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1.
Abdom Radiol (NY) ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38831073

ABSTRACT

As the use of cross-sectional abdominal and pelvic imaging has increased exponentially in the past several decades, incidental musculoskeletal findings have become commonplace. These are often unrelated to the indication for the examination and are frequently referred to as the "radiologist's blind spot" on these studies. The differential diagnosis for abnormalities of the paraspinal and pelvic musculature is, in many cases, quite different from the anterior abdominal wall muscles. Furthermore, due to their relatively deep location, pathology involving the former muscle groups is more likely to be clinically occult, often presenting only incidentally when the patient undergoes cross-sectional imaging. Effective treatment of diseases of these muscles is dependent on adherence to a diverse set of diagnostic and treatment algorithms. The purpose of this review article is to familiarize the radiologist with the unique pathology of these often-overlooked muscles of the abdomen and pelvis.

2.
Genet Med ; : 101145, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38836869

ABSTRACT

Myotonic dystrophy type 1 (DM1) is a form of muscular dystrophy causing progressive muscle loss and weakness. Although clinical features can manifest at any age, it is the most common form of muscular dystrophy with onset in adulthood. DM1 is an autosomal dominant condition, resulting from an unstable CTG expansion in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. The age of onset and the severity of the phenotype are roughly correlated with the size of the CTG expansion. Multiple methodologies can be used to diagnose affected individuals with DM1, including polymerase chain reaction, Southern blot, and triplet repeat-primed polymerase chain reaction. Recently, triplet repeat interruptions have been described, which may affect clinical outcomes of a fully-variable allele in DMPK. This document supersedes the Technical Standards and Guidelines for Myotonic Dystrophy originally published in 2009 and reaffirmed in 2015. It is designed for genetic testing professionals who are already familiar with the disease and the methods of analysis.

3.
J Neurooncol ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38837018

ABSTRACT

OBJECTIVE: Survivors of pediatric brain tumors (SPBT) are at risk for social deficits, fewer friendships, and poor peer relations. SPBT also experience reduced brain connectivity via microstructural disruptions to white matter from neurological insults. Research with other populations implicates white matter connectivity as a key contributor to poor social functioning. This case-controlled diffusion-weighted imaging study evaluated structural connectivity in SPBT and typically developing controls (TDC) and associations between metrics of connectivity and social functioning. METHODS: Diffusion weighted-imaging results from 19 SPBT and 19 TDC were analyzed using probabilistic white matter tractography. Survivors were at least 5 years post-diagnosis and 2 years off treatment. Graph theory statistics measured group differences across several connectivity metrics, including average strength, global efficiency, assortativity, clustering coefficient, modularity, and betweenness centrality. Analyses also evaluated the effects of neurological risk on connectivity among SPBT. Correlational analyses evaluated associations between connectivity and indices of social behavior. RESULTS: SPBT demonstrated reduced global connectivity compared to TDC. Several medical factors (e.g., chemotherapy, recurrence, multimodal therapy) were related to decreased connectivity across metrics of integration (e.g., average strength, global efficiency) in SPBT. Connectivity metrics were related to peer relationship quality and social challenges in the SPBT group and to social challenges in the total sample. CONCLUSIONS: Microstructural white matter connectivity is diminished in SPBT and related to neurological risk and peer relationship quality. Additional neuroimaging research is needed to evaluate associations between brain connectivity metrics and social functioning in SPBT.

4.
Support Care Cancer ; 32(7): 412, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842732

ABSTRACT

PURPOSE: Automated scalp cooling (ASC) is available to patients undergoing chemotherapy for breast cancer to decrease chemotherapy-induced alopecia. This study sought to elucidate patient and chemotherapy nursing perspectives on the ASC experience. METHODS: This is a survey-based study of chemotherapy nursing staff and patients with breast cancer regarding perceived efficacy, side effects, administration, support, and overall opinions of ASC. Chemotherapy nurses across a large, multi-regional tertiary healthcare system completed a one-time survey regarding their experiences in administering ASC. Breast cancer patients who utilized ASC were surveyed along with a control group who underwent alopecia-inducing chemotherapy without ASC use for comparison. RESULTS: The majority of nursing responses reported inadequate technical support, an increased burden of administering ASC compared to other clinical duties, and that they would not recommend ASC to a family member or friend. Patients who underwent ASC reported significantly less hair loss and were significantly less likely to shave their heads or wear a wig, but this did not translate into significant differences in body image or psychosocial wellbeing responses. Time investment was the most significant burden related to ASC. CONCLUSION: Patients using ASC reported significantly less hair loss compared to those not using ASC during alopecia-inducing breast cancer chemotherapy, but this did not translate to improved body image. The majority of chemotherapy nurses reported they lacked adequate support in administering ASC and would not recommend it. Enhanced nursing support may provide a means for improving the ASC experience for both nursing staff and patients.


