Design, implementation and usability analysis of patient empowerment in ADLIFE project via patient reported outcome measures and shared decision making.

INTRODUCTION: This paper outlines the design, implementation, and usability study results of the patient empowerment process for chronic disease management, using Patient Reported Outcome Measurements and Shared Decision-Making Processes. BACKGROUND: The ADLIFE project aims to develop innovative, digital health solutions to support personalized, integrated care for patients with severe long-term conditions such as Chronic Obstructive Pulmonary Disease, and/or Chronic Heart Failure. Successful long-term management of patients with chronic conditions requires active patient self-management and a proactive involvement of patients in their healthcare and treatment. This calls for a patient-provider partnership within an integrated system of collaborative care, supporting self-management, shared-decision making, collection of patient reported outcome measures, education, and follow-up. METHODS: ADLIFE follows an outcome-based and patient-centered approach where PROMs represent an especially valuable tool to evaluate the outcomes of the care delivered. We have selected 11 standardized PROMs for evaluating the most recent patients' clinical context, enabling the decision-making process, and personalized care planning. The ADLIFE project implements the "SHARE approach' for enabling shared decision-making via two digital platforms for healthcare professionals and patients. We have successfully integrated PROMs and shared decision-making processes into our digital toolbox, based on an international interoperability standard, namely HL7 FHIR. A usability study was conducted with 3 clinical sites with 20 users in total to gather feedback and to subsequently prioritize updates to the ADLIFE toolbox. RESULTS: User satisfaction is measured in the QUIS7 questionnaire on a 9-point scale in the following aspects: overall reaction, screen, terminology and tool feedback, learning, multimedia, training material and system capabilities. With all the average scores above 6 in all categories, most respondents have a positive reaction to the ADLIFE PEP platform and find it easy to use. We have identified shortcomings and have prioritized updates to the platform before clinical pilot studies are initiated. CONCLUSIONS: Having finalized design, implementation, and pre-deployment usability studies, and updated the tool based on further feedback, our patient empowerment mechanisms enabled via PROMs and shared decision-making processes are ready to be piloted in clinal settings. Clinical studies will be conducted based at six healthcare settings across Spain, UK, Germany, Denmark, and Israel.

Step-Growth Glycopolymers with a Defined Tacticity for Selective Carbohydrate-Lectin Recognition.

Glycopolymers are potent candidates for biomedical applications by exploiting multivalent carbohydrate-lectin interactions. Owing to their specific recognition capabilities, glycosylated polymers can be utilized for targeted drug delivery to certain cell types bearing the corresponding lectin receptors. A fundamental challenge in glycopolymer research, however, is the specificity of recognition to receptors binding to the same sugar unit (e.g., mannose). Variation of polymer backbone chirality has emerged as an effective method to distinguish between lectins on a molecular level. Herein, we present a facile route toward producing glycopolymers with a defined tacticity based on a step-growth polymerization technique using click chemistry. A set of polymers have been fabricated and further functionalized with mannose moieties to enable lectin binding to receptors relevant to the immune system (mannose-binding lectin, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin, and dendritic and thymic epithelial cell-205). Surface plasmon resonance spectrometry was employed to determine the kinetic parameters of the step-growth glycopolymers. The results highlight the importance of structural complexity in advancing glycopolymer synthesis, yet multivalency remains a main driving force in lectin recognition.

Poly(2-oxazoline)/saRNA Polyplexes for Targeted and Nonviral Gene Delivery.

RNA delivery has been demonstrated to be a potent method of vaccine delivery, as demonstrated by the recent success of the COVID-19 vaccines. Polymers have been shown to be effective vehicles for RNA delivery, with poly(ethylene imine) (PEI) being the current gold standard for delivery. Nonetheless, PEI has toxicity concerns, and so finding alternatives is desirable. Poly(2-oxazoline)s are a promising alternative to PEI, as they are generally biocompatible and offer a high degree of control over the polymer structure. Here, we have synthesized an ionizable primary amine 2-oxazoline and combined it with a double bond containing oxazoline to synthesize a small library of charged statistical and block copolymers. The pendant double bonds were reacted further to decorate the polymers with glucose via a thiol-ene click reaction. All polymers were shown to have excellent cell viability, and the synthesized block polymers showed promising complexation efficiencies for the saRNA, demonstrating a clear structure-property relationship. The polymer transfection potential was tested in various cell lines, and a polymer composition with an amine/glucose ratio of 9:27 has demonstrated the best transfection potential across all cell lines tested. Overall, the results suggest that block polymers with a cationic segment and high levels of glycosylation have the best complexation efficiency and RNA expression levels.

