162 research outputs found
Особливості формування самостійної пізнавальної діяльності майбутніх учителів математики
(uk) У статті зроблено спробу розкрити особливості самостійної пізнавальної діяльності майбутніх вчителів; досліджуються різні підходи до цього поняття; розкриваються такі його складові, як самостійність, пізнавальна самостійність, пізнавальна діяльність.(ru) В статье сделана попытка раскрыть особенности самостоятельной познавательной деятельности будущих учителей; исследуются различные подходы к этому понятию; раскрываются такие его составляющие, как самостоятельность, познавательная самостоятельность, познавательная деятельность
Autologous microsurgical breast reconstruction and coronary artery bypass grafting: an anatomical study and clinical implications
OBJECTIVE: To identify possible avenues of sparing the internal mammary artery (IMA) for coronary artery bypass grafting (CABG) in women undergoing autologous breast reconstruction with deep inferior epigastric artery perforator (DIEP) flaps. BACKGROUND: Optimal autologous reconstruction of the breast and coronary artery bypass grafting (CABG) are often mutually exclusive as they both require utilisation of the IMA as the preferred arterial conduit. Given the prevalence of both breast cancer and coronary artery disease, this is an important issue for women's health as women with DIEP flap reconstructions and women at increased risk of developing coronary artery disease are potentially restricted from receiving this reconstructive option should the other condition arise. METHODS: The largest clinical and cadaveric anatomical study (n=315) to date was performed, investigating four solutions to this predicament by correlating the precise requirements of breast reconstruction and CABG against the anatomical features of the in situ IMAs. This information was supplemented by a thorough literature review. RESULTS: Minimum lengths of the left and right IMA needed for grafting to the left-anterior descending artery are 160.08 and 177.80 mm, respectively. Based on anatomical findings, the suitable options for anastomosis to each intercostals space are offered. In addition, 87-91% of patients have IMA perforator vessels to which DIEP flaps can be anastomosed in the first- and second-intercostal spaces. CONCLUSION: We outline five methods of preserving the IMA for future CABG: (1) lowering the level of DIEP flaps to the fourth- and fifth-intercostals spaces, (2) using the DIEP pedicle as an intermediary for CABG, (3) using IMA perforators to spare the IMA proper, (4) using and end-to-side anastomosis between the DIEP pedicle and IMA and (5) anastomosis of DIEP flaps using retrograde flow from the distal IMA. With careful patient selection, we hypothesize using the IMA for autologous breast reconstruction need not be an absolute contraindication for future CABG
The anatomy and variations of the internal thoracic (internal mammary) artery and implications in autologous breast reconstruction: clinical anatomical study and literature review
The malarial exported PFA0660w is an Hsp40 co-chaperone of PfHsp70-x
Plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. Molecular chaperones of the heat shock protein (Hsp) family are prominent members of the exportome, including a number of Hsp40s and a Hsp70. PFA0660w, a type II Hsp40, has been shown to be exported and possibly form a complex with PfHsp70-x in the infected erythrocyte cytosol. However, the chaperone properties of PFA0660w and its interaction with human and parasite Hsp70s are yet to be investigated. Recombinant PFA0660w was found to exist as a monomer in solution, and was able to significantly stimulate the ATPase activity of PfHsp70-x but not that of a second plasmodial Hsp70 (PfHsp70-1) or a human Hsp70 (HSPA1A), indicating a potential specific functional partnership with PfHsp70-x. Protein binding studies in the presence and absence of ATP suggested that the interaction of PFA0660w with PfHsp70-x most likely represented a co-chaperone/chaperone interaction. Also, PFA0660w alone produced a concentrationdependent suppression of rhodanese aggregation, demonstrating its chaperone properties. Overall, we have provided the first biochemical evidence for the possible role of PFA0660w as a chaperone and as co-chaperone of PfHsp70-x. We propose that these chaperones boost the chaperone power of the infected erythrocyte, enabling successful protein trafficking and folding, and thereby making a fundamental contribution to the pathology of malaria
Anxiety and Depression in Adults with Autism Spectrum Disorder: A Systematic Review and Meta-analysis
Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations
Claudin-1 Is a p63 Target Gene with a Crucial Role in Epithelial Development
The epidermis of the skin is a self-renewing, stratified epithelium that functions as the interface between the human body and the outer environment, and acts as a barrier to water loss. Components of intercellular junctions, such as Claudins, are critical to maintain tissue integrity and water retention. p63 is a transcription factor essential for proliferation of stem cells and for stratification in epithelia, mutated in human hereditary syndromes characterized by ectodermal dysplasia. Both p63 and Claudin-1 null mice die within few hours from birth due to dehydration from severe skin abnormalities. These observations suggested the possibility that these two genes might be linked in one regulatory pathway with p63 possibly regulating Claudin-1 expression. Here we show that silencing of ΔNp63 in primary mouse keratinocytes results in a marked down-regulation of Claudin-1 expression (−80%). ΔNp63α binds in vivo to the Claudin-1 promoter and activates both the endogenous Claudin-1 gene and a reporter vector containing a –1.4 Kb promoter fragment of the Claudin-1 gene. Accordingly, Claudin-1 expression was absent in the skin of E15.5 p63 null mice and natural p63 mutant proteins, specifically those found in Ankyloblepharon–Ectodermal dysplasia–Clefting (AEC) patients, were indeed altered in their capacity to regulate Claudin-1 transcription. This correlates with deficient Claudin-1 expression in the epidermis of an AEC patient carrying the I537T p63 mutation. Notably, AEC patients display skin fragility similar to what observed in the epidermis of Claudin-1 and p63 null mice. These findings reinforce the hypothesis that these two genes might be linked in a common regulatory pathway and that Claudin-1 may is an important p63 target gene involved in the pathogenesis of ectodermal dysplasias
