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1.
Occup Med (Lond) ; 73(6): 324-331, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37523669

ABSTRACT

BACKGROUND: Little is known about the multi-dimensional nature of traumatic duty-related events encountered by firefighters in relation to their post-traumatic stress disorder (PTSD) risk. AIMS: To describe the types of duty-related events encountered by career firefighters and explore if years in the fire service or total event load moderated the association of trauma exposure to PTSD symptoms. METHODS: Participants included 755 career, male firefighters (19% of the department's firefighters and 76% of those who accessed the electronic anonymous survey). The Duty-Related Incident Stressors scale was used to assess exposure to 25 potentially traumatic events (event load) and self-appraisal of the stress associated with these events, grouped by type of event (indirect, direct and colleague-related). The Post-Traumatic Stress Disorder Checklist was used to assess PTSD symptoms. RESULTS: Firefighters rated colleague-related events as the most stressful, followed by indirect and direct events. Event load (r = 0.25) and indirect, direct and colleague-related events stress (r = 0.32-0.35) were positively associated with PTSD symptoms. Results of moderation analyses indicated that event load served as a risk factor in the relation of indirect events stress to PTSD symptoms, and as a buffer in the relation of direct events stress to PTSD symptoms. Years in the fire service were not associated with PTSD symptoms nor moderated the relation of event stress to PTSD symptoms. CONCLUSIONS: Findings underscored the importance of considering the differential effects that types of duty-related traumatic events and cumulative exposure to trauma may have on firefighters' PTSD symptoms.

2.
Clin Exp Immunol ; 203(3): 409-423, 2021 03.
Article in English | MEDLINE | ID: mdl-33205401

ABSTRACT

Biological treatments such as enzyme-replacement therapies (ERT) can generate anti-drug antibodies (ADA), which may reduce drug efficacy and impact patient safety and consequently led to research to mitigate ADA responses. Transient low-dose methotrexate (TLD-MTX) as a prophylactic ITI regimen, when administered concurrently with ERT, induces long-lived reduction of ADA to recombinant human alglucosidase alfa (rhGAA) in mice. In current clinical practice, a prophylactic ITI protocol that includes TLD-MTX, rituximab and intravenous immunoglobulin (optional), successfully induced lasting control of ADA to rhGAA in high-risk, cross-reactive immunological material (CRIM)-negative infantile-onset Pompe disease (IOPD) patients. More recently, evaluation of TLD-MTX demonstrated benefit in CRIM-positive IOPD patients. To more clearly understand the mechanism for the effectiveness of TLD-MTX, non-targeted transcriptional and proteomic screens were conducted and revealed up-regulation of erythropoiesis signatures. Confirmatory studies showed transiently larger spleens by weight, increased spleen cellularity and that following an initial reduction of mature red blood cells (RBCs) in the bone marrow and blood, a significant expansion of Ter-119+ CD71+ immature RBCs was observed in spleen and blood of mice. Histology sections revealed increased nucleated cells, including hematopoietic precursors, in the splenic red pulp of these mice. This study demonstrated that TLD-MTX induced a transient reduction of mature RBCs in the blood and immature RBCs in the bone marrow followed by significant enrichment of immature, nucleated RBCs in the spleen and blood during the time of immune tolerance induction, which suggested modulation of erythropoiesis may be associated with the induction of immune tolerance to rhGAA.


Subject(s)
Cell Differentiation/drug effects , Cell Proliferation/drug effects , Erythroblasts/drug effects , Immune Tolerance/drug effects , Methotrexate/administration & dosage , Animals , Cell Differentiation/genetics , Cell Differentiation/immunology , Dose-Response Relationship, Drug , Erythroblasts/cytology , Erythroblasts/metabolism , Erythrocytes/drug effects , Erythrocytes/immunology , Erythrocytes/metabolism , Erythropoiesis/drug effects , Erythropoiesis/genetics , Erythropoiesis/immunology , Female , Gene Expression Profiling/methods , Humans , Immune Tolerance/genetics , Immune Tolerance/immunology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/immunology , Methotrexate/immunology , Mice, Inbred C57BL , Proteomics/methods , Spleen/drug effects , Spleen/immunology , Spleen/metabolism , alpha-Glucosidases/administration & dosage
3.
Br J Dermatol ; 180(6): 1302-1311, 2019 06.
Article in English | MEDLINE | ID: mdl-30585627

