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Background: While formative and summative usability testing is essential to confirm safe and effective product use, it may not be sufficient to comprehensively understand user capabilities and limitations in device interactions. Therefore, this research aims to quantify user handling forces for different device handling steps of pen injectors through sensor-augmented simulated use studies. Research Design and methods: The study involved 46 participants who were divided into two groups: a healthy control group and a group of users with dexterity impairments. All participants were instructed to perform simulated handling steps using non-functional dummy devices equipped with force and torque sensors. Each handling step was performed twice: first at what participants considered a comfortable force level and then at their maximum force. The study then analyzed force data to investigate the impact of user characteristics and device geometry on force exertion during the different handling steps. Results: The study demonstrates differences in the perceived comfortable and maximum force levels between the control and patient groups. These force levels decrease slightly with the user's age and level of dexterity impairment. Furthermore, the forces applied by the users are dependent on the geometry of the device and the holding pattern. Conclusion: The results highlight the significance of sensor-augmented simulated use studies as a tool for providing quantitative insights into users' ability to exert force while handling self-injection devices. These data offer comprehensive insights that inform the definition of performance requirements and specifications for injection device design, thereby supporting the advancement of future self-injection devices.
This study explores how people interact with pen injectors; devices commonly used for self-injections. Traditional usability tests are vital for ensuring safe product use, but they may not fully capture users' capabilities and limitations. To address this gap, the research measures the forces exerted by users during different handling steps of pen injectors through a simulated use study with sensors. Forty-five participants, including a healthy control group and individuals with dexterity impairments, engaged in handling non-functional dummy devices with force and torque sensors. Each participant performed handling steps twice, first at a comfortable force level and then at their maximum force. The study analyzed force data to understand how user characteristics and device geometry affect force exertion. Results revealed differences in force levels between control and patient groups, with applied force levels decreasing slightly with age and dexterity impairment. The study emphasized the impact of device geometry and holding patterns on applied forces. Overall, the findings show the usefulness of sensor-augmented simulated use studies in quantifying users' force exertion, providing insights for designing future self-injection devices.
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BACKGROUND: Between 2015 and 2019 the Chronic Headache Education and Self-management Study (CHESS) developed and tested a supportive self-management approach that aimed to improve outcomes for people with chronic migraine or chronic tension type headache with/without episodic migraine. However, a paucity of qualitative research which explored the lived experiences of people with chronic headache was evidenced. In response, we undertook to explore the experiences of living with chronic headaches of people who participated in the CHESS study. METHODS: We adopted qualitative methodologies, inviting participants in the CHESS study to participate in semi-structured interviews. In phase 1 (feasibility study), a thematic analysis was conducted. In phase 2 (main CHESS trial), interviews were informed by topic guides developed from our learning from the phase 1 interviews. Pen portrait methodology and thematic analysis was employed allowing us to explore the data longitudinally. RESULTS: Phase 1, 15 interviews (10 female) age range 29 to 69 years (median 47 years) revealed the complexities of living with chronic headache. Six overarching themes were identified including the emotional impact and the nature of their headaches. Phase 2, included 66 interviews (26 participants; median age group 50s (range 20s-60s); 20 females. 14 were interviewed at three points in time (baseline, 4 and 12 months) Through an iterative process four overlapping categories of headache impact emerged from the data and were agreed: i) 'I will not let headaches rule my life'; ii) 'Headaches rule my life'; iii) 'Headaches out of control-something needs to change'; and iv) 'Headaches controlled-not ruling my life'. One of these categories was assigned to each pen portrait at each timepoint. The remaining 12 participants were interviewed at two time points during a year; pen portraits were again produced. Analysis revealed that the headache impact categories developed above held true in this sample also providing some validation of the categories. CONCLUSIONS: These data give an insight into the complexities of living with chronic headache. Chronic headache is unpredictable, permeating all aspects of an individual's life; even when an individual feels that their headache is controlled and not interfering, this situation can rapidly change. It shows us that more work needs to be done both medically and societally to help people living with this often-hidden condition. TRIAL REGISTRATION: ISRCTN79708100.
