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Changes in gene regulation represent an important path to generate developmental differences affecting anatomical traits. Interspecific divergence in gene expression often results from changes in transcription-stimulating enhancer elements. While gene repression is crucial for precise spatiotemporal expression patterns, the relative contribution of repressive transcriptional silencers to regulatory evolution remains to be addressed. Here, we show that the Drosophila pigmentation gene ebony has mainly evolved through changes in the spatial domains of silencers patterning its abdominal expression. By precisely editing the endogenous ebony locus of D. melanogaster, we demonstrate the requirement of two redundant abdominal enhancers and three silencers that repress the redundant enhancers in a patterned manner. We observe a role for changes in these silencers in every case of ebony evolution observed to date. Our findings suggest that negative regulation by silencers likely has an under-appreciated role in gene regulatory evolution.
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Proteínas de Drosophila , Drosophila , Animais , Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Pigmentação/genética , Regulação da Expressão Gênica/genética , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica no DesenvolvimentoRESUMO
Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed nonpolypoid lesions. Seven (88%) showed multifocal GI disease, including 5 with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single system), with the remaining 14 (36%) exhibiting multisystem disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multisystem LCH more frequently presented with GI symptoms (92%, P < .001), noncolorectal GI site involvement (50%, P = .02), multifocal GI lesions (43%, P = .005), nonpolypoid lesions (71%, P < .001), infiltrative histologic growth pattern (78%, P = .04), and persistent disease (57%, P < .001). Adult patients with multisystem LCH appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrated that adults with single-system LCH involving the GI tract have an excellent prognosis, whereas multisystem LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, noncolorectal GI involvement, multifocal GI disease, nonpolypoid lesions, and infiltrative growth pattern.
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We present an optimal configuration for Stokes polarimeters based on liquid crystal variable retarders, with the minimum number of measurements. Due to the inherent variations of the director orientation of the liquid crystal molecules, we propose a configuration that minimizes the sensibility of the polarimeter to fast-axis variations. For the optimization we consider a scheme that maximizes the volume of a tetrahedron inscribed in the Poincare sphere, to address additive and Poisson noise, with one of the vertices invariant to changes in the axis positions. We provide numerical simulations, considering misalignment errors, to analyze the robustness of the configuration. The results show that the proposed configuration helps to maintain the volume enclosed by the tetrahedron with high tolerance to fast-axis orientation errors. The condition number will remain below 3.07 for common misalignment errors and below 1.88 for more controlled liquid crystals. This optimization will improve the performance of liquid crystals polarimeters, with a more robust configuration that also considers misalignment errors, beyond additive and Poisson noise.
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Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered <120 days before hospitalization and 19% (95% CI = 2%-32%) if the interval was 120-364 days. VE of the original monovalent vaccine against COVID-19-related hospitalization was 31% (95% CI = 18%-43%) if the last dose was received any time within the previous year. VE against critical COVID-19-related illness, defined as receipt of noninvasive or invasive mechanical ventilation, vasoactive infusions, extracorporeal membrane oxygenation, and illness resulting in death, was 57% (95% CI = 21%-76%) when the most recent dose was received <120 days before hospitalization, 25% (95% CI = -9% to 49%) if it was received 120-364 days before hospitalization, and 38% (95% CI = 15%-55%) if the last dose was received any time within the previous year. VE was similar after excluding children and adolescents with documented immunocompromising conditions. Because of the low frequency of children who received updated COVID-19 vaccines and waning effectiveness of original monovalent doses, these data support CDC recommendations that all children and adolescents receive updated COVID-19 vaccines to protect against severe COVID-19.
