Miracle-dz/UniFAR-FTUs huggingface dataset:
Everyday activities for people with dementia in residential aged care: associations with person-centredness and quality of life.

BACKGROUND Providing everyday activities is central to high quality residential aged care, but further research is needed on the association between activity participation, person-centred care and quality of life. AIMS AND OBJECTIVES To explore the point-prevalence of participation in everyday activities for residents with dementia within a national sample of Swedish residential aged care units and to explore if residents participating in everyday activities lived in more person-centred units and/or had higher quality of life as compared to residents not participating in everyday activities. DESIGN AND METHODS A cross-sectional design was used to collect valid and reliable questionnaire data on activity participation, unit person-centredness and quality of life in a sample of residents in residential aged care (n = 1266). RESULTS Only 18% of residents participated in everyday activities such as making coffee, setting or clearing the table, cleaning or watering plants, 62% participated in outdoor walks, 27% participated in parlour games, and 14% and 13% participated in excursions and church visits, respectively. Those residents who had participated in everyday activities lived in more person-centred units, had significantly higher quality of life and higher cognitive scores as compared to those residents who had not participated in everyday activities. CONCLUSIONS Even though the prevalence of resident participation in everyday activities was low, resident participation was significantly associated with unit person-centredness and resident quality of life. It seems that everyday activities that are routine and commonplace to residential aged care can be potent nursing interventions for promoting resident quality of life.
The rate and role of diaphragmatic peritonectomy in optimal cytoreduction in patients with advanced stage ovarian cancer: a prospective study of 100 patients

Background. Diaphragmatic peritoneal metastasis by advanced epi­thelial ovarian cancer is a very common holdback precluding optimal cytoreduction. The aim of this study was to determine the rate of dia­phragmatic peritonectomy during optimal cytoreductive surgery and its role in postoperative morbidity and survival in patients with advanced ovarian cancer. Materials and methods. 100 consecutive patients with advanced epithelial ovarian cancer underwent cytoreductive surgery and were followed up prospectively (January 2009 – March 2014). Characteristics of surgery, rate of diaphragmatic peritonectomy and post operative complications were assessed. The Kaplan-Meier method was used for survival analysis. Results. The median age of the entire cohort at the time of primary cytoreduction was 58.5 years (23–83). Optimal cytoreduction was achieved in 73 cases out of 100 patients. From 73 patients in 30 cases (41.1%) upper abdominal procedures, specifically diaphragmatic peritonectomy, was performed to achieve the main goal of cytoreduction – no visible or palbable disease at the end of cytoreduction. Non-optimal cytoreduction was achieved in 27 cases. According to the Clavien-Dindo complication grading system grade I and grade II complications occurred more often in patients that underwent diaphragmatic surgery. The median overall survival from the time of diagnosis to the last follow-up or death was 28 months (range 0–63 months). The factors associated with the longest survival after primary cytoreductive surgery were the disease free interval from the primary cytoreduction of more than 19 months (n = 51) versus less than 19 months (n = 49) (95% confidence interval, 51.7–59.5; P = 0.013) and no visible or palpable residual disease at the end of cytoreduction (n = 73) versus visible or palpable residual di­sease (n = 27) (95% confidence interval, 52.7–61.2; P = 0.03). Conclusions. Based on our prospective analysis of advanced ovarian cancer patients, diaphragmatic peritonectomy is feasible and safe, ensures better rates of optimal cytoreduction and should not be an obstacle towards better survival.
Parasitological versus molecular diagnosis of strongyloidiasis in serial stool samples: how many?