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Transtornos da Cefaleia , Pesquisa Qualitativa , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Transtornos da Cefaleia/psicologia , Autogestão/métodos , Autogestão/psicologiaRESUMO
Introduction: Concizumab is a once-daily prophylactic treatment developed for patients with hemophilia A or B (HA/HB) with or without inhibitors. It is the first treatment for hemophilia patients to be delivered subcutaneously using a pre-filled, multi-dose pen-injector with a 4 mm, 32 G needle. Aim: To investigate patient and caregiver handling and preference for the concizumab pen-injector compared with current injection systems used to treat hemophilia. Methods: This preference and handling study was conducted in accordance with authority guidelines for approval of new devices and included adults and adolescents with HA/HB with or without inhibitors and caregivers currently administering factor replacement therapy or factor VIII mimetic (emicizumab) therapy. All participants underwent a training session, followed by a test session during which participants independently administered a single pen-injection into an injection pad or manikin. Time to train, time to prepare and inject, and number of complete independent injections handling the pen were assessed. Participants evaluated handling and preference via the Hemophilia Device Handling and Preference Assessment Questionnaire. Results: 80 participants (44 adults, 21 adolescents, 15 caregivers) currently using factor replacement therapy (n=41, 51%) or emicizumab (n=39, 49%) participated. Average training time and time to complete an injection were 7 min 49s and 1 min 21s. In total, 98% of independent complete injections were achieved at first attempt. 98% (n=78; 95% confidence interval [CI] 91-100%) of participants assessed the pen-injector as either "easy" or "very easy" to use. 88% of participants preferred the pen-injector (n=70; 95% CI 78-94%) over their current injection system, and 9% (n=7) reported "no preference". Conclusion: Participants found the concizumab pen-injector easy to learn and easy to use and preferred it over their current injection systems.
People with hemophilia lack clotting factors that help stop bleeding after an injury. If left untreated, it can lead to life-threatening bleeding episodes. Treatment such as replacement therapy with clotting factors needs to be administered at regular intervals to prevent bleeding. The administration of intravenous (inside the vein) medication can be challenging due to the required skills, injection pain and availability of a good vein to inject into. Factor VIII mimetic therapy now allows people to inject medication under the skin (subcutaneously). However, using vials and syringes still poses challenges with the time to prepare and inject medication. Pen-injectors have been developed to address these challenges and provide additional benefits, including increased dose accuracy, portability, reduced discomfort, and less administration time. Concizumab is a medication developed for once-daily subcutaneous injection for people with hemophilia A or hemophilia B, with or without inhibitors, using a pen-injector. The objective of this preference and handling study was to understand patient and caregiver pen-injector handling experiences, and device preferences compared to their existing devices. In this study, most participants found it easy to learn to use the pen-injector. 98% of participants reported that the pen-injector was easy or very easy to use compared with their current device. 88% of participants reported a preference for the concizumab pen-injector over their current device. This shows that the pen-injector can easily and effectively be used to inject concizumab, providing more control and independence in patients' treatment while reducing the burden caused by intravenous modes of administration.
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Introduction: Various clinical decision-making tools for penicillin allergy have been developed to guide delabeling strategies. Objective: To evaluate the penicillin allergy PEN-FAST decision score in a retrospective cohort of patients, adults and children, with penicillin-reported allergy. Methods: This monocentric retrospective cohort included patients with penicillin-reported allergy. All patients underwent penicillin allergy testing using skin tests and/or drug challenge. The PEN-FAST score sensitivity, specificity, negative (NPV) and positive (PPV) predictive values, and the area under the receiver operating characteristics curve (AUC) were calculated. Results: Two hundred and fourteen patients were included (64 children and 150 adults). Allergy was confirmed in 52 cases (24%). A PEN-FAST score <3 points showed a poor discrimination capacity for the whole population (AUC = 0.66; 95% CI: 0.58-0.75), while it demonstrated a better discrimination capacity in the adults group (AUC = 0.71; 95% CI: 0.63-0.80). The sensitivity to identify penicillin allergy using this cutoff of less than 3 points was 0.67 (95% CI: 0.52-0.80); specificity, 0.58 (95% CI: 0.48-0.68); PPV, 0.43 (95% CI: 0.32-0.55); and NPV, 0.78 (95% CI: 0.68-0.87). Conclusions: Although our data confirm a rather good discrimination value of a PEN-FAST score <3 points, its low negative predictive value (78%) did not advocate for its use as an accurate, simple and cost-effective clinical decision-making tool to effectively reduce the number of penicillin skin tests required before direct oral challenge. Further studies are required to improve the predictive capacity of the PEN-FAST score.
