The evolutionary history of hepaciviruses.

In the search for natural reservoirs of hepatitis C virus (HCV), a broad diversity of non-human viruses within the Hepacivirus genus has been uncovered. However, the evolutionary dynamics that shaped the diversity and timescale of hepaciviruses evolution remain elusive. To gain further insights into the origins and evolution of this genus, we screened a large dataset of wild mammal samples (n = 1,672) from Africa and Asia, and generated 34 full-length hepacivirus genomes. Phylogenetic analysis of these data together with publicly available genomes emphasizes the importance of rodents as hepacivirus hosts and we identify 13 rodent species and 3 rodent genera (in Cricetidae and Muridae families) as novel hosts of hepaciviruses. Through co-phylogenetic analyses, we demonstrate that hepacivirus diversity has been affected by cross-species transmission events against the backdrop of detectable signal of virus-host co-divergence in the deep evolutionary history. Using a Bayesian phylogenetic multidimensional scaling approach, we explore the extent to which host relatedness and geographic distances have structured present-day hepacivirus diversity. Our results provide evidence for a substantial structuring of mammalian hepacivirus diversity by host as well as geography, with a somewhat more irregular diffusion process in geographic space. Finally, using a mechanistic model that accounts for substitution saturation, we provide the first formal estimates of the timescale of hepacivirus evolution and estimate the origin of the genus to be about 22 million years ago. Our results offer a comprehensive overview of the micro- and macroevolutionary processes that have shaped hepacivirus diversity and enhance our understanding of the long-term evolution of the Hepacivirus genus.

The listening project: A qualitative study on the experiences of pre-registered nurses during the Covid-19 pandemic in Scotland.

Background: During the COVID 19 pandemic academic institutes worldwide were forced to shift to online or socially distanced learning. Nursing students faced unique challenges due to the limited practical learning environment and removal of supernumerary status to meet increased pressure on health care resources. Aim: To explore the experiences and perceptions of pre-registered nurses in relation to their university education during the COVID-19 pandemic. Methods: Underpinned by Lizzio (2006) [1] five senses of student success model, a novel qualitative approach using peer-to-peer discussion was utilized to explore the experiences of pre-registered nurses during the COVID-19 pandemic. Students who were on their second and final year in the nursing program were invited to participate. Interviews were conducted and transcribed using an online meeting platform. Data were analyzed using the five main stages of framework analysis. Results: Eleven peer-to-peer discussion with 22 students were conducted. The five themes were linked with the five senses student success model: capability, connectedness, purpose, resourcefulness, and culture. Six sub-themes emerged in the data: confidence and learning process, building relationships, communication, student as health professional and mental health consequences of COVID-19 pandemic. Conclusion: Whilst there was strength in university provision, the pandemic was an opportunity for students and academics to reflect and learn about how to further programme resilience and enhance student support processes. We recommend that nursing programmes should include concepts of transition, pandemic preparedness, collaboration with professional partners, and provision of catch-up sessions to analyse gaps on their skills and knowledge.

When Things Happen - The Story of COVID-19, Palliative Care, and An NGO.

Several natural disasters and the appearance of the coronavirus disease 2019 (COVID-19) pandemic created stressful situations to many health-care workers in the Philippines. New health-related challenges surfaced, and health-care workers felt lost since many of the challenges were either directly or indirectly caused by the fast-spreading coronavirus infections and its variants. Further, the way people die also changed, causing confusion and influencing the Filipino grief and bereavement processes. In response to the need of the health-care workers, a nongovernmental organization (NGO) through its education portal created and offered free webinars, aimed to help health-care workers understand and make sense of what was happening, thus empowering them with knowledge on how to manage the challenges and provide better care to the patients and the community as well. This article relates the process of planning and implementing online webinars during the era of social distancing and COVID-19 pandemic.

Molecular detection and characterization of Theileria sp. from hedgehogs (Paraechinus aethiopicus) in Saudi Arabia.

