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1.
Expert Opin Pharmacother ; 25(6): 727-742, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38808634

ABSTRACT

INTRODUCTION: The introduction of targeted therapy and immunotherapy has tremendously changed the clinical outcomes and prognosis of cancer patients. Despite innovative pharmacological therapies and improved radiotherapy (RT) techniques, patients continue to suffer from side effects, of which oral mucositis (OM) is still the most impactful, especially for quality of life. AREAS COVERED: We provide an overview of current advances in cancer pharmacotherapy and RT, in relation to their potential to cause OM, and of the less explored and more recent literature reports related to the best management of OM. We have analyzed natural/antioxidant agents, probiotics, mucosal protectants and healing coadjuvants, pharmacotherapies, immunomodulatory and anticancer agents, photobiomodulation and the impact of technology. EXPERT OPINION: The discovery of more precise pathophysiologic mechanisms of CT and RT-induced OM has outlined that OM has a multifactorial origin, including direct effects, oxidative damage, upregulation of immunologic factors, and effects on oral flora. A persistent upregulated immune response, associated with factors related to patients' characteristics, may contribute to more severe and long-lasting OM. The goal is strategies to conjugate individual patient, disease, and therapy-related factors to guide OM prevention or treatment. Despite further high-quality research is warranted, the issue of prevention is paramount in future strategies.


Subject(s)
Antineoplastic Agents , Chemoradiotherapy , Neoplasms , Quality of Life , Stomatitis , Humans , Stomatitis/prevention & control , Stomatitis/etiology , Stomatitis/drug therapy , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Antineoplastic Agents/adverse effects , Neoplasms/drug therapy , Neoplasms/radiotherapy , Molecular Targeted Therapy/adverse effects , Animals , Probiotics/therapeutic use , Probiotics/administration & dosage
2.
Nat Commun ; 15(1): 1968, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38438390

ABSTRACT

Stabilization of riverbanks by vegetation has long been considered necessary to sustain single-thread meandering rivers. However, observation of active meandering in modern barren landscapes challenges this assumption. Here, we investigate a globally distributed set of modern meandering rivers with varying riparian vegetation densities, using satellite imagery and statistical analyses of meander-form descriptors and migration rates. We show that vegetation enhances the coefficient of proportionality between channel curvature and migration rates at low curvatures, and that this effect wanes in curvier channels irrespective of vegetation density. By stabilizing low-curvature reaches and allowing meanders to gain sinuosity as channels migrate laterally, vegetation quantifiably affects river morphodynamics. Any causality between denser vegetation and higher meander sinuosity, however, cannot be inferred owing to more frequent avulsions in modern non-vegetated environments. By illustrating how vegetation affects channel mobility and floodplain reworking, our findings have implications for assessing carbon stocks and fluxes in river floodplains.

3.
J Plast Reconstr Aesthet Surg ; 91: 276-283, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38432085

ABSTRACT

BACKGROUND: The study aims to assess the safety and effectiveness of BoneTape™, a new resorbable bone fixation device, using a zygomatic fracture model in rabbits. METHODS: The study followed BoneTape™ samples and control (sham) groups over 2-, 6-, and 12-week periods post-zygomaticomaxillary (ZM) osteotomy and zygomaticofrontal (ZF) disarticulation. The osteotomized segments were analyzed for bone healing, inflammatory response, and tissue healing. µCT imaging and histological analysis were used to examine the axial alignment, offset, and quality of new bone formation. RESULTS: BoneTape™ samples demonstrated enhanced maintenance of the initial intraoperative positioning, reduced axial offset, and better alignment when compared with the control group, enabling stable bone healing under physiological loading conditions. Complete union was observed at 12-weeks in both groups. The BoneTape™ group experienced minimal immune and tissue reactions, classically associated with wound healing, and showed an increased number of giant cells at 6 and 12-weeks. CONCLUSION: BoneTape™ represents a promising advancement in osteosynthesis, demonstrating efficacy in maintaining stable zygomatic reconstruction and eliciting minimal immune response in a rabbit model. This study introduces BoneTape™ as a disruptive solution specifically designed for clinical application in cranio-maxillofacial fracture fixation, with the potential to eliminate the use of over-engineered solutions while offering benefits such as ease of application and fewer biologically disruptive steps.