Pharmacokinetics of meloxicam following intravenous administration at different doses in sheep.

The aim of this study is to determine the pharmacokinetic change after intravenous administration of meloxicam at doses of 0.5, 1 and 2 mg/kg to sheep. The study was carried out on six Akkaraman sheep. Meloxicam was administered intravenously to each sheep at 0.5, 1, and 2 mg/kg doses in a longitudinal pharmacokinetic design with a 15-day washout period. Plasma concentrations of meloxicam were determined using the high performance liquid chromatography-ultraviolet, and pharmacokinetic parameters were evaluated by non-compartmental analysis. Meloxicam was detected up to 48 h in the 0.5 mg/kg dose and up to 96 h in the 1 and 2 mg/kg doses. As the dose increased from 0.5 to 2 mg/kg, terminal elimination half-life, and dose normalized area under the concentration versus time curve increased and total clearance decreased. Compared to the 1 mg/kg dose, it was determined that Vdss decreased and C0.083h increased in the 2 mg/kg dose. Meloxicam provided the therapeutic concentration of >0.39 µg/mL reported in other species for 12, 48 and 96 h at 0.5, 1 and 2 mg/kg doses, respectively. These results show that meloxicam exhibits non-linear pharmacokinetics and will achieve unpredictable plasma concentrations when administered IV for a rapid effect at dose of ≥1 mg/kg in sheep.

The mediating role of nurse-physician collaboration in the effect of organizational commitment on turnover intention.

Despite extensive research having been carried out on nurse-physician collaboration, there remains a paucity of evidence on how collaboration interacts with organizational commitment and its effect on turnover intention. This study aims to determine the mediating role of nurse-physician collaboration on the effect of organizational commitment on turnover intention. We used a cross-sectional design based on voluntary paper surveys from the inpatient clinics of six public hospitals in the north of Turkey. Data including measures of nurse-physician collaboration, organizational commitment, and turnover intention were collected from a convenience sample of the nurses (n = 212) and physicians (n = 109). Pearson's correlation analysis was used to determine the relationships between variables, and the mediating effect was analyzed with PROCESS Macro "Model 4" for IBM SPSS. Statistical significance was specified at 95% confidence intervals and two-tailed P values of <0.05 for all tests. While most of the participants were nurses (66%), 34% were physicians. For both nurses and physicians, organizational commitment and nurse-physician collaboration negatively affected the turnover intention. However, the mediating role of nurse-physician collaboration was only significant for nurses (b = -0.025). The results demonstrate the importance of harmony, joint decision-making, and responsibility-sharing between nurses and physicians concerning dedication, engagement, and job satisfaction, especially for nurses.

Hierarchy of Complex Glycomacromolecules: From Controlled Topologies to Biomedical Applications.

Carbohydrates bearing a distinct complexity use a special code (Glycocode) to communicate with carbohydrate-binding proteins at a high precision to manipulate biological activities in complex biological environments. The level of complexity in carbohydrate-containing macromolecules controls the amount and specificity of information that can be stored in biomacromolecules. Therefore, a better understanding of the glycocode is crucial to open new areas of biomedical applications by controlling or manipulating the interaction between immune cells and pathogens in terms of trafficking and signaling, which would become a powerful tool to prevent infectious diseases. Even though a certain level of progress has been achieved over the past decade, synthetic glycomacromolecules are still lagging far behind naturally existing glycans in terms of complexity and precision because of insufficient and inefficient synthetic techniques. Currently, specific targeting at a cellular level using synthetic glycomacromolecules is still challenging. It is obvious that multidisciplinary collaborations are essential between different specialized disciplines to enhance the carbohydrate receptor-targeting paradigm for new biomedical applications. In this Perspective, recent developments in the synthesis of sophisticated glycomacromolecules are highlighted, and their biological and biomedical applications are also discussed in detail.

The diagnostic importance of periostin as a biomarker in chronic rhinosinusitis with nasal polyp.