In this study, we conducted molecular detection and characterization of piroplasms that infect the Ethiopian or desert hedgehogs (Paraechinus aethiopicus) in Saudi Arabia. Blood samples from 112 (68 males and 44 females) desert hedgehogs from Unaizah, Central Saudi Arabia were screened for Theileria/Babesia DNA using the polymerase chain reaction (PCR) employing specific primers amplifying the partial 18S small subunit rRNA gene. Theileria DNA was detected in 51 samples (45·5%), giving a prevalence of 45·5%. Theileria DNA was found in 33 (48·5%) males and 18 (40·9%) females, and there was no significant difference (P > 0·05) in the prevalence between males and females. Similarly, there was no significant difference (P > 0·05) in the prevalence between juveniles (40%) and adults (46·7%). There was a significant difference in the prevalence of Theileria in hedgehogs collected from May to September and the period from October to April (P = 0·003). Four haplotypes of Theileria sp. in hedgehogs were detected and designated as H1-H4. H1 was the predominant haplotype and found in 80·8% of the positive individuals. Partial sequences of the 18S rRNA of Theileria sp. from hedgehogs grouped with Theileria spp. that are benign. This study is the first report of the occurrence of Theileria spp. in Saudi Arabian desert hedgehogs.

Parathyroidectomy for refractory secondary hyperparathyroidism with severe bone disease / Journal of the ASEAN Federation of Endocrine Societies

Advances in the medical management of secondary hyperparathyroidism due to renal failure have decreased the use of parathyroidectomy as a treatment option. However, some patients with end-stage renal disease still progress to refractory hyperparathyroidism and debilitating bone disease, for which parathyroidectomy may be warranted. We describe a case of a 35-year-old female on chronic hemodialysis who presented with bone pains, deformities, decrease in height and recurrent pathologic fractures. She had markedly elevated parathyroid hormone (PTH), vitamin D deficiency, persistent hyperphosphatemia and hypocalcemia despite therapeutic measures. Subtotal parathyroidectomy was done with eventual improvement of biochemical abnormalities, resolution of bone pains and healing of fractures.

Golimumab and immunogenicity? 2010 and beyond.

Immunogenicity is a frequent adverse event observed with biological agents' therapy. Challenges of management in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis treated with golimumab, an anti-TNF-alpha blocker, include limited generation of antibodies like anti-nuclear, anti-golimumab, and anti-double stranded DNA antibodies. We conducted here a meta-analysis study in order to evaluate and compare the newly generated antibody levels after golimumab therapy. The examination of original clinical trials revealed that their levels were neither higher nor significant. Moreover, no evident associations between the induced-antibodies and lupus-like syndromes and/or infusion site reaction were reported. The reduced patients cohort and the absence of systematic newly generated antibodies follow-up might be implicated in the difficulty to evaluate their risk in delaying diseases therapy, and/or predicting for their worse prognosis. Hence, further studies are required to ascertain the real impact of the induced antibodies after golimumab's therapy.

Dermatologic adverse events: golimumab, friend or foe?

Golimumab is a fully human anti-TNF-alpha blocker that has demonstrated its efficacy in the treatment of numerous kinds of diseases. Although it is generally safe and well tolerated, various adverse events have been reported. The present aim is to improve the understanding of dermatologic adverse events associated with golimumab following a search of various scientific databases. This systematic review and meta-analysis shows that golimumab is associated neither with severe injection-site reactions nor with injection-site erythema. We found no significant lupus-like syndromes, and no significant skin squamous cell carcinoma. We further suggest systematic dermatologic monitoring in clinical practice during golimumab therapy. Subsequent research should employ a larger cohort of patients to ensure clear and significant future conclusions.

Computational modelling of biomaterial surface interactions with blood platelets and osteoblastic cells for the prediction of contact osteogenesis.

