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The acidic compounds such as Mercaptans, H2S and COS are commonly present in the liquid LPG streams in the south Pars gas processing plant. Sulfur contaminants not only lead to odor problems but can form objectionable oxides on combustion and cause environmental pollution. In present study, Support Vector Machine (SVM) is employed to develop an intelligent model to predict the sulfur content of propane and butane products of Liquefied Petroleum Gas (LPG) treatment unit of south Pars gas processing plant of Assaluyeh/Iran. A set of seven input/output plant data each consisting of 365 data has been used to train, optimize, and test the model. Model development that consists of training, optimization and test was performed using randomly selected 70%, 15%, and 15% of available data respectively. Test results from the SVM developed model showed good compliance with operating plant data. Squared correlation coefficients for developed models are 0.97 and 0.99 for propane and butane sulfur content, respectively. According to the results of the present case study, SVM could be regarded as a reliable accurate approach for modeling the sulfur content of LPG treatment unit of a natural gas processing plant.

Objective(s): To evaluate the etiology of cataract and prevalence and correlation of risk factors with various types of cataract.Methods: Among the patients who underwent cataract surgery in Labafinejad Hospital in 2004, 400 patients were chosen by a systemic sampling method. Information were collected from the patients' records and recorded in a check list.Results: Senile and congenital types of cataract were the most prevalent in the sample. There was a correlation between age, mean age, sex, type of involvement and type of cataract. Among systemic diseases, hypertension was the most common (35.5%), followed by diabetes mellitus (22%). In slit lamp examination, of congenital cases, the most common opacity was lamellar type and in other types of cataract, mixed opacity was the most common type. Conclusion: In this study the proportion of male cases was greater than that reported in other studies. Meanwhile, 65.5% of the patients were under the age of 70, which shows the need for evaluation of the relatively low age of onset in Iran.

Background: Prostate cancer manifests in various forms, ranging from occult and localized to metastatic disease. Analyzing prostate biopsies offers insights into histopathological characteristics, enhancing disease understanding and management., Methods: This 14-year study reviewed ultrasound-guided needle prostate biopsies, collecting data via questionnaires and medical records, focusing on Gleason group, tumor involvement percentage, and predicted cancer stage. A comparative analysis across 2 distinct 7-year intervals was conducted. Statistical analyses included the Kolmogorov-Smirnov test, chi-square test, Fisher's exact test, and Analysis of Covariance, all performed using SPSS software., Results: Among 1,598 biopsies, 624 cases of adenocarcinoma were identified. Malignancy incidence significantly correlated positively with age, prostate-specific antigen (PSA), and PSA density (PSAD), and inversely with prostate volume and the free-to-total PSA ratio (%fPSA). Notably, 30.8% of malignancies were classified as Gleason groups 4 or 5, displaying significantly higher PSA levels. Patients with prior transurethral resection of the prostate exhibited increased malignancy rates and higher Gleason groups. Diagnostic accuracy, measured by Area Under the Curve, was 0.719 for PSA, 0.730 for %fPSA, and 0.817 for PSAD. The later phase of the study showed higher cancer detection, lower PSA levels, and a greater incidence of higher Gleason groups despite a lower predicted stage., Conclusion: The prevalence of higher Gleason groups was similar to other studies. PSAD demonstrated greater diagnostic reliability than PSA alone. Additionally, higher malignancy rates and Gleason groups were observed in patients with prior transurethral resection of the prostate. The increase in cancer detection rates during the second period likely indicates improved biopsy candidate selection., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, largely attributable to complement activation resulting in intravascular and extravascular hemolysis. Pegcetacoplan is a subcutaneously administered C3-targeted therapy, which may be suitable for treating CAD and wAIHA. In this open-label phase 2 study, analyses were conducted in 2 cohorts, 1 for patients with CAD and the other for those with wAIHA. In each cohort, patients were randomly assigned to receive pegcetacoplan 270 mg/d or 360 mg/d for up to 48 weeks. Safety end points included the incidence and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Efficacy end points included change from baseline in hemoglobin (Hb), lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and functional assessment of chronic illness therapy (FACIT)-fatigue scale. Thirteen of 13 (100%) and 10 of 11 (91%) patients with CAD and wAIHA, respectively, experienced at least 1 TEAE. Ten patients had at least 1 serious AE; none were considered related to pegcetacoplan. The only treatment-related AESIs were injection site reactions. Pegcetacoplan increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in the first weeks; at week 48 the median (interquartile range) change from baseline Hb for the CAD and wAIHA total groups was 2.4 (0.90-3.00) and 1.7 g/dL (-1.40 to 2.90), respectively, and improvements in hemolysis and FACIT-fatigue scale scores were maintained. This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective for patients with CAD and wAIHA. This trial was registered at www.ClinicalTrials.gov as #NCT03226678., (© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Quercetin, a natural compound, shows promising potential in wound healing by reducing fibrosis, limiting scar formation, and boosting fibroblast proliferation. However, its effectiveness is hindered by poor solubility, resulting in low bioavailability and necessitating high doses for therapeutic efficacy. This study presents a novel approach, fabricating quercetin-loaded microarray patches (MAPs) using widely employed solubility enhancement strategies. Fabricated MAPs exhibited favourable mechanical strength and could be inserted into excised porcine skin to a depth of 650 μm. Furthermore, formulations containing Soluplus ® significantly increased the drug loading capacity, achieving up to 2.5 mg per patch and complete dissolution within an hour of application on excised porcine skin. In vitro studies on full-thickness neonatal porcine skin demonstrated that Soluplus ® -enhanced MAPs effectively delivered quercetin across various skin layers, achieving a delivery efficiency exceeding 80% over 24 h. Additionally, these prototype MAPs displayed anti-inflammatory properties and demonstrated biocompatibility with human keratinocyte skin cells. Therefore, quercetin-loaded MAPs employing Soluplus ® as a solubility enhancer present a promising alternative strategy for wound healing and anti-inflammatory therapy applications., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interest., (© 2024. The Author(s).)

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the primary causes of vision impairment and blindness worldwide. The current treatment for these diseases is an intravitreal injection of anti-VEGF agents, which are costly and require frequent injections. Implants can be used to sustain the release of drugs and minimize side effects. Axitinib (AX) is a potent VEGF receptor inhibitor and a promising candidate for treating posterior ocular diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). A sustained release of AX was successfully achieved from 3D-printed AX-loaded implants fabricated using the well-known 3D printing technique, semi-solid extrusion (SSE). AX at concentrations of 10% w/w and 20% w/w was incorporated within the polycaprolactone (PCL) and Precirol®-based matrix. The fabricated implants were characterized via FTIR spectroscopy, SEM imaging, and thermal analysis. The implants were also evaluated for their drug release and biocompatibility. The AX-loaded implants exhibited thermal stability, and no chemical interactions were found between AX and the matrix components. The release mechanism study of AX revealed that the concentration of drug loading influenced AX release from the implant, with a 10% w/w and 20 %w/w of AX showing first-order and Korsmeyer-Peppas mechanism, respectively. A biocompatibility study using ARPE-19 cells confirmed that AX-loaded implants are nontoxic and safe for ocular use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Tissue engineering combines biology and engineering to develop constructs for repairing or replacing damaged tissues. Over the last few years, this field has seen significant advancements, particularly in bone tissue engineering. 3D printing has revolutionised this field, allowing the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration, thus providing a personalised approach that offers unique control over the shape, size, and structure of 3D-printed constructs. Accordingly, thermoplastic polyurethane (TPU)-based 3D-printed scaffolds loaded with dipyridamole (DIP) were manufactured to evaluate their in vitro osteogenic capacity. The fabricated DIP-loaded TPU-based scaffolds were fully characterised, and their physical and mechanical properties analysed. Moreover, the DIP release profile, the biocompatibility of scaffolds with murine calvaria-derived pre-osteoblastic cells, and the intracellular alkaline phosphatase (ALP) assay to verify osteogenic ability were evaluated. The results suggested that these materials offered an attractive option for preparing bone scaffolds due to their mechanical properties. Indeed, the addition of DIP in concentrations up to 10% did not influence the compression modulus. Moreover, DIP-loaded scaffolds containing the highest DIP cargo (10% w/w) were able to provide sustained drug release for up to 30 days. Furthermore, cell viability, proliferation, and osteogenesis of MC3T3-E1 cells were significantly increased with the highest DIP cargo (10% w/w) compared to the control samples. These promising results suggest that DIP-loaded TPU-based scaffolds may enhance bone regeneration. Combined with the flexibility of 3D printing, this approach has the potential to enable the creation of customized scaffolds tailored to patients' needs at the point of care in the future., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Background: During dental school, students may encounter stressful events that contribute to stress, anxiety, and depression; in response to these factors, some students use vaping or electronic cigarettes., Objective: To evaluate the relationship between electronic cigarettes use and stress, anxiety, and depression among dental students., Methods: A cross-sectional study included 142 dental students in their preclinical, clinical, or internship year was conducted. The 142 participants were split evenly between two groups: smokers and nonsmokers. The average age of the study's male and female participants was 21.6 years. Using the DASS 21 scale, participants were instructed to complete an electronic questionnaire assessing the association between electronic cigarettes use and stress, anxiety, and depression in smokers and nonsmokers., Results: According to the findings of this study, stress, anxiety, and depression were significantly associated with electronic cigarette use. Compared to non-smokers, electronic cigarette smokers reported higher levels of severe/extremely severe depression (OR: 10.34, 95% CI: [4.23-24.1]), anxiety (OR: 13.8, 95% CI: [5.4-30.1]) and stress (OR: 27.6, 95% CI: [8.9-85.8]). Compared to males, females were 2.5 times (95% CI: [1.02-6.1]) more likely to report severe/extremely severe anxiety ( P < 0.05)., Conclusion: This study demonstrates a significant correlation between the use of electronic cigarettes and elevated levels of stress, anxiety, and depression among dental students in the UAE., Competing Interests: The authors declare that they have no competing interests., (© 2024 Tawba et al.)

