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Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior todoi:10.1186/s13023-015-0332-8 pmid:26490561 pmcid:PMC4618138 fatcat:fax6d7e4nbaabd4k2att6ihwpe
more »... starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le-and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethylfumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs.
Acute lymphoblastic leukemia (ALL) is one of the most frequent malignancies in childhood whose long-term survival has increased up to 80% thanks to modern therapy enhancements. Nevertheless, methotrexate (MTX) remains a mainstay of ALL therapy, but also represents one of the major causes of neurotoxicity in patients with ALL. MTX-induced toxicity occurs in about 9% of patients treated for ALL. It usually affects deep white matter region leading to leukoencephalopathy, which has varying clinicaldoi:10.1097/mph.0000000000001374 pmid:30543581 fatcat:u6ob3ihpbveyvlsmurailpz6zu
more »... manifestations ranging from acute neurologic disturbances to seizures or chronic permanent encephalopathy. Here we describe a 13-year-old girl affected with ALL who developed lower limbs hypesthesia and static ataxia due to transverse myelopathy after intrathec administration of MTX therapy. A high-dose corticotherapy combined to vitamin supplementation and rehabilitation was tested. Neurological evolution was characterized by slow and partial recovery.
LeRoy E. Wisce, M.D. PITTSBURGH, Pa. Many dermatologic and systemic diseases first manifest them- selves by lesions in the oral cavity, nose and pharynx. ...doi:10.1177/000348944605500113 pmid:21023129 fatcat:rwwqiowa2zgyle3wtjipfg32u4
Purpose of the Study: To explore cause and control illness representations in older adults with Alzheimer's disease (AD). Design and Methods: Six older adults living in the North West of England completed semi-structured interviews that were subject to an interpretative phenomenological analysis. Results: Three main themes emerged indicating that participants were trying to make sense of their AD by comparing it with their previous experience of physical health illnesses. All participantsdoi:10.1093/geront/gnt014 pmid:23512771 fatcat:uqdkizsn4jekxjjitzueqnmrxi
more »... ledged their diagnosis of AD but engaged with it in a graded way because of a lack of tangible diagnostic evidence. Participants developed pragmatic emotional responses to their situation. Implications: One of the main implications of the results is that caution needs to be exercised within clinical practice so that the pragmatic responses of individuals with AD are not pathologized.
Krebs, PhD, PT' Claire E. Robbins, MS, PT? Leroy Lavine, MD° Robert W. Mann, ScD * any studies describe hip biomechanics during gait (3,4,10,14, 15,18,21-—23,33,35). ...doi:10.2519/jospt.1918.104.22.168 pmid:9653690 fatcat:6wew6imx2ngezloorw7joswm6m
A strategy for the elaboration of a halogen-bonded porphyrin network with nano-sized tubular channels is reported.doi:10.1039/c4ce01704h fatcat:x6nig45ivrcn5kkvzwhlrv5pdi
A la lumiere de ces exemples, il est clair maintenant que la capacit~ de fecondation des spt. ...doi:10.1007/bf03040368 fatcat:guuxiyhvpza2zgiaplhdiitj3q
Background Regional citrate anticoagulation (RCA) is the gold standard of anticoagulation for continuous renal replacement therapy but is rarely used for intermittent hemodialysis (IHD) in ICU. Few studies assessed the safety and efficacy of RCA during IHD in ICU; however, no data are available comparing RCA to heparin anticoagulation, which are commonly used for IHD. The aim of this study was to assess the efficacy and safety of RCA compared to heparin anticoagulation during IHD. Methods Thisdoi:10.1186/s13613-021-00803-x pmid:33481169 fatcat:73xqgq4yknhbhpekxr2ynlqyqm
more »... etrospective single-center cohort study included consecutive ICU patients treated with either heparin anticoagulation (unfractionated or low-molecular-weight heparin) or RCA for IHD from July to September in 2015 and 2017. RCA was performed with citrate infusion according to blood flow and calcium infusion by diffusive influx from dialysate. Using a propensity score analysis, as the primary endpoint we assessed whether RCA improved efficacy, quantified with Kt/V from the ionic dialysance, compared to heparin anticoagulation. The secondary endpoint was safety. Exploratory analyses were performed on the changes in efficacy and safety between the implementation period (2015) and at long term (2017). Results In total, 208 IHD sessions were performed in 56 patients and were compared (124 RCA and 84 heparin coagulation). There was no difference in Kt/V between RCA and heparin (0.95 ± 0.38 vs. 0.89 ± 0.32; p = 0.98). A higher number of circuit clotting (12.9% vs. 2.4%; p = 0.02) and premature interruption resulting from acute high transmembrane pressure (21% vs. 7%; p = 0.02) occurred in the RCA sessions compared to the heparin sessions. In the propensity score-matching analysis, RCA was associated with an increased risk of circuit clotting (absolute differences = 0.10, 95% CI [0.03–0.18]; p = 0.008). There was no difference in efficacy and safety between the two time periods (2015 and 2017). Conclusion RCA with calcium infusion by diffusive influx from dialysate for IHD was easy to implement with stable long-term efficacy and safety but did not improve efficacy and could be associated with an increased risk of circuit clotting compared to heparin anticoagulation in non-selected ICU patients. Randomized trials to determine the best anticoagulation for IHD in ICU patients should be conducted in a variety of settings.
