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This review focuses on mature T cells, natural killer (NK) cells, and stroma-derived neoplasms in the fifth edition of the World Health Organization classification of hematolymphoid tumors, including changes from the revised fourth edition. Overall, information has expanded, primarily due to advancements in genomic understanding. The updated classification adopts a hierarchical format. The updated classification relies on a multidisciplinary approach, incorporating insights from a diverse group of pathologists, clinicians, and geneticists. Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract, Epstein-Barr virus-positive nodal T- and NK-cell lymphoma, and several stroma-derived neoplasms of lymphoid tissues have been newly introduced or included. The review also provides guidance on how the fifth edition of the World Health Organization classification of hematolymphoid tumors can be applied in routine clinical practice.
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Large or blastoid B-cell neoplasms that are SOX11+ are a diagnostic dilemma and raise a differential diagnosis of cyclin D1-negative blastoid/pleomorphic mantle cell lymphoma (MCL) versus diffuse large B-cell lymphoma (DLBCL) or blastoid high-grade B-cell lymphoma (HGBL) with aberrant SOX11 expression. Here we report a study cohort of 13 SOX11+ large/blastoid B-cell neoplasms. Fluorescence in situ hybridization analysis was negative for CCND1 rearrangement in all 13 cases; 1 of 8 (12.5%) cases tested showed CCND2 rearrangement and 2 (25%) cases had extracopies of CCND2. Gene expression profiling showed that the study group had a gene expression signature similar to cyclin D1+ blastoid/pleomorphic MCL but different from DLBCL. Principal component analysis revealed that the cohort cases overlapped with cyclin D1+ blastoid/pleomorphic MCL but had minimal overlap with DLBCL. All patients in the cohort had clinicopathologic features similar to those reported for patients with cyclin D1+ MCL. We also performed a survey of SOX11 expression in a group of 85 cases of DLBCL and 24 cases of blastoid HGBL. SOX11 expression showed a 100% specificity and positive predictive value for the diagnosis of MCL. Overall, the results support the conclusion that large or blastoid B-cell neoplasms that are positive for SOX11 are best classified as cyclin D1-negative blastoid/pleomorphic MCL, and not as DLBCL or blastoid HGBL. We also conclude that SOX11 is a specific marker for the diagnosis of MCL, including cyclin D1-negative blastoid/pleomorphic MCL cases and should be performed routinely on blastoid/large B-cell neoplasms to help identify potential cases of cyclin D1-negative blastoid/pleomorphic MCL.
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Linfoma de Células B Grandes Difuso , Linfoma de Células del Manto , Adulto , Humanos , Linfoma de Células del Manto/metabolismo , Ciclina D1/genética , Hibridación Fluorescente in Situ , Inmunohistoquímica , Linfoma de Células B Grandes Difuso/patología , Factores de Transcripción SOXC/genéticaRESUMEN
DISEASE OVERVIEW: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an aggressive B-cell lymphoma associated with EBV infection included in the WHO classification of lymphoid neoplasms since 2016. Although historically associated to poor prognosis, outcomes seem to have improved in the era of chemoimmunotherapy. DIAGNOSIS: The diagnosis is established through meticulous pathological evaluation. Detection of EBV-encoded RNA (EBER) is the standard diagnostic method. The ICC 2022 specifies EBV+ DLBCL, NOS as occurring when >80% of malignant cells express EBER, whereas the WHO-HAEM5 emphasizes that the majority of tumor cells should be EBER positive without setting a defined threshold. The differential diagnosis includes plasmablastic lymphoma, DLBCL associated with chronic inflammation, primary effusion lymphoma, among others. RISK-STRATIFICATION: The International Prognostic Index (IPI) and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers. MANAGEMENT: Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. Therefore, inclusion of patients in clinical trials when available is recommended. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.
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Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four with failed karyotyping. The most common additional alterations identified by OGM included chromoanagenesis (n = 23), KMT2A partial tandem duplication (n = 11), rearrangements involving MECOM (n = 7), NUP98 (n = 2), KMT2A (n = 2), JAK2 (n = 2), and other gene fusions in 17 patients, with 10 showing novel fusion gene partners. OGM also pinpointed fusion genes in 17 (11%) patients where chromosomal rearrangements were concurrently detected by OGM and CBA. Overall, 24 (15%) aberrations were identified exclusively by OGM and had the potential to alter AML classification, risk stratification, and/or clinical trial eligibility. OGM emerges as a powerful tool for identifying fusion genes and detecting subtle or cryptic cytogenomic aberrations that may otherwise remain undetectable by CBA.