Subject(s)
Alopecia , Antineoplastic Agents , Breast Neoplasms , Hypothermia, Induced , Scalp , Humans , Alopecia/chemically induced , Alopecia/prevention & control , Breast Neoplasms/drug therapy , Female , Middle Aged , Antineoplastic Agents/adverse effects , Adult , Hypothermia, Induced/methods , Aged , Surveys and Questionnaires , Attitude of Health Personnel
5.
J Pers Disord ; 38(3): 241-267, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38857161

ABSTRACT

Conceptual work integrating constructs from mainstream personality research (especially so-called "dark" traits) and clinical psychopathology research has been limited. Herein, we propose all socially and/or ethically aversive traits as "flavored" manifestations of the D factor of personality (D). We argue that the D framework provides the commonality of all aversive traits, including the aversive traits from the DSM-5 Alternative Model for Personality Disorders (AMPD), a more thorough theoretical foundation. Moreover, D covers aspects that are not captured by any of the aversive AMPD traits directly (e.g., greed), thus offering indications for possible expansions to the AMPD. We tested our predictions in two online studies (N = 1,781 and N = 2,006) using quota-representative samples of the German population regarding age and gender. Twelve aversive traits from mainstream personality research and eight aversive AMPD traits were assessed together with consequential behavior in an economic game. Analyses using structural equation modeling overall confirmed predictions.


Subject(s)
Personality Disorders , Personality , Humans , Female , Male , Adult , Middle Aged , Young Adult , Adolescent , Aged , Germany
6.
BMJ Open Qual ; 13(2)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858076

ABSTRACT

INTRODUCTION: Rapid response team (RRT) and code activation events occur relatively commonly in inpatient settings. RRT systems have been the subject of a significant amount of analysis, although this has been largely focused on the impact of RRT system implementation and RRT events on patient outcomes. There is reason to believe that the structured assessment of RRT and code events may be an effective way to identify opportunities for system improvement, although no standardised approach to event analysis is widely accepted. We developed and refined a protocolised system of RRT and code event review, focused on sustainable, timely and high value event analysis meant to inform ongoing improvement activities. METHODS: A group of clinicians with expertise in process and quality improvement created a protocolised analytic plan for rapid response event review, piloted and then iteratively optimised a systematic process which was applied to all subsequent cases to be reviewed. RESULTS: Hospitalist reviewers were recruited and trained in a methodical approach. Each reviewer performed a chart review to summarise RRT events, and collect specific variables for each case (coding). Coding was then reviewed for concordance, at monthly interdisciplinary group meetings and 'Action Items' were identified and considered for implementation. In any 12-month period starting in 2021, approximately 12-15 distinct cases per month were reviewed and coded, offering ample opportunities to identify trends and patterns. CONCLUSION: We have developed an innovative process for ongoing review of RRT-Code events. The review process is easy to implement and has allowed for the timely identification of high value improvement opportunities.


Subject(s)
Hospital Rapid Response Team , Quality Improvement , Humans , Hospital Rapid Response Team/standards , Hospital Rapid Response Team/statistics & numerical data , Hospital Rapid Response Team/trends
7.
Obes Surg ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918268

