The Serine/Threonine Protein Kinase (Akt)/ Protein Kinase B (PkB) Signaling Pathway in Breast Cancer

According to statistical data published in 2019, breast cancer is among the leading causes of death in women worldwide. The serine/threonine kinase (AKT) or protein kinase B (PkB) signaling pathway is activated by phosphorylation processes, which further is associated with cell growth, proliferation, and survival, but also with activation of glucose metabolism. Mutations of the AKT signaling pathway components (especially PI3KCA and PTEN) have been observed in breast cancer patients, which are associated with resistance to hormonal treatment. Many clinical trials are testing the effect of AKT inhibition in order to block the growth and proliferation of breast cancer cells. The purpose of this review is to present the incidence of this neoplastic disease, to describe AKT signaling pathways activation, mutations that occur at its level, and inhibitors that can block this protein kinase

Artera radială sau vena safenă în revascularizarea miocardică? Actualități, limite, controverse, perspective

Institutul de Boli Cardiovasculare „Prof. Dr. George I.M. Georgescu”, Universitatea de Medicină și Farmacie „Grigore T. Popa” Iași, Universitatea de Medicină și Farmacie Târgu Mureș, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaIntroducere: Bypass-ul aorto-coronarian (BAC) reprezintă tehnica de revascularizare de elecție la pacienții cu leziuni coronariene ce interesează trunchiul arterei coronare stângi sau mai mult de 3 artere coronare. Artera mamară internă constituie graftul gold standard, controverse existând în privința alegerii celui de al 2-lea sau al 3-lea graft. Ultima ediție a Ghidului de Revascularizare Miocardică elaborat de Societatea Europeană de Cardiologie în 2018, prezintă drept indicație de clasă IB utilizarea arterei radiale în detrimentul venei safene interne drept graft adițional după artera mamară internă în cazul pacienților cu stenoze coronariene severe. Materiale și metode: Studiul de față prezintă perspectiva Institutului de Boli Cardiovasculare „Prof. Dr. George I.M. Georgescu” din Iași asupra selecției, recoltării, tehnicii operatorii și prognosticului grafturilor de arteră radială și venă safenă internă cu analiza beneficiului clinic obiectiv în funcție de tipul de graft. În cadrul cercetării au fost analizați 1021 pacienți cu BAC realizat în perioada 2000-2018 utilizând cel puțin o arteră radială și care au supraviețuit perioadei postoperatorii. Vârsta medie a pacienților analizați a fost de 61,30±9,22 ani, iar 182 pacienți (17,83%) au fost de sex feminin. Bypass-ul a fost efectuat utilizând exclusiv grafturi arteriale în 698 cazuri, grafturi de venă safenă (BAC mixt) fiind folosite în 323 cazuri. În total au fost efectuate 1236 anastomoze distale utilizând grafturi de arteră radială și 411 folosind grafturi de venă safenă internă. Rezultate: Permeabilitatea grafturilor la peste 10 ani din momentul intervenției inițiale a fost evaluată în 136 cazuri prin angiografie computer tomografică și a fost constatată o permeabilitate mai mare pentru grafturile de arteră radială (77,05%) comparativ cu cele de venă safenă internă (72,97%) în special pentru teritoriul drept. Supraviețuirea pe termen lung a pacienților a fost de asemenea superioară în cazul revascularizării total arteriale utilizând grafturi de arteră mamară internă și arteră radială (72,31%) comparativ cu BAC mixt utilizând și grafturi de venă safenă (64,14%). Concluzii: Spre deosebire de vena safenă internă mai permisivă la fluxul competitiv, artera radială s-a dovedit mai susceptibilă la vasoconstricție și ocluzie în cazul anastomozării la vase fără stenoză critică. In concluzie, graftul de arteră radială este asociat cu un prognostic favorabil atunci când este utilizat drept al 2-lea sau al 3-lea graft asociat cu una sau ambele artere mamare interne în special pentru a revasculariza artere cu stenoze proximale severe, peste 90%. Studii adiționale sunt necesare pentru identificarea configurațiilor de grafturi cu cel mai mare beneficiu din punct de vedere clinic

The Serine/Threonine Protein Kinase (Akt)/ Protein Kinase B (PkB) Signaling Pathway in Breast Cancer

