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Waveguide-enhanced Raman spectroscopy (WERS) is an analytical technique frequently employed for chemical and biological sensing. Operation at visible wavelengths to harness the inverse fourth power with excitation wavelength signal scaling of Raman scattering intensity is desirable, to combat the inherent inefficiency of Raman spectroscopy. Until now, WERS demonstrations in the visible have required custom materials and fabrication, resulting in high losses and low yields. In this work, we demonstrate a silicon nitride (SIN) visible WERS platform fabricated in a 300 mm complementary metal-oxide semiconductor (CMOS) foundry. We measure the propagation loss, coupling loss, WERS signal, and background for WERS spirals designed for 532 nm and 633 nm pump wavelengths. We compare these results to the state-of-the-art near-infrared WERS platform at 785 nm. Further, we theoretically validate the relative performance of each of these WERS configurations, and we discuss the optimal WERS configuration at visible wavelengths. We conclude that a configuration optimized for 785 nm pumping provides the greatest signal-to-background ratio in the fingerprint region of the spectrum, and pumping at 633 nm maximizes Stokes signal out to 3000 cm-1.
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Cancer continues to remain a "Black Box," as there is no consensus on how it initiates, progresses, metastasizes, or recurs. Many imponderables exist about whether somatic mutations initiate cancer, do cancer stem cells (CSCs) exist, and if yes, are they a result of de-differentiation or originate from tissue-resident stem cells; why do cancer cells express embryonic markers, and what leads to metastasis and recurrence. Currently, the detection of multiple solid cancers through liquid biopsy is based on circulating tumor cells (CTCs) or clusters, or circulating tumor DNA (ctDNA). However, quantity of starting material is usually adequate only when the tumor has grown beyond a certain size. We posit that pluripotent, endogenous, tissue-resident, very small embryonic-like stem cells (VSELs) that exist in small numbers in all adult tissues, exit from their quiescent state due to epigenetic changes in response to various insults and transform into CSCs to initiate cancer. VSELs and CSCs share properties like quiescence, pluripotency, self-renewal, immortality, plasticity, enrichment in side-population, mobilization, and resistance to oncotherapy. HrC test, developed by Epigeneres, offers the potential for early detection of cancer using a common set of VSEL/CSC specific bio-markers in peripheral blood. In addition, NGS studies on VSELs/CSCs/tissue-specific progenitors using the All Organ Biopsy (AOB) test provide exomic and transcriptomic information regarding impacted organ(s), cancer type/subtype, germline/somatic mutations, altered gene expressions, and dysregulated pathways. To conclude, HrC and AOB tests can confirm the absence of cancer and categorize the rest of subjects into low/moderate/high risk of cancer, and also monitor response to therapy, remission, and recurrence.
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Neoplasias , Células-Tronco Pluripotentes , Adulto , Humanos , Células-Tronco Embrionárias/metabolismo , Diferenciação Celular , Células-Tronco Neoplásicas , Testes Hematológicos , Neoplasias/diagnóstico , Neoplasias/patologiaRESUMO
BACKGROUND: Patients with Inflammatory bowel disease (IBD) are susceptible to psychiatric co-morbidities. We aimed to ascertain the burden of anxiety, depression, and perceived stress in patients with IBD from north India. METHODS: Consenting adult patients with an established diagnosis of IBD were enrolled. The enrolled patients filled the Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS) questionnaires. The patient and disease characteristics were analyzed to determine the correlations and predictors of psychiatric comorbidities. RESULTS: A total of 318 patients (255 UC, 63 CD; mean age 40.13 ± 12.06 years, 168 [52.8%] males; mean partial Mayo score 2.10 ± 2.35; and mean HBI 2.77 ± 2.13) were enrolled. The prevalence of anxiety, depression and moderate to high perceived stress was 14%, 12%, and 41%, respectively. Females had higher mean