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1.
Cell Rep ; 43(7): 114452, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38968068

RESUMO

Macrophages are effector immune cells that experience substantial changes to oxygenation when transiting through tissues, especially when entering tumors or infected wounds. How hypoxia alters gene expression and macrophage effector function at the post-transcriptional level remains poorly understood. Here, we use TimeLapse-seq to measure how inflammatory activation modifies the hypoxic response in primary macrophages. Nucleoside recoding sequencing allows the derivation of steady-state transcript levels, degradation rates, and transcriptional synthesis rates from the same dataset. We find that hypoxia produces distinct responses from resting and inflammatory macrophages. Hypoxia induces destabilization of mRNA transcripts, though inflammatory macrophages substantially increase mRNA degradation compared to resting macrophages. Increased RNA turnover results in the upregulation of ribosomal protein genes and downregulation of extracellular matrix components in inflammatory macrophages. Pathways regulated by mRNA decay in vitro are differentially regulated in tumor-associated macrophages implying that mixed stimuli could induce post-transcriptional regulation of macrophage function in solid tumors.

2.
Eur J Haematol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780264

RESUMO

BACKGROUND: This study aimed to determine whether implementing a rapid response system (RRS) is associated with improved short-term outcomes in critically ill patients with haematological malignancies. METHODS: Our monocentric pre- versus post-intervention study was conducted between January 2012 and April 2020. RRS was activated at early signs of haemodynamic or respiratory failure. The primary outcome was the reduction in Sequential Organ Failure Assessment (SOFA) score on Day 3 after intensive care unit (ICU) admission. Secondary outcomes included time to ICU admission and mortality. RESULTS: A total of 209 patients with a median age of 59 years were enrolled (108 in the pre-intervention period and 101 in the post-intervention period). 22% of them had received an allogeneic transplant. The post-intervention period was associated with a shorter time to ICU admission (195 vs. 390 min, p < .001), a more frequent favourable trend in SOFA score (57% vs. 42%, adjusted odds ratio, 2.02, 95% confidence interval, 1.09 to 3.76), no significant changes in ICU (22% vs. 26%, p = .48) and 1-year (62% vs. 58%, p = .62) mortality rates. CONCLUSION: Detection of early organ failure and activation of an RRS was associated with faster ICU admission and lower SOFA scores on Day 3 of admission in critically ill patients with haematological malignancies.

3.
Public Health ; 226: 84-90, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38016200

RESUMO

OBJECTIVES: The association between asthma and COVID-19 mortality remains inconclusive. We examined the association between asthma and clinical outcomes of patients with COVID-19. STUDY DESIGN: A case-control study based on a surveillance cohort in Harris County, Texas. METHODS: Using the data of 21,765 patients who reported having at least one chronic health condition, we investigated the association between asthma and COVID-19 severity, characterized primarily by hospitalization and death. Unconditional logistic regression models were used to estimate the multivariable odds ratio (mOR) and its 95 % confidence interval (CI) of COVID-19 severity associated with asthma and other chronic lung diseases, adjusting for demographic and other comorbidities. A P-value < 0.005 was considered statistically significant after correcting multiple testing. RESULTS: In total, 3034 patients (13.9 %) had asthma, and 774 (3.56 %) had other chronic lung diseases. The case death rate among patients with asthma and other chronic lung diseases was 0.75 % and 19.0 %, respectively. Compared to patients without the respective conditions, patients with asthma had lower odds of death (mOR = 0.44, 95 % CI: 0.27-0.69), while patients with other chronic lung diseases had higher odds of hospitalization (mOR = 2.02, 95 % CI: 1.68-2.42) and death (mOR = 1.95, 95 % CI: 1.52-2.49) (P-values < 0.005). Risk factors for COVID-19 mortality included older age, male gender, diabetes, obesity, hypertension, cardiovascular disease, active cancer, and chronic kidney disease. CONCLUSIONS: The public health surveillance data suggested that preexisting asthma was inversely associated with COVID-19 mortality.


Assuntos
Asma , COVID-19 , Humanos , Masculino , COVID-19/epidemiologia , Comorbidade , Estudos de Casos e Controles , SARS-CoV-2 , Asma/epidemiologia , Fatores de Risco , Hospitalização , Estudos Retrospectivos
4.
Int Forum Allergy Rhinol ; 14(2): 149-608, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37658764

RESUMO

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.


