The cell line models to study tyrosine kinase inhibitors in non-small cell lung cancer with mutations in the epidermal growth factor receptor: A scoping review.

Non-Small Cell Lung Cancer (NSCLC) represents ∼85% of all lung cancers and ∼15-20% of them are characterized by mutations affecting the Epidermal Growth Factor Receptor (EGFR). For several years now, a class of tyrosine kinase inhibitors was developed, targeting sensitive mutations affecting the EGFR (EGFR-TKIs). To date, the main burden of the TKIs employment is due to the onset of resistance mutations. This scoping review aims to resume the current situation about the cell line models employed for the in vitro evaluation of resistance mechanisms induced by EGFR-TKIs in oncogene-addicted NSCLC. Adenocarcinoma results the most studied NSCLC histotype with the H1650, H1975, HCC827 and PC9 mutated cell lines, while Gefitinib and Osimertinib the most investigated inhibitors. Overall, data collected frame the current advancement of this topic, showing a plethora of approaches pursued to overcome the TKIs resistance, from RNA-mediated strategies to the innovative combination therapies.

Atypical Course of SarsCov-2 Infection in a Patient with Multiple Myeloma Treated with Autologous Stem Cell Transplantation.

Covid-19 infection has more relevant consequences in frail and comorbid patients, but little is known about its course in patients with hematologic malignancies. In this report, we would like to present the case of a patient with multiple myeloma treated with recent autologous bone marrow stem cell transplantation and affected by Covid-19 pneumonia, presenting with a possible reinfection or an extremely long viral shedding.

Anti-Inflammatory Effects of Olive Leaf Extract and Its Bioactive Compounds Oleacin and Oleuropein-Aglycone on Senescent Endothelial and Small Airway Epithelial Cells.

Olive tree by-products have been deeply studied as an invaluable source of bioactive compounds. Several in vitro and in vivo studies showed that olive leaf extract (OLE) has anti-inflammatory and antioxidant properties. Here, we wanted to assess the valuable benefits of two less-studied OLE components-3,4-DHPEA-EDA (Oleacin, OC) and 3,4-DHPEA-EA (Oleuropein-Aglycone, OA)-directly purified from OLE using a cost-effective and environmentally sustainable method, in line with the principles of circular economy. OLE, OC and OA were then tested in human cellular models involved in acute and chronic inflammation and in the pathogenesis of viral infections, i.e., lipopolysaccharide (LPS)-treated monocyte/macrophages (THP-1) and endothelial cells (HUVECs), senescent HUVECs and Poly(I:C)-treated small airway epithelial cells (hSAECs). Results showed that OC and OA are efficient in ameliorating almost all of the pro-inflammatory readouts (IL-1ß, TNF-α, IL-8, ICAM, VCAM) and reducing the release of IL-6 in all the cellular models. In hSAECs, they also modulate the expression of SOD2, NF-kB and also ACE2 and TMPRSS2, whose expression is required for SARS-CoV-2 virus entry. Overall, these data suggest the usefulness of OLE, OC and OA in controlling or preventing inflammatory responses, in particular those associated with viral respiratory infections and aging.

An easy and versatile approach for the regioselective de-O-benzylation of protected sugars based on the I2/Et3 SiH combined system.

The use of cheap and easy to handle reagents, such as I(2) and Et(3) SiH, at low temperature allows the regioselective removal of benzyl protecting groups from highly O-benzylated carbohydrates. The observed regioselectivity is dependent on the nature of the precursor, the least accessible carbinol often being liberated. A mechanistic investigation reveals that in situ generated HI is the promoter of the process, whereas the regioselectivity appears to be mainly controlled by steric effects. However, the presence of an electron withdrawing acyl protecting group can switch the regioselectivity to favour deprotection of the carbinol position farthest from the ester group. The protocol is experimentally simple and provides straightforward access in useful yields to a wide range of partially protected mono- and disaccharide building blocks that are valuable for the synthesis of either biologically useful oligosaccharides or highly functionalised chiral compounds. Partially protected sugars thus obtained can also be coupled in situ with a glycosyl donor, as illustrated by the one-pot synthesis of a Lewis X mimic from fully protected precursors.

Disentangling eumelanin "black chromophore": visible absorption changes as signatures of oxidation state- and aggregation-dependent dynamic interactions in a model water-soluble 5,6-dihydroxyindole polymer.