Abstract Strongyloidiasis is usually an asymptomatic disease in immunocompetent patients, caused by Strongyloides stercoralis. However, in immunocompromised patients it can produce a severe clinical profile. Therefore, a correct diagnosis is necessary in these cases and in those chronic asymptomatic patients. The low sensitivity of classical parasitological techniques requires the analysis of multiple serial stool samples. Molecular diagnostic techniques represent an improvement in the detection of the parasite. The objective of this study was to evaluate the minimum number of samples necessary to achieve maximum sensitivity by real-time polymerase chain reaction (PCR). A total of 116 stool samples from 39 patients were analysed by direct microscopic observation, agar culture, Harada–Mori and real-time PCR, in one, two, three and four or more consecutive samples. After two serial samples, 6 out of 39 patients were positive by parasitological and molecular techniques, while 16 of them were real-time PCR positive, and all the patients detected by parasitology were also detected by the molecular technique, reaching 100.00% sensitivity versus 83.00% when analysing a single sample. These data also reflect apparently low specificity (51.52%) and positive predictive value (PPV) (27.27 %) values, due to the high number of cases detected by real-time PCR and not by parasitological techniques. These cases were confirmed as true positives when analysing three, four or more samples from the same patient. In conclusion, the application of molecular techniques decreases the number of serial stool samples necessary to give a diagnosis with the maximum sensitivity.
Molecular identification of cryptic cysticercosis: Taenia ovis krabbei in wild intermediate and domestic definitive hosts

Abstract The complex life cycle of taeniids represents an ideal model of a multi-host system. The complexity of these parasites can therefore cover the epidemiological issues of the interface between wild and domestic animals, especially once spatial overlap between wild and domestic definitive and intermediate hosts occurs. Here we use the occurrence of Taenia ovis krabbei in two model areas as an example of this epidemiological complexity. In two contiguous areas in the Italian northern Apennines, two hunted roe deer (Capreolus capreolus) showed numerous cysticerci in the muscles of their whole body and an adult tapeworm was recorded in a semi-stray dog (Canis lupus familiaris). Through molecular typing of the mitochondrial cytochrome c oxidase I (cox1) gene, cysticerci and the adult tapeworm of T. krabbei were identified. Taenia krabbei cysticercosis was recorded for the first time in Italy. Although the role of dogs in the parasite's life cycle emerges, the overlap between wild and domestic definitive hosts and the increase of wild population densities raise concerns about the temporal (old or new) introduction and the spread of this parasite by one of these canid species (wolf (Canis lupus) or dog). Although T. krabbei is not a public health issue, economic concerns emerged for hunters and meat producers, related to the damage of carcasses by cysticerci. Therefore, there is a need to evaluate the spread of T. krabbei in the intermediate and definitive host populations, and to ensure the relevant sanitary education for hunters in order to avoid practices that could favour the spread and maintenance of its life cycle.
Kinetic analyses reveal potent and early blockade of hepatitis C virus assembly by NS5A inhibitors.

BACKGROUND & AIMS All-oral regimens combining different classes of direct-acting antivirals (DAA) are highly effective for treatment of patients with chronic hepatitis C. NS5A inhibitors will likely form a component of future interferon-sparing treatment regimens. However, despite their potential, the detailed mechanism of action of NS5A inhibitors is unclear. To study their mechanisms, we compared their kinetics of antiviral suppression with those of other classes of DAA, using the hepatitis C virus genotype 1a cell culture-infectious virus H77S.3. METHODS We performed detailed kinetic analyses of specific steps in the hepatitis C virus life cycle using cell cultures incubated with protease inhibitors, polymerase inhibitors, or NS5A inhibitors. Assays were designed to measure active viral RNA synthesis and steady-state RNA abundance, polyprotein synthesis, virion assembly, and infectious virus production. RESULTS Despite their high potency, NS5A inhibitors were slow to inhibit viral RNA synthesis compared with protease or polymerase inhibitors. By 24 hours after addition of an NS5A inhibitor, polyprotein synthesis was reduced <50%, even at micromolar concentrations. In contrast, inhibition of virus release by NS5A inhibitors was potent and rapid, with onset of inhibition as early as 2 hours. Cells incubated with NS5A inhibitors were rapidly depleted of intracellular infectious virus and RNA-containing hepatitis C virus particles, indicating a block in virus assembly. CONCLUSIONS DAAs that target NS5A rapidly inhibit intracellular assembly of genotype 1a virions. They also inhibit formation of functional replicase complexes, but have no activity against preformed replicase, thereby resulting in slow shut-off of viral RNA synthesis.
Arctic systems in the Quaternary: ecological collision, faunal mosaics and the consequences of a wobbling climate

