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1.
BMC Nurs ; 23(1): 263, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654226

RESUMEN

INTRODUCTION: Clinical education is an important aspect of the training of nursing students but it is faced with challenges in Ghana. The development of a framework will respond to the need for improvement in the quality of clinical nursing education. This study describes part of a larger study which culminated in the development of a framework for a clinical education programme for undergraduate nursing students in Ghana. The aim of the current study was to integrate findings from a scoping review and situational analysis to develop a framework for clinical education in nursing. METHODS: A sequential multimethod design approach was used to conduct the study. A scoping review on the practices that facilitate clinical nursing education and situational analysis were first conducted. The lessons learnt from the scoping review and the situational analysis provided the data matrix that was triangulated to develop the framework. The framework was developed using the model for clinical education developed by South African Nursing Education Stakeholders in consultation with experts in nursing education. An implementation plan was developed from the framework and evaluated using a Delphi technique. FINDINGS: The resulting framework indicates the need for effective communication and collaboration between nursing education institution and the service setting to ensure that there is a well-structured clinical placement, formal supervision system and effective clinical assessment of students. The framework also proposes that to ensure quality clinical nursing education there is the need for Nursing Education Institutions to implement innovative and cost-effective clinical teaching methods. CONCLUSION: The framework spells out the functions of the various stakeholders in nursing education and how these can be integrated and implemented to enhance quality clinical nursing education. Effectiveness of the thematic areas of the framework will increase the quality of clinical nursing education.

2.
J Vet Intern Med ; 38(2): 995-1004, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38351718

RESUMEN

BACKGROUND: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis. HYPOTHESIS: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers. ANIMALS: Healthy controls (n = 19) and dogs with naturally occurring pancreatitis (n = 17). METHODS: A retrospective case-control study. Dogs with pancreatitis were included if they satisfied diagnostic criteria for pancreatitis as adjudicated by 3 experts. MicroRNA was extracted from stored serum samples and sequenced. Reads were mapped to mature microRNA sequences in the canine, mouse, and human genomes. Differentially expressed microRNAs were identified and the potential mechanistic relevance explored using Qiagen Ingenuity Pathway Analysis (IPA). RESULTS: Reads mapping to 196 mature microRNA sequences were detected. Eight circulating microRNAs were significantly differentially expressed in dogs with pancreatitis (≥2-fold change and false discovery rate <0.05). Four of these mapped to the canine genome (cfa-miR-221, cfa-miR-222, cfa-miR-23a, and cfa-miR-205). Three mapped to the murine genome (mmu-miR-484, mmu-miR-6240, mmu-miR-101a-3p) and 1 to the human genome (hsa-miR-1290). Expression in dogs with pancreatitis was higher for 7 microRNAs and lower for mmu-miR-101a-3p. Qiagen IPA demonstrated a number of the differently expressed microRNAs are involved in a common pancreatic inflammatory pathway. CONCLUSIONS: The significantly differentially expressed microRNAs represent promising candidates for further validation as diagnostic biomarkers for canine pancreatitis.


Asunto(s)
MicroARN Circulante , Enfermedades de los Perros , MicroARNs , Pancreatitis Crónica , Enfermedades de los Roedores , Humanos , Perros , Animales , Ratones , MicroARN Circulante/genética , Estudios de Casos y Controles , Estudios Retrospectivos , MicroARNs/genética , Biomarcadores , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/genética , Pancreatitis Crónica/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/genética
3.
Cancer ; 130(1): 60-67, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37851512