ABSTRACT

BACKGROUND: Human polyomaviruses (HPyVs) are small, nonenveloped, double-stranded DNA viruses that express tumour antigen proteins. Fourteen species of polyomaviruses have been discovered in humans, and since the 2008 discovery of the first cutaneous polyomavirus - Merkel cell polyomavirus (MCPyV) - six more species have been detected in the skin: trichodysplasia spinulosa-associated polyomavirus (TSPyV), HPyV6, HPyV7, HPyV9, HPyV10 and HPyV13. Of these cutaneous species, only MCPyV, TSPyV, HPyV6 and HPyV7 have been definitively associated with diseases of the skin, most commonly in immunocompromised individuals. MCPyV is a predominant aetiology in Merkel cell carcinomas. TSPyV is one of the aetiological factors of trichodysplasia spinulosa. HPyV6 and HPyV7 have been recently linked to pruritic skin eruptions. The roles of HPyV9, HPyV10 and HPyV13 in pathogenesis, if any, are still unknown, but their molecular features have provided some insight into their functional biology. RESULTS: In this review, we summarize the known molecular mechanisms, clinical presentation and targeted therapies of each of the eight cutaneous HPyVs. CONCLUSIONS: We hope that heightened awareness and clinical recognition of HPyVs will lead to increased reports of HPyV-associated diseases and, consequently, a more robust understanding of how to diagnose and treat these conditions.


Subject(s)
Communicable Diseases, Emerging/virology , Polyomavirus Infections/virology , Polyomavirus/physiology , Skin Diseases, Viral/virology , Tumor Virus Infections/virology , Carcinogenesis , Communicable Diseases, Emerging/therapy , Humans , Immunocompromised Host , Polyomavirus/genetics , Polyomavirus Infections/therapy , Skin Diseases, Viral/therapy , Tumor Virus Infections/therapy
4.
Occup Med (Lond) ; 69(8-9): 577-585, 2019 Dec 31.
Article in English | MEDLINE | ID: mdl-31064010

ABSTRACT

BACKGROUND: Little is known regarding the mental health of women firefighters. AIMS: To identify demographic, work-related and mental health characteristics associated with post-traumatic stress disorder (PTSD) symptoms and lifetime suicidal ideation in female firefighters compared with male colleagues. METHODS: Participants were firefighters (75 women and 2564 men) employed in a large urban fire department in the USA. Chi-square, correlations, t-tests and analyses of variance were conducted to examine the predictors of PTSD symptoms and lifetime suicide ideation in men and women. RESULTS: Approximately 20% of women scored positively for PTSD and 30% reported lifetime suicidal ideation. Women with PTSD symptoms were more likely to be in their mid-career years (11-20) than in their first 10 years (87% versus 44%; χ2 = 8.77, P < 0.05) and to have received counselling (53% versus 14%; χ2 = 8.11, P < 0.01). Being single (73% versus 58%; χ2 = 6.02, P < 0.05), having a second job (68% versus 38%; χ2 = 5.79, P < 0.05) and having received counselling (41% versus 11%; χ2 = 8.51, P < 0.01) predicted suicide ideation. Depression and general stress positively predicted PTSD symptoms and suicide ideation. PTSD also predicted suicide ideation. CONCLUSIONS: Compared to male firefighters, women were at high risk for PTSD symptoms and suicide ideation. Particularly for women, few socio-demographic and work-related variables were associated with these outcomes. Mental health variables predicted depression and suicide ideation for both gender groups. Therefore, in screening and intervention efforts, it may be most fruitful to focus on mental health risk correlates of PTSD and suicide ideation.


