Expression of p27 and c-Myc by immunohistochemistry in breast ductal cancers in African American women.

OBJECTIVES: Proteins p27 and c-Myc are both key players in the cell cycle. While p27, a tumor suppressor, inhibits progression from G1 to S phase, c-Myc, a proto-oncogene, plays a key role in cell cycle regulation and apoptosis. The objective of our study was to determine the association between expression of c-Myc and the loss of p27 by immunohistochemistry (IHC) in the four major subtypes of breast cancer (BC) (Luminal A, Luminal B, HER2, and Triple Negative) and with other clinicopathological factors in a population of 202 African-American (AA) women. MATERIALS AND METHODS: Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 AA women. Five micrometer sections were stained with a mouse monoclonal antibody against p27 and a rabbit monoclonal antibody against c-Myc. The sections were evaluated for intensity of nuclear reactivity (1-3) and percentage of reactive cells; an H-score was derived from the product of these measurements. RESULTS: Loss of p27 expression and c-Myc overexpression showed statistical significance with ER negative (p < 0.0001), PR negative (p < 0.0001), triple negative (TN) (p < 0.0001), grade 3 (p = 0.038), and overall survival (p = 0.047). There was no statistical significant association between c-Myc expression/p27 loss and luminal A/B and Her2 overexpressing subtypes. CONCLUSION: In our study, a statistically significant association between c-Myc expression and p27 loss and the triple negative breast cancers (TNBC) was found in AA women. A recent study found that constitutive c-Myc expression is associated with inactivation of the axin 1 tumor suppressor gene. p27 inhibits cyclin dependent kinase2/cyclin A/E complex formation. Axin 1 and CDK inhibitors may represent possible therapeutic targets for TNBC.

Omenn Syndrome Presenting with Striking Erythroderma and Extreme Lymphocytosis in a Newborn.

Omenn syndrome is an autosomal recessive form of "leaky" severe combined immune deficiency resulting in distinct phenotypic features. The patient described herein had an atypical presentation of Omenn syndrome, with conspicuous erythroderma and extreme lymphocytosis at birth, in contrast to the typical evolution of rash seen during the first few weeks of life. In addition, the skin findings were secondary to infiltration of CD8+ (cytotoxic) T-cells in contrast to the CD4+ (helper) T-cells typically seen, which broadens the Omenn syndrome phenotype.

Environmental condition-dependent effects of aquatic humic substances on the distribution of phenanthrene in microplastic-contaminated aquatic systems.

Numerous studies have focused on the interaction between microplastics (MPs) and phenanthrene (PHE) in aquatic environments. However, the intricate roles of aquatic humic substances (HS), which vary with environmental conditions, in influencing PHE-MP interactions are not yet fully understood. This study investigates the variable and environmentally sensitive roles of HS in modifying the interactions between PHE and polyethylene (PE) MPs under laboratory-simulated aquatic conditions with varying solution chemistry, including pH, HS types, HS concentrations, and ionic strength. Our findings show that the presence of HS significantly reduces the adsorption of PHE onto both pristine and aged PE MPs, with a more pronounced reduction observed in aged PEs. This effect is highlighted by a notable decrease in the partitioning coefficient (Kd) of PHE, which falls from 2.60 × 104 to 1.30 × 104 L/kg on MPs in the presence of HS. The study also demonstrates that alterations in the net charge of HS solutions are crucial in modifying PHE distribution onto PEs. An initial decrease in Kd values at higher pH levels is reversed when HS is introduced. Furthermore, an increase in HS concentrations is associated with lower Kd values. In conditions of higher ionic strength, the retention of PHE by HS is intensified, likely due to an enhanced salting-out effect. This research highlights the significant role of aquatic HS in modulating the distribution of PHE in MP-polluted waters, which is highly influenced by various solution chemistry factors. The findings are vital for understanding the fate of PHE in MP-contaminated aquatic environments and can contribute to refining predictive models that consider diverse solution chemistry scenarios.

Change in adsorption behavior of aquatic humic substances on microplastic through biotic and abiotic aging processes.

