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The chaperone system (CS) is emerging as a key multistage participant in carcinogenesis. The CS chief components are the molecular chaperones (some of which are named heat shock proteins or Hsp), which are typically cytoprotective but if abnormal in structure, location, or quantity, can become etiopathogenic and cause diseases, known as chaperonopathies, including some cancers. For example, abnormal Hsp90 expression is associated with tumorigenesis and poor prognosis. Hsp90 is positioned at the center of several key oncogenic pathways by stabilizing and activating oncogenic kinases responsible for driving cell proliferation and survival. Consequently, inhibition of Hsp90 is being investigated as a possible anti-cancer strategy and some results are encouraging. However, the 5-year survival rate for patients suffering from salivary gland carcinomas is still unsatisfactory. Because of the rarity of these malignancies, they may have been overlooked and understudied and, thus, novel therapies (e.g., inhibition of CS components like Hsp90 and others) are urgently needed. In this review, we also summarize the histopathological quantitative patterns and the intra- and extra-cellular location characteristics of Hsp90 in tumors of salivary glands, pointing to their potential for differential diagnosis, prognostication, and patient monitoring.

Background: Anatomical variations and, in particular, arterial variations constitute an important chapter in the learning of Clinical Anatomy. Purpose: The purpose of this report is to describe a rare bilateral anatomical variation in the internal thoracic artery (ITA) in a 60-year-old corpse and to depict its extreme clinical importance in coronary artery bypass surgery. Methods: The rare bilateral aberrant branches of the internal thoracic artery and their course in the thorax were incidentally discovered during routine anatomy dissection of the thorax at the Faculty of Medicine and Medical Sciences of the University of Balamand. The findings were thoroughly documented using digital photography, and the dissection followed the instructions from the “16th Edition of Grant’s Dissector”. Results: In the observed case, the left aberrant branch of ITA descends laterally and gives medial and lateral anterior intercostal branches at the first six intercostal spaces. Conversely, the right aberrant artery, which branches from the ITA, descends laterally and gives medial and lateral branches to every intercostal space in the first five intercostal spaces. Conclusion: This report emphasizes that any unexpected variations in the lateral aberrant branches of the internal thoracic artery may complicate the surgical procedure. Bilateral aberrant lateral branches of the internal thoracic artery constitute rare anatomical variations of the internal thoracic artery and have been rarely reported in the literature. Such a course for aberrant lateral branches in the thorax poses possible lethal complications during several procedures involving the thorax, including basic coronary artery bypass graft, thoracocentesis and intercostal paracentesis and breast reconstruction.

ObjectiveWe recently demonstrated that EBV DNA is correlated with proinflammatory responses in mice and in rheumatoid arthritis (RA) patients; hence, we utilized an RA mouse model to examine whether EBV DNA enhances the risk and severity of arthritis and to assess its immunomodulatory effects.MethodsC57BL/6J mice were treated with collagen (arthritis-inducing agent), EBV DNA 6 days before collagen, EBV DNA 15 days after collagen, Staphylococcus epidermidis DNA 6 days before collagen, EBV DNA alone, or water. Mice were then monitored for clinical signs and affected joints/footpads were histologically analysed. The relative concentration of IgG anti- chicken collagen antibodies and serum cytokine levels of IL-17A and IFNϒ were determined by ELISA. The number of cells co-expressing IL-17A and IFNϒ in joint histological sections was determined by immunofluorescence.ResultsThe incidence of arthritis was significantly higher in mice that received EBV DNA prior to collagen compared to mice that only received collagen. Similarly, increased clinical scores, histological scores and paw thicknesses with a decreased gripping strength were observed in groups treated with EBV DNA and collagen. The relative concentration of IgG anti-chicken collagen antibodies was significantly increased in the group that received EBV DNA 6 days prior to collagen in comparison to the collagen receiving group. On the other hand, the highest number of cells co-expressing IFNϒ and IL-17A was observed in joints from mice that received both collagen and EBV DNA.ConclusionEBV DNA increases the incidence and severity of arthritis in a RA mouse model. Targeting mediators triggered by viral DNA may hence be a potential therapeutic avenue.