Assuntos
Neoplasias de Cabeça e Pescoço , Hipersensibilidade , Neoplasias dos Seios Paranasais , Humanos , Qualidade de Vida , Neoplasias dos Seios Paranasais/terapia , Neoplasias dos Seios Paranasais/patologia
5.
Rev Mal Respir ; 40(8): 692-699, 2023 Oct.
Artigo em Francês | MEDLINE | ID: mdl-37659881

RESUMO

In medicine, each decision is the result of a trade-off between medical scientific data, the rights of individuals (protection of persons, information, consent), individual desires, collective values and norms, and the economic constraints that guide our society. Whether or not to admit a cancer patient to an intensive care unit is very often an ethical dilemma. It is necessary to distinguish patients who would benefit from admission to an intensive care unit (ICU) from those for whom it would be futile. In this review, we will discuss the appropriateness of ICU admission and the concept of unreasonable admission, along with the different levels of intensity of ICU care and the alternatives to intensive care. We will then consider how and when to initiate reflection leading to a reasonable decision for the patient.

6.
Can Vet J ; 64(6): 545-548, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37265818

RESUMO

A 6-year-old neutered male bloodhound dog was presented for surgical evaluation of an intraoral hard palate mass noted during a routine dental cleaning performed by the primary veterinarian. Computed tomography (CT) of the skull revealed a well-defined, multilobular, mineralized mass with a coarse, granular appearance, centered along the palatomaxillary suture extending into both the nasal and oral cavities. Bilateral caudal maxillectomy was performed for curative-intent resection of the tumor. The histopathology of the mass was consistent with a completely excised palatomaxillary multilobular tumor of bone (MLTB). This is apparently the 1st successful report of surgical excision of an MLTB associated with the palatomaxillary suture line. Key clinical message: Our findings emphasized that MLTB should be considered as a differential diagnosis for masses arising in the location of cranial sutures, and a definitive diagnosis can be made postoperatively with histopathology of the mass.


Tumeur osseuse multi-lobulaire résultant de la ligne de suture palato-maxillaire dans le crâne d'un chien. Un chien Saint-Hubert mâle castré de 6 ans a été présenté pour évaluation chirurgicale d'une masse intrabuccale du palais dur notée lors d'un nettoyage dentaire de routine effectué par le vétérinaire initial. La tomodensitométrie (CT) du crâne a révélé une masse minéralisée multi-lobulaire bien définie avec un aspect grossier et granuleux, centrée le long de la suture palato-maxillaire s'étendant dans les cavités nasale et buccale. Une maxillectomie caudale bilatérale a été réalisée pour une résection à visée curative de la tumeur. L'histopathologie de la masse était compatible avec une tumeur osseuse multi-lobulaire palato-maxillaire complètement excisée (MLTB). Il s'agit apparemment du premier rapport réussi d'excision chirurgicale d'une MLTB associé à la ligne de suture palato-maxillaire.Message clinique clé :Nos résultats ont souligné que la MLTB doit être considérée comme un diagnostic différentiel pour les masses apparaissant à l'emplacement des sutures crâniennes, et un diagnostic définitif peut être posé en postopératoire avec l'histopathologie de la masse.(Traduit par Dr Serge Messier).


Assuntos
Neoplasias Ósseas , Doenças do Cão , Masculino , Cães , Animais , Suturas Cranianas , Crânio , Neoplasias Ósseas/veterinária , Suturas , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia
7.
J Comp Pathol ; 202: 8-15, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37018925

RESUMO

Proliferative tenosynovitis (PT) is an inflammatory and proliferative disorder of the synovial membrane of the tendon sheath that is rare in animals. The histological alterations are characterized by multinodular neovascularization, with infiltration of histiocytic and multinucleated giant cells and haemosiderin deposition. We reviewed necropsy and biopsy records of horses submitted to the Setor de Anatomia Patológica of the Universidade Federal Rural do Rio de Janeiro from January 2017 to December 2020 to select cases of PT. We identified PT in three adult Brazilian Mangalarga Marchador horses with nodular lesions on the metacarpophalangeal, metatarsophalangeal or carpal joints. The three horses were under 6 years of age and presented with lameness and pain on palpation. There were recurrences in two horses after surgical removal. Radiographic and ultrasound examinations detected masses in the flexor or extensor tendons and subtendinous bursa. Histological study of synovial membrane and tendon sheath revealed an increased number of vessels, fibroplasia, osseous metaplasia and infiltration of lymphocytes, plasma cells and siderophages. This is the first description of PT in horses, which should be included as an orthopaedic differential diagnosis, especially in Mangalarga Marchador horses with lameness.