perceived stress, anxiety and depression scores compared to males. The partial Mayo score (PMS) correlated poorly with anxiety (ρ = 0.083, p = 0.187), depression (ρ = 0.123, p = 0.49) and perceived stress (ρ = 0.169; p = 0.007). The Harvey Bradshaw index (HBI) correlated fairly with anxiety (ρ = 0.336, p = 0.007) and poorly with depression (ρ = 0.287, p = 0.022) and perceived stress (ρ = 0.20; p = 0.117). Younger age (OR 0.93, 95% CI 0.90-0.97; p = 0.001) and hand-grip strength (OR 4.63, 95% CI 1.88-11.42; p = 0.001) predicted anxiety in patients with UC while rural area of residence (OR 4.75, 95% CI 1.03-21.98; p = 0.046) and HBI (OR 1.60, 95% CI 1.12-2.29; p = 0.009) were significant predictors of anxiety in patients with CD. CONCLUSION: Psychiatric comorbidities are common in patients with IBD, with higher prevalence in females. Young adults with UC and sarcopenia; and individuals with active CD living in rural areas are at an increased risk of anxiety.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Testes Psicológicos , Autorrelato , Masculino , Adulto Jovem , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Doença de Crohn/diagnóstico , Colite Ulcerativa/diagnóstico , Estudos de Coortes , Depressão/diagnóstico , Depressão/epidemiologia , Doenças Inflamatórias Intestinais/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Índice de Gravidade de DoençaRESUMO
To study nanostructures on substrates, surface-sensitive reflection-geometry scattering techniques such as grazing incident small angle X-ray scattering are commonly used to yield an averaged statistical structural information of the surface sample. Grazing incidence geometry can probe the absolute three-dimensional structural morphology of the sample if a highly coherent beam is used. Coherent surface scattering imaging (CSSI) is a powerful yet non-invasive technique similar to coherent X-ray diffractive imaging (CDI) but performed at small angles and grazing-incidence reflection geometry. A challenge with CSSI is that conventional CDI reconstruction techniques cannot be directly applied to CSSI because the Fourier-transform-based forward models cannot reproduce the dynamical scattering phenomenon near the critical angle of total external reflection of the substrate-supported samples. To overcome this challenge, we have developed a multislice forward model which can successfully simulate the dynamical or multi-beam scattering generated from surface structures and the underlying substrate. The forward model is also demonstrated to be able to reconstruct an elongated 3D pattern from a single shot scattering image in the CSSI geometry through fast-performing CUDA-assisted PyTorch optimization with automatic differentiation.
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Glucocorticoid induced osteoporosis (GIOP) is the second most leading cause of osteoporosis. We have identified a compound, a benzofuran pyran hybrid compound 4e that has osteogenic potential and we wanted to assess its efficacy in GIOP in male mice. We assessed the effect of dexamethasone and compound 4e on primary osteoblasts using various cell based and immunofluorescence assays. For in vivo studies we administered methylprednisolone and compound 4e as a prophylactic measure in male Balb/c mice for 28 days and then evaluated the effect on bone microarchitecture by microCT, bone formation by histology along with clinically relevant bone markers. Compound 4e preserved osteoblast differentiation as evident by higher ALP positive cells and mineralization in compound treated groups. Compound 4e also increased the expression of osteogenic genes. This compound guarded ß-catenin expression both in vitro and in vivo as confirmed by western blot and immunofluorescence assays. This led to the preservation of bone microarchitecture and cortical thickness at 2.5 mg kg-1 and 5 mg kg-1 doses. Further compound 4e enhanced bone formation rate and regulated osteocyte death. The osteogenic potential of compound 4e was reflected by an increased level of serum marker osteocalcin and decreased levels of SOST and CTX-I. Overall, Compound 4e is able to overcome the catabolic effect of dexamethasone on bone by targeting the canonical WNT/ß-catenin signaling as evidenced by both in vitro and in vivo studies.
