37 research outputs found
Histological characteristics of HPV-associated and -independent squamous cell carcinomas of the vulva: A study of 1594 cases
There are at least two different etio-pathogenic pathways for
the development of vulvar squamous cell carcinoma (VSCC): one
associated with infection by human papillomavirus (HPV) and
another independent of HPV. We aimed to describe the
histological characteristics of HPV-associated and
HPV-independent tumors and to determine the best strategy to
identify HPV in VSCC. A single paraffin block was available for
review from a series of 1594 VSCCs. In all cases HPV DNA
detection was analyzed using the SPF10PCR/DEIA/LiPA25 system and
p16 immunohistochemistry (IHC). A tumor was considered as
unquestionably HPV-associated if both HPV DNA and p16 IHC were
positive. A tumor was considered indisputably HPV-independent if
both HPV DNA and p16 IHC were negative. Two groups of tumors
were classified as non-conclusive: 1) HPV DNA+/p16-; and 2) HPV
DNA-/p16+. WHO typing and a thorough histological evaluation
were conducted in all cases. 441 tumors were HPV DNA+ with 367
cases (23.0%) being HPV DNA+/p16+. These HPV DNA+/p16+ tumors
were more frequently basaloid or warty (49.8%), but 36.5% were
of the keratinizing type. 1153 tumors were HPV DNA-, with 1060
cases (66.5%) being HPV DNA-/p16-. These HPV DNA-/p16- tumors
were mostly keratinizing (81.2%) but were occasionally basaloid
or warty (5.2%). The features of HPV DNA-/p16+ cases (n=93) were
similar to those of the HPV-associated VSCC, and HPV DNA+/p16-
(n=74) cases had a more diverse profile, although they were more
similar to HPV-independent tumors. Several histological
characteristics were more frequently associated with HPV-related
VSCC (koilocytotic-like change, necrosis, moderate to marked
pleomorphism, invasive front in nests; p<0.001), however,
none of these characteristics allowed differentiation between
HPV-associated and -independent VSCC. In conclusion,
histological criteria do not allow differentiation between
HPV-associated and -independent VSCC. p16 alone is a clinically
easy strategy to determine HPV status in VSCC. This article is
protected by copyright. All rights reserved
Reprogramming human T cell function and specificity with non-viral genome targeting.
Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells
HPV-independent Precursors Mimicking High-grade Squamous intraepithelial Lesions (HSIL) of the Vulva
Two etiopathogenic types of vulvar squamous cell carcinoma (VSCC) have been described: human papillomavirus (HPV)-associated and HPV-independent. Precursor lesions, frequently identified in the adjacent skin, are also distinct in the 2 types of VSCC: high-grade squamous intraepithelial lesions
(HSILs) in HPV-associated VSCC and differentiated vulvar
intraepithelial neoplasia (dVIN) or vulvar acanthosis with
altered differentiation in HPV-independent VSCC. Although
HPV-independent precursors mimicking HSIL have been described in
the vulva, their frequency and morphologic spectrum have not
been completely characterized. We explored, in a large series of
HPV-independent VSSC, the frequency and the histologic features
of precursors mimicking HSIL. We included 779 DNA
HPV-negative/p16-negative VSCC with at least 1\xE2\x80\x89cm of
adjacent skin. We evaluated the histologic and
immunohistochemical (p16 and p53) characteristics of the
intraepithelial lesions, focusing on precursors mimicking
HPV-associated vulvar HSIL. A total of 254 tumors (33%) had
adjacent premalignant lesions. Of them, 186 (73%) had dVIN, 22
(9%) had vulvar acanthosis with altered differentiation, and 46
(18%) had lesions that mimicked HSIL. The mean age of the
patients with these HSIL-like lesions was 72\xC2\xB115 years.