Background: Although complement component 5 inhibitors (C5is) eculizumab and ravulizumab improve paroxysmal nocturnal hemoglobinuria (PNH) outcomes, patients may experience persistent anemia. This post hoc analysis investigated whether the complement component 3-targeted therapy pegcetacoplan also improved hematologic outcomes and reduced fatigue in patients with PNH and mild/moderate anemia., Methods: Patients with PNH and hemoglobin ≥10.0 g/dL at baseline of PADDOCK (N = 6), PRINCE (N = 8), and PEGASUS (N = 11) were included. Before receiving pegcetacoplan, PADDOCK and PRINCE patients were C5i-naive; PEGASUS patients had hemoglobin <10.5 g/dL despite stably dosed eculizumab. Hemoglobin concentrations, percentages of patients with concentrations ≥12 g/dL, and sex-specific normalization were assessed at baseline and after 16 weeks of pegcetacoplan, as were absolute reticulocyte counts (ARCs) and normalization and fatigue scores and normalization., Results: From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 [0.4] to 12.7 [1.1] g/dL; PRINCE: 11.3 [1.0] to 14.0 [1.3] g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 [0.2] to 12.8 [2.6] g/dL). Percentage of patients with hemoglobin ≥12 g/dL increased (PADDOCK: 0 to 60.0% [3 of 5 patients]; PRINCE: 25.0% [2 of 8] to 87.5% [7 of 8]; PEGASUS: 0 to 72.7% [8 of 11]). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation., Conclusion: Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan., Trial Registration: Trial registration numbers: PADDOCK (NCT02588833), PRINCE (NCT04085601; EudraCT, 2018-004220-11), PEGASUS (NCT03500549)., Competing Interests: JP: reports consultancy and honoraria at Blueprint Medicines, Amgen, F Hoffmann-La Roche, MSD, Bristol Myers Squibb, Alexion Pharmaceuticals, Novartis, Pfizer, Gilead, Boehringer Ingelheim, Swedish Orphan Biovitrum, and Apellis Pharmaceuticals; and honoraria from Swiss Biopharma. ND: has nothing to disclose SO: has nothing to disclose RPdL: has nothing to disclose PS: reports membership on an entity’s Board of Directors or advisory committees with Blueprint Medicines and Swedish Orphan Biovitrum AB; Honoraria, Membership on an entity’s Board of Directors or advisory committees and Speakers Bureau with Alexion and Bristol Myers Squibb; Honoraria and Membership on an entity’s Board of Directors or advisory committees with MSD and Novartis. NS: reports membership of advisory committee with Alexion. MA-A: was an employee at the time of this study and held stock options. EP: is an employee of Swedish Orphan Biovitrum AB. RSMW: has received consulting fees, honoraria, research funding, and speaker’s bureau fees from Alexion and F. Hoffmann-La Roche Ltd.; and research funding and speaker’s bureau fees from Apellis. These affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Panse et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: We determined normalization rates for hemoglobin, lactate dehydrogenase (LDH), and fatigue in patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with pegcetacoplan (PEG) in the PEGASUS (NCT03500549) and PRINCE (NCT04085601) phase III trials., Methods: Enrolled patients had PNH and hemoglobin < 10.5 g/dL despite ≥ 3 months of eculizumab (ECU) [PEGASUS], or were complement component 5 (C5) inhibitor-naive, receiving supportive care only, with hemoglobin less than the lower limits of normal (LLN) [PRINCE]. Hematologic and fatigue normalization endpoints were hemoglobin greater than or equal to the LLN (females: 12 g/dL; males: 13.6 g/dL) in the absence of transfusion; LDH ≤226 U/L in the absence of transfusion; and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue ≥ 43.6, the general population norm. Safety was assessed by investigators using standardized terms and definitions for seriousness and severity., Results: Hemoglobin normalization occurred in 34.1% (14/41) of PEG-treated patients at Week 16 (randomized controlled period) in PEGASUS (vs. 0% [0/39] of ECU-treated patients) and in 45.7% (16/35) of PEG-treated patients at Week 26 in PRINCE (vs. 0% [0/18] of supportive care-treated patients). At Week 48 (open-label period) in PEGASUS, 24.4% of PEG-treated patients (PEG-to-PEG) and 30.8% of patients treated with ECU through Week 16 who switched to PEG through Week 48 (ECU-to-PEG) had hemoglobin normalization. Rates of LDH normalization in PEGASUS were 70.7% (PEG-treated patients) and 15.4% (ECU-treated patients) at Week 16, and 56.1% (PEG-to-PEG) and 51.3% (ECU-to-PEG) at Week 48. In PRINCE, 67.5% of PEG-treated patients at Week 26 had normalized LDH concentrations. Rates of FACIT-Fatigue score normalization in PEGASUS were 48.8% and 10.3% in PEG- and ECU-treated patients, respectively, at Week 16, and 34.1% and 51.3% in PEG-to-PEG- and ECU-to-PEG-treated patients, respectively, at Week 48. In PRINCE, 68.6% of PEG-treated patients and 11.1% of supportive care patients had FACIT-Fatigue score normalization at Week 26. PEG was safe and well tolerated. Injection site reactions, mostly mild, were the most common adverse event of special interest in PEG-treated patients in the PEGASUS randomized controlled period (36.6%) and in PRINCE (30.4%)., Conclusion: PEG is superior to ECU and supportive care in hemoglobin, LDH, and FACIT-Fatigue score normalization for patients with PNH and persistent anemia despite ≥3 months of treatment with ECU, and in C5 inhibitor-naive patients., Clinical Trial Registration: The PEGASUS trial (NCT03500549) was registered on 18 August 2018, and the PRINCE trial (NCT04085601) was registered on 11 September 2019., (© 2024. The Author(s).)

The leading cause of death worldwide and a significant factor in decreased quality of life are the cardiovascular diseases. Endovascular operations like angioplasty, stent placement, or atherectomy are often used in vascular surgery to either dilate a narrowed blood artery or remove a blockage. As an alternative, a vascular transplant may be utilised to replace or bypass a dysfunctional or blocked blood vessel. Despite the advancements in endovascular surgery and its popularisation over the past few decades, vascular bypass grafting remains prevalent and is considered the best option for patients in need of long-term revascularisation treatments. Consequently, the demand for synthetic vascular grafts composed of biocompatible materials persists. To address this need, biodegradable clopidogrel (CLOP)-loaded vascular grafts have been fabricated using the digital light processing (DLP) 3D printing technique. A mixture of polylactic acid-polyurethane acrylate (PLA-PUA), low molecular weight polycaprolactone (L-PCL), and CLOP was used to achieve the required mechanical and biological properties for vascular grafts. The 3D printing technology provides precise detail in terms of shape and size, which lead to the fabrication of customised vascular grafts. The fabricated vascular grafts were fully characterised using different techniques, and finally, the drug release was evaluated. Results suggested that the performed 3D-printed small-diameter vascular grafts containing the highest CLOP cargo (20% w/w) were able to provide a sustained drug release for up to 27 days. Furthermore, all the CLOP-loaded 3D-printed materials resulted in a substantial reduction of the platelet deposition across their surface compared to the blank materials containing no drug. Haemolysis percentage for all the 3D-printed samples was lower than 5%. Moreover, 3D-printed materials were able to provide a supportive environment for cellular attachment, viability, and growth. A substantial increase in cell growth was detected between the blank and drug-loaded grafts., (© 2023. The Author(s).)