RESUMEN

BACKGROUND: A lack of onsite clinical trials is the largest barrier to participation of cancer patients in trials. Development of an automated process for regional trial eligibility screening first requires identification of patient electronic health record data that allows effective trial screening, and evidence that searching for trials regionally has a positive impact compared with site-specific searching. METHODS: To assess a screening framework that would support an automated regional search tool, a set of patient clinical variables was analyzed for prescreening clinical trials. The variables were used to assess regional compared with site-specific screening throughout the United States. RESULTS: Eight core variables from patient electronic health records were identified that yielded likely matches in a prescreen process. Assessment of the screening framework was performed using these variables to search for trials locally and regionally for an 84-patient cohort. The likelihood that a trial returned in this prescreen was a provisional trial match was 45.7%. Expanding the search radius to 20 miles led to a net 91% increase in matches across cancers within the tested cohort. In a U.S. regional analysis, for sparsely populated areas, searching a 100-mile radius using the prescreening framework was needed, whereas for urban areas a 20-mile radius was sufficient. CONCLUSION: A clinical trial screening framework was assessed that uses limited patient data to efficiently and effectively identify prescreen matches for clinical trials. This framework improves trial matching rates when searching regionally compared with locally, although the applicability of this framework may vary geographically depending on oncology practice density. PLAIN LANGUAGE SUMMARY: Clinical trials provide cancer patients the opportunity to participate in research and development of new drugs and treatment approaches. It can be difficult to find available clinical trials for which a patient is eligible. This article describes an approach to clinical trial matching using limited patient data to search for trials regionally, beyond just the patient's local care site. Feasibility testing shows that this process can lead to a net 91% increase in the number of potential clinical trial matches available within 20 miles of a patient. Based on these findings, a software tool based on this model is being developed that will automatically send limited, deidentified information from patient medical records to services that can identify possible clinical trials within a given region.


Asunto(s)
Neoplasias , Humanos , Registros Electrónicos de Salud , Determinación de la Elegibilidad , Estudios de Factibilidad , Neoplasias/diagnóstico , Neoplasias/terapia , Selección de Paciente , Ensayos Clínicos como Asunto
4.
Int J Surg Pathol ; 32(3): 478-485, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37501528

RESUMEN

Myxofibrosarcomas (MFS) present as slowly enlarging superficial masses in elderly patients. Even though these tumors fail to exhibit a distinct immunophenotype, diagnosis is straightforward when they present in subcutaneous tissue. Intramuscular MFS, however, are more challenging to diagnose as the differential also includes dedifferentiated liposarcoma with myxoid features. The vast majority of dedifferentiated liposarcomas show MDM2 amplification, whereas limited data exists as to the MDM2 status of MFS. We sought to explore the rate of MDM2 amplification in cases of classic MFS. Our archives were searched for MFS; only subcutaneous well-sampled resections were included. FISH for MDM2 amplification was performed on each tumor. A cohort of myxoid dedifferentiated liposarcoma resections was studied for comparison. Twenty-two MFS arose in patients aged 44 to 85 years. All tumors contained an infiltrative population of atypical cells embedded in a myxoid stroma with curvilinear blood vessels. MDM2 amplification by FISH was identified in 3 (of 22; 14%) tumors. Available follow up on 17 patients (range 1-96 months; median 13 months) revealed 6 patients with local recurrence and 1 with distant metastasis. Of 3 patients with MDM2- amplified MFS, 1 experienced recurrence and died of unrelated causes, while the second was alive without disease 12 months after diagnosis. Even though the rate of MDM2 amplification by FISH in MFS appears to be low, a subset of cases may show this genetic alteration, which pathologists should be aware of to avoid misclassification as myxoid dedifferentiated liposarcomas. Further studies are necessary to determine if amplification status adds prognostic value.


