Prolonged Time Research Articles

Peripheral GFAP and NfL as early biomarkers for dementia: longitudinal insights from the UK Biobank

BackgroundPeripheral glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are sensitive markers of neuroinflammation and neuronal damage. Previous studies with highly selected participants have shown that peripheral GFAP and NfL levels are elevated in the pre-clinical phase of Alzheimer’s disease (AD) and dementia. However, the predictive value of GFAP and NfL for dementia requires more evidence from population-based cohorts.MethodsThis was a prospective cohort study to evaluate UK Biobank participants enrolled from 2006 to 2010 using plasma GFAP and NfL measurements measured by Olink Target Platform and prospectively followed up for dementia diagnosis. Primary outcome was the risk of clinical diagnosed dementia. Secondary outcomes were cognition. Linear regression was used to assess the associations between peripheral GFAP and NfL with cognition. Cox proportional hazard models with cross-validations were used to estimate associations between elevated GFAP and NfL with risk of dementia. All models were adjusted for covariates.ResultsA subsample of 48,542 participants in the UK Biobank with peripheral GFAP and NfL measurements were evaluated. With an average follow-up of 13.18 ± 2.42 years, 1312 new all-cause dementia cases were identified. Peripheral GFAP and NfL increased up to 15 years before dementia diagnosis was made. After strictly adjusting for confounders, increment in NfL was found to be associated with decreased numeric memory and prolonged reaction time. A greater annualized rate of change in GFAP was significantly associated with faster global cognitive decline. Elevation of GFAP (hazard ratio (HR) ranges from 2.25 to 3.15) and NfL (HR ranges from 1.98 to 4.23) increased the risk for several types of dementia. GFAP and NfL significantly improved the predictive values for dementia using previous models (area under the curve (AUC) ranges from 0.80 to 0.89, C-index ranges from 0.86 to 0.91). The AD genetic risk score and number of APOE*E4 alleles strongly correlated with GFAP and NfL levels.ConclusionsThese results suggest that peripheral GFAP and NfL are potential biomarkers for the early diagnosis of dementia. In addition, anti-inflammatory therapies in the initial stages of dementia may have potential benefits.

Web-based diagnostic platform for microorganism-induced deterioration on paper-based cultural relics with iterative training from human feedback

PurposePaper-based artifacts hold significant cultural and social values. However, paper is intrinsically fragile to microorganisms, such as mold, due to its cellulose composition, which can serve as a microorganisms’ nutrient source. Mold not only can damage papers’ structural integrity and pose significant challenges to conservation works but also may subject individuals attending the contaminated artifacts to health risks. Current approaches for strain identification usually require extensive training, prolonged time for analysis, expensive operation costs, and higher risks of secondary damage due to sampling. Thus, in current conservation practices with mold-contaminated artifacts, little pre-screening or strain identification was performed before mold removal, and the cleaning techniques are usually broad-spectrum rather than strain-specific. With deep learning showing promising applications across various domains, this study investigated the feasibility of using a convolutional neural network (CNN) for fast in-situ recognition and classification of mold on paper.MethodsMolds were first non-invasively sampled from ancient Xuan Paper-based Chinese books from the Qing and Ming dynasties. Strains were identified using molecular biology methods and the four most prevalent strains were inoculated on Xuan paper to create mockups for image collection. Microscopic images of the molds as well as their stains situated on paper were collected using a compound microscope and commercial microscope lens for cell phone cameras, which were then used for training CNN models with a transfer learning scheme to perform the classification of mold. To enable involvement and contribution from the research community, a web interface that actuates the process while providing interactive features for users to learn about the information of the classified strain was constructed. Moreover, a feedback functionality in the web interface was embedded for catching potential classification errors, adding additional training images, or introducing new strains, all to refine the generalizability and robustness of the model.Results & ConclusionIn the study, we have constructed a suite of high-confidence classification CNN models for the diagnostic process for mold contamination in conservation. At the same time, a web interface was constructed that allows recurrently refining the model with human feedback through engaging the research community. Overall, the proposed framework opens new avenues for effective and timely identification of mold, thus enabling proactive and targeted mold remediation strategies in conservation.