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Benzofuranos , Osteoporose , Animais , Apoptose , Benzofuranos/farmacologia , Diferenciação Celular , Glucocorticoides/metabolismo , Masculino , Camundongos , Osteoblastos , Osteogênese , Osteoporose/induzido quimicamente , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Piranos/farmacologia , Via de Sinalização Wnt , beta Catenina/genética , beta Catenina/metabolismoRESUMO
With the spread of COVID-19, there is an urgent need for a fast and reliable diagnostic aid. For the same, literature has witnessed that medical imaging plays a vital role, and tools using supervised methods have promising results. However, the limited size of medical images for diagnosis of CoVID19 may impact the generalization of such supervised methods. To alleviate this, a new clustering method is presented. In this method, a novel variant of a gravitational search algorithm is employed for obtaining optimal clusters. To validate the performance of the proposed variant, a comparative analysis among recent metaheuristic algorithms is conducted. The experimental study includes two sets of benchmark functions, namely standard functions and CEC2013 functions, belonging to different categories such as unimodal, multimodal, and unconstrained optimization functions. The performance comparison is evaluated and statistically validated in terms of mean fitness value, Friedman test, and box-plot. Further, the presented clustering method tested against three different types of publicly available CoVID19 medical images, namely X-ray, CT scan, and Ultrasound images. Experiments demonstrate that the proposed method is comparatively outperforming in terms of accuracy, precision, sensitivity, specificity, and F1-score.
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The effect of substituents on the surface adsorption equilibria of thiophenols and isoquinolines on gold substrates was studied using surface-enhanced Raman spectroscopy (SERS) in order to determine the effects of the localized dipole moments and charge donating/withdrawing properties on the binding affinity. Two common classes of molecules used in SERS studies were examined, which included substituted aromatic thiols and nitrogen heterocyclic aromatic molecules (azaarenes), due to their strong affinity for gold surfaces. Unsubstituted thiophenol in aqueous solution binds strongly to gold surfaces. Therefore, it is difficult to measure an equilibrium constant, since even at concentrations of 10-8 M nearly a complete self-assembled monolayer (SAM) forms. In contrast, substituted thiophenols with electron-withdrawing groups, such as halogenated thiophenols, bind much less strongly, allowing equilibrium constants to be obtained. It is believed that the substituent withdrawing charge away from the sulfur atom affects the adsorption/binding between the analyte and surface. Thiophenols substituted with electron donating groups behaved similar to unsubstituted thiophenol, where a SAM was observed at concentrations as low as 10-8 M. These functional groups did not hinder the ability of the sulfur groups to bind with gold. In addition, a series of bromine-substituted isoquinolines, a group of azaarene compounds, were measured to determine the effects that the bromine substituent has when it is bound to the two different rings and if position on the rings has an effect. The azaarene class of molecules, including isoquinoline, adsorbs less strongly than thiophenols, and a dual Langmuir isotherm phenomenon is observed where protonated and neutral bromoisoquinoline molecules occupy two different types of sites on Klarite substrates, which consist of inverted micro-pyramids on Si wafers with rough/nanostructured Au coatings. Protonated isoquinolines bind to nucleophilic sites on the substrates which tend to occur on flatter regions of the substrate. By contrast, neutral isoquinolines bind to electrophilic sites which are predominant near microscopic edges on the substrate. The presence of the bromine substituent and its position in the fused ring structure changes the Gibbs free energies of adsorption, depending on which ring the substituent is in. These results can help to guide the development of SERS for analytical applications by demonstrating how changes in functional groups can affect the equilibrium constants, which are critical for determining the effectiveness of SERS as a tool for trace detection of analytes.
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Currently there are a dozen or so of new vaccine candidates in clinical trials for prevention of tuberculosis (TB) and each formulation attempts to elicit protection by enhancement of cell-mediated immunity (CMI). In contrast, most approved vaccines against other bacterial pathogens are believed to mediate protection by eliciting antibody responses. However, it has been difficult to apply this formula to TB because of the difficulty in reliably eliciting protective antibodies. Here, we developed capsular polysaccharide conjugates by linking mycobacterial capsular arabinomannan (AM) to either Mtb Ag85b or B. anthracis protective antigen (PA). Further, we studied their immunogenicity by ELISA and AM glycan microarrays and protection efficacy in mice. Immunization with either Abg85b-AM or PA-AM conjugates elicited an AM-specific antibody response in mice. AM binding antibodies stimulated transcriptional changes in Mtb. Sera from AM conjugate immunized mice reacted against a broad spectrum of AM structural variants and specifically recognized arabinan fragments. Conjugate vaccine immunized mice infected with Mtb had lower bacterial numbers in lungs and spleen, and lived longer than control mice. These findings provide additional evidence that humoral immunity can contribute to protection against Mtb.
