Deterioration and Recovery in Verbal Recall: Repetition Helps against Pro-Active Interference

The current study tests whether memory deterioration due to pro-active interference (PI) in verbal recall could be halted via block repetition potentially leading to an increased memory consolidation. We also tested whether bilinguals would be better shielded against memory deterioration than monolinguals because they constantly need to enrich their vocabulary to compensate for their smaller lexica in either language. We tested monolinguals and balanced bilinguals with an N-Back and a free verbal recall task. Repetition showed a significant main effect with a large effect size. In Study 1 (N=45), monolingual men showed less improvement in the repetition blocks, while bilingual men showed a significant doubling of their word recall on each repetition. In Study 2 (N=78), monolingual women were less likely to use the repetition opportunity to improve the word score. Thus, in both studies, a significant monolingual disadvantage showed. When the two data sets were merged (N=123), statistical effects showed that the single word list repetition had successfully and significantly increased resistance to PI, but all individual differences due to bilingualism and sex had disappeared. This supported a previous meta-analysis showing that a monolingual disadvantage does not hold in large samples with N > 100 (Paap effect)

Ultraschallbefunde und Therapie bei einer Kuh mit einem Hämangiosarkom in der Harnblase

A 4.5-year-old Swiss Braunvieh cow was presented to the Department of Farm Animals, University of Zurich, because of severe haematuria. All other clinical findings were within normal ranges. Transrectal ultrasonography revealed a 1 cm × 1 cm echogenic, irregularly-shaped, raised mass in the wall of the urinary bladder. Endoscopy identified the mass as a proliferation, approximately 0.5 cm in diameter, which was bleeding continuously. Thermocautery of the bleeding site was carried out twice five days apart via endoscopy. Clinical signs resolved for the remainder of the cow’s life; she was slaughtered 15 months later because of infertility. Histological examination of the mass revealed a haemangiosarcoma

FGFR-ERK signaling is an essential component of tissue separation

AbstractFormation of a constriction and tissue separation between parent and young polyp is a hallmark of the Hydra budding process and controlled by fibroblast growth factor receptor (FGFR) signaling. Appearance of a cluster of cells positive for double phosphorylated ERK (dpERK) at the late separation site indicated that the RAS/MEK/ERK pathway might be a downstream target of the Hydra Kringelchen FGFR. In fact, inhibition of ERK phosphorylation by the MEK inhibitor U0126 reversibly delayed bud detachment and prevented formation of the dpERK-positive cell cluster indicating de novo-phosphorylation of ERK at the late bud base. In functional studies, a dominant-negative Kringelchen FGFR prevented bud detachment as well as appearance of the dpERK-positive cell cluster. Ectopic expression of full length Kringelchen, on the other hand, induced a localized rearrangement of the actin cytoskeleton at sites of constriction, localized ERK-phosphorylation and autotomy of the body column. Our data suggest a model in which (i) the Hydra FGFR targets, via an unknown pathway, the actin cytoskeleton to induce a constriction and (ii) FGFR activates MEK/ERK signaling at the late separation site to allow tissue separation

What lies beneath: Hydra provides cnidarian perspectives into the evolution of FGFR docking proteins

Across the Bilateria, FGF/FGFR signaling is critical for normal development, and in both Drosophila and vertebrates, docking proteins are required to connect activated FGFRs with downstream pathways. While vertebrates use Frs2 to dock FGFR to the RAS/MAPK or PI3K pathways, the unrelated protein, downstream of FGFR (Dof/stumps/heartbroken), fulfills the corresponding function in Drosophila. To better understand the evolution of the signaling pathway downstream of FGFR, the available sequence databases were screened to identify Frs2, Dof, and other key pathway components in phyla that diverged early in animal evolution. While Frs2 homologues were detected only in members of the Bilateria, canonical Dof sequences (containing Dof, ankyrin, and SH2/SH3 domains) were present in cnidarians as well as bilaterians (but not in other animals or holozoans), correlating with the appearance of FGFR. Although these data suggested that Dof coupling might be ancestral, gene expression analysis in the cnidarian Hydra revealed that Dof is not upregulated in the zone of strong FGFRa and FGFRb expression at the bud base, where FGFR signaling controls detachment. In contrast, transcripts encoding other, known elements of FGFR signaling in Bilateria, namely the FGFR adaptors Grb2 and Crkl, which are acting downstream of Dof (and Frs2), as well as the guanyl nucleotide exchange factor Sos, and the tyrosine phosphatase Csw/Shp2, were strongly upregulated at the bud base. Our expression analysis, thus, identified transcriptional upregulation of known elements of FGFR signaling at the Hydra bud base indicating a highly conserved toolkit. Lack of transcriptional Dof upregulation raises the interesting question, whether Hydra FGFR signaling requires either of the docking proteins known from Bilateria

