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1.
PM R ; 16(4): 347-355, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38529764

ABSTRACT

BACKGROUND: In National Collegiate Athletic Association (NCAA) soccer athletes, men have higher rates of hip and groin strains, whereas women have higher rates of knee ligament injuries. Strength imbalances of the hip and thigh, specifically in agonist-antagonist muscles, are known risk factors for these injuries. OBJECTIVE: To perform hip and thigh strength assessments in NCAA soccer players to evaluate for differences between genders and correlations with gender-specific injury patterns. DESIGN: With a handheld dynamometer, weight-normalized isometric strength of six muscle groups (hip abductors, hip adductors, hip flexors, hip extensors, knee flexors, knee extensors) was calculated in NCAA soccer players. The strength ratio of each agonist-antagonist muscle was also calculated (hip abductors/adductors, hip flexors/extensors, knee extensors/flexors). PARTICIPANTS: Thirty-six NCAA soccer players (18 men, 18 women) from a single NCAA Division III institution. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Weight-normalized strength of six muscle groups and their agonist-antagonist strength ratios were compared between genders using linear mixed-effects models. RESULTS: Compared with male players, female players had decreased weight-normalized strength for hip abduction (0.170 vs. 0.204, p = .012) and hip extension (0.172 vs. 0.211, p = .021). Otherwise, weight-normalized strength was similar between genders. When comparing agonist-antagonist strength ratios, there was a significant difference between female and male players for hip flexion:extension (1.70 vs. 1.35, p = .008), whereas the hip abduction: adduction ratio did not reach statistical significance (1.45 vs. 1.62, p = .080). CONCLUSIONS: NCAA male and female soccer players had different hip strength profiles that fit their injury patterns. Male NCAA soccer players have higher rates of hip and groin strains, and men in the cohort had strength ratios that were deficient in the hip flexors and adductors compared with women. Female NCAA soccer players have higher rates of knee sprains and anterior cruciate ligament tears, and women in the cohort had strength ratios that were deficient in the hip abductors and extensors, which function to stabilize the knee. These strength disparities could be the focus of future gender-specific soccer injury prevention programs.


Subject(s)
Athletic Injuries , Soccer , Sprains and Strains , Humans , Male , Female , Soccer/injuries , Athletic Injuries/epidemiology , Lower Extremity , Universities , Muscle Strength
2.
Pathol Res Pract ; 254: 155097, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38277745

ABSTRACT

Exosomes are nanometric membrane vesicles of late endosomal origin that are released by most, if not all, cell types as a sophisticated means of intercellular communication. They play an essential role in the movement of materials and information between cells, transport a variety of proteins, lipids, RNA, and other vital data, and over time, they become an essential part of the drug delivery system and a marker for the early detection of many diseases. Dendritic cells have generated interest in cancer immunotherapy due to their ability to initiate and modify effective immune responses. Apart from their cytokine release and direct interactions with other cell types, DCs also emit nanovesicles, such as exosomes, that contribute to their overall activity. Numerous studies have demonstrated exosomes to mediate and regulate immune responses against cancers. Dendritic cell-derived exosomes (DCs) have attracted a lot of attention as immunotherapeutic anti-cancer treatments since it was found that they contain functional MHC-peptide complexes along with a variety of other immune-stimulating components that together enable immune cell-dependent tumor rejection. By enhancing tumor and immunosuppressive immune cells or changing a pro-inflammatory milieu to inhibit tumor advancement, exosomes generated from dendritic cells can initiate and support tumor growth. This study reviewed the immunogenicity of dendritic cell-derived exosomes and strategies for expanding their immunogenic potential as novel and effective anti-cancer therapies.