Abstract Climate oscillations and episodic processes interact with evolution, ecology and biogeography to determine the structure and complex mosaic that is the biosphere. Parasites and parasite–host assemblages are key components in a general explanatory paradigm for global biodiversity. We explore faunal assembly in the context of Quaternary time frames of the past 2.6 million years, a period dominated by episodic shifts in climate. Climate drivers cross a continuum from geological to contemporary timescales and serve to determine the structure and distribution of complex biotas. Cycles within cycles are apparent, with drivers that are layered, multifactorial and complex. These cycles influence the dynamics and duration of shifts in environmental structure on varying temporal and spatial scales. An understanding of the dynamics of high-latitude systems, the history of the Beringian nexus (the intermittent land connection linking Eurasia and North America) and downstream patterns of diversity depend on teasing apart the complexity of biotic assembly and persistence. Although climate oscillations have dominated the Quaternary, contemporary dynamics are driven by tipping points and shifting balances emerging from anthropogenic forces that are disrupting ecological structure. Climate change driven by anthropogenic forcing has supplanted a history of episodic variation and is eliminating ecological barriers and constraints on development and distribution for pathogen transmission. A framework to explore interactions of episodic processes on faunal structure and assembly is the Stockholm Paradigm, which appropriately shifts the focus from cospeciation to complexity and contingency in explanations of diversity.
ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection.

BACKGROUND & AIMS The interferon-free regimen of ABT-450 (a protease inhibitor), ritonavir, ombitasvir (an NS5A inhibitor), dasabuvir (a non-nucleoside polymerase inhibitor), and ribavirin has shown efficacy in patients with hepatitis C virus (HCV) genotype 1b infection-the most prevalent subgenotype worldwide. We evaluated whether ribavirin is necessary for ABT-450, ritonavir, ombitasvir, and dasabuvir to produce high rates of sustained virologic response (SVR) in these patients. METHODS We performed a multicenter, open-label, phase 3 trial of 179 patients with HCV genotype 1b infection, without cirrhosis, previously treated with peginterferon and ribavirin. Patients were assigned randomly (1:1) to groups given ABT-450, ritonavir, ombitasvir, and dasabuvir, with ribavirin (group 1) or without (group 2) for 12 weeks. The primary end point was SVR 12 weeks after treatment (SVR12). We assessed the noninferiority of this regimen to the rate of response reported (64%) for a similar population treated with telaprevir, peginterferon, and ribavirin. RESULTS Groups 1 and 2 each had high rates of SVR12, which were noninferior to the reported rate of response to the combination of telaprevir, peginterferon, and ribavirin (group 1: 96.6%; 95% confidence interval, 92.8%-100%; and group 2: 100%; 95% confidence interval, 95.9%-100%). The rate of response in group 2 was noninferior to that of group 1. No virologic failure occurred during the study. Two patients (1.1%) discontinued the study owing to adverse events, both in group 1. The most common adverse events in groups 1 and 2 were fatigue (31.9% vs 15.8%) and headache (24.2% vs 23.2%), respectively. Decreases in hemoglobin level to less than the lower limit of normal were more frequent in group 1 (42.0% vs 5.5% in group 2; P < .001), although only 2 patients had hemoglobin levels less than 10 g/dL. CONCLUSIONS The interferon-free regimen of ABT-450, ritonavir, ombitasvir, and dasabuvir, with or without ribavirin, produces a high rate of SVR12 in treatment-experienced patients with HCV genotype 1b infection. Both regimens are well tolerated, as shown by the low rate of discontinuations and generally mild adverse events. ClinicalTrials.gov number: NCT01674725.
Morphometric and molecular analyses of two digenean species from the mullet: Skrjabinolecithum spinosum n. sp. from the Russian southern Far East and Unisaccus tonkini n. sp. from Vietnam