Hydrogel-forming microneedles (HF-MNs) are composed of unique cross-linked polymers that are devoid of the active pharmaceutical ingredient (API) within the microneedle array. Instead, the API is housed in a reservoir affixed on the top of the baseplate of the HF-MNs. To date, various types of drug-reservoirs and multiple solubility-enhancing approaches have been employed to deliver hydrophobic molecules combined with HF-MNs. These strategies are not without drawbacks, as they require multiple manufacturing steps, from solubility enhancement to reservoir production. However, this current study challenges this trend and focuses on the delivery of the hydrophobic antibiotic rifampicin using SmartFilm-technology as a solubility-enhancing strategy. In contrast to previous techniques, smart drug-reservoirs (SmartReservoirs) for hydrophobic compounds can be manufactured using a one step process. In this study, HF-MNs and three different concentrations of rifampicin SmartFilms (SFs) were produced. Following this, both HF-MNs and SFs were fully characterised regarding their physicochemical and mechanical properties, morphology, Raman surface mapping, the interaction with the cellulose matrix and maintenance of the loaded drug in the amorphous form. In addition, their drug loading and transdermal permeation efficacy were studied. The resulting SFs showed that the API was intact inside the cellulose matrix within the SFs, with the majority of the drug in the amorphous state. SFs alone demonstrated no transdermal penetration and less than 20 ± 4 μg of rifampicin deposited in the skin layers. In contrast, the transdermal permeation profile using SFs combined with HF-MNs ( i.e . SmartReservoirs) demonstrated a 4-fold increase in rifampicin deposition (80 ± 7 μg) in the skin layers and a permeation of approx. 500 ± 22 μg. Results therefore illustrate that SFs can be viewed as novel drug-reservoirs ( i.e. SmartReservoirs) for HF-MNs, achieving highly efficient loading and diffusion properties through the hydrogel matrix.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease characterized by complement-mediated hemolysis and thrombosis. Pegcetacoplan, the first targeted complement component 3 (C3) PNH therapy, was safe and efficacious in treatment-naive and pre-treated patients with PNH in five clinical trials., Methods: The 307 open-label extension (OLE) study (NCT03531255) is a non-randomized, multicenter extension study of long-term safety and efficacy of pegcetacoplan in adult patients with PNH who completed a pegcetacoplan parent study. All patients received pegcetacoplan. Outcomes at the 48-week data cutoff (week 48 of 307-OLE or August 27, 2021, whichever was earlier) are reported. Hemoglobin concentrations, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores, and transfusion avoidance were measured. Hemoglobin > 12 g/dL and sex-specific hemoglobin normalization (i.e., male, ≥ 13.6 g/dL; female, ≥ 12 g/dL) were assessed as percentage of patients with data available and no transfusions 60 days before data cutoff. Treatment-emergent adverse events, including hemolysis, were reported., Results: Data from 137 patients with at least one pegcetacoplan dose at data cutoff were analyzed. Mean (standard deviation [SD]) hemoglobin increased from 8.9 (1.22) g/dL at parent study baseline to 11.6 (2.17) g/dL at 307-OLE entry and 11.6 (1.94) g/dL at data cutoff. At parent study baseline, mean (SD) FACIT-Fatigue score of 34.1 (11.08) was below the general population norm of 43.6; scores improved to 42.8 (8.79) at 307-OLE entry and 42.4 (9.84) at data cutoff. In evaluable patients, hemoglobin > 12 g/dL occurred in 40.2% (43 of 107) and sex-specific hemoglobin normalization occurred in 31.8% (34 of 107) at data cutoff. Transfusion was not required for 114 of 137 patients (83.2%). Hemolysis was reported in 23 patients (16.8%). No thrombotic events or meningococcal infections occurred., Conclusion: Pegcetacoplan sustained long-term improvements in hemoglobin concentrations, fatigue reduction, and transfusion burden. Long-term safety findings corroborate the favorable profile established for pegcetacoplan., Trial Registration: ClinicalTrials.gov identifier, NCT03531255., (© 2024. The Author(s).)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disease characterized by complement-mediated hemolysis and thrombosis. Complement component 5 (C5) inhibitors have decreased PNH-related thrombosis rates and reduced mortality compared with those of age-matched controls. A small but significantly increased risk of life-threatening Neisseria infections, especially N meningitidis , represents a long-term safety risk of complement inhibition., Objectives: To evaluate the rates of thrombosis and meningococcal infections in patients with PNH treated with the complement component 3-targeted therapy pegcetacoplan., Methods: Cumulative patient-year exposure to pegcetacoplan was calculated, and thrombotic events and meningococcal infections were reviewed in 7 clinical trials and in the postmarketing setting. The clinical trial protocols and pegcetacoplan labeling required vaccination against Streptococcus pneumoniae , N meningitidis , and Haemophilus influenzae before pegcetacoplan use; the label allowed for prophylactic antibiotic use if pegcetacoplan must be administered before vaccination., Results: As of November 13, 2022, 464 patients with PNH had 619.4 patient-years of pegcetacoplan exposure in completed/ongoing clinical trials and the postmarketing setting. Seven thrombotic events were reported: 5 in clinical trials (2 in the same patient) and 2 in the postmarketing setting. The overall thrombosis rate was 1.13 events per 100 patient-years (clinical trials: 1.22 events/100 patient-years in 409.4 years; postmarketing: 0.95 events/100 patient-years in 210.0 years). No infections with meningococcal bacteria were reported., Conclusion: Event rates for thrombosis were comparable between pegcetacoplan and previously reported rates of C5 inhibitors in patients with PNH, and no cases of meningococcal infection were reported with pegcetacoplan. Continued follow-up is required., (© 2024 Apellis Pharmaceuticals, Inc.)

Structural and contextual factors such as limited work and housing opportunities negatively affect the health and well-being of newly settled refugee migrants in receiving high-income countries. Health promotion initiatives aiming at strengthening health and integration have been tried out within the Swedish Introduction program for refugee migrants. However, longitudinal evaluations of these interventions are rare. The aim of the current study was to compare the effectiveness of a regular and an extended civic orientation course with added health communication and examine whether the latter would improve self-rated health and psychological well-being, health literacy and social capital among newly settled refugee migrants in Sweden. Pre- and post-assessment questionnaires were collected from the intervention group receiving the extended course (n = 143) and a control group receiving the regular course (n = 173). Linear mixed models and chi-square analyses showed a significant increase with a small effect size (0.21) in health literacy in the intervention group. However, there were no significant changes in emotional and practical support, general self-rated health or psychological well-being. The findings indicate that added health communication provided embedded in the civic orientation course can increase health literacy. However, further longitudinal studies are needed to confirm the sustainability of the observed effect and examine whether these short-term improvements in health literacy translate to long-term advances in health and integration., (© The Author(s) 2024. Published by Oxford University Press.)

In Iran, similar to other developing countries, groundwater quality has been seriously threatened. Therefore, this study aimed to apply Machine Learning Algorithms (MLAs) in Groundwater Quality Modeling (GQM) and determine the optimal algorithm using the Best-Worst Method (BWM) in Ardabil province, Iran. Groundwater quality parameters included calcium (Ca 2+ ), magnesium (Mg 2+ ), sodium (Na + ), potassium (K + ), chlorine (Cl - ), sulfate (SO 4 - ), total dissolved solids (TDS), bicarbonate (HCO 3 - ), electrical conductivity (EC), and acidity (pH). In the following, seven MLAs, including Support Vector Regression (SVR), Random Forest (RF), Decision Tree Regressor (DTR), K-Nearest Neighbor (KNN), Naïve Bayes, Simple Linear Regression (SLR), and Support Vector Machine (SVM), were used in the Python programming language, and groundwater quality was modeled. Finally, BWM was used to validate the results of MLAs. The results of examining the error statistics in determining the optimal algorithm in groundwater quality modeling showed that the RF algorithm with values of MAE = 0.28, MSE = 0.12, RMSE = 0.35, and AUC = 0.93 was selected as the most optimal MLA. The Schoeller diagram also showed that various ion ratios, including Na + K, Ca 2+ , Mg 2+ , Cl - , and HCO 3 +CO 3 , in most of the sampled points had upward average values. Based on the results of the BWM method, it can be concluded that a great similarity was observed between the results of the RF algorithm and the classification of the BWM method. These results showed that more than 50% of the studied area had low quality based on hydro-chemical parameters of groundwater quality. The findings of this research can assist managers and planners in developing suitable management models and implementing appropriate strategies for the optimal exploitation of groundwater resources., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Blunt traumatic diaphragmatic injury (TDI) is typically associated with severe trauma and concomitant injuries. It is a diagnostic challenge in the setting of blunt trauma and can be easily overlooked especially in the acute phase often dominated by concurrent injuries., Methods: A retrospective review was conducted of patients with blunt-TDI identified from a level 1 trauma registry. Variables associated with early versus delayed diagnosis as well as non-survivor and survivor groups were collected to examine factors associated with delayed diagnosis., Results: A total of 155 patients were included (mean age 46 ± 20, 60.6% male). Diagnosis was made <24 h in 126 (81.3%), and >24 h in 29 (18.7%). Of the delayed diagnosis group, 14 (48%) were diagnosed >7 days. Overall, 27 (21.4%) patients had a diagnostic initial CXR and 64 (50.8%) had a diagnostic initial CT. Fifty-eight (37.4%) patients were diagnosed intraoperatively. Of the delayed diagnosis group, 22 (75.9%) had no initial signs on CXR or CT, 15 (52%) of this group had persistent pleural-effusions/elevated-hemidiaphragm leading to further investigation and diagnosis. No significant difference in survival was observed between early and delayed diagnoses, no clinically significant injury patterns to predict delayed diagnoses were noted., Conclusion: The diagnosis of TDI is challenging. Without frank signs of herniation of abdominal contents on CXR or CT, the diagnosis is often not made on initial imaging. In patients with the evidence of blunt traumatic injury in the lower-chest/upper-abdomen, a high degree of clinical suspicion should be held and follow-up CXRs/CTs arranged., (© 2023 Australasian College for Emergency Medicine.)