Subject(s)
Exosomes , Neoplasms , Humans , Exosomes/genetics , Dendritic Cells , Neoplasms/pathology , Immunity , Immunotherapy
3.
Pathol Res Pract ; 253: 154999, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38118218

ABSTRACT

It is becoming more and more apparent that many of the genetic alterations associated with cancer are located in areas that do not encode proteins. lncRNAs are a class of RNAs that do not code for proteins but play a crucial role in maintaining cell function and regulating various cellular processes. By doing this, they have recently introduced what may be a brand-new and essential layer of biological control. These have more than 200 nucleotides and are linked to several diseases; as a result, they have become potential tools for therapeutic intervention. Emerging technologies suggest the presence of mutations on genomic loci that give rise to lncRNAs rather than proteins in a disease as complex as cancer. These lncRNAs play essential parts in gene regulation, which impacts several cellular homeostasis processes, including proliferation, survival, migration, and genomic stability. The leading cause of death in the world today is cancer. Delays in diagnosis and a lack of standard and efficient treatments are the leading causes of the high death rate. Clinically, surgery is frequently used successfully to remove cancers that have not spread, but it is less successful in treating metastatic cancer, which has a drastically lower chance of survival. Chemotherapeutic drugs are a typical therapy to treat the cancer that has spread to other organs. Drug resistance to chemotherapy, however, presents a significant challenge to achieving positive outcomes and is frequently the cause of treatment failure. A substantial barrier to progress in medical oncology is cancer drug resistance. Resistance can develop clinically either before or after cancer treatment. According to this study, lncRNAs influence drug resistance through several different methods. LncRNAs often impact drug resistance by controlling the expression of a few intermediary regulatory variables rather than by directly affecting drug resistance. Additionally, lncRNAs have a variety of roles in cancer medication resistance. Most lncRNAs induce drug resistance when overexpressed; however, other lncRNAs have inhibitory effects. This study provides an overview of the current understanding of lncRNAs, relevance to cancer, and potential therapeutic applications.


Subject(s)
Neoplasms , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Signal Transduction/genetics
4.
Gastrointest Endosc ; 98(6): 953-964, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37473969

ABSTRACT

BACKGROUND AND AIMS: Data on how to teach endosonographers needle-based confocal laser endomicroscopy (nCLE)-guided histologic diagnosis of pancreatic cystic lesions (PCLs) are limited. Hence, we developed and tested a structured educational program to train early-career endosonographers in nCLE-guided diagnosis of PCLs. METHODS: Twenty-one early-career nCLE-naïve endosonographers watched a teaching module outlining nCLE criteria for diagnosing PCLs. Participants then reviewed 80 high-yield nCLE videos, recorded diagnoses, and received expert feedback (phase 1). Observers were then randomized to a refresher feedback session or self-learning at 4 weeks. Eight weeks after training, participants independently assessed the same 80 nCLE videos without feedback and provided histologic predictions (phase 2). Diagnostic performance of nCLE to differentiate mucinous versus nonmucinous PCLs and to diagnose specific subtypes were analyzed using histopathology as the criterion standard. Learning curves were determined using cumulative sum analysis. RESULTS: Accuracy and diagnostic confidence for differentiating mucinous versus nonmucinous PCLs improved as endosonographers progressed through nCLE videos in phase 1 (P < .001). Similar trends were observed with the diagnosis of PCL subtypes. Most participants achieved competency interpreting nCLE, requiring a median of 38 assessments (range, 9-67). During phase 2, participants independently differentiated PCLs with high accuracy (89%), high confidence (83%), and substantial interobserver agreement (κ = .63). Accuracy for nCLE-guided PCL subtype diagnoses ranged from 82% to 96%. The learned nCLE skills did not deteriorate at 8 weeks and were not impacted by a refresher session. CONCLUSIONS: We developed a practical, effective, and durable educational intervention to train early-career endosonographers in nCLE-guided diagnosis of PCLs.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Pancreatic Cyst , Humans , Prospective Studies , Microscopy, Confocal , Pancreatic Cyst/diagnostic imaging , Pancreatic Cyst/pathology , Lasers
5.
J Gen Intern Med ; 38(14): 3252-3256, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37407762