Subject(s)
Skull Fractures , Zygomatic Fractures , Animals , Rabbits , Zygomatic Fractures/diagnostic imaging , Zygomatic Fractures/surgery , Internal Fixators , Fracture Fixation, Internal/methods , Skull Fractures/diagnostic imaging , Skull Fractures/surgery , Fracture Fixation , Bone Plates
4.
Plant Mol Biol ; 114(2): 21, 2024 Feb 18.
Article in English | MEDLINE | ID: mdl-38368585

ABSTRACT

Arbuscular mycorrhizal symbiosis (AM) is a beneficial trait originating with the first land plants, which has subsequently been lost by species scattered throughout the radiation of plant diversity to the present day, including the model Arabidopsis thaliana. To explore if elements of this apparently beneficial trait are still present and could be reactivated we generated Arabidopsis plants expressing a constitutively active form of Interacting Protein of DMI3, a key transcription factor that enables AM within the Common Symbiosis Pathway, which was lost from Arabidopsis along with the AM host trait. We characterize the transcriptomic effect of expressing IPD3 in Arabidopsis with and without exposure to the AM fungus (AMF) Rhizophagus irregularis, and compare these results to the AM model Lotus japonicus and its ipd3 knockout mutant cyclops-4. Despite its long history as a non-AM species, restoring IPD3 in the form of its constitutively active DNA-binding domain to Arabidopsis altered expression of specific gene networks. Surprisingly, the effect of expressing IPD3 in Arabidopsis and knocking it out in Lotus was strongest in plants not exposed to AMF, which is revealed to be due to changes in IPD3 genotype causing a transcriptional state, which partially mimics AMF exposure in non-inoculated plants. Our results indicate that molecular connections to symbiosis machinery remain in place in this nonAM species, with implications for both basic science and the prospect of engineering this trait for agriculture.


Subject(s)
Arabidopsis , Lotus , Arabidopsis/genetics , Symbiosis/genetics , Genotype , Agriculture , Biological Evolution , Lotus/genetics
5.
Plant Genome ; 17(1): e20429, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38243772

ABSTRACT

Circular RNAs (circRNAs) are covalently closed single-stranded RNAs, generated through a back-splicing process that links a downstream 5' site to an upstream 3' end. The only distinction in the sequence between circRNA and their linear cognate RNA is the back splice junction. Their low abundance and sequence similarity with their linear origin RNA have made the discovery and identification of circRNA challenging. We have identified almost 6000 novel circRNAs from Lotus japonicus leaf tissue using different enrichment, amplification, and sequencing methods as well as alternative bioinformatics pipelines. The different methodologies identified different pools of circRNA with little overlap. We validated circRNA identified by the different methods using reverse transcription polymerase chain reaction and characterized sequence variations using nanopore sequencing. We compared validated circRNA identified in L. japonicus to other plant species and showed conservation of high-confidence circRNA-expressing genes. This is the first identification of L. japonicus circRNA and provides a resource for further characterization of their function in gene regulation. CircRNAs identified in this study originated from genes involved in all biological functions of eukaryotic cells. The comparison of methodologies and technologies to sequence, identify, analyze, and validate circRNA from plant tissues will enable further research to characterize the function and biogenesis of circRNA in L. japonicus.