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Vacinas contra COVID-19 , COVID-19 , Humanos , Adolescente , Criança , Estados Unidos/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas de mRNA , Eficácia de Vacinas , SARS-CoV-2 , Hospitalização , RNA MensageiroRESUMO
BACKGROUND: Lymphocytic colitis (LC) in the pediatric population has been associated with immune dysregulation. METHODS: Single-center retrospective study of pediatric LC. RESULTS: 50 patients (35 female, 70%) with a median age of 12 years at diagnosis (interquartile range: 5.7-15.8) of LC were identified. At presentation, 11 patients (22%) had malnutrition, 16 (32%) had a known underlying immune dysregulation, 4 (8%) had celiac disease (CD), and none had a diagnosis of inflammatory bowel disease. The most common medications prior to diagnosis were non-steroidal anti-inflammatory drugs, proton pump inhibitor, and selective serotonin reuptake inhibitors (10% each). Colonic biopsies showed a median number of intraepithelial lymphocytes (IELs)/100 epithelial cells of 48 (range: 25-85), and only 10% of cases had neutrophilic cryptitis. Upper gastrointestinal tract findings included lymphocytic esophagitis (4%), and duodenal IELs without and with villous blunting (9% each) (n: 47). Ten patients (23%) had increased IELs in the terminal ileum (n: 43). Treatments including 5-ASA, budesonide, prednisone, and gluten-free diet improved symptoms in <50% of patients (n: 42), and all follow-up colonoscopies showed persistent LC (n: 13). CONCLUSION: Our study supports the association of LC with immune-mediated conditions, most commonly celiac disease. Symptomatic improvement was seen in <50% of patients with none of the patients with repeat colonoscopy showing histologic improvement.
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Doença Celíaca , Colite Linfocítica , Doenças Inflamatórias Intestinais , Humanos , Criança , Feminino , Colite Linfocítica/diagnóstico , Colite Linfocítica/patologia , Doença Celíaca/diagnóstico , Doença Celíaca/patologia , Estudos Retrospectivos , Duodeno/patologia , Doenças Inflamatórias Intestinais/patologiaRESUMO
BACKGROUND: Pediatric granular cell tumors (GCT) involving the gastrointestinal tract (GIT) are rare with limited case report/series reported to date. METHODS: Multicenter retrospective study of pediatric GIT GCT. RESULTS: A total of 10 cases were included in the study with a median age of 13.5 years (range: 7-18 years) and were predominantly female patients (60%). In half of the patients no significant medical history was present with the remaining 5 having Crohn disease (10%), eosinophilic esophagitis (EoE) (10%), Crohn disease and EoE (10%), growth hormone deficiency (10%), and aplasia cutis congenita (10%). The GCT median size was 1.3 cm (range: 1-1.6 cm) and were more commonly located in the esophagus (70%) followed by the stomach (20%) and rectum (10%). Most of the cases showed round/polygonal tumor cells with abundant granular cytoplasm, and none of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. None of our cases received specific therapy for GCT other than clinical follow-up, and none of the patients had evidence of local recurrence or metastatic disease. CONCLUSION: We present our multicenter experience with GIT GCT, all cases had a benign course. Interestingly, 4 of the esophageal GCT cases (including 2 patients with EoE) showed an eosinophil-rich esophagitis in the underlying mucosa.
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Neoplasias Gastrointestinais , Tumor de Células Granulares , Humanos , Tumor de Células Granulares/patologia , Tumor de Células Granulares/diagnóstico , Adolescente , Feminino , Criança , Masculino , Estudos Retrospectivos , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/diagnósticoRESUMO
BACKGROUND: Granulomas in pediatric liver biopsies (GPLB) are rare with the largest pediatric cohort reported over 25 years ago. METHODS: Single-center retrospective study of GPLB. RESULTS: Seventeen liver biopsies from 16 patients with granulomas were identified (9 boys, 56%) with a median age of 13 years (range: 1-18) for which the most common indication was the presence of a nodule/mass (47%). Significant comorbidities were seen in 13 patients (81%) and included: liver transplant (25%), history of a neoplasm (25%), autoimmune hepatitis (6%), Crohn disease (6%), bipolar disorder (6%), severe combined immunodeficiency (6%), and sickle cell disease (6%). Eleven patients were taking multiple medications at the time of biopsy. Granulomas were more commonly pan-acinar (11 cases) followed by subcapsular (4 cases), portal (1 case), and periportal (1 case). Necrosis was seen in 10 cases (59%). GMS stain was positive in 2 cases for Histoplasma-like yeast; microbiological cultures were negative in all cases (no: 4). A 18S and 16S rRNA gene sequencing performed in 15 cases revealed only 1 with a pathogenic microorganism, Mycobacterium angelicum. CONCLUSION: In our experience, GPLB are heterogenous with only 3 cases having an identifiable infectious etiology and many of the remaining cases being associated to multiple medications, suggesting drug-induced liver injury as possible etiology.