Whole genome sequencing of the response of Porphyromonas gingivalis W83 to hydrogen peroxide revealed an upregulation of several uncharacterized, novel genes. Under conditions of prolonged oxidative stress in P. gingivalis, increased expression of a unique transcriptional unit carrying the grpE, dnaJ and three other hypothetical genes (PG1777, PG1778 and PG1779) was observed. The transcriptional start site of this operon appears to be located 91 bp upstream of the translational start, with adoi:10.1099/mic.0.000213 pmid:26581883 pmcid:PMC4766595 fatcat:q5xuuy6m4rgg3kwmsugsrgngau
more »... ential 210 region at 23 nt and a 235 region at 239 nt. Isogenic P. gingivalis mutants FLL273 (PG1777 : : ermF-ermAM) and FLL293 (PG1779 : : ermF-ermAM) showed increased sensitivity to and decreased survival after treatment with hydrogen peroxide. P. gingivalis FLL273 showed a fivefold increase in the formation of spontaneous mutants when compared with the parent strain after exposure to hydrogen peroxide. The recombinant PG1777 protein displayed iron-binding properties when incubated with FeSO 4 and Fe(NH 4 ) 2 (SO 4 ).6H 2 O. The rPG1777 protein protected DNA from degradation when exposed to hydrogen peroxide in the presence of iron. Taken together, the data suggest that the grpE-dnaJ-PG1777-PG1778-PG1779 transcriptional unit may play an important role in oxidative stress resistance in P. gingivalis via its ability to protect against DNA damage.
Comparison between genealogical and molecular data Based on the comparison of 32 breeds in common with the study by Leroy et al. ... Considering 32 horse breeds with genotype available from the Leroy et al.  study, we compared coancestry rates with Reynolds et al. ...doi:10.1371/journal.pone.0061544 pmid:23630596 pmcid:PMC3632587 fatcat:u6hvt67bxndpdimuop7alcnase
Recently it has been shown that dominant mutations in the human hepatocyte nuclear factor 1 α (HNF1α) gene, encoding for a homeoprotein that is expressed in liver, kidney, pancreas and intestine, result in maturity onset diabetes of the young type 3 (MODY3). HNF1α-null mice are diabetic, but at the same time suffer from a renal Fanconi syndrome characterized by urinary glucose loss. Here we show that MODY3 patients are also characterized by a reduced tubular reabsorption of glucose. The renaldoi:10.1093/embo-reports/kvd071 pmid:11269503 pmcid:PMC1083745 fatcat:pvsmorcl7rdvpkikkruy3rbsvy
more »... rine defect is due to reduced expression of the low affinity/high capacity glucose cotransporter (SGLT2). Our results show that HNF1α directly controls SGLT2 gene expression. Together these data indicate that HNF1α plays a key role in glucose homeostasis in mammals. + Corresponding authors.
