ABSTRACT
Long noncoding RNAs (lncRNAs) are sequences of 200 nucleotides or more that are transcribed from a large portion of the mammalian genome. While hypothesized to have a variety of biological roles, many lncRNAs remain largely functionally uncharacterized due to unique challenges associated with their investigation. For example, some lncRNAs overlap with other genomic loci, are expressed in a cell-type-specific manner, and/or are differentially processed at the post-transcriptional level. The mammalian CNS contains a vast diversity of lncRNAs, and lncRNAs are highly abundant in the mammalian brain. However, interrogating lncRNA function in models of the CNS, particularly in vivo, can be complex and challenging. Here we review the breadth of methods used to investigate lncRNAs in the CNS, their merits, and the understanding they can provide with respect to neurodevelopment and pathophysiology. We discuss remaining challenges in the field and provide recommendations to assay lncRNAs based on current methods.
Subject(s)
Brain , RNA, Long Noncoding , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Humans , Animals , Brain/metabolism , Brain/growth & development , Neurodevelopmental Disorders/geneticsABSTRACT
BACKGROUND: Spirituality is an important component of recovery for many individuals with substance use disorder (SUD). However, few studies have compared patient and physician attitudes on spirituality in SUD recovery. OBJECTIVE: This study investigates patient and physician beliefs about the role of spirituality in SUD recovery and about discussing spirituality in relationship to recovery in primary care settings. DESIGN: Semi-structured interviews were conducted with primary care physicians recruited at two academic hospitals, and patients recruited from a faith-based residential therapeutic community. Interview transcripts were independently coded by two researchers and a grounded theory approach was used to generate themes that reflected participants' experiences. KEY RESULTS: Interviews were conducted with 15 patients and 10 physicians. Patients had diverse views about the impact of spirituality on their SUD recovery, including positive, negative, and neutral. Patient and physician opinions on discussing spirituality in a primary care setting differed: most physicians felt positively towards this, believing that understanding their patients' spirituality helped them care for their patients as whole people. Many patients felt neutral, stating that they did not feel like these conversations were necessary for their care, and that they believed physicians preferred not to discuss spirituality in medical settings. Tolerance from both the patient and physician, open-ended questioning, and an individualized approach were identified as facilitators to effective discussions about spirituality and recovery. CONCLUSIONS: Spirituality can have diverse effects on an individual's SUD recovery. Physicians endorsed the benefits of discussing spirituality in the context of their patients' recovery, while patients expressed reservations about engaging in these conversations with their physicians. This variation in perspectives highlights the need for additional research to understand the individual and structural factors that contribute to it, as well as best practices for engaging in effective, non-judgmental conversations about spirituality in recovery.
ABSTRACT
The human genome is pervasively transcribed, producing a majority of short and long noncoding RNAs (lncRNAs) that can influence cellular programs through a variety of transcriptional and post-transcriptional regulatory mechanisms. The brain houses the richest repertoire of long noncoding transcripts, which function at every stage during central nervous system development and homeostasis. An example of functionally relevant lncRNAs is species involved in spatiotemporal organization of gene expression in different brain regions, which play roles at the nuclear level and in transport, translation, and decay of other transcripts in specific neuronal sites. Research in the field has enabled identification of the contributions of specific lncRNAs to certain brain diseases, including Alzheimer's disease, Parkinson's disease, cancer, and neurodevelopmental disorders, resulting in notions of potential therapeutic strategies that target these RNAs to recover the normal phenotype. Here, we summarize the latest mechanistic findings associated with lncRNAs in the brain, focusing on their dysregulation in neurodevelopmental or neurodegenerative disorders, their use as biomarkers for central nervous system (CNS) diseases in vitro and in vivo, and their potential utility for therapeutic strategies.
Subject(s)
Brain , Neurodegenerative Diseases , Neurodevelopmental Disorders , Neurogenesis , RNA, Long Noncoding , Humans , Brain/growth & development , Brain/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Neurogenesis/genetics , Gene Expression Regulation, Developmental , Neurodevelopmental Disorders/genetics , Neurodevelopmental Disorders/therapy , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/therapyABSTRACT
Racial, ethnic, and socioeconomic disparities in the major risk factors for vascular disease and access to vascular specialist care are well-documented.1-3 The higher incidence of diabetes, peripheral artery disease (PAD), and related nontraumatic lower extremity amputation among racial and ethnic minority groups, those of low socioeconomic status, and those with poor access to care based on geography (together, referred to below as disadvantaged groups) are particularly pervasive.1,4-9 Practitioners of vascular surgery and endovascular therapy are uniquely positioned to address health inequities in lower extremity screening, medical management, intervention, and limb preservation among the population of adults at the highest risk for limb loss.