Backgrounds: Endoscopic thoracic sympathectomy (ETS) is a permanent and effective treatment for primary hyperhidrosis and facial blushing; however, severe compensatory sweating (SCS) remains a devastating complication. We aimed to (i) construct a nomogram to predict the risk of SCS, and (ii) investigate factors associated with the level of satisfaction., Methods: From Jan 2014 to Mar 2020, 347 patients underwent ETS by a single surgeon. These patients were asked to complete an online questionnaire regarding primary symptom resolution, level of satisfaction, and development of compensatory sweating. Multivariable analysis was conducted via logistic regression and ordinal regression to predict SCS and satisfaction level respectively. Nomogram was developed based on significant predictors., Results: In total, 298 (85.9%) patients responded to the questionnaire with a mean follow up of 4.9 ± 1.8 years. Significant factors associated with SCS in the nomogram included older age (OR 1.05, 95% CI 1.02-1.09, P = 0.001), primary indication other than palmar hyperhidrosis (OR 2.30, 95% CI 1.03-5.12, P = 0.04), and current smoking (OR 5.91, 95% CI 2.46-14.20, P < 0.001). The area under receiver operating characteristic curve was 0.713. Multivariable analysis revealed that longer follow up (β = -0.201 ± 0.078, P = 0.01), gustatory hyperhidrosis (β = -0.781 ± 0.267, P = 0.003), primary indication other than palmar hyperhidrosis (β = -1.524 ± 0.292, P < 0.001), and SCS (β = -3.061 ± 0.404, P < 0.001) were independently associated with a lower degree of patient satisfaction., Conclusion: The novel nomogram can provide a personalized numerical risk estimate to assist both the clinician and patient weigh the pros and cons as part of the decision-making process, mitigating the chance of patient dissatisfaction., (© 2023 Royal Australasian College of Surgeons.)

3D Printing is an innovative technology within the pharma and food industries that allows the design and manufacturing of novel delivery systems. Orally safe delivery of probiotics to the gastrointestinal tract faces several challenges regarding bacterial viability, in addition to comply with commercial and regulatory standpoints. Lactobacillus rhamnosus CNCM I-4036 (Lr) was microencapsulated in generally recognised as safe (GRAS) proteins, and then assessed for robocasting 3D printing. Microparticles (MP-Lr) were developed and characterised, prior to being 3D printed with pharmaceutical excipients. MP-Lr showed a size of 12.3 ± 4.1 µm and a non-uniform wrinkled surface determined by Scanning Electron Microscopy (SEM). Bacterial quantification by plate counting accounted for 8.68 ± 0.6 CFU/g of live bacteria encapsulated within. Formulations were able to keep the bacterial dose constant upon contact with gastric and intestinal pH. Printlets consisted in oval-shape formulations (15 mm × 8 mm × 3.2 mm) of ca. 370 mg of total weight, with a uniform surface. After the 3D printing process, bacterial viability remained even as MP-Lr protected bacteria alongside the process (log reduction of 0.52, p > 0.05) in comparison with non-encapsulated probiotic (log reduction of 3.05). Moreover, microparticle size was not altered during the 3D printing process. We confirmed the success of this technology for developing an orally safe formulation, GRAS category, of microencapsulated Lr for gastrointestinal vehiculation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by complement-mediated hemolysis. Pegcetacoplan is the first C3-targeted therapy approved for adults with PNH (United States), adults with PNH with inadequate response or intolerance to a C5 inhibitor (Australia), and adults with anemia despite C5-targeted therapy for ≥3 months (European Union). PRINCE was a phase 3, randomized, multicenter, open-label, controlled study to evaluate the efficacy and safety of pegcetacoplan vs control (supportive care only; eg, blood transfusions, corticosteroids, and supplements) in complement inhibitor-naive patients with PNH. Eligible adults receiving supportive care only for PNH were randomly assigned and stratified based on their number of transfusions (<4 or ≥4) 12 months before screening. Patients received pegcetacoplan 1080 mg subcutaneously twice weekly or continued supportive care (control) for 26 weeks. Coprimary end points were hemoglobin stabilization (avoidance of >1-g/dL decrease in hemoglobin levels without transfusions) from baseline through week 26 and lactate dehydrogenase (LDH) change at week 26. Overall, 53 patients received pegcetacoplan (n = 35) or control (n = 18). Pegcetacoplan was superior to control for hemoglobin stabilization (pegcetacoplan, 85.7%; control, 0; difference, 73.1%; 95% confidence interval [CI], 57.2-89.0; P < .0001) and change from baseline in LDH (least square mean change: pegcetacoplan, -1870.5 U/L; control, -400.1 U/L; difference, -1470.4 U/L; 95% CI, -2113.4 to -827.3; P < .0001). Pegcetacoplan was well tolerated. No pegcetacoplan-related adverse events were serious, and no new safety signals were observed. Pegcetacoplan rapidly and significantly stabilized hemoglobin and reduced LDH in complement inhibitor-naive patients and had a favorable safety profile. This trial was registered at www.clinicaltrials.gov as NCT04085601., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Newly settled refugee migrants face psychological stressors stemming from pre-, during- and post-migration experiences. In Sweden, mental health promotion is part of the health module in the civic orientation classes for newly settled refugee migrants. Training courses are offered to civic communicators and workshop leaders to facilitate communication about mental health; however, the training is seldom evaluated. In the current study, we aim to explore civic communicators' perceptions and experiences of an in-depth mental health training course in relation to observed needs among newly settled refugee migrants., Method: We interviewed ten civic communicators that had partaken in the in-depth training course on mental health. All respondents had prior migratory experience and worked as civic communicators in their native languages. The interviews were semi-structured and data were analyzed using thematic analysis., Results: Three themes were identified: (1) Intertwined mental health needs related to migration, (2) Multi-layered barriers to addressing mental health, and (3) Becoming aware of the mental health journey. One overarching theme was arrived at through synthesizing the three themes 'Acquired new tools to lead reflective conversations about mental health and well-being'., Conclusion: The in-depth mental health training course led to the attainment of new knowledge and new tools enabling civic communicators to lead reflective conversations about mental health and well-being with newly settled refugee migrants. Mental health needs were related to pre- and post-migration experiences. Barriers to talking about mental health included stigma and a lack of arenas to promote the mental health of refugee migrants. Increasing knowledge among civic communicators can facilitate the promotion of mental self-help capacity and resilience among newly settled refugee migrants., (© 2023. The Author(s).)

Introduction: In the absence of head-to-head trials, this study compared treatment outcomes with the C3 complement inhibitor pegcetacoplan versus the C5 complement inhibitor eculizumab or ravulizumab in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH)., Methods: A matching-adjusted indirect comparison was conducted using individual patient data from the pegcetacoplan arm of the PRINCE trial (NCT04085601; n = 34) and aggregate data from the ravulizumab (n = 125) and eculizumab (n = 121) arms of the ALXN1210-PNH-301 trial (NCT03056040). Clinical and quality of life endpoints were evaluated after matching patients in the two trials on baseline characteristics. The weighted Wald test with 95% confidence interval was used to compare categorical and continuous variables (i.e., weighted chi-squared and z tests, respectively). Bias factor analysis was performed to quantify the extent of residual bias from unmeasured confounders., Results: After weighting, treatment with pegcetacoplan was associated with statistically significant improvements in most clinical endpoints compared with ravulizumab or eculizumab treatment. These included: greater absolute and percent reductions in lactate dehydrogenase (LDH) level and increase in hemoglobin level from baseline; shorter time to first occurrence of LDH normalization; larger proportions of patients achieving hemoglobin stabilization and avoiding transfusion, with fewer packed red blood cell units transfused; and a smaller proportion of patients experiencing breakthrough hemolysis (all p < 0.05). Patients receiving pegcetacoplan also had a greater increase in general health status score from baseline compared with those receiving C5 complement inhibitors., Conclusion: Pegcetacoplan provides clinical benefits as first-line treatment for complement inhibitor-naïve patients with PNH., Trial Registration: ClinicalTrials.gov identifier, NCT04085601., (© 2023. The Author(s).)

Introduction: It is widely acknowledged that cardiovascular diseases (CVDs) continue to be the leading cause of death globally. Furthermore, CVDs are the leading cause of diminished quality of life for patients, frequently as a result of their progressive deterioration. Medical implants that release drugs into the body are active implants that do more than just provide mechanical support; they also have a therapeutic role. Primarily, this is achieved through the controlled release of active pharmaceutical ingredients (API) at the implementation site., Areas Covered: In this review, the authors discuss drug-eluting stents, drug-eluting vascular grafts, and drug-eluting cardiac patches with the aim of providing a broad overview of the three most common types of cardiac implant., Expert Opinion: Drug eluting implants are an ideal alternative to traditional drug delivery because they allow for accurate drug release, local drug delivery to the target tissue, and minimize the adverse side effects associated with systemic administration. Despite the fact that there are still challenges that need to be addressed, the ever-evolving new technologies are making the fabrication of drug-eluting implants a rewarding therapeutic endeavor with the possibility for even greater advances.

