Controversies in the management of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) remains a rare but significant disease, which affects mainly young males in association with inflammatory bowel disease. There have been few advances in the understanding of the pathogenesis of the condition and no therapeutics with proven mortality benefit aside from liver transplantation. There remain areas of controversy in the management of PSC which include the differentiation from other cholangiopathies, in particular immunoglobulin G4 related sclerosing cholangitis, the management of dominant biliary strictures, and the role of ursodeoxycholic acid. In addition, the timing of liver transplantation in PSC remains difficult to predict with standard liver severity scores. In this review, we address these controversies and highlight the latest evidence base in the management of PSC

Between life and death: strategies to reduce phototoxicity in super-resolution microscopy

Super-Resolution Microscopy enables non-invasive, molecule-specific imaging of the internal structure and dynamics of cells with sub-diffraction limit spatial resolution. One of its major limitations is the requirement for high-intensity illumination, generating considerable cellular phototoxicity. This factor considerably limits the capacity for live-cell observations, particularly for extended periods of time. Here, we overview new developments in hardware, software and probe chemistry aiming to reduce phototoxicity. Additionally, we discuss how the choice of biological model and sample environment impacts the capacity for live-cell observations

Can prior exposure to stress enhance resilience to ocean warming in two oyster species?

Securing economically and ecologically significant molluscs, as our oceans warm due to climate change, is a global priority. South eastern Australia receives warm water in a strengthening East Australia Current and so resident species are vulnerable to elevated temperature and marine heat waves. This study tested whether prior exposure to elevated temperature can enhance resilience of oysters to ocean warming. Two Australian species, the flat oyster, Ostrea angasi, and the Sydney rock oyster, Saccostrea glomerata, were obtained as adults and "heat shocked" by exposure to a dose of warm water in the laboratory. Oysters were then transferred to elevated seawater temperature conditions where the thermal outfall from power generation was used as a proxy to investigate the impacts of ocean warming. Shell growth, condition index, lipid content and survival of flat oysters and condition of Sydney rock oysters were all significantly reduced by elevated seawater temperature in the field. Flat oysters grew faster than Sydney rock oysters at ambient temperature, but their growth and survival was more sensitive to elevated temperature. "Stress inoculation" by heat shock did little to ameliorate the negative effects of increased temperature, although the survival of heat-shocked flat oysters was greater than non-heat shocked oysters. Further investigations are required to determine if early exposure to heat stress can enhance resilience of oysters to ocean warming

Norbornene-chitosan spray-dried microspheres for peptide conjugation using thiol-ene “photoclick” chemistry

This work was financed by Portuguese funds through FCT/MCTES (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação) in the framework of the projects 2022.06048.PTDC (i3S), UIDB/50006/2020 (LAQV-REQUIMTE), LA/P/0045/2020 (ALiCE) and UIDB/00511/2020 (LEPABE). P.A. (SFRH/BD/145471/2019) and D.F. (SFRH/ BD/146890/2019) doctoral grants, were financially supported by national (FCT/Norte 2020 Framework) and European Union (ESF – European Social Fund) funds. B.E. acknowledges FCT for the contract based on the “Lei do Emprego Científico” (DL 57/2016). Maria Cristina L. Martins also acknowledges FCT (LA/P/0070/2020), project Bio2Skin Advanced (2021-24):NORTE-01-0247-FEDER-047225; and MOBILIsE Project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 951723.The action of bioactive peptides, such as antimicrobial peptides (AMP), in the human body is often compromised by limited residence time and stability in the target site. Bioconjugation of peptides to biomaterial surfaces is one of the strategies that may overcome these limitations. Herein, norbornene-chitosan (NorChit) microspheres were engineered to react with thiolated peptides by thiolene “photoclick” chemistry. NorChit microspheres were produced by spray drying and crosslinked with dithiothreitol (DTT) to prevent their solubilization. Microspheres with a diameter of 5 ± 2 µm showed round and smooth morphology with pockets over the surface that could be related with hydrophobic interactions between internal norbornene groups. Thiol-ene bioconjugation carried out using a fluorescent model peptide, showed a yield of 45%, whereas using the peptide but without UV exposure indicated a maximum of peptide adsorption of 30%. Altogether, NorChit microspheres show the potential for carrying bioactive peptides, which may open avenues for AMP activity onto harsh environments in the bod