Subject(s)
Firefighters/psychology , Stress Disorders, Post-Traumatic/psychology , Suicidal Ideation , Adult , Aged , Depression/epidemiology , Female , Humans , Male , Marital Status , Middle Aged , Risk Factors , Sex Factors , Stress Disorders, Post-Traumatic/epidemiology , Surveys and Questionnaires , United States/epidemiology
5.
Org Biomol Chem ; 14(24): 5505-10, 2016 Jun 28.
Article in English | MEDLINE | ID: mdl-26751150

ABSTRACT

Mcl-1 has recently emerged as an attractive target to expand the armamentarium in the war on cancer. Using structure-based design, 3-carboxy-substituted 1,2,3,4-tetrahydroquinolines were developed as a new chemotype to inhibit the Mcl-1 oncoprotein. The most potent compound inhibited Mcl-1 with a Ki of 120 nM, as determined by a fluorescence polarization competition assay. Direct binding was confirmed by 2D (1)H-(15)N HSQC NMR spectroscopy with (15)N-Mcl-1, which indicated that interactions with R263 and T266, and occupation of the p2 pocket are likely responsible for the potent binding affinity. The short and facile synthetic chemistry to access target molecules is expected to mediate lead optimization.


Subject(s)
Drug Design , Myeloid Cell Leukemia Sequence 1 Protein/antagonists & inhibitors , Quinolines/chemistry , Quinolines/pharmacology , Molecular Docking Simulation , Myeloid Cell Leukemia Sequence 1 Protein/chemistry , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Protein Conformation , Quinolines/metabolism , Structure-Activity Relationship
6.
Spinal Cord ; 54(9): 640-8, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27163453

ABSTRACT

STUDY DESIGN: Meta-analysis. OBJECTIVES: Although the association between modifiable psychosocial factors and spinal cord injury (SCI) pain has been identified, the full range of psychological and social difficulties for those who experience acute and/or persistent pain remains unclear. This meta-analysis consolidates the available evidence, using the International Classification of Functioning, Disability and Health (ICF) as a reference framework. METHODS: Nineteen studies that examined persistent neuropathic, nociceptive or mixed pain subtypes in adults with a SCI (newly acquired and chronic; Nparticipants=2934) were identified from electronic database searches. Standardised mean differences between SCI pain and no-pain groups on self-reported psychosocial outcomes were calculated, along with 95% confidence intervals, fail-safe Ns and heterogeneity statistics. RESULTS: Twenty individual outcomes were grouped into nine ICF-related categories. Emotional functions were the most frequent (100%) psychosocial outcomes assessed, with pain contributing to heightened stress (d=-0.85), depression (d=-2.49) anxiety (d range=-0.85 to -1.45), poor self-efficacy (d=-0.77), lowered wellbeing (d range=-0.67 to -1.02) and decreased use of adaptive coping, such as illness acceptance (d=-0.85). Activity limitations and participation restriction were examined by seven studies (43%), although these findings were largely characterised by single studies. CONCLUSIONS: Multicomponent treatments that target mood disturbance and foster community connections are important in SCI pain management. However, to improve the comparability of future studies, SCI pain research must adopt definitions of pain consistent with the International Spinal Cord Injury Pain Classification along with validated outcomes that map onto the ICF framework.


Subject(s)
Pain/etiology , Pain/psychology , Spinal Cord Injuries/complications , Activities of Daily Living , Adaptation, Psychological , Databases, Bibliographic/statistics & numerical data , Humans , Mood Disorders/etiology , Pain/complications , Pain Management
7.
J Clin Pharm Ther ; 39(6): 577-83, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25070601

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Based on in vitro assays and select animal models, buprenorphine is commonly called a 'partial agonist'. An implication is that it should produce less analgesic effect in humans than so-called 'full agonists' such as morphine or fentanyl. However, buprenorphine has a multimechanistic pharmacology, and thus partial agonism at a specific receptor is not particularly relevant to its overall analgesic action. We review published clinical trials that directly compared the magnitude of buprenorphine's analgesic effect to analgesics commonly considered full agonists. COMMENT: Due to different signal transduction pathways, a drug can be a full agonist on one endpoint and a partial agonist on another. Therefore, we limited the present review to buprenorphine's analgesic effect. WHAT IS NEW AND CONCLUSION: Twenty-four controlled clinical trials were identified, plus a case report and dose-response curve. Based on complete or comparable pain relief, in buprenorphine had full clinical analgesic efficacy in 25 of the 26 studies.