A fundamental unsettled issue concerning eumelanins, the functional biopolymers of human skin and hair, is why they are black. The experimental difficulty lies in the virtual insolubility of these pigments, causing marked scattering effects and hindering characterization of the intrinsic absorption properties of the heterogeneous species produced by oxidative polymerization of 5,6-dihydroxyindole (DHI) and related monomer precursors. The synthesis of spectrally robust, water-soluble DHI polymers is therefore an important goal in the prospects of disentangling intrinsic absorption properties of eumelanin components by circumventing scattering effects. Reported herein is the first water-soluble DHI polymer produced by oxidation of ad hoc designed 5,6-dihydroxy-3-indolyl-1-thio-beta-D-galactopyranoside (1). The dark brown polymer exhibited a distinct band at 314 nm and a broad visible absorption, resembling that of natural eumelanins. Main isolable oligomer intermediates including 2,7'- and 2,4'-biindolyls 2 and 3, attest the close resemblance to the mode of coupling of the parent DHI. Sodium borohydride reduction caused decoloration and a marked absorbance decrease in the visible region around 550 nm, but did not affect the UV band at 314 nm. Measurements of absorbance variations with dilution indicated a linear response at 314 nm, but a significant deviation from linearity in the visible region, with the largest decrease around 500 nm. It is argued that eumelanin black color is not only intrinsically defined by the overlap of pi-electron conjugated chromophores within the individual polymer components, as commonly believed, but also by oxidation state- and aggregation-dependent interchromophoric interactions causing perturbations of the heterogeneous ensemble of pi-electron systems and overall spectral broadening.

Flexible esophagoscopy as a diagnostic tool for traumatic esophageal injuries.

BACKGROUND: The management and clinical outcome of patients suffering esophageal trauma depends on a prompt diagnosis. The detection of esophageal injuries by clinical examination, esophagography, or computed tomography is limited. This study aimed to assess the yield and clinical utility of flexible esophagoscopy (FE) in the diagnosis of traumatic esophageal injuries. PATIENTS: During 7 years, we conducted a retrospective (1998-2003) and prospective (2003-2005) study of 163 victims admitted to a trauma hospital, and submitted to FE because of suspected esophageal trauma. Esophageal injury was defined as laceration or perforation, hematoma, abrasion, hematin spots, or ecchymosis. The endoscopic diagnosis was compared with surgical findings or clinical follow-up. RESULTS: No traumatic lesion was observed in 139 patients (85.3%), esophageal injuries were detected in 23 (14.1%), and one examination was inconclusive (esophageal stricture, 0.6%). Lacerations were detected in 14 patients and confirmed surgically. Esophageal contusion was observed in nine patients and out of these, five patients underwent surgical exploration and four were managed nonoperatively. The assessment of esophageal injury by FE demonstrated 95.8% sensitivity, 100% specificity, 99.3% accuracy, 100% positive predictive value, and 99.2% negative predictive value. The likelihood ratio for a negative examination was 0.041 and the Youden J Index was 99.2%. CONCLUSIONS: FE appears to be an accurate diagnostic tool in the assessment of esophageal injuries. Two main lesions were noted: laceration and contusion. Laceration requires surgical repair. Contusion represents a nonperforative injury of the esophageal wall, requires correlation with computed tomography, and may be managed nonoperatively.

Rapid assembly of gp120 oligosaccharide moieties via one-pot glycosidation-deprotection sequences.

Mannosyl trihaloacetimidate donors equipped with a 2-O-Fmoc group can be effectively activated by catalytic Bi(OTf)(3) in glycosidations. Despite the expected participating effect of the Fmoc group, the reaction solvent was found to be decisive for obtaining highly selective alpha-mannosylations. The Fmoc 2-O-protecting group can be then simply removed from the obtained di-oligosaccharide in the same vessel where the glycosidation is conducted. The resulting oligosaccharide can thus be directly employed as a glycosyl acceptor for further elongation. The preparation of biologically important linear and branched oligomannoses incorporated into HIV gp120 demonstrates that iteration of this one-pot sequence leads to very straightforward oligosaccharide assembly. As an additional result, a rapid approach has been disclosed for accessing a 3,6-OH mannose building-block to be incorporated in branched structures. This relies on a double reductive opening of a di-O-benzylidene mannose intermediate whose regioselectivity appears to be independent of the configuration of the five-membered benzylidene.

Sequential one-pot glycosidations catalytically promoted: unprecedented strategy in oligosaccharide synthesis for the straightforward assemblage of the antitumor PI-88 pentasaccharide.

