EFFECTIVE DOSE ESTIMATION IN WHOLE BODY 18F-FDG PET/CT IMAGING.

Positron emission tomography-computed tomography (PET-CT) with internal administration of the FDG-18 is characterized as a widespread functional imaging modality in diagnostic radiation medicine, which increases the patient effective doses owing to the presence of internal and external radiation sources. Hence, patient effective dose estimation has been pinpointed as a significant factor in radiation protection assessment. A large number of studies have been published in this regard, and various dosimetry methods have been surveyed. According to our previous research, 10 patients had participated in PET-CT scans with three static time sequences imaging. PET effective doses were estimated using a simple method derived from Anderson et al. and Kaushik et al. coefficients, and the CT effective doses were surveyed with a CTDI phantom and cylindrical ionization chamber. The CT dose was tripled owing to the three static time-sequences imaging. The effective doses were calculated using different coefficients and the results of the PET effective doses were compared. The PET-CT effective dose was varied from 17.14 to 18.42 mSv based on Kaushik et al. coefficients which were measured for one low-dose CT scan. This study aimed to survey simple PET-CT effective dose estimation using three static-time imaging approaches which increases the total patient effective doses.

Regulation of blood-brain barrier integrity by microbiome-associated methylamines and cognition by trimethylamine N-oxide.

BACKGROUND: Communication between the gut microbiota and the brain is primarily mediated via soluble microbe-derived metabolites, but the details of this pathway remain poorly defined. Methylamines produced by microbial metabolism of dietary choline and L-carnitine have received attention due to their proposed association with vascular disease, but their effects upon the cerebrovascular circulation have hitherto not been studied. RESULTS: Here, we use an integrated in vitro/in vivo approach to show that physiologically relevant concentrations of the dietary methylamine trimethylamine N-oxide (TMAO) enhanced blood-brain barrier (BBB) integrity and protected it from inflammatory insult, acting through the tight junction regulator annexin A1. In contrast, the TMAO precursor trimethylamine (TMA) impaired BBB function and disrupted tight junction integrity. Moreover, we show that long-term exposure to TMAO protects murine cognitive function from inflammatory challenge, acting to limit astrocyte and microglial reactivity in a brain region-specific manner. CONCLUSION: Our findings demonstrate the mechanisms through which microbiome-associated methylamines directly interact with the mammalian BBB, with consequences for cerebrovascular and cognitive function. Video abstract.

Non-fatal opioid overdose, naloxone access, and naloxone training among people who recently used opioids or received opioid agonist treatment in Australia: The ETHOS Engage study.

BACKGROUND: Overdose is a major cause of morbidity and mortality among people who use opioids. Naloxone can reverse opioid overdoses and can be distributed and administered with minimal training. People with experience of overdose are a key population to target for overdose prevention strategies. This study aims to understand if factors associated with recent non-fatal opioid overdose are the same as factors associated with naloxone access and naloxone training in people who recently used opioids or received opioid agonist treatment (OAT). METHODS: ETHOS Engage is an observational study of people who inject drugs in Australia. Logistic regression models were used to estimate odds ratios for non-fatal opioid overdose, naloxone access and naloxone training. RESULTS: Between May 2018-September 2019, 1280 participants who recently used opioids or received OAT were enrolled (62% aged >40 years; 35% female, 80% receiving OAT, 62% injected drugs in the preceding month). Recent opioid overdose (preceding 12 months) was reported by 7% of participants, lifetime naloxone access by 17%, and lifetime naloxone training by 14%. Compared to people receiving OAT with no additional opioid use, recent opioid, benzodiazepine (preceding six months), and hazardous alcohol use was associated with recent opioid overdose (aOR 3.91; 95%CI: 1.68-9.10) and lifetime naloxone access (aOR 2.12; 95%CI 1.29-3.48). Among 91 people who reported recent overdose, 65% had never received take-home naloxone or naloxone training. CONCLUSIONS: Among people recently using opioids or receiving OAT, benzodiazepine and hazardous alcohol use is associated with non-fatal opioid overdose. Not all factors associated with non-fatal overdose correspond to factors associated with naloxone access. Naloxone access and training is low across all groups. Additional interventions are needed to scale up naloxone provision.

Evaluation of Blood Parameters Alteration Following Low-dose Radiation Induced by Myocardial Perfusion Imaging.