Impact of Surface Functionality on Biodistribution of Gold Nanoparticles in Silkworms

To date, animal models are still indispensable for studying biodistribution and elimination of nanomaterials. However, the use of mammals for in vivo experiments faces various challenges including increasing regulatory hurdles and costs. This study aims to validate larvae of the domestic silkworm Bombyx mori as an alternative invertebrate model for preliminary in vivo research. Organ distribution and elimination of gold nanoparticles (AuNPs) are compared with four different surface functionalities in silkworms after systemic administration: AuNPs coated with poly(ethylene glycol) (PEG), with polyglycidols (PGs) that are slightly hydrophobic (PG(alkyl)), positively charged (PG(+)), or negatively charged (PG(−)). Subsequent inductive coupled plasma mass spectrometry 6 or 24 h after AuNPs administration reveals the biodistribution in silkworm hemolymph, midgut, epidermis, and excrements. Even after 24 h incubation, hemolymph contains the highest AuNPs concentrations, independent of surface functionalization indicating a prolonged circulation time and slow distribution into different silkworm organs and tissues. Positively charged PG(+)AuNPs show three times higher concentrations in the midgut and are excreted at the fastest rate when compared to other AuNPs. In the findings, a surface‐dependent biodistribution and elimination of AuNPs are indicated in silkworms, and the feasibility of using this inexpensive animal model for time‐ and cost‐effective, preliminary in vivo studies of NPs is confirmed.

Electrodeposited ZIF-67 reinforced polypyrrole coating on ferritic stainless steel substrate with durable anticorrosion performance

The harsh acidic environment containing chloride ions has created serious corrosion hazards for ferritic stainless steels. Zeolitic imidazole frameworks (ZIFs) are a promising material for corrosion protection due to their microstructural and physicochemical properties. In this study, we proposed the electrodeposited ZIF-67 reinforced polypyrrole (PPY) coating (PPY/ZIF-67) for corrosion protection of 430 ferritic stainless steel (430SS). The morphology, microstructure, and anticorrosion behavior of the pristine PPY and hybrid PPY/ZIF-67 coating systems were characterized. The successful electrodeposition of ZIF-67 nanoparticles on the surface of the PPY layer resulted in a uniform distribution and a compact coating structure, which contributed to the overall uniformity of the coating and enhanced both the barrier and activity inhibition functions of the coating. The protective performance of PPY/ZIF-67 coatings was evaluated through electrochemical tests, the results indicated that the anticorrosion efficiency of PPY/ZIF-67 coating (with 0.4 mol/L pyrrole monomer content) reached to 99 %, and the coating demonstrated a durable corrosion protection ability (744 h) in 0.1 mol/L HCl solution. Such performance of can be attributed to the combined effect of the anodic protection provided by the inner PPY film, the active corrosion inhibiting properties of the ZIF-67 nanoparticle layer, and the hindrance of aggressive species by the compact coating structure over the prolonged service time.

Biocompatible polyethersulfone membrane modified by hydrophilic polymer decorated magnetic nanoparticles gilded by facile external magnetic field

AbstractPolymer‐based membranes such as polyethersulfone are widely used for hemodialysis and bio‐related applications; however, this type of membrane still fails to satisfy optimum performance in terms of clearance, safety, and bio‐adaptability. Herein, a polymer brush of polyvinylpyrrolidone is decorated on the surface of magnetic nanoparticles by using reversible addition‐fragmentation chain transfer polymerization (RAFT), and under the guidance of an external magnetic field, the prepared magnetic nanoparticles with the polymer brush system are blended with a polyethersulfone membrane during a liquid‐liquid phase inversion process. The prepared membranes with different loads of the pure magnetic nanoparticle and polyvinylpyrrolidone@magnetic nanoparticle polymer brushes are prepared, compared with the pristine membrane, the modified membrane shows a high flux value at 349 L m−2 h−1 and 99.9% bovine serum albumin protein rejection. This membrane also demonstrated improved hydrophilicity and pore structure compared with the pristine membrane. Concerning the blood biocompatibility analysis, the modified membranes acquire prolonged time for clotting factors such as prothrombin time, activated partial thromboplastin time, and thrombin time while exhibiting less fibrinogen concertation at 0.4 g L−1. Furthermore, for the first time, an innovative method for fouling detection based on magnetic field attenuation due to protein accumulation on the membrane surface is reported; the method in this work could be a positive booster for the safe use of polymeric membranes in hemodialysis and bio‐based applications.