Assuntos
Doenças dos Cavalos , Tenossinovite , Cavalos , Animais , Tenossinovite/veterinária , Tenossinovite/diagnóstico , Tenossinovite/patologia , Coxeadura Animal/patologia , Coxeadura Animal/cirurgia , Brasil , Tendões , Doenças dos Cavalos/patologia
8.
Top Companion Anim Med ; 52: 100757, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36592860

RESUMO

FOP is a rare genetic condition, described mainly in man and cats, characterized by progressive, painful debilitation and shortened lifespan. A 10-month-old neutered male Savannah cat was referred for progressive gait abnormalities and multifocal firm masses within the soft-tissues that were unresponsive to previous treatment. Diagnosis of FOP was based on histopathological evaluation of intralesional biopsies, which revealed osteo-cartilaginous metaplasia and fibrocellular proliferation with intralesional chondrogenesis and endochondral ossification. The cat was managed with 5 mg/kg BID enrofloxacin and hydrotherapy for 3 years until acute death. During that three-year period, the cat displayed consistent improvement in endurance, quality of life, and range of motion. Postmortem histopathology further confirmed the diagnosis of FOP via identification of intramuscular and intra-fascial ossification with lymphoplasmacytic infiltration, degeneration, and regeneration of adjacent myocytes. To the authors' knowledge, this is the first report of long-term enrofloxacin treatment and hydrotherapy for the management of FOP in a cat, leading to improved mobility and survival time, and the first report of FOP in an exotic breed cat.


Assuntos
Hidroterapia , Miosite Ossificante , Ossificação Heterotópica , Masculino , Animais , Miosite Ossificante/genética , Miosite Ossificante/patologia , Miosite Ossificante/veterinária , Ossificação Heterotópica/genética , Ossificação Heterotópica/patologia , Ossificação Heterotópica/veterinária , Enrofloxacina/uso terapêutico , Qualidade de Vida , Hidroterapia/veterinária
9.
Am J Clin Pathol ; 159(2): 164-171, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36495298

RESUMO

OBJECTIVES: Fumarate hydratase (FH)-deficient tumors can occur due to germline or somatic mutations and have distinctive morphologic features. The aims of this study are to refine morphologic criteria and identify mutations in FH-deficient smooth muscle tumors (SMTs). METHODS: The morphology of SMTs and kidney tumors submitted to a national reference laboratory for FH immunohistochemistry (IHC) was reviewed by two gynecologic and two genitourinary pathologists, respectively. Fisher exact test was used for analysis. Fourteen SMTs were sequenced using the Illumina TruSight Oncology 500 Assay. RESULTS: Twenty-two kidney tumors (5 FH deficient) and 51 SMTs (27 FH deficient) were reviewed. FH-deficient kidney tumors exclusively showed cord-like growth, rhabdoid change, and absence of coagulative tumor necrosis and psammoma bodies. FH-deficient SMTs were significantly more likely to have staghorn vessels, eosinophilic cytoplasmic inclusions, schwannoma-like areas, or hereditary leiomyomatosis and renal cell cancer-like nuclei (P < .05 for each). Seven of 14 sequenced SMTs showed mutations of the FH gene and no other driver mutations. CONCLUSIONS: FH-deficient SMTs submitted for FH immunohistochemistry (IHC) showed distinct morphology. Although FH IHC is used for screening of FH-deficient tumors, FH mutations were identified in only 50% of FH-deficient SMTs. This highlights the need for additional exploration of mechanisms of FH protein loss in tumors lacking FH mutations.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Tumor de Músculo Liso , Neoplasias Uterinas , Feminino , Humanos , Fumarato Hidratase/genética , Fumarato Hidratase/análise , Rim/patologia , Neoplasias Renais/genética , Tumor de Músculo Liso/genética , Neoplasias Uterinas/diagnóstico
10.
Tob Induc Dis ; 20: 109, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530212

