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31 result(s) for "Aziz, Pauline"
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Cell-Based Therapy for the Treatment of Glioblastoma: An Update from Preclinical to Clinical Studies
Glioblastoma (GB), an aggressive primary tumor of the central nervous system, represents about 60% of all adult primary brain tumors. It is notorious for its extremely low (~5%) 5-year survival rate which signals the unsatisfactory results of the standard protocol for GB therapy. This issue has become, over time, the impetus for the discipline of bringing novel therapeutics to the surface and challenging them so they can be improved. The cell-based approach in treating GB found its way to clinical trials thanks to a marvelous number of preclinical studies that probed various types of cells aiming to combat GB and increase the survival rate. In this review, we aimed to summarize and discuss the up-to-date preclinical studies that utilized stem cells or immune cells to treat GB. Likewise, we tried to summarize the most recent clinical trials using both cell categories to treat or prevent recurrence of GB in patients. As with any other therapeutics, cell-based therapy in GB is still hampered by many drawbacks. Therefore, we highlighted several novel techniques, such as the use of biomaterials, scaffolds, nanoparticles, or cells in the 3D context that may depict a promising future when combined with the cell-based approach.
Genomic profiling of small bowel adenocarcinoma: a pooled analysis from 3 databases
Background Small bowel adenocarcinoma is a rare disease. The genomic profiling tumours according to clinical characteristics and its impact on the prognosis remains unclear. Methods A pooled analysis of clinical data, genomic profiling and MisMatch Repair (MMR) status from three databases was performed. Results A total of 188 tumour samples were analysed. A predisposing disease was reported in 22.3%, mainly Lynch syndrome and Crohn’s disease. The tumours were localized in 80.2% and metastatic in 18.8%. The most frequent mutations were KRAS (42.0%) among them 7/79 are G12C , TP53 (40.4%), APC (19.1%), PIK3CA (18.6%), SMAD4 (12.8%) and ERBB2 (9.6%). Mutation distribution differed according to predisposing disease for TP53 , ERBB2, IDH1, FGFR3, FGFR1 and KDR. KRAS and SMAD4 mutations were more frequent in metastatic tumour, whereas ERBB2 mutations were absent in metastatic tumour. For localized tumour, APC mutation was independently associated with a poor overall survival (OS) ( p  = 0.0254). 31.8% of localized tumours and 11.3% of metastatic tumours were dMMR (29.8% of the entire cohort). A dMMR status was associated with a better OS (HR = 0.61 [0.39–0.96], p  = 0.0316). Conclusions There is a different genomic profile according to the stage and predisposing disease. dMMR and APC mutation in localized tumour predict a better prognosis.
Neurodevelopmental Disorder Caused by Deletion of CHASERR, a lncRNA Gene
CHASERR encodes a human long noncoding RNA (lncRNA) adjacent to CHD2 , a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Here, we report our findings in three unrelated children with a syndromic, early-onset neurodevelopmental disorder, each of whom had a de novo deletion in the CHASERR locus. The children had severe encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination — a phenotype that is distinct from the phenotypes of patients with CHD2 haploinsufficiency. We found that the CHASERR deletion results in increased CHD2 protein abundance in patient-derived cell lines and increased expression of the CHD2 transcript in cis . These findings indicate that CHD2 has bidirectional dosage sensitivity in human disease, and we recommend that other lncRNA-encoding genes be evaluated, particularly those upstream of genes associated with mendelian disorders. (Funded by the National Human Genome Research Institute and others.) Deletions in a gene ( CHASERR ) that encodes a long noncoding RNA cause severe developmental delay and an increase in expression of a neighboring gene, CHD2 .