ABSTRACT

PURPOSE: Metabolic and bariatric surgery (MBS) is presently the most evidence-based, effective treatment of obesity. Nevertheless, only half of the eligible individuals who are referred for this procedure complete it. This study aims to investigate the association between social support and MBS completion, considering race and ethnicity. METHODS: In this prospective cohort study, 413 participants were enrolled between 2019 and 2022. Using the 19-item Brief Family Relationship Scale, which comprises three subscales (eight-item Cohesion subscale, four-item Expressiveness subscale, and seven-item Conflict subscale), the quality of family relationship functioning was assessed. Multivariable logistic regression models were used to determine the association between MBS completion and social support status, adjusting for variables including race, ethnicity, age, gender, body mass index, and insurance. RESULTS: The mean age of the sample was 47.55 years (SD 11.57), with 87% of the participants being female and 39% non-Hispanic White. Nearly 35% of participants (n = 145) completed MBS. Multivariable logistic regression analysis showed overall cohesion (adjusted odds ratio [aOR], 1.52 [95% CI, 1.15-2.00]; p = .003) and overall expressiveness (aOR, 1.58 [95% CI, 1.22-2.05]; p < .001) were associated with higher odds of pursuing MBS. There was no significant interaction between overall cohesion, expressiveness, conflict, and race/ethnicity (p = .61, p = .63, p = .25, respectively). CONCLUSION: The findings indicated that there is a link between family-based social support and MBS completion, regardless of race and ethnicity. Future research should continue to explore the complex interplay between family dynamics and MBS outcomes, considering cultural variations to enhance the effectiveness of obesity interventions within diverse communities.

8.
J Orthop Case Rep ; 14(6): 89-95, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38910980

ABSTRACT

Introduction: Osteochondromas are the most common benign tumors of the bone and can be sessile or pedunculated. Although osteochondromas are typically seen in the long bones, they are rarely seen in the small bones of the hand or foot. Verruca vulgaris, also known as the common wart, is one of the most common skin conditions presenting to physicians and must be distinguished either clinically or histologically from other hyperkeratotic conditions, including bone conditions such as bone tumors that can place pressure on the skin and cause callus formation that can mimic a wart or create skin deformity. A high index of suspicion for underlying bone mass or tumor should be entertained when evaluating patients for skin conditions, particularly of the hand or foot, with failure to improve with treatment. Case Report: This case report presents a 20-year-old male with a pedunculated osteochondroma of the left fourth distal phalanx with hyperkeratotic skin overlying the mass at the end of the toe. He was initially treated by a family doctor and podiatrist for verruca vulgaris for over 5 years with two treatments of liquid nitrogen cryotherapy and surgical excision of the mass when the treating podiatrist encountered bone and recommended radiographs. The family requested follow-up with our practice several days later after they were told the patient had a bone tumor. The patient requested surgical excision of the osteochondroma secondary to pain with activities and difficulties with his vocation as a pilot. Conclusion: All physicians must be mindful of an underlying bone tumor or mass in patients presenting with skin changes, particularly about the foot or hand. Knowledge that an underlying bone tumor can present as a verruca vulgaris may prevent a delay in diagnosis or unnecessary treatment when evaluating and treating a patient with a skin lesion. Fortunately, our case was a benign osteochondroma; a malignant tumor with a delay in diagnosis could lead to loss of limb or life.

9.
Urol Case Rep ; 55: 102762, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38911466

ABSTRACT

Penile strangulation secondary to utilization of a constrictive ring is a rare urologic emergency that requires urgent decompression to prevent prolonged vascular obstruction resulting in necrosis and gangrene. Current literature is mainly comprised of case presentations that focus on management in the acute setting via removal of the ring. Herein, we describe surgical management of a patient who presents in delayed fashion after self-removal of the constrictive ring. We discuss our penectomy-sparing technique of debridement and split thickness skin graft.

