying the anatomical location of the jugular bulb. This new classification includes the following types: type 1, no bulb; type 2, below the inferior margin of the posterior semicircular canal (SCC), subclassified as type 2a (without dehiscence into the middle ear) or type 2b (with dehiscence into the middle ear); type 3, between the inferior margin of the posterior SCC and the inferior margin of the IAC, subclassified as type 3a (without dehiscence into the middle ear) and type 3b (with dehiscence into the middle ear); type 4, above the inferior margin of the IAC, subclassified as type 4a (without dehiscence into the IAC) and type 4b (with dehiscence into the IAC); and type 5, combination of dehiscences. Appropriate CT and MR images of the skull base were selected to validate the criteria and further demonstrated using 3D reconstruction of DICOM files. The microsurgical significance of the proposed classification is evaluated with reference to specific skull base/posterior fossa pathologies. RESULTS The authors validated the role of a novel classification of jugular bulb location that can help effective communication between providers treating skull base lesions. Effective utilization of the above grading system can help plan surgical procedures and anticipate complications. CONCLUSIONS The authors have proposed a novel anatomical/radiological classification system for jugular bulb location with respect to surgical implications. This classification can help surgeons in complication avoidance and management when addressing HRJBs.

Xenotransplantation has been proposed as a solution to the shortage of suitable human donors for transplantation and pigs are currently favoured as donor animals. However, xenotransplantation may be associated with the transmission of zoonotic microorganisms. Whereas most porcine microorganisms representing a risk for the human recipient may be eliminated by designated pathogen free breeding, multiple copies of porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs and cannot be eliminated this way. PERVs are released as infectious particles and infect human cells. The zinc finger nuclease (ZFN) technology allows knocking out specifically cellular genes, however it was not yet used to eliminate multiple integrated proviral sequences with a strong conservation in the target sequence. To reduce the risk of horizontal PERV transmission and to knock out as many as possible proviruses, for the first time the powerful tool of the ZFN technology was used. ZFN were designed to bind specifically to sequences conserved in all known replication-competent proviruses. Expression and transport of the ZFN into the nucleus was shown by Western blot analysis, co-localisation analysis, PLA and FRET. Survival of transfected cells was analysed using fluorescent ZFN and cell counting. After transfection a strong expression of the ZFN proteins and a co-localisation of the expressed ZFN proteins were shown. However, expression of the ZFN was found to be extremely toxic for the transfected cells. The induced cytotoxicity was likely due to the specific cutting of the high copy number of the PERV proviruses, which is also commonly observed when ZFN with low specificity cleave numerous off-target sites in a genome. This is the first attempt to knock out multiple, nearly identical, genes in a cellular genome using ZFN. The attempt failed, and other strategies should be used to prevent PERV transmission.

Background: Squamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness., Methods: To extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models., Results: We found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively., Conclusions: Taken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients.

This case is an example of a translabyrinthine resection of a small intracanalicular acoustic tumor. The patient is a 69-year-old right-handed woman with complaints of progressive incapacitating vertigo and right-sided hearing loss worsening over the past 3 years. She had normal facial nerve function with imaging demonstrating progressive increase in size of a small right-sided acoustic tumor. A translabyrinthine approach was performed, and the mass was resected completely. Facial nerve function remained normal immediately after surgery. The video can be found here: http://youtu.be/27ARlLLSbKE .

The transmembrane envelope protein gp41 of the human immunodeficiency virus HIV-1 plays an important role during infection allowing fusion of the viral and cellular membrane. In addition, there is increasing evidence that gp41 may contribute to the immunodeficiency induced by HIV-1. Recombinant gp41 and a synthetic peptide corresponding to a highly conserved domain in gp41, the immunosuppressive (isu) domain, have been shown to inhibit mitogen-induced activation of human peripheral blood mononuclear cells (PBMCs) and to increase release of IL-6 and IL-10 from these cells. We recently reported that a single mutation in the isu domain of gp41 abrogated the immunosuppressive properties and that HIV-1 sequences containing such abrogating mutations had never been isolated from infected individuals. Here, we studied the influence of the isu peptide on the release of 66 cytokines and the expression of 27,000 genes in PBMCs. Incubation of PBMCs with isu peptide homopolymers increased the expression of 16 cytokines among them IL-6 and IL-10, and decreased that of IL-2 and CXCL9. Interestingly, the extend of cytokine modulation was donor-dependent. Among the genes up-regulated were IL-6, IL-8, IL-10 but also MMP-1, TREM-1 and IL-1beta. Most importantly, genes involved in innate immunity such as FCN1 and SEPP1 were found down-regulated. Many changes in cytokine expression demonstrated in our experiments were also found in HIV-1 infected individuals. These data indicate that the isu domain of gp41 has a broad impact on gene expression and cytokine release and therefore may be involved in HIV-1 induced immunopathogenesis.

The design, implementation, and characterization of a microelectromechanical systems (MEMS) capacitive accelerometer-based middle ear microphone are presented in this paper. The microphone is intended for middle ear hearing aids as well as future fully implantable cochlear prosthesis. Human temporal bones acoustic response characterization results are used to derive the accelerometer design requirements. The prototype accelerometer is fabricated in a commercial silicon-on-insulator (SOI) MEMS process. The sensor occupies a sensing area of 1 mm × 1 mm with a chip area of 2 mm × 2.4 mm and is interfaced with a custom-designed low-noise electronic IC chip over a flexible substrate. The packaged sensor unit occupies an area of 2.5 mm × 6.2 mm with a weight of 25 mg. The sensor unit attached to umbo can detect a sound pressure level (SPL) of 60 dB at 500 Hz, 35 dB at 2 kHz, and 57 dB at 8 kHz. An improved sound detection limit of 34-dB SPL at 150 Hz and 24-dB SPL at 500 Hz can be expected by employing start-of-the-art MEMS fabrication technology, which results in an articulation index of approximately 0.76. Further micro/nanofabrication technology advancement is needed to enhance the microphone sensitivity for improved understanding of normal conversational speech.