Challenges Related to Surgical Site Infection Prevention—Results after Standardized Bundle Implementation
Aim: The aim of this study was to assess the implementation of an intraoperative standardized surgical site infection (SSI) prevention bundle. Methods: The multimodal, evidence-based care bundle included nine intraoperative items (antibiotic type, timing, and re-dosing; disinfection; induction temperature control > 36.5°; glove change; intra-cavity lavage; wound protection; and closure strategy). The bundle was applied to all consecutive patients undergoing colonic resections. The primary outcome, SSI, was independently assessed by the National Infection Surveillance Committee for up to 30 postoperative days. A historical, institutional pre-implementation control group (2012–2017) with an identical methodology was used for comparison. Findings: In total, 1516 patients were included, of which 1256 (82.8%) were in the control group and 260 (17.2%) were in the post-implementation group. After 2:1 propensity score matching, the groups were similar for all items (p > 0.05). Overall compliance with the care bundle was 77% (IQR 77–88). The lowest compliance rates were observed for temperature control (53% overall), intra-cavity lavage (64% overall), and wound protection and closure (68% and 63% in the SSI group, respectively). Surgical site infections were reported in 58 patients (22.2%) vs. 21.4% in the control group (p = 0.79). Infection rates were comparable throughout the Centers for Disease Control and Prevention (CDC) categories: superficial, 12 patients (4.5%) vs. 4.2%, p = 0.82; deep incisional, 10 patients (3.7%) vs. 5.1%, p = 0.34; organ space, 36 (14%) vs. 12.4%, p = 0.48. After propensity score matching, rates remained comparable throughout all comparisons (all p > 0.05). Conclusions: The implementation of an intraoperative standardized care bundle had no impact on SSI rates. This may be explained by insufficient compliance with the individual measures.
Factors Associated with Increased or Decreased Stress Level in French Children during the First COVID-19 Lockdown
In spring 2020, governments of many countries implemented lockdown measures to prevent the spread of the COVID-19 pandemic. Worldwide, the pandemic forced about 1.5 billion children to stay at home for several weeks and to experience homeschooling. The objective of this study was to assess the variation in stress levels and associated factors in school-aged children in France during the first COVID-19 lockdown. A cross-sectional study using an online questionnaire was designed by an interdisciplinary team involving hospital child psychiatrists and school doctors. Between 15 June and 15 July 2020, Educational Academy of Lyon (France) invited the parents of school-aged children to participate in this survey. The first part of the questionnaire concerned the children with data on lockdown conditions, socio-demographic data, daily rhythms (eating and sleeping), perceived stress variations, and feelings. The second part assessed parental perspectives on their child’s psychological state and use of the mental health care system. Multivariate logistic regression was performed to identify factors associated with stress variation (increased or decreased). A total of 7218 questionnaires were fully completed by children from elementary school to high school with a balanced sex ratio. In summary, 29% of children reported a higher stress level during the lockdown, 34% reported a lower stress level, and 37% reported no stress variation in the usual situation prior to COVID-19. Parents were most often able to identify signs of increased stress levels in their children. The most influential factors in the variation of stress for children were academic pressure, family relationships, and fear of being infected or infecting a family member with SARS-CoV-2. Our study underlines the high impact of school attendance stressors on children in usual conditions and encourages vigilance for children whose stress levels have decreased during the lockdown but who may have increased difficulty re-exposing themselves upon deconfinement.
Patient safety in healthcare preregistration educational curricula: multiple case study-based investigations of eight medicine, nursing, pharmacy and physiotherapy university courses
Background We sought to investigate the formal and informal ways preregistration students from medicine, nursing, pharmacy and the allied healthcare professions learn about patient safety. Methods We drew on Eraut's framework on formal and informal acquisition of professional knowledge to undertake a series of phased theoretically informed, in-depth comparative qualitative case studies of eight university courses. We collected policy and course documentation; interviews and focus groups with educators, students, health service staff, patients and policy makers; and course and work placement observations. Data were analysed thematically extracting emerging themes from different phases of data collection within cases, and then comparing these across cases. Results We conducted 38 focus groups with a total of 162 participants, undertook 82 observations of practice placements/learning activities and 33 semistructured interviews, and analysed 44 key documents. Patient safety tended to be either implicit in curricula or explicitly identified in a limited number of discrete topic areas. Students were predominantly taught about safety-related issues in isolation, with the consequence of only limited opportunities for interprofessional learning and bridging the gaps between educational, practice and policy contexts. Although patient safety role models were key to student learning in helping to develop and maintain a consistent safety ethos, their numbers were limited. Conclusions Consideration needs to be given to the appointment of curriculum leads for patient safety who should be encouraged to work strategically across disciplines and topic areas; development of stronger links with organisational systems to promote student engagement with organisation-based patient safety practice; and role models should help students to make connections between theoretical considerations and routine clinical care.