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BACKGROUND: We assessed pain, acceptability, patient preference, and tolerability of patients with psoriasis and psoriatic arthritis after switching guselkumab from a prefilled syringe to One-Press autoinjector pen. METHODS: Patients with psoriasis and psoriatic arthritis treated for at least 6â¯months with guselkumab syringe were recruited from Jan 2019 to Dec 2022. Gender, age, diagnosis, self-administration, and pain perception of guselkumab prefilled syringe were recorded. At the first visit, patients completed a post-auto-injection syringe questionnaire before starting auto-injection pen administration. After 2 and 6â¯months of guselkumab self-injection using the One-Press autoinjector pen, patient experience, adherence, preference, pain, and safety of each administration were assessed using post-guselkumab by One-Press autoinjector pen questionnaire. RESULTS: 40 patients [psoriasis n=34, psoriatic arthritis n=6] were included. All patients self-administered guselkumab by One-Press autoinjector pen. Pain at the injection site was significantly reduced with the use of the One-Press autoinjector pen. All patients considered that using One-Press autoinjector pen was easier than the syringe, 98% chose the pen as their preferred delivery system. CONCLUSION: The One-Press autoinjector pen for guselkumab administration is presented as a preferred option, with a high satisfaction and less painful compared to the administration of guselkumab in a prefilled syringe.
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Non-cultured epidermal suspension (NCES) is one of the most widely used surgical therapy for stable vitiligo patients in which recipient size preparation plays an important role in the outcome of NCES. The primary objective is to evaluate and compare the efficacy and safety of conventional suspension delivery after manual dermabrasion (CSMD) versus tattooing pen-assisted suspension delivery (TPSD) in NCES. Paired vitiligo units (VU) in 36 patients, matched with respect to size and location were divided into two groups. The VU in Group 1 underwent suspension delivery by CSMD while the VU in Group 2 underwent same by TPSD. All the VU were followed up at regular intervals until 24 weeks. At the end of 24 weeks, 31 VU (86.1%) in Group 1 achieved >75% repigmentation which was significantly higher (p = .02, chi-square test) as compared to 22 VU (61.1%) in Group 2. The color matching in both the groups VU was also comparable (p = .84, chi-square test). The patient global assessment (PGA) was significantly higher in Group 1 VU as compared to Group 2. Treatment response in terms of repigmentation and PGA was significantly better in VU treated with CSMD as compared to TPSD. Recipient site complications were seen more commonly in Group 1 VU as compared to Group 2. Perilesional halo at the recipient site was seen in none of the VU in Group 2 which was significantly lower than 6 VU in Group 1 than (p = .02, chi-square test). Better results may be possible with technical improvisations in tattooing pen needle diameter and depth of penetration.