Quantitative flow ratio versus fractional flow reserve for Heart Team decision-making in multivessel disease: the randomised, multicentre DECISION QFR trial.

Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time. The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated. Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa. The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00]). QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

The impact of resident training on robotic operative times: is there a July Effect?

It is unknown whether the July Effect (a theory that medical errors and organizational inefficiencies increase during the influx of new surgical residents) exists in urologic robotic-assisted surgery. The aim of this study was to investigate the impact of urology resident training on robotic operative times at the beginning of the academic year. A retrospective chart review was conducted for urologic robotic surgeries performed at a single institution between 2008 and 2019. Univariate and multivariate mix model analyses were performed to determine the association between operative time and patient age, estimated blood loss, case complexity, robotic surgical system (Si or Xi), and time of the academic year. Differences in surgery time and non-surgery time were assessed with/without resident presence. Operative time intervals were included in the analysis. Resident presence correlated with increased surgery time (38.6 min (p < 0.001)) and decreased non-surgery time (4.6 min (p < 0.001)). Surgery time involving residents decreased by 8.7 min after 4 months into the academic year (July–October), and by an additional 5.1 min after the next 4 months (p = 0.027, < 0.001). When compared across case types stratified by complexity, surgery time for cases with residents significantly varied. Cases without residents did not demonstrate such variability. Resident presence was associated with prolonged surgery time, with the largest effect occurring in the first 4 months and shortening later in the year. However, resident presence was associated with significantly reduced non-surgery time. These results help to understand how new trainees impact operating room times.

Activated charcoal helps in the diagnosis of dabigatran overdose: Acase study.

The direct-acting oral anticoagulant dabigatran etexilate (DE) targets thrombin and is used widely to prevent thromboembolism. A 79-year-old man was admitted to the Emergency Department due to anuria for 2 days. An urgent laboratory examination revealed a serum creatinine concentration of 888 µmol/L. He was diagnosed with acute exacerbation of chronic renal insufficiency. During continuous renal replacement therapy (CRRT), the coagulation test showed a severe reduction in the fibrinogen level as well as a significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). The patient had been taking DE (110mg twice daily) for a long time and had not suspended the medication or reduced the dose during the worsening of anuria. Therefore, it should be evaluated before considering plasma replacement therapy for the patient, whether the abnormal coagulation parameters were induced by interference of excessive DE. Tentatively, we used activated charcoal to treat the plasma and then retested the fibrinogen, PT, and APTT. Results showed that the coagulation indices nearly returned to normal. The present case indicated that activated charcoal could adsorb DE in plasma effectively and eliminate its interference with coagulation test results, thereby providing support for clinical diagnosis and treatment.

Early postoperative beta-blockers are associated with improved cardiac output after late complete repair of tetralogy of Fallot: a retrospective cohort study