ABSTRACT

BACKGROUND: Arts-and-humanities-based interventions are commonly implemented in medical education to promote well-being and mitigate the risk of burnout. However, mechanisms for achieving these effects remain uncertain within graduate medical education. The emerging field of the positive humanities offers a lens to examine whether and how arts-based interventions support well-being in internal medicine interns. AIM: Through program evaluation of this visual art workshop, we used a positive humanities framework to elucidate potential mechanisms by which arts-based curricula support well-being in internal medicine interns. SETTING: We launched the re-FRAME workshop at the Philadelphia Museum of Art in winter 2020. PARTICIPANTS: Fifty-six PGY-1 trainees from one internal medicine residency program. PROGRAM DESCRIPTION: The 3-h re-FRAME workshop consisted of an introductory session on emotional processing followed by two previously described arts-based interventions. PROGRAM EVALUATION: Participants completed an immediate post-workshop survey (91% response rate) assessing attitudes towards the session. Analysis of open-ended survey data demonstrated 4 categories for supporting well-being among participants: becoming emotionally aware/expressive through art, pausing for reflection, practicing nonjudgmental observation, and normalizing experiences through socialization. DISCUSSION: Our project substantiated proposed mechanisms from the positive humanities for supporting well-being-including reflectiveness, skill acquisition, socialization, and expressiveness-among medical interns.


Subject(s)
Education, Medical , Humanities , Humans , Humanities/education , Curriculum , Education, Medical, Graduate , Burnout, Psychological
6.
World Neurosurg ; 174: 119-125, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36894002

ABSTRACT

BACKGROUND: Low back pain (LBP) is a common cause of disability worldwide; multiple causes and risk factors have been proposed in the genesis of back pain. Some studies reported an association between diastasis recti abdominis (DRA), a surrogate for decreased core strength muscle, and low back pain. We aimed to investigate the relationship between DRA and LBP through a systematic review. METHODS: A systematic review of the literature of clinical studies in English literature was conducted. PubMed, Cochrane, and Embase databases were used to conduct the search up to January 2022. The strategy included the following keywords: "Lower Back Pain" AND "Diastasis Recti" OR "Rectus abdominis" OR "abdominal wall" OR "paraspinal musculature". RESULTS: From 207 records initially found, 34 were suitable for full review. Thirteen studies were finally included in this review, with a total of 2,820 patients. Five studies found a positive association between DRA and LBP (5 of 13 = 38.5%) whereas 8 studies did not find any association between DRA and LBP (8 of 13 = 61.5%). CONCLUSIONS: Of the studies included in this systematic review, 61.5% did not find an association between DRA and LBP whereas a positive correlation was observed in 38.5% of studies included. Based on the quality of the studies included in our review, better studies are warranted to understand the association between DRA and LBP.


Subject(s)
Abdominal Wall , Diastasis, Muscle , Low Back Pain , Humans , Rectus Abdominis , Low Back Pain/epidemiology , Low Back Pain/etiology , Diastasis, Muscle/complications , Muscle Strength
7.
NPJ Biofilms Microbiomes ; 7(1): 87, 2021 12 08.
Article in English | MEDLINE | ID: mdl-34880222

ABSTRACT

Bacterial biofilms represent a challenge to the healthcare system because of their resilience against antimicrobials and immune attack. Biofilms consist of bacterial aggregates embedded in an extracellular polymeric substance (EPS) composed of polysaccharides, nucleic acids and proteins. We hypothesised that carbohydrates could contribute to immune recognition of Pseudomonas aeruginosa biofilms by engaging C-type lectins. Here we show binding of Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN, CD209), mannose receptor (MR, CD206) and Dectin-2 to P. aeruginosa biofilms. We also demonstrate that DC-SIGN, unlike MR and Dectin-2, recognises planktonic P. aeruginosa cultures and this interaction depends on the presence of the common polysaccharide antigen. Within biofilms DC-SIGN, Dectin-2 and MR ligands appear as discrete clusters with dispersed DC-SIGN ligands also found among bacterial aggregates. DC-SIGN, MR and Dectin-2 bind to carbohydrates purified from P. aeruginosa biofilms, particularly the high molecular weight fraction (HMW; >132,000 Da), with KDs in the nM range. These HMW carbohydrates contain 74.9-80.9% mannose, display α-mannan segments, interfere with the endocytic activity of cell-associated DC-SIGN and MR and inhibit Dectin-2-mediated cellular activation. In addition, biofilm carbohydrates reduce the association of the DC-SIGN ligand Lewisx, but not fucose, to human monocyte-derived dendritic cells (moDCs), and alter moDC morphology without affecting early cytokine production in response to lipopolysaccharide or P. aeruginosa cultures. This work identifies the presence of ligands for three important C-type lectins within P. aeruginosa biofilm structures and purified biofilm carbohydrates and highlights the potential for these receptors to impact immunity to P. aeruginosa infection.