According to statistical data published in 2019, breast cancer is among the leading causes of death in women worldwide. The serine/threonine kinase (AKT) or protein kinase B (PkB) signaling pathway is activated by phosphorylation processes, which further is associated with cell growth, proliferation, and survival, but also with activation of glucose metabolism. Mutations of the AKT signaling pathway components (especially PI3KCA and PTEN) have been observed in breast cancer patients, which are associated with resistance to hormonal treatment. Many clinical trials are testing the effect of AKT inhibition in order to block the growth and proliferation of breast cancer cells. The purpose of this review is to present the incidence of this neoplastic disease, to describe AKT signaling pathways activation, mutations that occur at its level, and inhibitors that can block this protein kinase

Searching for cold-adapted microorganisms in the underground glacier of Scarisoara Ice Cave, Romania

Scarisoara Ice Cave (Romania) hosts one of world’s largest and oldest underground glacier. While no studies were carried out on the existence of microorganisms in this cave’s ice block, our interest is to investigate the presence of microorganisms and their chronological distribution in the cave’s subterranean ice in relationship with past climatic changes. Samples were collected from ice layers of different age (from present to ~900 cal. yrs. BP), and the diversity of embedded microbial communities was assessed by classical cultivation and molecular techniques. The microorganisms from icesediments were cultivated at 4 °C and 15 °C, in the presence and absence of light. Epifluorescence microscopy analysis indicates the presence of autotrophic prokaryotes and eukaryotes in sunlightexposed ice and water samples. Total DNA was isolated from each ice sample and the bacterial and eukaryotic SSU-rRNA genes were amplified by PCR. The chemical composition and organic content of both deeply buried (>10 m inside the ice block) and surface (supra- glacial pond water) habitats were analyzed in relation to their age and organic composition. This study is the first to report on the presence of both prokaryotic and eukaryotic microorganisms in the subterranean ice block of Scarisoara Ice Cave, thriving in both organic-rich ice and clear ice layers. Phototrophic prokaryotes and eukaryotes were identified in sun-exposed recent ice. The composition of cold-adapted ice embedded microbiota varied with the habitat age and organic content, as resulting from dissimilarities in growth curve profiles at two different temperatures. The presence of bacteria and eukaryotes in all the analyzed samples was asserted by PCR amplification of SSU-rRNA gene fragments. These findings can be further used to reconstruct changes in the microbial diversity over the past approximately 5000 years, in correlation with climatic and environmental changes recorded by the ice block

Adjunctive use of a nanocolloidal silver-based local antiseptic solution in the nonsurgical treatment of periodontitis: A split-mouth clinical study

Objectives. The aim of the present study was to evaluate the potential additional clinical benefit of a commercial nanocolloidal silver-based local antiseptic used as irrigation solution after subgingival mechanical instrumentation. Material and methods. Periodontitis patients were treated following the current guidelines. Two randomly assigned hemiarches of each patient received subgingival mechanical instrumentation plus irrigations with the commercial product (experimental group); the other two hemiarches received mechanical instrumentation plus saline irrigations (control group). A clinical periodontal examination at baseline moment and after 3 months was performed. The parameters considered for analysis were oral hygiene index (IHI), bleeding on probing score (BoP), periodontal pocket probing depth (PD), gingival recession (GR) and clinical attachment level (CAL). 72 sites were included in the analysis, the site with the highest PD/quadrant for each patient. Data were analyzed using GraphPad Prism version 8.0.1 (GraphPad Software Inc., La Jolla, CA, USA). p<0.05 was set as statistical significance level. Outcomes. Eighteen periodontitis patients were treated. All clinical parameters improved at re-evaluation, compared to baseline, both in experimental and control group. The differences were statistically significant in terms of IHI, BoP and PD reduction. At re-evaluation, there were no statistically significant differences between periodontal parameters registered in the experimental and control sites. Conclusions. The present study failed to prove an adjunctive clinical benefit of the antiseptic product in the nonsurgical treatment of periodontitis. These results support the gold standard role of subgingival mechanical instrumentation in the periodontitis’ therapeutic protocol

The importance of implementing a HACCP plan in food service operations and restaurants