PURPOSE: The current studies in the literature report that periostin contributes to the formation of nasal polyps and may be a molecular biomarker for chronic rhinosinusitis with nasal polyps (CRSwNP). This study aims to investigate the effect of periostin in determining polyp burden in CRSwNP patients and evaluate its impact on postoperative surgical results and its functionality as a biomarker. METHODS: The study included 26 patients who underwent endoscopic sinus surgery due to CRSwNP and 30 patients who were scheduled to undergo septoplasty due to isolated nasal septum deviation. We performed preoperative Lund-Mackay scoring and preoperative and postoperative SNOT-22 and Modified Lund-Kennedy scoring for the patients. Tissue and serum samples were collected from all patients in surgery and another serum sample was taken from CRSwNP patients at postoperative month 6. RESULTS: Tissue eosinophil (p < 0.001), preoperative serum (p < 0.001), and tissue (p = 0.002) periostin were significantly higher in the CRSwNP group. We observed a statistically significant positive correlation between tissue eosinophil values and tissue periostin values in CRSwNP patients (p = 0.004). We found a statistically significant positive correlation between the tissue periostin values and postoperative SNOT-22 scores of the CRSwNP group patients (p = 0.005). CONCLUSION: According to the results of our study, we think that periostin can be used as a biomarker in the prediction, determination of disease severity, and prognosis of CRSwNP. Comprehensive cohort studies with larger patient series are needed to provide more information on the role and effects of periostin in cases of CRSwNP undergoing surgical treatment.

Learning Curve of Laparoscopic Surgery for Colorectal Cancer at a New Regional State Hospital: A Single-Surgeon Experience Of 106 Consecutive Cases Without Supervision.

BACKGROUND: Laparoscopic surgery for colorectal cancer is mostly performed in university hospitals or experienced centers. This study aimed at determining the learning curve of laparoscopic surgery for colorectal cancer at a new regional state hospital. PATIENTS AND METHODS: Clinico-pathological data of 106 consecutive patients who underwent laparoscopic surgery for colorectal cancer at a new regional state hospital between August 2018 and September 2021 were prospectively recorded and analyzed. All surgeries were performed by a single inexperienced surgeon without supervision. The primary outcome of the study was the operative time, which was used for a Cumulative Sum (CUSUM) analysis of the learning curve. The secondary outcomes included a comparison of preoperative, intraoperative, and postoperative outcomes during the learning curve period. RESULTS: According to the CUSUM analysis, the learning curve consisted of three unique phases: phase 1 [the initial learning period (cases 1-53)], phase 2 [the consolidation period (cases 54-68)], and phase 3 [the experienced period (cases 69-106)]. Of the intraoperative outcomes, operative time and estimated blood loss were significantly reduced from phase 1 to phase 3 (p<0.001). Of the postoperative outcomes, time to pass stool (p<0.05), time to oral feeding (p=0.001), drain removal time (p<0.001), and length of hospital stay (p=0.042) were shorter in phase 3 compared to phases 1 and 2. Of the histopathological results, the specimen length and the number of harvested lymph nodes increased with experience (p=0.001). CONCLUSIONS: The present results suggest that a surgeon at a new regional state hospital must experience 53-68 cases to achieve competence in laparoscopic colorectal cancer surgery.

Self-Assembled Multi- and Single-Chain Glyconanoparticles and Their Lectin Recognition.

In this work, we describe the physicochemical characterization of amphiphilic glycopolymers synthesized via copper(0)-mediated reversible-deactivation radical polymerization (Cu-RDRP). Depending on the chemical composition of the polymer, these glycopolymers are able to form multi-chain or single-chain polymeric nanoparticles. The folding of these polymers is first of all driven by the amphiphilicity of the glycopolymers and furthermore by the supramolecular formation of helical supramolecular stacks of benzene-1,3,5-tricarboxamides (BTAs) stabilized by threefold hydrogen bonding. The obtained polymeric nanoparticles were subsequently evaluated for their lectin-binding affinity toward a series of mannose- and galactose-binding lectins via surface plasmon resonance. We found that addition of 2-ethylhexyl acrylate to the polymer composition results in compact particles, which translates to a reduction in binding affinity, whereas with the addition of BTAs, the relation between the nature of the particle and the binding ability system becomes more unpredictable.

Short-term Results of Platelet-Rich Plasma in the Treatment of Chronic Anal Fissure: Randomized Controlled Clinical Study.