Subject(s)
Mannose Receptor , Pseudomonas aeruginosa , Biofilms , Carbohydrates , Dendritic Cells , Extracellular Polymeric Substance Matrix , Humans , Lectins, C-Type
8.
J Subst Abuse Treat ; 126: 108331, 2021 07.
Article in English | MEDLINE | ID: mdl-34116809

ABSTRACT

BACKGROUND: The treatment gap for alcohol use disorders (AUD) in India is the highest among all mental health and substance use disorders. Despite evidence of the cost effectiveness of brief interventions (BIs) for hazardous drinking, implementation in low- and middle-income countries (LMICs) is rare due to several human resource-related barriers. This paper describes the processes and outputs of a study aimed at systematically developing a mobile phone-delivered BI to overcome such barriers. METHODS: This is a mixed methods study with four steps: (1) Review of existing relevant evidence base by extracting data from studies cited in two recent, relevant and high-quality systematic reviews; (2) In-depth interviews (IDIs) with 11 national experts in addictions research and practice, and 22 hazardous drinkers; (3) Delphi survey (2 rounds) to identify components for the intervention package through consensus building; and (4) Content and intervention development workshops with a range of stakeholders to develop the intervention package. RESULTS: The research team sourced 72 journal articles from two selected systematic reviews. Key content areas extracted from the studies included facts and statistics about health related to drinking behavior, self-reflection, goal-setting messages, motivational messages, and skills to manage risky situations. The IDIs with experts and hazardous drinkers endorsed most of these content areas as well. The Delphi survey achieved consensus on 19 content areas, which included targeted recommendations, personalized feedback and information, goal management, and coping skills. The content and intervention development workshops resulted in an intervention package delivered over 8 weeks, with the following seven themes guiding the content of the weekly messages: safe drinking/health education, alcohol reduction, drinking and risk management, drinking alternatives, situational content, urge management, and maintenance and relapse prevention. CONCLUSION: The research team designed this study to consider contextual factors while developing the intervention, which is important to ensure acceptability and feasibility of the intervention. Interestingly, the contextually informed intervention components had several commonalities with BIs developed and tested in high-income countries.


Subject(s)
Alcoholism , Cell Phone , Alcohol Drinking , Crisis Intervention , Humans , India
9.
Surg Endosc ; 35(12): 7027-7033, 2021 12.
Article in English | MEDLINE | ID: mdl-33433676

ABSTRACT

INTRODUCTION: Sleeve gastrectomy (SG) is the commonest bariatric procedure worldwide. Yet there is significant variation in practice concerning its various aspects. This paper report results from the first modified Delphi consensus-building exercise on SG. METHODS: We established a committee of 54 globally recognized opinion makers in this field. The committee agreed to vote on several statements concerning SG. An agreement or disagreement amongst ≥ 70.0% experts was construed as a consensus. RESULTS: The committee achieved a consensus of agreement (n = 71) or disagreement (n = 7) for 78 out of 97 proposed statements after two rounds of voting. The committee agreed with 96.3% consensus that the characterization of SG as a purely restrictive procedure was inaccurate and there was 88.7% consensus that SG was not a suitable standalone, primary, surgical weight loss option for patients with Barrett's esophagus (BE) without dysplasia. There was an overwhelming consensus of 92.5% that the sleeve should be fashioned over an orogastric tube of 36-40 Fr and a 90.7% consensus that surgeons should stay at least 1 cm away from the angle of His. Remarkably, the committee agreed with 81.1% consensus that SG patients should undergo a screening endoscopy every 5 years after surgery to screen for BE. CONCLUSION: A multinational team of experts achieved consensus on several aspects of SG. The findings of this exercise should help improve the outcomes of SG, the commonest bariatric procedure worldwide, and guide future research on this topic.