Interactions between microplastics (MPs) and humic substances (HS) are inevitable in MP-contaminated aquatic environment because of the ubiquitous presence of HS. In this study, we explored the effects of abiotic and biotic aging processes on the adsorption behavior of aquatic HS on MPs. Aging experiments were conducted using polyethylene (PE) as a representative MP, in which UV irradiation and microbial incubation were applied for 15 to 18 days to mimic the natural abiotic and biotic aging processes. Surface modifications after the aging treatments were evidenced by the appearance of CO, CO, O-C=O, and -OH groups; the formation of grooves on UV-aged PE; and the formation of biofilms on the surface of bio-aged PE. The specific surface areas of both treated PE MPs increased with aging. Higher HS adsorption on PE surface was observed after the aging treatments, with a highest kinetic rate for UV-aged PE than that for bio-aged PE. The adsorption isotherm models revealed that the aging processes enhanced the HS adsorption tendency, as evidenced by the highest adsorption capacity for UV-aged PE (~187 µg C/m2), followed by bio-aged PE (~157 µg C/m2) and pristine PE (~87.5 µg C/m2) for a comparable extended aging period (15-18 days). The difference was more pronounced at a lower pH. The enhanced HS adsorption was mainly attributed to the formation of hydrogen bonds, whereas HS adsorption on pristine PE was dominated by hydrophobic interactions and weak van der Waals interactions. Among the two identified fluorescent components (terrestrial humic-like C1 and protein-like C2), C1 exhibited a higher affinity for adsorption onto PE irrespective of aging. Our findings provide insights into the substantial changes that occur in the interactions between MPs and aquatic organic matter with aging processes, which may alter the fate and environmental impacts of MPs in many aquatic systems.

Visible light-driven photocatalytic rapid degradation of organic contaminants engaging manganese dioxide-incorporated iron oxide three dimensional nanoflowers.

Water pollution via hazardous organic pollutants poses a high threat to the environment and globally imperils aquatic life and human health. Therefore, the elimination of toxic organic waste from water sources is vital to ensure a healthy green environment. In the current work, we synthesized α-MnO2-Fe3O4 3D-flower like structure using a two-step hydrothermal method and explored the combination in a visible-light-assisted photocatalytic degrdation of dyes. The attained high specific surface area of 82 m2/g with mesoporous nature of α-MnO2 and Fe3O4 together can generate more active sites after exposure to visible light, leading to remarkable photodegradation performance. Significantly, twofold higher dye (methylene blue, MB (94.8%/120 min; crystal violet, CV (93.7%/120 min)) and drug (LVO 91%/90 min) photodegradations were observed with α-MnO2-Fe3O4 as catalyst than pure α-MnO2 and Fe3O4 at pH 6, respectively. This is attributed to the higher surface area and synergistic effect between Mn and Fe. More than 85% stability was observed with optimized catalysts employing MB and CV dyes, demonstrating the excellent reusability of the α-MnO2-Fe3O4. The underlying mechanism indicates that the formation of reactive oxygen species predominantly plays a role in the photodegradation of dyes under visible light. Consequently, these new insights will shed light on the practical applications of the α-MnO2-Fe3O4 3D-flower-like spherical structure for eco-friendly remediation via wastewater treatment.

A diagnostic approach to paratesticular lesions with tubulopapillary architecture: a series of 16 serous borderline tumors/low-grade serous carcinoma and 14 well-differentiated papillary mesothelial tumors and mesothelioma.

As there is limited literature on paratesticular tumors of müllerian and mesothelial origin, we reviewed archived cases of serous borderline tumors (n = 15), low-grade serous carcinoma (n = 1), well-differentiated papillary mesothelial tumors (WDPMTs; n = 2), and mesothelioma (n = 12), for relevant clinicopathologic features. Molecular profiling data from the American Association for Cancer Research (AACR) GENIE registry was accessed for 8 additional patients with testicular mesothelioma. For tumors of mesothelial origin, the median age at surgical excision was 62 years, the median size was 4.5 cm, and they consistently exhibited positivity for mesothelial markers (CK5/6, calretinin, WT1, and D2-40). Recurrent alterations of the NF2 gene were identified in 3 of 8 patients (38%), and alterations of BAP1 and CDKN2A were relatively infrequent. While one patient with WDPMT had a recurrence, a second patient with WDPMT progressed to a biphasic mesothelioma 2 years after initial resection. For tumors of müllerian origin, the median age at surgical excision was 45 years, the median size was 2.5 cm, and these exhibited consistent positivity for ER, WT1, and PAX8. Although no recurrences were documented in patients with serous borderline tumors, a single patient with a low-grade serous carcinoma developed widely metastatic disease and died of disease-related complications. Our study emphasizes the need for close clinical follow-up in patients with WDPMT and highlights the prognostic significance of documenting invasive behavior in tumors of müllerian origin as they can have an aggressive clinical course. Finally, our results suggest that NF2 alterations may play an important role in the pathogenesis of testicular mesothelioma.