Subject(s)
Ethnicity , Peripheral Arterial Disease , Adult , Humans , Empathy , Treatment Outcome , Minority Groups , Risk Factors , Lower Extremity/blood supply , Peripheral Arterial Disease/diagnostic imaging , Peripheral Arterial Disease/surgery , Risk Assessment , Amputation, Surgical , Limb SalvageABSTRACT
BACKGROUND: There has been an increasing focus on gender disparities in the medical field and in the field of vascular surgery specifically. We aimed to characterize gender representation in vascular surgery innovation over the past 10 years, using metrics of patents and National Institutes of Health (NIH) support. METHODS: We performed a retrospective review of all vascular-related patent filings (Google Scholar) and NIH-funded grants (NIH RePORTER) over a 10-year period (January 1st, 2012, to December 31st, 2021). Gender-API (Application Programming Interface) was used to identify the gender of the inventors, with manual confirmation of a 10% random sample. Gender representation for patent inventors and grant principal investigators (PIs) were compared using Chi-squared and Student's t-tests as appropriate. Yearly temporal changes in representation were analyzed using Wilcoxon signed-rank tests and linear regression analyses. RESULTS: We identified 2,992 unique vascular device patents with 6,093 associated inventors over 10 years. Women were underrepresented in patent authorship overall (11.5%), and were least likely to be listed as first inventor (8.9%) and most commonly fourth and fifth inventors (15.5% and 14.1%, respectively) compared to men. There was no significant change in representation of women inventors over time (-0.2% females per year, 95% confidence interval (CI) -0.54 to 0.10). We identified 1736 total unique NIH grants, with 23.8% of funded projects having women PIs. There was an increase in the proportion of women PIs over time (+1.31% per year, 95% CI 0.784 to 1.855; P < 0.001). Projects with women PIs received mean total awards that were significantly lower than projects with men PIs ($350,485 ± $220,072 vs. $451,493 ± $411,040; P < 0.001), but the overall ratio of funding:women investigators improved over time (+$11,531 per year, 95% CI $6,167 to $16,895; P = 0.0011). CONCLUSIONS: While we have made strides in increasing the number of women in the surgical research space, there is still room for improvement in funding parity. In addition, we found substantial and persistent room for improvement in representation of women in surgical innovation. As we enter a new frontier of surgery hallmarked by equalizing gender representation, these data should serve as a call-to-action for initiative aimed at rebuilding the foundation of surgical innovations upon equal gender representation.
Subject(s)
Biomedical Research , National Institutes of Health (U.S.) , Male , United States , Humans , Female , Treatment Outcome , Financing, Organized , Retrospective Studies , Vascular Surgical ProceduresABSTRACT
Unicornuate uterus with rudimentary horn is a rare structural uterine anomaly resulting from incomplete Mullerian duct development and/or fusion. Pregnancy in rudimentary horn is an uncommon presentation of a Mullerian anomaly and may lead to substantial morbidity and mortality due to high risk of uterine rupture with intraabdominal hemorrhage. Medical and/or surgical management may be undertaken; however, currently, no treatment guidelines exist. We describe the management of a 12-week rudimentary horn pregnancy in a 25-year-old multiparous patient with a prior spontaneous preterm breech vaginal delivery and one spontaneous early term cephalic vaginal delivery in whom this congenital uterine condition was previously unknown. The rudimentary horn, nonviable pregnancy, and contiguous ipsilateral fallopian tube were excised laparoscopically without complication. Given the infrequency of rudimentary horn pregnancies and the high risk for obstetric complications, a high index of suspicion should be maintained. We emphasize that a history of preterm birth or malpresentation should raise suspicion for maternal Mullerian anomaly, and that a minimally invasive approach can be feasible for treatment of a rudimentary horn pregnancy.
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INTRODUCTION: Transarterial radioembolization (TARE) is one of the most promising therapeutic options for hepatic masses. Radiomics features, which are quantitative numeric features extracted from medical images, are considered to have potential in predicting treatment response in TARE. This article aims to provide meta-analytic evidence and critically appraise the methodology of radiomics studies published in this regard. METHODS: A systematic search was performed on PubMed, Scopus, Embase, and Web of Science. All relevant articles were retrieved, and the characteristics of the studies were extracted. The Radiomics Quality Score and Checklist for Evaluation of Radiomics Research were used to assess the methodologic quality of the studies. Pooled sensitivity, specificity, and area under the receiver operating characteristic curve in predicting objective response were determined. RESULTS: The systematic review included 15 studies. The average Radiomics Quality Score of these studies was 11.4 ± 2.1, and the average Checklist for Evaluation of Radiomics Research score was 33± 6.7. There was a notable correlation (correlation coefficient = 0.73) between the two metrics. Adherence to quality measures differed considerably among the studies and even within different components of the same studies. The pooled sensitivity and specificity of the radiomics models in predicting complete or partial response were 83.5% (95% confidence interval 76%-88.9%) and 86.7% (95% confidence interval 78%-92%), respectively. CONCLUSION: Radiomics models show great potential in predicting treatment response in TARE of hepatic lesions. However, the heterogeneity seen between the methodologic quality of studies may limit the generalizability of the results. Future initiatives should aim to develop radiomics signatures using multiple external datasets and adhere to quality measures in radiomics methodology.
