Human iPSC-Derived Neural Crest Stem Cells Exhibit Low Immunogenicity

Recent clinical trials are evaluating induced pluripotent stem cells (iPSCs) as a cellular therapy in the field of regenerative medicine. The widespread clinical utility of iPSCs is expected to be realized using allogeneic cells that have undergone thorough safety evaluations, including assessment of their immunogenicity. IPSC-derived neural crest stem cells (NCSCs) have significant potential in regenerative medicine; however, their application in cellular therapy has not been widely studied to date, and no reports on their potential immunogenicity have been published so far. In this study, we have assessed the expression of immune-related antigens in iPSC-NCSCs, including human leukocyte antigen (HLA) class I and II and co-stimulatory molecules. To investigate functional immunogenicity, we used iPSC-NCSCs as stimulator cells in a one-way mixed lymphocyte reaction. In these experiments, iPSC-NCSCs did not stimulate detectable proliferation of CD3+ and CD3+CD8+ T cells or induce cytokine production. We show that this was not a result of any immunosuppressive features of iPSC-NCSCs, but rather more consistent with their non-immunogenic molecular phenotype. These results are encouraging for the potential future use of iPSC-NCSCs as a cellular therapy

Weathering the storm: parental effort and experimental manipulation of stress hormones predict brood survival

BACKGROUND:Unpredictable and inclement weather is increasing in strength and frequency, challenging organisms to respond adaptively. One way in which animals respond to environmental challenges is through the secretion of glucocorticoid stress hormones. These hormones mobilize energy stores and suppress non-essential physiological and behavioral processes until the challenge passes. To investigate the effects of glucocorticoids on reproductive decisions, we experimentally increased corticosterone levels (the primary glucocorticoid in birds) in free-living female tree swallows, Tachycineta bicolor, during the chick-rearing stage. Due to an unprecedented cold and wet breeding season, 90% of the nests in our study population failed, which created a unique opportunity to test how challenging environmental conditions interact with the physiological mechanisms underlying life-history trade-offs.RESULTS:We found that exogenous corticosterone influenced the regulation of parental decisions in a context-dependent manner. Control and corticosterone-treated females had similar brood failure rates under unfavorable conditions (cold and rainy weather), but corticosterone treatment hastened brood mortality under more favorable conditions. Higher female nest provisioning rates prior to implantation were associated with increased probability of brood survival for treatment and control groups. However, higher pre-treatment male provisioning rates were associated with increased survival probability in the control group, but not the corticosterone-treated group.CONCLUSIONS:These findings reveal complex interactions between weather, female physiological state, and partner parental investment. Our results also demonstrate a causal relationship between corticosterone concentrations and individual reproductive behaviors, and point to a mechanism for why naturally disturbed populations, which experience multiple stressors, could be more susceptible and unable to respond adaptively to changing environmental conditions

Treating rhinitis in the older population: special considerations

Rhinitis in the elderly is a common but often neglected condition. Structural changes in the nose associated with aging, predisposes the elderly to rhinitis. There are a number of specific factors that affect medical treatment of the elderly including polypharmacy, cognitive dysfunction, changes in body composition, impairment of liver and renal function and the cost of medications in the face of limited resources. Rhinitis in the elderly can be placed in several categories and treatment should be appropriate for each condition. The most important aim is to moisten the nasal mucosa since the nose of the elderly is so dry. Great caution should be used in treatment with first generation antihistamines and decongestants. Medications generally well tolerated by the elderly are second generation antihistamines, intra-nasal anti-inflammatory agents, leukotriene modifiers and iprapropium nasal spray

Punica granatum (Pomegranate) juice provides an HIV-1 entry inhibitor and candidate topical microbicide