Anal. Chem. Journal paper entitled "A new label-free approach to glioblastoma cancer stem cell sorting and detection."doi:10.5281/zenodo.3408559 fatcat:wf5tcsyhnzd2bk2jdeetzcgtoe
The present research aims at quantifying the impact of practicing a new coordination pattern with an online visual feedback on the postural coordination performed on a mechanical horse. Forty-four voluntary participants were recruited in this study. They were randomly assigned to four practice groups based on i) with or without feedback ( i.e., group 1, control, did not receive the feedback; group 2, 3 and 4 received an online feedback during practice) and ii) the specific trunk/horsedoi:10.1101/2020.07.02.184234 fatcat:a4houggw5rbmrdsvp2w4hbc67m
more »... on to target during practice (group 1, target coordination = 180° (without feedback); group 2, target coordination = 0°; group 3, target coordination = 90°; group 4, target coordination = 180°). All participants performed pre-, practice, post- and retention sessions. The pre-, post- and retention sessions consisted of four trials, with one trial corresponding to one specific target coordination to maintain between their own oscillations and the horse oscillations (spontaneous, 0°, 90°, and 180°). The practice phase was composed of three different sessions during which participants received an online feedback about the coordination between their own oscillations and the horse oscillations. Results showed a significant change with practice in the trunk/horse coordination patterns which persisted even after one month (retention-test). However, all the groups did not show the same nature of change, evidenced by a high postural variability during post-test for 0° and 90° target coordination groups, in opposition to the 180° and spontaneous groups who showed a decrease in coordination variability for the 180° group. The coordination in anti-phase was characterized as spontaneously adopted by participants on the mechanical horse, explaining the ease of performing this coordination (compared to the 0° and 90° target coordination). The effect of online visual feedback appeared not only on the coordination pattern itself, but most importantly on its variability during practice, including concerning initially stable coordination patterns.
Journal of Virology
Analysis of disease induction by simian immunodeficiency viruses (SIV) in macaques was initially hampered by a lack of molecularly defined pathogenic strains. The first molecularly cloned SIV strains inoculated into macaques, SIVmacBK28 and SIVmacBK44 (hereafter designated BK28 and BK44, respectively), were cases in point, since they failed to induce disease within 1 year postinoculation in any inoculated animal. Here we report the natural history of infection with BK28 and BK44 in inoculateddoi:10.1128/jvi.72.1.405-414.1998 fatcat:klc73dcbk5dhfmbr44cnsip5ye
more »... esus macaques and efforts to increase the pathogenicity of BK28 through genetic manipulation and in vivo passage. BK44 infection resulted in no disease in four animals infected for more than 7 years, whereas BK28 induced disease in less than half of animals monitored for up to 7 years. Elongation of the BK28 transmembrane protein (TM) coding sequence truncated by prior passage in human cells marginally increased pathogenicity, with two of four animals dying in the third year and one dying in the seventh year of infection. Modification of the BK28 long terminal repeat to include four consensus nuclear factor SP1 and two consensus NF-κB binding sites enhanced early virus replication without augmenting pathogenicity. In contrast, in vivo passage of BK28 from the first animal to die from immunodeficiency disease (1.5 years after infection) resulted in a consistently pathogenic strain and a 50% survival time of about 1.3 years, thus corresponding to one of the most pathogenic SIV strains identified to date. To determine whether the diverse viral quasispecies that evolved during in vivo passage was required for pathogenicity or whether a more virulent virus variant had evolved, we generated a molecular clone composed of the 3′ half of the viral genome derived from the in vivo-passaged virus (H824) fused with the 5′ half of the BK28 genome. Kinetics of disease induction with this cloned virus (BK28/H824) were similar to those with the in vivo-passaged virus, with four of five animals surviving less than 1.7 years. Thus, evolution of variants with enhanced pathogenicity can account for the increased pathogenicity of this SIV strain. The genetic changes responsible for this virulent transformation included at most 59 point mutations and 3 length-change mutations. The critical mutations were likely to have been multiple and dispersed, including elongation of the TM and Nef coding sequences; changes in RNA splice donor and acceptor sites, TATA box sites, and Sp1 sites; multiple changes in the V2 region of SU, including a consensus neutralization epitope; and five new N-linked glycosylation sites in SU.
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