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BACKGROUND: In hematologic cancers, including leukemia, cells depend on amino acids for rapid growth. Anti-metabolites that prevent their synthesis or promote their degradation are considered potential cancer treatment agents. Amino acid deprivation triggers proliferation inhibition, autophagy, and programmed cell death. L-lysine, an essential amino acid, is required for tumor growth and has been investigated for its potential as a target for cancer treatment. L-lysine α-oxidase, a flavoenzyme that degrades L-lysine, has been studied for its ability to induce apoptosis and prevent cancer cell proliferation. In this study, we describe the use of L-lysine α-oxidase (LO) from the filamentous fungus Trichoderma harzianum for cancer treatment. RESULTS: The study identified and characterized a novel LO from T. harzianum and demonstrated that the recombinant protein (rLO) has potent and selective cytotoxic effects on leukemic cells by triggering the apoptotic cascade through mitochondrial dysfunction. CONCLUSIONS: The results support future translational studies using the recombinant LO as a potential drug for the treatment of leukemia.
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Hypocreales , Leucemia , Neoplasias , Trichoderma , Humanos , Lisina , Apoptosis , Leucemia/tratamiento farmacológico , NecrosisRESUMEN
BACKGROUND: Trichoderma reesei is an organism extensively used in the bioethanol industry, owing to its capability to produce enzymes capable of breaking down holocellulose into simple sugars. The uptake of carbohydrates generated from cellulose breakdown is crucial to induce the signaling cascade that triggers cellulase production. However, the sugar transporters involved in this process in T. reesei remain poorly identified and characterized. RESULTS: To address this gap, this study used temporal membrane proteomics analysis to identify five known and nine putative sugar transporters that may be involved in cellulose degradation by T. reesei. Docking analysis pointed out potential ligands for the putative sugar transporter Tr44175. Further functional validation of this transporter was carried out in Saccharomyces cerevisiae. The results showed that Tr44175 transports a variety of sugar molecules, including cellobiose, cellotriose, cellotetraose, and sophorose. CONCLUSION: This study has unveiled a transporter Tr44175 capable of transporting cellobiose, cellotriose, cellotetraose, and sophorose. Our study represents the first inventory of T. reesei sugar transportome once exposed to cellulose, offering promising potential targets for strain engineering in the context of bioethanol production.
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Celulasa , Glucanos , Hypocreales , Trichoderma , Celobiosa/metabolismo , Proteoma/metabolismo , Proteínas de la Membrana/metabolismo , Celulosa/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Saccharomyces cerevisiae/metabolismo , Celulasa/metabolismo , Azúcares/metabolismo , Oligosacáridos/metabolismo , Trichoderma/metabolismoRESUMEN
OBJECTIVE: To characterize and compare microbiological profiles in tympanostomy tube otorrhea for children with and without cleft palate. DESIGN: Retrospective cohort study. SETTING: Pediatric otolaryngology and multidisciplinary cleft/craniofacial clinic at a single tertiary care center. PATIENTS: Children with and without cleft palate <18 years of age who underwent tympanostomy tube placement between 2017-2021. MAIN OUTCOME MEASURES: Otopathogen profiles and antibiotic resistance patterns in ear culture specimens obtained in children presenting for treatment of recalcitrant post-tympanostomy tube otorrhea. RESULTS: Of the 886 children with tympanostomy tubes placed between 2017-2021, 345 (38.9%) had clinically significant otorrhea defined as requiring at least one otolaryngology visit for treatment. Children with cleft palate had higher rates of otorrhea (50.0% versus 35.7%; P < .01). In the 128 cultures obtained, Staphylococcus aureus was the most common organism in both groups present in 39.8% of cultures; 49% were methicillin-resistant (MRSA). Pseudomonas aeruginosa was also frequently isolated (20.0% versus 23.4%, P = .69) in children with and without cleft palate. Collectively, fluoroquinolone resistance was observed in 68.6% and 27.6% of the S. aureus and P. aeruginosa isolates, respectively, however, no differences in fluoroquinolone resistance were observed between cleft and non-cleft cohorts. Corynebacterium species were isolated more frequently in children with cleft palate (26.7% versus 6.1%, P < .01), a finding of unclear significance. CONCLUSIONS: Recalcitrant post-tympanostomy tube otorrhea is more common in children with cleft palate. MRSA was the most common isolate, which was commonly resistant to first-line fluoroquinolone therapy.