Subject(s)
Lotus , RNA, Circular , RNA, Circular/genetics , RNA, Circular/metabolism , Lotus/genetics , Lotus/metabolism , RNA , RNA Splicing , Gene Expression Regulation
6.
Ann Pharmacother ; 58(5): 494-500, 2024 May.
Article in English | MEDLINE | ID: mdl-37559251

ABSTRACT

BACKGROUND: Sprue-like enteropathy (SE) related to olmesartan use was first reported in 2012. In 2017, the manufacturer of Benicar paid $300 million for 2300 claims for olmesartan-related SE. OBJECTIVE: A study in 2019 suggested that SE was related to olmesartan and with the possibility of angiotensin receptor blocker (ARB) class effect. To further characterize this condition, our group examined reports of ARB-related SE to Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: All reports of ARB-related SE from January 2017 to December 2021 were downloaded from the FAERS database. Gastrointestinal adverse events including SE were reviewed. Reporter categories included physicians, pharmacists, other health care professionals, consumers, and attorneys. RESULTS: A total of 106 590 reports of ARB-related adverse effects were analyzed. Sprue-like enteropathy was identified in 4337 cases (4.1% of total reports). Of these, 4240 cases (98.0%) of ARB-related SE were reported in patients using products with olmesartan, and 97 cases of SE were reported for all other ARBs (eprosartan, losartan, telmisartan, irbesartan, valsartan, and candesartan). Reports of olmesartan-related SE increased rapidly in 2017, continued at a high rate in 2018 and 2019, and essentially stopped in 2020 and 2021. CONCLUSIONS AND RELEVANCE: Reports to FAERS for ARB-related SE are mostly related to olmesartan. There was a steep decline in reports of olmesartan-related SE following the lawsuit with potential of lawyer interference. There are reports of SE related to ARBs other than olmesartan, with increased physician awareness and the potential to discover a class effect with future studies.


Subject(s)
Celiac Disease , Hypertension , United States , Humans , Celiac Disease/chemically induced , Angiotensin Receptor Antagonists/adverse effects , United States Food and Drug Administration , Angiotensin-Converting Enzyme Inhibitors , Tetrazoles/adverse effects , Losartan , Hypertension/chemically induced , Antihypertensive Agents
7.
J Res Adolesc ; 34(1): 85-95, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37975498

ABSTRACT

Peer victimization can negatively impact emotion regulation in youth and is associated with harmful mental health outcomes. One protective factor against the impacts of peer victimization is a strong attachment to family and positive peer relationships. Given that pets are commonly seen as family members and that youth report turning to their pet for emotional comfort, companion animals could provide an avenue of support for youth experiencing victimization. A geographically diverse sample of 5725 adolescents in the United States from the Adolescent Brain Cognitive Development (ABCD) Study® was used to explore whether the relationship between peer victimization and emotion regulation was moderated by whether a pet lives in the home. Having a pet in the home did not moderate the relationship between peer victimization and emotion regulation; however, mean-level differences were present across types of household pet (i.e., youth with no pets, youth with at least one dog, and youth with non-dog pets). Participants who did not live with a companion animal showed higher levels of both maladaptive emotion regulation (expressive suppression) and adaptive emotion regulation (cognitive reappraisal), suggesting that having a pet might lower overall emotion regulation pathways regardless of adaptive directionality. Relational victimization was a significant predictor of expressive suppression regardless of whether there was a pet in the home, although overt victimization was not a predictor of either kind of emotion regulation. This research demonstrates the complex nature of human-animal relationships and suggests more research is needed to understand the nuanced relationship between pets, peer victimization, and emotion regulation.


Subject(s)
Crime Victims , Emotional Regulation , Humans , Adolescent , United States/epidemiology , Animals , Dogs , Pets , Emotions , Peer Group , Crime Victims/psychology
8.
R Soc Open Sci ; 10(11): 230750, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38026018

ABSTRACT

Animal activity patterns are highly variable and influenced by internal and external factors, including social processes. Quantifying activity patterns in natural settings can be challenging, as it is difficult to monitor animals over long time periods. Here, we developed and validated a machine-learning-based classifier to identify behavioural states from accelerometer data of wild spotted hyenas (Crocuta crocuta), social carnivores that live in large fission-fusion societies. By combining this classifier with continuous collar-based accelerometer data from five hyenas, we generated a complete record of activity patterns over more than one month. We used these continuous behavioural sequences to investigate how past activity, individual idiosyncrasies, and social synchronization influence hyena activity patterns. We found that hyenas exhibit characteristic crepuscular-nocturnal daily activity patterns. Time spent active was independent of activity level on previous days, suggesting that hyenas do not show activity compensation. We also found limited evidence for an effect of individual identity on activity, and showed that pairs of hyenas who synchronized their activity patterns must have spent more time together. This study sheds light on the patterns and drivers of activity in spotted hyena societies, and also provides a useful tool for quantifying behavioural sequences from accelerometer data.