TLR4 Asp299Gly and Thr399Ile Polymorphisms: No Impact on Human Immune Responsiveness to LPS or Respiratory Syncytial Virus
A broad variety of natural environmental stimuli, genotypic influences and timing all contribute to expression of protective versus maladaptive immune responses and the resulting clinical outcomes in humans. The role of commonly co-segregating Toll-like receptor 4 (TLR4) non-synonymous single nucleotide polymorphisms Asp299Gly and Thr399Ile in this process remains highly controversial. Moreover, what differential impact these polymorphisms might have in at risk populations with respiratory dysfunction, such as current asthma or a history of infantile bronchiolitis, has never been examined. Here we determine the importance of these polymorphisms in modulating LPS and respiratory syncytial virus (RSV)--driven cytokine responses. We focus on both healthy children and those with clinically relevant respiratory dysfunction.To elucidate the impact of TLR4 Asp299Gly and Thr399Ile on cytokine production, we assessed multiple immune parameters in over 200 pediatric subjects aged 7-9. Genotyping was followed by quantification of pro- and anti-inflammatory cytokine responses by fresh peripheral blood mononuclear cells upon acute exposure to LPS or RSV.In contrast to early reports, neither SNP influenced immune responses evoked by LPS exposure or RSV infection, as measured by the intermediate phenotype of pro- and anti-inflammatory cytokine responses to these ubiquitous agents. There is no evidence of altered sensitivity in populations with "at risk" clinical phenotypes.Genomic medicine seeks to inform clinical practice. Determination of the TLR4 Asp299Gly/Thr399Ile haplotype is of no clinical benefit in predicting the nature or intensity of cytokine production in children whether currently healthy or among specific at-risk groups characterized by prior infantile broncholitis or current asthma
The process of recovery of people with mental illness: The perspectives of patients, family members and care providers: Part 1
<p>Abstract</p> <p>Background</p> <p>It is a qualitative design study that examines points of divergence and convergence in the perspectives on recovery of 36 participants or 12 triads. Each triad comprising a patient, a family member/friend, a care provider and documents the procedural, analytic of triangulating perspectives as a means of understanding the recovery process which is illustrated by four case studies. Variations are considered as they relate to individual characteristics, type of participant (patient, family, member/friend and care provider), and mental illness. This paper which is part of a larger study and is based on a qualitative research design documents the process of recovery of people with mental illness: Developing a Model of Recovery in Mental Health: A middle range theory.</p> <p><b>Methods</b></p> <p>Data were collected in field notes through semi-structured interviews based on three interview guides (one for patients, one for family members/friends, and one for caregivers). Cross analysis and triangulation methods were used to analyse the areas of convergence and divergence on the recovery process of all triads.</p> <p>Results</p> <p>In general, with the 36 participants united in 12 triads, two themes emerge from the cross-analysis process or triangulation of data sources (12 triads analysis in 12 cases studies). Two themes emerge from the analysis process of the content of 36 interviews with participants: (1) <it>Revealing dynamic context</it>, situating patients in their dynamic context; and (2) <it>Relationship issues in a recovery process</it>, furthering our understanding of such issues. We provide four case studies examples (among 12 cases studies) to illustrate the variations in the way recovery is perceived, interpreted and expressed in relation to the different contexts of interaction.</p> <p>Conclusion</p> <p>The perspectives of the three participants (patients, family members/friends and care providers) suggest that recovery depends on constructing meaning around mental illness experiences and that the process is based on each person's dynamic context (e.g., social network, relationship), life experiences and other social determinants (e.g., symptoms, environment). The findings of this study add to existing knowledge about the determinants of the recovery of persons suffering with a mental illness and significant other utilizing public mental health services in Montreal, Canada.</p
Reducing Adverse Self-Medication Behaviors in Older Adults with Hypertension: Results of an e-health Clinical Efficacy Trial
A randomized controlled efficacy trial targeting older adults with hypertension (age 60 and over) provided an e-health, tailored intervention with the “next generation” of the Personal Education Program (PEP-NG). Eleven primary care practices with advanced practice registered nurse (APRN) providers participated. Participants (N = 160) were randomly assigned by the PEP-NG (accessed via a wireless touchscreen tablet computer) to either control (entailing data collection and four routine APRN visits) or tailored intervention (involving PEP-NG intervention and four focused APRN visits) group. Compared to patients in the control group, patients receiving the PEP-NG e-health intervention achieved significant increases in both self-medication knowledge and self-efficacy measures, with large effect sizes. Among patients not at BP targets upon entry to the study, therapy intensification in controls (increased antihypertensive dose and/or an additional antihypertensive) was significant (p = .001) with an odds ratio of 21.27 in the control compared to the intervention group. Among patients not at BP targets on visit 1, there was a significant declining linear trend in proportion of the intervention group taking NSAIDs 21–31 days/month (p = 0.008). Satisfaction with the PEP-NG and the APRN provider relationship was high in both groups. These results suggest that the PEP-NG e-health intervention in primary care practices is effective in increasing knowledge and self-efficacy, as well as improving behavior regarding adverse self-medication practices among older adults with hypertension
BTN3A2 Expression in Epithelial Ovarian Cancer Is Associated with Higher Tumor Infiltrating T Cells and a Better Prognosis
BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells
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