BACKGROUND: For ≈ 24 years the AIDS pandemic has claimed ≈ 30 million lives, causing ≈ 14,000 new HIV-1 infections daily worldwide in 2003. About 80% of infections occur by heterosexual transmission. In the absence of vaccines, topical microbicides, expected to block virus transmission, offer hope for controlling the pandemic. Antiretroviral chemotherapeutics have decreased AIDS mortality in industrialized countries, but only minimally in developing countries. To prevent an analogous dichotomy, microbicides should be: acceptable; accessible; affordable; and accelerative in transition from development to marketing. Already marketed pharmaceutical excipients or foods, with established safety records and adequate anti-HIV-1 activity, may provide this option. METHODS: Fruit juices were screened for inhibitory activity against HIV-1 IIIB using CD4 and CXCR4 as cell receptors. The best juice was tested for inhibition of: (1) infection by HIV-1 BaL, utilizing CCR5 as the cellular coreceptor; and (2) binding of gp120 IIIB and gp120 BaL, respectively, to CXCR4 and CCR5. To remove most colored juice components, the adsorption of the effective ingredient(s) to dispersible excipients and other foods was investigated. A selected complex was assayed for inhibition of infection by primary HIV-1 isolates. RESULTS: HIV-1 entry inhibitors from pomegranate juice adsorb onto corn starch. The resulting complex blocks virus binding to CD4 and CXCR4/CCR5 and inhibits infection by primary virus clades A to G and group O. CONCLUSION: These results suggest the possibility of producing an anti-HIV-1 microbicide from inexpensive, widely available sources, whose safety has been established throughout centuries, provided that its quality is adequately standardized and monitored

TLR9-induced interferon β is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis

Abstract Background We have shown previously that murine gammaherpesvirus 68 (γHV68) infection exacerbates established pulmonary fibrosis. Because Toll-like receptor (TLR)-9 may be important in controlling the immune response to γHV68 infection, we examined how TLR-9 signaling effects exacerbation of fibrosis in response to viral infection, using models of bleomycin- and fluorescein isothiocyanate-induced pulmonary fibrosis in wild-type (Balb/c) and TLR-9-/- mice. Results We found that in the absence of TLR-9 signaling, there was a significant increase in collagen deposition following viral exacerbation of fibrosis. This was not associated with increased viral load in TLR-9-/- mice or with major alterations in T helper (Th)1 and Th2 cytokines. We examined alveolar epithelial-cell apoptosis in both strains, but this could not explain the altered fibrotic outcomes. As expected, TLR-9-/- mice had a defect in the production of interferon (IFN)-β after viral infection. Balb/c fibroblasts infected with γHV68 in vitro produced more IFN-β than did infected TLR-9-/- fibroblasts. Accordingly, in vitro infection of Balb/c fibroblasts resulted in reduced proliferation rates whereas infection of TLR-9-/- fibroblasts did not. Finally, therapeutic administration of CpG oligodeoxynucleotides ameliorated bleomycin-induced fibrosis in wild-type mice. Conclusions These results show a protective role for TLR-9 signaling in murine models of lung fibrosis, and highlight differences in the biology of TLR-9 between mice and humans.http://deepblue.lib.umich.edu/bitstream/2027.42/112877/1/13069_2011_Article_57.pd

Estadificación del cáncer infantil para registros de base poblacional

La recogida de información internacional fiable sobre estadificación de cáncer infantil por los registros de cáncer de base poblacional es esencial para el análisis epidemiológico y la realización de comparaciones evaluativas internacionales explicativas de la incidencia y los resultados asistenciales. En 2014 la Unión International Contra el Cáncer (UICC), el Dana-Farber Cancer Institute y el Hospital for Sick Children de Toronto, convocaron una reunión de consenso para abordar la ausencia de información consistente en la estadificación del cáncer infantil en los registros de cáncer poblacionales. Para cada subconjunto de los grupos/subgrupos diagnósticos mayores de cáncer infantil, en la reunión fueron revisados todos los sistemas de estadificación específicos de cada enfermedad utilizados habitualmente y se recomendó el más adecuado para utilizar en los registros de cáncer de base poblacional. Los sistemas de estadificación recomendados están enumerados como Guías de Toronto para la Estadificación del Cáncer Pediátrico. Las Guías recomiendan sistemas de estadificación específicos para la Leucemia Linfoblástica Aguda, Leucemia Mieloblástica Aguda, Linfoma de Hodgkin, Linfoma no-Hodgkin, Neuroblastoma, Tumor de Wilms, Rabdomiosarcoma, Sarcomas de Tejidos Blandos no-Rabdomiosarcoma, Osteosarcoma, Sarcoma de Ewing, Retinoblastoma, Hepatoblastoma, Tumor de Células Germinales (Cáncer Testicular y Ovárico), Meduloblastoma y Ependimoma. En este texto se proporcionan descripciones detalladas de los sistemas de estadificación recomendados en las Guías, para ayudar a los registros poblacionales de cáncer a recoger información internacionalmente consistente y comparable sobre el estadio del cáncer infantil al diagnóstico utilizando los documentos clínicos disponibles. La viabilidad y validez de estas Guías se ha evaluado con éxito en la práctica2. Están avaladas por el proyecto Factores pronósticos TNM de la UICC y publicadas en la Clasificación TNM de los Tumores Malignos UICC 8ª edición

