The reasons for development of complications in soft contact lenses wearers: A qualitative study

© 2020, Serbian Medical Society. All rights reserved. Objective. To determine reasons and their actual role in occurrence of complications in users of soft contact lenses. Methods. This was a qualitative study in which a constructivist grounded theory approach was used to analyze obtained data. The study population consisted of two groups of subjects: 10 students who were identified as users of soft contact lenses and 4 ophthalmologists. Each of the respondents participated ina single interview. Based on audio recordings of these interviews appropriate transcripts of conversations were made and analyzed. After elimination of waste words 11 key categories were crystallized. Results. Recommendations of the ophthalmologists perhaps have the decisive role in the formation of attitude that users will have regarding the adequate hygiene of soft contact lenses: hand hygiene, proper cleanliness of storage for soft contact lenses and using the solution in the allotted time are imperative for users of soft contact lenses. Sleeping with soft contact lenses for a long period and more frequently than it was specified in the recommendation of an ophthalmologist is one of the greatest reasons for development of dry eye symptoms, while swimming with soft contact lenses increases the risk for occurrence of eye infections. Conclusion. The main reasons for the occurrence of complications in soft contact lenses users are inadequate hygiene and weakening of compliance of soft contact lenses users over time

The effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia

Background/Aim. Immune system disorder, including inflammation, takes a significant place when considering still unclear etiology of schizophrenia. The aim of this study was to determine the blood levels of nonspecific inflammation markers in the first episode of schizophrenia and their relation to the therapy response. Methods. In this study we determined the blood levels of nonspecific inflammation markers: white blood cells count (WBC), C-reactive protein (CRP), erythrocytes sedimentation rate (ESR) and the elements of differential white blood cell counts (or the leukocyte formula): granulocytes (Gra), lymphocytes (Lym) and monocytes (Mon), in the first episode of schizofrenia, in 78 patients hospitalized at the Clinic for Psychiatric Disorders “Dr Laza Lazarević” in Belgrade. The levels were measured at admission to the clinic, as well as after 4 weeks of antipsychotic treatment. The Positive and negative syndrome scale for schizophrenia (PANSS) was applied to measure the severity of psychopathology and response to the treatment. Results. During the first episode of schizophrenia, before initiation of antipsychotic treatment, the frequency of abnormal values was high (≥ 25% of the patients) for the following non-specific inflammation markers: WBC, CRP, ESR and Gra, in the leukocyte formula, but dropped after 4 weeks of antipsychotic treatment at the level of high statistical significance for WBC and Gra (p < 0.001). The ESR remained unchanged in as many as 50% of the patients even after 4-week antipsychotic treatment, at the level of statistical significance in the non-responders compared to the responders (p = 0.045). Conclusion. The obtained results indicate that in the first episode of schizophrenia the blood levels of non-specific inflammation markers (WBS, CRP, ESR and Gra from the leukocyte formula) were high in the subpopulation of patients with the tendency towards normalization of inflammation parameters after a 4-week antipsychotic treatment

Primena prebiotika MOS-a u ishrani pastrmki

Ispitivan je uticaj manan oligosaharida (MOS) kao aditiva hrane, primenjenog u koncentraciji od 0,2% (O-I grupa riba) i 0,3% (O-II grupa riba) na morfometrijske karakteristike i osnovne proizvodne pokazatelje gajenja kalifornijske pastrmke. Ogled je sproveden na 450 riba podeljenih u tri grupe sa po 150 jedinki u svakoj grupi i trajao je 40 dana. Analizom dobijenih rezultata, ustanovljen je povoljan efekat primenjenog aditiva na morfometrijske pokazatelje tempa rasta riba, kako njihove završne komadne mase i završnih dužinskih mera, tako i njihovog prirasta, ali bez utvrđenih statistički značajnih razlika (p>0,05). Najveću prosečnu telesnu masu i dužinu tela kod ispitavanih grupa, ostvarile su pastrmke O-II grupe (118,49 g i 19,59 cm), zatim pastrmke O-I grupe (118,04 g i 19,58 cm), a najmanju K-grupa riba (115,94 g i 19,56 cm). Dodavanje MOS-a u smeše za ishranu pastrmki je imalo povoljan uticaj (p>0,05) na ostvarivanje niže konverzije hrane (HK) i boljih vrednosti osnovnih proizvodnih pokazatelja: faktora kondicije (FK), koeficijenta proteinske efikasnosti (PER), specifične stope rasta (SGR) i proizvodnog indeksa (PI) u odnosu na ribe K grupe, koje su hranjene smešama bez dodatka mananoligosaharida. Najbolje rezultate su ostvarile ribe O-II grupe, a iskazano u relativnim pokazateljima u odnosu na K grupu riba: bolju konverziju hrane za 5,61%; bolju vrednost iskorišćenja proteina hrane za 5,94%; veću vrednost faktora kondicije za 1,73%; specifične stopa rasta za 2,26% i bolju vrednost proizvodnog indeksa za 8,27%

