ABSTRACT
BACKGROUND: To examine if the COVID-19 pandemic was associated with a differential effect longitudinally in relation to its psychological and functional impact on patients with bipolar disorder and Emotionally Unstable Personality Disorder (EUPD). METHODS: Semi-structured interviews were conducted with 29 individuals attending the Galway-Roscommon Mental Health Services with an ICD-10 diagnosis of either bipolar disorder (n = 18) or EUPD (n = 11). The impact of the COVID-19 pandemic was assessed in relation to anxiety and mood symptoms, social and occupational functioning, and quality of life utilising psychometric instruments and Likert scale data, with qualitative data assessing participants' subjective experiences. RESULTS: Individuals with EUPD exhibited significant anxiety and depressive symptoms and increased hopelessness compared to individuals with bipolar disorder. Repeated measures data demonstrated no significant change in symptomatology for either the EUPD or bipolar disorder group over time, but demonstrated an improvement in social (t = 4.40, p < 0.001) and occupational functioning (t = 3.65, p = 0.03), and in quality of life (t = 4.03, p < 0.001) for both participant groups. Themes attained from qualitative data included the positive impact of the discontinuation of COVID-19 mandated restrictions (n = 19), and difficulties experienced secondary to reductions in the provision of mental health services during the COVID-19 pandemic (n = 17). CONCLUSION: Individuals with EUPD demonstrated increased symptomatology over a two-year period compared to those with bipolar disorder. The importance of face-to-face mental health supports for this cohort are indicated, particularly if future pandemics impact the delivery of mental health services.
ABSTRACT
Nurses and midwives of Australia now is the time for change! As powerfully placed, Indigenous and non-Indigenous nursing and midwifery professionals, together we can ensure an effective and robust Indigenous curriculum in our nursing and midwifery schools of education. Today, Australia finds itself in a shifting tide of social change, where the voices for better and safer health care ring out loud. Voices for justice, equity and equality reverberate across our cities, our streets, homes, and institutions of learning. It is a call for new songlines of reform. The need to embed meaningful Indigenous health curricula is stronger now than it ever was for Australian nursing and midwifery. It is essential that nursing and midwifery leadership continue to build an authentic collaborative environment for Indigenous curriculum development. Bipartisan alliance is imperative for all academic staff to be confident in their teaching and learning experiences with Indigenous health syllabus. This paper is a call out. Now is the time for Indigenous and non-Indigenous nurses and midwives to make a stand together, for justice and equity in our teaching, learning, and practice. Together we will dismantle systems, policy, and practices in health that oppress. The Black Lives Matter movement provides us with a 'now window' of accepted dialogue to build a better, culturally safe Australian nursing and midwifery workforce, ensuring that Black Lives Matter in all aspects of health care.
Subject(s)
Administrative Personnel/psychology , Black or African American/psychology , Culturally Competent Care/organization & administration , Midwifery/education , Nursing Care/psychology , Nursing Staff, Hospital/psychology , Racism/prevention & control , Students, Nursing/psychology , Adult , Australia , Curriculum , Education, Nursing, Baccalaureate , Female , Humans , Leadership , Male , Middle Aged , Nursing Staff, Hospital/education , Pregnancy , Racism/psychologyABSTRACT
Stromal invasion is identified commonly in cutaneous malignancies; however, invasive patterns are defined inconsistently and their clinical relevance is uncertain. This study aimed to define objective, quantifiable histomorphological invasive patterns in low-grade canine mast cell tumours (MCTs) and grade I/II soft tissue sarcomas (STSs), and correlate invasive patterns with overall excisional status. Haematoxylin and eosin-stained glass slides prepared for routine histopathology of surgically-excised tumours from client-owned dogs were evaluated for invasion beyond their subgross edge, asymmetrical invasion, satellite lesions, lymphovascular invasion, perineurovascular growth, growth along fascial planes, intramuscular invasion and multicompartmental involvement. Digital histological tumour-free margins <1 mm in any direction were considered to represent an incomplete excision. Fifty-one dogs with 69 tumours (50 MCTs and 19 STSs) were included in the study. Invasion in both circumferential and deep directions was significantly greater in MCTs compared with STSs (exact 2-tailed P <0.0001 circumferential; P = 0.0095 deep). Within the MCT group, circumferential invasion was greater than deep invasion (P = 0.0076). Multivariate logistic regression analysis found two variables that were significantly associated with incomplete MCT excision: intraoperative grossly normal circumferential surgical margin size (odds ratio of 0.776, 95% confidence interval: 0.651-0.925) and asymmetry invasion index (odds ratio of 1.318, 95% confidence interval: 1.039-1.671). These data may help create evidence-based strategies for planning surgical resections of cutaneous malignancies. Presence of asymmetrical microscopical invasion might prompt pathologists to perform more comprehensive surgical margin evaluation.