Subject(s)
Gastric Bypass , Obesity, Morbid , Consensus , Delphi Technique , Gastrectomy , Humans , Obesity, Morbid/surgery , Retrospective Studies , Treatment Outcome , Weight Loss
10.
Obes Surg ; 31(1): 451-456, 2021 01.
Article in English | MEDLINE | ID: mdl-32740826

ABSTRACT

The purpose of this study was to achieve consensus amongst a global panel of expert bariatric surgeons on various aspects of resuming Bariatric and Metabolic Surgery (BMS) during the Coronavirus Disease-2019 (COVID-19) pandemic. A modified Delphi consensus-building protocol was used to build consensus amongst 44 globally recognised bariatric surgeons. The experts were asked to either agree or disagree with 111 statements they collectively proposed over two separate rounds. An agreement amongst ≥ 70.0% of experts was construed as consensus as per the predetermined methodology. We present here 38 of our key recommendations. This first global consensus statement on the resumption of BMS can provide a framework for multidisciplinary BMS teams planning to resume local services as well as guide future research in this area.


Subject(s)
Bariatric Surgery , COVID-19 , Consensus , Delphi Technique , Humans , Obesity, Morbid/surgery , Pandemics , SARS-CoV-2
11.
Br Dent J ; 229(6): 355-360, 2020 09.
Article in English | MEDLINE | ID: mdl-32978578

ABSTRACT

The rates of oropharyngeal squamous cell carcinoma have continued to rise secondary to the increasing prevalence of the human papillomavirus (HPV). HPV-related disease is typically found in younger patients who do not have the traditional risk factors for malignancy. General dental practitioners (GDPs) often examine patients regularly and may therefore have an opportunity to identify oropharyngeal malignancies at an early stage. However, many GDPs are unfamiliar with oropharyngeal anatomy, pathology and clinical examination. This review summarises the key points in identifying patients with oropharyngeal malignancy who necessitate urgent referral.


Subject(s)
Alphapapillomavirus , Oropharyngeal Neoplasms , Papillomavirus Infections , Dentists , Humans , Oropharyngeal Neoplasms/diagnosis , Oropharyngeal Neoplasms/epidemiology , Papillomaviridae , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Professional Role
12.
Violence Against Women ; 26(8): 787-802, 2020 06.
Article in English | MEDLINE | ID: mdl-31066342

ABSTRACT

This mixed-methods study uses baseline data from a program evaluation in the Democratic Republic of Congo to examine two outcomes of interest: self-reported exposure to forced sex and belief that a girl's community would force her to marry her hypothetical rapist, for married and unmarried 13- to 14-year-old girls (n = 377). Married girls are more likely to report both outcomes. Qualitative in-depth interviews with girl participants (n = 30) and their caregivers (n = 31) were analyzed for themes related to forced sex and marriage, revealing the normalcy of girls marrying perpetrators and suggesting that some married girls in this setting may have been forced to marry their rapist.


Subject(s)
Armed Conflicts , Child Abuse, Sexual , Coercion , Marriage , Rape , Residence Characteristics , Adolescent , Age Factors , Crime Victims , Democratic Republic of the Congo , Female , Humans , Self Report
13.
J Hosp Med ; 14(8): 482-485, 2019 08 01.
Article in English | MEDLINE | ID: mdl-31251153

ABSTRACT

In-hospital arrests are uncommon in pediatrics, making it difficult to identify the risk factors for unrecognized deterioration and to determine the effectiveness of rapid response systems. An emergency transfer (ET) is a transfer from an acute care floor to an intensive care unit (ICU) where the patient received intubation, inotropes, or ≥3 fluid boluses in the first hour after arrival or before transfer. Improvement science work has reduced ETs, but ETs have not been validated against important health outcomes. This case-control study aimed to determine the predictive validity of an ET for outcomes in a free-standing children's hospital. Controls were matched in terms of age, hospital unit, and time of year. Patients who experienced an ET had a significantly higher likelihood of in-hospital mortality (22% vs 9%), longer ICU length of stay (4.9 vs 2.2 days), and longer posttransfer length of stay (26.4 vs 14.7 days) compared with controls (P < .03 for each).