Subject(s)
Embolization, Therapeutic , Liver Neoplasms , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/radiotherapy , Embolization, Therapeutic/methods , Treatment Outcome , Radiopharmaceuticals , Sensitivity and Specificity , Predictive Value of Tests , RadiomicsABSTRACT
INTRODUCTION: Black and underinsured women in the United States are more likely than their counterparts to develop uterine fibroids (UFs) and experience more severe symptoms. Uterine artery embolization (UAE), a uterine-sparing therapeutic procedure, is less invasive than the common alternative, open hysterectomy. To determine whether demographic disparities persist in UF treatment utilization, we reviewed patient characteristics associated with UAE versus hysterectomy for UF among studies of US clinical practices. METHODS: A systematic literature review was conducted via PubMed, Embase, and CINAHL (PROSPERO CRD42023455051), yielding 1,350 articles (January 1, 1995, to July 15, 2023) that outlined demographic characteristics of UAE compared with hysterectomy. Two readers screened for inclusion criteria, yielding 13 full-text US-based comparative studies specifying at least one common demographic characteristic. Random effects meta-analysis was performed on the data (STATA v18.0). Egger's regression test was used to quantify publication bias. RESULTS: Nine (138,960 patients), four (183,643 patients), and seven (312,270 patients) studies were analyzed for race, insurance status, and age as predictors of treatment modality, respectively. Black race (odds ratio = 3.35, P < .01) and young age (P < .05) were associated with UAE, whereas private insurance (relative to Medicare and/or Medicaid) was not (odds ratio = 1.06, P = .52). Between-study heterogeneity (I2 > 50%) was detected in all three meta-analyses. Small-study bias was detected for age but not race or insurance. CONCLUSIONS AND IMPLICATIONS: Knowledge of demographic characteristics of patients with UFs receiving UAE versus hysterectomy is sparse (n = 13 studies). Among these studies, which seem to be racially well distributed, Black and younger women are more likely to receive UAE than their counterparts.
Subject(s)
Hysterectomy , Leiomyoma , Uterine Artery Embolization , Uterine Neoplasms , Female , Leiomyoma/therapy , Leiomyoma/surgery , Humans , Uterine Neoplasms/therapy , Uterine Neoplasms/surgery , United StatesABSTRACT
CONTEXT.: Spontaneous (nontraumatic) subdural hematomas have been reported yet have not been well studied. OBJECTIVE.: To identify the neuropathologic features of acute spontaneous SDHs (ASSDHs) and their associated medical conditions. DESIGN.: A retrospective study of 235 autopsy cases of SDH was conducted. Review of demographics, underlying medical conditions, and coagulation profile as well as gross and histopathologic examination of the brain and other organs were performed. RESULTS.: Among the 32 cases of ASSDH, 5 cases (15.6%) had severe hemorrhage and 4 (12.5%) demonstrated brain herniation. Twenty-two cases (68.8%) had concurrent but nonconnecting subarachnoid hemorrhage or intraparenchymal hemorrhage. The most common underlying medical condition was thrombocytopenia (n = 21; 65.6%), followed by immunosuppression (n = 15; 46.9), bloodstream infections or sepsis (n = 12; 37.5%), hypertension (n = 13; 40.6%), and coronary artery disease (n = 12; 37.5%). Many patients with thrombocytopenia or immunosuppression had underlying malignancies, with leukemia being the most common type (n = 11; 34.4%). The use of circulatory devices or hemodialysis was noted in a significant portion of ASSDH cases. In terms of coagulation factors, most of our ASSDH patients had normal prothrombin time and activated partial thromboplastin time, but abnormal platelet count and D-dimer levels. CONCLUSIONS.: ASSDHs can be severe and are often associated with subarachnoid hemorrhage and/or intraparenchymal hemorrhage. The causes of ASSDH are limited to certain underlying medical conditions that ultimately lead to bleeding tendency. Autopsies are helpful in determining the etiology. Given their association with abnormal platelet count, correcting platelet deficiencies is a potential preventive measure for ASSDHs.