Subject(s)
Dog Diseases/pathology , Mast-Cell Sarcoma/veterinary , Sarcoma/veterinary , Soft Tissue Neoplasms/veterinary , Animals , DogsABSTRACT
Background: Atrial fibrillation (Afib) patients are at an increased risk of stroke. Patients at moderate to high risk of stroke typically receive antithrombotics, placing them at an increased risk of bleeding. The HAS-BLED tool has been validated in Afib patients receiving warfarin for prediction of major bleeding events. Although HAS-BLED has been researched in patients receiving warfarin, this tool has not been validated with the novel anticoagulant rivaroxaban. Methods: The trial design was retrospective case-control approved by the Institutional Review Board at University of Tennessee Medical Center. Patients who were identified as having a bleeding event were cross-referenced with a list of patients receiving rivaroxaban. Inclusion criteria were adult patients with atrial fibrillation who were taking rivaroxaban for at least six months, with a CHA2DS2-VASc score greater than or equal to 2 OR CHADS2 score greater than or equal to 1. The primary endpoint is the predictive ability of HAS-BLED as measured through the c-statistic. Secondary endpoints include correlation of HAS-BLED and bleeding risk. Results: After reviewing 9621 medical records, 15 patients met the inclusion criteria for major bleeding. Ninety patients were randomly selected for inclusion as the matched control group. The predictive ability of HAS-BLED was not statistically significant (c statistic = 0.68; p = 0.07), but did show some diagnostic ability to predict major bleeding events. Patients with major bleeding were more likely to have a history of bleeding and use concomitant antiplatelet agents. There were significantly more patients with a HAS-BLED score greater than or equal to 3 in the patients that experienced a major bleeding event. Conclusion: HAS-BLED demonstrated some diagnostic ability to predict major bleeding events in patients receiving rivaroxaban but this was not statistically significant due to limited sample size.
ABSTRACT
The goal of this study was to investigate the potential of biofiltration to reduce the formation potential of disinfection byproducts (DBPs). Particularly, the work investigates the effect of the duration of the filter cycle on the formation potential of total trihalomethanes (TTHM) and five species of haloacetic acids (HAA5), dissolved oxygen (DO), organic carbon, nitrogen and total phosphorous concentrations along with biofilm coverage of the filter media and biomass viability of the attached cells. The study was conducted on a full-scale biologically active filter, with anthracite and sand media, at the Britannia water treatment plant (WTP), located in Ottawa, Ontario, Canada. The formation potential of both TTHMs and HAA5s decreased due to biofiltration. However the lowest formation potentials for both groups of DBPs and or their precursors were observed immediately following a backwash event. Hence, the highest percent removal of DBPs was observed during the early stages of the biofiltration cycle, which suggests that a higher frequency of backwashing will reduce the formation of DBPs. Variable pressure scanning electron microscopy (VPSEM) analysis shows that biofilm coverage of anthracite and sand media increases as the filtration cycle progressed, while biomass viability analysis demonstrates that the percentage of cells attached to the anthracite and sand media also increases as the filtration cycle progresses. These results suggest that the development and growth of biofilm on the filters increases the DPB formation potential.
