Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles.

Acid-degradable cationic nanoparticles encapsulating a model antigen (i.e., ovalbumin) were prepared by inverse microemulsion polymerization with acid-cleavable acetal cross-linkers. Incubation of these degradable nanoparticles with dendritic cells derived from bone marrow (BMDCs) resulted in the enhanced presentation of ovalbumin-derived peptides, as quantified by B3Z cells, a CD8+ T cell hybridoma. The cationic nature of the particles contributed to the increased surface endocytosis (or phagocytosis) observed with BMDCs, which is the first barrier to overcome for successful antigen delivery. The acid sensitivity of the particles served to direct more ovalbumin antigens to be processed into the appropriately trimmed peptide fragments and presented via the major histocompatibility complex (MHC) class I pathway following hydrolysis within the acidic lysosomes. It was also shown that adjuvant molecules such as unmethylated CpG oligonucleotides (CpG ODN) and anti-interleukin-10 oligonucleotides (AS10 ODN) could be co-delivered with the protein antigen for maximized cellular immune response

Fatty acid composition of Nile tilapia (Oreochromis niloticus) and Red hybrid tilapia (Oreochromis mossambicus X Oreochromis niloticus) reared in intensive and extensive systems

Fish and marine mammals are among the richest sources of long–chain n-3 and n-6 polyunsaturated fatty acids (PUFA) in nature. As farmed fish becomes a major contributor to world fish supplies, hence it is important to maintain the high lipid nutritional quality of the product and to continue to provide large amounts of the health-promoting n-3 and n-6 PUFA to the consumers. Therefore, a study was conducted to examine the nutritional content, mainly fatty acid composition, of Nile (Oreochromis niloticus and Red hybrid tilapia (Oreochromis mossambicus x Oreochromis niloticus), derived from intensive and extensive culture systems. Twenty-two samples of Nile tilapia and 16 samples of Red tilapia cultured intensively and 10 samples of extensively cultured Nile tilapia were used in this study. All samples were subjected to total fatty acids extraction and their fatty acid compositions were determined using gas liquid chromatography. Results showed no significant differences in the concentration of saturated fatty acids (SFA) between intensively and extensively cultured Nile tilapia. For monounsaturated fatty acids (MUFA), the concentration was higher (p<0.05) in the intensively cultured Nile tilapia compared to the extensively cultured Nile tilapia. For n-3 PUFA, the concentration was higher (p<0.05) in Nile tilapia from the extensive system compared to Nile tilapia from the intensive system. But for n-6 PUFA, the intensively cultured Nile tilapia had a higher (p<0.05) concentration compared to the extensively cultured Nile tilapia. For n-6:n-3 PUFA ratio the intensively cultured Nile tilapia had a higher ratio (p<0.05) than the extensively cultured Nile tilapia. The different fatty acid composition of Nile tilapia cultured in different systems could be due to the different types of feed consumed by the fish. Future research could be directed at increasing the PUFA level in tilapia through the manipulation of the PUFA level in the fish diet

Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD

Medborgerliga rättigheter i totalitära stater - En komparativ studie av konstitutionella rättigheters betydelse i Östeuropa

Sammanfattning I slutet av andra världskriget låg stora delar av Europa i ruiner efter att ha drabbats hårt av krig och ockupation. Europa var uppdelat i två områden, öst och väst. Ett antal länder i Östeu-ropa var av stort intresse för Sovjetunionen och väldigt snart efter krigsslutet började en om-fattande sovjetisering av dessa länder. Ungern, Polen och Tjeckoslovakien kom alla att bli kommunistiska totalitära stater under Sovjetunionens styre. Länderna fick genomgå omfattan-de förändringar på alla nivåer i samhället, inte minst lagarna och rättssystemen förändrades, i överrensstämmelse med den kommunistiska andan. De mänskliga rättigheterna yttrandefrihet, tryckfrihet, mötes- och föreningsfrihet var rättigheter som alla de ovannämnda länderna hade i sina konstitutioner, även efter att de blev totalitära stater. Denna uppsatsen kommer att hand-la om hur dessa rättigheter formulerades i de olika konstitutionerna, hur de behandlades i praktiken samt vad som var utmärkande för rättsystemen i dessa totalitära regimer. Efter att ha kommit fram till att det fanns en stor skillnad i hur rättigheterna framstod i lagtexten och hur de tillämpas i praktiken, så analyseras även varför lagen hade utformats som den gjorde

Specialized adaptation of a lactic acid bacterium to the milk environment: the comparative genomics of Streptococcus thermophilus LMD-9