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BACKGROUND: Postoperative stroke is a potentially devastating neurological complication following surgical revascularization for Moyamoya disease. We sought to evaluate whether peri-operative hemoglobin levels were associated with the risk of early post-operative stroke following revascularization surgery in adult Moyamoya patients. METHODS: Adult patients having revascularization surgeries for Moyamoya disease between 1999-2022 were identified through single institutional retrospective review. Logistic regression analysis was used to test for the association between hemoglobin drop and early postoperative stroke. RESULTS: In all, 106 revascularization surgeries were included in the study. A stroke occurred within 7 days after surgery in 9.4% of cases. There were no significant associations between the occurrence of an early postoperative stroke and patient age, gender, or race. Mean postoperative hemoglobin drop was greater in patients who suffered an early postoperative stroke compared with patients who did not (2.3±1.1 g/dL vs. 1.3±1.1 g/dL, respectively; P=0.034). Patients who experienced a hemoglobin drop post-operatively had 2.03 times greater odds (95% confidence interval, 1.06-4.23; P=0.040) of having a stroke than those whose hemoglobin levels were stable. Early postoperative stroke was also associated with an increase in length of hospital stay (P<0.001), discharge to a rehabilitation facility (P=0.014), and worse modified Rankin scale at 1 month (P=0.001). CONCLUSION: This study found a significant association between hemoglobin drop and early postoperative stroke following revascularization surgery in adult patients with Moyamoya disease. Based on our findings, it may be prudent to avoid hemoglobin drops in Moyamoya patients undergoing surgical revascularization.
ABSTRACT
Major nontraumatic lower extremity amputation (LEA) is a morbid complication of longstanding or poorly controlled diabetes and/or end-stage peripheral artery disease. Incidence of major LEAs consistently declined during the 1990s and 2000s, but rates have plateaued or increased in many regions during the past decade. Marked racial, ethnic, socioeconomic, and geographic disparities in risk of LEA persist and are related to inequalities in access to care and differential rates of attempted limb preservation. Multidisciplinary diabetic foot care (MDFC) is increasingly recognized as a necessary model for optimal management of patients with diabetic foot and vascular disease. This article reviews the role of MDFC in reducing major LEAs and the specific ways in which MDFC can mitigate disparities in care delivery and limb preservation outcomes. Access to MDFC among vulnerable populations remains a significant barrier to systematic reduction in major LEAs.
Subject(s)
Diabetes Mellitus , Diabetic Foot , Peripheral Arterial Disease , Humans , Diabetic Foot/diagnosis , Diabetic Foot/surgery , Amputation, Surgical , Lower Extremity/blood supply , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/surgery , IncidenceABSTRACT
BACKGROUND: Non-Hispanic Black (NHB) patients experience increased prevalence of stroke risk factors and stroke incidence compared with non-Hispanic White (NHW) patients. However, little is known about >90-day post-stroke functional outcomes following mechanical thrombectomy. OBJECTIVE: To describe patient characteristics, evaluate stroke risk factors, and analyze the adjusted impact of race on long-term functional outcomes to better identify and limit sources of disparity in post-stroke care. METHODS: We retrospectively reviewed 326 patients with ischemic stroke who underwent thrombectomy at two centers between 2019 and 2022. Race was self-reported as NHB, NHW, or non-Hispanic Other. Stroke risk factors, insurance status, procedural parameters, and post-stroke functional outcomes were collected. Good outcomes were defined as modified Rankin Scale score ≤2 and/or discharge disposition to home/self-care. To assess the impact of race on outcomes at 3-, 6-, and 12-months' follow-up, we performed univariate and multivariate logistic regression. RESULTS: Patients self-identified as NHB (42%), NHW (53%), or Other (5%). 177 (54.3%) patients were female; the median (IQR) age was 67.5 (59-77) years. The median (IQR) National Institutes of Health Stroke Scale score was 15 (10-20). On univariate analysis, NHB patients were more likely to have poor short- and long-term functional outcomes, which persisted on multivariate analysis as significant at 3 and 6 months but not at 12 months (3 months: OR=2.115, P=0.04; 6 months: OR=2.423, P=0.048; 12 months: OR=2.187, P=0.15). NHB patients were also more likely to be discharged to rehabilitation or hospice/death than NHW patients after adjusting for confounders (OR=1.940, P=0.04). CONCLUSIONS: NHB patients undergoing thrombectomy for ischemic stroke experience worse 3- and 6-month functional outcomes than NHW patients after adjusting for confounders. Interestingly, this disparity was not detected at 12 months. Future research should focus on identifying social determinants in the short-term post-stroke recovery period to improve parity in stroke care.
ABSTRACT
This quality improvement study describes the lack of diversity in trial leadership, especially in arterial disease device trials, and recommends action steps.