Abstract Adults of Skrjabinolecithum spinosum n. sp. were discovered in Mugil cephalus from the Gulf of Peter the Great in southern Far-East Russia. Additionally, adults of Unisaccus tonkini n. sp. were found in the intestine of Moolgarda cunnesius and Moolgarda seheli from the coastal waters of Cat Ba Island, Tonkin Bay, northern Vietnam. Skrjabinolecithum spinosum n. sp. possesses a larger body, and ventral and oral sucker size in comparison with Skrjabinolecithum vitellosum, a smaller pharynx size and body length/width rate ratio in comparison to Skrjabinolecithum pyriforme, a smaller body length and prepharynx size in comparison to Skrjabinolecithum lobolecitum and a smaller pharynx length and egg size in comparison to Skrjabinolecithum indicum and S. lobolecitum. The new species also differs from S. indicum, S. lobolecitum and S. vitellosum by the form of the testis, and from the last two species by the presence of a two-branched intestine. The morphometric parameters of S. spinosum n. sp. are similar to those of Skrjabinolecithum spasskii. However, S. spinosum n. sp. , unlike S. spasskii, has an armed hermaphroditic duct. Unisaccus tonkini n. sp. is similar to Unisaccus spinosus (Martin, 1973), Unisaccus brisbanensis (Martin, 1973) and Unisaccus overstreeti (Ahmad, 1987) in body size but differs in oral sucker, pharynx and hermaphroditic sac size from U. spinosus, and in ventral sucker and ovary size from U. brisbanensis and U. overstreeti. Bayesian phylogenetic analysis, based on combined data of internal transcribed spacer 2 (ITS2) and partial 28S rRNA gene sequences, confirmed the validity of S. spinosum n. sp. and U. tonkini n. sp. Analysis of interrelationships of the family Haploporidae, including molecular data on new species, showed that the Waretrematinae subfamily is more heterogeneous in comparison with Haploporinae and Forticulcitinae, and includes U. tonkini n. sp.
miR‐149* induces apoptosis by inhibiting Akt1 and E2F1 in human cancer cells

microRNAs (miRNAs) play vital roles in several biological processes, including apoptosis, by negatively regulating the expression of target genes. The molecular mechanisms of the key survival signal, Akt family, have been widely explored. However, it remains to be ascertained whether Akt1, the predominant isoform in most tissue, is a direct target of miRNA. In this study, we identified Akt1 and E2F1 to be two direct targets of miR‐149* and b‐Myb to be an indirect target by reporter assays and Western blot analyses. Ectopic expression of miR‐149*‐induced apoptosis in Be2C, a neuroblastoma cell line, and in HeLa cells. Silencing of Akt1 or E2F1 expression also led to similar apoptotic changes in these two cell lines, suggesting that the pro‐apoptotic effects of miR‐149* were exerted by repressing Akt1 and E2F1 expressions. Importantly, analysis of primary neuroblastoma samples revealed a significant inverse correlation of miR‐149* with E2F1 expressions (P = 0.026). Interestingly, using the reporter assays, excess miR‐149 introduced by transfection to simulated its preponderance in the in vivo condition, could not overcome the repressive function of miR‐149* on the target genes. This implies that the pro‐apoptotic function of miR‐149* may not be dampened by its predominant cognate, miR‐149, in vivo. Our findings not only provided the first evidence that Akt1 is a direct target of miRNA but also demonstrated that miR‐149* is a pro‐apoptotic miRNA by repressing the expression of Akt1 and E2F1. © 2010 Wiley‐Liss, Inc.
Large-scale hypomethylated blocks associated with Epstein-Barr virus–induced B-cell immortalization

Altered DNA methylation occurs ubiquitously in human cancer from the earliest measurable stages. A cogent approach to understanding the mechanism and timing of altered DNA methylation is to analyze it in the context of carcinogenesis by a defined agent. Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with lymphoma and nasopharyngeal carcinoma, but also used commonly in the laboratory to immortalize human B-cells in culture. Here we have performed whole-genome bisulfite sequencing of normal B-cells, activated B-cells, and EBV-immortalized B-cells from the same three individuals, in order to identify the impact of transformation on the methylome. Surprisingly, large-scale hypomethylated blocks comprising two-thirds of the genome were induced by EBV immortalization but not by B-cell activation per se. These regions largely corresponded to hypomethylated blocks that we have observed in human cancer, and they were associated with gene-expression hypervariability, similar to human cancer, and consistent with a model of epigenomic change promoting tumor cell heterogeneity. We also describe small-scale changes in DNA methylation near CpG islands. These results suggest that methylation disruption is an early and critical step in malignant transformation.
UVB‐irradiation regulates VLA‐4‐mediated melanoma cell adhesion to endothelial VCAM‐1 under flow conditions