Petrochemical constrains on the origin and tectonic setting of mafic to intermediate dykes from Tikar plain, Central Cameroon Shear Zone
The Tikar plain is located on the Cameroon Central Shear Zone. It is also part of the North Equatorial Pan-African Belt. It is formed of granitoids intruded in places by mafic and intermediate dykes. The mafic dykes are essentially banded gabbros composed of plagioclases, pyroxenes, amphiboles, biotites and opaques. Their textures range from porphyroblastic to porphyritic. The intermediate dykes are monzonites and monzodiorites and are characterized, respectively, by cataclastic and mylonitic textures. The minerals identified are amphiboles, potassium feldspar, pyroxenes, epidotes, sphenes and opaques. Seritization reaction is mostly present on the mafic and intermediate dykes, while chloritization is much more pronounced on the intermediate dykes. The Tikar plain dykes are high-k calc-alkaline to shoshonitic. They are characterized by low to moderate SiO 2 content (42.08–61.96 wt%), low to high TiO 2 (0.47–2 wt%) and low Ni (1.48–99.18 ppm) contents. The mafic dykes show fractional trends with negative anomalies of Zr, U and P and positive Rb, Ba, Ta, Pb and Sr in multi-element diagrams, while the intermediate dykes present negative anomalies of Nb, Ta, Zr, Sr P and Ti and relative positive anomalies of Rb, Ba and Pb. The rare-earth elements (REE) patterns show positive Eu anomalies for the mafic dykes and negative anomalies for the intermediate dykes. The REE spectrum of all the dykes shows enrichment in LREE with relatively flat HREE, which can indicate arc magmatism. In the Zr–Ti/100–Sr/2 diagram, the mafic dykes plot in the island arc tholeiite and calc-alkaline basalt fields. The Th, Nb and LREE concentrations indicate that the subducted lithosphere with crustal component contributed to generation of the intermediate dykes of the Tikar plain. The geochemical characteristics of the mafic to intermediate dykes suggest their derivation from a various degree of partial melting in the garnet spinel facies, probably between depths of 80 and 100 km. The collision between the Central African Fold Belt and the northern edge of the Congo craton resulting in crustal thickening, sub-crustal lithospheric delamination and upwelling of the asthenosphere may have been the principal process in the generation of the intermediate dykes in the Tikar plain. The magma for the mafic and intermediate dyke would have migrated through the faults network of the Central Cameroon Shear Zone before crystallizing in the granito-gneissic basement rocks.
Acceptability, barriers and facilitators of using dried blood spots-point-of-care testing for sickle cell disease in Africa: an implementation science protocol for a multinational qualitative study
BackgroundSickle cell disease (SCD) is a prevalent inherited blood disorder. Globally, approximately 515 000 babies are born with SCD annually, with 75% of these births occurring in Africa. Integrating newborn screening (NBS) for SCD into primary healthcare structures, such as immunisation programmes, holds significant promise, with dried blood spots (DBS)-point-of-care technologies (POCT) like HaemoTypeSC offering cost-effective screening solutions. However, scaling up DBS-POCT for NBS of SCD in Africa remains challenging.ObjectiveThis study aims to explore individual, organisational and external factors that may influence the reliability, feasibility, acceptability, adoption and sustainability of using DBS-POCT with HaemoTypeSC for NBS of SCD at primary healthcare centres in African countries.MethodThis qualitative study will be conducted in seven African countries that are part of the SickleInAfrica consortium sites. The study design is informed by the Consolidated Framework for Implementation Research (CFIR) and the Implementation Outcome Model. Participants will be mothers whose babies have been diagnosed with SCD, healthcare professionals and policy-makers. In-depth interviews and focus group discussions will be used for data collection. Data analysis will be through thematic analysis.Ethics and disseminationResearch ethics approvals have been obtained from the seven countries. Written informed consent will be obtained from all participants. The study results will be disseminated in peer-reviewed scientific journals, scientific conferences, reports to national ministries of public health and webinars.