The pentasaccharide sequence of the most active components of the antitumor drug PI-88, currently in phase II clinical trial, has been rapidly assembled in high overall yield and in only three steps starting from three monosaccharide building blocks. The procedure takes advantage of the first reported strategy of sequential one-pot glycosidations conducted exclusively under catalytic activation. In addition, the procedure relies only on shelf-stable and mild promoters such as Yb(OTf)(3) and Bi(OTf)(3).

Novel approaches for the synthesis and activation of thio- and selenoglycoside donors.

Alkyl thio-, phenyl seleno-, and phenyl thioglycosides can be prepared through short synthetic sequences based on the generation of glycosyl iodides as versatile intermediates. In addition, a novel cheap combined system (stoichiometric NBS and catalytic Bi(OTf)3) has been developed for rapid and efficient activation of a wide variety of thio- and selenoglycoside donors.

Abdutor lateral: uma alternativa no pós-operatório de prótese total de quadril / Lateral abductor: an alternative in the total hip arthroplasty surgery in the post operative period

Buscando amenizar os inconvenientes que os pacientes submetidos a Prótese Total de Quadril enfrentam no pós-operatório, as autoras vêm apresentar um aparelho idealizado e elaborado por elas, para auxiliar na manutençäo do paciente em decúbito lateral, sem que isso concorra em risco de luxaçäo da prótese. Este aparelho foi denominado Abdutor Lateral, sendo uma nova alternativa para melhoria da assistência de enfermagem e consequente recuperaçäo mais segura e confortável aos pacientes submetidos a Prótese Total de Quadril. As autoras descrevem sua forma estrutural, divulgam sua finalidade e demonstram sua forma de uso.

Eficácia da escleroterapia endoscópica no controle da hemorragia varicosa aguda / Efficacy of endoscopic injection sclerotherapy to control acute variceal bleeding

Introdução e Objetivos: Apesar dos avanços recentes, o tratamento de pacientes com hemorragia digestiva por varizes esofagogástricas continua desafiador: A escleroterapia endoscópica constitui um dos métodos mais eficazes na terapêutica desses pacientes. O presente estudo, conduzido em um hospital de pronto-socorro, objetivou analisar a eficácia da escleroterapia endoscópica no controle da hemorragia varicosa aguda e sua correlação com a função hepática. Pacientes e método:Foram estudados, prospectivamente, 424 pacientes consecutivos admitidos no período de janeiro/1998 a junho/2001, com hemorragia digestiva alta proveniente de varizes esofagogástricas. Após a estabilização clínica inicial, todos os pacientes foram submetidos a endoscopia digestiva alta e a escleroterapia de urgência para tratamento das varizes sangrantes. Avaliou-se o controle do sangramento agudo em 48 horas, o ressangramento em até seis semanas e a mortalidade intra-hospitalar: Nos 176 pacientes portadores de cirrose hepática atribuída ao alcoolismo crônico, verificou-se a correlação entre o sucesso do tratamento endoscópico e o grau de disfunção hepática baseado no escore de Child-Pugh. Resultados: As etiologias mais frequentes da hipertensão portal foram cirrose hepática etanólica (48,3 por cento) e esquitossomose(36,6 por cento). O controle do sangramento agudo foi obtido através da escleroterapia em 88 por cento dos pacientes com varizes esofagianas ou juncionais sangrantes. Ressangramento ocorreu em 19,9 por cento dos casos. Ocorreram 74 óbitos(mortalidade de 18,5 por cento), sendo que 46 pacientas(62,2 por cento) faleceram por hemorragia não controlada e 28(37,8por cento), apesar da interrupção do sangramento. Os pacientes com cirrose hepática etanólica Child-Pugh C apresentaram índices mais baixos de controle da hemorragia aguda(73 por cento)e mortalidade mais elevada(52,7por cento) quando comparados com os cirróticos Child-Pugh A(97,7por cento, 4,4por cento) e B(94,7por cento, 10,5por cento),(p<0,05). Conclusão: A escleroterapia endoscópica apresenta índices elevados de controle de hemorragia varicosa aguda. Entretanto, pacientes portadores de cirrose etanólica, a insuficiência hepática avançada afeta negativamente a eficácia da escleroterapia e se associa a elevada mortalidade. Outras opções terapêuticas, tais como injeção de cianoacrilato ou Tips, devem ser consideradas para esse subgrupo de pacientes, porém são necessários estudos comparativos para definir esta questão.