The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro. All the nanoparticles presented a size of approximately 200 nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1.     

Vitamin E Supplementation,Superoxide Dismutase Status,and Outcome of Scaling and Root Planing in Patients With Chronic Periodontitis: A Randomized Clinical Trial

Background: This study investigates the levels of superoxide dismutase (SOD) activity in serum and saliva of patients with chronic periodontitis (CP). In addition, the outcome of scaling and root planing (SRP) with and without vitamin E supplementation is evaluated in terms of changes in periodontal parameters and SOD activity in patients with CP. Methods: Serum and salivary SOD activity in 38 patients with CP were compared with those of 22 systemically and periodontally healthy individuals (control group). At periodontal examination, serum and saliva samples were obtained. Patients with CP were randomly divided into treatment groups 1 (TG‐1) and 2 (TG‐2). SRP was performed for both groups, and TG‐2 also received 200 mg (300 IU) vitamin E every other day. Periodontal parameters and SOD activity were evaluated after 3 months. SOD activity was determined using an SOD assay and enzyme‐linked immunosorbent assay reader at 450 nm. Results: SOD activity in both serum (P <0.05) and saliva (P <0.001) was lower in patients with CP compared with controls. After 3 months of follow‐up, SOD activity improved in both treatment groups; however, the improvement in TG‐2 was higher than in TG‐1, along with more improvement in periodontal parameters. Serum SOD levels in TG‐2 increased even above the level of the control group. Conclusions: Systemic and local SOD levels are lowered in CP. Adjunctive vitamin E supplementation improves periodontal healing as well as antioxidant defense.     

Neuroanatomy of dyslexia: An allometric approach

Despite evidence for a difference in total brain volume between dyslexic and good readers, no previous neuroimaging study examined differences in allometric scaling (i.e. differences in the relationship between regional and total brain volumes) between dyslexic and good readers. The present study aims to fill this gap by testing differences in allometric scaling and regional brain volume differences in dyslexic and good readers. Object‐based morphometry analysis was used to determine grey and white matter volumes of the four lobes, the cerebellum and limbic structures in 130 dyslexic and 106 good readers aged 8–14 years. Data were collected across three countries (France, Poland and Germany). Three methodological approaches were used as follows: principal component analysis (PCA), linear regression and multiple‐group confirmatory factor analysis (MGCFA). Difference in total brain volume between good and dyslexic readers was Cohen's d = 0.39. We found no difference in allometric scaling, nor in regional brain volume between dyslexic and good readers. Results of our three methodological approaches (PCA, linear regression and MGCFA) were consistent. This study provides evidence for total brain volume differences between dyslexic and control children, but no evidence for differences in the volumes of the four lobes, the cerebellum or limbic structures, once allometry is taken into account. It also finds no evidence for a difference in allometric relationships between the groups. We highlight the methodological interest of the MGCFA approach to investigate such research issues.     

Torsade de pointes: A nested case–control study in an integrated healthcare delivery system

BackgroundTdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There are limited data describing risk factors, treatment, and outcomes of this potentially fatal arrhythmia.ObjectiveOur goals were as follows: (1) to validate cases presenting with Torsade de Pointes (TdP), (2) to identify modifiable risk factors, and (3) to describe the management strategies used for TdP and its prognosis in a real‐world healthcare setting.MethodsCase–control study (with 2:1 matching on age, sex, and race/ethnicity) nested within the Genetic Epidemiology Research on Aging (GERA) cohort. Follow‐up of the cohort for case ascertainment was between January 01, 2005 and December 31, 2018.ResultsA total of 56 cases of TdP were confirmed (incidence rate = 3.6 per 100,000 persons/years). The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female, and 16 percent were non‐white. The independent predictors of TdP were potassium concentration <3.6 mEq/L (OR = 10.6), prior history of atrial fibrillation/flutter (OR = 6.2), QTc >480 ms (OR = 4.4) and prior history of coronary artery disease (OR = 2.6). Exposure to furosemide and amiodarone was significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in‐hospital and 1‐year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively.ConclusionsThese findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.     