Background: Melanoma is a malignancy with increasing incidence that underlies most skin cancer-related deaths. Advanced melanoma patients still have poor prognosis despite recently developed immunotherapies. This study devises a triple immunotherapy to treat melanoma in a mouse model. The combination includes anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies, Monophosphoryl-lipid-A (MPLA), and an Indolamine-Dioxygenase-1 (IDO1) inhibitor. The aim of the study is, first, to rule out any major toxic effects related to this therapy and, second, to assess its antitumor effects.Methods: Cancer-free C57BL/6 mice were randomized into control groups and groups receiving single, dual, or triple therapies of the defined treatments. Clinical signs, weight gain, and histological sections from their main organs were assessed. Then, melanoma-bearing mice were segregated into similar groups, monitored for survival, and their tumor size was measured repeatedly. Finally, flow cytometry was used to analyze immune cell populations in the tumor masses including CD4+, CD8+, and regulatory T cells in addition to natural killer cells.Results: No adverse effects were detected in any of the treated groups. Survival analysis indicated that the groups receiving dual or triple therapies had prolonged survival compared to the controls. However, the group receiving triple therapy was the only group to show statistically significant increase in survival compared to the controls. Tumor size progression paralleled the survival outcome. The group receiving the triple therapy showed statistically significant smaller tumor sizes compared to all the other groups throughout the whole monitoring period. Flow cytometry used to analyze immune cell populations in the tumor mass indicated that the triple immune therapy was capable of significantly enhancing the natural killer cell counts as well as the CD3+CD4+/Treg and CD3+CD8+/Treg ratios possibly enhancing the anti-tumorigenic environment.Conclusions: Generated data rule out any major adverse events pertaining to the triple immunotherapy and reveal its enhanced effectiveness in thwarting melanoma progression over all other tested treatments.

Summary:. Restoring function after traumatic defects of the palm is a reconstructive challenge, considering the need for flexible, elastic, and resistant skin. Dermal skin substitutes are biologically engineered materials composed of collagen and glycosaminoglycan, devoid of cellular structures. These biodegradable materials act as artificial dermis and stimulate neovascularization: they have been used for many years, mainly on the dorsal side of the hand and fingers, whereas the palmar side of the hand has been generally addressed by local flaps. In this study, we described our experience with dermal skin substitutes in two cases of palmar defects associated with exposed tendinous structures. Coverage of palmar defects in hand and fingers with dermal substitute and split thickness skin graft was performed on two patients. Both patients presented palmar-only loss of tissue (traumatic palmar amputation in the first patient and degloving-type injury in the second patient). Range of motion, functional outcomes, and satisfaction and aesthetical results were evaluated. The resulting skin showed good quality, thickness, pliability, and Disabilities of the Arm, Shoulder, and Hand (DASH) score. Additionally, the patients regained full range of motion and reported high satisfaction. The association of split thickness skin graft with dermal substitutes in palmar traumatic hand showed optimal functional and aesthetic outcomes. Although being more adapted to dorsal loss of substance, collagen-based dermal substitutes can also be useful reconstructive tools in palmar defects with exposed structures and could be used to a larger extent in the future.