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Granuloma , Hepatopatias , Humanos , Masculino , Criança , Feminino , Adolescente , Estudos Retrospectivos , Pré-Escolar , Lactente , Biópsia , Granuloma/patologia , Granuloma/diagnóstico , Hepatopatias/patologia , Hepatopatias/diagnóstico , Fígado/patologiaRESUMO
OBJECTIVES: Characterize the clinicopathologic features of liver biopsies from patients with celiac disease (CD). METHODS: Single center, retrospective search for liver biopsies from patients with CD. RESULTS: 36 unique patients were included, median age of 46 years (range: 2-75), including 5 pediatric patients, with an overall female predominance (25, 69 %) but in in children a male predominance was seen (p = 0.023). Most cases (75 %) had an underlying condition including autoimmune hepatitis (AIH) (11 %), AIH/primary biliary cholangitis (PBC) overlap (3 %) and PBC (3 %). The median body mass index was 28, with 4 (11 %) underweight and 22 (61 %) overweight/obese patients. The most common histologic pattern was steatosis (18, 50 %), considered severe in 5 (14 %) and in 7 (19 %) regarded as steatohepatitis. The other histologic patterns included a nonspecific portal and/or lobular inflammation ("celiac hepatitis") in 9 cases (25 %), autoimmune hepatitis (3, 8 %), chronic cholestatic pattern (3, 8 %), chronic hepatitis (1, 3 %), acute lobular hepatitis (1, 3 %) and stablished cirrhosis (1, 3 %). Additionally, 2 of the cases with steatosis show cirrhosis. CONCLUSIONS: The biopsy findings from patients with CD are heterogenous and in most represent a concomitant underlying disease, particularly metabolic dysfunction-associated steatotic liver disease. Additionally, CD injury should remain in the differential diagnosis in liver biopsies with a nonspecific portal and/or lobular inflammation.
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Doença Celíaca , Hepatite Autoimune , Fígado , Humanos , Doença Celíaca/patologia , Doença Celíaca/complicações , Feminino , Masculino , Criança , Estudos Retrospectivos , Pré-Escolar , Adolescente , Adulto , Pessoa de Meia-Idade , Hepatite Autoimune/patologia , Hepatite Autoimune/complicações , Fígado/patologia , Biópsia , Idoso , Adulto Jovem , Fígado Gorduroso/patologia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/complicações , Cirrose Hepática Biliar/patologia , Cirrose Hepática Biliar/complicaçõesRESUMO
Intraoperative consultation of donor liver is an important part of transplant evaluation and determination of liver eligibility. In this study, we describe incidental pathologic findings discovered during the pretransplant evaluation of liver donors in our Institution from 1/2010 to 12/2022. During this 13-year period 369 intraoperative consultations from 262 liver donors were performed. Of those cases, incidental findings were identified in 22 cases (5.9 %) from 19 donors (7.3 %); two donors had more than one lesion. The median age of this subset of patients was 53 years (range: 18-70) and females predominated (63 %). Sixteen of the donors had abnormal findings in the liver: 6 bile duct hamartoma (BDH), 5 hyalinized nodule with Histoplasma capsulatum, 5 focal nodular hyperplasia (FNH), 2 bile duct adenomas (BDA), 1 biliary cyst and 1 hemangioma. One donor had both FNH and a BDH. One BDH and 1 BDA case was misdiagnosed as malignancy during the frozen section evaluation. Three donors had extrahepatic pathologies: a pancreatic tail schwannoma, a low-grade appendiceal mucinous neoplasm, and a lymph node with metastatic endometrial endometrioid adenocarcinoma. Of the 19 livers, the final organ disposition was available for 9: 6 were transplanted (67 %) and 3 were discarded (33 %). Two of the 3 discarded organs were misdiagnosed BDH and BDA cases, and one was incorrectly reported as having 90 % microvesicular steatosis during the frozen assessment. We present the clinicopathologic characteristics of liver donors with incidental findings during the pre-transplant evaluation which could lead to unwarranted graft dismissal if misdiagnosed. Additionally, incidental fungal infections can have implications for immunosuppressive therapy and the decision to use or reject the graft.