The major aspect contributing to the mortality of melanoma is its ability to spread, or metastasize. Ultraviolet B light (UVB) is considered an indirect cause of melanoma formation. However, little is known about the potential effects of UVB to melanoma metastasis. Integrins, a large family of cell adhesion molecules (CAMs) expressed on the melanoma cell surface, are important for cell signaling, growth, and migration during metastasis. Most critically, tumor cell tissue invasion is dependent on the initial interaction of tumor cells with vascular endothelium at the target organ, and there is increasing evidence for a prominent role of melanoma very late antigen‐4 (VLA‐4) integrin binding to its endothelial ligand vascular cell adhesion molecule‐1 (VCAM‐1) in this process. This research focuses on the quantitative modulation of VLA‐4 integrin expression and function on melanoma cells after UVB irradiation. The present data show that at 3, 12, and 18 h post‐UVB irradiation, VLA‐4 expression was unchanged relative to untreated cells, but adhesion to VCAM‐1 decreased significantly. Immunofluorescence studies implied that the spatial organization of VLA‐4 on the melanoma cell surface contributed to the changes in avidity for VCAM‐1 upon UVB irradiation. With increased understanding of the molecular mechanisms underlying melanoma–endothelial interactions upon UVB irradiation, clinical advances for melanoma may be developed. © 2010 Wiley‐Liss, Inc.
Flow Cytometric Analysis of Platelet Function in Micro- and Macroangiopathy.

Aim of this study was the development of a flow cyiometric assay to detect platelet activation using in vitro stimulation with physiological agonists. Therefore, in healthy subjects and insulin-dependent diabetics with and without microangiopathy (retinopathy and/or nephropathy) the surface expression density of fibrinogen receptor complex gpIIb/IIIa (CD41), von Willebrand factor complex gpIb/IX (CD42b), ctgranule protein GMP-140 (CD62P), and of lysosomal protein gp53 (CD63) were measured ex vivo and after in vitro stimulation using ADP and thrombin receptor activator peptide 6 (TRAP-6). Best discrimination (p<0.05) between diabetics and controls were observed in the surface expression density of GMP-140 after maximum stimulation with the weak agonist ADP (20 μπιοΐ/ΐ) and sub-maximal stimulation with the strong agonist TRAP-6 (5 μπιοΐ/ΐ). Induced platelet aggregometry using collagen, ristocetin, ADP, and TRAP-6 and plasma concentrations of platelet factor 4 and -thromboglobulin failed to show any differences between the groups. GMP-140 levels were analyzed in a dual-color whole blood assay (CD41-PE and CD62P-F1TC) in 50 healthy controls and 60 patients suffering from peripheral arterial occlusive disease. Highly significant differences (p<0.005) were found between the two groups in the ex vivo as well as in the in vitro stimulated samples (mean fluorescence ±SEM ex vivo: 0.43 ±0.02 vs. 0.50 ±0.02; 5 μπιοΐ/ΐ ADP 0.93 ±0.03 vs. 1.30 ±0.04; 10 μιηοΐ/ΐ TRAP-6 3.30 ±0.17 vs. 3.91 ±0.16; all p<0.005). In conclusion, the in vitro platelet stimulation assay is an easy, fast, and sensitive tool for the detection of platelet hyperreactivity.
P53 is transported into the nucleus via an Hsf1‐dependent nuclear localization mechanism

Loss of p53 function can occur through disruption of its ability to localize to the nucleus. Previously we showed through characterization a set of mutant cell lines that lacked the ability to import p53 into the nucleus that nuclear translocation of p53 appeared to be mechanistically different from that of the SV40 T‐antigen (SV40TAg). Here we extend that work by examining nuclear importation of p53 and SV40TAg using both in vivo and in vitro assays for nuclear localization. We show that disruption of microtubule polymerization using colchicine suppresses nuclear localization of p53 but not of SV40TAg. We also show, for the first time, that the heat shock transcription factor (Hsf1), is required for establishment of the microtubule network in cells and for nuclear localization of p53. In contrast, SV40TAg does not interact with polymerized microtubules suggesting that it is transported into the nucleus through an alternative mechanism. Interestingly, lacking of Hsf1 expression and suppressing Hsf1 by siRNA also made cells more resistant to the cytotoxic effects of paclitaxel. Hence, loss of Hsf1 activity not only suppressed p53 function, but also led to reduced sensitivity to killing by drugs that target microtubules. © 2010 Wiley‐Liss, Inc.