Subject(s)
Analgesics, Opioid/pharmacology , Buprenorphine/pharmacology , Pain/drug therapy , Analgesics, Opioid/administration & dosage , Animals , Buprenorphine/administration & dosage , Controlled Clinical Trials as Topic , Dose-Response Relationship, Drug , Drug Partial Agonism , Humans , Pain/physiopathology , Signal Transduction/drug effects
8.
Local Environ ; 29(1): 57-73, 2024.
Article in English | MEDLINE | ID: mdl-38313002

ABSTRACT

Colfax, Louisiana hosts a commercial hazardous waste thermal treatment (TT) facility, which treats fireworks, explosives, and military ordnances by open-burn/open-detonation one mile from the edge of the nearest community. Seventy-one percent of Colfax's residents are Black, and forty-six percent live below poverty, indicating the community's structural vulnerability. This community-based study originated at the behest of Colfax community members. We hypothesized that the close relationships among members of this enclave may have enhanced the community's ability to mobilize in opposition to the TT facility. We conducted semi-structured oral history interviews with nineteen community members and examined the social and interorganizational networks used by the Colfax community to claim its role in decision-making regarding the TT facility after years of exclusion from this process. Interview transcripts were analyzed through the lens of community capacity theory to gain insight into how interactions among community members about the environmental hazards led to social mobilization and improved participation in the decision-making process using codes for communication, organization, and outcome. Additionally, we reviewed Louisiana Department of Environmental Quality records for complaints about the facility to gauge public participation. One notable theme across several interviews was exclusion from the initial decision-making process related to the facility. However, interviewees noted a sustained effort was made among community members to educate themselves about the facility, organize a response through neighbor-to-neighbor contact, and take action by submitting formal complaints and participating in public hearings. Through the lens of environmental justice, this study illustrates an evolving condition of procedural justice.

9.
Rev Neurol (Paris) ; 169(11): 892-7, 2013 Nov.
Article in French | MEDLINE | ID: mdl-24139245

ABSTRACT

INTRODUCTION: Nutritional status is a major clinical parameter in multiple cancers. Indeed, nutritional status is a prognostic factor and a predictor of response and toxicity to treatments in breast and lung cancers for instance. To our knowledge, in patients suffering from malignant primary brain tumors, nutritional status has been poorly investigated. METHODS: Nutritional status of 26 glioblastoma patients relapsing after a first line of treatment was studied. The body mass index (BMI), the prognostic inflammatory and nutritional index (PINI) and the instant nutritional score (INS) were assessed. RESULTS: The BMI was abnormal in 12 patients, two were malnourished while 10 were overweight. The BMI was not correlated to age of patients. Overweight status did not impact patient survival but it was associated with reduced performance status. The PINI was abnormal in three patients. Finally, the INS was abnormal in 24 patients, noted 2 (n=22) or 4 (n=4). CONCLUSIONS/DISCUSSION: Our results were not in favor of systematic nutritional support in patients with recurrent glioblastoma after a first line of treatment. Being overweight does not influence prognosis but may influence performance status. Steroid therapy and chemotherapy (inducing sodium and water retention and lymphopenia) weaken the relevance of BMI and INS for nutritional assessment in patients with recurrent glioblastoma. Further studies using additional nutritional tests in larger, independent and prospective cohorts of patients are warranted to obtain more details.