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Fígado Gorduroso , Transplante de Fígado , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Achados Incidentais , Doadores Vivos , Fígado/patologia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/patologiaRESUMO
This study introduces a lightweight storage system for wearable devices, aiming to optimize energy efficiency in long-term and continuous monitoring applications. Utilizing Direct Memory Access and the Serial Peripheral Interface protocol, the system ensures efficient data transfer, significantly reduces energy consumption, and enhances the device autonomy. Data organization into Time Block Data (TBD) units, rather than files, significantly diminishes control overhead, facilitating the streamlined management of periodic data recordings in wearable devices. A comparative analysis revealed marked improvements in energy efficiency and write speed over existing file systems, validating the proposed system as an effective solution for boosting wearable device performance in health monitoring and various long-term data acquisition scenarios.
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Introduction Implant-based breast reconstructions (IBBRs) increased last years despite the growing indications for radiotherapy in the treatment of breast cancer. As a result, complications and reconstructive failures associated to IBBR have increased. Autologous breast reconstruction (ABR) using fat-augmented latissimus dorsi (FALD) has become popular in recent years. Methods We aimed to evaluate conversion to ABR using latissimus dorsi and immediate fat grafting in 61 cases with IBBR failure. Results Immediate reconstruction was found significatively related with an increased number of surgeries resulting from IBBR complications ( p < 0.001). Note that 41% of the cases presented a grade III/IV Baker and Palmer capsular contracture, 29% implant extrusion, and 21% implant infection. Mean survival of the first implant was 16.95 months. ABR process was completed in 47% of cases with a single surgery. Statistically significant differences were observed between this fact and previous IBBR failure due to infection ( p = 0.03) or extrusion ( p = 0.01). Mean volume of fat graft was 429.61 mL, mean length of the surgical procedure was 3.17 hours, and the average length of hospital stay after surgery was 2.67 days. Only 3.3% of the cases developed some major complication. None of the cases presented reconstructive failure. Conclusion FALD is a very safe total ABR technique, an important fact in patients with previous reconstructive failures. The large volume of fat that can be grafted in a single surgery allows the reconstruction of breast in a reasonable size. The reduced length of surgery and hospital stay make the FALD technique an option to consider when an autologous but efficient and safe reconstruction is desired.
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Selective harvest, such as poaching, impacts group-living animals directly through mortality of individuals with desirable traits, and indirectly by altering the structure of their social networks. Understanding the relationship between disturbance-induced, structural network changes and group performance in wild animals remains an outstanding problem. To address this problem, we evaluated the immediate effect of disturbance on group sociality in African savanna elephants-an example, group-living species threatened by poaching. Drawing on static association data from ten free-ranging groups, we constructed one empirically based, population-wide network and 100 virtual networks; performed a series of experiments 'poaching' the oldest, socially central or random individuals; and quantified the immediate change in the theoretical indices of network connectivity and efficiency of social diffusion. Although the social networks never broke down, targeted elimination of the socially central conspecifics, regardless of age, decreased network connectivity and efficiency. These findings hint at the need to further study resilience by modeling network reorganization and interaction-mediated socioecological learning, empirical data permitting. The main contribution of our work is in quantifying connectivity together with global efficiency in multiple social networks that feature the sociodemographic diversity likely found in wild elephant populations. The basic design of our simulation makes it adaptable for hypothesis testing about the consequences of anthropogenic disturbance or lethal management on social interactions in a variety of group-living species with limited, real-world data.