Model zaštite prirodnih resursa integracijom upravljačkih funkcija ribarskog i lovnog područja

Ribarska i lovna područja u zakonodavnom, organizacionom i funkcionalnom smislu ispoljavaju veliku sličnost, koja proistiće iz zakonskih definicija. Kvalitet upravljanje obnovljivim resursima u oblasti ribarstva i lovstva uslovljen je političko-zakonodavnim, ekonomskim, socijalnim i tehnološko-ekološkim parametrima (kategorijama) određenim širokim spektrom različitih interesa i potreba. Zato je veoma važno odabrati model upravljanja pomenutim prirodnim resursima koji može zadovoljiti više ciljnih grupa, a da pri tome bude efikasan i ekonomičan. Cilj ovog rada je da se na realan i praktičan način prikažu kriterijumi i alternative za poboljšanje upravljačkih funkcija kroz model zaštite prirodnih resursa integracijom upravljačkih funkcija ribarskog i lovnog područja. Kao polazni materijal u ovom radu korišćeni su zakonska i planska dokumenta iz oblasti održivog korišćenja ribljeg fonda i lovstva. Izvršena je višekriterijumska analiza na osnovu kriterijuma PEST analize u odnosu na moguće alternative (posebno ribarsko, posebno lovno, integralno upravljanje ribarsko-lovnim područjem). PEST analiza se zasniva na analizi eksternih uticaja (Političko-zakonodavna, Ekonomska, Sociološka i Tehnološko-ekološka analiza) koji utiču na izbor organizacionog oblika upravljanja ribarskim i lovnim područijima. Kao kontrolni metod korišćen je analitičko hijerarhijski proces (AHP), sa namerom da se utvrdi u kojoj meri eksterni kriterijumi okruženja deluju na izbor ponuđenih alternativa (Saaty, 1980). Prema većini autora u Srbijii postoji potreba integralnog upravljanja vodnim resursima i vodoprivrednim objektima, koja bi kroz adekvatnu pravnu regulativu ostvarila svoj puni tehnološko-tehnički kapacitet, ekonomičnost, efikasnost i efektivnost. Srbija raspolaže velikim brojem reka, prirodnih i veštačkih akumulacija. Integralno upravljanje rečnim slivom pretpostavlja plansko upravljanje i izradu monitoringa baziranih na ekološkim karakteristikama i kontinuiranom praćenju biotičkih i abiotičkih faktora (Simonović i sar., 2005). U Srbiji je ustanovljeno oko 300 lovišta, u kojima su uočeni kao najčešći nedostaci: nedosledna primena i nepoštovanje zakonskih propisa, monopolizam određenih organizacija i interesnih grupa, nizak nivo tehničko-tehnološkog i institucionalnog razvoja, nepostojanje dokumenta strateškog planiranja u lovstvu, nerazvijeni monitoring divljači i njihovih staništa Sa aspekta održivog upravljanja lovnim područjima osnovni ciljevi su: povećanje brojnosti populacije sitne i krupne divljači, poboljšanje polne i starosne strukture populacija, očuvanje retkih i ugroženih vrsta lovne divljači (Medarević i sar., 2008). Radovi i dokumenta, kao i iskustva drugih zemalja upućuju na potrebu objedinjenog upravljanja pomenutim obnovljivim resursima. Može se zaključiti da bi integralno gazdovanje ribarskim i lovnim područjima poboljšalo upravljačke funkcije, smanjilo troškove i povećalo efikasnost poslovanja. Sigurno bi pozitivno uticalo i na socijalni aspekt i promenu svesti u javnosti da ribolov i lov nisu samo socijalna već i značajna privredna kategorija. Integralnim upravljanjem ribarskim i lovnim područjima bio bi olakšan monitoring sa jasnijim i uporedivim rezultatima, a kontrola i korišćenje finansijskih sredstava bila bi neuporedivo bolja i racionalnija. U pogledu funkcionisanja stručnih i čuvarskih službi potrebno je izvršiti detaljnu analizu geografskog rasporeda, veličine i broja lovnih tj. ribolovnih područja, sa ciljem optimizacije upravljanja istim na ekonomskim i ekološkim principima. Potencijalna korist za državu se vidi u smanjenju troškova uprave, pri čemu bi se mogli formirati regionalni centri na nivou jednog ili više područja, a koji bi služili za obuku kadrova, organizaciju monitoringa, reagovanja u akcidentnim situacijama i slično. Pre toga potrebno je zakonsku regulativu, a potom ribarska i lovna područja učiniti međusobno kompatibilnim