AbstractTetralogy of Fallot is the most common cyanotic congenital heart disease. For decades, our institution has cared for humanitarian patients with late presentation of tetralogy of Fallot. They are characterized by severe right ventricular hypertrophy with consecutive diastolic dysfunction, increasing the risk of postoperative low cardiac output syndrome (LCOS). By right ventricular restrictive physiology, we hypothesized that patients receiving early postoperative beta-blockers (within 48 h after cardiopulmonary bypass) may have better diastolic function and cardiac output. This is a retrospective cohort study in a single-center tertiary pediatric intensive care unit. We included &gt; 1-year-old humanitarian patients with a confirmed diagnosis of tetralogy of Fallot undergoing a complete surgical repair between 2005 and 2019. We measured demographic data, preoperative echocardiographic and cardiac catheterization measures, postoperative mean heart rate, vasoactive-inotropic scores, LCOS scores, length of stay, and mechanical ventilation duration. One hundred sixty-five patients met the inclusion criteria. Fifty-nine patients (36%) received early postoperative beta-blockers, associated with a lower mean heart rate, higher vasoactive-inotropic scores, and lower LCOS scores during the first 48 h following cardiopulmonary bypass. There was no significant difference in lengths of stay and ventilation. Conclusion: Early postoperative beta-blockers lower the prevalence of postoperative LCOS at the expense of a higher need for vasoactive drugs without any consequence on length of stay and ventilation duration. This approach may benefit the specific population of children undergoing a late complete repair of tetralogy of Fallot. What is Known:• Prevalence of low cardiac output syndrome is high following a late complete surgical repair of tetralogy of Fallot. What is New:• Early postoperative beta-blockade is associated with lower heart rate, prolonged relaxation time, and lower prevalence of low cardiac output syndrome.• Negative chronotropic agents like beta-blockers may benefit selected patients undergoing a late complete repair of tetralogy of Fallot, who are numerous in low-income countries.

Predictors of surgical difficulty according to surgical proficiency in robot-assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is a standard treatment for localized prostate cancer. We previously reported that a large amount of pelvic visceral fat and a small working space, as measured by three-dimensional image analysis, were significantly associated with prolonged console time in RARP, and these factors could be alternatives to the more clinically practical body mass index (BMI) and pelvic width (PW), respectively. Herein, we further investigated whether surgical proficiency affected surgical difficulty as measured by console time. Medical records of 413 patients who underwent RARP between 2014 and 2020 at our institution were reviewed. Surgeons who had experience with over and under 100 cases were defined as "experienced" and "non-experienced," respectively. Multivariate logistic regression analyses were performed to identify factors that prolonged console time. The median console times for RARP by experienced and non-experienced surgeons were 87.5 and 149.0min, respectively; a difficult case was defined as one requiring time greater than the median. Among inexperienced surgeons, higher BMI (p < 0.001, odds ratio: 1.89) and smaller PW (p = 0.001, odds ratio: 1.86) were significant factors that increased console time; the complication rate was increased in patients with these factors. However, these factors did not significantly affect the console time or complication rate among experienced surgeons. This study demonstrates that experienced surgeons may be able to overcome obesity- and small workspace-related surgical difficulties. The current analysis may provide useful information regarding unpredictable surgical risks and identify suitable cases for novices.

Impacts of free nitrous acid on stabilizing food waste and sewage sludge for anaerobic digestion

This work investigated the effectiveness of free nitrous acid (FNA) in enhancing organic waste solubilization to improve biogas production in anaerobic digestion (AD). The results indicated that FNA pretreatment can enhance soluble organic content and control H2S odor in tested organic wastes, including food waste, sewage sludge, and their combination. However, a significant decrease (>50 %) in FNA concentration was found in the reactors, possibly due to denitrifier-driven NO2– consumption. Biochemical methane potential (BMP) tests showed a 25 ± 8 % enhancement in CH4 production in the reactors fed with mixed substrate pretreated with 2.9 mg FNA-N/L. However, the presence of NO2– (325.6–2368.0 mg N/L) in some BMP reactors, due to carryover from FNA pretreatment, adversely affected CH4 production (>55 %) and prolonged lag time (>4.2 times). These findings are valuable for researchers and practitioners in waste management, offering insights for implementing FNA pretreatment to enhance the biodegradability of organic wastes in AD.

Oil Palm Bunch Ripeness Classification and Plantation Verification Platform: Leveraging Deep Learning and Geospatial Analysis and Visualization