Twenty-six of these HSIL-like lesions had basaloid morphology,
13 warty, and 7 mixed basaloid/warty features. All the HSIL-like
precursors were DNA HPV-negative/p16-negative; 74% of them
showed p53 abnormal staining and 35% of them had areas of
conventional dVIN. In conclusion, about one fifth of the
HPV-independent precursors mimic HSIL, showing either basaloid
or warty features. Older age and the presence of areas of
typical HPV-independent intraepithelial lesions, together with
p16 negativity, should raise suspicion of an HPV-independent
etiology
Physiological and anthocyanin biosynthesis genes response induced by vanadium stress in mustard genotypes with distinct photosynthetic activity
The present study aimed to elucidate the photosynthetic performance, antioxidant enzyme activities, anthocyanin contents, anthocyanin biosynthetic gene expression, and vanadium uptake in mustard genotypes (purple and green) that differ in photosynthetic capacity under vanadium stress. The results indicated that vanadium significantly reduced photosynthetic activity in both genotypes. The activities of the antioxidant enzymes were increased significantly in response to vanadium in both genotypes, although the purple exhibited higher. The anthocyanin contents were also reduced under vanadium stress. The anthocyanin biosynthetic genes were highly expressed in the purple genotype, notably the genes TT8, F3H, and MYBL2 under vanadium stress. The results indicate that induction of TT8, F3H, and MYBL2 genes was associated with upregulation of the biosynthetic genes required for higher anthocyanin biosynthesis in purple compared with the green mustard. The roots accumulated higher vanadium than shoots in both mustard genotypes. The results indicate that the purple mustard had higher vanadium tolerance
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A Qualitative Study of Multilevel Faculty Motivations for Pursuing Engaged Scholarship
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Comparing the efficacies of alginate, foam, hydrocolloid, hydrofiber, and hydrogel dressings in the management of diabetic foot ulcers and venous leg ulcers: a systematic review and meta-analysis examining how to dress for success
Diabetic foot ulcers and venous leg ulcers are chronic wounds frequently encountered by dermatologists. Choosing appropriate wound dressings can effectively promote wound healing and potentially reduce morbidity and financial burden experienced by patients. The objective of our systematic review and meta-analysis was to evaluate wound healing efficacies of synthetic active dressings in diabetic foot ulcer and venous leg ulcer management. For data collection, PubMed, Embase, Cochrane Library, CINAHL, and clinicaltrials.gov online databases were searched from database inception to 10 May 2015. Fixed and random effects modeling were used to calculate pooled risk ratios for complete ulcer healing from pairwise dressing comparisons. The results of our review showed moderate-quality level evidence that hydrogels were more effective in healing diabetic foot ulcers than basic wound contact dressings (RR 1.80 [95% CI, 1.27-2.56]). The other dressing comparisons showed no statistically significant differences between the interventions examined in terms of achieving complete diabetic foot ulcer healing. Non-adherent dressings were more cost-effective than hydrofiber dressings for diabetic foot ulcers in terms of mean total cost per patient of the dressings themselves. All venous leg ulcer pairwise dressing comparisons showed equivalent dressing efficacies in terms of promoting complete ulcer healing. Overall, most synthetic active dressings and traditional wound dressings are equally efficacious in treating diabetic foot ulcers and venous leg ulcers. For treating diabetic foot ulcers, hydrogels are more efficacious than basic wound contact dressings, and non-adherent dressings are more cost-effective than hydrofiber dressings. Ultimately, dressing choice should be tailored to the wound and the patien
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Adenoid Cystic Carcinoma of the Base of the Tongue Metastasizing to the Scalp
Adenoid cystic carcinoma is a rare neoplasm that originates from secretory glands, most commonly from the salivary glands. We present a 76 year-old white man with a history of adenoid cystic carcinoma from the base of the tongue diagnosed 15 years prior to the development of the metastatic lesion on his mid-posterior scalp. The present case represents the second reported instance of an extracutaneous adenoid cystic carcinoma metastasizing to the scalp. Differentiating between a primary cutaneous adenoid cystic carcinoma and an extracutaneous adenoid cystic carcinoma metastasizing to cutaneous structures is crucial in determining prognosis and management
Targeting Representation: Interpreting Calls for Diversity in Precision Medicine Research.