Subject(s)
Disinfectants/analysis , Drinking Water/chemistry , Water Pollutants, Chemical/analysis , Water Purification/methods , Canada , Disinfection/methods , Drinking Water/analysis , Filtration , Nitrogen/analysis , Ontario , Silicon Dioxide/analysis , Trihalomethanes/analysis , Water SupplyABSTRACT
Accelerometers objectively monitor physical activity and sedentary patterns and are increasingly used in the research setting. It is important to maintain consistency in data analysis and reporting, therefore, we: (1) systematically identified studies using accelerometry (ActiGraph, Pensacola, FL, USA) to measure moderate-to-vigorous physical activity (MVPA) and sedentary time in older adults, and (2) based on the review findings, we used different cut-points obtained to analyze accelerometry data from a sample of community-dwelling older women. We identified 59 articles with cut-points ranging between 574 and 3,250 counts/min for MVPA and 50 and 500 counts/min for sedentary time. Using these cut-points and data from women (mean age, 70 years), the median MVPA minutes per day ranged between 4 and 80 min while percentage of sedentary time per day ranged between 62 % and 86 %. These data highlight (1) the importance of reporting detailed information on the analysis assumptions and (2) that results can differ greatly depending on analysis parameters.
ABSTRACT
SUMMARY: This randomized controlled trial evaluated the effect of resistance training frequency (0, 1, and 2 times/week) on cortical volumetric bone mineral density (vBMD) at the tibia in older women. There was no mean difference in change in tibial cortical vBMD in older women who engaged in resistance training (RT) one or two times/week compared with the control group over 12 months after adjusting for baseline values. INTRODUCTION: National guidelines recommend RT two to three times/week to optimize bone health. Our objective was to determine the effect of a 12-month intervention of three different RT frequencies on tibial volumetric cortical density (CovBMD) in healthy older women. METHODS: We randomized participants to the following groups: (1) 2×/week balance and tone group (i.e., no resistance beyond body weight, BT), (2) 1×/week RT (RT1), and (3) 2×/week RT (RT2). Treatment allocation was concealed, and measurement team and the bone data analyst were blinded to group allocation. We used peripheral quantitative computed tomography to acquire one 2.3-mm scan at the 50 % tibia, and the primary outcome was CovBMD. Data were collected at baseline, 6 and 12 months, and we used linear mixed modeling to assess the effect at 12 months. RESULTS: We assessed 147 participants; 100 women provided data at all three points. Baseline unadjusted mean (SD) tibial CovBMD (in milligrams per cubic centimeter) at the 50 % site was 1,077.4 (43.0) (BT), 1,087.8 (42.0) (RT1), and 1,058.7 (60.4) (RT2). At 12 months, there were no statistically significant differences (-0.45 to -0.17 %) between BT and RT groups for mean difference in change in tibial CovBMD for exercise interventions (BT, RT1, RT2) after adjusting for baseline tibial CovBMD. CONCLUSION: We note no mean difference in change in tibial CovBMD in older women who engaged in RT one or two times/week compared with the control group over 12 months. It is unknown if RT of 3× or 4×/week would be enough to promote a statistically significant difference in change of bone density.
Subject(s)
Bone Density/physiology , Osteoporosis, Postmenopausal/prevention & control , Resistance Training/methods , Tibia/physiology , Aged , Exercise Test/methods , Female , Humans , Motor Activity/physiology , Osteoporosis, Postmenopausal/physiopathology , Postural Balance/physiology , Resistance Training/adverse effects , Single-Blind Method , Tibia/anatomy & histology , Tibia/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor α (FRα), as well as possible effects of parental demographics or prenatal exposures. METHODS: We conducted a nested case-control study within the Norwegian Mother and Child Cohort Study. The study included mothers of children with an NTD (n = 11), cleft lip with or without cleft palate (CL/P, n= 72), or cleft palate only (CPO, n= 27), and randomly selected mothers of controls (n = 221). The inhibition of folic acid binding to FRα was measured in maternal plasma collected around 17 weeks of gestation. On the basis of prior literature, the maternal age, gravidity, education, smoking, periconception folic acid supplement use and milk consumption were considered as potential confounding factors. RESULTS: There was an increased risk of NTDs with increased binding inhibition [adjusted odds ratio (aOR) = 1.4, 95% confidence interval (CI) 1.0-1.8]. There was no increased risk of oral facial clefts from inhibited folic acid binding to FRα (CL/P aOR = 0.7, 95% CI 0.6-1.0; CPO aOR = 1.1, 95% CI 0.8-1.4). No association was seen between smoking, folate supplementation or other cofactors and inhibition of folic acid binding to FRα. CONCLUSIONS: Inhibition of folic acid binding to FRα in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts.
