Multi-acrylamides improve bond stability through collagen reinforcement under physiological conditions.

OBJECTIVES: Acrylamides were shown to significantly improve bonding stability in adhesive restorations, but the reinforcement mechanism has not been fully elucidated. We tested the hypothesis that hydrogen bonding reinforcement of the collagen network (with secondary or tertiary acrylamides), as well as degree of crosslinking of the polymer network (with di- or tri-functional acrylamides), can be two of the factors at play. METHODS: Two-step total etch adhesives comprising UDMA (60 wt%) and 40 wt% of: TAAEA, TMAAEA (secondary, tertiary tri-acrylamides), BAAP, DEBAAP (secondary, tertiary di-acrylamides) or HEMA (mono-methacrylate - control) were formulated. Simulated composite restorations (n = 5) were tested after cyclic mechanical and biological (S. mutans biofilm) challenges. Gap formation before and after aging was assessed with SEM imaging. Micro-tensile bond strength (µTBS, n = 6) was assessed after seven-day incubation in water or S. mutans-containing culture medium. Collagen reinforcement was assessed with hydroxyproline assay (n = 10) and rheology (n = 3). Data were analyzed with one-way/two-way ANOVA/Tukey's test (alpha=5%). RESULTS: Gap formation increased and bond strength decreased for all monomers after biofilm incubation (p < 0.001). Except for DEBAAP, secondary and tertiary di/tri-acrylamides showed lower occlusal gap width values, but no significant differences overall gap length compared to HEMA. µTBS increased for tri-acrylamides compared with HEMA. Samples treated with multi-acrylamides had lower concentration of hydroxyproline (by-product of collagen degradation) (p < 0.001), except for DEBAAP, which showed values close to HEMA (p > 0.05). Dentin shear modulus increased for all acrylamides after 72 h, especially TMAAEA. SIGNIFICANCE: In general, multi-acrylamides promote collagen reinforcement, leading to reduced gap formation, and stabilize the bond strength under physiological conditions.

Host response during unresolved urinary tract infection alters female mammary tissue homeostasis through collagen deposition and TIMP1.

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells are absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue are mediated by the systemic host response to local infection. Furthermore, broad spectrum antibiotic treatment resolves the infection and restores mammary cellular and tissue homeostasis. Systemically, unresolved UTI correlates with increased plasma levels of the metalloproteinase inhibitor, TIMP1, which controls extracellular matrix remodeling and neutrophil function. Treatment of nulliparous and post-lactation UTI-bearing female mice with a TIMP1 neutralizing antibody, restores mammary tissue normal homeostasis, thus providing evidence for a link between the systemic host response during UTI and mammary gland alterations.

General neurology: Current challenges and future implications.

BACKGROUND AND PURPOSE: In the coming decades, the world will face an increasing burden of neurological disorders (ND) and an urgent need to promote brain health. These challenges contrast with an insufficient neurological workforce in most countries, as well as decreasing numbers of general neurologists and neurologists attracted to work in general neurology (GN). This white paper aims to review the current situation of GN and reflect on its future. METHODS: The European Academy of Neurology (EAN) task force (TF) met nine times between November 2021 and June 2023. During the 2023 EAN annual meeting, attendees were asked to answer five questions concerning the future of GN. The document was sent for suggestions and eventually approval to the board and the presidents of the 47 national societies of the EAN. RESULTS: The TF first identified four relevant current and future challenges related to GN: (i) definition, (ii) practice, (iii) education, and (iv) research. The TF then identified seven initiatives to further develop GN at both the academic and community level. Finally, the TF formulated 16 recommendations to promote GN in the future. CONCLUSIONS: GN will remain essential in the coming decades to provide rapid, accessible, and comprehensive management of patients with ND that is affordable and cost-effective. There is also a need for research, education, and other initiatives aiming to facilitate improved working conditions, recognition, and prestige for those pursuing a career in GN.