Asunto(s)
Fibrosarcoma , Liposarcoma Mixoide , Liposarcoma , Anciano , Adulto , Humanos , Liposarcoma/diagnóstico , Liposarcoma/genética , Liposarcoma/patología , Hibridación Fluorescente in Situ , Liposarcoma Mixoide/patología , Pronóstico , Fibrosarcoma/genética , Amplificación de Genes , Proteínas Proto-Oncogénicas c-mdm2/metabolismo
5.
Genes Chromosomes Cancer ; 63(1): e23203, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37724942

RESUMEN

Spindle cell mesenchymal neoplasms are a diverse and often challenging diagnostic group. While morphological impression is sufficient for some diagnoses, increasingly immunohistochemical and even molecular data is required to render an accurate diagnosis, which can lead to the characterization of new entities. We describe five cases of novel mesenchymal neoplasms with rearrangements in the NCOA2 and NCOA3 genes partnered with either CTCF or CRTC1. Three tumors occurred in the head and neck (palate, auditory canal), while the other two were in visceral organs (lung, urinary bladder). All cases occurred in adults (range 33-86) with a median age of 42 and fairly even sex distribution = (male-to-female = 3:2). Morphologically, they had similar features consisting of monotonous, bland spindle to ovoid cells with fascicular and reticular arrangements in a myxohyaline to collagenous stroma. However, immunophenotypically they had essentially a null phenotype, with only two tumors staining partially for CD34 and smooth muscle actin. Targeted RNA sequencing detected in-frame CTCF::NCOA2 (one case), CRTC1::NCOA2 (two cases), and CTCF::NCOA3 (two cases) fusions. Treatment was surgical resection in all cases. Local recurrence and/or distant metastases were not observed in any case (median follow-up, 7.5 months; range, 2-19 months). Given their morphologic, immunohistochemical, and molecular similarities, we believe that these cases may represent an emerging family of low-grade NCOA2/3-rearranged fibroblastic spindle cell neoplasms.


Asunto(s)
Neoplasias de los Tejidos Conjuntivo y Blando , Neoplasias de los Tejidos Blandos , Adulto , Humanos , Masculino , Femenino , Fibroblastos/patología , Secuencia de Bases , Neoplasias de los Tejidos Conjuntivo y Blando/genética , Fenotipo , Biomarcadores de Tumor/genética , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Coactivador 2 del Receptor Nuclear/genética
6.
Int J Surg Pathol ; 32(3): 556-564, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37461232

RESUMEN

Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease.


Asunto(s)
Quistes Óseos Aneurismáticos , Neoplasias Óseas , Tumor Óseo de Células Gigantes , Neoplasias Primarias Secundarias , Humanos , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Queratinas , Huesos/patología , Células Gigantes/patología , Neoplasias Primarias Secundarias/patología , Tumor Óseo de Células Gigantes/diagnóstico , Tumor Óseo de Células Gigantes/genética , Co-Represor 2 de Receptor Nuclear
7.
J Cutan Pathol ; 51(1): 70-75, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37666661

RESUMEN

BACKGROUND: Desmoplastic fibroblastoma (collagenous fibroma) is a rare soft tissue tumor that usually arises in the subcutis or skeletal muscle. Cases superficial to fascia are unusual and can cause diagnostic difficulty. We present 11 cases of superficial desmoplastic fibroblastoma involving a wide anatomic distribution. METHODS: Archives were searched using the term "desmoplastic fibroblastoma" over a 10-year period (2012-2022). Cases superficial to fascia were retrieved, and available clinicopathologic features were recorded. Only cases involving the dermis were included. RESULTS: Eleven cases were identified, all of which were received in consultation. Tumors involved the head and neck (2), lower extremity (2), back (2), foot (1), shoulder (1), axilla (1), hand (1), and breast (1). Each consisted of a hypocellular proliferation of bland stellate to spindled fibroblasts set in a collagenous to focally myxoid stroma. The immunohistochemical stains available for review demonstrated SMA positivity (4/7) and negative immunoreactivity for CD34 (0/6), EMA (0/3), desmin (0/3), and S100 (0/7). CONCLUSIONS: Desmoplastic fibroblastoma may present superficially in the dermis to subcutis, posing a potential source of diagnostic difficulty. Recognition of the characteristic histopathologic features of desmoplastic fibroblastoma with judicial use of immunohistochemical stains should allow for accurate diagnosis.