10.
J Pediatr Surg ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38914510

ABSTRACT

INTRODUCTION: Inguinal hernia repair (IHR) is a common pediatric operation performed via open or laparoscopic approaches. The objective of this survey study was to assess current approaches to IHR in a national sample of pediatric general surgeons. METHODS: A REDCap survey was distributed to all pediatric general surgeons at 21 US institutions in 2023. Descriptive statistics were used to analyze responses. RESULTS: The response rate was 70.0% (145/207) with median fellowship graduation year of 2011. Respondents reported they were primarily taught either an open (73.1%) or laparoscopic (6.9%) technique in fellowship, while 18.6% reported being taught both techniques equally. Overall, 60.7% of respondents reported currently performing both laparoscopic and open IHR, while 27.6% reported performing only open IHR and 11.7% reported performing only laparoscopic IHR. During unilateral open IHR, 75.8% of respondents check for and repair a contralateral inguinal hernia, most commonly by placing a laparoscope via the hernia sac (76.3%). Selective mesh use in adolescents was similar between laparoscopic and open repair approaches. For recurrent hernias, 37.2% of respondents indicated performing the approach that was not performed previously, while 38.6% and 22.8% indicated they routinely perform a laparoscopic or open approach, respectively, regardless of initial repair approach. CONCLUSION: Over two thirds of surgeons reported incorporating laparoscopic IHR into their practice despite nearly three-quarters of respondents indicating they were primarily taught an open approach in training. Training in laparoscopic IHR has been increasing over time, and respondents reported a wide variety of laparoscopic and open repair techniques. LEVEL OF EVIDENCE: IV.

11.
ACS Nano ; 18(25): 16151-16165, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38861479

ABSTRACT

Immune modulation through the intracellular delivery of nucleoside-modified mRNA to immune cells is an attractive approach for in vivo immunoengineering, with applications in infectious disease, cancer immunotherapy, and beyond. Lipid nanoparticles (LNPs) have come to the fore as a promising nucleic acid delivery platform, but LNP design criteria remain poorly defined, making the rate-limiting step for LNP discovery the screening process. In this study, we employed high-throughput in vivo LNP screening based on molecular barcoding to investigate the influence of LNP composition on immune tropism with applications in vaccines and systemic immunotherapies. Screening a large LNP library under both intramuscular (i.m.) and intravenous (i.v.) injection, we observed differential influences on LNP uptake by immune populations across the two administration routes, gleaning insight into LNP design criteria for in vivo immunoengineering. In validation studies, the lead LNP formulation for i.m. administration demonstrated substantial mRNA translation in the spleen and draining lymph nodes with a more favorable biodistribution profile than LNPs formulated with the clinical standard ionizable lipid DLin-MC3-DMA (MC3). The lead LNP formulations for i.v. administration displayed potent immune transfection in the spleen and peripheral blood, with one lead LNP demonstrating substantial transfection of splenic dendritic cells and another inducing substantial transfection of circulating monocytes. Altogether, the immunotropic LNPs identified by high-throughput in vivo screening demonstrated significant promise for both locally- and systemically-delivered mRNA and confirmed the value of the LNP design criteria gleaned from our screening process, which could potentially inform future endeavors in mRNA vaccine and immunotherapy applications.


Subject(s)
Lipids , Mice, Inbred C57BL , Nanoparticles , RNA, Messenger , Animals , Nanoparticles/chemistry , RNA, Messenger/genetics , Mice , Lipids/chemistry , High-Throughput Screening Assays , Female , Injections, Intramuscular , Dendritic Cells/immunology , Dendritic Cells/metabolism , Injections, Intravenous , Immunotherapy , Liposomes
12.
JCO Clin Cancer Inform ; 8: e2300174, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38870441

ABSTRACT

PURPOSE: The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors. METHODS: Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference standard benchmark. The Dice similarity coefficient (DSC) was primarily used as a metric for the comparisons. DSC was stratified into binary groups on the basis of structure-specific expert-derived interobserver variability (IOV) cutoffs. Generalized linear mixed-effects models using Bayesian estimation were used to investigate the association between demographic variables and the binarized DSC for each disease site. Variables with a highest density interval excluding zero were considered to substantially affect the outcome measure. RESULTS: Five hundred seventy-four, 110, 452, 112, and 48 segmentations were used for the breast, sarcoma, H&N, GYN, and GI cases, respectively. The median percentage of segmentations that crossed the expert DSC IOV cutoff when stratified by structure type was 55% and 31% for OARs and tumors, respectively. Regression analysis revealed that the structure being tumor-related had a substantial negative impact on binarized DSC for the breast, sarcoma, H&N, and GI cases. There were no recurring relationships between segmentation quality and demographic variables across the cases, with most variables demonstrating large standard deviations. CONCLUSION: Our study highlights substantial uncertainty surrounding conventionally presumed factors influencing segmentation quality relative to benchmarks.