Subject(s)
Brain Neoplasms/physiopathology , Glioblastoma/physiopathology , Neoplasm Recurrence, Local/physiopathology , Nutritional Status/physiology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/epidemiology , Brain Neoplasms/surgery , Cohort Studies , Combined Modality Therapy , Disease Progression , Female , Glioblastoma/epidemiology , Glioblastoma/surgery , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Nutrition Disorders/epidemiology
10.
Diabetologia ; 55(4): 1071-80, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22234649

ABSTRACT

AIMS/HYPOTHESIS: Glucokinase activators (GKAs) are currently being developed as new therapies for type 2 diabetes and have been shown to enhance beta cell survival and proliferation in vitro. Here, we report the effects of chronic GKA treatment on the development of hyperglycaemia and beta cell loss in the male Zucker diabetic fatty (ZDF) rat, a model of type 2 diabetes with severe obesity. METHODS: Cell protection by GKA was studied in MIN6 and INS-1 cells exposed to hydrogen peroxide. Glucose homeostasis and beta cell mass were evaluated in ZDF rats dosed for 41 days with Cpd-C (a GKA) or glipizide (a sulfonylurea) as food admixtures at doses of approximately 3 and 10 mg kg(-1) day(-1). RESULTS: Incubation of MIN6 and INS-1 832/3 insulinoma cell cultures with GKA significantly reduced cell death and impairment of intracellular NADH production caused by exposure to hydrogen peroxide. Progression from prediabetes (normoglycaemia and hyperinsulinaemia) to overt diabetes (hyperglycaemia and hypoinsulinaemia) was significantly delayed in male ZDF rats by in-feed treatment with Cpd-C, but not glipizide. Glucose tolerance, tested in the fifth week of treatment, was also significantly improved by Cpd-C, as was pancreatic insulin content and beta cell area. In a limited immunohistochemical analysis, Cpd-C modestly and significantly enhanced the rate of beta cell proliferation, but not rates of beta cell apoptosis relative to untreated ZDF rats. CONCLUSIONS/INTERPRETATION: These findings suggest that chronic activation of glucokinase preserves beta cell mass and delays disease in the ZDF rat, a model of insulin resistance and progressive beta cell failure.


Subject(s)
Diabetes Mellitus, Type 2/prevention & control , Enzyme Activators/pharmacology , Glucokinase/metabolism , Hyperglycemia/prevention & control , Insulin Resistance/physiology , Insulin-Secreting Cells/drug effects , Animals , Apoptosis/drug effects , Cell Line, Tumor , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Hyperglycemia/drug therapy , Hyperglycemia/metabolism , Insulin/metabolism , Male , Mice , Rats , Rats, Zucker , Sulfones/pharmacology , Thiadiazoles/pharmacology
11.
J Fr Ophtalmol ; 45(7): 700-709, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35779968

ABSTRACT

PURPOSE: To utilize data mining for analysis of corneal transplantations (CT) in Florida from 2005-2014, segmented by demographics, geography, and transplantation technique. METHODS: A retrospective, database study was performed utilizing data queried from the Healthcare and Cost Utilization Project using Current Procedural Terminology codes for lamellar keratoplasty (ALK), endothelial keratoplasty (EK), and penetrating keratoplasty (PKP). Payer status, ethnic group, age, gender, and geography (urban versus rural) was extracted from each surgical encounter and reconfigured to provide a "clean", congruous dataset for statistical analysis. This Institutional Review Board-approved study did not utilize identifiable patient information; thus, individual informed consent was not required. RESULTS: From 2005-2014, CT (n=28,607) represented less than 1% of the total ambulatory surgeries (n=12,695,932) performed in Florida. EK volume increased while PKP and ALK volume decreased, year-over-year. Statistical significance was found between transplantation technique by sex (P<0.001) and ethnic group (P<0.001). The largest sex discrepancy was EK (59% female, 41% male). White patients underwent relatively fewer PKP than EK (71% vs. 83% of totals), while Black patients underwent relatively more PKP than EK (14% vs 6% of totals). Statistical significance was found between techniques by payer (P<0.001). Medicare was the most common payer for all techniques, but ALK and PKP had higher percentages of private insurance and self-pay. No statistical significance was found between techniques by geographic location. Corneal edema (22.4%), endothelial dystrophy (17.5%), and bullous keratopathy (10.9%) were erroneously coded as indications for ALK. Corneal scars (2.5%) and corneal opacity (1.7%) were erroneously coded as indications for EK. CONCLUSIONS: CT rates in Florida appear to overrepresent the female sex and underrepresent ethnic minorities, with propensities between PKP and African Americans, EK and female patients, and EK and Medicare reimbursement. Our study further confirms the utility of data mining for providing efficient, detailed, and practical insights into ophthalmology procedures, while highlighting the intrinsic challenges of large datasets.