Myocardial perfusion imaging-derived left ventricular strain: Regional abnormalities associated with transthyretin cardiac amyloidosis.

Background: Transthyretin (ATTR) cardiac amyloidosis is associated with an apical-sparing strain pattern on TTE. We hypothesize that strain indices derived from myocardial perfusion imaging (MPI) can identify this abnormality. Methods: A group with ATTR amyloidosis was compared to age-matched controls with LVH but without amyloidosis who underwent PET or SPECT MPI. Strain values were used to calculate the apical strain index (ASI), apex-to-base ratio (ABR), and ejection fraction to global strain ratio in multiple planes. Results: A direct comparison using Welch's t-tests reveals 6 statistically significant metrics. After regression analysis, the circumferential ASI and ABR at rest remain significantly greater in the ATTR group compared to controls. Conclusion: MPI-derived strain from the circumferential plane at rest may distinguish cardiac amyloidosis from other forms of LVH. If these findings are confirmed with validation studies, routine MPI-derived strain analysis could identify patients with subclinical amyloidosis who may benefit from further testing.

Family planning competency following medical school Ob/Gyn clerkships at faith-based and secular sites.

Contraception and abortion topics are variably, but often poorly, addressed in medical school curricula. Restrictions on contraceptive and abortion care at faith-based hospitals may hinder comprehensive family planning training for medical students during Ob/Gyn clerkships. Here we investigated whether medical students at faith-based and non-faith-based clerkships experienced different observations during their Ob/Gyn clerkship and/or differences in self-perceived competency in patient counseling, objective knowledge, and perceived adequacy of training in contraception and abortion topics post-clerkship. A survey was distributed to third- and fourth-year medical students at New York Institute of Technology, College of Osteopathic Medicine. Across all clerkship sites (n = 102 students), observations of, and competency in, contraceptive care was higher than in abortion care. Students at non-faith-based clerkship sites (n = 54) reported the highest levels of observation of contraceptive and abortion care (19.6-90.7%), while those at Catholic sites (n = 26) typically reported the lowest (7.7-34.6%). Students at non-faith-based sites reported significantly higher competency in contraceptive care and some aspects of abortion care, than those at Catholic, and some other faith-based sites (n = 48). Clerkship training at faith-based sites, specifically Catholic sites, resulted in poorer Ob/Gyn training, particularly in contraceptive care. Training outcomes in abortion care were poor at all Ob/Gyn clerkship sites.

Single-Cell Transcription Mapping of Murine and Human Mammary Organoids Responses to Female Hormones.

During female adolescence and pregnancy, rising levels of hormones result in a cyclic source of signals that control the development of mammary tissue. While such alterations are well understood from a whole-gland perspective, the alterations that such hormones bring to organoid cultures derived from mammary glands have yet to be fully mapped. This is of special importance given that organoids are considered suitable systems to understand cross species breast development. Here we utilized single-cell transcriptional profiling to delineate responses of murine and human normal breast organoid systems to female hormones across evolutionary distinct species. Collectively, our study represents a molecular atlas of epithelial dynamics in response to estrogen and pregnancy hormones.

Functional and radiographic results of anatomic total shoulder arthroplasty in the setting of subscapularis dysfunction: 5-year outcomes analysis.