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Pen shells (PS), a type of shellfish, are abundantly consumed, and their inedible shell residues are often discarded near the coast without consideration of reutilization. This study sought to investigate the use of natural pen shells (NPS) and calcined pen shells (CPS) to stabilize Pb and As-contaminated soil. During the investigation, NPS and CPS were applied to the contaminated soil in amounts ranging from 1 to 10 wt% and cured for 28 days. After the curing process, the mineral phase was examined through X-ray powder diffraction (XRD) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX) analysis. The XRD and SEM-EDX results revealed the presence of riversideite and ettringite, which contribute to Pb and As stabilization in the CPS-treated soil. The leachability of Pb and As in the treated soil was further examined with three types of chemical extraction methods. Extraction results using 0.1 M HCl displayed a notable pH fluctuation in the extractant due to the residual amendments (NPS and CPS). The fluctuation resulted in a strong correlation of leached Pb and As with the pH of the extractant, which might hinder an accurate assessment of stabilization. In order to minimize the effect of pH, an EDTA-NH4OAc extraction was employed, suggesting its potential as a suitable assessment method. EDTA-NH4OAc extraction showed a higher effectiveness of CPS than NPS at 10 wt% of input amounts. In the SBET extraction, that uses a strongly acidic solution, a higher As leachability was observed by increasing the addition of CPS, which implied a CPS-related chemical fixation mechanism. The comparison of various extraction methods showed a higher CPS effectiveness as compared to NPS. However, it was recommended that CPS-treated soil required caution in strongly acidic conditions, especially for arsenic. This study explores the applicability of PS, which has not been investigated as an amendment for Pb and As-contaminated soil previously. Furthermore, this study revealed that utilization of various extraction methods is beneficial for gaining a comprehensive understanding of the role of CaCO3-based amendment in Pb and As-contaminated soil.
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Arsênio , Chumbo , Poluentes do Solo , Solo , Chumbo/química , Arsênio/química , Poluentes do Solo/química , Solo/química , AnimaisRESUMO
BACKGROUND: The purpose of the study was to conduct a comprehensive genomic characterization of gene alterations, microsatellite instability (MSI), and tumor mutational burden (TMB) in submucosal-penetrating (Pen) early gastric cancers (EGCs) with varying prognoses. METHODS: Samples from EGC patients undergoing surgery and with 10-year follow-up data available were collected. Tissue genomic alterations were characterized using Trusight Oncology panel (TSO500). Pathway instability (PI) scores for a selection of 218 GC-related pathways were calculated both for the present case series and EGCs from the TCGA cohort. RESULTS: Higher age and tumor location in the upper-middle tract are significantly associated with an increased hazard of relapse or death from any cause (p = 0.006 and p = 0.032). Even if not reaching a statistical significance, Pen A tumors more frequently present higher TMB values, higher frequency of MSI-subtypes and an overall increase in PI scores, along with an enrichment in immune pathways. ARID1A gene was observed to be significantly more frequently mutated in Pen A tumors (p = 0.006), as well as in patients with high TMB (p = 0.027). Tumors harboring LRP1B alterations seem to have a higher hazard of relapse or death from any cause (p = 0.089), being mutated mainly in relapsed patients (p = 0.093). CONCLUSIONS: We found that the most aggressive subtype Pen A is characterized by a higher frequency of ARID1A mutations and a higher genetic instability, while LRP1B alterations seem to be related to a lower disease-free survival. Further investigations are needed to provide a rationale for the use of these markers to stratify prognosis in EGC patients.
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This study examines the electromechanical characteristics of aluminium-doped zinc oxide (AZO) films. The films were produced using the RF magnetron sputtering process with a consistent thickness of 150 nm on various polymer substrates. The study focuses on assessing the electro-mechanical failure processes of coated segments using flexible substrates, namely polyethylene naphthalate (PEN) and polyethylene terephthalate (PET), with a specific emphasis on typical cracking and delamination occurrences. This examination involves conducting twisting deformation together with using standardised electrical resistance measurements and optical microscope monitoring instruments. It was found that the crack initiation angle is mostly dependent on the mechanical mismatch between the coating and substrate. Higher critical twisting angle values are observed for the AZO/PEN film during twisting testing. Relative to the perpendicular plane of the untwisted sample, it was found that cracks initiated at a twist angle equal to 42° ± 2.1° and 38° ± 1.7° for AZO/PEN and AZO/PET, respectively, and propagated along the sample length. SEM images indicate that the twisting motion results in deformation in the thin film material, leading to the presence of both types of stress in the film structure. These discoveries emphasise the significance of studying the mechanical properties of thin films under different stress conditions, as it can impact their performance and reliability in real-world applications. The electromechanical stability of AZO was found to be similar on both substrates during fatigue testing. Studying the electromechanical properties of various material combinations is important for selecting polymer substrates and predicting the durability of flexible electronic devices made from polyester.