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Diferenciación Celular , Leucemia Mieloide Aguda , Mastocitos , Proteína p53 Supresora de Tumor , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patología , Mastocitos/patología , Mastocitos/metabolismo , Proteína p53 Supresora de Tumor/genética , Pronóstico , Masculino , Femenino , Persona de Mediana Edad , Mutación , Anciano , Cariotipo , AdultoRESUMEN
As we conclude this Special Issue on fungal biology and interactions, it is only appropriate to reflect on the remarkable progress our scientific community has made in unraveling the mysteries of the fungal kingdom [...].
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INTRODUCTION: Pediatric Relapsing Polychondritis (RP) is a rare autoimmune disorder that causes inflammation and damage to cartilage in children. Common symptoms include pain, swelling and deformities in the ears, nose, trachea, joints, and eyes. The lack of research on the pediatric population necessitates further evaluation of the literature on pediatric RP to summarize existing patterns in presentation, management, and treatment. METHODS: A systematic review was conducted on PubMed and Embase from 1947 to April 2023 on RP in patients under 21 years old abiding by the 2020 PRISMA checklist. Only patient presentations meeting McAdam criteria for RP and including information on management were included. RESULTS: From the 304 initial studies, 54 studies were included for final analysis with a total of 68 patients, who were predominantly female (65%). With a median diagnostic delay of 1 year, the mean age of onset was 12 years old. The most common symptoms on presentation included bilateral auricular chondritis (69%), nasal cartilage inflammation (62%), and respiratory tract chondritis (63%). The most commonly reported information in the literature for the initial workup usually included CT/MRI (72%), bronchoscopy (57%), biopsy (51%), and labs (88%), which most commonly displayed elevated ESR (59%). The most common medications were corticosteroids (91%) and methotrexate (35%) and the most common procedural treatment was tracheostomy (38%). The most efficacious treatment options were monoclonal antibodies (87%, n = 15) and corticosteroids (66%, n = 62) used in 22% and 91% of patients, respectively. The most commonly used monoclonal antibody therapy was infliximab (13%, n = 9). CONCLUSION: The most common presentation for pediatric RP includes chondritis of the ear, nose, and respiratory tract. The most effective treatment options include corticosteroids and monoclonal antibody therapy, such as infliximab. Our findings highlight increasing remission achieved with anti-rheumatic drugs and monoclonal antibody treatment, especially alongside corticosteroids.
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BACKGROUND: Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far. OBJECTIVE: We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts. METHOD: We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts. RESULTS: Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality. CONCLUSION: This is the first study supporting the mediational role of RF in the relationship between EA and SA, and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required.
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Experiencias Adversas de la Infancia , Pruebas Psicológicas , Intento de Suicidio , Humanos , Autoinforme , Ideación Suicida , Factores de RiesgoRESUMEN
Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients with GMF and MF with large cell transformation (MFLCT). Skin biopsies from 49 patients (28 GMF and 21 MFLCT) were studied. Patients with GMF were associated with early clinical stage (p = 0.036) and lower levels of lactate dehydrogenase (p = 0.042). An increased percentage of cells positive for Tbet (p = 0.017), RORγT (p = 0.001), and PD-L1 (p = 0.011) was also observed among the GMF specimens, while a stronger PD-1 intensity was detected in cases of MFLCT. In this cohort, LCT, RORγT < 10%, Foxp3 < 10%, age, and advanced stage were associated with worse overall survival (OS) in univariate analysis. GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.
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Micosis Fungoide , Neoplasias Cutáneas , Humanos , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Neoplasias Cutáneas/patología , Antígeno B7-H1/metabolismo , Regulación hacia Arriba , Receptor de Muerte Celular Programada 1/metabolismo , Factor de Maduración de la Glia/metabolismo , Micosis Fungoide/patología , Factores de Transcripción Forkhead/metabolismoRESUMEN
OBJECTIVES: Flow cytometric immunophenotyping (FCI) is a fast and sensitive method for characterizing hematolymphoid neoplasms. It is not widely used in the workup of systemic mastocytosis (SM), in part because of the technical challenges and in part because the utility of FCI in assessing mast cells is not well understood. The objectives of this study were to assess the diagnostic utility of FCI in establishing a diagnosis of SM and distinguishing SM from nonneoplastic mast cells and to examine the immunophenotypic findings among SM subtypes. METHODS: We performed FCI on bone marrow samples suspicious for SM using a panel consisting of CD2, CD25, CD30, CD45, CD117, and HLA-DR. RESULTS: The cohort included 88 SM cases: 67 without an associated hematologic neoplasm (AHN) (PureSM) and 21 with an AHN (SM-AHN). We also assessed 40 normal/reactive controls. Overall, FCI was adequate for interpretation in 87 of 88 (99%) cases and detected at least 1 immunophenotypic aberrancy in 100% of SM cases. CD2, CD25, and CD30 were positive in 78%, 98%, and 90% of SM cases vs 0%, 13%, and 13% of cases with normal/reactive mast cells (P < .0001 for all). Two or 3 abnormalities were observed in 92% of SM cases but not in normal/reactive mast cells. Among SM cases, SM-AHN showed statistically significant less CD2 (38% vs 91%, P < .0001) and less co-expression of all 3 aberrant markers (CD2, CD25, and CD30 positive in 38% vs 86% of cases; P < .0001) than PureSM. Immunohistochemical analysis showed consistently weaker or focal expression of CD2, CD25, and CD30 than FCI, with CD2 and CD30 being falsely negative in 40% and 50% cases, respectively. A KIT D816V mutation was detected in 67% of PureSM cases and 76% of SM-AHN cases. CONCLUSIONS: Flow cytometric immunophenotyping is a quick, sensitive, high-yield tool for evaluating the immunophenotype of mast cells. An abnormal FCI finding should prompt careful histologic evaluation and sensitive KIT D816V mutation testing to address the possibility of SM. CD2, CD25, and CD30 are important markers for the detection of immunophenotypic aberrancy of mast cells, and their frequencies of aberrancy differ across SM subtypes.