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Animais Selvagens/fisiologia , Elefantes/fisiologia , Comportamento Social , Animais , Biologia Computacional , Conservação dos Recursos Naturais , Crime , Feminino , Humanos , Caça , Masculino , Dinâmica PopulacionalRESUMO
BACKGROUND: Focal nodular hyperplasia (FNH) is a benign liver lesion classically presenting in young females. In children, FNH is rare and its detailed clinicopathologic characteristics remain largely unknown. Furthermore, there are no studies comparing pediatric FNH features to those presenting in adults. METHODS: In this study, we analyzed a total of 47 FNH cases in pediatric patients (age range: 23 days to 18 years) from 3 centers and compared them to a cohort of 31 FNH cases in adult patients (age range: 20-64 years). RESULTS: Of the pediatric cases, 13 cases (28%) had a history of a prior malignancy of which 4 were treated with chemoradiation and stem cell transplantation (SCT), 5 with chemoradiation alone and 3 with chemotherapy and SCT. In the pediatric cases 41 (87%) had a central scar and 46 (98%) had fibrous septa. Both pediatric and adult FNH were more common in female patients. Cases in pediatric patients were also significantly associated with larger size (P = .047), absence of dystrophic vessels (P = .001), absence of sinusoidal dilatation (P = .029), pseudoacini formation (P = .013), and steatosis (P = .029). CONCLUSION: In our experience although most cases of pediatric FNH show the classic histologic features seen in adults, some significant differences exist, and awareness of these findings could aid in the evaluation of these rare cases.
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Hiperplasia Nodular Focal do Fígado , Neoplasias Hepáticas , Neoplasias , Adulto , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Quimiorradioterapia , Hiperplasia Nodular Focal do Fígado/diagnóstico , Hiperplasia Nodular Focal do Fígado/terapia , Hiperplasia Nodular Focal do Fígado/complicações , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias/patologia , Estudos Retrospectivos , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , MasculinoRESUMO
BACKGROUND: Motion analysis of surgical maneuvers provides useful quantitative information for the objective evaluation of the surgeons. However, surgical simulation laboratories for laparoscopic training do not usually integrate devices that help quantify the level of skills of the surgeons due to their limited resources and the high costs of new technologies. The purpose of this study is to present the construct and concurrent validity of a low-cost motion tracking system, based on a wireless triaxial accelerometer, employed to objectively evaluate psychomotor skills of surgeons during laparoscopic training. METHODS: An accelerometry system, a wireless three-axis accelerometer with appearance of wristwatch, was placed on the dominant hand of the surgeons to register the motion during the laparoscopy practice with the EndoViS simulator, which simultaneously recorded the motion of the laparoscopic needle driver. This study included the participation of 30 surgeons (6 experts, 14 intermediates and 10 novices) who performed the task of intracorporeal knot-tying suture. Using 11 motion analysis parameters (MAPs), the performance of each participant was assessed. Subsequently, the scores of the three groups of surgeons were statistically analyzed. In addition, a validity study was conducted comparing the metrics between the accelerometry-tracking system and the EndoViS hybrid simulator. RESULTS: Construct validity was achieved for 8 of the 11 metrics examined with the accelerometry system. Concurrent validity demonstrated that there is a strong correlation between the results of the accelerometry system and the EndoViS simulator in 9 of 11 parameters, showing reliability of the accelerometry system as an objective evaluation method. CONCLUSION: The accelerometry system was successfully validated. This method is potentially useful to complement the objective evaluation of surgeons during laparoscopic practice in training environments such as box-trainers and simulators.
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Competência Clínica , Laparoscopia , Humanos , Reprodutibilidade dos Testes , Laparoscopia/métodos , Desempenho Psicomotor , AcelerometriaRESUMO
The aims of this study were (1) to describe and examine differences in change of direction (COD) performance and the magnitude of asymmetries in para-footballers with cerebral palsy (CP) and controls and (2) to evaluate the association between COD outcomes and linear sprint performance. Twenty-eight international para-footballers with CP and thirty-nine non-impaired football players (control group) participated in this study. All participants completed a 10-m sprint and two attempts of the 505 COD test with the dominant and non-dominant leg. The COD deficit was calculated using the difference between the 505 test and the 10-m sprint time, while the asymmetry index was determined by comparing each leg's completion time and COD deficit. Players across groups showed interlimb asymmetries between the dominant and non-dominant legs in COD outcomes and deficit (p < 0.05, dg = -0.40 to -1.46), although these asymmetries imbalance were not significantly different between the sexes with and without impairment. Males with CP exhibited a faster directional COD speed and a shorter COD deficit than their female counterparts (p < 0.01, dg = -1.68 to -2.53). Similarly, the control group had faster scores than the CP groups of the same sex (p < 0.05, dg = 0.53 to 3.78). Lastly, the female CP group and male control groups showed a significant association between sprint and the COD deficit in the dominant leg (p < 0.05, r = -0.58 to 0.65). Therefore, the use of directional dominance, the COD deficit, and asymmetry outcomes could be helpful for classification purposes to assess the impact of the impairment on sport-specific activity testing according to sex.