Subject(s)
Folate Receptor 1/blood , Folic Acid/metabolism , Neural Tube Defects/etiology , Adult , Autoantibodies/analysis , Case-Control Studies , Cleft Lip/etiology , Cleft Palate/etiology , Female , Folate Receptor 1/immunology , Folic Acid Deficiency/complications , Humans , Norway , PregnancyABSTRACT
A 10-year-old intact male Labrador Retriever dog was euthanized because of rapid deterioration after suffering from mild chronic cough, hematuria, acute blindness, ataxia, and lethargy. Clinical examination revealed blepharospasm and hyphema, with clear discharge from the right eye; a firm mass in an enlarged right testicle; a mass in the irregularly enlarged prostate; and nodules in the left kidney, liver, and spleen detected by abdominal sonography. Cytologic evaluation of fine needle aspirates from the prostate, testis, and kidney comprised large, clustered or individualized, anaplastic cells that lacked convincing tissue differentiation. Necropsy examination revealed an irregularly enlarged prostate with dark tan to red zones and multiple, discrete, beige to dark red nodules that ranged from 0.5 to 6 cm in diameter in the lung, liver, left kidney, right testis, colon wall, stomach wall, and brain. On histologic examination, discrete nests of anaplastic carcinoma-like tumor cells were found in sections of all affected organs. Results of immunohistochemical examination revealed widespread expression of von Willebrand factor and the absence of cytokeratin in neoplastic cells. The diagnosis was metastatic epithelioid hemangiosarcoma, primary site unknown.
Subject(s)
Dog Diseases/pathology , Hemangiosarcoma/veterinary , Prostatic Neoplasms/veterinary , Animals , Dogs , Hemangiosarcoma/pathology , Male , Prostatic Neoplasms/pathologyABSTRACT
Chlorofluorocarbons CFC-11 (CCl(3)F), CFC-12 (CCl(2)F(2)), and CFC-113 (CCl(2)F-CClF(2)) are used in hydrology as transient tracers under the assumption of conservative behavior in the unsaturated and saturated soil zones. However, laboratory and field studies have shown that these compounds are not stable under anaerobic conditions. To determine the degradation rates of CFCs in a tropical environment, atmospheric air, unsaturated zone soil gas, and anoxic groundwater samples were collected in Araihazar upazila, Bangladesh. Observed CFC concentrations in both soil gas and groundwater were significantly below those expected from atmospheric levels. The CFC deficits in the unsaturated zone can be explained by gas exchange with groundwater undersaturated in CFCs. The CFC deficits observed in (3)H/(3)He dated groundwater were used to estimate degradation rates in the saturated zone. The results show that CFCs are degraded to the point where practically no (<5%) CFC-11, CFC-12, or CFC-113 remains in groundwater with (3)H/(3)He ages above 10 yr. In groundwater sampled at our site CFC-11 and CFC-12 appear to degrade at similar rates with estimated degradation rates ranging from approximately 0.25 yr(-1) to approximately 6 yr(-1). Degradation rates increased as a function of reducing conditions. This indicates that CFC dating of groundwater in regions of humid tropical climate has to be carried out with great caution.