Antimicrobial treatment of Corynebacterium striatum invasive infections: a systematic review

The aim of this study was to establish an evidence-based guideline for the antibiotic treatment of Corynebacterium striatum infections. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with systemic inflammatory response syndrome, harboring C. striatum isolated from body fluids or tissues in which it is not normally present. C. striatum had to be identified as the only causative agent of the invasive infection, and its isolation from blood, body fluids or tissues had to be confirmed by one of the more advanced diagnostic methods (biochemical methods, mass spectrometry and/or gene sequencing). This systematic review included 42 studies that analyzed 85 individual cases with various invasive infections caused by C. striatum. More than one isolate of C. striatum exhibited 100% susceptibility to vancomycin, linezolid, teicoplanin, piperacillin-tazobactam, amoxicillin-clavulanate and cefuroxime. On the other hand, some strains of this bacterium showed a high degree of resistance to fluoroquinolones, to the majority majority of β-lactams, aminoglycosides, macrolides, lincosamides and cotrimoxazole. Despite the antibiotic treatment, fatal outcomes were reported in almost 20% of the patients included in this study. Gene sequencing methods should be the gold standard for the identification of C. striatum, while MALDI-TOF and the Vitek system can be used as alternative methods. Vancomycin should be used as the antibiotic of choice for the treatment of C. striatum infections, in monotherapy or in combination with piperacillin-tazobactam. Alternatively, linezolid, teicoplanin or daptomycin may be used in severe infections, while amoxicillin-clavulanate may be used to treat mild infections caused by C. striatum

Angiogenin secretion from hepatoma cells activates hepatic stellate cells to amplify a self-sustained cycle promoting liver cancer

Hepatocellular carcinoma (HCC) frequently develops in a pro-inflammatory and pro-fibrogenic environment with hepatic stellate cells (HSCs) remodeling the extracellular matrix composition. Molecules secreted by liver tumors contributing to HSC activation and peritumoral stromal transformation remain to be fully identified. Here we show that conditioned medium from HCC cell lines, Hep3B and HepG2, induced primary mouse HSCs transdifferentiation, characterized by profibrotic properties and collagen modification, with similar results seen in the human HSC cell line LX2. Moreover, tumor growth was enhanced by coinjection of HepG2/LX2 cells in a xenograft murine model, supporting a HCC-HSC crosstalk in liver tumor progression. Protein microarray secretome analyses revealed angiogenin as the most robust and selective protein released by HCC compared to LX2 secreted molecules. In fact, recombinant angiogenin induced in vitro HSC activation requiring its nuclear translocation and rRNA transcriptional stimulation. Moreover, angiogenin antagonism by blocking antibodies or angiogenin inhibitor neomycin decreased in vitro HSC activation by conditioned media or recombinant angiogenin. Finally, neomycin administration reduced tumor growth of HepG2-LX2 cells coinjected in mice. In conclusion, angiogenin secretion by HCCs favors tumor development by inducing HSC activation and ECM remodeling. These findings indicate that targeting angiogenin signaling may be of potential relevance in HCC managementThis study was funded by grants from the Instituto de Salud Carlos III (FIS PI12/00110, PI09/00056 to A.M., FIS PI10/02114, PI13/00374 to M.M., PI12/01265 to J.C. and PI11/0325 to J.F.C.), Ministerio de Economía y Competitividad (SAF 2012/34831 to J.F.C. and SAF2011-23031 to C.G.R.) and co-funded by FEDER (Fondo Europeo de Desarrollo Regional, Unión Europea. “Una manera de hacer Europa”); center grant P50-AA-11999 from Research Center for Liver and Pancreatic Diseases, US NIAAA to J.F.C.); Fundació la Marató de TV3 to J.F.C., Mutua Madrilea (AP103502012) to C.G.R., and by CIBERehd from the Instituto de Salud Carlos IIIPeer Reviewe

Antiapoptotic BCL-2 proteins determine Sorafenib/regorafenib resistance and BH3-mimetic efficacy in hepatocellular carcinoma