9.
Nano Lett ; 23(21): 9760-9768, 2023 11 08.
Article in English | MEDLINE | ID: mdl-37669509

ABSTRACT

Collagen biomineralization is fundamental to hard tissue assembly. While studied extensively, collagen mineralization processes are not fully understood, with the majority of theories derived from electron microscopy (EM) under static, dehydrated, or frozen conditions, unlike the liquid phase environment where mineralization occurs. Herein, novel liquid transmission EM (TEM) strategies are presented, in which collagen mineralization was explored in liquid for the first time via TEM. Custom thin-film enclosures were employed to visualize the mineralization of reconstituted collagen fibrils in a calcium phosphate and polyaspartic acid solution to promote intrafibrillar mineralization. TEM highlighted that at early time points precursor mineral particles attached to collagen and progressed to crystalline mineral platelets aligned with fibrils at later time points. This aligns with observations from other techniques and validates the liquid TEM approach. This work provides a new liquid imaging approach for exploring collagen biomineralization, advancing toward understanding disease pathogenesis and remineralization strategies for hard tissues.


Subject(s)
Biomineralization , Collagen , Collagen/chemistry , Extracellular Matrix , Microscopy, Electron, Transmission , Minerals
11.
medRxiv ; 2023 Jun 12.
Article in English | MEDLINE | ID: mdl-37398208

ABSTRACT

Importance: Individuals whose chronic pain is managed with opioids are at high risk of developing an opioid use disorder. Large data sets, such as electronic health records, are required for conducting studies that assist with identification and management of problematic opioid use. Objective: Determine whether regular expressions, a highly interpretable natural language processing technique, could automate a validated clinical tool (Addiction Behaviors Checklist1) to expedite the identification of problematic opioid use in the electronic health record. Design: This cross-sectional study reports on a retrospective cohort with data analyzed from 2021 through 2023. The approach was evaluated against a blinded, manually reviewed holdout test set of 100 patients. Setting: The study used data from Vanderbilt University Medical Center's Synthetic Derivative, a de-identified version of the electronic health record for research purposes. Participants: This cohort comprised 8,063 individuals with chronic pain. Chronic pain was defined by International Classification of Disease codes occurring on at least two different days.18 We collected demographic, billing code, and free-text notes from patients' electronic health records. Main Outcomes and Measures: The primary outcome was the evaluation of the automated method in identifying patients demonstrating problematic opioid use and its comparison to opioid use disorder diagnostic codes. We evaluated the methods with F1 scores and areas under the curve - indicators of sensitivity, specificity, and positive and negative predictive value. Results: The cohort comprised 8,063 individuals with chronic pain (mean [SD] age at earliest chronic pain diagnosis, 56.2 [16.3] years; 5081 [63.0%] females; 2982 [37.0%] male patients; 76 [1.0%] Asian, 1336 [16.6%] Black, 56 [1.0%] other, 30 [0.4%] unknown race patients, and 6499 [80.6%] White; 135 [1.7%] Hispanic/Latino, 7898 [98.0%] Non-Hispanic/Latino, and 30 [0.4%] unknown ethnicity patients). The automated approach identified individuals with problematic opioid use that were missed by diagnostic codes and outperformed diagnostic codes in F1 scores (0.74 vs. 0.08) and areas under the curve (0.82 vs 0.52). Conclusions and Relevance: This automated data extraction technique can facilitate earlier identification of people at-risk for, and suffering from, problematic opioid use, and create new opportunities for studying long-term sequelae of opioid pain management.