Subject(s)
Biodegradation, Environmental , Chlorofluorocarbons/chemistry , Soil Pollutants/chemistry , Water Pollutants, Chemical/chemistry , Bangladesh , Helium/chemistry , Tritium/chemistryABSTRACT
Substance use continues to be closely associated with both HIV infection and treatment considerations in all at-risk populations. Among those groups heretofore not well characterized epidemiologically or clinically are those dual-risk men who have sex with other men (MSM) and use and/or inject drugs. Of particular current concern with regard to drug-using MSM is the growth in popularity of a group of recreational or so-called party drugs associated with specific social and sexual environments and networks. Chief among these drugs are hallucinogens, such as MDMA, ketamine, and GHB, and stimulants, such as cocaine, amphetamines, and methamphetamine. Increased methamphetamine use by MSM is particularly alarming because of its reported associations with high-risk injecting and sexual behaviors. Preliminary data are reported from an ethnographic exploration of MSM methamphetamine users in the Pacific Northwest of the United States. Case studies drawn from the data illustrate the complex and variable patterns of methamphetamine use among MSM. Finally, implications for nursing are discussed, and "upstream nursing" is suggested as a means of patient advocacy for HIV nurses working with substance-using populations.
Subject(s)
HIV Infections/complications , Homosexuality, Male , Substance-Related Disorders/virology , Adult , Focus Groups , HIV Infections/nursing , HIV Infections/psychology , Humans , Los Angeles , Male , Middle Aged , Nursing Research , Patient Care Planning , San Francisco , Specialties, Nursing/education , Substance-Related Disorders/nursing , Substance-Related Disorders/psychology , WashingtonABSTRACT
All permanent pacemakers and implantable defibrillators (PPM/ICDs) will continue to function as programmed without regard to the date in the year 2000 (Y2K). All manufacturers contacted reassured us that some of these devices incorporate a day/year clock in the circuitry; however, these are not involved in sensing or delivering programmed therapy. Some manufacturers' device programmers will roll over to the year 2000 without any problems at all, whereas others may have difficulty with date and time stamping on printed reports. We tested 14 different types of PPM/ICD programmers for Y2K compliance using 8 tests. Five of the 14 models passed each test and were labeled at our institution with a green "Y2K" sticker to identify them as Y2K compatible and needing no special attention after December 31, 1999. The most common test failed was the ability to roll the date forward from December 31, 1999, with the programmer power off. Organizations should consider testing and replacing noncompliant device programmers or placing a red sticker with "Y2K" crossed out on noncompliant pieces. The red sticker alerts the advanced practice nurse or physician to the need to confirm the appropriate date and time in the programmer after startup in the year 2000 and before interrogating or programming any PPM/ICD, to avoid inappropriate date and time stamping on printed reports from that programmer.
Subject(s)
Defibrillators, Implantable , Pacemaker, Artificial , Software , Attitude of Health Personnel , Computer Systems , Equipment Design , Humans , Nurse Clinicians , Nurse Practitioners , Physicians , Software DesignABSTRACT
BACKGROUND: Available assays for cardiac troponin I (cTnI) yield numerically different results. The aim of this study was to compare patient values obtained from four cTnI immunoassays. METHODS: We studied the Stratus(R) II assay, the Opus(R) II assay, the Access(R) assay, and a research-only cTnI heterogeneous immunoassay that uses the Dade Behring aca(R) plus immunoassay system equipped with two new noncommercial monoclonal antibodies. Because the aca plus cTnI assay is for research only, we first evaluated and analytically validated it for serum and citrated plasma. Initially, each method was calibrated using the method-specific calibrator supplied by each manufacturer; however, the aca plus cTnI assay was calibrated using patient serum pools containing cTnI and selected on the basis of increased creatine kinase MB isoenzyme and with values assigned by use of the Stratus cTnI assay. For method comparisons, individual patient sample cTnI values were determined and compared with the Stratus II assay. RESULTS: Passing and Bablock regression analysis yielded slopes of 1.44 (r = 0.96; n = 72) for the Opus II vs Stratus II assays; 0.07 (r = 0.91; n = 72) for the Access vs Stratus II assays; and 0.90 (r = 0.91, n = 72) for the aca plus vs Stratus II assays. The recalibration of each method with a Stratus II-assigned serum pool improved, but did not entirely eliminate, the slope differences between the different assays (range, 1.00-1.16). The observed scatter in the correlation curves remained. CONCLUSION: There is a need to further explore the specificities of these assays with respect to the different circulating forms of cTnI.