Infection with EBV has been associated with various inflammatory disorders including inflammatory bowel diseases (IBD). Contribution of this virus to intestinal disease processes has not been assessed. We previously detected that EBV DNA triggers proinflammatory responses via the activation of endosomal Toll-like receptor (TLR) signaling. Hence, to examine the colitogenic potential of EBV DNA, we used the dextran sodium sulfate (DSS) mouse colitis model. C57BL/6J mice received either DSS-containing or regular drinking water. Mice were then administered EBV DNA by rectal gavage. Administration of EBV DNA to the DSS-fed mice aggravated colonic disease activity as well as increased the damage to the colon histologic architecture. Moreover, we observed enhanced expression of IL-17A, IFNγ and TNFα in colon tissues from the colitis mice (DSS-treated) given the EBV DNA compared to the other groups. This group also had a marked decrease in expression of the CTLA4 immunoregulatory marker. On the other hand, we observed enhanced expression of endosomal TLRs in colon tissues from the EBV DNA-treated colitis mice. These findings indicate that EBV DNA exacerbates proinflammatory responses in colitis. The ubiquity of EBV in the population indicates that possible similar responses may be of pertinence in a relevant proportion of IBD patients.

Background. Hydrocephalus is a prevalent condition in children, affecting both developed and developing countries. Neurosurgical interventions such as ventriculoperitoneal shunts are common, but are associated with a high risk of complications, including infections, which can lead to additional issues and costs. This study aims to review the incidence of infection in pediatric patients before and after ventriculoperitoneal shunt placement, in order to address this issue. Methods. A standard process of analyzing scientific questions using the Population, Intervention, Control, and Outcome (PICO) method was used to develop a protocol for searching research articles in online databases such as PubMed, Cochrane, POPLINE, and Sciencedirect. The articles selected for inclusion in this study met the following criteria: 1) described interventional ventriculoperitoneal shunt placement in pediatrics, 2) focused on cases of ventriculoperitoneal shunt complications with a focus on infection, 3) were published within the last 10 years, and 4) were published in English-language journals with peer review standards. Results. Sixteen articles were identified for review. Seven of these articles mentioned surgical or mechanical interventions as a means of preventing infections, while six articles discussed medical treatment for infection prevention. Three articles described the microorganisms found in cerebrospinal fluid. Conclusion. Future studies should focus on the issues related to ventriculoperitoneal shunt complications and interventions related to immunological, neuroendocrine, and biophysical factors to prevent infections, as well as surgical management and medication administration.

Abstract Background The human papillomavirus (HPV), a prevalent sexually transmitted infection, is linked to a wide range of diseases, with cervical cancer being the most common and serious one. HPV vaccination is crucial for preventing cervical cancer and other HPV-related problems. The low acceptability of HPV vaccination among teenagers globally is largely due to a lack of understanding and information about HPV among parents. Our study aimed to evaluate the level of knowledge, attitude, intention, and HPV vaccination among parents in Lebanon as well as the variables influencing Lebanese mothers' intentions to vaccinate their children. Methods A cross-sectional survey-based study involving 392 participants was conducted between May and June 2022. The study assessed parents' intention to vaccinate their children against HPV, their knowledge about HPV, and the HPV vaccine. The data was collected through an anonymous electronic questionnaire. A bivariate analysis was conducted using Student t-test and ANOVA to examine the relationship between the dependent variable “Intention to vaccination” and the secondary variables. The level of statistical significance was set at 0.05 for all data. Results Our findings showed that only 63% of the 392 participants claimed they would give their child the HPV vaccination. A positive significant association was demonstrated between "Intention to vaccinate against HPV" and mother's nationality, father's educational level, family income per month, information received about the HPV vaccine, parents' HPV vaccination, insurance coverage of the HPV vaccine, children's vaccinations with all required vaccines, knowledge of HPV, and knowledge of the HPV vaccine. Furthermore, when parents know about HPV, their desire to vaccinate their child increases by a factor of 1.832 times, and by 1.207 times when their knowledge level increases by one point. Conclusion The majority of parents lacked a general understanding of most HPV-related statements, which highlights the requirement for educational interventions to raise parental awareness, understanding, and attitudes toward HPV and, as a result, increase parental acceptance of vaccinating their children. To increase the vaccination rate among adolescents, government authorities should ensure that the HPV vaccine is available in all hospitals and clinics and should be provided free of charge.