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /

Severe gastric variceal haemorrhage due to splenic artery thrombosis and consecutive arterial bypass

<p>Abstract</p> <p>Background</p> <p>Upper gastrointestinal haemorrhage is mainly caused by ulcers. Gastric varicosis due to portal hypertension can also be held responsible for upper gastrointestinal bleeding. Portal hypertension causes the development of a collateral circulation from the portal to the caval venous system resulting in development of oesophageal and gastric fundus varices. Those may also be held responsible for upper gastrointestinal haemorrhage.</p> <p>Case presentation</p> <p>In this study, we describe the case of a 69-year-old male with recurrent severe upper gastrointestinal bleeding caused by arterial submucosal collaterals due to idiopathic splenic artery thrombosis. The diagnosis was secured using endoscopic duplex ultrasound and angiography. The patient was successfully treated with a laparoscopic splenectomy and complete dissection of the short gastric arteries, resulting in the collapse of the submucosal arteries in the gastric wall. Follow-up gastroscopy was performed on the 12^thpostoperative week and showed no signs of bleeding and a significant reduction in the arterial blood flow within the gastric wall. Subsequent follow-up after 6 months also showed no further gastrointestinal bleeding as well as subjective good quality of life for the patient.</p> <p>Conclusion</p> <p>Submucosal arterial collaterals must be excluded by endosonography via endoscopy in case of recurrent upper gastrointestinal bleeding. Laparoscopic splenectomy provides adequate treatment in preventing any recurrent bleeding, if gastric arterial collaterals are caused by splenic artery thrombosis.</p

The motor development of orphaned children with and without HIV: Pilot exploration of foster care and residential placement

<p>Abstract</p> <p>Background</p> <p>The AIDS epidemic has lead to an increase in orphaned children who need residential care. It is known that HIV leads to delayed motor development. However, the impact of place of residence on motor function has not been investigated in the South African context. The aim of the study was therefore to establish if children in institutionalised settings performed better or worse in terms of gross motor function than their counterparts in foster care. A secondary objective was to compare the performance of children with HIV in these two settings with those of children who were HIV negative.</p> <p>Methods</p> <p>Forty-four children both with and without HIV, were recruited from institutions and foster care families in Cape Town. The Peabody Development Motor Scale (PDMS II) was used to calculate the total motor quotient (TMQ) at baseline and six months later. Comparisons of TMQ were made between residential settings and between children with and without HIV.</p> <p>Results</p> <p>Twenty-one children were infected with HIV and were significantly delayed compared to their healthy counterparts. Antiretroviral therapy was well managed among the group but did not appear to result in restoration of TMQ to normal over the study period. HIV status and place of residence emerged as a predictor of TMQ with children in residential care performing better than their counterparts in foster care. All children showed improvement over the six months of study.</p> <p>Conclusions</p> <p>Foster parents were well supported administratively in the community by social welfare services but their children might have lacked stimulation in comparison to those in institutional settings. This could have been due to a lack of resources and knowledge regarding child development. The assumption that foster homes provide a better alternative to institutions may not be correct in a resource poor community and needs to be examined further.</p