Subject(s)
Myocardium/metabolism , Troponin I/blood , Antibodies, Monoclonal , Antibody Specificity , Blotting, Western , Calibration , Humans , Reagent Kits, Diagnostic , Reference Standards , Regression Analysis , Reproducibility of Results , Troponin I/immunologyABSTRACT
The increasing interest in the measurement of serum C-reactive protein in relation to the risk stratification of patients with chest pain has demonstrated the need for more sensitive routine methods of measurement and an accurate definition of the reference range. We report the determination of a reference range in serum samples from 491 blood donors using a particle enhanced turbidimetric immunoassay that has been modified to offer better imprecision within the reference range. The median values were found to be 2.40 and 2.20 mg/l for males and females, respectively with 95th percentile range of 1.20-5.20 and 0.40-5.40 mg/l, respectively.
Subject(s)
Blood Donors , C-Reactive Protein/metabolism , Scattering, Radiation , Adult , Female , Humans , Light , Male , Middle Aged , Reference Values , Sensitivity and SpecificityABSTRACT
Mitochondria proliferate when cellular energy demand increases. However, the pathways leading to enhanced expression of mitochondrial genes are largely unknown. We tested the hypothesis that an altered flux through energy metabolism is the key regulatory event by decreasing mitochondrial energy supply to rat heart cells by creatine depletion. Electron microscopy showed that the density of mitochondria increased by 75% in such hearts (p < 0.01). Levels of representative mRNAs encoded on mitochondrial DNA (mtDNA) or on nuclear chromosomes were elevated 1.5 to 2-fold (p < 0.05), while the mtDNA content was unchanged. The mRNA for the nuclear encoded mitochondrial transcription factor A (mtTFA) was increased after GPA feeding (p < 0.05). Thus, we have shown that an impairment of mitochondrial energy supply causes stimulation of gene expression resulting in mitochondrial proliferation, probably as a compensatory mechanism. The observed activation of the mtTFA gene corroborates the important function of this protein in nuclear-mitochondrial communication.
Subject(s)
Energy Transfer/drug effects , Heart Ventricles/metabolism , Mitochondria/genetics , Mitochondria/physiology , Phosphocreatine/antagonists & inhibitors , Phosphocreatine/physiology , Xenopus Proteins , Animals , Blotting, Northern , DNA, Mitochondrial/biosynthesis , DNA, Mitochondrial/drug effects , Electron Transport Complex IV/analysis , Electron Transport Complex IV/drug effects , Electron Transport Complex IV/genetics , Female , Gene Expression/drug effects , Guanidines/pharmacology , Heart Ventricles/chemistry , Heart Ventricles/ultrastructure , Mitochondria/drug effects , Propionates/pharmacology , RNA, Messenger/biosynthesis , RNA, Messenger/drug effects , Rats , Rats, Sprague-Dawley , Trans-Activators/biosynthesis , Trans-Activators/drug effects , Transcription, Genetic/drug effectsABSTRACT
Feeding beta-guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, decreases mortality and increases brain ATP stability in hypoxic mice. To study brain ATP metabolism in GPA-fed animals, respiratory rates were measured in grey matter and white matter slices as well as cerebral hemisphere mitochondria from GPA-fed mice and rats. Creatine kinase and adenylate kinase activities were measured in rat cerebral grey matter and white matter. Respiratory rates and oxidative phosphorylation were the same in GPA-fed mice and control mice. The adenylate kinase activity increased 50% and creatine kinase showed a small decrease in grey matter. In white matter, creatine kinase increased 50% while adenylate kinase decreased. Thus, GPA produces opposite adaptive changes in adenylate kinase and creatine kinase in grey matter and in white matter. These results suggest that the creatine kinase reaction in grey matter acts to regulate cellular ADP and ATP concentrations.