12.
J Oral Maxillofac Surg ; 81(10): 1311-1318, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37480941

ABSTRACT

PURPOSE: Recent case reports highlight an association between osteonecrosis of the jaw (ONJ) and antitumor necrosis factor (anti-TNF) medications. Our study reviewed and described reports of anti-TNF associated ONJ reported to the United States of America's Food and Drug Administration Adverse Event Reporting System to explore this potential adverse drug reaction further. METHODS: Using the Food and Drug Administration Adverse Event Reporting System database, we identified reported cases of ONJ between 2010 and 2021. Cases were included in our study if they reported any prior or concomitant anti-TNF medication use. Additionally, only adults (age 18+) and reports from health-care professionals were included. Cases lacking subject age or gender were excluded. After duplicates were removed, a dataset was created and demographics were described including age, gender, and indication for use. Naranjo scoring was conducted to assess adverse drug reaction probability. Subject demographics were then separately described for cases without reported denosumab or bisphosphonate therapy history and compared to those with reported history or concomitant denosumab or bisphosphonate therapy. RESULTS: Over twenty thousand cases of ONJ were reported. Forty-four potential cases (0.22%) of anti-TNF medication-associated ONJ were identified and reviewed. Of these, female gender comprised 77.3% (35 cases) and there was an average age of 61.3 years ± 13.7 years. Twenty cases (45.5%) had no prior/concomitant bisphosphonate or denosumab therapy. Of these, 55% (11 cases) were female and the average age was 54.5 ± 17.3 years. Rheumatoid arthritis was the most frequent indication for use (5 cases, 25%) followed by inflammatory bowel disease (IBD) and psoriatic arthritis (4 cases each, 20%) in this cohort. CONCLUSIONS: Twenty potential cases of anti-TNF-associated ONJ without prior or concomitant medications known to be associated with ONJ were identified and described. Interestingly, male gender was more frequent and subjects were younger in these cases compared to those with prior/concomitant bisphosphonates or denosumab therapy. Naranjo scoring indicated a probable interaction for three cases. Further studies are needed to clarify the association of ONJ and anti-TNF therapy, including investigating potential mechanisms and reporting future cases with sufficient detail to assess possible confounding factors.

13.
Philos Trans R Soc Lond B Biol Sci ; 378(1883): 20220308, 2023 08 14.
Article in English | MEDLINE | ID: mdl-37381857

ABSTRACT

Individuals and societies are linked through a feedback loop of mutual influence. Demographic turnover shapes group composition and structure by adding and removing individuals, and social inheritance shapes social structure through the transmission of social traits from parents to offspring. Here I examine how these drivers of social structure feedback to influence individual outcomes. I explore these society-to-individual effects in systems with social inheritance of hierarchy position, as occur in many primates and spotted hyenas. Applying Markov chain models to empirical and simulated data reveals how demography and social inheritance interact to strongly shape individual hierarchy positions. In hyena societies, demographic processes-not status seeking-account for the majority of hierarchy dynamics and cause an on-average lifetime decline in social hierarchy position. Simulated societies clarify how social inheritance alters demographic effects-demographic processes cause hierarchy position to regress to the mean, but the addition of social inheritance modifies this pattern. Notably, the combination of social inheritance and rank-related reproductive success causes individuals to decline in rank over their lifespans, as seen in the hyena data. Further analyses explore how 'queens' escape this pattern of decline, and how variation in social inheritance generates variability in reproductive inequality. This article is part of the theme issue 'Evolutionary ecology of inequality'.


Subject(s)
Hyaenidae , Animals , Biological Evolution , Ecology , Inheritance Patterns , Demography
14.
J Adolesc ; 95(6): 1152-1167, 2023 08.
Article in English | MEDLINE | ID: mdl-37165514