Dengue is among the fastest-spreading vector-borne infectious disease, with outbreaks often overwhelm the health system and result in huge morbidity and mortality in its endemic populations in the absence of an efficient warning system. A large number of prediction models are currently in use globally. As such, this study aimed to systematically review the published literature that used quantitative models to predict dengue outbreaks and provide insights about the current practices. A systematic search was undertaken, using the Ovid MEDLINE, EMBASE, Scopus and Web of Science databases for published citations, without time or geographical restrictions. Study selection, data extraction and management process were devised in accordance with the 'Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies' ('CHARMS') framework. A total of 99 models were included in the review from 64 studies. Most models sourced climate (94.7%) and climate change (77.8%) data from agency reports and only 59.6% of the models adjusted for reporting time lag. All included models used climate predictors; 70.7% of them were built with only climate factors. Climate factors were used in combination with climate change factors (13.4%), both climate change and demographic factors (3.1%), vector factors (6.3%), and demographic factors (5.2%). Machine learning techniques were used for 39.4% of the models. Of these, random forest (15.4%), neural networks (23.1%) and ensemble models (10.3%) were notable. Among the statistical (60.6%) models, linear regression (18.3%), Poisson regression (18.3%), generalized additive models (16.7%) and time series/autoregressive models (26.7%) were notable. Around 20.2% of the models reported no validation at all and only 5.2% reported external validation. The reporting of methodology and model performance measures were inadequate in many of the existing prediction models. This review collates plausible predictors and methodological approaches, which will contribute to robust modelling in diverse settings and populations., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright: © 2023 Leung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Structural barriers such as inadequate housing, lack of employment opportunities, and discrimination are known to adversely affect the health of newly settled refugee migrants. However, these barriers remain largely unresolved and unaddressed. Thus, there is a need to better understand how other factors, such as individual-level health resources, may influence health and mitigate ill health in the early post-migration phase. In this study, we aimed to explore the relationship between health outcomes and individual health resources including health literacy, social support, and self-efficacy in newly settled refugee migrants. Survey data was collected from 787 refugee migrants in Sweden. Logistical regression analysis showed that limited health literacy, lack of emotional support, and low self-efficacy were consistently associated with poor health outcomes. Demographic variables such as gender, education, and type of residence permit were not as imperative. Individual-level health resources may play an important role in the general and psychological well-being of newly settled migrants. Promoting health literacy and facilitating the attainment of social support may buffer for structural challenges in the establishment phase and enhance the prospects of later health and social integration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Al-Adhami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors (eculizumab/ravulizumab) control intravascular hemolysis but do not prevent residual extravascular hemolysis. The newly approved complement inhibitor, pegcetacoplan, inhibits C3, upstream of C5, and has the potential to improve control of complement-mediated hemolysis. The PADDOCK and PALOMINO clinical trials assessed the safety and efficacy of pegcetacoplan in complement inhibitor-naïve adults (≥ 18 years) diagnosed with PNH. Patients in PADDOCK (phase 1b open-label, pilot trial) received daily subcutaneous pegcetacoplan (cohort 1: 180 mg up to day 28 [n = 3]; cohort 2: 270-360 mg up to day 365 [n = 20]). PALOMINO (phase 2a, open-label trial) used the same dosing protocol as PADDOCK cohort 2 (n = 4). Primary endpoints in both trials were mean change from baseline in hemoglobin, lactate dehydrogenase, haptoglobin, and the number and severity of treatment-emergent adverse events. Mean baseline hemoglobin levels were below the lower limit of normal in both trials (PADDOCK: 8.38 g/dL; PALOMINO: 7.73 g/dL; normal range: 11.90-18.00 g/dL), increased to within normal range by day 85, and were sustained through day 365 (PADDOCK: 12.14 g/dL; PALOMINO: 13.00 g/dL). In PADDOCK, 3 serious adverse events (SAE) led to study drug discontinuation, 1 of which was deemed likely related to pegcetacoplan and 1 SAE, not deemed related to study drug, led to death. No SAE led to discontinuation/death in PALOMINO. Pegcetacoplan was generally well tolerated and improved hematological parameters by controlling hemolysis, while also improving other clinical PNH indicators in both trials. These trials were registered at www.clinicaltrials.gov (NCT02588833 and NCT03593200)., (© 2022. The Author(s).)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, acquired, hematologic, life-threatening disease characterized by thrombosis, impaired bone marrow function, and complement-mediated hemolysis. The PEGASUS phase III clinical trial demonstrated superiority of pegcetacoplan over eculizumab regarding improvements in hemoglobin levels in patients with suboptimal response to prior eculizumab treatment. The objective of this post hoc analysis was to compare the patient-reported outcome (PRO) response rates observed among PEGASUS participants and the relationships between their PRO scores with clinical and hematological parameters. Data from the 16-week randomized, controlled (1:1 to pegcetacoplan or eculizumab) period of the PEGASUS trial included comparisons of weekly PRO measurements taken using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) scales. A clinically meaningful FACIT-F response was defined as an increase from baseline of ≥5 points. Convergent validity was assessed using conventional threshold correlations between FACIT-F, EORTC QLQ-C30, and laboratory parameters. A clinically meaningful improvement in FACIT-F score was seen in 72.2% of pegcetacoplan-treated patients compared to 22.9% of eculizumab-treated patients. At week 16, the FACIT-F total score correlated with hemoglobin levels (r=0.47, p< 0.0001), absolute reticulocyte count (r=-0.37, p<0.01), and indirect bilirubin levels (r=-0.25, p<0.05). Clinically meaningful improvements in pegcetacoplan-treated patients were also observed for multiple EORTC scales. Fatigue and other self-reported outcomes were correlated with clinically meaningful improvements in clinical and hematological parameters. Clinical trial registration: NCT03500549., (© 2022. The Author(s).)