Scientists have identified a diversity gap in genetic samples and health data, which have been drawn predominantly from individuals of European ancestry, as posing an existential threat to the promise of precision medicine. Inadequate inclusion as articulated by scientists, policymakers, and ethicists has prompted large-scale initiatives aimed at recruiting populations historically underrepresented in biomedical research. Despite explicit calls to increase diversity, the meaning of diversity - which dimensions matter for what outcomes and why - remain strikingly imprecise. Drawing on our document review and qualitative data from observations and interviews of funders and research teams involved in five precision medicine research (PMR) projects, we note that calls for increasing diversity often focus on representation as the goal of recruitment. The language of representation is used flexibly to refer to two objectives: achieving sufficient genetic variation across populations and including historically disenfranchised groups in research. We argue that these dual understandings of representation are more than rhetorical slippage, but rather allow for the contemporary collection of samples and data from marginalized populations to stand in as correcting historical exclusion of social groups towards addressing health inequity. We trace the unresolved historical debates over how and to what extent researchers should procure diversity in PMR and how they contributed to ongoing uncertainty about what axes of diversity matter and why. We argue that ambiguity in the meaning of representation at the outset of a study contributes to a lack of clear conceptualization of diversity downstream throughout subsequent phases of the study
Dibujo Arquitect贸nico - AR286 - 202100
Descripci贸n:
Curso de especialidad en la carrera de Arquitectura y el segundo curso dentro del 谩rea de Expresi贸n Gr谩fica. El
curso-taller de Dibujo Arquitect贸nico y se sustenta en la identificaci贸n, interpretaci贸n y uso del lenguaje
arquitect贸nico, por lo que se desarrolla de manera te贸rica y pr谩ctica. Este lenguaje permite a los arquitectos
desarrollar una idea, transmitir y conseguir la comprensi贸n y aceptaci贸n de sus dise帽os adem谩s de facilitar las
instrucciones que permiten la construcci贸n del proyecto dise帽ado. En este proceso de dise帽o, es indispensable
familiarizarse con los c贸digos, las t茅cnicas gr谩ficas y dem谩s recursos universalmente aceptados.
Por la naturaleza del curso es un Taller porque implica ser pr谩ctico y vivencial, adem谩s del dinamismo que
implica al crear a partir de la teor铆a diferentes evidencias; este material producido por los participantes es donde
se aprecia de manera clara la aplicaci贸n de lo aprendido.
Prop贸sito:
El curso-taller tiene como prop贸sito contribuir al perfil profesional del estudiante en el uso y la comprensi贸n de
la simbolog铆a y el lenguaje gr谩fico-arquitect贸nico como base fundamental para la comunicaci贸n y ejecuci贸n del
dise帽o arquitect贸nico, el desarrollo de su formaci贸n acad茅mica y su labor proyectual, desarrollando las
competencias espec铆ficas de la carrera de Pensamiento Cr铆tico & Representaci贸n y Desarrollo de Pr谩cticas
Constructivas, Habilidades T茅cnicas & Conocimiento, ambas en el nivel 1. Asimismo, contribuye al desarrollo
de las capacidades de NAAB (A1): Habilidades comunicativas profesionales y (B4) Documentaci贸n t茅cnica.
Tiene como requisito el curso AR287 Expresi贸n art铆stica y Espacial.
Histological characteristics of HPV-associated and -independent squamous cell carcinomas of the vulva: A study of 1594 cases
There are at least two different etio-pathogenic pathways for
the development of vulvar squamous cell carcinoma (VSCC): one
associated with infection by human papillomavirus (HPV) and
another independent of HPV. We aimed to describe the
histological characteristics of HPV-associated and
HPV-independent tumors and to determine the best strategy to
identify HPV in VSCC. A single paraffin block was available for
review from a series of 1594 VSCCs. In all cases HPV DNA
detection was analyzed using the SPF10PCR/DEIA/LiPA25 system and
p16 immunohistochemistry (IHC). A tumor was considered as
unquestionably HPV-associated if both HPV DNA and p16 IHC were
positive. A tumor was considered indisputably HPV-independent if
both HPV DNA and p16 IHC were negative. Two groups of tumors
were classified as non-conclusive: 1) HPV DNA+/p16-; and 2) HPV
DNA-/p16+. WHO typing and a thorough histological evaluation
were conducted in all cases. 441 tumors were HPV DNA+ with 367
cases (23.0%) being HPV DNA+/p16+. These HPV DNA+/p16+ tumors
were more frequently basaloid or warty (49.8%), but 36.5% were
of the keratinizing type. 1153 tumors were HPV DNA-, with 1060
cases (66.5%) being HPV DNA-/p16-. These HPV DNA-/p16- tumors
were mostly keratinizing (81.2%) but were occasionally basaloid
or warty (5.2%). The features of HPV DNA-/p16+ cases (n=93) were
similar to those of the HPV-associated VSCC, and HPV DNA+/p16-
(n=74) cases had a more diverse profile, although they were more
similar to HPV-independent tumors. Several histological
characteristics were more frequently associated with HPV-related
VSCC (koilocytotic-like change, necrosis, moderate to marked
pleomorphism, invasive front in nests; p<0.001), however,
none of these characteristics allowed differentiation between
HPV-associated and -independent VSCC. In conclusion,
histological criteria do not allow differentiation between
HPV-associated and -independent VSCC. p16 alone is a clinically
easy strategy to determine HPV status in VSCC. This article is
protected by copyright. All rights reserved