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus thermophilus</it> represents the only species among the streptococci that has “Generally Regarded As Safe” status and that plays an economically important role in the fermentation of yogurt and cheeses. We conducted comparative genome analysis of <it>S. thermophilus</it> LMD-9 to identify unique gene features as well as features that contribute to its adaptation to the dairy environment. In addition, we investigated the transcriptome response of LMD-9 during growth in milk in the presence of <it>Lactobacillus delbrueckii</it> ssp. <it>bulgaricus</it>, a companion culture in yogurt fermentation, and during lytic bacteriophage infection.</p> <p>Results</p> <p>The <it>S. thermophilus</it> LMD-9 genome is comprised of a 1.8 Mbp circular chromosome (39.1% GC; 1,834 predicted open reading frames) and two small cryptic plasmids. Genome comparison with the previously sequenced LMG 18311 and CNRZ1066 strains revealed 114 kb of LMD-9 specific chromosomal region, including genes that encode for histidine biosynthetic pathway, a cell surface proteinase, various host defense mechanisms and a phage remnant. Interestingly, also unique to LMD-9 are genes encoding for a putative mucus-binding protein, a peptide transporter, and exopolysaccharide biosynthetic proteins that have close orthologs in human intestinal microorganisms. LMD-9 harbors a large number of pseudogenes (13% of ORFeome), indicating that like LMG 18311 and CNRZ1066, LMD-9 has also undergone major reductive evolution, with the loss of carbohydrate metabolic genes and virulence genes found in their streptococcal counterparts. Functional genome distribution analysis of ORFeomes among streptococci showed that all three <it>S. thermophilus</it> strains formed a distinct functional cluster, further establishing their specialized adaptation to the nutrient-rich milk niche. An upregulation of CRISPR1 expression in LMD-9 during lytic bacteriophage DT1 infection suggests its protective role against phage invasion. When co-cultured with <it>L. bulgaricus</it>, LMD-9 overexpressed genes involved in amino acid transport and metabolism as well as DNA replication.</p> <p>Conclusions</p> <p>The genome of <it>S. thermophilus</it> LMD-9 is shaped by its domestication in the dairy environment, with gene features that conferred rapid growth in milk, stress response mechanisms and host defense systems that are relevant to its industrial applications. The presence of a unique exopolysaccharide gene cluster and cell surface protein orthologs commonly associated with probiotic functionality revealed potential probiotic applications of LMD-9.</p

Comparison of whole body magnetic resonance imaging (WBMRI) to whole body computed tomography (WBCT) or 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) in patients with myeloma: Systematic review of diagnostic performance

Objectives To undertake a systematic review to determine the diagnostic performance of whole body MRI (WBMRI) including diffusion weighted sequences (DWI) compared to whole body computed tomography (WBCT) or 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG PET/CT) in patients with myeloma. Methods Two researchers searched the primary literature independently for WBMRI studies of myeloma. Data were extracted focusing on the diagnostic ability of WBMRI versus WBCT and 18F-FDG PET/CT. Meta-analysis was intended. Results 6 of 2857 articles were eligible that included 147 patients, published from 2008-2016. Studies were heterogeneous including both newly diagnosed &amp; relapsed patients. All were single centre studies. Four of the six studies (66.7%) accrued prospectively and 5/6 (83.3%, 3 prospective) included WBMRI and 18F-FDG PET/CT. Three of seven (42.9%) included DWI. The lack of an independent reference standard for individual lesions was noted in 5/6 (83.3%) studies. Studies reported that WBMRI detected more lesions than 18F-FDG PET/CT (sensitivity 68-100% versus 47-100%) but was less specific (specificity 37-83% versus 62-85.7%). No paper assessed impact on management. Conclusions Studies were heterogeneous, the majority lacking an independent reference standard. Future prospective trials should address these limitations and assess the impact of WBMRI on management

Patterns of immunotherapy-induced pneumonitis in patients with non-small-cell lung cancer: A case series

Background: Immunotherapy has become an efficacious option in the management of solid organ malignancies. Immune-related adverse events including pneumonitis are well described and may be particularly of concern in patients receiving immunotherapy for non-small-cell lung cancer. Case presentations: In this paper, we describe three cases of immunotherapy-induced pneumonitis occurring in the management of lung malignancy. Our cases include a 54-year-old Caucasian woman with squamous cell lung cancer who was successfully rechallenged with immunotherapy after prior significant pneumonitis, a 65-year-old Caucasian man with metastatic squamous cell lung cancer who developed pneumonitis after multiple cycles of uneventful immunotherapy, and a 73-year-old Caucasian man with squamous cell lung cancer who developed early-onset pneumonitis with rebound on steroid taper. Conclusions: This case series has provided further insight into the presentation and risk factors for pneumonitis in patients with non-small-cell lung cancer. Each of the cases of immunotherapy-induced pneumonitis illustrates the different potential patterns that may arise when immunotherapy-induced pneumonitis develops. This case series provides key learning points that may assist physicians managing non-small-cell lung cancer with immunotherapy