Surface microroughness can induce contact osteogenesis (bone formation initiated at the implant surface) around oral implants, which may result from different mechanisms, such as blood platelet-biomaterial interactions and/or interaction with (pre-)osteoblast cells. We have developed a computational model of implant endosseous healing that takes into account these interactions. We hypothesized that the initial attachment and growth factor release from activated platelets is crucial in achieving contact osteogenesis. In order to investigate this, a computational model was applied to an animal experiment [7] that looked at the effect of surface microroughness on endosseous healing. Surface-specific model parameters were implemented based on in vitro data (Lincks et al. Biomaterials 1998;19:2219-32). The predicted spatio-temporal patterns of bone formation correlated with the histological data. It was found that contact osteogenesis could not be predicted if only the osteogenic response of cells was up-regulated by surface microroughness. This could only be achieved if platelet-biomaterial interactions were sufficiently up-regulated as well. These results confirmed our hypothesis and demonstrate the added value of the computational model to study the importance of surface-mediated events for peri-implant endosseous healing.

Golimumab therapy of rheumatoid arthritis: an overview.

Golimumab is a new approved humanized antibody for the treatment of rheumatoid arthritis (RA). This antibody belonging to biologic agents is raised against the pro-inflammatory cytokine tumour necrosis factor-alpha playing an essential role in the initiation of RA. To date, Golimumab administration for patients with RA, as indicated by USA Food and Drug Administration, is subcutaneous combined with methotrexate (MTX). Here, we have reviewed current literature with a focus on characteristics of Golimumab and also have exposed the clinical trials either using MTX or not using MTX. We have also highlighted the incoming clinical trials on Golimumab and have proposed some indications for the future studies based on a setting of clinical data and post-marketing observational studies. These studies will advance rheumatologists' decisions in the beginning of RA therapeutic interventions to insure the best outcomes for patients with RA and to improve their quality of life.

Enfermería en el pasado, presente y futuro del tabaquismo / The role of nursery in the past, present and future of smoking control

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Magnetic resonance imaging of dissolved hyperpolarized 129Xe using a membrane-based continuous flow system.

A technique for continuous production of solutions containing hyperpolarized (129)Xe is explored for MRI applications. The method is based on hollow fiber membranes which inhibit the formation of foams and bubbles. A systematic analysis of various carrier agents for hyperpolarized (129)Xe has been carried out, which are applicable as contrast agents for in vivo MRI. The image quality of different hyperpolarized Xe solutions is compared and MRI results obtained in a clinical as well as in a nonclinical MRI setting are provided. Moreover, we demonstrate the application of (129)Xe contrast agents produced with our dissolution method for lung MRI by imaging hyperpolarized (129)Xe that has been both dissolved in and outgassed from a carrier liquid in a lung phantom, illustrating its potential for the measurement of lung perfusion and ventilation.

Modelling the early phases of bone regeneration around an endosseous oral implant.

The objective of this study was to see whether a mathematical model of fracture healing was able to mimic bone formation around an unloaded screw-shaped titanium implant as it is well-believed that both processes exhibit many biological similarities. This model describes the spatio-temporal evolution of cellular activities, ranging from mesenchymal stem cell migration, proliferation, differentiation to bone formation, which are initiated and regulated by the growth factors present at the peri-implant site. For the simulations, a finite volume code was used and adequate initial and boundary conditions were applied. Two sets of analyses have been performed, in which either initial and boundary condition or model parameter values were changed with respect to the fracture healing model parameter values. For a number of combinations, the spatio-temporal evolution of bone density was well-predicted. However reducing cell proliferation rate and increasing osteoblast differentiation and osteogenic growth factor synthesis rates, the simulation results were in agreement with the experimental data.

Unusual chromosomal distribution of a major satellite DNA from Discoglossus pictus (Amphibia, Anura).