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BACKGROUND: A study to assess the glucose levels of people with type 1 diabetes (T1D) overnight, based on the insulin type and timing. METHODS: A real-world, retrospective study of T1D, using multiple daily insulin injections. Continuous glucose monitoring and insulin injection data were collected for ten hours after dinner using the Insulclock® connected cap. Meal events were identified using the ROC detection methodology. The timing of the rapid insulin, second injections, and the type of insulin analogs used, were evaluated. RESULTS: The nocturnal profiles (n = 775, 49 subjects) were analyzed. A higher glucose AUC of over 180 mg/dL was observed in subjects with delayed injections (number; %; mg/dL × h): -45-15 min (n = 136; 17.5%, 175.9 ± 271.0); -15-0 min (n = 231; 29.8%, 164.0 ± 2 37.1); 0 + 45 min (n = 408; 52.6%, 203.6 ± 260.9), (p = 0.049). The use of ultrarapid insulin (FiAsp®) (URI) vs. rapid insulin (RI) analogs was associated with less hypoglycemia events (7.1 vs. 13.6%; p = 0.005) and TBR70 (1.7 ± 6.9 vs. 4.6 ± 13.9%; p = 0.003). Users of glargine U300 vs. degludec had a higher TIR (70.7 vs. 58.5%) (adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n = 144, 18.6%) was associated with a higher number of hypoglycemia events (18.1 vs. 9.5%; p = 0.003), TBR70 (5.5 ± 14.2 vs. 3.0 ± 11.1%; p = 0.003), a glucose AUC of over 180 mg/dL (226.1 ± 257.8 vs. 178.0 ± 255.3 mg/dL × h; p = 0.001), and a lower TIR (56.0 ± 27.4 vs. 62.7 ± 29.6 mg/dL × h; p = 0.004). CONCLUSION: The dinner rapid insulin timing, insulin type, and the use of correction injections affect the nocturnal glucose profile in T1D.
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In this paper, as Black scholars, we address ways that interventions designed to promote equity in health can create pathways for coupling decolonization with antiracism by drawing on the intersection of the health of Africans and African Americans. To frame this intersection, we offer the Public Health Critical Race Praxis (PHCRP) and the PEN-3 Cultural Model as antiracism and decolonization tools that can jointly advance research on colonization and racism globally. We argue that racism is a global reality; PHCRP, an antiracism framework, and PEN-3, a decolonizing framework, can guide interventions to promote equity for Africans and African Americans.
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OBJECTIVES: We aimed to appraise the real-life efficacy of Crohn's disease exclusion diet (CDED) coupled with partial enteral nutrition (PEN) in inducing clinical and biochemical remission at disease onset and in patients with loss of response to biologics and immunomodulators. METHODS: We retrospectively gathered data of patients aged less than 18 years of age with a diagnosis of Crohn's disease (CD), who received CDED coupled with PEN at a tertiary level pediatric inflammatory bowel disease center. RESULTS: Sixty-six patients were identified. Forty (60.6%) started CDED plus PEN at disease onset and 26 (39.4%) received CDED with PEN as add-on therapy. Forty-six (69.7%) patients achieved clinical remission (weighted Pediatric Crohn's Disease Activity Index < 12.5) at the end of Phase 1, 44 (66.7%) normalized c-reactive protein levels (<0.5 mg/dL) and 18 (27.2%) patients normalized calprotectin levels (<150 microg/g). Nine of 19 (47.3%) of patients with clinically severe disease (defined by Physician Global Assessment) achieved clinical remission at the end of Phase I. Patients with extraintestinal manifestations had statistically lower clinical response rates to the dietary regimen (p = 0.018). Among patients who received CDED + PEN as add-on treatment, a previous successful course of Exclusive Enteral Nutrition was associated with statistically higher clinical remission rates at Week 8 (p = 0.026). Clinical response at Week 4 was an independent predictor of clinical remission and fecal calprotectin normalization at Week 8 (p = 0.002). CONCLUSION: CDED with PEN confirmed its efficacy in a real-life setting, proving to be effective also in refractory patients and those with severe disease. Early clinical response predicts clinical remission at the end of Phase 1.