Understanding our peritoneal dialysis patients during COVID-19 pandemic and beyond

Providing the information about the advanced kidney disease diagnosis and the need for starting dialysis to the patient and their family can be a real challenge for healthcare professionals. Nephrologists and nurses are usually not efficiently prepared to understand the emotional and mental status of patients starting dialysis, from the psychological point of view. This understanding would allow patients to take a decision which is more suitable for them, and help to choose home dialysis, especially peritoneal dialysis (PD), more widely. To learn about the significant change in patients’ life due to the necessity for renal replacement therapy (RRT) can be difficult enough to raise anxiety to a level resulting in different personality defence mechanisms. To help patients to better understand healthcare professionals, one has to adjust our perspective and the way we perceive patients, in order to empathize with their situation, their emotions and reactions, in order to communicate more efficiently, to provide the information in a more understandable way, and achieve better compliance of patients and better clinical outcomes, by involving patients into the shared decision making. We describe the potential reactions of people exposed to information about the overlapping danger of the kidney disease and current COVID-19 pandemic, and death coming in form of news, text messages, social media, internet, and interpersonal communication, and the similarities in the communication process experienced by PD patients and their families and nephrology healthcare professionals

Wie aufgeklärt sind unsere Grundschüler? Befragung von 111 Kindern der 4. Jahrgangsstufe zum Thema Sexualität

Die Untersuchung fand 2006 in 5 Klassen der vierten Jahrgangsstufe in ländlicher Umgebung statt. Von den befragten 111 Schülern waren 45 Jungen und 66 Mädchen. 70 der 111 Schüler hatten bereits Sexualkundeunterricht. Dieser führte nach dem Ergebnis dieser Untersuchung nicht zu einem umfassenden Wissensstand. Im Rahmen der Lehrerausbildung in Niedersachsen ist eine Vorbereitung auf den Sexualkundeunterricht nicht verpflichtend und das, obwohl die Pubertät im Vergleich zu den vorhergehenden Generationen früher einsetzt. Eine qualitativ hochwertige sexuelle Aufklärung scheint daher für alle Kinder vor Einsetzen der Pubertät sinnvoll

Sciatica - radiating pain affecting an increasing part of society

Introduction: Sciatica is a current and more common problem affecting normal functioning. Along with the development of civilization, the lifestyle has also changed, contributing to spend a large amount of time in a sitting position. Material and Methods: Review of literature data available in the Pubmed, Cochrane and Google Scholar databases. Results: Both in a standing and sitting position, the pressure exerted on the intervertebral discs increases leading to a hernia which, pressing on the roots of the L4-S1 nerves, lead to symptoms characterized by pain in the lumbar region, back of the buttock, thigh, calf, foot and paresthesia of these areas. Due to the progressive changes associated with aging, the frequency of sciatica increases with age. The basis for the diagnosis of sciatica is a carefully collected interview and examination of the patient, while imaging and neurophysiological tests can be helpful in determining the degree of compression on nerve structures. Treatment of sciatica is dependent on the cause and can be both conservative and surgical. Conclusions: Due to the increasing number of cases of sciatica, it seems necessary to expand the knowledge on the diagnostic and therapeutic possibilities of this disease

Ratio of proliferation markers and HSP90 gene expression as a predictor of pathological complete response in breast cancer neoadjuvant chemotherapy