BACKGROUND: Anal fissure is one of the most common benign anal disorders, and medical treatments play an important role in its management. OBJECTIVE: The purpose of this study was to investigate the short-term effects and success of platelet-rich plasma in the treatment of chronic anal fissure. DESIGN: The study is a 2 parallel group, randomized, controlled clinical trial. SETTINGS: The study was performed in 2 tertiary university hospitals. PATIENTS: Forty-four patients with chronic anal fissure were randomly assigned to platelet-rich plasma treatment or control group. Presenting symptoms and pain scores were recorded on enrollment. The control patient self-administered topical glyceryl trinitrate. Platelet-rich plasma was injected locally in the intervention group followed by self-administered glyceryl trinitrate. MAIN OUTCOME MEASURES: The primary outcome measure is a reduction in pain scores. RESULTS: On day 10 and 1 month after treatment, the mean pain score was significantly lower in the patients treated with platelet-rich plasma than in the controls (p = 0.005 and p < 0.005). By 1 month after treatment, the mean pain score declined by 5.7 points in the platelet-rich plasma-treated group compared with a 4.1 mean pain score decline in the control group (mean difference:1.6 points (95% CI, 0.3-2.9)). According to the repeated-measures analyses, pain scores decreased in both groups, but the decrease in the treatment group was statistically higher than in the control group (p < 0.001). Complete epithelialization and recovery rates were significantly higher in the platelet-rich plasma group than in controls at all follow-up times, with p values ranging from 0.034 to <0.001. The observed difference in complete epithelialization after 2 months of treatment between the platelet-rich plasma group and the control group was 56.2% with a 95% CI of 14.03% to 98.4%. LIMITATIONS: This study was limited by its small sample size, and long-term follow-up of the patients was not presented. CONCLUSIONS: Platelet-rich plasma reduced concerns and accelerated epithelialization and healing in patients with chronic anal fissures. See Video Abstract at http://links.lww.com/DCR/B461.RESULTADOS A CORTO PLAZO DEL PLASMA RICO EN PLAQUETAS EN EL TRATAMIENTO DE LA FISURA ANAL CRÓNICA: ESTUDIO CLÍNICO CONTROLADO ALEATORIZADO. ANTECEDENTES: La fisura anal es uno de los trastornos anales benignos más comunes y los tratamientos médicos juegan un papel importante en su manejo. OBJETIVO: El propósito de este estudio fue investigar los efectos a corto plazo y el éxito del plasma rico en plaquetas en el tratamiento de la fisura an33al crónica. DISEO: El estudio es un ensayo clínico controlado, aleatorizado y de dos grupos paralelos. ESCENARIO: El estudio se llevó a cabo en dos hospitales universitarios terciarios. PACIENTES: Cuarenta y cuatro pacientes con fisura anal crónica fueron asignados aleatoriamente al grupo de tratamiento con plasma rico en plaquetas o al grupo control. Los síntomas de presentación y las puntuaciones de dolor se registraron en la inscripción. Los pacientes de control se autoadministraron trinitrato de glicerilo tópico. El plasma rico en plaquetas se inyectó localmente en el grupo de intervención seguido de trinitrato de glicerilo autoadministrado. PRINCIPALES MEDIDAS DE RESULTADO: La principal medida de resultado es una reducción en las puntuaciones de dolor. RESULTADOS: El día 10 y un mes después del tratamiento, la puntuación media de dolor fue significativamente menor en los pacientes con plasma rico en plaquetas que en los controles (p = 0.005 y p <0.005, respectivamente). Un mes después del tratamiento, la puntuación media de dolor disminuyó 5.7 puntos en el grupo tratado con plasma rico en plaquetas en comparación con una disminución de la puntuación media de dolor de 4.1 en el grupo de control (diferencia media: 1.6 puntos [intervalo de confianza del 95%; 0.3-2.9] Según los análisis de medidas repetidas, las puntuaciones de dolor disminuyeron en ambos grupos, pero la disminución en el grupo de tratamiento fue estadísticamente mayor que en el grupo de control (p <0.001). Las tasas de epitelización completa y recuperación fueron significativamente más altas en los pacientes con plasma rico en plaquetas que en los controles en todos los tiempos de seguimiento, con valores de p que van desde 0.034 a <0.001. La diferencia observada en la epitelización completa después de dos meses de tratamiento entre el grupo de plasma rico en plaquetas y el grupo de control fue del 56.2% con un intervalo de confianza del 95% del 14.03% al 98.4%. LIMITACIONES: Este estudio estuvo limitado por el pequeño tamaño de la muestra y porque no se proporcionó un seguimiento a largo plazo de los pacientes. CONCLUSIONES: El plasma rico en plaquetas redujo las molestias y aceleró la epitelización y la curación en pacientes con fisuras anales crónicas. Consulte Video Resumen en http://links.lww.com/DCR/B461. (Traducción-Dr. Jorge Silva Velazco).