Background: In the PEGASUS trial, the complement C3 inhibitor, pegcetacoplan, showed superiority to eculizumab in improving haematological outcomes in adult patients with paroxysmal nocturnal haemoglobinuria and suboptimal response to eculizumab at 16 weeks. The aim of the open-label period was to evaluate the long-term efficacy and safety of pegcetacoplan through to 48 weeks., Methods: PEGASUS was a phase 3, randomised, open-label, active-comparator controlled trial conducted in 44 centres in Australia, Belgium, Canada, France, Germany, Japan, Russia, South Korea, Spain, the UK, and the USA. Eligible participants were aged 18 years or older, had paroxysmal nocturnal haemoglobinuria, and had a haemoglobin concentration of less than 10·50 g/dL after 3 months or longer of stable eculizumab treatment. After a 4-week run-in with eculizumab plus pegcetacoplan, patients were randomly assigned (1:1) by interactive response technology to pegcetacoplan (1080 mg subcutaneously twice weekly) or eculizumab (according to their regimen at enrolment) for 16 weeks and could continue to the open-label period (32 weeks of pegcetacoplan monotherapy [pegcetacoplan-to-pegcetacoplan] or 28 weeks of pegcetacoplan monotherapy [eculizumab-to-pegcetacoplan]). Randomisation was stratified by platelet count and number of previous blood transfusions. The primary endpoint was change from baseline in haemoglobin at week 16, which has previously been reported. The outcomes of the open-label period (week 16 to week 48) are reported here. At 48 weeks, efficacy (including mean haemoglobin concentration and quality of life measured on the Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue scale) was assessed in the intention-to-treat population and safety was assessed per protocol. This trial was registered with ClinicalTrials.gov, NCT03500549, and has been completed., Findings: Between June 14, 2018, and Nov 14, 2019, 80 patients were randomly assigned to receive treatment with pegcetacoplan (41 patients) or eculizumab (39 patients). Most participants were women (49 [61%]) and 31 (39%) were men; 12 (15%) were Asian, two (3%) were Black, 49 (61%) were White, and 17 (21%) were another race or did not report their race. The open-label period had 77 participants (38 pegcetacoplan-to-pegcetacoplan, 39 eculizumab-to-pegcetacoplan). Patients in the pegcetacoplan-to-pegcetacoplan group maintained high mean haemoglobin concentrations between 16 weeks (11·54 g/dL [SD 1·96]) and 48 weeks (11·30 g/dL [1·77]; p=0·14). Patients in the eculizumab-to-pegcetacoplan group had significantly greater mean haemoglobin concentrations at 48 weeks (11·57 g/dL [2·21]) versus 16 weeks (8·58 g/dL [0·96]; p<0·0001). Clinically meaningful improvements in FACIT-Fatigue scores were observed at 48 weeks, with a mean change from baseline for all patients receiving pegcetacoplan monotherapy of 9·89 points (SD 9·63), for patients in the pegcetacoplan-to-pegcetacoplan group mean 10·14 points (9·06), and for patients in the eculizumab-to-pegcetacoplan group mean 9·62 points (10·34). During the entire study period, 13 (16%) of 80 patients discontinued treatment (three [7%] of 41 through to week 16 due to breakthrough haemolysis, and ten [13%] of 77 due to severe treatment-emergent adverse events) and 18 patients (eight pegcetacoplan-to-pegcetacoplan, ten eculizumab-to-pegcetacoplan) had at least one serious treatment-emergent adverse event during the open-label period, four were considered to be related to pegcetacoplan treatment. The most common treatment-emergent adverse events (in ≥10% patients) among both pegcetacoplan-treated groups during the open-label period were injection site reactions (in 20 [26%] of 77 patients), haemolysis (15 [19%]), nasopharyngitis (12 [16%]), and diarrhoea (ten [13%]). No treatment-related deaths occurred throughout the duration of the study., Interpretation: The durability of improved haematological outcomes and favourable safety profile over 48 weeks of treatment suggests that pegcetacoplan has the potential to improve treatment benefit and alter treatment goals in patients with paroxysmal nocturnal haemoglobinuria., Funding: Apellis Pharmaceuticals., Competing Interests: Declaration of interests RPdL reports consultancy at Novartis, Pfizer, Amgen, Alexion Pharmaceuticals, Apellis Pharmaceuticals, and Swedish Orphan Biovitrum; honoraria from Novartis, Pfizer, Amgen, Alexion Pharmaceuticals, Apellis Pharmaceuticals, and Swedish Orphan Biovitrum; research funding from Novartis, Pfizer, Amgen, and Alexion Pharmaceuticals; and grants from Alexion Pharmaceuticals, Amgen, Novartis, and Pfizer. JS reports consultancy at Novartis, Alexion Pharmaceuticals, and Apellis Pharmaceuticals; honoraria from Takeda, Pfizer, Novartis, Prevail Therapeutics, and Alexion Pharmaceuticals; speakers’ bureau at Takeda, Pfizer, Novartis, and Alexion Pharmaceuticals; and membership on an entity's board of directors or advisory committees at Prevail Therapeutics and Alexion Pharmaceuticals. ICW reports consultancy at Alexion Pharmaceuticals, Apellis Pharmaceuticals, Biocryst, Novartis, and Sanofi Genxyme; honoraria from Alexion Pharmaceuticals, Apellis Pharmaceuticals, Biocryst, Novartis, and Sanofi Genxyme; and speakers’ bureau at Alexion Pharmaceuticals. AR reports personal fees from Alexion Pharmaceuticals, Apellis Pharmaceuticals, Kira, Novartis, Roche, Swedish Orphan Biovitrum, Sanofi, Bioverativ, and Grifols; and grants from Roche. BH reports honoraria and advisory board member at Novartis, Roche, Alexion Pharmaceuticals, and Apellis Pharmaceuticals. JP reports consultancy and honoraria at Blueprint Medicines, Amgen, F Hoffmann-La Roche, MSD, Bristol Myers Squibb, Alexion Pharmaceuticals, Novartis, Pfizer, Gilead, Boehringer Ingelheim, Swedish Orphan Biovitrum, and Apellis Pharmaceuticals; and honoraria from SwixxBiopharma. KU reports grants from Alexion Pharmaceuticals, Apellis Pharmaceuticals, Chugai, and Novartis; and personal fees from Novartis, Chugai, and Alexion Pharmaceuticals. MG reports consultancy at Biocryst and Regeneron Pharmaceuticals; honoraria from Alexion Pharmaceuticals and Swedish Orphan Biovitrum; advisory board member at Novartis, Biocryst, Alexion Pharmaceuticals, and Swedish Orphan Biovitrum; and educational work sponsored by Apellis with unrestricted grant paid to Medscape. J-JK reports membership on an entity's board of directors or advisory committees at AbbVie, Novartis, Bristol Myers Squibb, and AOP Orphan. CMdC reports consultancy at Apellis Pharmaceuticals; honoraria from Novartis, Alexion Pharmaceuticals, Biocryst, and Apellis Pharmaceuticals; and research funding from Alexion Pharmaceuticals, and Apellis Pharmaceuticals. TA reports current employment and current equity holder at Apellis Pharmaceuticals. MA-A reports current employment at Apellis Pharmaceuticals. PD reports being a founder, Chief Scientific Officer, and current equity holder at Apellis Pharmaceuticals. CF and FG report current employment and current equity holder at Apellis Pharmaceuticals. AMR reports consultancy at Novartis and Amyndas; membership on an entity's board of directors or advisory committees at Novartis, Alexion Pharmaceuticals, Samsung, Biocryst, Achillion, Roche, Sanofi, and Apellis Pharmaceuticals; and grants from Alexion Pharmaceuticals, Novartis, Alnylam, and Rapharma. PH reports consultancy at Alexion Pharmaceuticals, Apellis Pharmaceuticals, AbbVie, AstraZeneca, Janssen, and Roche; research funding from Alexion Pharmaceuticals, Apellis Pharmaceuticals, AbbVie, Gilead, Janssen, Pharmacyclics, and Roche; and speakers bureau at Alexion Pharmaceuticals, Apellis Pharmaceuticals, AbbVie, AstraZeneca, Janssen, and Roche. HN declares no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Despite preoperative optimization, hemodynamic instability can be a major challenge during adrenalectomy. Even brief episodes of intraoperative hypotension can be associated with ischemia-reperfusion injury. This study aimed to compare intraoperative hemodynamic parameters between posterior retroperitoneoscopic adrenalectomy (PRA) and transperitoneal laparoscopic adrenalectomy (TPA)., Methods: This is a retrospective study of patients undergoing PRA and TPA without conversion or concomitant intraabdominal pathology from 2008 to 2019. The primary outcome was intraoperative hypotension defined by mean arterial pressure <60 mm Hg or the need for ≥1 intravenous vasopressors at least 30 min after anesthetic induction., Results: Overall, 108 patients met the inclusion criteria; 33 (30.6%) had pheochromocytoma, 26 (24.1%) had aldosterone excess, 8 (7.4%) had corticosteroid excess, and 41 (38.0%) had nonfunctioning adrenal tumors. Of these, 68 (63.0%) underwent PRA and 40 (37.0%) underwent TPA. Age, sex, body mass index, preinduction blood pressure, number of preoperative antihypertensives, and histopathological diagnosis were similar in the two groups. Tumor size was greater in the TPA group. The presence of pheochromocytoma was an independent risk factor for hypotension. Multivariate analysis revealed that PRA was associated with a higher risk of experiencing a mean arterial pressure <60 mm Hg (odds ratio 4.44, 95% confidence interval 1.27-15.54, P = 0.02) and the need for ≥1 intravenous vasopressors (odds ratio 9.97, 95% confidence interval 3.34-29.78, P < 0.001) compared with TPA., Conclusions: Although PRA offers several advantages over TPA, it carries a greater risk of intraoperative hypotension. A prospective trial is required to validate these findings. Nevertheless, institution of risk reduction strategies is encouraged to be considered for individuals undergoing PRA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

COVID-19 is spreading all over Iran, and Kerman is one of the most affected cities. We conducted this study to predict COVID-19-related deaths, hospitalization, and infected cases under different scenarios (scenarios A, B, and C) by 31 December 2021 in Kerman. We also aimed to assess the impact of new COVID-19 variants and vaccination on the total number of COVID-19 cases, deaths, and hospitalizations (scenarios D, E, and F) using the modified susceptible-exposed-infected-removed (SEIR) model. We calibrated the model using deaths reported from the start of the epidemic to August 30, 2021. A Monte Carlo Markov Chain (MCMC) uncertainty analysis was used to estimate 95% uncertainty intervals (UI). We also calculated the time-varying reproductive number ( R t ) following time-dependent methods. Under the worst-case scenario (scenario A; contact rate = 10, self-isolation rate = 30%, and average vaccination shots per day = 5,000), the total number of infections by December 31, 2021, would be 1,625,000 (95% UI: 1,112,000-1,898,000) with 6,700 deaths (95% UI: 5,200-8,700). With the presence of alpha and delta variants without vaccine (scenario D), the total number of infected cases and the death toll were estimated to be 957,000 (95% UI: 208,000-1,463,000) and 4,500 (95% UI: 1,500-7,000), respectively. If 70% of the population were vaccinated when the alpha variant was dominant (scenario E), the total number of infected cases and deaths would be 608,000 (95% UI: 122,000-743,000) and 2,700 (95% UI: 700-4,000), respectively. The R t was ≥1 almost every day during the epidemic. Our results suggest that policymakers should concentrate on improving vaccination and interventions, such as reducing social contacts, stricter limitations for gathering, public education to promote social distancing, incensing case finding and contact tracing, effective isolation, and quarantine to prevent more COVID-19 cases, hospitalizations, and deaths in Kerman., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Mehran Nakhaeizadeh et al.)

Introduction: The 2015 American Thyroid Association guidelines (ATA15) consider hemithyroidectomy (HT) a viable treatment option for low-risk papillary thyroid cancers (PTCs) between 1 and 4 cm. We aimed to examine the impact of ATA15 in a high-volume Australian endocrine surgery unit., Methods: A retrospective study of all patients undergoing thyroidectomy from January 2010 to December 2019., Inclusion Criteria: PTC histopathology, Bethesda V-VI, size 1-4 cm, and absence of clinical evidence of lymph node or distant metastases pre-operatively. Primary outcome was rate of HT before and after ATA15., Results: Of 5408 thyroidectomy patients, 339 (6.3%) met the inclusion criteria - 186 (54.9%) pre-ATA15 (2010-2015) and 153 (45.1%) post-ATA15 (2016-2019). The patient groups were similar; there were no significant differences between groups in age, sex, tumour size, proportion with Bethesda VI cytology, compressive symptoms, or thyrotoxicosis. Post-ATA15, there was a significant increase in HT rate from 5.4% to 19.6% (P = 0.0001). However, there was no corresponding increase in completion thyroidectomy (CT) rate (50.0% versus 27.6%, P = 0.2). The proportion managed with prophylactic central neck dissection (pCND) fell from 80.5% to 10.8% (P < 0.0001). Pre-ATA15, the only factor significantly associated with HT was Bethesda V. In contrast, post-ATA15, HT was more likely in patients with younger age, smaller tumours, and Bethesda V., Conclusion: After the release of 2015 ATA guidelines, we observed a significant increase in HT rate and a significant decrease in pCND rate for low-risk PTCs in our specialised thyroid cancer unit. This reflects a growing clinician uptake of a more conservative approach as recommended by ATA15., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Migrants face structural, socio-political barriers in their resettlement processes that negatively affect their health. Migration also adversely impacts resources such as social capital and health literacy that are of importance for health and integration into society. Hence, there is a need for health promotion in the early post-migration phase. In Sweden, newly settled refugee migrants who have received a residence permit are offered an Introduction programme including a civic orientation course. The program is intended to facilitate access to the labour market and promote integration. The aim of the study was to explore participants' perceptions and experiences of a civic orientation course with added health communication., Methods: We performed six focus group discussions: two in Arabic, two in Farsi and two in Somali. The discussions were facilitated by native speaking moderators. Participants were 32 men and women recruited from civic orientation classes in the county of Stockholm. We used an interview guide with semi-structured questions. The data were analysed using a method for content analysis for focus group discussions., Results: Three main categories were identified: (1) 'The course gives valuable information but needs adjustments', which includes that the civic and health orientation is needed earlier, during the asylum phase, and that planning and course content need adjustments. (2) 'The health communication inspired participants to focus on their health', which includes that the health communication was useful and inspired uptake of healthier habits. (3) 'Participation in the course promoted independence and self-confidence', which includes that the course gave insights into society and values in Sweden, and promoted independence and new social contacts., Conclusion: This study adds knowledge about the users' perspectives on the potential of civic orientation to promote the health and integration of newly settled migrants, describing ways in which civic orientation with added health communication promoted health and empowerment. However, the content and delivery of the course need adjustment to better fit the migrants' life situations and varying pre-existing knowledge., (© 2021. The Author(s).)