RESUMO

INTRODUCTION: Proper understanding of the prevalence and determinants of nicotine dependence is crucial for developing and implementing effective tobacco control interventions. The aim of the study was to identify the intrinsic and extrinsic barriers to smoking cessation, and to assess the association between nicotine dependence with demographic variables in Malaysia. METHODS: A cross-sectional survey based on the Challenges to Stopping Smoking Scale (CSS-21) and Fagerström test for nicotine dependence (FTND) was performed on smoking Malaysian citizens aged ≥18 years, from February to June 2021. RESULTS: A total of 1026 parents responded to the survey. As for the smoking dependence based on FTND, 39.1% suffered low-moderate dependence, while about 33.6% suffered moderate dependence. Only 1.8% suffered high dependence. Considering the barriers of quitting smoking based on CSS-21, the mean score of the intrinsic barriers domain was 5.7 ± 2.9, and for the extrinsic domain was 7.4 ± 4.0. The most common barrier reported in the intrinsic domain was the easy availability of cigarettes (69.8%), followed by experiencing withdrawal symptoms (68.5%). On the other hand, the most common barrier reported in the extrinsic domain was the belief in the capability of stopping smoking in the future (72.8%), followed by the fear of having side effects after stopping smoking (63.2%). Gender, race, education level, occupation, marital status, place of residence, and monthly income were also significantly associated with the FTND nicotine dependence category (all p<0.05). Pearson correlation analysis reported a positive association between intrinsic score (r=0.38), extrinsic score (r=0.43) and FTND score (all p<0.001). CONCLUSIONS: Barriers to stopping smoking should be taken into consideration in initiatives to decrease smoking-related mortality. Vulnerable populations that are susceptible to high nicotine dependence should be given particular attention.

11.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1440963

RESUMO

Introducción: El tumor neuroectodérmico primitivo periférico de riñón (PNETk) es una enfermedad rara muy agresivo que afecta mayormente a varones jóvenes. Reporte de caso: paciente varón de 19 años con cuadro clínico dolor abdominal, hematuria y masa palpable, en la tomografía se evidencia una enorme tumoración renal izquierda, Se le realiza nefrectomía radical convencional y se envía a estudio patológico más histoquímica resultando de PNETk. Luego paciente siguió su manejo por oncología para quimiterapia inicialmente. Conclusión: El PNETk que describimos representa el primer caso reportado en nuestro país, constituye una entidad clínica única por su rareza siendo un reto hacer diagnóstico y su comportamiento y manejo se sigue basando a reportes de casos debido a su poca frecuencia.


Introduction: Peripheral primitive neuroectodermal tumor of the kidney (PNETk) is a very aggressive rare disease that mainly affects young men. Case report: A 19-year-old male patient with symptoms of abdominal pain, hematuria and a palpable mass, the tomography shows a large left renal tumor. Conventional radical nephrectomy was performed and sent for pathology study plus histochemistry, resulting in PNETk. The patient then continued his oncology management for chemotherapy initially. Conclusion: The PNETk that we describe represents the first case reported in our country, it constitutes a unique clinical entity due to its rarity, being a challenge to make a diagnosis and its behavior and management is still based on case reports due to its infrequency.

12.
Comp Med ; 72(5): 306-319, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36113969

RESUMO

Osteosarcoma (OSA) is the most common primary bone tumor in both dogs and humans. The dog is an important research model for OSA, yet dogs have much higher prevalence of bone tumors than do humans, a disparity that has yet to be explained. Neoplastic transformation of cells within or adjacent to bone infarcts into primary bone tumors has been described in humans but only sparsely characterized in the veterinary literature. In this study, 653 cases of canine bone infarcts were received through a referral veterinary osteopathology service over a 14-y period. We identified an idiopathic disorder affecting the nutrient artery, termed canine idiopathic arteriopathy (CIA), which to our knowledge has no direct counterpart in human medicine. This disorder was documented alongside ischemic necrosis of the medullary cavity in 114 bone infarcts in 108 dogs. We hypothesize that CIA precipitated an ischemic environment, resulting in development of a bone infarct down- stream of the abnormal artery. In 52% (59 of 114) of cases, bone infarcts demonstrated evidence of repair (termed reparative bone infarcts [RBI]), while in 48% (55 of 114) of infarcts, a bone tumor was also present, including pleomorphic sarcoma, OSA, fibrosarcoma, and chondrosarcoma. In some cases, a spectrum of tumors was present. We hypothesize that the ischemic infarct environment provoked bone marrow mesenchymal stem cells (MSCs) to attempt repair of the stroma, and in approximately half of cases, MSCs underwent neoplastic transformation (BINT) to produce tumors. The most common sites of bone infarcts were the distal femur, distal radius, proximal humerus, and distal tibia, coinciding with common sites of canine OSA. The authors propose that CIA leading to bone infarcts and infarct-derived tumors, in combination with possible underdiagnosis of canine bone infarcts and misdiagnosis of some RBI as neoplasia, may contribute to the higher reported proportion of bone tumors in dogs compared with humans.