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Mananas/imunologia , Vacinas contra a Tuberculose/imunologia , Tuberculose/imunologia , Vacinas Conjugadas/imunologia , Aciltransferases/imunologia , Transferência Adotiva , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Imunidade Humoral/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica , Mycobacterium tuberculosis/imunologia , Análise de Sequência com Séries de OligonucleotídeosRESUMO
BACKGROUND: Spinacia oleracea is an important dietary vegetable in India and throughout the world and has many beneficial effects. It is cultivated globally. However, its effect on osteoarthritis that mainly targets the cartilage cells remains unknown. In this study we aimed to evaluate the anti-osteoarthritic and chondro-protective effects of SOE on chemically induced osteoarthritis (OA). METHODS: OA was induced by intra-patellar injection of monosodium iodoacetate (MIA) at the knee joint in rats. SOE was then given orally at 250 and 500 mg.kg- 1 day- 1 doses for 28 days to these rats. Anti-osteoarthritic potential of SOE was evaluated by micro-CT, mRNA and protein expression of pro-inflammatory and chondrogenic genes, clinically relevant biomarker's and behavioural experiments. RESULTS: In vitro cell free and cell based assays indicated that SOE acts as a strong anti-oxidant and an anti-inflammatory agent. Histological analysis of knee joints at the end of the experiment by safranin-o and toluidine blue staining established its protective effect. Radiological data corroborated the findings with improvement in the joint space and irregularity of the articular and atrophied femoral condyles and tibial plateau. Micro-CT analysis of sub-chondral bone indicated that SOE had the ability to mitigate OA effects by increasing bone volume to tissue volume (BV/TV) which resulted in decrease of trabecular pattern factor (Tb.Pf) by more than 200%. SOE stimulated chondrogenic marker gene expression with reduction in pro-inflammatory markers. Purified compounds isolated from SOE exhibited increased Sox-9 and Col-II protein expression in articular chondrocytes. Serum and urine analysis indicated that SOE had the potential to down-regulate glutathione S-transferase (GST) activity, clinical markers of osteoarthritis like cartilage oligometric matrix protein (COMP) and CTX-II. Overall, this led to a significant improvement in locomotion and balancing activity in rats as assessed by Open-field and Rota rod test. CONCLUSION: On the basis of in vitro and in vivo experiments performed with Spinacea oleracea extract we can deduce that SOE has the ability to alleviate the MIA induced deleterious effects.
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Osteoartrite/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Spinacia oleracea/química , Animais , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Índia , Iodoacetatos/efeitos adversos , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Osteoartrite/induzido quimicamente , Osteoartrite/genética , Osteoartrite/metabolismo , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Tíbia/efeitos dos fármacos , Tíbia/metabolismo , Tíbia/patologiaRESUMO
A microfluidic device is being developed by University of California-Santa Barbara as part of a joint effort with the United States Army to develop a portable, rapid drug detection device. Surface-enhanced Raman spectroscopy (SERS) is used to provide a sensitive, selective detection technique within the microfluidic platform employing metallic nanoparticles as the SERS medium. Using several illicit drugs as analytes, the work presented here describes the efforts of the Edgewood Chemical Biological Center to optimize the microfluidic platform by investigating the role of nanoparticle material, nanoparticle size, excitation wavelength, and capping agents on the performance, and drug concentration detection limits achievable with Ag and Au nanoparticles that will ultimately be incorporated into the final design. This study is particularly important as it lays out a systematic comparison of limits of detection and potential interferences from working with several nanoparticle capping agents-such as tannate, citrate, and borate-which does not seem to have been done previously as the majority of studies only concentrate on citrate as the capping agent. Morphine, cocaine, and methamphetamine were chosen as test analytes for this study and were observed to have limits of detection (LOD) in the range of (1.5-4.7) × 10-8 M (4.5-13 ng/mL), with the borate capping agent having the best performance.