Oil palm cultivation thrives as a prominent agricultural endeavor within the southern region of Thailand, where the country ranks third globally in production, following Malaysia and Indonesia. The assessment of oil palm bunch ripeness serves various purposes, notably in determining purchasing prices, pre-harvest evaluations, and evaluating the impacts of disasters or low market prices. Presently, two predominant methods are employed for this assessment, namely human evaluation, and machine learning for ripeness classification. Human assessment, while boasting high accuracy, necessitates the involvement of farmers or experts, resulting in prolonged processing times, especially when dealing with extensive datasets or dispersed fields. Conversely, machine learning, although capable of accurately classifying harvested oil palm bunches, faces limitations concerning its inability to process images of oil palm bunches on trees and the absence of a platform for on-tree ripeness classification. Considering these challenges, this study introduces the development of a classification platform leveraging machine learning (deep learning) in conjunction with geospatial analysis and visualization to ascertain the ripeness of oil palm bunches while they are still on the tree. The research outcomes demonstrate that oil palm bunch ripeness can be accurately and efficiently classified using a mobile device, achieving an impressive accuracy rate of 99.89% with a training dataset comprising 8779 images and a validation accuracy of 96.12% with 1160 images. Furthermore, the proposed platform facilitates the management and processing of spatial data by comparing coordinates derived from images with oil palm plantation data obtained through crowdsourcing and the analysis of cloud or satellite images of oil palm plantations. This comprehensive platform not only provides a robust model for ripeness assessment but also offers potential applications in government management contexts, particularly in scenarios necessitating real-time information on harvesting status and oil palm plantation conditions.

Shape Matters: Impact of Mesoporous Silica Nanoparticle Morphology on Anti-Tumor Efficacy

A nanoparticle’s shape is a critical determinant of its biological interactions and therapeutic effectiveness. This study investigates the influence of shape on the performance of mesoporous silica nanoparticles (MSNs) in anticancer therapy. MSNs with spherical, rod-like, and hexagonal-plate-like shapes were synthesized, with particle sizes of around 240 nm, and their other surface properties were characterized. The drug loading capacities of the three shapes were controlled to be 47.46%, 49.41%, and 46.65%, respectively. The effects of shape on the release behaviors, cellular uptake mechanisms, and pharmacological behaviors of MSNs were systematically investigated. Through a series of in vitro studies using 4T1 cells and in vivo evaluations in 4T1 tumor-bearing mice, the release kinetics, cellular behaviors, pharmacological effects, circulation profiles, and therapeutic efficacy of MSNs were comprehensively assessed. Notably, hexagonal-plate-shaped MSNs loaded with PTX exhibited a prolonged circulation time (t1/2 = 13.59 ± 0.96 h), which was approximately 1.3 times that of spherical MSNs (t1/2 = 10.16 ± 0.38 h) and 1.5 times that of rod-shaped MSNs (t1/2 = 8.76 ± 1.37 h). This research underscores the significance of nanoparticles’ shapes in dictating their biological interactions and therapeutic outcomes, providing valuable insights for the rational design of targeted drug delivery systems in cancer therapy.

Validation of MELD 3.0 in patients with alcoholic liver cirrhosis using prospective KACLiF cohort.

The Model for End-Stage Liver Disease (MELD) is a reliable prognostic tool for short-term outcome prediction in patients with end-stage liver disease. MELD 3.0 was introduced to enhance the predictive accuracy. This study assessed the performance of MELD 3.0, in comparison to MELD and MELD-Na, in patients with alcoholic liver cirrhosis. This multicenter prospective cohort study comprised patients with alcoholic cirrhosis admitted for acute deterioration of liver function in the Republic of Korea between 2015 and 2019. This study compared the predictive abilities of MELD, MELD-Na, and MELD 3.0, for 30-day and 90-day outcomes, specifically death or liver transplantation, and explored the factors influencing these outcomes. A total of 1096 patients were included in the study, with a mean age of 53.3±10.4years, and 82.0% were male. The mean scores for MELD, MELD-Na, and MELD 3.0 at the time of admission were 18.7±7.2, 20.6±7.7, and 21.0±7.8, respectively. At 30 and 90days, 7.2% and 14.1% of patients experienced mortality or liver transplantation. The areas under the receiver operating characteristic curves for MELD, MELD-Na, and MELD 3.0 at 30days were 0.823, 0.820, and 0.828; and at 90days were 0.765, 0.772, and 0.776, respectively. Factors associated with the 90-day outcome included concomitant chronic viral hepatitis, prolonged prothrombin time, elevated levels of aspartate transaminase, bilirubin, and creatinine, and low albumin levels. MELD 3.0 demonstrated improved performance compared to previous models, although the differences were not statistically significant.