Subject(s)
Child, Hospitalized , Clinical Deterioration , Hospitals, Pediatric , Intensive Care Units, Pediatric/statistics & numerical data , Patient Transfer , Case-Control Studies , Child , Female , Hospital Mortality/trends , Humans , Length of Stay/statistics & numerical data , Male , Outcome Assessment, Health Care/statistics & numerical data , Risk Factors
15.
Gut Microbes ; 10(1): 45-58, 2019.
Article in English | MEDLINE | ID: mdl-29883265

ABSTRACT

Paneth cells (PCs) are epithelial cells found in the small intestine, next to intestinal stem cells (ISCs) at the base of the crypts. PCs secrete antimicrobial peptides (AMPs) that regulate the commensal gut microbiota. In contrast, little is known regarding how the enteric microbiota reciprocally influences PC function. In this study, we sought to characterize the impact of the enteric microbiota on PC biology in the mouse small intestine. This was done by first enumerating jejunal PCs in germ-free (GF) versus conventionally raised (CR) mice. We next evaluated the possible functional consequences of altered PC biology in these experimental groups by assessing epithelial proliferation, ISC numbers, and the production of AMPs. We found that PC numbers were significantly increased in CR versus GF mice; however, there were no differences in ISC numbers or cycling activity between groups. Of the AMPs assessed, only Reg3γ transcript expression was significantly increased in CR mice. Intriguingly, this increase was abrogated in cultured CR versus GF enteroids, and could not be re-induced with various bacterial ligands. Our findings demonstrate the enteric microbiota regulates PC function by increasing PC numbers and inducing Reg3γ expression, though the latter effect may not involve direct interactions between bacteria and the intestinal epithelium. In contrast, the enteric microbiota does not appear to regulate jejunal ISC census and proliferation. These are critical findings for investigators using GF mice and the enteroid system to study PC and ISC biology.


Subject(s)
Gastrointestinal Microbiome , Intestine, Small/cytology , Intestine, Small/microbiology , Multipotent Stem Cells/cytology , Paneth Cells/cytology , Paneth Cells/metabolism , Animals , Antimicrobial Cationic Peptides/genetics , Antimicrobial Cationic Peptides/metabolism , Cell Count , Cell Proliferation , Female , Germ-Free Life , Intestinal Mucosa/cytology , Mice, Inbred C57BL , Pancreatitis-Associated Proteins/genetics , Transcription, Genetic
16.
Front Microbiol ; 9: 3018, 2018.
Article in English | MEDLINE | ID: mdl-30619119

ABSTRACT

Pseudomonas aeruginosa causes infections in patients with compromised epithelial barrier function. Multiple virulence factors produced by P. aeruginosa are controlled by quorum sensing (QS) via 2-alkyl-4(1H)-quinolone (AQ) signal molecules. Here, we investigated the impact of AQs on P. aeruginosa PAO1 infection of differentiated human bronchial epithelial cells (HBECs). The pqsA-E operon is responsible for the biosynthesis of AQs including the 2-alkyl-3-hydroxy-4-quinolones, 4-hydroxy-2-alkylquinolines, and 4-hydroxy-2-alkylquinoline N-oxides as exemplified by pseudomonas quinolone signal (PQS), 2-heptyl-4-hydroxyquinoline (HHQ), and 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), respectively. PQS and HHQ both act as QS signal molecules while HQNO is a cytochrome inhibitor. PqsE contributes both to AQ biosynthesis and promotes virulence in a PQS-independent manner. Our results show that PQS, HHQ, and HQNO were produced during PAO1 infection of HBECs, but no differences in growth or cytotoxicity were apparent when PAO1 and an AQ-negative ΔpqsA mutant were compared. Both strains promoted synthesis of inflammatory cytokines TNF-α, interleukin (IL)-6, and IL-17C by HBECs, and the provision of exogenous PQS negatively impacted on this response without affecting bacterial growth. Expression of pqsE and the PQS-independent PqsE-regulated genes mexG and lecA was detected during HBEC infection. Levels were reduced in the ΔpqsA mutant, that is, in the absence of PQS, and increased by exogenous PQS. These results support an AQ-independent role for PqsE during initial infection of HBEC by P. aeruginosa and for PQS as an enhancer of PqsE and PqsE-controlled virulence determinants and as an immunomodulator.