Asunto(s)
Fibroma Desmoplásico , Fibroma , Neoplasias de los Tejidos Blandos , Humanos , Fibroma Desmoplásico/patología , Fibroma/patología , Fibroblastos/patología , Neoplasias de los Tejidos Blandos/patología , Mama/patología
8.
Pathol Res Pract ; 249: 154777, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37639955

RESUMEN

BACKGROUND: Head and neck SFT (HNSFT) exhibit diverse histological features and can mimic various neoplasms with different treatment and behavior. While risk stratification systems have been developed for this tumor at various anatomic sites, a specific scheme for head and neck tumors is lacking. Our aim was to describe the histologic patterns present in HNSFT cases as well as assess the utility of risk assessment models in this location. METHODS: A retrospective review of pathology reports and microscopy glass slides of HNSFT cases diagnosed between January 2010 and August 2022 was performed.STAT6 was additionally performed on selected cases if needed. Follow up was obtained and various risk stratification models were applied. RESULTS: Sixty seven cases of HNSFT were collected (age range from 11 to 87 years; median 42 years; M:F 1.6:1). Most common tumor sites were orbit (n = 21; 31.3 %), sinonasal tract (n = 18; 26.9 %), and oral cavity (n = 13; 19.4 %). Tumor size ranged from 1 to 16 cm (median 4cm). Apart from common histological features, tumor cells also showed focal epithelioid morphology, clear cell change and nuclear atypia in a subset of cases. Stromal findings included myxoid and lipomatous change, pseudoglandular spaces, pseudovascular spaces and multinucleated stromal giant cells. CD34 and STAT6 were expressed in 57/67 (85.1 %) and 56/56 (100 %) cases, respectively. Recurrence was observed in 4/26 (15.4 %) cases, while none (0/22) of the patients experienced distant metastasis (follow up 1-150 months; median 20.5 months). Clinical outcome was partially concordant with risk-categories of different risk stratification models. CONCLUSION: Knowledge about histological diversity of HNSFT is essential for establishing correct diagnosis. Current risk stratification models do not perfectly predict outcome, and larger studies are needed to develop more accurate criteria for aggressive behavior.


Asunto(s)
Hemangiopericitoma , Lipoma , Tumores Fibrosos Solitarios , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Boca , Antígenos CD34
9.
Open Forum Infect Dis ; 10(5): ofad190, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37180592

RESUMEN

Background: COVID-19 presents with a breadth of symptomatology including a spectrum of clinical severity requiring intensive care unit (ICU) admission. We investigated the mucosal host gene response at the time of gold standard COVID-19 diagnosis using clinical surplus RNA from upper respiratory tract swabs. Methods: Host response was evaluated by RNA-sequencing, and transcriptomic profiles of 44 unvaccinated patients including outpatients and in-patients with varying levels of oxygen supplementation were included. Additionally, chest X-rays were reviewed and scored for patients in each group. Results: Host transcriptomics revealed significant changes in the immune and inflammatory response. Patients destined for the ICU were distinguished by the significant upregulation of immune response pathways and inflammatory chemokines, including cxcl2 which has been linked to monocyte subsets associated with COVID-19 related lung damage. In order to temporally associate gene expression profiles in the upper respiratory tract at diagnosis of COVID-19 with lower respiratory tract sequalae, we correlated our findings with chest radiography scoring, showing nasopharygeal or mid-turbinate sampling can be a relevant surrogate for downstream COVID-19 pneumonia/ICU severity. Conclusions: This study demonstrates the potential and relevance for ongoing study of the mucosal site of infection of SARS-CoV-2 using a single sampling that remains standard of care in hospital settings. We highlight also the archival value of high quality clinical surplus specimens, especially with rapidly evolving COVID-19 variants and changing public health/vaccination measures.