Assuntos
Neoplasias Ósseas , Doenças do Cão , Osteossarcoma , Lobos , Animais , Cães , Humanos , Neoplasias Ósseas/veterinária , Doenças do Cão/patologia , Infarto/veterinária , Osteossarcoma/veterinária , Osteossarcoma/patologia
13.
Nat Microbiol ; 7(10): 1605-1620, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36138165

RESUMO

Pharmaceuticals have extensive reciprocal interactions with the microbiome, but whether bacterial drug sensitivity and metabolism is driven by pathways conserved in host cells remains unclear. Here we show that anti-cancer fluoropyrimidine drugs inhibit the growth of gut bacterial strains from 6 phyla. In both Escherichia coli and mammalian cells, fluoropyrimidines disrupt pyrimidine metabolism. Proteobacteria and Firmicutes metabolized 5-fluorouracil to its inactive metabolite dihydrofluorouracil, mimicking the major host mechanism for drug clearance. The preTA operon was necessary and sufficient for 5-fluorouracil inactivation by E. coli, exhibited high catalytic efficiency for the reductive reaction, decreased the bioavailability and efficacy of oral fluoropyrimidine treatment in mice and was prevalent in the gut microbiomes of colorectal cancer patients. The conservation of both the targets and enzymes for metabolism of therapeutics across domains highlights the need to distinguish the relative contributions of human and microbial cells to drug efficacy and side-effect profiles.


Assuntos
Antineoplásicos , Escherichia coli , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Bactérias/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Fluoruracila/metabolismo , Fluoruracila/farmacologia , Humanos , Mamíferos , Redes e Vias Metabólicas , Camundongos
14.
Oncoimmunology ; 11(1): 2111904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990518

RESUMO

B cell lymphoma therapy has been transformed by CD19-targeting cellular therapeutics that induce high clinical response rates and impressive remissions in relapsed and refractory patients. However, approximately half of all patients who respond to CD19-directed cell therapy relapse, the majority within 6 months. One characteristic of relapse is loss or reduction of CD19 expression on malignant B cells. We designed a unique therapeutic to prevent and reverse relapses due to lost or reduced CD19 expression. This novel biologic, a CAR T Engager, binds CD20 and displays the CD19 extracellular domain. This approach increases the apparent CD19 antigen density on CD19-positive/CD20-positive lymphoma cells, and prevents antigen-loss induced relapse, as CD19 bound to CD20 remains present on the cell surface. We demonstrate that this novel therapeutic prevents and reverses lymphoma relapse in vitro and prevents CD19-negative lymphoma growth and relapse in vivo.


Assuntos
Linfoma , Receptores de Antígenos Quiméricos , Antígenos CD19 , Antígenos CD20 , Humanos , Linfoma/terapia , Recidiva Local de Neoplasia , Receptores de Antígenos de Linfócitos T , Linfócitos T
15.
Artigo em Inglês | MEDLINE | ID: mdl-35619936