A Scoping Review on the Concept of Physician Caring

BackgroundPhysicians’ interest in the health and well-being of their patients is a tenet of medical practice. Physicians’ ability to act upon this interest by caring for and about their patients is central to high-quality clinical medicine and may affect burnout. To date, a strong theoretical and empirical understanding of physician caring does not exist. To establish a practical, evidence-based approach to improve health care delivery and potentially address physician burnout, we sought to identify and synthesize existing conceptual models, frameworks, and definitions of physician caring.MethodsWe performed a scoping review on physician caring. In November 2019 and September 2020, we searched PubMed MEDLINE, Embase, PsycINFO, CINAHL, and CENTRAL Register of Controlled Trials to identify conceptual models, frameworks, and definitions of physician caring. Eligible articles involved discussion or study of care or caring among medical practitioners. We created a content summary and performed thematic analysis of extracted data.ResultsOf 11,776 articles, we reviewed the full text of 297 articles; 61 articles met inclusion criteria. Commonly identified concepts referenced Peabody’s “secret of care” and the ethics of care. In bioethics, caring is described as a virtue. Contradictions exist among concepts of caring, such as whether caring is an attitude, emotion, or behavior, and the role of relationship development. Thematic analysis of all concepts and definitions identified six aspects of physician caring: (1) relational aspects, (2) technical aspects, (3) physician attitudes and characteristics, (4) agency, (5) reciprocity, and (6) physician self-care.DiscussionCaring is instrumental to clinical medicine. However, scientific understanding of what constitutes caring from physicians is limited by contradictions across concepts. A unifying concept of physician caring does not yet exist. This review proposes six aspects of physician caring which can be used to develop evidence-based approaches to improve health care delivery and potentially mitigate physician burnout.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07382-4.KEY WORDS: caring, physician-patient relationships, burnout, wellness, purpose     

Ossifying Fibromas of the Head and Neck Region: A Clinicopathological Study of 45 Cases

Ossifying fibromas of the head and neck region are classified as cemento-ossifying fibroma (COF) (odontogenic origin), and two types of juvenile ossifying fibromas: juvenile trabecular ossifying fibroma (JTOF), and juvenile psammomatous ossifying fibroma (JPOF). The potential for recurrence in JTOF and JPOF and the discovery of newer molecular signatures necessitates accurate histological classification. Over 12 years (2005–2017), a total of 45 patients with 51 tumours were retrieved and reviewed for clinic-pathological features from the archives of a tertiary care oncology centre. Of 45 cases, COF, JTOF and JPOF comprised 13 (28.9%), 11 (24.4%) and 18 (40%) cases respectively. Three cases were unclassifiable. M: F ratio was 1:3.3, 1.1:1, 2:1 for COF, JTOF and JPOF respectively with an age range of 6–66 years (mean: 24.6, median; 18.1 years). The most common site for COF was mandible, for JTOF was maxilla, and for JPOF was ethmoid sinus. One case of mixed JTOF and JPOF histology was seen. Aneurysmal bone cyst-like areas were seen in 26.6% of cases, most commonly in JPOF. Follow up was available in 23 cases, and ranged from 4 to 207 months. Three cases of JPOF had a recurrence and one patient with JTOF had residual disease after surgery. One case of COF demonstrated increased parathyroid hormone levels. COF, JTOF, and JPOF are clinically, radiologically and histologically distinct entities. Surgical resection is the mainstay of treatment. JPOF has a higher incidence of recurrence as compared to JTOF and COF and hence needs a more aggressive follow-up.     

Digital phenotyping in depression diagnostics: Integrating psychiatric and engineering perspectives

Depression is a serious medical condition and is a leading cause of disability worldwide. Current depression diagnostics and assessment has significant limitations due to heterogeneity of clinical presentations, lack of objective assessments, and assessments that rely on patients' perceptions, memory, and recall. Digital phenotyping (DP), especially assessments conducted using mobile health technologies, has the potential to greatly improve accuracy of depression diagnostics by generating objectively measurable endophenotypes. DP includes two primary sources of digital data generated using ecological momentary assessments (EMA), assessments conducted in real-time, in subjects' natural environment. This includes active EMA, data that require active input by the subject, and passive EMA or passive sensing, data passively and automatically collected from subjects' personal digital devices. The raw data is then analyzed using machine learning algorithms to identify behavioral patterns that correlate with patients' clinical status. Preliminary investigations have also shown that linguistic and behavioral clues from social media data and data extracted from the electronic medical records can be used to predict depression status. These other sources of data and recent advances in telepsychiatry can further enhance DP of the depressed patients. Success of DP endeavors depends on critical contributions from both psychiatric and engineering disciplines. The current review integrates important perspectives from both disciplines and discusses parameters for successful interdisciplinary collaborations. A clinically-relevant model for incorporating DP in clinical setting is presented. This model, based on investigations conducted by our group, delineates development of a depression prediction system and its integration in clinical setting to enhance depression diagnostics and inform the clinical decision making process. Benefits, challenges, and opportunities pertaining to clinical integration of DP of depression diagnostics are discussed from interdisciplinary perspectives.