Synthetic Routes to Single Chain Polymer Nanoparticles (SCNPs): Current Status and Perspectives.

Recent advances in polymer science make it possible to create single chain polymer nanoparticles (SCNPs), which can mimic the folding of natural macromolecules, such as protein and nucleic acid, in terms of their native and functional state. Even though considerable progress has been done during the last years, the synthesis of relatively controlled SCNPs with a good folding accuracy is still challenging due to lack of appropriate chemical synthesis techniques. Different types of SCNPs are developed with enhanced properties and used for various applications, e.g., delivery systems, imaging agents, and nanomedicine. As it is believed that SCNPs are so crucial to elucidate single chain technology, in this review, recent developments in SCNPs are discussed comprehensively according to their synthetic approaches to keep readers updated on this important research field. First, selective point folding methods are classified and highlighted, and then repeat unit folding routes are discussed with exciting examples.

Laparoscopic Inguinal Hernia Repair-TAPP versus TEP: Results of 301 Consecutive Patients.

INTRODUCTION: Transabdominal preperitoneal (TAPP) and totally extraperitoneal (TEP) hernia repair are the two most commonly used techniques in laparoscopic inguinal hernia repair, and the results of comparative studies are conflicting. The objective of this study is to compare the two methods in unilateral inguinal hernia repair. MATERIALS AND METHODS: The data of consecutive patients who underwent TEP and TAPP due to unilateral inguinal hernia between December 7, 2017, and March 15, 2020, were analyzed retrospectively. The primary outcome was to compare the clinical outcomes of the two techniques in terms of complications, conversion, pain, and operative time. The secondary outcome was recurrence rates. RESULTS: A total of 301 (TEP n=234, TAPP n=67) patients were included in the study. The mean age was 43 years, and the follow-up period was two years. The groups were similar in terms of demographic characteristics and hernia type. The mean operative time was longer in the TAPP group than in the TEP group (67 min and 58 min, p=0.007). The recurrence rate was 4.3% in the TEP group and 5.9% in the TAPP group (p>0.05). The conversion rate was 6% in both groups. In total, 19 (6.3%) patients had intraoperative complications (TEP n=16, TAPP n=3), and 23 (7.6%) patients had postoperative complications (TEP n=16, TAPP n=7). Both intraoperative and postoperative complication rates were similar between the groups (p=0.31 and p=0.051, respectively). The early postoperative pain was less in the TEP group (p=0.004). CONCLUSION: Less early postoperative pain and shorter operative time were detected in patients who underwent TEP.

Measuring the Optic Nerve Sheath Diameter with Ultrasound in Acute Middle Cerebral Artery Stroke Patients.

BACKGROUND: Measurement of the optic nerve sheath diameter (ONSD) with ultrasound enables non-invasive and indirect assessment of increased intracranial pressure (ICP). Although most of the studies were employed with traumatic brain injury patients, it's increasingly popular in acute ischemic stroke (AIS) studies. OBJECTIVES: Evaluating whether using ONSD as a follow-up measurement would help monitor the thrombolytic therapy (TT) effectiveness and determine the high-risk patients for malignant middle cerebral artery (MCA) syndrome. METHODS: This prospective observational study was conducted between August 1, 2019, and February 1, 2020, in a tertiary hospital. Forty-four patients were eligible. We determined the TT moment as the time when the first ocular ultrasound measurement would be made (time 0). Also, we decided on the 24th h after the treatment as the time to perform the second ocular ultrasound measurement (time 24). The National Institute of Health Stroke Scale (NIHSS), the Glasgow Coma Scale (GCS), and the Alberta Stroke Program Early Computed Tomography (ASPECT) scores were evaluated blindly at the time-0 and the time-24. The cut-off value of ONSD was 0.55 mm. RESULTS: There was no difference in ONSD results before and after the TT (p = 0.414). But, patients with an equal or higher value than cut-off had an increased risk for complications such as malignant-MCA, bleeding, seizure, etc. (p = 0.05). Malignant-MCA was observed in four patients with higher ONSD values. At the time-24, NIHSS decreased, GCS and ASPECT scores increased. Finally, ONSD was positively correlated with the NIHSS and negatively correlated with the GCS at the time-24. CONCLUSIONS: Monitoring ONSD values in both the emergency department and the intensive care unit may be useful in the early diagnosis of MCA stroke complications and the follow-up of TT's effectiveness.