RESUMO

Objective: Endoscopic repair of large anterior skull base (ASB) defects has excellent results when using multilayered repairs with a nasoseptal flap. However, in extensive intranasal tumors, a nasoseptal flap may not always be available. One alternative option is a flexible single-layer ASB repair. Initial studies indicate low cerebrospinal fluid leak rates with a single-layer repair. However, the level of frontal lobe support, particularly the propensity for a significant inferior displacement of the frontal lobe, is not known. The goal of this study is to determine the frontal lobe position after single-layer acellular dermal allograft repair in large ASB defects. Study Design: Retrospective cohort study. Setting: Tertiary care medical center. Subjects and Methods: This cohort study compares the frontal lobe position in adults who underwent endoscopic endonasal ASB tumor resection and single-layer cadaveric dermal matrix repair (ASB cohort) with control subjects without intracranial abnormalities (control cohort). The ASB cohort includes subjects with an ASB defect of ≥5 cm anterior/posterior and ≥1.5 cm wide and who had imaging at least 2 months after surgery. The frontal lobe position is measured on sagittal CT/MRI using a reference line from the base of the sella to the nasion. A value of zero indicates that the inferior-most aspect of the frontal lobe is at the level of the nasion-sellar line. A positive value indicates that the frontal lobe is inferior to the nasion-sellar line. The ASB cohort frontal lobe position is compared with the control cohort using the Mann-Whitney U test. A priori we set an absolute difference of 5 mm as a clinically significant difference. Results: The ASB cohort includes 47 subjects who are 57% male with an average age of 60 years (range: 31-89 years). The most common ASB pathology is esthesioneuroblastoma (n = 21) and 81% of the ASB cohort had postoperative radiation. The control cohort includes 20 subjects who are 60% male, with a mean age of 45 years (range: 19-74 years). The majority of controls underwent imaging for head trauma (n = 13). The ASB mean frontal lobe position is -0.2 mm superior to the nasion-sellar line (range: -9.2 to 10.4 mm), while the control's mean frontal lobe position is 1.1 mm inferior to the nasion-sellar line. This difference is not statistically significant (P = 0.13) and does not reach our a priori definition of clinical significance. The frontal lobe position of ASB subjects who had radiation is closer to the nasion-sellar line as compared with those who did not undergo radiation. Conclusions: Single-layer acellular dermal graft repair maintains frontal lobe support and position in large ASB defects.

16.
Cell Chem Biol ; 29(2): 328-338.e4, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-34363759

RESUMO

Potent, specific ligands drive precision medicine and fundamental biology. Proteins, peptides, and small molecules constitute effective ligand classes. Yet greater molecular diversity would aid the pursuit of ligands to elicit precise biological activity against challenging targets. We demonstrate a platform to discover protein-small molecule (PriSM) hybrids to combine unique pharmacophore activities and shapes with constrained, efficiently engineerable proteins. In this platform, a fibronectin protein library is displayed on yeast with a single cysteine coupled to acetazolamide via a maleimide-poly(ethylene glycol) linker. Magnetic and flow cytometric sorts enrich specific binders to carbonic anhydrase isoforms. Isolated PriSMs exhibit potent, specific inhibition of carbonic anhydrase isoforms with efficacy superior to that of acetazolamide or protein alone, including an 80-fold specificity increase and 9-fold potency gain. PriSMs are engineered with multiple linker lengths, protein conjugation sites, and sequences against two different isoforms, which reveal platform flexibility and impacts of molecular designs. PriSMs advance the molecular diversity of efficiently engineerable ligands.


Assuntos
Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Fibronectinas/química , Engenharia de Proteínas , Bibliotecas de Moléculas Pequenas/farmacologia , Inibidores da Anidrase Carbônica/química , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Saccharomyces cerevisiae/citologia , Bibliotecas de Moléculas Pequenas/química
17.
Chemosphere ; 286(Pt 1): 131545, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34293563

RESUMO

Several studies have reported exposure of humans to various endocrine disrupting chemicals (EDCs) worldwide. However, there is a lack of data regarding EDC exposures in humans living in Southeast Asian countries, such as the Philippines. Hence, this study measured levels of 41 EDCs in women residing in the Greater Manila Area, home to the second largest city in Southeast Asia. Urine samples from women with versus without breast cancer were analyzed for 11 phthalate metabolites, 8 environmental phenols, and 10 bisphenols, while serum samples were analyzed for 12 perfluoroalkyl substances (PFAS). Out of the four groups of EDCs analyzed, PFAS were significantly associated with breast cancer (adjusted OR = 13.63, 95% CI: 3.24-94.88 p-trend = 0.001 for PFDoA; adjusted OR = 9.26, 95% CI 2.54-45.10, p-trend = 0.002 for PFDA; and adjusted OR = 2.66, 95% CI: 0.95-7.66, p-trend = 0.004 for PFHxA). Long-chain PFAS levels were positively correlated with age and were significantly higher in women from Region IV-A, a heavily industrialized region, than from the National Capital Region. Overall, this study showed baseline information regarding the level of EDCs in Filipinas, providing a glimpse of EDC exposure in women living in a megalopolis city in Southeast Asia.