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Dispositivos Lab-On-A-Chip , Análise Espectral Raman/instrumentação , Detecção do Abuso de Substâncias/instrumentação , Analgésicos Opioides/análise , Anestésicos Locais/análise , Estimulantes do Sistema Nervoso Central/análise , Cocaína/análise , Ouro/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Metanfetamina/análise , Morfina/análise , Prata/química , Propriedades de SuperfícieRESUMO
We propose a new approach to robustly retrieve the exit wave of an extended sample from its coherent diffraction pattern by exploiting sparsity of the sample's edges. This approach enables imaging of an extended sample with a single view, without ptychography. We introduce nonlinear optimization methods that promote sparsity, and we derive update rules to robustly recover the sample's exit wave. We test these methods on simulated samples by varying the sparsity of the edge-detected representation of the exit wave. Our tests illustrate the strengths and limitations of the proposed method in imaging extended samples.
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Ptychographic coherent x-ray diffractive imaging is a form of scanning microscopy that does not require optics to image a sample. A series of scanned coherent diffraction patterns recorded from multiple overlapping illuminated regions on the sample are inverted numerically to retrieve its image. The technique recovers the phase lost by detecting the diffraction patterns by using experimentally known constraints, in this case the measured diffraction intensities and the assumed scan positions on the sample. The spatial resolution of the recovered image of the sample is limited by the angular extent over which the diffraction patterns are recorded and how well these constraints are known. Here, we explore how reconstruction quality degrades with uncertainties in the scan positions. We show experimentally that large errors in the assumed scan positions on the sample can be numerically determined and corrected using conjugate gradient descent methods. We also explore in simulations the limits, based on the signal to noise of the diffraction patterns and amount of overlap between adjacent scan positions, of just how large these errors can be and still be rendered tractable by this method.
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Algoritmos , Artefatos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Microscopia/métodos , Análise Numérica Assistida por Computador , Refratometria/métodosRESUMO
Understanding electronic structure at the nanoscale is crucial to untangling fundamental physics puzzles such as phase separation and emergent behavior in complex magnetic oxides. Probes with the ability to see beyond surfaces on nanometer length and subpicosecond time scales can greatly enhance our understanding of these systems and will undoubtedly impact development of future information technologies. Polarized X-rays are an appealing choice of probe due to their penetrating power, elemental and magnetic specificity, and high spatial resolution. The resolution of traditional X-ray microscopes is limited by the nanometer precision required to fabricate X-ray optics. Here we present a novel approach to lensless imaging of an extended magnetic nanostructure, in which a scanned series of dichroic coherent diffraction patterns is recorded and numerically inverted to map its magnetic domain configuration. Unlike holographic methods, it does not require a reference wave or precision optics. In addition, it enables the imaging of samples with arbitrarily large spatial dimensions, at a spatial resolution limited solely by the coherent X-ray flux, wavelength, and stability of the sample with respect to the beam. It can readily be extended to nonmagnetic systems that exhibit circular or linear dichroism. We demonstrate this approach by imaging ferrimagnetic labyrinthine domains in a Gd/Fe multilayer with perpendicular anisotropy and follow the evolution of the domain structure through part of its magnetization hysteresis loop. This approach is scalable to imaging with diffraction-limited resolution, a prospect rapidly becoming a reality in view of the new generation of phenomenally brilliant X-ray sources.
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Our case report is of an elderly male with a history of IgM κ lymphoplasmacytic lymphoma (LPL) presenting with generalized neuropathy and weakness. Due to his LPL history and worsening renal function, he underwent a renal biopsy revealing the presence of µ heavy and λ light chains, revealing a diagnosis of amyloidosis with unbound heavy & light chains (AHL), a rare type of amyloidosis. His bone marrow biopsy demonstrated κ light chain restriction by flow cytometry and amyloid deposition. The patient's serum had elevated free κ and λ light chains with a free light chain (FLC) ratio of 3.17. Serum immunofixation was positive for IgM κ and λ light chain clones. He completed six cycles of cyclophosphamide, bortezomib, dexamethasone, and rituximab (CyBorD+R), normalizing the FLC ratio. Still, he continued to present with persistently elevated M protein, IgM κ, and λ light chains on immunofixation. Thereafter, daratumumab, a human monoclonal antibody directed against CD38 expressed on myeloma cells was initiated, which led to a negative immunofixation study after two cycles accompanied by a reduction in protein excretion in the urine. The patient achieved a complete hematological response with daratumumab. To date, our case is the only reported µ heavy and λ light chain amyloidosis patient with bi-clonal (IgM κ and λ) gammopathy to be successfully treated with daratumumab.