Background: The coronavirus disease-19 (COVID-19) emerged in Wuhan, China and rapidly spread worldwide. Researchers are trying to find a way to treat this disease as soon as possible. The present study aimed to identify the genes involved in COVID-19 and find a new drug target therapy. Currently, there are no effective drugs targeting SARS-CoV-2, and meanwhile, drug discovery approaches are time-consuming and costly. To address this challenge, this study utilized a network-based drug repurposing strategy to rapidly identify potential drugs targeting SARS-CoV-2. To this end, seven potential drugs were proposed for COVID-19 treatment using protein-protein interaction (PPI) network analysis. First, 524 proteins in humans that have interaction with the SARS-CoV-2 virus were collected, and then the PPI network was reconstructed for these collected proteins. Next, the target miRNAs of the mentioned module genes were separately obtained from the miRWalk 2.0 database because of the important role of miRNAs in biological processes and were reported as an important clue for future analysis. Finally, the list of the drugs targeting module genes was obtained from the DGIDb database, and the drug-gene network was separately reconstructed for the obtained protein modules., Results: Based on the network analysis of the PPI network, seven clusters of proteins were specified as the complexes of proteins which are more associated with the SARS-CoV-2 virus. Moreover, seven therapeutic candidate drugs were identified to control gene regulation in COVID-19. PACLITAXEL, as the most potent therapeutic candidate drug and previously mentioned as a therapy for COVID-19, had four gene targets in two different modules. The other six candidate drugs, namely, BORTEZOMIB, CARBOPLATIN, CRIZOTINIB, CYTARABINE, DAUNORUBICIN, and VORINOSTAT, some of which were previously discovered to be efficient against COVID-19, had three gene targets in different modules. Eventually, CARBOPLATIN, CRIZOTINIB, and CYTARABINE drugs were found as novel potential drugs to be investigated as a therapy for COVID-19., Conclusions: Our computational strategy for predicting repurposable candidate drugs against COVID-19 provides efficacious and rapid results for therapeutic purposes. However, further experimental analysis and testing such as clinical applicability, toxicity, and experimental validations are required to reach a more accurate and improved treatment. Our proposed complexes of proteins and associated miRNAs, along with discovered candidate drugs might be a starting point for further analysis by other researchers in this urgency of the COVID-19 pandemic.

Background: Indeterminate fine-needle aspiration cytology (FNAC) imposes challenges in the management of thyroid nodules. This study aimed to examine whether preoperative anti-thyroid antibodies (Abs) and TSH are indicators of thyroid malignancy and aggressive behavior in patients with indeterminate FNAC., Methods: This was a retrospective study of thyroidectomy patients from 2008 to 2016. We analyzed Abs and TSH levels, FNAC, and histopathology. Serum antibody levels were categorized as 'Undetectable', 'In-range' if detectable but within normal range, and 'Elevated' if above upper limit of normal. 'Detectable' levels referred to 'In-range' and 'Elevated' combined., Results: There were 531 patients included. Of 402 patients with preoperative FNAC, 104 (25.9%) had indeterminate cytology (Bethesda III-V). Of these, 39 (37.5%) were malignant and 65 (62.5%) benign on histopathology. In the setting of indeterminate FNAC, an increased risk of malignancy was associated with 'Elevated' thyroglobulin antibodies (TgAb) (OR 7.25, 95% CI 1.13-77.15, P = 0.01) and 'Elevated' thyroid peroxidase antibodies (TPOAb) (OR 6.79, 95% CI 1.23-45.88, P = 0.008). Similarly, while still 'In-range', TSH ≥ 1 mIU/L was associated with an increased risk of malignancy (OR 3.23, 95% CI 1.14-9.33, P = 0.01). In all patients with malignancy, the mean tumor size was 8 mm larger in those with TSH ≥ 1 mIU/L (P = 0.03); furthermore, in PTC patients, 'Detectable' TgAb conferred a 4 × risk of lymph node metastasis (95% CI 1.03-13.77, P = 0.02)., Conclusion: In this cohort, in indeterminate FNAC patients, Abs and TSH were associated with an increased risk of malignancy. Additionally, TgAb and TSH were potential markers of aggressive biology. As such, they may be diagnostic and prognostic adjuncts.

Importance: For men with metastatic castration-resistant prostate cancer (mCRPC) whose condition is responding to enzalutamide, new unconfirmed bone lesions detected at posttreatment scinitigraphy may reflect an osteoblastic reaction that represents healing, known as pseudoprogression, which can lead to premature discontinuation of therapy., Objective: To determine the association between new unconfirmed lesions detected on a follow-up bone scintigram (bone scan) and outcomes in enzalutamide-treated men with mCRPC., Design, Setting, and Participants: This post hoc, retrospective secondary analysis of 1672 enzalutamide-treated men from 2 phase 3, randomized mCRPC studies (PREVAIL and AFFIRM) before or after treatment with docetaxel was conducted from April 12, 2018, to July 25, 2019. Participants were men from the enzalutamide groups of the 2 studies with a decrease in prostate-specific antigen level at any time or with stable disease or soft-tissue disease responding to treatment based onradiologic findings., Intervention: Enzalutamide, 160 mg once daily., Main Outcomes and Measures: The clinical significance of new lesions detected on the first (early) or second (late) posttreatment bone scan, without an unfavorable change in prostate-specific antigen level or soft-tissue progression, was investigated. Associations of new unconfirmed lesions with radiographic progression-free survival, overall survival, decrease in prostate-specific antigen level, objective response in soft tissue, and quality of life were evaluated., Results: Among the 643 men (median age, 72 years [range, 43-93 years]) in PREVAIL, early and late unconfirmed lesions were observed in 177 men (27.5%) with stable disease or disease responding to enzalutamide. Among the 404 men (median age, 70 years [range, 41-88 years]) in AFFIRM, early and late unconfirmed lesions were observed in 73 men (18.1%) with stable disease or disease responding to enzalutamide. In PREVAIL, men with new unconfirmed lesions had median radiographic progression-free survival (hazard ratio [HR], 1.37 [95% CI, 0.81-2.30]; P = .23) and median overall survival (HR, 1.25 [95% CI, 0.85-1.83]) in the chemotherapy-naive setting similar to men those of men without such new lesions. In AFFIRM, the median overall survival (HR, 1.94 [95% CI, 1.10-3.44]) was reduced among men with unconfirmed bone lesions, but the median radiographic progression-free survival was not reduced (HR, 1.21 [95% CI, 0.83-1.75]; P = .32). Quality of life over time was similar regardless of the presence of new unconfirmed lesions detected on a follow-up bone scan in either setting., Conclusions and Relevance: These results suggest that new unconfirmed lesions detected on follow-up bone scans may represent pseudoprogression in men with mCRPC and are indicative of a favorable treatment response to enzalutamide. The detection of new unconfirmed bone lesions in men with mCRPC that responded to treatment with enzalutamide after docetaxel appears to be associated with worse overall survival and may represent true progression, thus highlighting the need for improved functional bone metastasis imaging., Trial Registration: ClinicalTrials.gov Identifiers: NCT01212991 and NCT00974311.

