Investigation of possible virulence factors in Candida strains isolated from blood cultures

Background: The Candida species, which are one of the most common causes of nosocomial bloodstream infections, present with high mortality and morbidity rates. This study aims to investigate the production of esterase, phospholipase, proteinase, and biofilm formation ability of the Candida strains isolated from the blood cultures.Materials and Methods: Between June 2011 and July 2012, the Candida strains, which were isolated from blood cultures of a total of 50 patients, were studied. The esterase activity was analyzed in the Tween.80 agar, while phospholipase activity was studied in the egg yolk agar. The proteinase activity and biofilm formation were identified by using the petridish method and microplate method, respectively.Results: Of 50 specimens obtained from individual patients, 17 (34%) were identified as C. albicans, 14 (28%) as C. glabrata, 9 (18%) as C. parapsilosis, 5 (10%) as C. krusei, 4 (8%) as C. kefyr, and 1 (2%) as C. tropicalis. The rate of proteinase, phospholipase, and esterase positivity was higher in the C. albicans isolates. Biofilm formation was the highest in the C. parapsilosis strains.Conclusions: Higher rate of virulence factors in the most commonly isolated Candida species than other species indicates that these virulence factors play a crucial role in the pathogenesis.Key words: Biofilm, blood culture, candidemia, esterase, phospholipase, proteinas

IDH-mutant glioma specific association of rs55705857 located at 8q24.21 involves MYC deregulation

The single nucleotide polymorphism rs55705857, located in a non-coding but evolutionarily conserved region at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a causal variant. However, the molecular mechanism underlying this association has remained unknown. With a case control study in 285 gliomas, 316 healthy controls, 380 systemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the association was specific to IDH-mutant gliomas. Odds-ratios were 9.25 (5.17–16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94–27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas. Decreasing strength with increasing anaplasia implied a modulatory effect. No somatic mutations were noted at this locus in 114 blood-tumor pairs, nor was there a copy number difference between risk-allele and only-ancestral allele carriers. CCDC26 RNA-expression was rare and not different between the two groups. There were only minor subtype-specific differences in common glioma driver genes. RNA sequencing and LC-MS/MS comparisons pointed to significantly altered MYC-signaling. Baseline enhancer activity of the conserved region specifically on the MYC promoter and its further positive modulation by the SNP risk-allele was shown in vitro. Our findings implicate MYC deregulation as the underlying cause of the observed association

The treatment-related experiences of parents, children and young people with regular prescribed medication

Background Taking regular medication has been shown to have an impact on the daily lives of patients and their families. Objective To explore the medication-related experiences of patients and their families when a child or young person is prescribed regular medication. Setting A specialist U.K. paediatric hospital. Method Semi-structured face-to-face interviews of 24 parents/carers, children or young people, who had been taking two or more medications for 6 weeks or longer. The themes explored included the medication regimen, formulation, supplies, social aspects and adverse effects. The data was analysed using NVIVO version 11. Main outcome measure The experiences of patients, and their parents/carers, when a child/young person takes regular medication. Results Participants described a range of experiences associated with taking regular medication. Medication-related challenges were experienced around the timing of administration which was managed over 24 h rather than waking hours. Updating medication doses for administration at school was often delayed. Unintended nonadherence was cited as the biggest challenge with a range of strategies employed to manage this. The internet was commonly used as a source of additional information accessed for reassurance and adverse effects but there were varying experiences of using patient forums/help groups. Other challenges included the adequacy of information, travelling with medication, formulation issues, arranging supplies and adverse effects. Conclusion Patients and parents experience many challenges with children’s medication. Individualised treatment options should be considered. Further research is required to determine how these experiences may be managed including the role of paediatric medication review

The impact of cardiovascular medication use on patients’ daily lives: a cross-sectional study