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Desempenho Atlético , Paralisia Cerebral , Futebol Americano , Humanos , Masculino , Feminino , Caracteres Sexuais , Estudos TransversaisRESUMO
Leptocarpha rivularis is a native South American plant used ancestrally by Mapuche people to treat gastrointestinal ailments. L. rivularis flower extracts are rich in molecules with therapeutic potential, including the sesquiterpene lactone leptocarpin, which displays cytotoxic effects against various cancer types in vitro. However, the combination of active molecules in these extracts could offer a hitherto unexplored potential for targeting cancer. In this study, we investigated the effect of L. rivularis flower extracts on the proliferation, survival, and spread parameters of gastric cancer cells in vitro. Gastric cancer (AGS and MKN-45) and normal immortalized (GES-1) cell lines were treated with different concentrations of L. rivularis flower extracts (DCM, Hex, EtOAc, and EtOH) and we determined the changes in proliferation (MTS assay, cell cycle analysis), cell viability/cytotoxicity (trypan blue exclusion assay, DEVDase activity, mitochondrial membrane potential MMP, and clonogenic ability), senescence (ß-galactosidase activity) and spread potential (invasion and migration assays using the Boyden chamber approach) in all these cells. The results showed that the DCM, EtOAc, and Hex extracts display a selective antitumoral effect in gastric cancer cells by affecting all the cancer parameters tested. These findings reveal an attractive antitumoral potential of L. rivularis flower extracts by targeting several acquired capabilities of cancer cells.
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Antineoplásicos , Neoplasias Gástricas , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular TumoralRESUMO
BACKGROUND: Indications for breast-conserving surgery and adjuvant radiotherapy (BCSAR) in patients with breast carcinoma are increasing, as are indications for risk-reducing mastectomy (RRM) in healthy subjects. Most of these cases are reconstructed with silicone shell breast implants (SSBIs). OBJECTIVES: The aim of this work was to study complications of SSBIs in breast reconstruction in patients undergoing RRM with previous BCSAR. METHODS: A prospective cohort study was designed. The study group included cases of RRM reconstructed with SSBI in patients who had previously undergone BCSAR in the same breast. The control group consisted of patients with high-risk breast cancer who had undergone RRM and immediate SSBI reconstruction without previous BCSAR. RESULTS: There was a history of BCSAR in 15.8% of cases. The first SSBI used in immediate reconstruction after RRM was replaced in 51.5% of cases with a mean [standard deviation] survival of 24.04 [28.48] months. BCSAR was significantly associated with pathological capsular contracture (P = .00) with this first SSBI (37.5% vs 5.9%). Of the cases requiring the replacement of the first SSBI, 44.23% suffered failure of the second SSBI, with a mean survival of 27.95 [26.53] months. No significant association was found between the consecutive development of capsular contracture in the second SSBI and a previous history of BCSAR (P = .10). CONCLUSIONS: BCSAR prior to RRM reconstructed with an SSBI is associated with a significant increase in pathological capsular contracture. Patients should be warned of the high rate of SSBI complications and reconstruction failure. Polyurethane-coated implants may provide an alternative in cases in which alloplastic reconstruction is considered in patients with previous BCSAR.