17.
J Mol Cell Cardiol ; 112: 114-122, 2017 11.
Article in English | MEDLINE | ID: mdl-28478047

ABSTRACT

BACKGROUND: Patients with chronic kidney disease (CKD) experience high rates of atherosclerotic cardiovascular disease and death that are not fully explained by traditional risk factors. In animal studies, defective cellular cholesterol efflux pathways which are mediated by the ATP binding cassette transporters ABCA1 and ABCG1 are associated with accelerated atherosclerosis. We hypothesized that cholesterol efflux in humans would vary in terms of cellular components, with potential implications for cardiovascular disease. METHODS: We recruited 120 CKD patients (eGFR<30mL/min/1.73m2) and 120 control subjects (eGFR ≥60mL/min/1.73m2) in order to measure cholesterol efflux using either patients' HDL and THP-1 macrophages or patients' monocytes and a flow cytometry based cholesterol efflux assay. We also measured cell-surface levels of the common ß subunit of the IL-3/GM-CSF receptor (IL-3Rß) which has been linked to defective cholesterol homeostasis and may promote monocytosis. In addition, we measured plasma inflammatory cytokines and plasma metabolite profiles. RESULTS: There was a strong positive correlation between cell-surface IL-3Rß levels and monocyte counts in CKD (P<0.001). ABCA1 mRNA was reduced in CKD vs. control monocytes (P<0.05), across various etiologies of CKD. Cholesterol efflux to apolipoprotein A1 was impaired in monocytes from CKD patients with diabetic nephropathy (P<0.05), but we found no evidence for a circulating HDL-mediated defect in cholesterol efflux in CKD. Profiling of plasma metabolites showed that medium-chain acylcarnitines were both independently associated with lower levels of cholesterol transporter mRNA in CKD monocytes at baseline (P<0.05), and with cardiovascular events in CKD patients after median 2.6years of follow-up. CONCLUSIONS: Cholesterol efflux in humans varies in terms of cellular components. We report a cellular defect in ABCA1-mediated cholesterol efflux in monocytes from CKD patients with diabetic nephropathy. Unlike several traditional risk factors for atherosclerotic cardiovascular disease, plasma metabolites inversely associated with endogenous cholesterol transporters predicted cardiovascular events in CKD patients. (Funded by the National Institute of Diabetes and Digestive and Kidney DiseasesK23DK097288 and others.).


Subject(s)
Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Cholesterol/metabolism , Metabolome , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/complications , ATP Binding Cassette Transporter 1/metabolism , Aged , Biological Transport , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Carnitine/analogs & derivatives , Carnitine/metabolism , Cell Line , Cytokine Receptor Common beta Subunit/metabolism , Diabetic Nephropathies/blood , Diabetic Nephropathies/complications , Diabetic Nephropathies/metabolism , Female , Follow-Up Studies , Humans , Male , Middle Aged , Monocytes/metabolism , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Risk Factors
18.
Curr Treat Options Psychiatry ; 3(2): 151-160, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27648401