ABSTRACT

INTRODUCTION: Relationships with companion animals have been associated with higher levels of prosocial behavior and lower levels of socioemotional difficulties for children and adolescents. Companion animals may be supportive of developing prosocial behavior in youth through practice with positive social interactions and the development of empathy and reciprocity skills. The goal of this study was to use a person-centered approach to investigate if living with a pet (including pet species) is associated with profiles of adolescent peer social behaviors (i.e., prosocial, aggressive), and size of their peer network. METHODS: This study used data from the Adolescent Brain Cognitive Development (ABCD) Study®, a large, nationally representative data set of American adolescents. RESULTS: In a cross-sectional sample of 5218 adolescents, we found that youth clustered into four different distinct profiles of peer social behavior. Female youth living with dogs were less likely to be in the High Aggression profile as compared to youth without pets or youth with other types of pets. However, having a pet was not associated with whether youth were in the profiles characterized by prosocial behaviors or size of peer network. CONCLUSIONS: Overall, future research should explore how gender intersects with companion animal interactions-both in terms of frequency of interactions as well as relationship quality/emotional attachment-as well as examine these relationships over time to assess causality.


Subject(s)
Adolescent Behavior , Pets , Humans , Female , Animals , Dogs , Adolescent , Cross-Sectional Studies , Social Behavior , Peer Group , Aggression/psychology , Adolescent Behavior/psychology
15.
J Prev Med Public Health ; 56(2): 190-195, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37055361

ABSTRACT

OBJECTIVES: Pregnancy complications, including pre-eclampsia, gestational diabetes (GDM), and perinatal mood and anxiety disorders (PMADs), impact long-term health. We compared the frequency of screening documentation for pregnancy complications versus a general medical history at well woman visits between providers in primary care and obstetrics and gynecology. METHODS: We conducted a retrospective cohort study of subjects with at least 1 prior birth who presented for a well woman visit in 2019-2020. Charts were reviewed for documentation of a general medical history (hypertension, diabetes, and mood disorders) versus screening for comparable obstetric complications (pre-eclampsia, GDM, and PMADs). The results were compared using the McNemar and chi-square tests as appropriate. RESULTS: In total, 472 encounters were identified, and 137 met the inclusion criteria. Across specialties, clinicians were significantly more likely to document general medical conditions than pregnancy complications, including hypertensive disorders (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.18 to 5.48), diabetes (OR, 7.67; 95% CI, 3.27 to 22.0), and mood disorders (OR, 10.5; 95% CI, 3.81 to 40.3). Obstetrics and gynecology providers were more likely to document any pregnancy history (OR, 4.50; 95% CI, 1.24 to 16.27); however, they were not significantly more likely to screen for relevant obstetric complications (OR, 2.49; 95% CI, 0.90 to 6.89). Overall, the rate of pregnancy complication documentation was low in primary care and obstetrics and gynecology clinics (8.8 and 19.0%, respectively). CONCLUSIONS: Obstetrics and gynecology providers more frequently documented a pregnancy history than those in primary care; however, the rate was low across specialties, and providers reported screening for clinically relevant complications less frequently than for general medical conditions.


Subject(s)
Diabetes, Gestational , Hypertension , Pre-Eclampsia , Pregnancy Complications , Pregnancy , Female , Humans , Pre-Eclampsia/prevention & control , Retrospective Studies , Pregnancy Complications/diagnosis , Pregnancy Complications/epidemiology , Diabetes, Gestational/diagnosis , Diabetes, Gestational/epidemiology , Hypertension/diagnosis , Primary Health Care
16.
BMC Pharmacol Toxicol ; 24(1): 15, 2023 03 06.
Article in English | MEDLINE | ID: mdl-36879299