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Implantes de Mama , Neoplasias da Mama , Contratura , Mamoplastia , Humanos , Feminino , Mastectomia/efeitos adversos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Implantes de Mama/efeitos adversos , Mastectomia Segmentar , Silicones , Radioterapia Adjuvante/efeitos adversos , Estudos Prospectivos , Contratura/cirurgia , Estudos RetrospectivosRESUMO
Graft-versus-host disease (GVHD) remains a major complication for patients who have undergone hematopoietic stem cell transplantation. The Lerner system is the most widely used histologic grading score for gastrointestinal GVHD but its clinic utility is debated. The aim of our study was to develop a novel histologic grading system for gastrointestinal GVHD that incorporates independent evaluation of both apoptotic counts and crypt destruction. Colonic biopsies taken to assess for GVHD were retrospectively assessed for: Crypt damage (No crypt dropout or ulceration-0; crypt dropout without ulceration-1; ulceration-2) and crypt apoptotic counts (No apoptosis-0; 1-6 apoptotic bodies per 10 contiguous crypts-1; >6apoptotic bodies per 10 contiguous crypts-2). The two scores were added together to get an overall grade (0-4). Alternative apoptotic cutoff points were examined. An apoptotic cutoff of >9 apoptotic bodies per 10 contiguous crypts marginally improved the area under the curve (AUC), but the AUCs from the resulting novel grade calculations were not significantly different (p = 0.10). Lerner grading was also applied. The study group consisted of an initial analysis cohort (n = 191) and a second validation cohort from a separate institution (n = 97). In the initial analysis cohort, our histologic grading system provided prognostic stratification for GVHD-related death within 6 months (p = 0.0004, AUC = 0.705). The Lerner system performed similarly in terms of providing prognostic stratification for GVHD-related death (p = 0.0001, AUC = 0.707). In the external validation cohort, our histologic grading system was not associated with GVHD-related death (p = 0.14, AUC = 0.621), but the Lerner system was associated with GVHD-related death (p = 0.048, AUC = 0.663). While our grading system may have some advantages compared to the Lerner system, due to lack of reproducibility we do not currently recommend widespread adoption of this system. Nonetheless, we present a standardized tool for assessing both apoptosis and crypt damage. Future studies assessing alternative histologic grading systems with external validation and further examination the lower apoptotic threshold for GVHD diagnosis are warranted.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Colo/patologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation in DICER1 provided the opportunity to identify and continue to recognize a number seemingly unrelated extrapulmonary neoplasms: Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations. Each of these neoplasms is characterized by a second somatic mutation in DICER1. In this review, we have summarized the salient clinicopathologic aspects of these tumors whose histopathologic features have several overlapping morphologic attributes particularly the primitive mesenchyme often with rhabdomyoblastic and chondroid differentiation and an uncommitted spindle cell pattern. Several of these tumors have an initial cystic stage from which there is progression to a high grade, complex patterned neoplasm. These pathologic findings in the appropriate clinical setting should serve to alert the pathologist to the possibility of a DICER1-associated neoplasm and initiate appropriate testing on the neoplasm and to alert the clinician about the concern for a DICER1 mutation.
Assuntos
Neoplasias Pulmonares/etiologia , Neoplasias Pleurais/etiologia , Blastoma Pulmonar/etiologia , Ribonuclease III/genética , Causalidade , Mutação em Linhagem Germinativa , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pleurais/complicações , Blastoma Pulmonar/complicações , SíndromeRESUMO
We offer a new perspective on the problem of characterizing mesoscopic fluctuations in the interplateau regions of the integer quantum Hall transition. We found that longitudinal and transverse conductance fluctuations, generated by varying the external magnetic field within a microscopic model, are multifractal and lead to distributions of conductance increments (magnetoconductance) with heavy tails (intermittency) and signatures of a hierarchical structure (cascade) in the corresponding stochastic process, akin to Kolmogorov's theory of fluid turbulence. We confirm this picture by interpreting the stochastic process of the conductance increments in the framework of H theory, which is a continuous-time stochastic approach that incorporates the basic features of Kolmogorov's theory. The multifractal analysis of the conductance "time series," combined with the H-theory formalism, provides strong support for the overall characterization of mesoscopic fluctuations in the quantum Hall transition as a multifractal stochastic phenomenon with multiscale hierarchy, intermittency, and cascade effects.