ABSTRACT

The last decade has seen considerable advances in the treatment of anxiety disorders in children and adolescents and a considerable expansion of the evidence base for psychopharmacologic in this population. The extant data suggest that, for fear-based anxiety disorders (e.g., generalized anxiety disorder, social phobia/social anxiety disorder, and separation anxiety disorder), selective serotonin reuptake inhibitors (SSRIs) and selective serotonin norepinephrine reuptake inhibitors (SSNRIs) are well tolerated and offer considerable benefit. However, the salutary effects of SSRIs and SSNRIs in pediatric anxiety disorders are consistently amplified by the addition of psychotherapy, particularly in individuals with social anxiety disorder. Additionally, several key demographic and clinical factors, including male sex, non-minority status, and better family functioning and younger age predict greater symptomatic improvement in youth with fear-based anxiety disorders. Thus, current data suggest that in addition to several forms of psychotherapy, including cognitive-behavioral therapy (CBT), SSRIs and SSNRIs are efficacious in the treatment of these conditions in youth and that CBT + an SSRI may be associated with greater improvement than would be expected with either treatment as monotherapy. Finally, given that some children and adolescents may exhibit partial response to current pharmacotherapies, benzodiazepines, anti-histamines and other agents may have adjunctive roles, despite a lack of data in terms of large, randomized controlled trials.

19.
Clin Nephrol ; 86 (2016)(13): 37-40, 2016.
Article in English | MEDLINE | ID: mdl-27469155

ABSTRACT

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are growing public health issues associated with significant morbidity and mortality around the world. In the United States, Black and Hispanic minorities suffer higher rates of CKD and ESRD, mostly attributed to Diabetic Kidney Disease (DKD). DKD is the leading cause of both CKD and ESRD in the developed world and disproportionately affects minority populations such as African Americans, Hispanic Americans, and Aboriginal Americans in comparison with Whites. This review will discuss the incidence, prevalence, and etiology of renal disease in disadvantaged minorities in the U.S. and will take a closer look at diabetic kidney disease as it is the primary cause of kidney disease in these populations.


Subject(s)
Black or African American/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Kidney Failure, Chronic/epidemiology , Minority Groups/statistics & numerical data , Vulnerable Populations/statistics & numerical data , White People/statistics & numerical data , Cardiovascular Diseases/epidemiology , Humans , Incidence , Kidney Failure, Chronic/complications , Prevalence , Risk Factors , United States/epidemiology , Vulnerable Populations/ethnology
20.
Surg Endosc ; 27(8): 2801-6, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23392982

ABSTRACT

BACKGROUND: Live donor nephrectomy is routinely performed. However, little is known regarding the incision-related outcome. The aim of the present study was to evaluate the prevalence of incisional hernias (IH) and to assess body image and cosmesis scores after donation. METHODS: Questionnaires on IH, body image, and cosmesis were sent to all donors who underwent laparoscopic donor nephrectomy or mini-incision donor nephrectomy between January 2000 and December 2009. RESULTS: In total, 444 replies were received (75 %). Seven donors (1.5 %) had undergone a surgical correction of an IH. Surgical site infection and steroid use appeared to be independent risk factors for the development of an IH (p = 0.001 and 0.021, respectively). Body image and cosmesis scores were excellent. Elderly donors had significantly higher cosmesis scores when compared with young donors (p < 0.001). Donor age of 60 years or higher, correction of an IH, and survival of the recipient appeared to be independent factors associated with a higher score on the cosmesis scale in multivariate analysis. CONCLUSIONS: This is the largest study describing the prevalence of IH and cosmetic outcome after donor nephrectomy. The prevalence of IH after live donor nephrectomy is very low, and body image and cosmesis scores are excellent. Consequently, incision-related outcomes pose no barrier to live donor nephrectomy.


Subject(s)
Hernia, Abdominal/epidemiology , Kidney Transplantation , Laparoscopy/methods , Living Donors , Nephrectomy/methods , Tissue and Organ Harvesting/methods , Adolescent , Adult , Aged , Female , Follow-Up Studies , Hernia, Abdominal/etiology , Hernia, Abdominal/prevention & control , Humans , Incidence , Male , Middle Aged , Nephrectomy/adverse effects , Netherlands/epidemiology , Postoperative Complications , Retrospective Studies , Risk Factors , Surveys and Questionnaires , Time Factors , Young Adult
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