Sorafenib, systemic treatment for advanced hepatocellular carcinoma (HCC), and regorafenib, novel second line treatment after sorafenib failure, have efficacy limited by evasive mechanisms of acquired-drug resistance. BCL-2 proteins participate in the response to tyrosine kinase inhibitors; however, their role in HCC therapy with sorafenib/regorafenib remains uncertain. BH3-mimetic ABT-263 (navitoclax) enhanced sorafenib activity, inducing cell death via a mitochondrial caspase-dependent mechanism, after BCL-xL/BCL-2 inhibition. Sorafenib-resistant hepatoma cells (HepG2R and Hep3BR) exhibited altered mRNA expression of BCL-2 and other anti-apoptotic family members, such as MCL-1, priming drug-resistant cancer cells to death by BH3-mimetics. ABT-263 restored sorafenib efficacy in sorafenib-resistant cell lines and HCC mouse models. Moreover, in mice xenografts from patient-derived BCLC9 cells, better tumor response to sorafenib was associated to higher changes in the BCL-2 mRNA pattern. HCC non-treated patients displayed altered BCL-2, MCL-1 and BCL-xL mRNA levels respect to adjacent non-tumoral biopsies and an increased BCL-2/MCL-1 ratio, predictive of navitoclax efficacy. Moreover, regorafenib administration also modified the BCL-2/MCL-1 ratio and navitoclax sensitized hepatoma cells to regorafenib by a mitochondrial caspase-dependent mechanism. In conclusion, sorafenib/regorafenib response is determined by BCL-2 proteins, while increased BCL-2/MCL-1 ratio in HCC sensitizes drug resistant-tumors against ABT-263 co-administration. Thus, changes in the BCL-2 profile, altered in HCC patients, could help to follow-up sorafenib efficacy, allowing patient selection for combined therapy with BH3-mimetics or early switch them to second line therapy

Orthoxenografts of testicular germ cell tumors demonstrate genomic changes associated with cisplatin resistance and identify PDMP as a resensitizing agent

[Purpose] To investigate the genetic basis of cisplatin resistance as efficacy of cisplatin-based chemotherapy in the treatment of distinct malignancies is often hampered by intrinsic or acquired drug resistance of tumor cells.[Experimental Design] We produced 14 orthoxenograft transplanting human nonseminomatous testicular germ cell tumors (TGCT) in mice, keeping the primary tumor features in terms of genotype, phenotype, and sensitivity to cisplatin. Chromosomal and genetic alterations were evaluated in matched cisplatin-sensitive and their counterpart orthoxenografts that developed resistance to cisplatin in nude mice.[Results] Comparative genomic hybridization analyses of four matched orthoxenografts identified recurrent chromosomal rearrangements across cisplatin-resistant tumors in three of them, showing gains at 9q32-q33.1 region. We found a clinical correlation between the presence of 9q32-q33.1 gains in cisplatin-refractory patients and poorer overall survival (OS) in metastatic germ cell tumors. We studied the expression profile of the 60 genes located at that genomic region. POLE3 and AKNA were the only two genes deregulated in resistant tumors harboring the 9q32-q33.1 gain. Moreover, other four genes (GCS, ZNF883, CTR1, and FLJ31713) were deregulated in all five resistant tumors independently of the 9q32-q33.1 amplification. RT-PCRs in tumors and functional analyses in Caenorhabditis elegans (C. elegans) indicate that the influence of 9q32-q33.1 genes in cisplatin resistance can be driven by either up- or downregulation. We focused on glucosylceramide synthase (GCS) to demonstrate that the GCS inhibitor DL-threo-PDMP resensitizes cisplatin-resistant germline-derived orthoxenografts to cisplatin[Conclusions] Orthoxenografts can be used preclinically not only to test the efficiency of drugs but also to identify prognosis markers and gene alterations acting as drivers of the acquired cisplatin resistance.Several authors are grateful recipients of predoctoral fellowships: J.M. Piulats from the AECC and F.J. García-Rodríguez from the Instituto de Salud Carlos III (ISCIII). This study was supported by grants from the Spanish Ministry of Economy and Competitiveness (SAF2002-02265 and FIS: BFU2007-67123; PI10-0222, PI13-01339, and PI16/01898, to A. Villanueva; PI15-00895, to J. Ceron; SAF2013-46063R, to F. Vi nals; PI030264, to ~ X. García-del-Muro), Fundacio La Marat o TV3 (051430, to F. Vi nals and X. ~ García-del-Muro), Generalitat de Catalunya (2014SGR364, to A. Villanueva and F. Vinals; FIS09/0059, to A. Morales), cofunded by FEDER funds/ ~ European Regional Development Fund (ERDF) — a way to Build Europe. A. Villanueva received a BAE11/00073 grant. We thank the staff of the Animal Core Facility of IDIBELL for mouse care and maintenance.Peer reviewe

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat