Pathological Complete Response After Neoadjuvant Imatinib in a Recurrent Duodenal Gastrointestinal Stromal Tumor (GIST).

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal (GI) tract. Although surgery is the treatment of choice in resectable disease, neoadjuvant therapy is indicated in advanced, metastatic, and recurrent tumors. Decreasing tumor burden may facilitate resection and reduce surgical morbidity. We describe a case of a 66-year-old male with a recurrent duodenal GIST, after surgery and adjuvant imatinib five years before. Following neoadjuvant therapy with imatinib for 12 months, the patient underwent a cephalic pancreaticoduodenectomy, without complications. The final histopathology showed a pathological complete response (pCR) with no residual neoplasm. A pathological complete response to imatinib in a recurrent disease is extremely rare. Molecular testing should be performed before neoadjuvant therapy to identify response-predictive mutations. In recurrent/metastatic disease, systemic therapy is the standard treatment for all patients. Surgery should be considered in a tailored approach in patients with good responses to systemic therapy before developing therapeutic resistance.

Fibrous Structures: An Overview of Their Responsiveness to External Stimuli towards Intended Application.

In recent decades, the interest in responsive fibrous structures has surged, propelling them into diverse applications: from wearable textiles that adapt to their surroundings, to filtration membranes dynamically altering selectivity, these structures showcase remarkable versatility. Various stimuli, including temperature, light, pH, electricity, and chemical compounds, can serve as triggers to unleash physical or chemical changes in response. Processing methodologies such as weaving or knitting using responsive yarns, electrospinning, as well as coating procedures, enable the integration of responsive materials into fibrous structures. They can respond to these stimuli, and comprise shape memory materials, temperature-responsive polymers, chromic materials, phase change materials, photothermal materials, among others. The resulting effects can manifest in a variety of ways, from pore adjustments and altered permeability to shape changing, color changing, and thermal regulation. This review aims to explore the realm of fibrous structures, delving into their responsiveness to external stimuli, with a focus on temperature, light, and pH.

Developmental validation of the ForenSeq® Kintelligence kit, MiSeq FGx® sequencing system and ForenSeq Universal Analysis Software.

Forensic Investigative Genetic Genealogy, a recent sub discipline of forensic genomics, leverages the high throughput and sensitivity of detection of next generation sequencing and established genetic and genealogical approaches to support the identification of human remains from missing persons investigations and investigative lead generation in violent crimes. To facilitate forensic DNA evidence analysis, the ForenSeq® Kintelligence multiplex, consisting of 10,230 SNPs, was developed. Design of the ForenSeq Kintelligence Kit, the MiSeq FGx® Sequencing System and the ForenSeq Universal Analysis Software is described. Developmental validation in accordance with SWGDAM guidelines and forensic quality assurance standards, using single source samples, is reported for the end-to-end workflow from library preparation to data interpretation. Performance metrics support the conclusion that more genetic information can be obtained from challenging samples compared to other commercially available forensic targeted DNA assays developed for capillary electrophoresis (CE) or other current next generation sequencing (NGS) kits due to the higher number of markers, the overall shorter amplicon sizes (97.8% <150 bp), and kit design. Data indicate that the multiplex is robust and fit for purpose for a wide range of quantity and quality samples. The ForenSeq Kintelligence Kit and the Universal Analysis Software allow transfer of the genetic component of forensic investigative genetic genealogy to the operational forensic laboratory.

Clinical course and disease burden of patients with generalized pustular psoriasis in Portugal: a multicenter retrospective cohort study.

OBJECTIVES: Generalized pustular psoriasis (GPP) is a rare, life-threatening skin inflammatory disorder. This study aimed to describe the disease course, treatment strategies, and healthcare utilization among patients with GPP in Portugal. METHODS: This multicentric, observational, retrospective study included consecutive adult patients with GPP undergoing a dermatology evaluation in different reporting institutions by experienced dermatologists between 2002 and 2023. RESULTS: A total of 59 patients were assessed. Most of the cohort had a previous history of plaque psoriasis (71%) and 83% presented at least one comorbidity. At the initial encounter, 64% of the cohort needed hospitalization. Systemic involvement was common, including fever (37%), and elevated white blood cell count and erythrocyte sedimentation rate/C-reactive protein (49%). Nearly, 73% of patients initiated systemic drugs, and 70% had to discontinue the first treatment. During the study, 98% of patients experienced at least one flare. At the last visit, 3.4% of patients had died, and 71.2% exhibited signs of active disease despite undergoing treatment. CONCLUSIONS: Our study demonstrates that GPP is a chronic, debilitating condition associated with systemic involvement, frequent flares, and hospitalizations, despite receiving multiple systemic treatments. Improved disease awareness and new treatments are needed to improve patient care and decrease the burden of the disease.

Microplastics in beach sediments of the Azores archipelago, NE Atlantic.

Oceanic islands are exposed to plastic debris that has accumulated in the open ocean, particularly in the subtropical gyres. This study investigates the abundance and typology of microplastics (from 0.1 to 5 mm) on 19 sandy beaches spread across 8 oceanic islands of the Azores archipelago. Between January and April 2016, a total of 341 particles retrieved from all beaches, were identified as microplastics. The highest concentration (50.19 ± 21.93 particles kg-1 dw) was found in Terceira Island. Beach morphology and grain size were important factors explaining microplastic concentration. Fibres were the most dominant morphology recovered (80.9 %), followed by fragments (12.3 %). Fourier transform infrared spectroscopy (FTIR) revealed that 41 % of the fibres consisted of polyester and 60 % of the fragments were polyethylene. This research underlines the widespread contamination of microplastics in oceanic islands of the Atlantic Ocean.

Utility of realistic microscopy-based cell models in simulation studies of nanoparticle-enhanced photon radiotherapy.

To enhance the effect of radiation on the tumor without increasing the dose to the patient, the combination of high-Z nanoparticles with radiotherapy has been proposed. In this work, we investigate the effects of the physical parameters of nanoparticles (NPs) on the Dose Enhancement Factor (DEF), and on the Sensitive Enhancement Ratio (SER) by applying a version of the Linear Quadratic Model. A method for constructing voxelized realistic cell geometries in Monte Carlo simulations from confocal microscopy images was developed and applied to Gliobastoma Multiforme cell lines (U87 and U373). The comparison of simulations with realistic geometry and spherical geometry shows that there is significant impact on the survival curves obtained for the same irradiation conditions. Using this model, the DEF and the SER are determined as a function of the concentration, size and distribution of gold nanoparticles within the cell. For small NPs,dAuNP= 10 nm, no clear trend in the DEF and SER was observed when the number of NPs within the cell increases. Experimentally, the variable number of NPs measured inside the U373 cells (ranging between 1.48 × 105and 1.19 × 106) also did not influence much the observed cell survival upon irradiation of the cells with a Co-60 source. The same lack of trend is obtained when the Au content in the cell is kept constant, 0.897 mg/g, but the size of the NPs is changed. However, if the number of NPs is kept constant (7.91 × 105) and the size changes, there is a critical diameter above which the dose effect increases significantly. Using the realistic geometries, it was verified that the key parameter for the DEF and the SER enhancement is the volume fraction of Au in the cell, with NP size being a more important parameter than the number of NPs.

Secukinumab-induced systemic lupus erythematosus in psoriatic arthritis.

CASE REPORT: A 68-year-old male treated with secukinumab for psoriatic arthritis suspended treatment for three months due to COVID pandemic. Upon secukinumab reintroduction, anorexia and weight loss ensued and four months later he had an abrupt onset of low-grade fever, fatigue, flu-like symptoms, dyspnoea and widespread inflammatory arthralgias. Laboratory investigations showed de novo anaemia, leukopenia, lymphopenia, cytocholestasis, elevated acute phase reactants, C3 complement consumption, proteinuria (1630mg/24h), active urine sediment, positive antinuclear (1:1280) and anti-double-stranded DNA (212.3 IU/mL) antibodies. Chest imaging showed peripheral pulmonary embolism, lobar pneumonia, and a small bilateral pleural effusion. Drug-induced lupus erythematosus (DILE) was suspected, and the patient was hospitalised. Secukinumab was discontinued and treatment with enoxaparin, antibiotics, enalapril, hydroxychloroquine and prednisolone 0.5mg/kg qd was started. Clinical and laboratorial remission ensued after one month except for proteinuria (decreased to 653mg/24h). Proliferative lupus nephritis was assumed and mycophenolate mofetil was introduced, with sustained complete remission over a 33-month follow-up. DISCUSSION: This is the second reported case of systemic secukinumab-associated DILE, and the first with renal involvement. Clinical and laboratory features of DILE are reviewed and compared with previously described cases.

Nanoplastics activate a TLR4/p38-mediated pro-inflammatory response in human intestinal and mouse microglia cells.

The crescent presence of nanoplastics in the environment raises concerns regarding their potential impact on health. This study exposed human colon adenocarcinoma cells (HT29) and microglia cells (N9) to nanoplastics (25 nm, 50 nm, and 100 nm Polystyrene) to investigate their inflammatory responses, which are vital for body's defence. Although cytotoxicity remained generally low, HT29 cells exhibited a notable upregulation of p50 and p38 expression, concomitant with elevated TLR4 expression, in contrast with N9 cells that showed a less pronounced upregulation of these proteins. Additionally, nanoplastic exposure increased IL-1ß levels, partially attenuated by pre-exposure to TLR4 or p38 inhibitors. Intriguingly, N9 cells exposed to nanoplastics exhibited substantial increases in iNOS mRNA. This effect was entirely prevented by pre-exposure to TLR4 or p38 inhibitors, while TNF-α mRNA levels remained relatively stable. These findings underscore the potential of nanoplastics to activate inflammatory pathways, with response kinetics varying depending on the cell type.

Comparison of Zinc Oxide Nanoparticle Integration into Non-Woven Fabrics Using Different Functionalisation Methods for Prospective Application as Active Facemasks.

The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP content and distribution within the textile fibres by morphological and chemical analysis, the samples were evaluated regarding their antimicrobial properties. The functionalised fabrics obtained via dip-pad-dry unveiled the most promising data, with 0.017 ± 0.013wt% ZnO NPs being mostly located at the fibre's surface and capable of total eradication of Staphylococcus aureus and Escherichia coli colonies within the tested 24 h (ISO 22196 standard), as well as significantly contributing (**** p < 0.0001) to the growth inhibition of the bacteriophage MS2, a surrogate of the SARS-CoV-2 virus (ISO 18184 standard). A three-layered structure was assembled and thermoformed to obtain facemasks combining the previously chosen NWF, and its resulting antimicrobial capacity, filtration efficiency and breathability (NP EN ISO 149) were assessed. The developed three-layered and multiscaled fibrous structures with antimicrobial capacities hold immense potential as active individual protection facemasks.

Nanoparticle Synthesis and Their Integration into Polymer-Based Fibers for Biomedical Applications.

The potential of nanoparticles as effective drug delivery systems combined with the versatility of fibers has led to the development of new and improved strategies to help in the diagnosis and treatment of diseases. Nanoparticles have extraordinary characteristics that are helpful in several applications, including wound dressings, microbial balance approaches, tissue regeneration, and cancer treatment. Owing to their large surface area, tailor-ability, and persistent diameter, fibers are also used for wound dressings, tissue engineering, controlled drug delivery, and protective clothing. The combination of nanoparticles with fibers has the power to generate delivery systems that have enhanced performance over the individual architectures. This review aims at illustrating the main possibilities and trends of fibers functionalized with nanoparticles, focusing on inorganic and organic nanoparticles and polymer-based fibers. Emphasis on the recent progress in the fabrication procedures of several types of nanoparticles and in the description of the most used polymers to produce fibers has been undertaken, along with the bioactivity of such alliances in several biomedical applications. To finish, future perspectives of nanoparticles incorporated within polymer-based fibers for clinical use are presented and discussed, thus showcasing relevant paths to follow for enhanced success in the field.

Translation, validity, and reliability of the European Portuguese version of the Touch Experiences and Attitudes Questionnaire.

Background: Positive touch experiences have proved to be extremely important throughout our lifespan, with cascading effects on our social life. However, few questionnaires are available to measure attitudes and experiences of touch in the Portuguese population. This study aimed to translate and validate the European Portuguese version of the Touch Experiences and Attitudes Questionnaire (TEAQ), as a reliable and valid instrument to measure different aspects of affective touch experiences and attitudes. Methods: Therefore, an online sample of 384 (299 females and 85 males) participants, aged between 18 and 75 years (M = 24.59; SD = 9.56) was collected. Multidimensional Rasch model and confirmatory factor analysis were carried out, and also reliability and convergent and discriminant validity were determined. In addition, we examined sex differences in attitudes and experiences of touch. Results: Results showed good fit indexes for the 52-item six-factor model structure (friends and family touch, current intimate touch, childhood touch, attitudes to self-care, attitudes to intimate touch, and attitudes to unfamiliar touch). This instrument also showed good reliability and acceptable convergent and discriminant validity. Significant sex differences were found, with female participants reporting more positive touch experiences (including childhood touch, friends and family touch, and current intimate touch) and a more favourable attitude to self-care, with males showing a more positive attitude towards unfamiliar touch. Regarding attitudes towards the intimate touch, scores for both groups were comparable. Conclusion: Overall, the European Portuguese version of the TEAQ presented good psychometric properties and appears to be a reliable and valid self-report measure, being a useful and beneficial instrument in research and clinical settings.

An Atypical Presentation of Non-Hodgkin's Lymphoma.

Lymphomas result from the proliferation of malignant lymphocytes, which can affect lymph nodes, blood, and other organs. Primary involvement of the spine by haematological diseases is rare. Non-Hodgkin's lymphoma with an extranodal location most frequently involves the gastrointestinal tract and airways, affecting the bone, muscle, and nervous system. We present a clinical case of an atypical form of non-Hodgkin's lymphoma. A 78-year-old woman was admitted to the hospital with complaints of pain in the lumbar region, hip, and left leg for the last month. Computed tomography of the lumbar spine revealed a mass of left paravertebral tissue with involvement from L3 to L5. Thoraco-abdominal CT-guided biopsy revealed diffuse large-cell non-Hodgkin B lymphoma. The remainder of the study did not show lymphatic involvement, so a diagnosis of primary extranodal large cell non-Hodgkin B lymphoma was made.

Fast and accurate kinship estimation using sparse SNPs in relatively large database searches.

Forensic genetic genealogy (FGG) has primarily relied upon dense single nucleotide polymorphism (SNP) profiles from forensic samples or unidentified human remains queried against online genealogy database(s) of known profiles generated with SNP microarrays or from whole genome sequencing (WGS). In these queries, SNPs are compared to database samples by locating contiguous stretches of shared SNP alleles that allow for detection of genomic segments that are identical by descent (IBD) among biological relatives (kinship). This segment-based approach, while robust for detecting distant relationships, generally requires DNA quantity and/or quality that are sometimes not available in forensic casework samples. By focusing on SNPs with maximal discriminatory power and using an algorithm designed for a sparser SNP set than those from microarray typing, performance similar to segment matching was reached even in difficult casework samples. This algorithm locates shared segments using kinship coefficients in "windows" across the genome. The windowed kinship algorithm is a modification of the PC-AiR and PC-Relate tools for genetic relatedness inference, referred to here as the "whole genome kinship" approach, that control for the presence of unknown or unspecified population substructure. Simulated and empirical data in this study, using DNA profiles comprised of 10,230 SNPs (10K multiplex) targeted by the ForenSeq™ Kintelligence Kit demonstrate that the windowed kinship approach performs comparably to segment matching for identifying first, second and third degree relationships, reasonably well for fourth degree relationships, and with fewer false kinship associations. Selection criteria for the 10K SNP PCR-based multiplex and functionality of the windowed kinship algorithm are described.

Magneto-mechanical destruction of cancer-associated fibroblasts using ultra-small iron oxide nanoparticles and low frequency rotating magnetic fields.

The destruction of cells using the mechanical activation of magnetic nanoparticles with low-frequency magnetic fields constitutes a recent and interesting approach in cancer therapy. Here, we showed that superparamagnetic iron oxide nanoparticles as small as 6 nm were able to induce the death of pancreatic cancer-associated fibroblasts, chosen as a model. An exhaustive screening of the amplitude, frequency, and type (alternating vs. rotating) of magnetic field demonstrated that the best efficacy was obtained for a rotating low-amplitude low-frequency magnetic field (1 Hz and 40 mT), reaching a 34% ratio in cell death induction; interestingly, the cell death was not maximized for the largest amplitudes of the magnetic field. State-of-the-art kinetic Monte-Carlo simulations able to calculate the torque undergone by assemblies of magnetic nanoparticles explained these features and were in agreement with cell death experiments. Simulations showed that the force generated by the nanoparticles once internalized inside the lysosome was around 3 pN, which is in principle not large enough to induce direct membrane disruption. Other biological mechanisms were explored to explain cell death: the mechanical activation of magnetic nanoparticles induced lysosome membrane permeabilization and the release of the lysosome content and cell death was mediated through a lysosomal pathway depending on cathepsin-B activity. Finally, we showed that repeated rotating magnetic field exposure halted drastically the cell proliferation. This study established a proof-of-concept that ultra-small nanoparticles can disrupt the tumor microenvironment through mechanical forces generated by mechanical activation of magnetic nanoparticles upon low-frequency rotating magnetic field exposure, opening new opportunities for cancer therapy.

Antibacterial and hemostatic capacities of cellulose nanocrystalline-reinforced poly(vinyl alcohol) electrospun mats doped with Tiger 17 and pexiganan peptides for prospective wound healing applications.

Infection is a major issue in chronic wound care. Different dressings have been developed to prevent microbial propagation, but an effective, all-in-one (cytocompatible, antimicrobial and promoter of healing) solution is still to be uncovered. In this research, polyvinyl alcohol (PVA) nanofibrous mats reinforced with cellulose nanocrystal (CNC), at 10 and 20% v/v ratios, were produced by electrospinning, crosslinked with glutaraldehyde vapor and doped with specialized peptides. Crosslinking increased the mats' fiber diameters but maintained their bead-free morphology. Miscibility between polymers was confirmed by Fourier-transform infrared spectroscopy and thermal evaluations. Despite the incorporation of CNC having reduced the mats' mechanical performance, it improved the mats' surface energy and its structural stability over time. Pexiganan with an extra cysteine group was functionalized onto the mats via hydroxyl- polyethylene glycol 2-maleimide, while Tiger 17 was physisorbed to preserve its cyclic conformation. Antimicrobial assessments demonstrated the peptide-doped mat's effectiveness against Staphylococcus aureus and Pseudomonas aeruginosa; pexiganan contributed mostly for such outcome. Tiger 17 showed excellent capacity in accelerating clotting. Cytocompatibility evaluations attested to these mats' safety. C90/10 PVA/CNC mats were deemed the most effective from the tested group and, thus, a potentially effective option for chronic wound treatments.

Invasive Lobular Carcinoma Arising in Ectopic Breast Tissue: A Case Report.

Incomplete regression of the embryonic mammary line occurs in 0.3-6% of the population. Ectopic breast tissue is mostly asymptomatic and can undergo malignant transformation. Ectopic breast cancer accounts for 0.2-0.6% of all breast cancers. Screening breast examinations can miss these lesions due to their location making the diagnosis more challenging. We describe a case of a primary invasive lobular carcinoma in an ectopic breast on the left axilla detected in a 49-year-old woman. Firstly diagnosed as a sebaceous cyst, the lesion was excised under local anesthesia. Histopathology showed breast tissue widely infiltrated by an invasive carcinoma. Excision of the remnant tissue with axillary lymph node dissection was performed. Ectopic breast carcinoma is a rare diagnosis and there is a general lack of awareness. The presence of an abnormal mass along the mammary ridge should raise clinicians' attention. Management of primary ectopic breast carcinoma should be based on a multidisciplinary approach under the same principles as breast cancer. Furthermore, it does not appear to bring a worse prognosis when diagnosed at similar disease stages.

Extraction of Cellulose-Based Polymers from Textile Wastes.

The extraction and exploration of cellulose-based polymers is an exciting area of research [...].