Divergent trophic responses to biogeographic and environmental gradients

Following environmental changes, communities disassemble and reassemble in seemingly unpredictable ways. Whether species respond to such changes individualistically or collectively (e.g. as functional groups) is still unclear. To address this question, we used an extensive new dataset for the lake communities in the Azores' archipelago to test whether: 1) individual species respond concordantly within trophic groups; 2) trophic groups respond concordantly to biogeographic and environmental gradients. Spatial concordance in individual species distributions within trophic groups was always greater than expected by chance. In contrast, trophic groups varied non-concordantly along biogeographic and environmental gradients revealing idiosyncratic responses to them. Whether communities respond individualistically to environmental gradients thus depends on the functional resolution of the data. Our study challenges the view that modelling environmental change effects on biodiversity always requires an individualist approach. Instead, it finds support for the longstanding idea that communities might be modelled as a cohort if the functional resolution is appropriate

Investigating Hepatitis C Virus Infection Using Super-Resolution Microscopy

Super-resolution microscopy (SRM) can provide a window on the nanoscale events of virus replication. Here we describe a protocol for imaging hepatitis C virus-infected cells using localization SRM. We provide details on sample preparation, immunostaining, data collection, and super-resolution image reconstruction. We have made all efforts to generalize the protocol to make it accessible to all budding super-resolution microscopists

Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding

The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4+ T cells and macrophages. Although there is considerable knowledge of the molecular interactions between Env and host cell receptors that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the nanoscale organisation of CD4 on the surface of CD4+ T cells following HIV-1 binding. Using singlemolecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4 clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation triggered by HIV-1 on host CD4+ T cells. Our quantitative approach provides a robust methodology for characterising the nanoscale organisation of plasma membrane receptors in general with the potential to link spatial organisation to function

Well-being and quality of life in a sample of bakers and confectioners from the central region

info:eu-repo/semantics/publishedVersio

Postoperative outcome of caesarean sections and other major emergency obstetric surgery by clinical officers and medical officers in Malawi

<p>Abstract</p> <p>Background</p> <p>Clinical officers perform much of major emergency surgery in Malawi, in the absence of medical officers. The aim of this study was to validate the advantages and disadvantages of delegation of major obstetric surgery to non-doctors.</p> <p>Methods</p> <p>During a three month period, data from 2131 consecutive obstetric surgeries in 38 district hospitals in Malawi were collected prospectively. The interventions included caesarean sections alone and those that were combined with other interventions such as subtotal and total hysterectomy repair of uterine rupture and tubal ligation. All these surgeries were conducted either by clinical officers or by medical officers.</p> <p>Results</p> <p>During the study period, clinical officers performed 90% of all straight caesarean sections, 70% of those combined with subtotal hysterectomy, 60% of those combined with total hysterectomy and 89% of those combined with repair of uterine rupture. A comparable profile of patients was operated on by clinical officers and medical officers, respectively. Postoperative outcomes were almost identical in the two groups in terms of maternal general condition – both immediately and 24 hours postoperatively – and regarding occurrence of pyrexia, wound infection, wound dehiscence, need for re-operation, neonatal outcome or maternal death.</p> <p>Conclusion</p> <p>Clinical officers perform the bulk of emergency obstetric operations at district hospitals in Malawi. The postoperative outcomes of their procedures are comparable to those of medical officers. Clinical officers constitute a crucial component of the health care team in Malawi for saving maternal and neonatal lives given the scarcity of physicians.</p

Ergonomics in "remote work" activities: a workstation adaptation case study in Brazil

The coronavirus disease 2019 (COVID-19) pandemic decreed by the outbreak of the new coronavirus culminated in the need to implement jobs in the homes of employees who had to adhere to the “remote work” style, due to social isolation actions in Brazil. Many of the employees started to work in the absence of adequate working conditions in their homes, impacting the three dimensions of ergonomics, i.e., physical, organizational and cognitive. The objective of this chapter is to report the adjustments made in a workplace after the change of modality from face-to-face (f2f) activities to “remote work” after the beginning of the pandemic in 2020, aiming to adopt actions aimed at ergonomics. The research was carried out with a professional in the area of Environmental and Sanitary Engineering who started remote work in March 2020. The work is of a qualitative nature, using photos to illustrate the changes occurring before and after the installation of the equipments and reports on strategies to improve working conditions in the “remote work”. The cost of physical adaptations was also computed. The most reported complaints collected by the professional were back pain, neck, forearm, wrist and eye pain, in addition to mental fatigue. The necessary equipment and furniture were acquired for the physical adaptation of the workspace. Issues of working hours, days off, means of communication were also addressed, but aspects of cognitive and organizational ergonomics must have the participation of the entire work group to achieve effective results. The accompaniment of a specialized technical professional would be important for the establishment of further assertive actions, seeking the productivity and quality of life of the employee.info:eu-repo/semantics/publishedVersio