10.
Health SA ; 28: 2163, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36873781

RESUMEN

Background: Antenatal care is essential for all expectant mothers and assists in reducing maternal mortality rates thus addressing the Sustainable Development Goal 3. Obstetric ultrasound complements antenatal care and is used in pregnancy to identify and monitor high-risk pregnancies. However, disparities exist and in low- and middle-income countries, ultrasound services are not readily available. This contributes to maternal and neonatal morbidity and mortality within these populations. Short ultrasound training programmes for midwives can be beneficial in alleviating some of the challenges experienced. Aim: The aim of this scoping review was to identify global ultrasound education programmes for midwives. Method: Articles containing suitable keywords were retrieved from databases suitable to nursing, education and ultrasound. Themes were developed based on the articles included in the review. Results: A total of 238 articles were identified, and after the duplicates and irrelevant studies were removed, 22 articles were included. Articles were analysed and discussed under the identified themes and categories. Conclusion: It is essential that sufficient training is provided to medical professionals performing obstetric ultrasound so that adequate and safe care is offered to expectant mothers. With the introduction of ultrasound in low-resource settings, the knowledge of safety and competencies required to operate the equipment necessitate adequate training. Developed programmes have been found to meet the demands of the ever-changing workforce and allow for midwives to perform focused obstetric ultrasound examinations. Contribution: This scoping review highlighted ultrasound training programmes for midwives and provided guidance on the development of future midwifery ultrasound training programmes.

11.
J Feline Med Surg ; 24(8): e289-e294, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35703473

RESUMEN

OBJECTIVES: Current blood tests to diagnose feline liver diseases are suboptimal. Serum concentrations of microRNA (miR)-122 have been shown in humans, dogs and rodents to be a sensitive and specific biomarker for liver injury. To explore the potential diagnostic utility of measuring serum concentrations of miR-122 in cats, miR-122 was measured in a cohort of ill, hospitalised cats with known serum alanine aminotransferase (ALT) activity. METHODS: In this retrospective study, cats were grouped into those with an ALT activity within the reference interval (0-83 U/l; n = 38) and those with an abnormal ALT activity (>84 U/l; n = 25). Serum concentrations of miR-122 were measured by real-time quantitative PCR and the relationship between miR-122 and ALT was examined. RESULTS: miR-122 was significantly higher in the group with high ALT activity than the ALT group, within normal reference limits (P <0.0004). There was also a moderately positive correlation between serum ALT activity and miR-122 concentrations (P <0.001; r = 0.52). CONCLUSIONS AND RELEVANCE: Concentrations of miR-122 were reliably quantified in feline serum and were higher in a cohort of cats with increased ALT activity than in cats with normal ALT activity. This work highlights the potential diagnostic utility of miR-122 as a biomarker of liver damage in cats and encourages further investigation to determine the sensitivity and specificity of miR-122 as a biomarker of hepatocellular injury in this species.


Asunto(s)
Enfermedades de los Gatos , Enfermedades de los Perros , Hepatopatías , MicroARNs , Alanina Transaminasa , Animales , Biomarcadores , Enfermedades de los Gatos/diagnóstico , Gatos , Enfermedades de los Perros/diagnóstico , Perros , Hepatopatías/veterinaria , MicroARNs/genética , Estudios Retrospectivos
12.
SAGE Open Nurs ; 8: 23779608221097162, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35547862

RESUMEN

Introduction: Clinical nursing education is an important component of the professional development of nursing students. Key informants such as nursing lecturers, nurse managers and clinical placement coordinators play an essential role in clinical education. Purpose: The purpose of the study was to explore the perspectives of key informants on how the current state of clinical nursing education in Northern Ghana can be improved. Methods: The study used an exploratory qualitative design. Sixteen participants were purposively selected and data were collected through face-to-face individual interviews. Data were analysed using framework analysis. Findings: The study findings indicate that clinical nursing education can be improved by decreasing the overcrowding of students in the clinical setting, decreasing the theory-practice gap and providing relevant material resources in the clinical facilities. Also, nursing education institutions can improve clinical nursing education by equipping the skills laboratories, engaging an adequate number of lecturers, and carrying out clinical accompaniment. Conclusion: There is a need to improve clinical education through collaboration between nursing education institutions and clinical facilities. Effective collaboration will ensure the planning of clinical placement to avoid overcrowding, provision of continuous professional development programmes for preceptors and improvement in clinical supervision. Also, the provision of material resources in skills laboratories and clinical facilities to enhance clinical teaching should be given priority.