A facile mechanochemical preparation of Co3O4@g-C3N4 for application in supercapacitors and degradation of pollutants in water.

Our study is aimed at synthesizing cobalt oxide (Co3O4) with graphite carbon nitride (g-C3N4) to form a Co3O4@g-C3N4 hybrid through a green mechanochemical one-pot synthetic approach for manufacturing efficient supercapacitor electrodes and photocatalysts. In the present study, the Co3O4@g-C3N4 hybrid revealed a significantly higher specific capacitance (Cs) (of ~ 457.2 Fg-1 at a current density of 1 Ag-1) than that of the pristine Co3O4, which proved its pseudocapacitive behavior, with a couple of redox peaks observed in three electrode measurements (obtained by using a 3.0-M KOH aqueous electrolyte). The optimized Co3O4@g-C3N4 hybrid was further embedded for a symmetric supercapacitor performance, delivering an excellent Cs of ~ 92 Fg-1 at a current density of 1 Ag-1; this was supplemented with a remarkable cycling stability (~ 92% over 5000 cycles). The Co3O4@g-C3N4 hybrid was further examined for photocatalysis activity using a rhodamine B (RhB) dye, and more than 95% RhB dye was degraded through the photocatalytic reduction process (after 60 min of UV irradiation). This Co3O4@g-C3N4 hybrid catalyst exhibited excellent reusability and stability and appears to be a highly efficient, cost-effective, eco-friendly, and reusable catalyst; the g-C3N4 present with the Co3O4 acted as a conductive nano-network, leading to a higher capacitive and photocatalytic performance.

Multi-Focus Image Fusion: Algorithms, Evaluation, and a Library.

Image fusion is a process that integrates similar types of images collected from heterogeneous sources into one image in which the information is more definite and certain. Hence, the resultant image is anticipated as more explanatory and enlightening both for human and machine perception. Different image combination methods have been presented to consolidate significant data from a collection of images into one image. As a result of its applications and advantages in variety of fields such as remote sensing, surveillance, and medical imaging, it is significant to comprehend image fusion algorithms and have a comparative study on them. This paper presents a review of the present state-of-the-art and well-known image fusion techniques. The performance of each algorithm is assessed qualitatively and quantitatively on two benchmark multi-focus image datasets. We also produce a multi-focus image fusion dataset by collecting the widely used test images in different studies. The quantitative evaluation of fusion results is performed using a set of image fusion quality assessment metrics. The performance is also evaluated using different statistical measures. Another contribution of this paper is the proposal of a multi-focus image fusion library, to the best of our knowledge, no such library exists so far. The library provides implementation of numerous state-of-the-art image fusion algorithms and is made available publicly at project website.

Rare case of non-producer variant of plasma cell dyscrasias with circulating plasma cells.

Non-producing variant of plasma cell disorders with circulating plasma cells is an aggressive variant of plasma cell dyscrasias with relatively poor outcomes. A 75-year-old man was admitted due to anaemia (90 g/L) and thrombocytopenia (9×109/L). Comprehensive metabolic panel showed creatinine of 1.34 mg/dL, total protein of 6 g/dL, and corrected calcium was normal. Peripheral smear review showed 8% circulating atypical plasmacytoid cells. Bone marrow biopsy (BMB) confirmed plasma cell myeloma involving 90%-95% of bone marrow cellularity. Serum protein electrophoresis showed no monoclonal protein. Due to aggressive biology of non-producer variant and outcomes based on circulating plasma cells, he was started on VD-PACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide) chemotherapy. BMB after cycle 1 chemotherapy showed no morphologic, immunophenotypic, or flow cytometric features of a plasma cell neoplasm. Given excellent treatment response cycle 2 was changed to VRD (bortezomib, lenalidomide and dexamethasone). Following two cycles of VRD, he underwent autologous haematopoietic cell transplantation. Day 80 BMB suggested stringent complete response.

Loss of PTEN in high grade advanced stage triple negative breast ductal cancers in African American women.