Effect of Arm Number and Length of Star-Shaped Glycopolymers on Binding to Dendritic and Langerhans Cell Lectins.

Many cell types in Nature are covered by glycans with a sugar shell on their surface. Synthetic glycopolymer-based materials can mimic these glycans in terms of their variety of biological processes, such as cell growth regulation, adhesion, inflammation by bacteria and viruses, and immune responses. However, the complexity of glycans is still very challenging to be mimicked completely to obtain specific and selective binding ability. Therefore, in this study we aimed to understand how the complexity in the sense of the effect of number of arms and lengths in star-shaped glycopolymers affect the binding activity with different lectins. The Cu-mediated reversible deactivation radical polymerization (Cu-RDRP) technique was employed for the synthesis of mannose containing star-shaped glycopolymers with varying arm number and length. Two sets of star-shaped glycopolymers with on average 1, 3, 7, 8, and 15 arms were successfully synthesized and characterized via 1H NMR, GPC, and DLS. The first set of glycopolymers (Set S1) encompasses 5 star-shaped glycopolymers with a different amount of arms per macromolecule but with equal arm length, whereas in the second set of 5 glycopolymers (Set S2), the amount of sugars per macromolecule was kept constant to obtain glycopolymers with similar glycovalency but in different configuration. Both glycopolymer sets were subsequently evaluated for their lectin-binding affinity toward a series of both newly and previously studied C-type mannose specific lectins present on dendritic and Langerhans cells. Briefly, while Set S1 glycopolymers with the same arm length and different molecular weight showed considerably different biological activities, Set S2 glycopolymers with different arm lengths and the same molecular weight displayed very similar binding abilities, which can indicate that multivalency can be more important than structure complexity to improve the binding behavior of glycopolymers.

Bottlebrush Glycopolymers from 2-Oxazolines and Acrylamides for Targeting Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin and Mannose-Binding Lectin.

Lectins are omnipresent carbohydrate binding proteins that are involved in a multitude of biological processes. Unearthing their binding properties is a powerful tool toward the understanding and modification of their functions in biological applications. Herein, we present the synthesis of glycopolymers with a brush architecture via a "grafting from" methodology. The use of a versatile 2-oxazoline inimer was demonstrated to open avenues for a wide range of 2-oxazoline/acrylamide bottle brush polymers utilizing aqueous Cu-mediated reversible deactivation radical polymerization (Cu-RDRP). The polymers in the obtained library were assessed for their thermal properties in aqueous solution and their binding toward the C-type animal lectins dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and mannose-binding lectin (MBL) via surface plasmon resonance spectrometry. The encapsulation properties of a hydrophobic drug-mimicking compound demonstrated the potential use of glyco brush copolymers in biological applications.

Mannosylated Poly(ethylene imine) Copolymers Enhance saRNA Uptake and Expression in Human Skin Explants.

Messenger RNA (mRNA) is a promising platform for both vaccines and therapeutics, and self-amplifying RNA (saRNA) is particularly advantageous, as it enables higher protein expression and dose minimization. Here, we present a delivery platform for targeted delivery of saRNA using mannosylated poly(ethylene imine) (PEI) enabled by the host-guest interaction between cyclodextrin and adamantane. We show that the host-guest complexation does not interfere with the electrostatic interaction with saRNA and observed that increasing the degree of mannosylation inhibited transfection efficiency in vitro, but enhanced the number of cells expressing GFP by 8-fold in human skin explants. Besides, increasing the ratio of glycopolymer to saRNA also enhanced the percentage of transfected cells ex vivo. We identified that these mannosylated PEIs specifically increased protein expression in the epithelial cells resident in human skin in a mannose-dependent manner. This platform is promising for further study of glycosylation of PEI and targeted saRNA delivery.

Synthesis of Brush-Like Glycopolymers with Monodisperse, Sequence-Defined Side Chains and Their Interactions with Plant and Animal Lectins.