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Multiple theories exist to explain cancer initiation, although a consensus on this is crucial for developing effective therapies. 'Somatic mutation theory' suggests that mutations in somatic cells during DNA repair initiates cancer but this concept has several attached paradoxes. Research efforts to identify quiescent cancer stem cells (CSCs) that survive therapy and result in metastasis and recurrence have remained futile. In solid cancers, CSCs are suggested to appear during epithelial-mesenchymal transition by the dedifferentiation and reprogramming of epithelial cells. Pluripotent and quiescent very small embryonic-like stem cells (VSELs) exist in multiple tissues but remain elusive owing to their small size and scarce nature. VSELs are developmentally connected to primordial germ cells, undergo rare, asymmetrical cell divisions and are responsible for the regular turnover of cells to maintain tissue homeostasis throughout life. VSELs are directly vulnerable to extrinsic endocrine insults because they express gonadal and gonadotropin hormone receptors. VSELs undergo epigenetic changes due to endocrine insults and transform into CSCs. CSCs exhibit genomic instability and develop mutations due to errors during DNA replication while undergoing excessive proliferation and clonal expansion to form spheroids. Thus tissue-resident VSELs offer a connection between extrinsic insults and variations in cancer incidence reported in various body tissues. To conclude, cancer is indeed a stem cell disease with mutations occurring as a consequence. In addition to immunotherapy, targeting mutations, and Lgr5 + organoids for developing new therapeutics, targeting CSCs (epigenetically altered VSELs) by improving their niche and epigenetic status could serve as a promising strategy to treat cancer.
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Epigênese Genética , Mutação , Neoplasias , Células-Tronco Neoplásicas , Humanos , Neoplasias/genética , Neoplasias/patologia , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Animais , Células-Tronco Embrionárias/metabolismoRESUMO
Gynecological disorders such as endometriosis, polycystic ovary syndrome, and gynecological cancers are increasingly recognized as potential risk factors for cardiovascular disease (CVD). Endometriosis, a chronic inflammatory condition, exhibits shared pathogenic mechanisms with CVD, including endothelial dysfunction and an atherogenic lipid profile. Emerging evidence suggests a link between endometriosis and an elevated risk of cardiovascular events such as myocardial infarction, ischemic heart disease, and hypertension. Polycystic ovary syndrome, characterized by hormonal imbalances and metabolic derangements, is associated with an increased risk of hypertension, myocardial infarction, and structural cardiac abnormalities, even after controlling for obesity. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, are also associated with an increased burden of cardiovascular comorbidities and mortality. Cancer treatments, including chemotherapy and radiation therapy, can further contribute to cardiovascular toxicity. Understanding the interplay between gynecological disorders and CVD is crucial for identifying high-risk individuals, implementing preventive strategies, and providing comprehensive care. A multidisciplinary approach involving gynecologists, cardiologists, and other specialists is essential for optimizing the management of these complex conditions and improving overall patient outcomes.
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Atrial fibrillation (AF) stands as a prevalent and escalating cardiac arrhythmia in the United States, with obesity emerging as a prominent modifiable risk factor. This article explores the intricate relationship between obesity and AF, delving into the multifaceted pathophysiological mechanisms linking the 2 conditions. Various factors, such as autonomic dysfunction, left atrial stretch, inflammation, and hormonal imbalances, contribute to the initiation and perpetuation of AF in obese individuals. The Atrial Fibrillation Better Care pathway, emphasizing lifestyle modifications and weight loss strategies, emerges as a practical guideline for managing AF in obesity. This comprehensive review underscores the critical role of obesity as a significant modifiable risk factor for AF, urging a proactive approach to its management. Implementing the Atrial Fibrillation Better Care approach, focusing on encouraging physical activity, promoting healthy dietary habits, and raising awareness about the risks associated with obesity prove essential in preventing and mitigating the burden of AF in the obese population.