ABSTRACT

BACKGROUND: Osteonecrosis of the jaw (ONJ) is a rare but serious adverse drug reaction (ADR) commonly associated with bisphosphonate and denosumab therapy. Prior research utilized an online, public FDA Adverse Event Reporting System (FAERS) Database to explore this ADR. This data identified and described several novel medications associated with ONJ. Our study aims to build upon the prior findings, reporting trends of medication induced ONJ over time and identifying newly described medications. METHODS: We searched the FAERS database for all reported cases of medication related osteonecrosis of the jaw (MRONJ) from 2010 to 2021. Cases lacking patient age or gender were excluded. Only adults (18 +) and reports from Healthcare Professions were included. Duplicate cases were removed. The top 20 medications were identified and described for April 2010-December 2014 and April 2015-January 2021. RESULTS: Nineteen thousand six hundred sixty-eight cases of ONJ were reported to the FAERS database from 2010-2021. 8,908 cases met inclusion criteria. 3,132 cases were from 2010-2014 and 5,776 cases from 2015-2021. Within the cases from 2010-2014, 64.7% were female and 35.3% were male, and the average age was 66.1 ± 11.1 years. Between 2015-2021, 64.3% were female and 35.7% were male, and the average age was 69.2 ± 11.5 years. Review of the 2010-2014 data identified several medications and drug classes associated with ONJ not previously described. They include lenalidomide, corticosteroids (prednisolone and dexamethasone), docetaxel and paclitaxel, letrozole, methotrexate, imatinib, and teriparatide. Novel drugs and classes described between 2015-2021 include palbociclib, pomalidomide, radium 223, nivolumab, and cabozantinib. DISCUSSION: While stricter inclusion criteria and removal of duplicate cases led to fewer overall identified cases of MRONJ when compared to prior research, our data represents a more reliable analysis of MRONJ reports to the FAERS database. Denosumab was the most frequently reported medication associated with ONJ. While unable to imply incidence rates from our data due to the nature of the FAERS database, our findings provide further description of the various medications associated with ONJ and elucidate patient demographics associated with the ADR. Additionally, our study identifies cases of several newly described drugs and drug classes that have not been previously described in literature.


Subject(s)
Denosumab , Osteonecrosis , United States/epidemiology , Adult , Humans , Female , Male , Middle Aged , Aged , Aged, 80 and over , United States Food and Drug Administration , Databases, Factual , Diphosphonates
17.
bioRxiv ; 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36945518

ABSTRACT

Arbuscular mycorrhizal symbiosis (AM) is a beneficial trait originating with the first land plants, which has subsequently been lost by species scattered throughout the radiation of plant diversity to the present day, including the model Arabidopsis thaliana. To explore why an apparently beneficial trait would be repeatedly lost, we generated Arabidopsis plants expressing a constitutively active form of Interacting Protein of DMI3, a key transcription factor that enables AM within the Common Symbiosis Pathway, which was lost from Arabidopsis along with the AM host trait. We characterize the transcriptomic effect of expressing IPD3 in Arabidopsis with and without exposure to the AM fungus (AMF) Rhizophagus irregularis, and compare these results to the AM model Lotus japonicus and its ipd3 knockout mutant cyclops-4. Despite its long history as a non-AM species, restoring IPD3 in the form of its constitutively active DNA-binding domain to Arabidopsis altered expression of specific gene networks. Surprisingly, the effect of expressing IPD3 in Arabidopsis and knocking it out in Lotus was strongest in plants not exposed to AMF, which is revealed to be due to changes in IPD3 genotype causing a transcriptional state which partially mimics AMF exposure in non-inoculated plants. Our results indicate that despite the long interval since loss of AM and IPD3 in Arabidopsis, molecular connections to symbiosis machinery remain in place in this nonAM species, with implications for both basic science and the prospect of engineering this trait for agriculture.

18.
Philos Trans R Soc Lond B Biol Sci ; 378(1874): 20220064, 2023 04 10.
Article in English | MEDLINE | ID: mdl-36802775

ABSTRACT

How individuals' prior experience and population evolutionary history shape emergent patterns in animal collectives remains a major gap in the study of collective behaviour. One reason for this is that the processes that can shape individual contributions to collective actions can happen over very different timescales from each other and from the collective actions themselves, resulting in mismatched timescales. For example, a preference to move towards a specific patch might arise from phenotype, memory or physiological state. Although providing critical context to collective actions, bridging different timescales remains conceptually and methodologically challenging. Here, we briefly outline some of these challenges, and discuss existing approaches that have already generated insights into the factors shaping individual contributions in animal collectives. We then explore a case study of mismatching timescales-defining relevant group membership-by combining fine-scaled GPS tracking data and daily field census data from a wild population of vulturine guineafowl (Acryllium vulturinum). We show that applying different temporal definitions can produce different assignments of individuals into groups. These assignments can then have consequences when determining individuals' social history, and thus the conclusions we might draw on the impacts of the social environment on collective actions. This article is part of a discussion meeting issue 'Collective behaviour through time'.