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APS is a cheap and eco-friendly oxidant which enables one-step extraction of nanochitin (NCh) from fishery wastes. However, it is challenging to improve the preparation efficiency and NCh quality simultaneously, owing to the uneven or uncontrollable oxidation. Herein, we propose a simple and controllable way to isolate chitin nanofibers (ChNFs) from squid pen by gradient heating activated (GHA)- ammonium persulfate (APS) oxidation. Compared to the isothermal activated (ITA)-APS oxidation, our strategy reduced the mass ratio of squid pen to APS from 1:45 to 1:6 and reaction time from 15 h to 8 h. Meanwhile, the as-prepared ChNFs exhibited high yield (91.5 %), light transmittance (98 % at 500 nm), crystallinity index (96.9 %), and carboxyl content (1.53 mmol/g). GHA-APS oxidation involved multiple continuous heating and isothermal stages. The former stimulates a moderate activation of APS and enhances the oxidation rate, while the latter provides a duration for surface chemistry. This non-isothermal heating facilitates the continuous decomposition of APS at a relatively high and consistent rate, thereby enhances its oxidation efficiency. Furthermore, green assessments indicate this method is simple, time-saving, eco-friendly and cost-effective. Overall, this work introduces a novel perspective for the industrial extraction of high-efficiency and high-quality nanomaterials.
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Lung cancer is a prevalent malignancy associated with a high mortality rate, with a 5-year relative survival rate of 23%. Traditional survival analysis methods, reliant on clinician judgment, may lack accuracy due to their subjective nature. Consequently, there is growing interest in leveraging AI-based systems for survival analysis using clinical data and medical imaging. The purpose of this study is to improve survival classification for lung cancer patients by utilizing a 3D-CNN architecture (ResNet-34) applied to CT images from the NSCLC-Radiomics dataset. Through comprehensive ablation studies, we evaluate the effectiveness of different features and methodologies in classification performance. Key contributions include the introduction of a novel feature (GTV1-SliceNum), the proposal of a novel loss function (PEN-BCE) accounting for false negatives and false positives, and the showcasing of their efficacy in classification. Experimental work demonstrates results surpassing those of the existing literature, achieving a classification accuracy of 0.7434 and an ROC-AUC of 0.7768. The conclusions of this research indicate that the AI-driven approach significantly improves survival prediction for lung cancer patients, highlighting its potential for enhancing personalized treatment strategies and prognostic modeling.
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Flexible perovskite solar cells (f-PSCs) have achieved significant success. However, high-quality tin dioxide (SnO2) electron transport layers (ETLs) fabricated via chemical bath deposition (CBD) have not been achieved on flexible PEN/ITO substrates. This limitation is primarily due to the corrosion of the poor-quality ITO layer by the strongly acidic CBD solution. Here, we analyzed the reasons for the poor corrosion resistance of ITO films on PEN substrate from multiple perspectives, such as element composition, microstructure, and crystallinity. Then, we proposed a modified CBD method for SnO2films suitable for flexible PEN/ITO substrates. We employed SnCl2·2H2O as the tin source and regulated the pH of the CBD solution by NH3·H2O, which effectively avoided the corrosion of the ITO layer by the CBD solution and achieved high-quality SnO2films on the ITO layers. Compared to the commercial SnO2dispersion, the SnO2films prepared by this method have smaller grains and higher transmittance. As a result, we achieved an unprecedented power conversion efficiency (PCE) of 20.71% for f-PSCs fabricated on PEN/ITO substrates with SnO2ETLs by CBD method. This breakthrough facilitates the development of high-performance f-PSCs by a low-cost and large-scale chemical bath deposition of high-quality ETLs on flexible substrates.