Subject(s)
Corneal Diseases , Corneal Transplantation , Aged , Algorithms , Corneal Diseases/epidemiology , Corneal Diseases/surgery , Corneal Transplantation/methods , Data Mining , Female , Humans , Keratoplasty, Penetrating/methods , Male , Medicare , Receptor Protein-Tyrosine Kinases , Retrospective Studies , United States
12.
BMJ Mil Health ; 168(5): 359-361, 2022 Oct.
Article in English | MEDLINE | ID: mdl-32753538

ABSTRACT

INTRODUCTION: Ketamine is a vital component for acute pain management in emergency trauma care for both civilian and military hospitals. This preliminary analysis examined whether combat-injured US service members sustaining traumatic brain injuries (TBI) experienced increased odds of ketamine side effects compared with those without TBI. METHODS: This preliminary analysis included combat-injured service members, ages ≥18 years with documented pain scores during the 24 hours before and 48 hours after receiving an intravenous ketamine infusion at Walter Reed National Military Medical Center (WRNMMC) between 2007 and 2014. Logistic regression modeling examined the association between TBI and ketamine side effects (eg, hallucinations, nightmares, dysphoria, nausea, decreased oxygen saturation) during hospitalisation. RESULTS: Of the 77 patients, 62% presented with a documented TBI. Side effects were documented for 18.8% of those without TBI and 24.4% of those with TBI. Analyses were unable to find evidence against the null hypothesis with the current sample size, even when adjusting for injury characteristics and preinfusion opioid doses (adjusted OR=0.90 (95% CI 0.26 to 3.34), p=0.87). CONCLUSION: In this small sample of combat-injured service members, we were unable to detect a difference in ketamine-related side effects by documented TBI status. These hypothesis-generating findings support the need for future studies to examine the use of intravenous ketamine infusions for pain management, and subsequent care outcomes in patients who experience polytraumatic trauma inclusive of TBI.


Subject(s)
Brain Injuries, Traumatic , Ketamine , Military Personnel , Adolescent , Analgesics, Opioid , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Hospitals, Military , Humans , Ketamine/adverse effects , United States
13.
Hum Immunol ; 83(3): 264-269, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35109976

ABSTRACT

Advances in immunology support the understanding that precise structural epitopes on the antibody-accessible region of the HLA molecule determine antigenicity and challenge the need for identity across the full HLA molecule to minimize graft immunogenicity. Retrospective studies confirm that quantitative measurement of epitope-level mismatching between donor and recipient is an informative marker of graft rejection and survival and suggest that prospective allocation of donor organs based on this principle may improve graft survival. Here we describe the process for rigorous prospective evaluation of this hypothesis in a formal national proof-of-concept program for epitope-based matching. This encompasses broad societal consultation to engage the public, patients and providers; the development of clear allocation policies with strategies to support candidates who may be difficult to match; molecular and sequencing methods and web-based calculators enabling rapid epitope typing and recipient selection; precise immunological monitoring of the graft response; information systems permitting real-time monitoring of clinical outcomes; and assessment of health benefit and economic cost. The results of this objective evaluation can then be provided to payers and policy-makers for review, and adoption if of proven benefit.