Patterns of immunotherapy-induced pneumonitis in patients with non-small-cell lung cancer: A case series

Background: Immunotherapy has become an efficacious option in the management of solid organ malignancies. Immune-related adverse events including pneumonitis are well described and may be particularly of concern in patients receiving immunotherapy for non-small-cell lung cancer. Case presentations: In this paper, we describe three cases of immunotherapy-induced pneumonitis occurring in the management of lung malignancy. Our cases include a 54-year-old Caucasian woman with squamous cell lung cancer who was successfully rechallenged with immunotherapy after prior significant pneumonitis, a 65-year-old Caucasian man with metastatic squamous cell lung cancer who developed pneumonitis after multiple cycles of uneventful immunotherapy, and a 73-year-old Caucasian man with squamous cell lung cancer who developed early-onset pneumonitis with rebound on steroid taper. Conclusions: This case series has provided further insight into the presentation and risk factors for pneumonitis in patients with non-small-cell lung cancer. Each of the cases of immunotherapy-induced pneumonitis illustrates the different potential patterns that may arise when immunotherapy-induced pneumonitis develops. This case series provides key learning points that may assist physicians managing non-small-cell lung cancer with immunotherapy

3D distortion-free, reduced field of view diffusion-prepared GRE at 3T

Purpose: To develop a 3D distortion-free reduced-FOV diffusion-prepared GRE sequence and demonstrate its in-vivo application for diffusion imaging of the spinal cord in healthy volunteers. Methods: A 3D multi-shot reduced-FOV diffusion-prepared GRE (RFOV-DP-GRE) acquisition is achieved using a slice-selective tip-down pulse in the phase encoding direction in the diffusion preparation, combined with magnitude stabilisers. The efficacy of the developed reduced FOV approach and accuracy of ADC estimates were evaluated in a phantom. In addition, 5 healthy volunteers were enrolled and scanned at 3T using the proposed sequence and a standard spin echo diffusion-weighted single-shot EPI sequence (DW-SS-EPI) for spinal cord imaging. Image quality, perceived SNR and image distortion were assessed by two expert readers and quantitative measurements of apparent SNR were performed. Results: The phantom scan demonstrates the efficacy of the proposed reduced FOV approach. Consistent ADC estimates were measured with RFOV-DP-GRE when compared with DW-SS-EPI. In-vivo, RFOV-DP-GRE demonstrated improved image quality and reduced perceived distortion, while maintaining perceived SNR compared to DW-SS-EPI. Conclusion: 3D Distortion-free diffusion-prepared imaging can be achieved using the proposed sequenceComment: 16 pages, 4 figures, submitted to Magnetic Resonance in Medicin

The S-layer Associated Serine Protease Homolog PrtX Impacts Cell Surface-Mediated Microbe-Host Interactions of Lactobacillus acidophilus NCFM

Health-promoting aspects attributed to probiotic microorganisms, including adhesion to intestinal epithelia and modulation of the host mucosal immune system, are mediated by proteins found on the bacterial cell surface. Notably, certain probiotic and commensal bacteria contain a surface (S-) layer as the outermost stratum of the cell wall. S-layers are non-covalently bound semi-porous, crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (SLPs). Recent evidence has shown that multiple proteins are non-covalently co-localized within the S-layer, designated S-layer associated proteins (SLAPs). In Lactobacillus acidophilus NCFM, SLP and SLAPs have been implicated in both mucosal immunomodulation and adhesion to the host intestinal epithelium. In this study, a S-layer associated serine protease homolog, PrtX (prtX, lba1578), was deleted from the chromosome of L. acidophilus NCFM. Compared to the parent strain, the PrtX-deficient strain (ΔprtX) demonstrated increased autoaggregation, an altered cellular morphology, and pleiotropic increases in adhesion to mucin and fibronectin, in vitro. Furthermore, ΔprtX demonstrated increased in vitro immune stimulation of IL-6, IL-12, and IL-10 compared to wild-type, when exposed to mouse dendritic cells. Finally, in vivo colonization of germ-free mice with ΔprtX led to an increase in epithelial barrier integrity. The absence of PrtX within the exoproteome of a ΔprtX strain caused morphological changes, resulting in a pleiotropic increase of the organisms’ immunomodulatory properties and interactions with some intestinal epithelial cell components