Introduction The management of multiple long-term medicines use in patients with chronic diseases creates a burden for patients. However, limited research is performed on patients’ experienced medication-related burden and its impact on daily lives. Therefore, the aim of this study was to explore the impact of cardiovascular medication on different aspects of patients’ daily lives and to examine the differences of these aspects between adherent and non-adherent patients. Methods A cross-sectional study was performed in two community pharmacies in the Netherlands. Patients (?45 years) using cardiovascular medication participated. Data were collected by means of the Living with Medicines Questionnaire (LMQ-2) measuring the burden of medicines use on patients’ daily lives. Two equally group-sized samples of patients non-adherent to prescribed medicines as assessed with pharmacy refill data, and patients adherent to prescribed medicines were selected. Results In total, 196 patients participated (51% male, 71.0±10.6 years), of whom 96 patients were non-adherent to cardiovascular medication. Substantial proportions of patients experienced medication-related burden on different daily life aspects. This burden was mainly related to the acceptance of long-term medication use, medication-related concerns or dissatisfaction, the interference of medicines with social and daily lives, and the interaction and communication with health care providers. No statistically significant results were found when comparing the impact on patients’ daily lives between the adherent and non-adherent sample. Conclusion Health care providers should acknowledge the impact of multiple long-term medicine use on patient’s daily lives and should make an effort to diminish patients’ medication-related burden by improving patient-provider relationships and by providing adequate treatment information incorporating patients’ individual circumstances and preferences. This may facilitate the integration of long-term medicines use in patients’ daily lives

Searches for Ultra-High-Energy Photons at the Pierre Auger Observatory

The Pierre Auger Observatory, which is the largest air-shower experiment in the world, offers unprecedented exposure to neutral particles at the highest energies. Since the start of data collection more than 18 years ago, various searches for ultra-high-energy (UHE, E greater than or similar to 10^(17) eV) photons have been performed, either for a diffuse flux of UHE photons, for point sources of UHE photons or for UHE photons associated with transient events such as gravitational wave events. In the present paper, we summarize these searches and review the current results obtained using the wealth of data collected by the Pierre Auger Observatory

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Medroxyprogesterone acetate alone or synergistic with chemotherapy suppresses colony formation and DNA synthesis in C6 glioma in vitro

We have studied the effects of medroxyprogesterone acetate (MPA) on C6 glioma growth in vitro in order to prove the hypothesis that it could arrest growth and induce drug sensitisation in a glial tumour as it does in breast cancer cells. Plating, thymidine-labelling index, ultra-structure, and soft agar colony growth were determined after incubation with MPA, and/or cisplatin, procarbazine and methotrexate (MTX). MPA (1 mug/ml) reduced the thymidine-labelling index by 41 and 73% at 48 and 96 h, respectively, and decreased colon growth by 61%. Soft agar colony inhibition by NIPA was almost as potent as MTX (0.3 mug/ml), but the latter drug showed very high cytotoxicity. Electron ri-i-icroscopy revealed that in medroxyprogesterone treated cells myeloid bodies developed, but MTX treatment caused mainly necrosis. Medroxyprogesterone increased procarbazine and cisplatin-induced colony growth and S-phase inhibition, but reduced MTX-induced thymidine-labelling inhibition. In conclusion, progesterone may inhibit growth and sensitize to drugs. (C) 2001 ISDN. Elsevier Science Ltd. All rights reserved

Patients with fixed flexion deformity after total knee arthroplasty do just as well as those without: ten-year prospective data

Range of motion (ROM) is an important outcome variable after total knee arthroplasty (TKA). This may be compounded by a pre-existing fixed flexion deformity (FFD). We therefore examined the long-term outcomes of patients with a flexion deformity undergoing TKA compared to those without a preoperative fixed flexion deformity. Participants who had undergone TKA at our centre between 1989 and 2002 were examined preoperatively, one, five and ten years after TKA (Kinemax PS; Howmedica, Rutherford, NJ, USA). Examining those with a preoperative FFD of greater than ten degrees with complete ten year follow-up data revealed 77 individuals. Seventy seven age, sex and body mass index matched patients were identified and the effect of TKA on indices of knee function (fixed flexion, maximum flexion, total ROM and Knee Society score (KSS) in both groups were analysed using repeated measures ANOVA. A significant difference between the groups with respect to fixed flexion (p < 0.001), total ROM (p = 0.001) and KSS (p < 0.001) was observed between baseline and year one suggesting that those with a preoperative FFD improved more than those without. A significant difference with regard to fixed flexion was also observed between years one to five (p = 0.001) and just failed to reach statistical significance between five to ten years (p = 0.052) between the groups. This study demonstrates that patients with a preoperative fixed flexion deformity show continued improvement in their fixed flexion up to ten years post arthroplasty and have similar outcomes to those with no preoperative fixed flexion