Introduction. Prediction of response to preoperative breast cancer chemotherapy may offer a substantial optimization of medical management of this disease. The most efficient prediction would be done a priori, before the start of chemotherapy and based on the biological features of patient and tumor. Numerous markers have been proposed but none of them has been applied as a routine. The role of MKI67 and HSP90 expression has been recently suggested to predict treatment sensitivity in HER2-positive breast cancer. The aim of this study was to validate the utility of proliferation based markers (MKI67 and CDK1) and heat shock proteins (namely HSP90) to predict response to chemotherapy in cohort of breast cancer patients treated preoperatively. Material and methods. Ninety-three patients with breast cancer, all females, mean age 42.2 years, among them 32% T1-T2 patients, 49% T3 patients and 13% with T4 tumor stage, 27% N0, 42% N1, 16% N2, 15% N3 were subjected to initial chemotherapy. The majority of patients (86%) received anthracycline and taxane chemotherapy. Among the patients there were 9 individuals with metastatic disease (M1) at initial presentation, and 11 patients were not treated surgically after initial chemotherapy (no sufficient disease response). From 82 patients operated on, 20 patients (24%) showed pathological complete response (pCR), while in 62 patients there was no pCR. 42% of patients were hormone-sensitive HER2-negative, 20% hormone-sensitive HER2-positive, 9% only HER-positive and 29% with triple negative breast cancer. Four gene transcripts (MKI67, cyclin-dependent kinase 1 [CDK1], heat shock proteins HSP90AA1 and HSP- 90AB1) were analyzed in total RNA isolated from single core obtained during preoperative core needle biopsy by quantitative real-time PCR with fluorescent probes (Universal Probe Library, Roche). Results were normalized to the panel of reference genes. Results. There were no statistically significant differences in MKI67 and CDK1 expression between pCR and no pCR groups (p = 0.099 and 0.35, respectively), although the median expression of both genes was slightly higher in pCR group. In contrast, both HSP90AA1 and HSP90AB1 transcripts showed decreased expression in pCR group (medians 0.77 and 0.55) when compared to no p CR group (median 0.86 and 0.73), statistically significant for HSP90AA1 (p = 0.031) and of borderline significance for HSP90AB1 (p = 0.054). The most significant predictor of pCR was the ratio of CDK1 transcript to HSP90AA transcript. This ratio was significantly higher in CR group (median 0.99) than in no CR group (median 0.68, p = 0.0023), and showed a potential diagnostic utility (area under receiver operating characteristic [ROC] curve 0.72). Conclusions. HSP90AA1 and AB1 genes exhibit low expression in breast cancers highly sensitive to chemotherapy and may indicate the patients with higher probability of pathological complete response. The ratio of HSP90AA1 to proliferation-related markers (CDK1 or MKI67) may be even better predictor of pCR chance, with higher expression of proliferation genes and lower stress response in patients sensitive to chemotherapy

Mast cells and their role in pathogenesis of selected skin diseases

Mastocyty, powstające w komórkach hematopoetycznych szpiku kostnego, uwalniają wiele substancji biologicznie czynnych (cytokiny, chemokiny, czynniki wzrostu, neuropeptydy oraz enzymy proteolityczne). Na powierzchni mastocytów znajduje się wiele receptorów determinujących ich funkcje oraz umożliwiających ich interakcje z komórkami układu immunologicznego i neuroendokrynnego skóry. W mastocytozie dochodzi do klonalnej proliferacji MCs, które gromadzą się w tkankach, przede wszystkim w skórze i w szpiku kostnym. W ciężkich postaciach układowych choroby nacieczenie narządów prowadzi do upośledzenia ich funkcji. U chorych zarówno na skórną, jak i układową postać mastocytozy dochodzi do rozwoju objawów zależnych od mediatorów uwalnianych przez mastocyty w procesie degranulacji. W atopowym zapaleniu skóry MCs biorą udział w reakcji nadwrażliwości typu I, promują różnicowanie się limfocytów w kierunku Th2 lub Th1, wydzielają mediatory biorące udział w patogenezie świądu, pobudzają chemotaksję limfocytów i komórek dendrytycznych do skóry oraz przyczyniają się do rozwoju przewlekłego stanu zapalnego skóry. W łuszczycy w obrębie zmian skórnych obserwuje się zwiększoną liczbę MCs, które wydzielają cytokiny prozapalne, stymulują migrację neutrofilów, monocytów i limfocytów do skóry oraz wydzielają mediatory indukujące świąd.Mast cells derived from bone marrow hematopoetic stem cells, have the ability to release multiple biologically active substances (such as cytokines, chemokines, growth factors, neuropeptides, and proteolytic enzymes). On the surface of mast cells, there are numerous receptors that determine the function of these cells and enable them to interact with the cells of the immune system and the neuroendocrine system of the skin. In mastocytosis, there is a clonal proliferation of mast cells which accumulate in various tissues, particularly in the skin and the bone marrow. In severe forms of systemic disease infiltration of organs leads to an impairment of their function. Both patients with cutaneous and systemic mastocytosis suffer from mast cell mediator-related symptoms. In atopic dermatitis MCs are involved in type I hypersensitivity reactions, promote the differentiation of cells towards Th2 or Th1, secrete mediators involved in the pathogenesis of pruritus, stimulate chemotaxis of lymphocytes and dendritic cells into the skin and contribute to the development of chronic inflammation of the skin. In psoriasis an increased number of MCs was found in skin lesions. Moreover, these cells secrete numerous proinflammatory cytokines, stimulate migration of neutrophils, monocytes and lymphocytes into the skin and secrete mediators which induce itching

Population Pharmacokinetic Model and Pharmacokinetic Target Attainment of Micafungin in Intensive Care Unit Patients

_Objective:_ To study the pharmacokinetics of micafungin in intensive care patients and assess pharmacokinetic (PK) target attainment for various dosing strateg