A new highly abundant satellite DNA from Discoglossus pictus (Dp-sat1) was isolated and characterized. The repetitive unit (0.51 kb) has 2 HindIII sites and only one SpeI site: digestion of genomic DNA with HindIII produces 3 fragments: HA (0.17 kb), HB (0.34 kb), and HC = HA + HB (0.51 kb), while digestion with SpeI produces the whole repetitive unit (0.51 kb) that contains both HindIII sites. Sequence analysis of cloned repeats indicates an average A + T content of 71%, with many A- and T-runs. Southern blot analysis shows an arrangement of multiple bands of the 0.51 kb monomer in SpeI-digested DNA, while HindIII-digested DNA shows a ladder composed of all the possible combinations of the 3 digested fragments. Quantitative dot-blot indicates that Dp-sat1 accounts for about 6% of the D. pictus genome: this value represents about 1.5 x 10(6) copies of repetitive units per nucleus. This satellite DNA is also a major repetitive DNA in 4 other Discoglossus species, in which the repetitive unit presents the same size and restriction sites except in D. montalentii where it contains a unique HindIII site. This satellite DNA was absent in all the other tested archaeo- and neo-bratrachian species, as well as non-amphibian species. Fluorescent in situ hybridization (FISH) analysis shows that Dp-sat1 is localized only in peri- and/or para-centromeric areas of the 7 small chromosome pairs, while no labeling was observed in the 7 large chromosome pairs. Remarkably, Dp-sat1 heterochromatin is found only at one pole of the nucleus, suggesting that during interphase all 7 small chromosome pairs are located in the same nuclear region.

Influence of the halogen ligand on the near-UV-visible spectrum of [Ru(X)(Me)(CO)2(alpha-diimine)] (X = Cl, I; alpha-diimine = Me-DAB, iPr-DAB; DAB = 1,4-diaza-1,3-butadiene): an ab initio and TD-DFT analysis.

The near-UV-vis electronic spectroscopy of [Ru(X)(Me)(CO)(2)(iPr-DAB)] (X = Cl or I; iPr-DAB = N,N'-di-isopropyl-1,4-diaza-1,3-butadiene) is investigated through CASSCF/CASPT2 and TD-DFT calculations on the model complexes [Ru(X)(Me)(CO)(2)(Me-DAB)] (X = Cl or I). Convergence of the calculated transition energies for the low-lying metal-to-ligand charge-transfer (MLCT), X-to-ligand charge-transfer (XLCT, X halide ligand), or sigma-bond-to-ligand charge-transfer (SBLCT) to experimental values is analyzed for both methods. On the basis of these accurate calculations, it is shown that whereas the lowest singlet state can be assigned to a nearly pure XLCT state in [Ru(I)(Me)(CO)(2)(Me-DAB)], its character is mainly MLCT in [Ru(Cl)(Me)(CO)(2)(Me-DAB)]. These results are in agreement with time-resolved emission/IR and resonance Raman experimental data. The experimental UV-vis bands are well reproduced by the CASSCF/CASPT2 calculations. The TD-DFT transition energies to the long-range charge transfer states are dramatically affected by the nature of the functional, with lowering leading to meaningless values in the case of nonhybrid functionals. Both methods reproduce well the red shift of the absorption bands on going from the chloride to the iodide complex as well as the shift of the strongly absorbing higher MLCT transition from the visible to the UV domain of energy.

Percutaneous treatment of hydatid cysts (Echinococcus granulosus).

A new method called PAIR (Puncture-Aspiration of cyst contents--Injection of hypertonic saline solution--Reaspiration) was used as a percutaneous treatment of hydatid cysts. In 37 patients, 120 cysts were punctured. All patients had not been considered surgical candidates. The cysts were localized in the liver, peritoneum, spleen, kidneys, muscles, and bones. In 70% of patients, good results were obtained. Recurrence occurred in 5 of 120 cysts, all at the beginning of our experience when a low concentration of sodium chloride solution was injected. Moderate allergic reactions occurred during seven cyst aspirations. No anaphylactic shock, sudden deaths or dissemination of cyst contents were observed.