Polycystic kidney disease concurrent with feline parvovirus and bacterial infections in domestic shorthair cat: a case report
Feline polycystic kidney disease (PKD) is an inherited disorder caused by the mutation of PKD1 gene that eventually lead to the development of chronic kidney disease. The latter condition causes hypertension and eventually progress into congestive heart failure. Feline parvovirus (FPV) is a highly contagious and often fatal disease infecting cats and other members of Felidae. An 8-month-old female domestic shorthair cat was presented with complaint of wound dehiscence a day after ovarian hysterectomy procedure. The wound at the suture site appeared necrotic, purulent with foul smell. The cat was found to have diarrhoea during the fixation of suture breakdown and, later, was tested positive with parvovirus infection. Complete blood count revealed anaemia, neutrophilia, lymphopenia and thrombocytosis. Biochemistry profiles showed hypoproteinaemia and elevated of urea and creatinine. The cat was hospitalised, and symptomatic treatments were given. During hospitalisation, the cat showed symptoms of polydipsia and polyuria and found dead 2 days later. Post-mortem findings demonstrated the cat had oral ulceration, thoracic effusion, fibrinopleuropneumonia, pericardial effusion, left ventricular hypertrophy and right ventricular dilation, chronic passive liver congestion, mesenteric lymphadenomegaly, intestinal haemorrhage, adrenomegaly and polycystic kidney. Histopathological evaluation revealed fibrinous pleuropneumonia, pulmonary atelectasis, emphysema and oedema, hypertrophic cardiomyopathy, hepatic necrosis, splenic necrosis, intestinal necrosis, renal necrosis and renal polycystic. Staphylococcus aureus and Escherichia coli were isolated from bronchus swab and intestinal segment, respectively. Polymerase chain reaction (PCR) revealed parvovirus infection. The cat was definitely diagnosed with polycystic kidney disease concurrent with parvoviral and secondary bacterial infections.
Learning About Patient Safety: Organizational Context and Culture in the Education of Health Care Professionals
Objectives This study investigated the formal and informal ways pre-registration students from medicine, nursing, physiotherapy and pharmacy learn about keeping patients safe. This paper gives an overview of the study and explores findings in relation to organizational context and culture. Methods The study employed a phased design using multiple qualitative methods. The overall approach drew on ‘illuminative evaluation’. Ethical approval was obtained. Phase 1 employed a convenience sample of 13 pre-registration courses across the UK. Curriculum documents were gathered, and course directors interviewed. Phase 2 used eight case studies, two for each professional group, to develop an in-depth investigation of learning across university and practice by students and newly-qualified practitioners in relation to patient safety, and to examine the organizational culture that students and newly-qualified staff are exposed to. Analysis was iterative and ongoing throughout the study, using frameworks agreed by all researchers. Results Patient safety was felt to have become a higher priority for the health care system in recent years. Incident reporting was a key feature of the patient safety agenda within the organizations examined. Staff were often unclear or too busy to report. On the whole, students were not engaged and may not be aware of incident reporting schemes. They may not have access to existing systems in their organization. Most did not access employers’ induction programmes. Some training sessions occasionally included students but this did not appear to be routine. Conclusions Action is needed to develop an efficient interface between employers and education providers to develop up-to-date curricula for patient safety.