Subject(s)
Bayes Theorem , Benchmarking , Radiation Oncologists , Humans , Benchmarking/methods , Female , Radiotherapy Planning, Computer-Assisted/methods , Neoplasms/epidemiology , Neoplasms/radiotherapy , Organs at Risk , Male , Radiation Oncology/standards , Radiation Oncology/methods , Demography , Observer Variation
13.
Kidney Int Rep ; 9(6): 1590-1600, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38899170

ABSTRACT

In the United States, kidney care payment models are migrating toward value-based care (VBC) models incentivizing quality of care at lower cost. Current kidney VBC models will continue through 2026. We propose a future transplant-inclusive VBC (TIVBC) model designed to supplement current models focusing on patients with advanced chronic kidney disease (CKD) and end-stage kidney disease (ESKD). The proposed TIVBC is structured as an episode-of-care model with risk-based reimbursement for "referral/evaluation/waitlisting" (REW, referencing kidney transplantation), "primary hospitalization to 180 days posttransplant," and "long-term graft survival." Challenges around organ acquisition costs, adjustments to quality metrics, and potential criticisms of the proposed model are discussed. We propose next steps in risk-adjustment and cost-prediction to develop as an end-to-end, TIVBC model.

14.
Brain ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916996

ABSTRACT

Lewy body dementia and Alzheimer's disease (AD) are leading causes of cognitive impairment, characterized by distinct but overlapping neuropathological hallmarks. Lewy body disease (LBD) is characterized by alpha-synuclein aggregates in the form of Lewy bodies as well as the deposition of extracellular amyloid plaques, with many cases also exhibiting neurofibrillary tangle (NFT) pathology. In contrast, Alzheimer's disease is characterized by amyloid plaques and neurofibrillary tangles. Both conditions often co-occur with additional neuropathological changes, such as vascular disease and TDP-43 pathology. To elucidate shared and distinct molecular signatures underlying these mixed neuropathologies, we extensively analyzed transcriptional changes in the anterior cingulate cortex, a brain region critically involved in cognitive processes. We performed bulk tissue RNAseq from the anterior cingulate cortex and determined differentially expressed genes (q-value < 0.05) in control (n = 81), Lewy body disease (n = 436), Alzheimer's disease (n = 53), and pathological amyloid cases consisting of amyloid pathology with minimal or no tau pathology (n = 39). We used gene set enrichment and weighted gene correlation network analysis (WGCNA) to understand the pathways associated with each neuropathologically defined group. Lewy body disease cases had strong up-regulation of inflammatory pathways and down-regulation of metabolic pathways. The Lewy body disease cases were further subdivided into either high Thal amyloid, Braak NFT, or low pathological burden cohorts. Compared to the control cases, the Lewy body disease cohorts consistently showed up-regulation for genes involved in protein folding and cytokine immune response, as well as down-regulation of fatty acid metabolism. Surprisingly, concomitant tau pathology within the Lewy body disease cases resulted in no additional changes. Some core inflammatory pathways were shared between Alzheimer's disease and Lewy body disease but with numerous disease-specific changes. Direct comparison of Lewy body disease cohorts versus Alzheimer's disease cases revealed strong enrichment of synaptic signaling, behavior, and neuronal system pathways. Females had a stronger response overall in both Lewy body and Alzheimer's disease, with several sex-specific changes. Overall, the results identify genes commonly and uniquely dysregulated in neuropathologically defined Lewy body disease and Alzheimer's disease cases, shedding light on shared and distinct molecular pathways. Additionally, the study underscores the importance of considering sex-specific changes in understanding the complex transcriptional landscape of these neurodegenerative diseases.