BACKGROUND: Subscapularis management is a critical component to the success of anatomic total shoulder arthroplasty (TSA). Failure to heal the subscapularis can result in pain, weakness, loss of function, and revision. However, not all patients have poor outcomes. The purpose of this study is to compare patients with normal and dysfunctional subscapularis function following TSA in regard to (1) patient-reported outcome measures (PROMs); (2) range of motion (ROM) and strength; (3) achievement of minimal clinically important differences (MCIDs); and (4) specific functional internal rotation tasks. METHODS: A retrospective review of patients treated with TSA for osteoarthritis with a minimum 2-year follow-up was performed to identify patients with subscapularis dysfunction. Subscapularis dysfunction was diagnosed when any degree of weakness in internal rotation was detected on physical examination (positive belly press sign). These patients were case controlled matched on a 1:3 ratio to patients with normal subscapularis function based on age and sex. PROMs, measured active motion, revision rates, patient satisfaction, and postoperative radiographic findings were compared. Population-specific institutional anchor-based MCID values were used to compare the improvement in PROM. RESULTS: Of the 668 patients included, 34 patients (5.1%) demonstrated evidence of subscapularis dysfunction. Mean follow-up for the normal subscapularis function cohort was 63.4 ± 29.7 and 58.7 ± 26.8 for the dysfunctional subscapularis cohort. Patients with subscapularis dysfunction demonstrated significantly worse postoperative Simple Shoulder Test, Single Assessment Numerical Evaluation, visual analog scale (VAS) function, VAS pain, and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores with higher rates of unsatisfactory results when compared to patients with normal subscapularis function. Abduction, elevation, internal rotation ROM, along with supraspinatus and external rotation strength were also significantly worse in the dysfunctional group. Similarly, these patients were more likely to have decreased ability to perform functional internal rotation tasks, with only 47% of the patients being able to reach the small of their back compared to 85% with normal subscapularis function. Radiographically, the dysfunctional cohort demonstrated higher rates of anterior subluxation (56% vs. 7%; P < .001) and glenoid loosening (24% vs. 5%; P = .004). Similarly, revision rates were significantly higher for patients with subscapularis dysfunction (8 patients, 23.5%). Nonetheless, the dysfunctional subscapularis cohort demonstrated improvements in VAS pain (4.0 ± 3.7) and ASES (46.4 ± 35.9) scores that exceeded MCID thresholds. CONCLUSION: Patients who develop subscapularis dysfunction after TSA have significantly worse PROMs, ROM, functional tasks of internal rotation, and radiographic outcomes, as well as increased rates of revision. Although patients show worse outcomes and high revision rates compared with their normal-functioning counterparts, these patients maintained improvement above MCID thresholds for pain and function at a mean 5-year follow-up.

Impact of humeral stem length on calcar resorption in anatomic total shoulder arthroplasty.

BACKGROUND: Use of standard-length anatomic total shoulder (TSA) humeral stems has been associated with high rates of medial calcar bone loss. Calcar bone loss has been attributed to stress shielding, debris-induced osteolysis, and undiagnosed infection. Short stem and canal-sparing humeral components may provide more optimal stress distribution and thus lower rates of calcar bone loss related to stress shielding. The purpose of this study is to determine whether implant length will affect the rate and severity of medial calcar resorption. METHODS: A retrospective review was performed on TSA patients treated with three different-length humeral implants (canal-sparing, short, and standard-length designs). Patients were matched 1:1:1 based on both gender and age (±4 years), resulting in 40 patients per cohort. Radiographic changes in medial calcar bone were evaluated and graded on a 4-point scale, from the initial postoperative radiographs to those at 3 months, 6 months, and 12 months. RESULTS: The presence of any degree of medial calcar resorption demonstrated an overall rate of 73.3% at one year. At 3 months, calcar resorption was observed in 20% of the canal-sparing cohort, while the short and standard designs demonstrated resorption in 55% and 52.5%, respectively (P = .002). At 12 months, calcar resorption was seen in 65% of the canal-sparing design, while both the short and standard designs had a 77.5% rate of resorption (P = .345). The severity of calcar resorption for the canal-sparing cohort was significantly lower at all time points when compared to the short stem (3 months, P = .004; 6 months, P = .003; 12 months, P = .004) and at 3 months when compared to the standard-length stem (P = .009). CONCLUSION: Patients treated with canal-sparing TSA humeral components have significantly lower rates of early calcar resorption with less severe bone loss when compared to patients treated using short and standard-length designs.

An overview of clinical machine learning applications in neurology.