13.
Pathogens ; 10(10)2021 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-34684195

RESUMEN

A proportion of patients with COVID-19 have symptoms past the acute disease phase, which may affect quality of life. It is important for clinicians to be aware of this "long-COVID-19" syndrome to better diagnose, treat, and prevent it. We reviewed clinical and laboratory characteristics of a COVID-19 cohort in a Toronto, Ontario tertiary care center. Demographic, clinical, and laboratory data were collected, and patients were classified as "long-COVID-19" or "non-long-COVID-19" using consensus criteria. Of 397 patients who tested positive for COVID-19, 223 met inclusion criteria, and 62 (27%) had long-COVID-19. These patients had a similar age distribution compared to non-long-COVID-19 patients overall but were younger in the admitted long COVID-19 group. The long-COVID-19 group had more inpatients compared to the non-long-COVID-19 group (39% vs. 25%) and more frequent supplemental oxygen or mechanical ventilation use. However, long-COVID-19 patients did not differ by duration of mechanical ventilation, length of stay, comorbidities, or values of common laboratory tests ordered. The most frequent symptoms associated with long-COVID-19 were fatigue and weakness, as reported most commonly by the infectious disease, respirology and cardiology disciplines. In conclusion, by retrospective chart review, 27% of COVID-19 patients presenting to a tertiary care center in Toronto, Canada, were found to meet criteria for long-COVID-19. Past medical history and routine laboratory testing at presentation did not predict for long-COVID-19 development.

14.
Acad Pathol ; 8: 23742895211013533, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34027056

RESUMEN

Despite global digitization, evaluating pathology trainees by paper exams remains the norm. As new social distancing practices require new ways of administering exams, we assessed the viability of an online format for in-house exams from the resident and examiner perspectives. First, pathology residents participated in a practice exam, while staff who were experienced in creating exams were given an online exam-creation demonstration. Subsequently, residents completed a formal 3-hour online exam comprised of multiple-choice, matching, short answer, and whole slide images in place of the paper exam regularly used to evaluate trainees. The experience of the participants was evaluated by surveys. Eighteen residents completed the practice exam; 67% were receptive to the new format and 94% were in favor of moving to digital exams. Seven staff evaluated the digital format and 6 were in favor of it. For the formal online in-house exam, 20 residents participated and 14 completed the survey. Feedback was generally positive with the most common issue being slow-loading digital slides. Exam scores stratified by postgraduate training years in a statistically significant manner, showing positive correlation with resident training level. The online exam format was preferred over paper exams by trainees, with support from both staff and trainees for a permanent transition. Online exams have clear advantages, but technical issues should be addressed before widespread implementation. Our study demonstrates that online exams are a feasible alternative for trainee assessment, especially in socially distanced environments.