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Citometría de Flujo , Inmunofenotipificación , Mastocitos , Mastocitosis Sistémica , Humanos , Inmunofenotipificación/métodos , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/patología , Mastocitosis Sistémica/inmunología , Citometría de Flujo/métodos , Mastocitos/patología , Mastocitos/inmunología , Persona de Mediana Edad , Femenino , Masculino , Adulto , Anciano , Sensibilidad y Especificidad , Anciano de 80 o más Años , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: In the absence of high-quality evidence, there is a need to provide guidelines and multidisciplinary consensus recommendations on Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis, and management of BIA-ALCL caused by textured implants. The aim is to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL. METHODS: A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, supplemented by manual searches of relevant English language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants were included for analysis. Meta-analyses were performed and reviewed by experts selected by the American Association of Plastic Surgeons by a Delphi consensus method. RESULTS: 840 articles between January 2011 and January 2023 were initially identified and screened. Full-text of 188 articles were assessed. An additional 43 articles were excluded for focus, and 145 articles were included in the synthesis of results, with 105 of them being case reports or case series. The analysis encompassed a comprehensive examination of the selected articles to determine the incidence, risk factors, clinical presentation, diagnostic approaches, and treatment modalities related to BIA-ALCL. CONCLUSIONS: Plastic surgeons should be aware of the elevated risks by surface type, implement appropriate patient surveillance, and follow the recommendations outlined in this statement to ensure patient safety and optimize outcomes. Ongoing research on pathogenesis, genetic drivers, and preventative and prophylactic measures is crucial for improving patient care.
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BACKGROUND: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy. OBJECTIVE: Our aim was to characterize treatment options for PCSM-LPD, with a focus on the role of radiotherapy. METHODS: This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM-LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy. RESULTS: All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra-low-dose radiotherapy (4 Gy in 1-2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids. CONCLUSION: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra-low-dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy.
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Epilepsy designates a group of chronic brain disorders, characterized by the recurrence of hypersynchronous, repetitive activity, of neuronal clusters. Epileptic seizures are the hallmark of epilepsy. The primary goal of epilepsy treatment is to eliminate seizures with minimal side effects. Nevertheless, approximately 30% of patients do not respond to the available drugs. An imbalance between excitatory/inhibitory neurotransmission, that leads to excitotoxicity, seizures, and cell death, has been proposed as an important mechanism regarding epileptogenesis. Recently, it has been shown that microreactors composed of platinum nanoparticles (Pt-NP) and glutamate dehydrogenase possess in vitro and in vivo activity against excitotoxicity. This study investigates the in vivo effects of these microreactors in an animal model of epilepsy induced by the administration of the GABAergic antagonist bicuculline. Male Wistar rats were administered intracerebroventricularly (i.c.v.) with the microreactors or saline and, five days later, injected with bicuculline or saline. Seizure severity was evaluated in an open field. Thirty min after behavioral measurements, animals were euthanized, and their brains processed for neurodegeneration evaluation and for neurogenesis. Treatment with the microreactors significantly increased the time taken for the onset of seizures and for the first tonic-clonic seizure, when compared to the bicuculline group that did not receive the microreactor. The administration of the microreactors also increased the time spent in total exploration and grooming. Treatment with the microreactors decreased bicuculline-induced neurodegeneration and increased neurogenesis in the dorsal and ventral hippocampus. These observations suggest that treatment with Pt-NP-based microreactors attenuates the behavioral and neurobiological consequences of epileptiform seizure activity.