The European Union has shown that the post-industrial market economy has led to the production of food products above the level of consumer needs in the member states. This development has generated new types of issues, due to the production of food at industrial scale. In order to cope with food and nutrition illnesses and to restore consumer confidence in food safety, the European Commission has launched a series of new legislative amendments on food safety (Marin V. et al, 2007). The Good Hygiene Practices Guide in restaurants establishes, according to the legislation in force, a set of rules referring to the part of food hygiene, which must be followed and applied in restaurants. Potential risks of contamination of food and/or beverages are identified in these plans and a series of measures are developed to prevent these risks. The plan also includes the hygiene rules that must be observed by the employees and the kitchen staff. Operators operating in the field of food must guarantee for its products, comply with the legislative requirements and permanently implement these requirements, in order to release for consumption safe products for the final consumer. The purpose of this paper is to keep in mind the scope of this study focusing on the storage, handling, processing and distribution of all products, including the cooked product to be consumed. Thus, all biological, chemical or physical hazards that may occur during the cooking process of the product are taken into account. The HACCP team will ensure that all foodstuffs used in the preparation of cooked products comply with food safety legislation

Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms

Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization. Both independent mechanisms reduce SLC16A11 function and suggest SLC16A11 is the causal gene at this locus. To gain insight into how SLC16A11 disruption impacts T2D risk, we demonstrate that SLC16A11 is a proton-coupled monocarboxylate transporter and that genetic perturbation of SLC16A11 induces changes in fatty acid and lipid metabolism that are associated with increased T2D risk. Our findings suggest that increasing SLC16A11 function could be therapeutically beneficial for T2D. Video Abstract [Figure presented] Keywords: type 2 diabetes (T2D); genetics; disease mechanism; SLC16A11; MCT11; solute carrier (SLC); monocarboxylates; fatty acid metabolism; lipid metabolism; precision medicin

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

PERTURBAREA AUZULUI – COMPONENTĂ A SINDROMULUI ALCOOL FETAL

Sindromul alcool fetal (SAF) (1-2/1.000 nou-născuţi viabili), consecinţă a ingestiei precoce de alcool în timpul gravidităţii, asociază: deficienţa persistentă a creşterii taliei, greutăţii şi circumferinţei craniene, anomalii faciale caracteristice, malformaţii cardiace (predomină defectele septale), anomalii minore ale articulaţiilor şi extremităţilor, deficienţe ale dezvoltării şi funcţiei sistemului nervos central. Complexitatea, gravitatea şi frecvenţa modificărilor este variabilă în funcţie de consumul de alcool asociat sau nu altor riscuri: status socioeconomic scăzut, perturbări psihologice, fumat, droguri. Afectarea auzului sub efectul alcoolului, neinclusă clasic în sindromul alcool fetal precum şi infecţiile cronice ale urechii se asociază cu grade variabile de severitate. Examinările de specialitate aplicate sistematic la copiii cu SAF mai mult sau mai puţin sever au dus la conturarea a patru tipuri principale de perturbări ale auzului: întârzierea dezvoltării funcţiei auditive asociată cu perturbări ale vorbirii, pierderea neuro-senzorială a auzului (afectarea urechii medii şi a căilor auditive), pierderi intermitente ale funcţiei de conducere a vibraţiilor sunetului, pierderea auzului prin leziuni centrale. Identificarea precoce a anomaliilor de auz, de origine conductivă sau neuro-senzorială, contribuie la ameliorarea prognosticului prin intervenţii recuperatorii precoce

HEARING DISORDERS – PART OF FETAL ALCOHOL SYNDROME

Fetal alcohol syndrome (FAS) (1-2/1000 newborns), resulting from maternal consumption of alcohol early in the pregnancy, consists in: persistent growth failure, low weight, microcephaly, characteristic facial features, congenital heart diseases (especially septal defects), minor anomalies of joints and limbs, disorders of central nervous system development and function. The complexity, severity and frequency of the anomalies depends on the amount of the ingested alcohol associated or not with other risk factors: low socio-economic level, psychologic disturbances, smoking, drugs. Hearing disorders determined by maternal alcohol consumption, although not classically included in the FAS, and also chronic ear infections, are associated in variable severity degrees. Audiologic procedures performed in FAS children revealed four main hearing disorders: delayed development of auditory function associated with language disorders, sensorineural hearing loss (disorders of middle ear and conductive system), intermittent loss of sound vibrations conduction, hearing loss by central auditory nervous system deficits. Early detection of hearing anomalies alleviates the prognosis by early interventions