16.
J Exp Bot ; 72(8): 3012-3027, 2021 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-33502451

RESUMEN

Meiosis generates genetic variation through homologous recombination (HR) that is harnessed during breeding. HR occurs in the context of meiotic chromosome axes and the synaptonemal complex. To study the role of axis remodelling in crossover (CO) formation in a crop species, we characterized mutants of the axis-associated protein ASY1 and the axis-remodelling protein PCH2 in Brassica rapa. asy1 plants form meiotic chromosome axes that fail to synapse. CO formation is almost abolished, and residual chiasmata are proportionally enriched in terminal chromosome regions, particularly in the nucleolar organizing region (NOR)-carrying chromosome arm. pch2 plants show impaired ASY1 loading and remodelling, consequently achieving only partial synapsis, which leads to reduced CO formation and loss of the obligatory CO. PCH2-independent chiasmata are proportionally enriched towards distal chromosome regions. Similarly, in Arabidopsis pch2, COs are increased towards telomeric regions at the expense of (peri-) centromeric COs compared with the wild type. Taken together, in B. rapa, axis formation and remodelling are critical for meiotic fidelity including synapsis and CO formation, and in asy1 and pch2 CO distributions are altered. While asy1 plants are sterile, pch2 plants are semi-sterile and thus PCH2 could be an interesting target for breeding programmes.


Asunto(s)
Brassica rapa , Recombinación Homóloga , Meiosis , Brassica rapa/genética , Emparejamiento Cromosómico , Proteínas de Unión al ADN/genética , Meiosis/genética , Fitomejoramiento , Complejo Sinaptonémico/genética
17.
J Immunother Cancer ; 9(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33483342

RESUMEN

PURPOSE: Anti-programmed cell death protein 1 (PD1)±anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint inhibitors (ICIs) are standard therapeutic options for metastatic melanoma. We assessed whether biologic subtype according to primary tumor type or genomic subtype can function as predictive biomarkers for anti-PD1±anti-CTLA4 ICI in patients with advanced melanoma. METHODS: We performed a single-center retrospective cohort analysis of patients who received anti-PD1±anti-CTLA4 ICI for advanced melanoma between 2012 and 2019. Primary tumor type, BRAF and NRAS mutation status, and other covariates were abstracted from chart review. Log-rank tests and multivariable Cox regression models were used to assess differences in clinical progression-free (cPFS) and overall survival (OS). RESULTS: We identified 230 patients who received 249 lines of anti-PD1±anti-CTLA4 ICI for unresectable or metastatic disease. Of these patients, 74% were cutaneous, 11% mucosal, 8% unknown primary and 7% acral. BRAF and NRAS mutations were identified in 35% and 28% of patients, respectively. In multivariable analyses of the entire cohort, acral or mucosal primary tumor type, >3 metastatic sites, elevated LDH were predictive of shorter cPFS and OS. Combination ICI therapy was associated with longer cPFS (HR 0.57, 95% CI 0.38 to 0.86, p=0.007) and OS (HR 0.42, 95% CI 0.28 to 0.65, p<0.001). Combination ICI was significantly associated with longer OS in unknown primary and mucosal melanoma. There was a non-significant trend toward longer OS with anti-PD1+anti-CTLA4 in cutaneous melanoma, but not in acral melanoma. In multivariable analyses, combination ICI was associated with longer OS in NRAS (HR 0.24, 95% CI 0.10 to 0.62, p=0.003, n=69) and BRAF V600E/K (HR 0.47, 95% CI 0.24 to 0.90, p=0.024, n=86) mutant melanoma but not BRAF/NRAS wild-type (n=94) melanoma. CONCLUSIONS: In our cohort, primary melanoma tumor type and genomic subtype were independent predictive markers of cPFS and OS for patients with metastatic melanoma receiving anti-PD1 ICI. Primary tumor type and genomic subtype-including NRAS-should be further evaluated in prospective clinical trials to determine their value as predictive markers. Biologic subtypes may facilitate clinical decision-making when recommending combination ICI treatment (anti-PD1±anti-CTLA4) versus anti-PD1 alone for patients with metastatic melanoma.


Asunto(s)
GTP Fosfohidrolasas/genética , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Ipilimumab/administración & dosificación , Melanoma/tratamiento farmacológico , Proteínas de la Membrana/genética , Nivolumab/administración & dosificación , Proteínas Proto-Oncogénicas B-raf/genética , Sinergismo Farmacológico , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Ipilimumab/farmacología , Masculino , Melanoma/clasificación , Melanoma/genética , Mutación , Metástasis de la Neoplasia , Nivolumab/farmacología , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento
18.
Front Endocrinol (Lausanne) ; 12: 795184, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34975765

RESUMEN

Objective: The main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population. Methods: Patients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome. Results: In total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p<0.001), extra-thyroidal extension (HR 24.95; p<0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p<0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease. Conclusion: We present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.