15.
J Affect Disord ; 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38897296

ABSTRACT

BACKGROUND: Sympathetic and blood pressure (BP) hyper-reactivity to stress may contribute to increased cardiovascular disease (CVD) risk in adults with major depressive disorder (MDD); however, whether this is evident in young adults with MDD without comorbid disease remains unclear. We hypothesized that acute stress-induced increases in muscle sympathetic nerve activity (MSNA) and BP would be exaggerated in young adults with MDD compared to healthy non-depressed young adults (HA) and that, in adults with MDD, greater symptom severity would be positively related to MSNA and BP reactivity. METHODS: In 28 HA (17 female) and 39 young adults with MDD of mild-to-moderate severity (unmedicated; 31 female), MSNA (microneurography) and beat-to-beat BP (finger photoplethysmography) were measured at rest and during the cold pressor test (CPT) and Stroop color word test (SCWT). RESULTS: There were no group differences in resting MSNA (p = 0.24). Neither MSNA nor BP reactivity to either the CPT [MSNA: ∆24 ±â€¯10 HA vs. ∆21 ±â€¯11 bursts/min MDD, p = 0.67; mean arterial pressure (MAP): ∆22 ±â€¯7 HA vs. ∆21 ±â€¯10 mmHg MDD, p = 0.46)] or the SCWT (MSNA: ∆-4 ±â€¯6 HA vs. ∆-5 ±â€¯8 bursts/min MDD, p = 0.99; MAP: ∆7 ±â€¯8 HA vs ∆9 ±â€¯5 mmHg MDD; p = 0.82) were different between groups. In adults with MDD, symptom severity predicted MAP reactivity to the CPT (ß = 0.78, SE = 0.26, p = 0.006), but not MSNA (p = 0.42). LIMITATIONS: The mild-to-moderate symptom severity reflects only part of the MDD spectrum. CONCLUSIONS: Neither sympathetic nor BP stress reactivity are exaggerated in young adults with MDD; however, greater symptom severity may amplify BP reactivity to stress, thereby increasing CVD risk.

16.
Science ; 384(6703): ado7082, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38935715

ABSTRACT

Prion disease is caused by misfolding of the prion protein (PrP) into pathogenic self-propagating conformations, leading to rapid-onset dementia and death. However, elimination of endogenous PrP halts prion disease progression. In this study, we describe Coupled Histone tail for Autoinhibition Release of Methyltransferase (CHARM), a compact, enzyme-free epigenetic editor capable of silencing transcription through programmable DNA methylation. Using a histone H3 tail-Dnmt3l fusion, CHARM recruits and activates endogenous DNA methyltransferases, thereby reducing transgene size and cytotoxicity. When delivered to the mouse brain by systemic injection of adeno-associated virus (AAV), Prnp-targeted CHARM ablates PrP expression across the brain. Furthermore, we have temporally limited editor expression by implementing a kinetically tuned self-silencing approach. CHARM potentially represents a broadly applicable strategy to suppress pathogenic proteins, including those implicated in other neurodegenerative diseases.


Subject(s)
Brain , DNA Methylation , Dependovirus , Epigenesis, Genetic , Gene Silencing , Histones , Prion Proteins , Animals , Dependovirus/genetics , Mice , Brain/metabolism , Prion Proteins/genetics , Prion Proteins/metabolism , Histones/metabolism , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA (Cytosine-5-)-Methyltransferases/genetics , Prion Diseases/genetics , Prion Diseases/metabolism , Humans , Transgenes
17.
Urol Clin North Am ; 51(3): 327-334, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38925735

ABSTRACT

Penile cancer is a rare cancer, where patients not only need to deal with the anxiety around a cancer diagnosis, but also manage the consequences of treatment on their self-esteem, body image, and intimate relationships. Many find it embarrassing and difficult to talk to family and friends. Due to this, changes in urination and other physical effects of treatment, many will withdraw from social activities too. Patients need psychosocial support and more needs to be done to address this unmet need. Holistic and multidisciplinary approaches in clinic, with access to counseling, may help patients adjust to their new situation.


Subject(s)
Penile Neoplasms , Psychosocial Support Systems , Humans , Male , Communication , Penile Neoplasms/complications , Penile Neoplasms/psychology , Penile Neoplasms/therapy , Social Interaction , Spouses/psychology , Suicide/psychology , Recurrence , Counseling
18.
J Control Release ; 371: 455-469, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38789090