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Epilepsia , Nanopartículas del Metal , Fármacos Neuroprotectores , Humanos , Ratas , Animales , Masculino , Bicuculina/farmacología , Platino (Metal)/efectos adversos , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológicoRESUMEN
Breast implant-associated anaplastic large cell lymphoma has been recognized as a distinct entity in the World Health Organization classification of hematolymphoid neoplasms. These neoplasms are causally related to textured implants that were used worldwide until recently. Consequently, there is an increased demand for processing periprosthetic capsules, adding new challenges for surgeons, clinicians, and pathologists. In the literature, the focus has been on breast implant-associated anaplastic large cell lymphoma; however, benign complications related to the placement of breast implants occur in up to 20% to 30% of patients. Imaging studies are helpful in assessing patients with breast implants for evidence of implant rupture, changes in tissues surrounding the implants, or regional lymphadenopathy related to breast implants, but pathologic examination is often required. In this review, we couple our experience with a review of the literature to describe a range of benign lesions associated with breast implants that can be associated with different clinical presentations or pathogenesis and that may require different diagnostic approaches. We illustrate the spectrum of the most common of these benign disorders, highlighting their clinical, imaging, gross, and microscopic features. Finally, we propose a systematic approach for the diagnosis and handling of breast implant specimens in general.
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Implantación de Mama , Implantes de Mama , Linfoma Anaplásico de Células Grandes , Humanos , Implantes de Mama/efectos adversos , Femenino , Linfoma Anaplásico de Células Grandes/patología , Linfoma Anaplásico de Células Grandes/etiología , Implantación de Mama/efectos adversos , Implantación de Mama/instrumentación , Valor Predictivo de las Pruebas , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Relevancia ClínicaRESUMEN
The fungus Trichoderma reesei is an essential producer of enzymes that degrade lignocellulosic biomass to produce value-added bioproducts. The cellulolytic system of T. reesei is controlled by several transcription factors (TFs) that efficiently regulate the production of these enzymes. Recently, a new TF named Azf1 was identified as a positive regulator of cellulase expression. Here, we investigated novel regulatory functions of Azf1 by its overexpression. In the mutant strain OEazf1, overexpression of azf1 was achieved under both repression and induction conditions. Although azf1 was more abundant in transcript and protein, overexpression of this TF did not activate transcription of the cellulase gene in the presence of the repressor glucose, suggesting that Azf1 may be subject to posttranslational regulation. In cellulose, the expression of swo, encoding the accessory protein swollenin, and the ß-glucosidases cel1a, cel1b, cel3b, and cel3g increases in the early stages of cultivation. The increased production of these ß-glucosidases increases the hydrolysis rate of cellobiose and sophorose, which activates carbon catabolite repression (CCR) and causes repression of cellulase genes and the regulator Xyr1 in the later stages of cultivation. Moreover, overexpression of azf1 led to increased cellulase activity in T. reesei during long-term cultivation in cellulose and sugarcane bagasse. Our results provide new insights into the mechanisms regulating Azf1 and novel genes that are important targets of this TF. This work contributes to a better understanding of the complex mechanisms regulating cellulase expression in T. reesei. It will contribute to the development of strains with higher production of these essential enzymes.
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The overview of the upcoming Blue Book of the 5th edition of the World Health Organization Classification of Hematolymphoid Tumors was published in Leukemia in June 2022. The updates on mature T-/NK-cell lymphomas and leukemias are organized in nine groups based on cell of origin, morphology, clinical scenario, and localization, and are highlighted in this newsletter.
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In the last two decades gastroesophageal reflux disease (GERD), initially thought to be a disease only common in the West, is described increasingly in Asia, including the Philippines. A recent local report indicated that the prevalence of erosive esophagitis (EE), a common complication of GERD, has more than doubled, i.e., 2.9% to 6.3%, between the two time periods of 1994-1997 and 2000-2003, respectively. GERD causes recurrent annoying symptoms which are common reasons for clinic visits and consultations thus, it is the objective of these guidelines to provide both primary care physicians (PCPs) and specialists a current, evidence-based, country-specific recommendations for the optimal management of GERD. These guidelines are intended to empower PCPs to make a clinic-based diagnosis of GERD, to start an empiric acid-suppressive therapy in the appropriate patient,and direct them to select which GERD patient may need to undergo investigations to ascertain further the diagnosis of GERD or to assess outcomes of therapy. We acknowledge that studies published in the future may influence the impact on our confidence on the recommendations enumerated in these guidelines thus, we commit to update this document when it is deemed appropriate.