The synthesis of brush glycopolymers mimicking the architecture of proteoglycans is achieved by grafting sequence-defined glycooligomers derived from solid-phase polymer synthesis onto a poly(active ester) scaffold. This approach gives access to a first library of brush glycopolymers with controlled variations in the degree of branching and number of carbohydrate ligands per branch. When studying lectin binding of linear and brush glycopolymers to lectins Concanavalin A (ConA), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and mannose-binding lectin (MBL), different preferences are observed with MBL showing higher binding to linear glycopolymer and ConA and DC-SIGN favoring brush glycopolymers. This finding suggests that the architecture of polymeric glycan mimetics affects binding to lectins not only in terms of creating higher avidity but potentially also selectivity ligands.

Risk Factors Influencing Recovery of Neurosensory Disturbances Following Sagittal Split Ramus Osteotomy.

PURPOSE: The aim of this study is to determine the risk factors influencing the recovery time of neurosensory disturbances (NSD) following sagittal split ramus osteotomy. METHODS: One hundred twenty-seven patients (254 operated sites) underwent sagittal split ramus osteotomy due to dentofacial deformities between the period of 2011 and 2017. These patients were followed up for at least 1 year, and the data obtained from changes in sensation of inferior alveolar nerve were recorded subjectively. The subjects were categorized according to age, gender, type of deformity, nerve manipulation, side of the jaw, and the amount of the mandibular movement. The relationship between the above-mentioned parameters, and the recovery time of NSD were investigated. Pearson χ analysis was used, and the value of significance was accepted as P < 0.05. RESULTS: The recovery time of NSD is significantly correlated with the age of the patients, the amount of the mandibular movement (>7 mm), and the nerve manipulation (P < 0.05). There was no statistically significant correlation found between the recovery time of NSD and gender, type of deformity, side of the jaw (P > 0.05). CONCLUSIONS: The recovery time of NSD may prolong in cases of large amounts of mandibular movements more than 7 mm or the nerve manipulation. The older age may increase the risk of permanent NSD.

Splenic Infarction after Warfarin Overdose Treatment: Is It a Coincidence or Complication?

Splenic infarction is a rare clinical condition seen in the emergency department and can mimic acute abdomen. Hematologic, vascular, and thromboembolic events are considered in the etiology. Treatment options vary between symptomatic treatment and splenectomy. Warfarin is a vitamin K antagonist used for the prevention and treatment of thromboembolic disorders. In overdose situations, there is a possibility of bleeding in every part of the body. Prothrombin complex concentrates, vitamin K, and fresh-frozen plasma are used in the treatment of warfarin overdose. We describe a case of splenic infarction coexistent with warfarin overdose treatment, which has never been published in literature. Prothrombin complex concentrate was administered to the patient because of warfarin overdose. A spleen infarction was detected in computerized tomography of the patient after the occurrence of abdominal pain, and there was no infarction three days before hospitalization. The patient was monitored with symptomatic treatment in the general surgery clinic and discharged without the need for operation. In the pathogenesis, it was thought that prothrombin complex concentrates might be caused by early thrombosis or by warfarin not affecting the existing clot. Emergency physicians should not forget spleen infarction in the differential diagnosis of abdominal pain.

Single-Chain Glycopolymer Folding via Host-Guest Interactions and Its Unprecedented Effect on DC-SIGN Binding.

Reversible self-folding actions of natural biomacromolecules play crucial roles for specific and unique biological functions in Nature. Hence, controlled folding of single polymer chains has attracted significant attention in recent years. Herein, reversible single-chain folded glycopolymer structures in α-shape with different density of sugar moieties in the knot were created. The influence of folding as well as the sugar density in the knot was investigated on the binding capability with lectins, such as ConA, DC-SIGN, and DC-SIGNR. The synthesis of triblock glycocopolymers bearing ß-CD and adamantane for the host-guest interaction and also mannose residues for the lectin interaction was achieved using the reversible addition-fragmentation chain transfer (RAFT) polymerization technique. The reversible single-chain folding of glycopolymers was achieved under a high dilution of an aqueous solution and the self-assembled folding was monitored by 2D nuclear overhauser enhancement spectroscopy (NOESY) NMR and dynamic light scattering. The lectin binding profiles consistently provided an unprecedented effect of single chain folding as the single-chain folded structures enhanced greatly the binding ability in comparison to the unfolded linear structures.