Subject(s)
Galliformes , Social Behavior , Animals , Mass Behavior , Social Environment , Longitudinal Studies
19.
Oral Dis ; 29(7): 2845-2853, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36458549

ABSTRACT

OBJECTIVES: Current methods for periodontal regeneration do not promote collagen fiber insertions into new bone and cementum. We used a pig wound model to screen different functionalized collagen membranes in promoting periodontal reattachment to root surfaces. METHODS: Treatment groups included (1) control with no membranes, (2) collagen-coated membranes, (3) membranes with insulin-like growth factor-1 (IGF-1), (4) membranes with amelotin, or (5) membranes attached with calcium phosphate cement (CPC), or with CPC combined with IGF-1. Flap procedures were performed on mandibular and maxillary premolars of each pig. RESULTS: Histomorphometric, micro-CT, and clinical measurements obtained at 4 and 12 weeks after surgery showed cementum formation on denuded roots and reformation of alveolar bone, indicating that the pig model can model healing responses in periodontal regeneration. Calcium phosphate cement simplified procedures by eliminating the need for sutures and improved regeneration of alveolar bone (p < 0.05) compared with other treatments. There was a reduction (p < 0.05) of PD only for the IGF group. Large observed variances between treatment groups indicated that a priori power analyses should be conducted to optimize statistical analysis. CONCLUSIONS: Pigs can model discrete elements of periodontal healing using collagen-based, functionalized membranes. Screening indicates that membrane anchorage with calcium phosphate cements improve regeneration of alveolar bone.


Subject(s)
Alveolar Bone Loss , Insulin-Like Growth Factor I , Animals , Swine , Bone Regeneration , Collagen , Dental Cementum , Calcium Phosphates/pharmacology , Guided Tissue Regeneration, Periodontal/methods , Periodontal Ligament , Alveolar Bone Loss/drug therapy
20.
Mil Med ; 188(11-12): 3309-3315, 2023 11 03.
Article in English | MEDLINE | ID: mdl-35880588

ABSTRACT

INTRODUCTION: The Military Health Care System trains approximately 1,500 resident physicians in over 100 specialties. In addition to requirements for their specific program, active duty military trainees must complete military-specific trainings that vary by the branch of service. Excessive training requirements could contribute to physician burnout and/or negatively affect patient care. Therefore, the objective of this study was to quantify the time active duty resident physicians dedicate to this training, stratified by the branch of service. MATERIALS AND METHODS: The study protocol was submitted to the Clinical Investigations Department at Naval Medical Center Portsmouth (Portsmouth, VA, USA) and deemed exempt from the Institutional Review Board review. We conducted a descriptive study in 2021 wherein lists of all training requirements were obtained from a military treatment facility in the Army, Navy, and Air Force supporting residency training. Individual requirements were reviewed and sorted into military-specific and general categories. Information was gathered on duration, frequency, and platform for applicable requirements. RESULTS: Residents are required to complete a mean of 17.2 hours of training annually, of which 11.2 hours were military-specific. This consisted of 50, 57, and 53 individual requirements for Army, Navy, and Air Force personnel, respectively. Army resident physicians had the greatest time burden of military-specific training at 14.8 hours/year, followed by the Air Force and Navy (10.2 and 8.7 hours/year, respectively). CONCLUSIONS: Annually, active duty resident physicians spend the equivalent of more than two work days completing additional training requirements on multiple platforms. Standardizing training requirements and platforms across the Military Health Care System and aligning required trainings with job responsibilities could free up additional time for patient care, potentially decreasing fatigue and burnout.


Subject(s)
Burnout, Professional , Internship and Residency , Military Personnel , Physicians , Humans , Education, Medical, Graduate/methods , Delivery of Health Care
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