Asunto(s)
Adenoma Oxifílico/patología , Radioisótopos de Yodo/uso terapéutico , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Adenoma Oxifílico/radioterapia , Adenoma Oxifílico/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia/patología , Estudios Retrospectivos , Cáncer Papilar Tiroideo/radioterapia , Cáncer Papilar Tiroideo/cirugía , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Resultado del Tratamiento
19.
New Phytol ; 229(6): 3281-3293, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33020949

RESUMEN

Ensuring faithful homologous recombination in allopolyploids is essential to maintain optimal fertility of the species. Variation in the ability to control aberrant pairing between homoeologous chromosomes in Brassica napus has been identified. The current study exploited the extremes of such variation to identify genetic factors that differentiate newly resynthesised B. napus, which is inherently unstable, and established B. napus, which has adapted to largely control homoeologous recombination. A segregating B. napus mapping population was analysed utilising both cytogenetic observations and high-throughput genotyping to quantify the levels of homoeologous recombination. Three quantitative trait loci (QTL) were identified that contributed to the control of homoeologous recombination in the important oilseed crop B. napus. One major QTL on BnaA9 contributed between 32 and 58% of the observed variation. This study is the first to assess homoeologous recombination and map associated QTLs resulting from deviations in normal pairing in allotetraploid B. napus. The identified QTL regions suggest candidate meiotic genes that could be manipulated in order to control this important trait and further allow the development of molecular markers to utilise this trait to exploit homoeologous recombination in a crop.


Asunto(s)
Brassica napus , Brassica napus/genética , Cromosomas de las Plantas/genética , Genoma de Planta , Poliploidía , Sitios de Carácter Cuantitativo/genética
20.
BMJ Open ; 10(6): e035580, 2020 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-32554723

RESUMEN

OBJECTIVES: The implementation of advanced practice nursing (APN) programmes in sub-Saharan Africa (SSA) has been difficult due to lack of SSA-specific curriculum frameworks or benchmarks to guide institutions in developing and implementing APN programmes. A few APN programmes in SSA were benchmarked on western philosophy and materials, making local ownership and sustainability challenging. This paper presents an SSA-specific concept-based APN (Child Health Nurse Practitioner, CHNP) curriculum framework developed to guide institutions in developing relevant and responsive APN curricula in order to qualify CHNP and contribute to a decreased incidence of preventable deaths of children in the SSA region. DESIGN: A sequential multimethod study design consisting of a scoping review, Delphi study, development of a framework by a curriculum team, and evaluation of the curriculum framework by faculty from 15 universities in SSA. SETTING: This study included universities from East, West, Central and Southern Africa. PARTICIPANTS: The study included international multidisciplinary health professionals and curriculum development experts from 15 universities in 10 SSA countries. RESULTS: A concept-based Advanced CHNP curriculum framework was developed. The faculty who evaluated the curriculum framework for applicability within their institutions and the SSA context unanimously stated that the framework is detailed, evidenced-based and could be adapted for other APN specialty areas. CONCLUSION: The Child Health Nurse Practitioner curriculum framework is comprehensive, context-specific and has the potential to respond to the special child healthcare needs of SSA. It is adaptable for other APN specialty programmes in SSA. Nursing leaders should lobby for funding and advocate for the introduction of the CHNP programme as a collaborative process between government, clinical services, communities and educational institutions.


Asunto(s)
Enfermería de Práctica Avanzada/educación , Curriculum , Educación de Postgrado en Enfermería/organización & administración , África del Sur del Sahara , Técnica Delphi , Humanos
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