Subject(s)
Kidney Transplantation , Epitopes , Graft Rejection/prevention & control , Graft Survival , HLA Antigens/genetics , Histocompatibility Testing/methods , Humans , Precision Medicine , Retrospective Studies
14.
Int J Obes (Lond) ; 35(2): 217-25, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20603627

ABSTRACT

OBJECTIVE: To investigate the impact of reduced adipocyte fatty acid-binding protein 4 (FABP4) in control of body weight, glucose and lipid homeostasis in diet-induced obese (DIO) mice. METHODS: We applied RNA interference (RNAi) technology to generate FABP4 germline knockdown mice to investigate their metabolic phenotype. RESULTS: RNAi-mediated knockdown reduced FABP4 mRNA expression and protein levels by almost 90% in adipocytes of standard chow-fed mice. In adipocytes of DIO mice, RNAi reduced FABP4 expression and protein levels by 70 and 80%, respectively. There was no increase in adipocyte FABP5 expression in FABP4 knockdown mice. The knockdown of FABP4 significantly increased body weight and fat mass in DIO mice. However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity. CONCLUSION: Our data indicate that robust knockdown of FABP4 increases body weight and fat mass without improving glucose and lipid homeostasis in DIO mice.


Subject(s)
Adipocytes/metabolism , Body Weight/genetics , Fatty Acid-Binding Proteins/metabolism , Obesity/genetics , RNA Interference , Animals , Energy Intake/physiology , Energy Metabolism/physiology , Fatty Acid-Binding Proteins/genetics , Gene Knockdown Techniques/methods , Germ-Line Mutation , Insulin Resistance/genetics , Insulin Resistance/physiology , Lipid Metabolism/genetics , Mice , Mice, Knockout , Mice, Obese , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Obesity/metabolism , RNA, Messenger/metabolism
15.
Semin Ultrasound CT MR ; 41(1): 2-9, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31964491

ABSTRACT

Infections of the male and female reproductive system can lead to significant morbidity and mortality. This article will review the relevant embryology and anatomy of the male and female reproductive systems and will discuss the imaging findings of different infections. An understanding of the clinical presentation and imaging findings of infections of the reproductive system is critical in order to allow for prompt and accurate diagnosis. A delay in diagnosis for these infections can have significant morbidity, and occasional mortality.


Subject(s)
Genital Diseases, Female/diagnostic imaging , Genital Diseases, Female/microbiology , Genital Diseases, Male/diagnostic imaging , Genital Diseases, Male/microbiology , Genitalia, Female/anatomy & histology , Genitalia, Male/anatomy & histology , Infections/diagnostic imaging , Infections/microbiology , Diagnosis, Differential , Female , Genitalia, Female/embryology , Genitalia, Male/embryology , Humans , Male
16.
Semin Ultrasound CT MR ; 41(1): 99-105, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31964498

ABSTRACT

Acute urinary tract infection diagnosis is primarily performed on clinical grounds. Diagnostic imaging is, however, often necessary as part of the workup for poor response to treatment, to evaluate causative or contributory factors, complicated infections and chronic presentations. Appropriate knowledge of the most relevant radiological findings in urinary tract infections provides pertinent differential diagnosis and guides clinical management, including emergent and aggressive interventions. In this article we review ultrasound and CT imaging findings of acute and chronic urinary tract infections.


Subject(s)
Urinary Tract Infections/diagnostic imaging , Diagnosis, Differential , Humans , Tomography, X-Ray Computed , Ultrasonography , Urinary Tract Infections/microbiology
17.
Neuroscience ; 158(2): 885-95, 2009 Jan 23.
Article in English | MEDLINE | ID: mdl-19032979

ABSTRACT

During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of cerebrospinal fluid (CSF) production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the small inducible cytokine A2 (SCYA2) gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared with other rat CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the nuclear factor-kappa B (NF-kappaB) signaling cascade including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and inhibitor of kappa B alpha (IkappaBalpha) in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding endothelial leukocyte adhesion molecule 1 (E-selectin), a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during peripheral tissue inflammation, likely initiated by blood-borne inflammatory mediators, which may modify events in CNS.