Machine learning techniques for clinical applications are evolving, and the potential impact this will have on clinical neurology is important to recognize. By providing a broad overview on this growing paradigm of clinical tools, this article aims to help healthcare professionals in neurology prepare to navigate both the opportunities and challenges brought on through continued advancements in machine learning. This narrative review first elaborates on how machine learning models are organized and implemented. Machine learning tools are then classified by clinical application, with examples of uses within neurology described in more detail. Finally, this article addresses limitations and considerations regarding clinical machine learning applications in neurology.

Single-cell transcription mapping of murine and human mammary organoids responses to female hormones.

During female adolescence and pregnancy, rising levels of hormones result in a cyclic source of signals that control the development of mammary tissue. While such alterations are well understood from a whole-gland perspective, the alterations that such hormones bring to organoid cultures derived from mammary glands have yet to be fully mapped. This is of special importance given that organoids are considered suitable systems to understand cross species breast development. Here we utilized single-cell transcriptional profiling to delineate responses of murine and human normal breast organoid systems to female hormones across evolutionary distinct species. Collectively, our study represents a molecular atlas of epithelial dynamics in response to estrogen and pregnancy hormones.

Isolated effect of filler particle size on surface properties of experimental resin composites before and after toothbrush abrasion.

OBJECTIVE: This study aimed to isolate the relationship between filler size and the surface properties of roughness and gloss before and after toothbrush abrasion for experimental resin-based composites (RBCs) containing uniform spherical fillers. MATERIALS AND METHODS: Five experimental light-cured RBCs with different spherical filler sizes and three commercial RBCs were studied. Forty specimens were polished using silicon carbide papers. Gloss was measured after 0, 90, 180, and 360 min of simulated toothbrushing, and surface roughness was measured before and after 360 min of toothbrushing. Two-way ANOVA/Tukey's multiple comparison tests were used to compare the RBCs, and the correlation between particle size and surface roughness or gloss was also determined. RESULTS: After polishing and toothbrushing, RBCs with smaller fillers exhibited significantly higher gloss and lower surface roughness, and RBCs with larger fillers exhibited lower gloss and higher surface roughness. A significant correlation was found between filler particle size and gloss and surface roughness both before and after toothbrush abrasion. CONCLUSIONS: Gloss of RBCs containing fillers with larger particle sizes was significantly reduced. After toothbrushing abrasion, the surface roughness increased for all RBCs, except those containing the finest-sized fillers. The particle size of the filler is a critical determinant of the surface roughness and gloss of RBCs, after polishing and after toothbrushing. CLINICAL SIGNIFICANCE: Increased surface roughness caused by toothbrush abrasion reduces the gloss of resin-based composites. Resin-based composites containing finer fillers best maintain glossiness after routine tooth brushing.

The potential use of glycosyl-transferase inhibitors for targeted reduction of S. mutans biofilms in dental materials.

Streptococcus mutans is the primary oral caries-forming bacteria, adept at producing "sticky" biofilms via the synthesis of insoluble extracellular polysaccharides (EPS), catalyzed by glucosyltransferases (GTFs). To circumvent the use of broad-spectrum antibiotics to combat these bacteria, this study sought to modify existing EPS-targeting small molecules with the ultimate goal of producing anti-biofilm polymer surfaces specifically targeting S. mutans. To achieve this, a known GTF inhibitor (G43) was modified with methoxy or tetraethyleneglycol substitutions in different positions (nine derivatives, tested at 50-µM) to pinpoint potential sites for future methacrylate functionalization, and then assessed against single-species S. mutans biofilms. As expected, the compounds did not diminish the bacterial viability. In general, the compounds with methoxy substitution were not effective in reducing EPS formation, whereas the tetraethyleneglycol substitution (G43-C3-TEG) led to a decrease in the concentration of insoluble EPS, although the effect is less pronounced than for the parent G43. This aligns with the reduced GTF-C activity observed at different concentrations of G43-C3-TEG, as well as the consequent decrease in EPS formation, and notable structural changes. In summary, this study determined that G43-C3-TEG is non-bactericidal and can selectively reduce the biofilm formation, by decreasing the production of EPS. This molecule will serve to functionalize surfaces of materials to be tested in future research.