ABSTRACT

The full potential of ionizable lipid nanoparticles (LNPs) as an in vivo nucleic acid delivery platform has not yet been realized given that LNPs primarily accumulate in the liver following systemic administration, limiting their success to liver-centric conditions. The engineering of LNPs with antibody targeting moieties can enable extrahepatic tropism by facilitating site-specific LNP tethering and driving preferential LNP uptake into receptor-expressing cell types via receptor-mediated endocytosis. Obstetric conditions stemming from placental dysfunction, such as preeclampsia, are characterized by overexpression of cellular receptors, including the epidermal growth factor receptor (EGFR), making targeted LNP platforms an exciting potential treatment strategy for placental dysfunction during pregnancy. Herein, an EGFR antibody-conjugated LNP (aEGFR-LNP) platform was developed by engineering LNPs with increasing densities of antibody functionalization. aEGFR-LNPs were screened in vitro in immortalized placental trophoblasts and in vivo in non-pregnant and pregnant mice and compared to non-targeted formulations for extrahepatic, antibody-targeted mRNA LNP delivery to the placenta. Our top performing LNP with an intermediate density of antibody functionalization (1:5 aEGFR-LNP) mediated a âˆ¼twofold increase in mRNA delivery in murine placentas and a âˆ¼twofold increase in LNP uptake in EGFR-expressing trophoblasts compared to non-targeted counterparts. These results demonstrate the potential of antibody-conjugated LNPs for achieving extrahepatic tropism, and the ability of aEGFR-LNPs in promoting mRNA delivery to EGFR-expressing cell types in the placenta.


Subject(s)
ErbB Receptors , Lipids , Nanoparticles , Placenta , RNA, Messenger , Female , Animals , ErbB Receptors/metabolism , Pregnancy , Placenta/metabolism , Nanoparticles/chemistry , RNA, Messenger/administration & dosage , Lipids/chemistry , Humans , Mice , Trophoblasts/metabolism , Liposomes
19.
Cureus ; 16(3): e57280, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38690491

ABSTRACT

This investigation explores the potential efficacy of machine learning algorithms (MLAs), particularly convolutional neural networks (CNNs), in distinguishing between benign and malignant breast cancer tissue through the analysis of 1000 breast cancer images gathered from Kaggle.com, a domain of publicly accessible data. The dataset was meticulously partitioned into training, validation, and testing sets to facilitate model development and evaluation. Our results reveal promising outcomes, with the developed model achieving notable precision (92%), recall (92%), accuracy (92%), sensitivity (89%), specificity (96%), an F1 score of 0.92, and an area under the curve (AUC) of 0.944. These metrics underscore the model's ability to accurately identify malignant breast cancer images. Because of limitations such as sample size and potential variations in image quality, further research, data collection, and integration of theoretical models in a real-world clinical setting are needed to expand the reliability and generalizability of these MLAs. Nonetheless, this study serves to highlight the potential use of artificial intelligence models as supporting tools for physicians to utilize in breast cancer detection.

20.
Pilot Feasibility Stud ; 10(1): 72, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715142

ABSTRACT

BACKGROUND: Treatment for anterior cruciate ligament (ACL) rupture may follow a surgical or nonsurgical pathway. At present, there is uncertainty around treatment choice. Two shared decision-making tools have been codesigned to support patients to make a decision about treatment following an ACL rupture. The shared decision-making tools include a patient information leaflet and an option grid. We report the protocol for a mixed-methods feasibility study, with nested qualitative interviews, to understand feasibility, acceptability, indicators of effectiveness and implementation factors of these shared decision-making tools (combined to form one shared decision-making intervention). METHODS: A single-centre non-randomised feasibility study will be conducted with 20 patients. Patients diagnosed with an ACL rupture following magnetic resonance imaging will be identified from an orthopaedic clinic. The shared decision-making intervention will be delivered during a clinical consultation with a physiotherapist. The primary feasibility outcomes include the following: recruitment rate, fidelity, acceptability and follow-up questionnaire completion. The secondary outcome is the satisfaction with decision scale. The nested qualitative interview will explore experience of using the shared decision-making intervention to understand acceptability, implementation factors and areas for further refinement. DISCUSSION: This study will determine the feasibility of using a newly developed shared decision-making intervention designed to support patients to make a decision about treatment of their ACL rupture. The acceptability and indicators of effectiveness will also be explored. In the long term, the shared decision-making intervention may improve service and patient outcomes and ensure cost-effectiveness for the NHS; ensuring those most likely to benefit from surgical treatment proceed along this pathway. TRIAL REGISTRATION: Pending registration on ISRCTN.

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