Subject(s)
Brain/pathology , Chemokine CCL2/metabolism , Choroid Plexus/metabolism , Cytokines/metabolism , Gene Expression Regulation/physiology , Inflammation/pathology , Analysis of Variance , Animals , Brain/metabolism , Carrageenan , Caspase 1/genetics , Caspase 1/metabolism , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Chemokine CCL2/genetics , Cytokines/genetics , Disease Models, Animal , Gene Expression Regulation/drug effects , Inflammation/chemically induced , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Time Factors
19.
Aust Dent J ; 64(3): 246-255, 2019 09.
Article in English | MEDLINE | ID: mdl-30972755

ABSTRACT

BACKGROUND: The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representative sample of older Australian men. The aim of this paper is to describe the oral health behaviours and dental service use of CHAMP participants and explore associations between oral health behaviours with and general health status. METHOD: Information collected related to socio-demographics, general health, oral health service-use and oral health behaviours. Key general health conditions were ascertained from the health questionnaire and included physical capacity and cognitive status. RESULTS: Fifty-seven percent of the men reported visiting a dental provider at least once or more a year and 56.7% did so for a "dental check-up". Of those with some natural teeth, 59.3% claimed to brush their teeth at least twice or more a day. Most men (96%) used a standard fluoride toothpaste. Few participants used dental floss, tooth picks or mouth-rinses to supplement oral hygiene. Cognitive status and self-rated general health were associated with dental visiting patterns and toothbrushing behaviour. CONCLUSIONS: Most older men in CHAMP perform favourable oral health behaviours. Smoking behaviour is associated with less favourable dental visiting patterns, and cognitive status with toothbrushing behaviour.


Subject(s)
Health Behavior , Oral Health , Toothbrushing , Aged , Aging , Australia , Cohort Studies , Humans , Male
20.
Ecol Appl ; 17(3): 882-99, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17494404

ABSTRACT

Predicting population dynamics is a fundamental problem in applied ecology. Temperature is a potential driver of short-term population dynamics, and temperature data are widely available, but we generally lack validated models to predict dynamics based upon temperatures. A generalized approach involves estimating the temperatures experienced by a population, characterizing the demographic consequences of physiological responses to temperature, and testing for predicted effects on abundance. We employed this approach to test whether minimum winter temperatures are a meaningful driver of pestilence from Dendroctonus frontalis (the southern pine beetle) across the southeastern United States. A distance-weighted interpolation model provided good, spatially explicit, predictions of minimum winter air temperatures (a putative driver of beetle survival). A Newtonian heat transfer model with empirical cooling constants indicated that beetles within host trees are buffered from the lowest air temperatures by approximately 1-4 degrees C (depending on tree diameter and duration of cold bout). The life stage structure of beetles in the most northerly outbreak in recent times (New Jersey) were dominated by prepupae, which were more cold tolerant (by >3 degrees C) than other life stages. Analyses of beetle abundance data from 1987 to 2005 showed that minimum winter air temperature only explained 1.5% of the variance in interannual growth rates of beetle populations, indicating that it is but a weak driver of population dynamics in the southeastern United States as a whole. However, average population growth rate matched theoretical predictions of a process-based model of winter mortality from low temperatures; apparently our knowledge of population effects from winter temperatures is satisfactory, and may help to predict dynamics of northern populations, even while adding little to population predictions in southern forests. Recent episodes of D. frontalis outbreaks in northern forests may have been allowed by a warming trend from 1960 to 2004 of 3.3 degrees C in minimum winter air temperatures in the southeastern United States. Studies that combine climatic analyses, physiological experiments, and spatially replicated time series of population abundance can improve population predictions, contribute to a synthesis of population and physiological ecology, and aid in assessing the ecological consequences of climatic trends.


Subject(s)
Coleoptera , Models, Biological , Temperature , Animals , Population Dynamics , Seasons , Southeastern United States , Trees
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