Urinary Tract Infection Predictors in Patients Undergoing Retrograde IntraRenal Surgery for Renal Stones: Does the Instrument Make the Difference?

Background: Retrograde intrarenal surgery (RIRS) using flexible ureterorenoscopes is a cornerstone approach for renal stone removal, yet it carries a significant risk of postoperative urinary tract infection (UTI). With the emergence of single-use ureterorenoscopes, there is growing interest in their potential to mitigate this risk. This study aimed to compare the postoperative infection rates between single-use and multi-use ureterorenoscopes in RIRS procedures and to identify predictors of postoperative UTI. Methods: Data were collected from 112 consecutive patients who underwent RIRS for renal stones between March 2022 and September 2023. Peri-operative variables including age, gender, body mass index (BMI), stone size, stone location, type of ureterorenoscope, Hounsfield Units (HU), pre-operative hydronephrosis, laboratory analysis, and operative time were evaluated. Univariate and multivariate logistic regression analyses were performed to assess the predictors of postoperative UTI. Results: Of the cohort, 77 surgeries (68.7%) utilized multi-use ureterorenoscopes, while 35 (31.3%) utilized single-use devices. Stone diameter, number of stones, type of ureterorenoscope, and operative time were significant predictors of postoperative UTI in the univariate analysis. Multivariable logistic regression showed that operative time (OR, 1.3; 95% CI, 0.55–0.99; p = 0.03) and type of ureterorenoscope (multi-use vs. single-use) (OR, 1.14; 95% CI, 1.08–1.2; p &lt; 0.001) were independent predictors of postoperative UTI. Conclusions: In conclusion, this study highlights that multi-use ureterorenoscopes and prolonged operative time are associated with an increased risk of postoperative UTI in RIRS procedures. Careful pre-operative evaluation and meticulous patient selection are essential to minimize the occurrence of postoperative UTIs and optimize patient outcomes in RIRS for renal stones.

The Potential Role of Viral Persistence in the Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

The infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated not only with the development of acute disease but also with long-term symptoms or post-acute sequelae of SARS-CoV-2 (PASC). Multiple lines of evidence support that some viral antigens and RNA can persist for up to 15 months in multiple organs in the body, often after apparent clearance from the upper respiratory system, possibly leading to the persistence of symptoms. Activation of the immune system to viral antigens is observed for a prolonged time, providing indirect evidence of the persistence of viral elements after acute infection. In the gastrointestinal tract, the persistence of some antigens could stimulate the immune system, shaping the local microbiota with potential systemic effects. All of these interactions need to be investigated, taking into account predisposing factors, multiplicity of pathogenic mechanisms, and stratifying populations of vulnerable individuals, particularly women, children, and immunocompromised individuals, where SARS-CoV-2 may present additional challenges.

Immediate Breast Reconstruction With Latissimus Dorsi Myocutaneous Flap and Silicone Implant Followed by Adjuvant Radiotherapy for Breast Cancer.

About 30% to 50% of women with breast cancer undergo mastectomy, and approximately 50% of them will receive adjuvant radiotherapy (ART). This study evaluates the medium- and long-term impact of ART after immediate breast reconstruction (IBR) with latissimus dorsi myocutaneous (LDM) flap and silicone implants. Clinical, surgical, and oncological data were retrospectively collected and analyzed based on the medical records of 176 patients who had undergone IBR with LDM flap and silicone implants. The data showed that 7.4% of patients had a history of previous radiotherapy, 56.3% received ART, 31.8% developed capsular contracture with a mean follow-up of 58.1 months, and 14.2% of surgeries were categorized as procedures with a prolonged operating time, lasting above 1 SD of the observed mean. Those who experienced prolonged operating time (odds ratio, 4.72; 95% confidence interval, 1.72-12.93; P = 0.003) and those who received ART (odds ratio, 7.38; 95% confidence interval, 3.18-17.10; P < 0.001) were more likely to develop capsular contracture. Thirty-two patients (18%) underwent capsulectomy with implant replacement, and 7 patients (4%) had the implant removed. The mean time between IBR and reoperation was 29.1 months. Patients who received ART were 2.84 times more likely to experience reconstruction failure or undergo implant-related reoperation (P = 0.002). The results indicated that IBR with LDM flap and silicone implant followed by ART is a safe procedure, resulting in low rates of reconstruction failure. However, ART increased the likelihood of capsular contracture development and implant-related reoperation, having a negative effect on reconstructed breasts.