Subject(s)
Adenosine Triphosphate/metabolism , Brain/metabolism , Guanidines/pharmacology , Hypoxia/metabolism , Propionates/pharmacology , Adenosine Diphosphate/metabolism , Adenylate Kinase/metabolism , Animals , Creatine Kinase/metabolism , Drug Resistance/physiology , Female , Mice , Mice, Inbred Strains , Mitochondria/metabolism , Oligomycins/pharmacology , Oxygen Consumption/physiology , Potassium Chloride/pharmacology , Rats , Rats, Sprague-Dawley , Respiration/drug effectsABSTRACT
Creatine kinase (CK) isoenzymes, specifically located at places of energy demand and energy production, are linked by a phosphocreatine/creatine (PCr/Cr) circuit, found in cells with intermittently high energy demands. Cytosolic CKs, in close conjunction with Ca(2+)-pumps, play a crucial role for the energetics of Ca(2+)-homeostasis. Mitochondrial Mi-CK, a cuboidal-shaped octamer with a central channel, binds and crosslinks mitochondrial membranes and forms a functionally coupled microcompartment with porin and adenine nucleotide translocase for vectorial export of PCr into the cytosol. The CK system is regulated by AMP-activated protein kinase via PCr/Cr and ATP/AMP ratios. Mi-CK stabilizes and cross-links cristae- or inner/outer membranes to form parallel membrane stacks and, if overexpressed due to creatine depletion or cellular energy stress, forms those crystalline intramitochondrial inclusions seen in some mitochondrial cytopathy patients. Mi-CK is a prime target for free radical damage by peroxynitrite. Mi-CK octamers, together with CK substrates have a marked stabilizing and protective effect against mitochondrial permeability transition pore opening, thus providing a rationale for creatine supplementation of patients with neuromuscular and neurodegenerative diseases.
Subject(s)
Creatine Kinase/chemistry , Creatine Kinase/physiology , Energy Metabolism , Mitochondria/enzymology , Adenine Nucleotides/metabolism , Animals , Calcium/metabolism , Cytosol/enzymology , Humans , Isoenzymes , Mitochondria/physiology , Phosphocreatine/metabolismABSTRACT
Fifteen years into the HIV/AIDS epidemic, a great deal is now known about the different populations impacted by the disease, including those affected directly or indirectly by drug use. Anthropology has played a critical role in assisting with this task by identifying hidden populations, developing new methodological approaches, and targeting outreach efforts. In spite of this considerable body of ethnographic knowledge, men who have sex with other men (i.e., MSM, or gay and bisexual men) who use drugs have not received the same research attention as other drug users, despite the fact that they represent nearly one-fifth of AIDS cases in the U.S. with injection drug histories. In response to the alarming increase in HIV seroprevalence among this population, this ethnographic project provides preliminary data about those who are at dual risk for HIV through both homosexual behavior and injection drug use.
Subject(s)
Amphetamine-Related Disorders/psychology , HIV Infections/ethnology , HIV Infections/psychology , Sexual Behavior/psychology , Adult , Amphetamines/adverse effects , Amphetamines/pharmacology , Homosexuality, Male/psychology , Humans , Male , Mental Health , Middle Aged , Risk Factors , Substance Abuse, Intravenous/ethnology , Substance Abuse, Intravenous/psychologyABSTRACT
Mitochondrial inclusion bodies are often described in skeletal muscle of patients suffering diseases termed mitochondrial myopathies. A major component of these structures was discovered as being mitochondrial creatine kinase. Similar creatine kinase enriched inclusion bodies in the mitochondria of creatine depleted adult rat cardiomyocytes have been demonstrated. Structurally similar inclusion bodies are observed in mitochondria of ischemic and creatine depleted rat skeletal muscle. This paper describes the various methods for inducing mitochondrial inclusion bodies in rodent skeletal muscle, and compares their effects on muscle metabolism to the metabolic defects of mitochondrial myopathy muscle. We fed rats with a creatine analogue guanidino propionic acid and checked their solei for mitochondrial inclusion bodies, with the electron microscope. The activity of creatine kinase was analysed by measuring creatine stimulated oxidative phosphorylation in soleus skinned fibres using an oxygen electrode. The guanidino propionic acid-rat soleus mitochondria displayed no creatine stimulation, whereas control soleus did, even though the GPA solei had a five fold increase in creatine kinase protein per mitochondrial protein. The significance of these results in light of their relevance to human mitochondrial myopathies and the importance of altered cell energetics and metabolism in the formation of these crystalline structures are discussed.