INTRODUCTION: PTEN is a tumor suppressor gene that inhibits cell proliferation by inhibiting the phosphoinositide 3-kinase (PI3 K) signaling pathway. The significance of PTEN mutations resulting in variable PTEN expression and their impact on prognosis of breast cancer is not well established. The objective of our study was to correlate the immunohistochemical expression of PTEN in the four major subtypes of breast carcinoma (Luminal A, Luminal B, HER2 positive, and Triple Negative) in a population of 202 African-American (AA) females with other clinicopathological factors. MATERIALS AND METHODS: Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 African-American females. Five micrometer sections were stained with a mouse monoclonal antibody against PTEN. The sections were evaluated for the intensity of cytoplasmic and nuclear reactivity. Bivariate analysis was done via χ2 analysis and survivability data was calculated via the generation of Kaplan-Meier curves (SPSS v19). RESULTS: Loss of PTEN expression was associated with ER negative (p = 0.021), PR negative (p = 0.024) and triple negative (p = 0.0024) breast ductal cancers. It was marginally associated with distant metastasis (p = 0.074). There was no association between PTEN loss and recurrence-free survival or overall survival. CONCLUSION: In our study, a statistically significant association between PTEN loss and the triple negative breast cancers (TNBC) was found in AA women. PTEN inhibits PI3 K resulting in decreased activation of downstream effector, mammalian target of rapamycin (mTOR). Loss of PTEN results in cell proliferation through activation of mTOR. Targeted therapy with mTOR inhibitors might be useful in the treatment of TNBC.

De novo development of gliomas in a child with neurofibromatosis type 1, fragile X and previously normal brain magnetic resonance imaging.

Fifteen to 20% of children with neurofibromatosis type 1 develop low-grade glial neoplasms. However, since neuroimaging is not routinely obtained until a child is clinically symptomatic, little is known about presymptomatic radiographic characteristics of gliomas in this at-risk population. Herein, we describe a child with neurofibromatosis type 1 who initially had normal brain imaging before the development of multifocal gliomas. Comparison of these serial images demonstrated that brain tumors can arise de novo in children with this cancer predisposition syndrome, further underscoring the limited prognostic value of normal baseline magnetic resonance imaging.

Polysaccharide based bionanocomposites, properties and applications: A review.

Bio-nanocomposites, composed of biopolymers and inorganic solids, show dimensions in the nanometer range (1-100nm) which can be widely used in variety of areas owing to multidimensional properties like biocompatibility, antimicrobial activity and biodegradability. Considering these versatile properties of the bio-nanocomposites this review sheds a light on the synthesis, modification, characterization and applications of bio-nanocomposites based on different polysaccharides functionalized by different nanofillers such as MMT, Ag, SiO2, TiO2, and ZnO. Most of them have been used in regenerative medicine, drug delivery, tissue engineering, electronics and food packaging. The modification of clays with biopolymers results an attractive alternative in the development of environmentally friendly materials for pollutants removal. All the technical scientific issues have been addressed highlighting the recent advancement.

Adeno associated viral vector-mediated expression of somatostatin in rat hippocampus suppresses seizure development.

Somatostatin (SST) has been suggested to play an important role in maintaining hippocampal homeostasis by modulating excitatory neurotransmission. The putative anticonvulsant role for SST was tested in an electrical amygdala kindling model. SST was cloned into serotype 5 of the adeno-associated viral (AAV) vector and delivered bilaterally into the hippocampus of adult male Sprague Dawley rats that were subsequently electrically kindled. Behavioral severity and duration of kindled seizures was compared to uninjected and GFP-injected control rats. Results demonstrated that 70% of SST treated animals did not experience class IV or V seizures without affecting the threshold for individual stimulation-evoked seizures. This result was significantly different from control groups where 100% of animals reached class V seizures. No difference in the number of stimulations required to reach the first class I-III seizures was observed in the experimental cohort relative to age-matched controls. These preclinical results suggest a putative role for SST as an anticonvulsant therapeutic modality for epilepsy.

Cortical neurovascular coupling driven by stimulation of channelrhodopsin-2.

While functional imaging is widely used in studies of the brain, how well the hemodynamic signal represents the underlying neural activity is still unclear. And there is a debate on whether hemodynamic signal is more tightly related to synaptic activity or action potentials. This study intends to address these questions by examining neurovascular coupling driven by pyramidal cells in the motor cortex of rats. Pyramidal cells in the motor cortex of rats were selectively transduced with the light sensitive cation channel channelrhodopsin-2 (ChR2). Electrophysiological recordings and optical intrinsic signal imaging were performed simultaneously and synchronously to capture the neural activity and hemodynamics induced by optical stimulation of ChR2-expressing pyramidal cells. Our results indicate that both synaptic activity (local field potential, LFP) and action potentials (multi-unit activity, MUA) are tightly related to hemodynamic signals. While LFPs in γ band are better in predicting hemodynamic signals elicited by short stimuli, MUA has better predictions to hemodynamic signals elicited by long stimuli. Our results also indicate that strong nonlinearity exists in neurovascular coupling.