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Self-reported penicillin allergy is highly prevalent. Different studies estimate that 10% of the population is labeled as such. This label, confirmed or suspected, forces us to take precautions and replace the antibiotic treatment of choice (frequently beta-lactams) with other 2nd or 3rd choice alternatives with worse overall results: side effects, resistance, costs, etc. The penicillin allergy label, once placed, remains in the medical record. It is only confirmed in less than 5% of patients, either because it has been placed inappropriately or because over time the sensitivity decreases and may disappear. Penicillin Allergy Decision Rule -PEN-FAST- is a validated and simple clinical prediction rule that estimates the risk of presenting an allergic reaction. Its use, together with algorithms that involve primary care in the study and delabeling of low-risk patients, can change our clinical practice.
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BACKGROUND: To evaluate the agreement between the Goldman applanation tonometer (GAT), Tono-Pen, and noncontact tonometer (NCT) in the measurement of intraocular pressure (IOP) in pseudophakic children. METHODS: The medical records of nonglaucomatous pseudophakic children between 2009 and 2019 were retrospectively analyzed. A total of 46 eyes of 23 patients operated for bilateral pediatric cataract were included in the study. The patients' mean age was 13.4 ± 4.1 years. Central corneal thickness (CCT) and IOP values measured with the GAT, Tono-Pen, and NCT were recorded. Agreement between the tonometers was evaluated by intraclass correlation coefficients (ICC) and the Bland-Altman method. RESULTS: The mean IOP of the 46 eyes included in the study was measured as 13.7 ± 2.3 mm Hg with the GAT, 16.0 ± 2.3 mm Hg with NCT, and 16.5 ± 2.3 mm Hg with the Tono-Pen (p < 0.001). There is no statistical difference between NCT and Tono-Pen measurements, while GAT measurements were significantly lower than those of the NCT and Tono-pen. ICC values showed fair agreement between NCT and Tono-Pen (ICC = 0.720), whereas there was poor agreement between GAT and NCT (ICC = 0.501) and Tono-pen (ICC = 0.314). CONCLUSIONS: With all devices included in the study, thicker corneas were associated with higher IOP measurements. Although there was moderate agreement between the NCT and Tono-Pen, there was a statistically significant difference in the IOP values provided by the three devices. Our results suggest these devices should not be used interchangeably.
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Pressão Intraocular , Pseudofacia , Tonometria Ocular , Humanos , Pressão Intraocular/fisiologia , Tonometria Ocular/instrumentação , Feminino , Masculino , Estudos Retrospectivos , Criança , Pseudofacia/fisiopatologia , Pseudofacia/diagnóstico , Adolescente , Reprodutibilidade dos Testes , Pré-Escolar , Córnea/patologiaRESUMO
Cancer stem cells (CSCs) are critical for progression, invasion, metastasis, and chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC). Presenilin enhancer 2 (Pen2), a vital component of the gamma-secretase complex, is overexpressed in various cancers and plays a significant role in carcinogenesis. Here, we investigated the association between Pen2 expression and the stem-like properties of PDAC cells. We analyzed Pen2 and its downstream target, Erb-B2 Receptor Tyrosine Kinase 4 (ErbB4), using public databases. The expression of Pen2 in CSC populations, marked by CD133+, CD44+, or epithelial cell adhesion molecule (EpCAM)+, was evaluated. Pen2-positive cells were sorted from Pen2-negative ones in PDAC cells transduced with a vector designed to express green fluorescent protein (GFP) under the Pen2 promoter. Stemness was examined in vitro and in vivo in Pen2-positive versus Pen2-negative cells. Our results showed that Pen2 was significantly upregulated, while ErbB4 was significantly downregulated in PDAC tissues compared to adjacent non-tumorous tissues, with an inverse relationship between Pen2 and Erbb4 levels. PDACs with high Pen2 expression are associated with considerably poorer patient survival. The CSC populations identified by CD133+, CD44+, and EpCAM+ markers displayed significantly higher Pen2 and lower EpCAM levels. Compared to Pen2-negative PDAC cells, Pen2-positive cells formed more tumor spheres, were more invasive and migratory, and showed significantly increased resistance to chemotherapy-induced apoptosis. Altering Pen2 levels reversed these oncogenic effects. In vivo, Pen2-positive cells formed larger tumors in immunodeficient mice. Overall, our findings suggest that Pen2 is highly expressed in CSCs within PDAC cells, being a novel therapeutic target.