Assuntos
Neoplasias da Mama , Disruptores Endócrinos , Poluentes Ambientais , Fluorocarbonos , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Filipinas
18.
Urol Case Rep ; 41: 101967, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34950565

RESUMO

Primary amyloidosis of the ureter is a rare disease that is difficult to distinguish from urothelial carcinoma. Only 50 cases of primary ureter amyloidosis have been reported since it was first described in 1937. Of these, only five cases of ureter amyloidosis with osseous metaplasia were reported. In this study, we report the clinical presentation of ureter primary amyloidosis that presented as a mass with osseous metaplasia. The aim of this study is to provide clinicians with knowledge about the clinical/radiologic manifestation that raise the suspicion of amyloidosis, bearing in mind the importance of differentiating it from other "malignant" processes.

19.
Am J Otolaryngol ; 43(1): 103214, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34607277

RESUMO

PURPOSE: Research indicates that most providers give opiates after endoscopic sinonasal surgery. The effectiveness of non-opiate medications after sinonasal surgery is poorly understood and most studies do not assess medication failure. This study compares oral opiate, oral opiate and topical steroid, and oral non-opiate pain control. Patient call-backs are used as a proxy for pain medication failure. MATERIALS AND METHODS: This study compares three medication regiments after sinonasal surgery for 180 adults with chronic rhinosinusitis. Patients were instructed to take acetaminophen for mild pain. For moderate/severe pain, patients used: 1) oxycodone-acetaminophen, 2) oxycodone-acetaminophen + budesonide nasal rinses, or 3) meloxicam + acetaminophen. Patients were instructed to call clinic if pain was not controlled. Descriptive statistics compared cohorts. Chi-square tests compared call-backs between cohorts. Logistic regression adjusted for baseline differences in covariates, comorbidities, and operative sites. RESULTS: Cohorts had similar age, sex distribution, disease features, and extent of surgery. The meloxicam cohort had less subjects with pain disorders. The oxycodone cohort had less subjects with diabetes, septoplasty, and turbinate reduction. After adjusting for baseline differences and using oxycodone as the reference group (n = 50), the odds of calling clinic for poorly controlled pain was 0.18 (95% Confidence Interval (CI): 0.05-0.6) in the meloxicam cohort (n = 45) and 0.19 (95% CI:0.07-0.5) in the oxycodone + budesonide rinses cohort (n = 85). CONCLUSION: In this study, both meloxicam and oxycodone + budesonide rinses were more effective at controlling pain after sinonasal surgery than oxycodone alone.


Assuntos
Acetaminofen/administração & dosagem , Budesonida/administração & dosagem , Endoscopia/métodos , Meloxicam/administração & dosagem , Procedimentos Cirúrgicos Nasais/métodos , Oxicodona/administração & dosagem , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Rinite/cirurgia , Sinusite/cirurgia , Irrigação Terapêutica/métodos , Adulto , Doença Crônica , Estudos de Coortes , Combinação de Medicamentos , Endoscopia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Nasais/efeitos adversos , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Resultado do Tratamento
20.
J Am Anim Hosp Assoc ; 57(6): 285-289, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606584

RESUMO

This case report details a previously undescribed malignancy of the tendon sheath in a golden retriever. This dog originally presented with lameness of the left forelimb, at which point radiographs revealed a monostotic, lytic lesion of the distal radius with overlying soft-tissue swelling. A fine-needle aspirate was performed, and cytology was compatible with a sarcoma, with the primary differential being an osteosarcoma. After amputation, the leg was submitted for histopathology, which revealed inconsistencies with a typical osteosarcoma lesion, including lack of osteoid deposition. Second opinion histopathology showed a fibrosarcoma that appeared to have originated in the tendon sheath of an extensor tendon and then secondarily invaded the radius. At the time of publication, ∼17 mo after amputation, the dog continues to do well without any evidence of recurrent or metastatic disease.


Assuntos
Neoplasias Ósseas , Doenças do Cão , Fibrossarcoma , Osteólise , Animais , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/veterinária , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Fibrossarcoma/cirurgia , Fibrossarcoma/veterinária , Osteólise/veterinária , Rádio (Anatomia) , Tendões
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