World Brain Day 2023 - Brain Health and Disability: "Leave no one behind".

Worldwide, the number of persons with disability is assumed to be around 1.3 billion. Although several definitions exist, such as the medical and social models, the social model has more holistic approaches and engulfs more aspects. Historically, many considerations were based on eugenics until the middle of the 20th century when a change of paradigm occurred, and disability has since been subject to many developments in the past decades. Previously dependent on mercy and good will, disability has now become a human right, and the implementation of this change is still ongoing. Neurological diseases contribute worldwide to a large proportion of disability and can be classified as reversible or permanent, by their time course, and by disease specific elements. Addtionally, neurological diseases are often accepted and managed differently across cultures and are exposed to variable degrees of stigma. The World Federation of Neurology (WFN) has initiated and continues to promote the concept of brain health, which has a wide range of inclusion and is best summarized in the World Health Organization paper (World Health Organization, 2022a). This concept is embedded in the Intersectoral Global Action Plan (IGAP) (World Health Organization, 2022b), which created a global tool to promote neurology, and the WFN is using this tool for the 2023 World Brain Day to promote and introduce the concept of disability.

Coaxial Placement of Balloon-Expandable and Self-Expanding Stents: Impact on Crush Resistance and Luminal Recovery in a Benchtop Model.

During endovascular interventions, coaxial deployment of stents may be required to preserve luminal gain. This study characterized in vitro the effect on crush resistance and postcompression recovery when 316L stainless steel balloon-expandable (BE) and laser-cut nitinol self-expanding (SE) venous stents were deployed coaxially. Various stent configurations were parallel-plate compressed from a fully expanded state to 50% diameter reduction (Criterion, Model 42; MTS, Eden Prairie, Minnesota) in a 37 °C ± 1 water bath. Coaxial deployments of SE stent inside BE stent and BE stent inside SE stent demonstrated higher crush resistances compared with each stent individually or their mathematical summation (analysis of variance P < .0001; pairwise comparison P < .01). The configuration of SE stent inside BE stent showed higher postcompression luminal recovery at 48.7% compared with that of BE stent inside SE stent at 27.5% (P = .0001). Coaxial deployment of SE stent inside BE stent may improve crush resistance and luminal recovery after compression in the appropriate clinical context.

Twelve tips for the pre-brief to promote psychological safety in simulation-based education.

It is recognised that simulation-based education can be stressful, and this can impact negatively on learning. A fundamental aspect of facilitating simulation is creating a safe educational environment. Edmondson's seminal work on creating psychological safety among interpersonal teams has been embraced by the healthcare simulation community. Psychological safety is an underpinning philosophy for creating simulation experiences in which learners can develop within a stimulating and challenging yet supportive social atmosphere. Through careful design and thoughtful delivery, the introductory phase of simulation, the pre-briefing, can effectively prepare learners for simulation, reduce learner anxiety, and promote psychological safety, to enhance learning experiences. These twelve tips provide guidance for conducting a pre-brief and promoting a psychologically safe environment for simulation-based education.

The Intersectoral Global Action Plan (IGAP): A unique opportunity for neurology across the globe.

The World Health Assembly (WHA) approved the Intersectoral Global Action Plan (IGAP) in 2022. This ambitious project, formally called the Intersectoral Global Action Plan for Epilepsy and Other Neurological Disorders, is a 10-year plan to enhance neurology implementation worldwide and to raise the status of brain health and neurology services for patients with neurological diseases. The IGAP has 5 important components: relation with policy makers, therapy, prophylaxis, research, and public health. The implementation of IGAP is a challenge, not only for the specialty of neurology but for the whole neurological community, encompassing patients, carers, healthcare providers, and the public. The lack of a unified definition of neurology and the great variety of health systems, as well as the dependency on socioeconomic status, will necessitate custom-made solutions in all regions.