New diagnostic miRNA biomarkers for different types of cancer have been studied extensively, particularly for breast cancer (BC), which is a leading cause of death among women and has many different subtypes. In the present study, a systems biology approach was used to find remarkable and novel miRNA biomarkers for five molecular subtypes of BC: luminal A, luminal B, ERBB2, basal-like and normal-like. The mRNA expression data from the five BC subtypes was used to reconstruct co-expression networks. The important mRNA-miRNA interactions were considered when reconstructing the bipartite networks from which the five bipartite sub-networks were reconstructed for further analysis. The novel biomarkers detected for each subtype are as follows: miRNAs 26b-5p and 124-3p for basal-like, 26b-5p, 124-3p and 5011-5p for ERBB2, 26b-5p and 5011-5p for LumA, 124-3p, 26b-5p and 7-5p for LumB and 26b-5p, 124-3p and 193b-3p for normal-like. The roles of the identified miRNAs in the occurrence or development of each subtype of BC remain unclear and should be investigated in future studies. In addition, the target genes of these miRNAs may be critical to the mechanisms underlying each subtype and should be analyzed as therapeutic targets in future studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Collaborative management is increasingly applied to indicate environmental and socio-economic negotiations in every corner of the world. The engagement of multiple stakeholders accompanying experience, science, and economy probing skills is expected to unravel such issues. However, the collaborative approaches to manage existing issues at watershed scale have not been adequately applied. Therefore, the present study has exemplified the establishment of a comanagement framework for the soil management for two case studies i.e., Schleswig-Holstein State of Germany and Galazchai Watershed of Iran using a stakeholder oriented approach applying game theory based methods. Due to management perspectives, different stakeholder groups were involved to investigate effective soil conservation practices. Farmers, consultants, and service providing companies in Germany and residents, policy making institutions and executive organizations in Iran were detected as key stakeholders. The Condorcet and Fallback bargaining methods were used to diagnosis agreement point. Based upon the results, the developed case study in Germany demonstrated close relation among farmers and consultants (53%) in contrast with service providing companies. The same situation was observed among residents and policy makers in Iran. Besides, the tendency to implement mechanical practices among farmers in Iran was about 60% (149 of 243), however, in Germany 86% of farmers prefer to use managerial practices., (Copyright © 2019 Elsevier B.V. All rights reserved.)

As nonbiodegradable plastics continue to pollute our land and oceans, countries are starting to ban the use of single-use plastics. In this paper, we demonstrated the fabrication of wood-based microfluidic devices and their adaptability for single-use, point-of-care (POC) applications. These devices are made from easily sourced renewable materials for fabrication while exhibiting all the advantages of plastic devices without the problem of nonbiodegradable waste and cost. To build these wood devices, we utilized laser engraving and traditional mechanical methods and have adapted specific surface coatings to counter the wicking effect of wood. To demonstrate their versatility, wood microfluidic devices were adapted for (i) surface plasmon coupled enhancement (SPCE) of fluorescence for detection of proteins, (ii) T-/Y-geometry microfluidic channel mixers, and (iii) devices for rapid detection of microbial contamination. These provide proof of concept for the use of wooden platforms for POC applications. In this study, we measured the fluorescence intensities of recombinant green fluorescent protein (GFP) standards (ranging from 1.5-25 ng/μL) and 6XHis-G-CSF (ranging from 0.1-100 ng/μL) expressed in cell-free translation systems. All tested devices perform as well as or better than their plastic counterparts.

Biopharmaceutical separations require tremendous amounts of optimization to achieve acceptable product purity. Typically, large volumes of reagents and biological materials are needed for testing different parameters, thus adding to the expense of biopharmaceutical process development. This study demonstrates a versatile and customizable microscale column (µCol) for biopharmaceutical separations using immobilized metal affinity chromatography (IMAC) as an example application to identify key parameters. µCols have excellent precision, efficiency, and reproducibility, can accommodate any affinity, ion-exchange or size-exclusion-based resin and are compatible with any high-performance liquid chromatography (HPLC) system. µCols reduce reagent amounts, provide comparable purification performance and high-throughput, and are easy to automate compared with current conventional resin columns. We provide a detailed description of the fabrication methods, resin packing methods, and µCol validation experiments using a conventional HPLC system. Finite element modeling using COMSOL Multiphysics was used to validate the experimental performance of the µCols. In this study, µCols were used for improving the purification achieved for granulocyte colony stimulating factor (G-CSF) expressed using a cell-free CHO in vitro translation (IVT) system and were compared to a conventional 1 ml IMAC column. Experimental data revealed comparable purity with a 10-fold reduction in the amount of buffer, resin, and purification time for the μCols compared with conventional columns for similar protein yields., (© 2018 Wiley Periodicals, Inc.)

Manufacturing technologies for biologics rely on large, centralized, good-manufacturing-practice (GMP) production facilities and on a cumbersome product-distribution network. Here, we report the development of an automated and portable medicines-on-demand device that enables consistent, small-scale GMP manufacturing of therapeutic-grade biologics on a timescale of hours. The device couples the in vitro translation of target proteins from ribosomal DNA, using extracts from reconstituted lyophilized Chinese hamster ovary cells, with the continuous purification of the proteins. We used the device to reproducibly manufacture His-tagged granulocyte-colony stimulating factor, erythropoietin, glucose-binding protein and diphtheria toxoid DT5. Medicines-on-demand technology may enable the rapid manufacturing of biologics at the point of care.

Background: Breast cancer (BC) is the most prevalent cancer and the main cause of cancer deaths among females around the world. For early diagnosis of BC, there would be an immediate and essential requirement to search for sensitive biomarkers., Methods: To identify candidate miRNA biomarkers for BC, we performed a general systematic review regarding the published miRNA profiling researches comparing miRNA expression level between BC and normal tissues. A miRNA ranking system was selected, which considered frequency of comparisons in direction and agreement of differential expression., Results: We determined that two miRNAs (mir-21 and miR-210) were upregulated consistently and six miRNAs (miR-145, miR-139-5p, miR-195, miR-99a, miR-497 and miR-205) were downregulated consistently in at least three studies. MiR-21 as the most consistently reported miRNA was upregulated in six profiling studies., Conclusions: Although these miRNAs require being validated and further investigated, they could be potential candidates for BC miRNA biomarkers and used for early prognosis or diagnosis.

A portable kinetics fluorometer is developed to detect viable cells which may be contaminating various samples. The portable device acts as a single-excitation, single-emission photometer that continuously measures fluorescence intensity of an indicator dye and plots it. The slope of the plot depends on the number of colony forming units per milliliter. The device uses resazurin as the indicator dye. Viable cells reduce resazurin to resorufin, which is more fluorescent. Photodiode is used to detect fluorescence change. The photodiode generated current proportional to the intensity of the light that reached it, and an op-amp is used in a transimpedance differential configuration to ensure amplification of the photodiode's signal. A microfluidic chip is designed specifically for the device. It acts as a fully enclosed cuvette, which enhances the resazurin reduction rate. In tests, the E. coli-containing media are injected into the microfluidic chip and the device is able to detect the presence of E. coli in LB media based on the fluorescence change that occurred in the indicator dye. The device provides fast, accurate, and inexpensive means to optical detection of the presence of viable cells and could be used in the field in place of more complex methods, i.e., loop-meditated isothermal amplification of DNA (LAMP) to detect bacteria in pharmaceutical samples (Jimenez et al., J Microbiol Methods 41(3):259-265, 2000) or measuring the intrinsic fluorescence of the bacterial or yeast chromophores (Estes et al., Biosens Bioelectron 18(5):511-519, 2003).

Choanal polyps are unilateral sinonasal lesions that are classified according to their site of origin. The aim of this report is to highlight an unusual form of choanal polyp and to present a thorough literature review. To the best of our knowledge, only 6 cases of a choanal polyp originating in the inferior turbinate have been previously reported in the literature. We describe 2 new cases. One patient was a 14-year-old boy who presented with nasal obstruction, facial headaches, and obstructive sleep apnea; the other patient was a 70-year-old man who presented with right mucopurulent rhinorrhea and right nasal obstruction. In both cases, nasal fibroscopy detected a polyp arising from the right inferior turbinate and extending toward the right choana. Endoscopic sinus surgery was performed in both cases to ensure a complete excision. Cases of choanal polyp arising from the inferior, middle, and superior turbinates and the septum are rare, although some appear to be more common than is generally believed, especially in the pediatric population. We therefore recommend that unusual forms of choanal polyp be included in the differential diagnosis of a unilateral sinonasal mass.

The development of neutralizing anti-factor VIII (FVIII) antibodies complicates the treatment of many hemophilia A patients. The C-terminal C2 domain is a particularly antigenic FVIII region. A crystal structure of recombinant FVIII-C2 bound to an Fab fragment of the patient-derived monoclonal antibody BO2C11, which recognizes an immunodominant inhibitor epitope on FVIII and blocks its ability to bind von Willebrand factor (VWF) and phospholipids, revealed that 15 amino acids in FVIII contact this antibody. Forty-three recombinant FVIII-C2 proteins, each with a surface-exposed side chain mutated to alanine or another residue, were generated, and surface plasmon resonance studies were carried out to evaluate effects of these substitutions on BO2C11/FVIII-C2 binding affinity. Thermodynamic analysis of experiments carried out at three temperatures indicated that one beta hairpin turn at the antigen-antibody interface (FVIII-F2196, N2198, M2199 and F2200) plus two non-contiguous arginines (FVIII-R2215 and R2220), contributed appreciably to the affinity. B-domain-deleted (BDD) FVIII-F2196A, FVIII-F2196K and FVIII-M2199A were generated and characterized. Their pro-coagulant activities and binding to VWF were similar to those of WT-BDD-FVIII, and FVIII-F2196K avoided neutralization by BO2C11 and murine inhibitory mAb 1B5. This study suggests specific sites for amino acid substitutions to rationally design FVIII variants capable of evading immunodominant neutralizing anti-FVIII antibodies.