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Carcinoma Ductal Pancreático , Células-Tronco Neoplásicas , Neoplasias Pancreáticas , Receptor ErbB-4 , Transdução de Sinais , Humanos , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Animais , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Camundongos , Receptor ErbB-4/metabolismo , Receptor ErbB-4/genética , Linhagem Celular Tumoral , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Masculino , Proliferação de CélulasRESUMO
The beta-lactam antibiotics are some of the safest and best-tolerated antibiotic agents; however, many patients have reported allergies against penicillin. All beta-lactam antibiotics are only restrictively prescribed for these patients and alternative antibiotics are increasingly given, which carries the risk of negative clinical results and socioeconomic sequelae; however, over 95% of patients who reported an allergy to penicillin show a negative result in the allergy tests for penicillin and this antibiotic can safely be prescribed. The use of sensitive and specific instruments for identification of false penicillin allergies should be an important topic within the framework of antibiotic stewardship. Anesthesists can play a central role in the reduction of the enormous individual and public health burden associated with the classification of penicillin allergy by taking an appropriate medical history and a risk stratification for the identification of patients with a penicillin allergy. This overview article presents a possible delabelling algorithm within the framework of the clarification of a beta-lactam antibiotic allergy. The focus is on a structured allergy anamnesis using the penicillin allergy, five or fewer years ago, anaphylaxis/angioedema, severe cutaneous adverse reaction (SCAR) and treatment required for allergy episode (PEN-FAST) score.
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Antibacterianos , Hipersensibilidade a Drogas , Penicilinas , Hipersensibilidade a Drogas/diagnóstico , Humanos , Penicilinas/efeitos adversos , Antibacterianos/efeitos adversos , Anafilaxia/diagnóstico , AlgoritmosRESUMO
The Au partially embedded nanostructure (PEN) is synthesized by ion irradiation on an Au thin film deposited on a glass substrate using a 50 keV Ar ion. Scanning electron microscopy results show ion beam-induced restructuring from irregularly shaped nanostructures (NSs) to spherical Au NSs, and further ion irradiation leads to the formation of well-separated spherical nanoparticles. Higuchi's algorithm of surface analysis is utilized to find the evolution of surface morphology with ion irradiation in terms of the Hurst exponent and fractal dimension. The Au PEN is evidenced by Rutherford backscattering spectrometry and optical studies. Also, the depth of the mechanism behind synthesized PEN is explained on the basis of theoretical simulations, namely, a unified thermal spike and a Monte Carlo simulation consisting of dynamic compositional changes (TRIDYN). Another set of plasmonic NSs was formed on the surface by thermal annealing of the Au film on the substrate. Glucose sensing has been studied on the two types of plasmonic layers: nanoparticles on the surface and PEN. The results reveal the sensing responses of both types of plasmonic layers. However, PEN retains its plasmonic behavior as the NSs are still present after washing with water, which demonstrates the potential for reusability. RESEARCH HIGHLIGHTS: Synthesis of PENs by ion irradiation Utilization of Higuchi's algorithm to explore the surface morphology. Unified thermal spike and TRIDYN simulations being used to explain the results. Glucose is only used as a test case for reusability of substrate.