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The leading cause of cancer-related deaths worldwide is skin cancer. Effective therapy depends on the early diagnosis of skin cancer through the precise classification of skin lesions. However, dermatologists may find it difficult and time-consuming to accurately classify skin lesions. The use of transfer learning to boost skin cancer classification model precision is a promising strategy. In this work, we proposed a hybrid CNN with a transfer learning model and a random forest classifier for skin cancer disease detection. To evaluate the efficacy of the proposed model, it was verified over two datasets of benign skin moles and malignant skin moles. The proposed model is able to classify images with an accuracy of up to 90.11%. The empirical results and analysis assure the feasibility and effectiveness of the proposed model for skin cancer classification.
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Bone is one of the most prevalent sites of metastases in various epithelial malignancies, including breast cancer and this metastasis to bone often leads to severe skeletal complications in women due to its osteolytic nature. To address this, we devised a novel drug delivery approach using an Alendronate (ALN) functionalized self-assembled porous crystalsomes for concurrent targeting of Oleanolic acid (OA) and ALN (ALN + OA@NCs) to bone metastasis. Initially, the conjugation of both PEG-OA and OA-PEG-ALN with ALN and OA was achieved, and this conjugation was then self-assembled into porous crystalsomes (ALN + OA@NCs) by nanoemulsion crystallization. The reconstruction of a 3D single particle using transmission electron microscopy ensured the crystalline porous structure of ALN + OA@NCs, was well aligned with characteristic nanoparticle attributes including size distribution, polydispersity, and zeta potential. Further, ALN + OA@NCs showed enhanced efficacy in comparison to OA@NCs suggesting the cytotoxic roles of ALN towards cancer cells, followed by augmentation ROS generation (40.81%), mitochondrial membrane depolarization (57.20%), and induction of apoptosis (40.43%). We found that ALN + OA@NCs facilitated inhibiting osteoclastogenesis and bone resorption followed by inhibited osteolysis. In vivo activity of ALN + OA@NCs in the 4 T1 cell-induced tibia model rendered a reduced bone loss in the treated mice followed by restoring bone morphometric markers which were further corroborated bone-targeting effects of ALN + OA@NCs to reduce RANKL-stimulated osteoclastogenesis. Further, In vivo intravenous pharmacokinetics showed the improved therapeutic profile of the ALN + OA@NCs in comparison to the free drug, prolonging the levels of the drug in the systemic compartment by reducing the clearance culminating the higher accumulation at the tumor site. Our finding proposed that ALN + OA@NCs can effectively target and treat breast cancer metastasis to bone and its associated complications.
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Alendronato , Neoplasias Ósseas , Nanopartículas , Osteólise , Tíbia , Alendronato/administração & dosagem , Alendronato/farmacocinética , Alendronato/química , Animais , Osteólise/prevenção & controle , Osteólise/tratamento farmacológico , Feminino , Nanopartículas/química , Nanopartículas/administração & dosagem , Tíbia/efeitos dos fármacos , Tíbia/patologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Porosidade , Linhagem Celular Tumoral , Humanos , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/farmacocinética , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/farmacocinética , Ácido Oleanólico/química , Ácido Oleanólico/análogos & derivados , Camundongos Endogâmicos BALB C , Camundongos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologiaRESUMO
Hydrogen peroxide (H2O2) is a highly effective decontaminant against chemical warfare agents (CWAs) when present both in a liquid and as a solid powder. For the latter, this can be in the form of H2O2 being complexed to a polymer, such as polyvinylpyrrolidone (PVP). While a H2O2-PVP complex is indeed effective at decontaminating CWAs, it is vulnerable to environmental conditions such as high relative humidities (RH), which can dissociate the H2O2 from the complex before it is given the opportunity to react with CWAs. In this paper, we demonstrate that the cross-linked version of PVP forms a highly stable complex with H2O2, which can withstand both high (40 °C) and low (-20 °C) temperatures as well as maintain stability at high RH up to 90% over several days. Collectively, this lays the framework for processing the H2O2-PVP complex in a variety of form factors that can maintain efficacy under a wide range of real-world environmental conditions.