Prolongation of the gastric residence time of caffeine after administration in fed state: Comparison of effervescent granules with an extended release tablet

The aim of the present study was to investigate the gastroretentive capacity of different formulation principles. This was indirectly determined by the absorption behavior of caffeine from the dosage forms. A slow and continuous appearance of caffeine in the saliva of healthy volunteers was used as a parameter for a prolonged gastric retention time. For this purpose, a four-way study was conducted with twelve healthy volunteers using the following test procedures: (1) Effervescent granules with 240 mL of still water administered in fed state, (2) effervescent granules with 20 mL of still water in fed state, (3) extended release (ER) tablet with 240 mL of still water in fed state, and (4) effervescent granules with 240 mL of still water in fasted state. The initial rise of the caffeine concentrations was more pronounced after the intake of the effervescent granules in the fed state compared to that of the ER tablets. However, tmax tended to be shorter in the fed study arms following administration of the ER tablet compared to the granules. Overall, the application of active pharmaceutical ingredients formulated as effervescent granules seems to be a promising approach to increase their gastric residence time after intake in fed state.

Ultrafast gelling bioadhesive based on blood plasma and gelatin for wound closure and healing

Tissue adhesives offer a plethora of advantages in achieving efficient wound closure over conventional sutures and staples. Such materials are of great value, especially in cases where suturing could potentially damage tissues or compromise blood flow or in cases of hard-to-reach areas. Besides providing wound closure, the tissue adhesives must also facilitate wound healing. Previously, plasma-based tissue adhesives and similar bioinspired strategies have been utilized to aid in wound healing. Still, their application is constrained by factors such as high cost, diminished biocompatibility, prolonged gelation times, inadequate swelling, quick resorption, as well as short-term and inconsistent efficacy. To address these limitations, we report the development of a highly biocompatible and ultrafast-gelling tissue adhesive hydrogels. Freeze-dried platelet-rich plasma, heat-denatured freeze-dried platelet-poor plasma, and gelatin were utilized as the base matrix. Gelation was initiated by adding tetrakis hydroxymethyl phosphonium chloride. The fabricated gels displayed rapid gelation (3–4 s), low swelling, increased proliferation, and migration against L929 cells and had porcine skin tissue adhesion strength similar to that of plasma-based commercial glue (Tisseel®).

Characterization of Freezing Processes in Drug Substance Bottles by Ice Core Sampling

Freezing of biological drug substance (DS) is a critical unit operation that may impact product quality, potentially leading to protein aggregation and sub-visible particle formation. Cryo-concentration has been identified as a critical parameter to impact protein stability during freezing and should therefore be minimized. The macroscopic cryo-concentration, in the following only referred to as cryo-concentration, is majorly influenced by the freezing rate, which is in turn impacted by product independent process parameters such as the DS container, its size and fill level, and the freezing equipment. (At-scale) process characterization studies are crucial to understand and optimize freezing processes. However, evaluating cryo-concentration requires sampling of the frozen bulk, which is typically performed by cutting the ice block into pieces for subsequent analysis. Also, the large amount of product requirement for these studies is a major limitation. In this study, we report the development of a simple methodology for experimental characterization of frozen DS in bottles at relevant scale using a surrogate solution. The novel ice core sampling technique identifies the axial ice core in the center to be indicative for cryo-concentration, which was measured by osmolality, and concentrations of histidine and polysorbate 80 (PS80), whereas osmolality revealed to be a sensitive read-out. Finally, we exemplify the suitability of the method to study cryo-concentration in DS bottles by comparing cryo-concentrations from different freezing protocols (-80°C vs -40°C). Prolonged stress times during freezing correlated to a higher extent of cryo-concentration quantified by osmolality in the axial center of a 2 L DS bottle.Graphical