INTRODUCTION: With increasing the usage of myocardial perfusion imaging (MPI) for the diagnosis of ischemic heart disease, we aimed to evaluate the side effects of low-dose radiation induced by this technique on blood elements, especially proteins and liver function factors. MATERIAL AND METHODS: 40 eligible patients (Mean age: 54.62±10.35, 22 female and 18 male), who had referred to the nuclear medicine department for MPI from May till August 2014, were enrolled in the study. A blood sample was taken from each patient just before and 24 hours after the injection of 740Mbq of Tecnetium-99m Methoxy isobutyl isonitrile (99mTc-MIBI) in the rest phase of the MPI in a reference medical laboratory; blood tests included total protein (TP), albumin (Alb), globulin (Glo), aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), direct bilirubin (D.Bili), total bilirubin (T.Bili), serum iron (SI), total iron bounding capacity (TIBC), Albumin globulin ratioA/G ratio), and complete blood count (CBC). RESULTS: Injection of 740Mbq99mTc-MIBI caused a significant increase in serum levels of AST (p= 0.001), ALT (p= 0.001), SI (p= 0.030), TIBC (p= 0.003) and A/G Ratio (p= 0.020). However, following radiotracer injection, a significant decrease was noted in the serum levels of TP (p= 0.002), Alb (p= 0.014), Glo(p= 0.002), ALP (p= 0.001), D.Bili (p= 0.003) and T.Bili (p= 0.000). CONCLUSION: Due to increased usage of MPI, our data highlights the importance of monitoring the clinical and paraclinical effects of the procedure on vital organs and physiological pathways to reduce their adverse effects.

Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era.

At a population level, little is known regarding the risk of liver- and nonliver-related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated cirrhosis (DC). This large-scale national record-linkage study estimates these outcomes following first hospital admission for DC. Record-linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow-up the disease course of all identified HCV-diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994-2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the relative risks of liver-related or all-cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver-related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver-related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV-infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured.

Look Different: Effect of Radiation Hormesis on the Survival Rate of Immunosuppressed Mice.

BACKGROUND: Hormesis is defined as the bio-positive response of something which is bio-negative in high doses. In the present study, the effect of radiation hormesis was evaluated on the survival rate of immunosuppressed BALB/c mice by Cyclosporine A. MATERIAL AND METHODS: We used 75 consanguine, male, BALB/c mice in this experiment. The first group received Technetium-99m and the second group was placed on a sample radioactive soil of Ramsar region (800Bq) for 20 days. The third group was exposed to X-rays and the fourth group was placed on the radioactive soil and then injected Technetium-99m. The last group was the sham irradiated control group. Finally, 30mg Cyclosporine A as the immunosuppressive agent was orally administered to all mice 48 hours after receiving X-rays and Technetium-99m. The mean survival rate of mice in each group was estimated during time. RESULTS: A log rank test was run to determine if there were differences in the survival distribution for different groups and related treatments. According to the results, the survival rate of all pre-irradiated groups was more than the sham irradiated control group (p < .05). The highest survival time was related to the mice which were placed on the radioactive soil of Ramsar region for 20 days and then injected Technetium-99m. CONCLUSION: This study confirmed the presence of hormetic models and the enhancement of survival rate in immunosuppressed BALB/c mice as a consequence of low-dose irradiation. It is also revealed the positive synergetic radioadaptive response on survival rate of immunosuppressed animals.

A Comparative Study on the Life-Saving Radioprotective Effects of Vitamins A, E, C and Over-the-Counter Multivitamins.

INTRODUCTION: Oral intake of vitamins which present antioxidant characteristics can protect living organisms against oxidative damage caused by exposure to ionizing radiation. It was previously reported that administration of high levels of vitamin C can lead to increased DNA damage through production of hydroxyl radicals from hydrogen peroxide by the Fenton reaction. However, our early experiments did not confirm this hypothesis. The main goal of this study was to determine if high doses of Vit C can show life-saving radioprotective effects. MATERIALS AND METHODS: Phase I: Seventy two male Balb/c mice weighing 20-25g were randomly divided into six groups of 12 animals each. Group I; Vit E for five days, Groups II and III; Vit C and Vit A. Group 4; all three vitamins. Group V; an over-the-counter multivitamin. Group VI; none of the above. Phase II: 120 male BALB/c mice weighing 20-25g were randomly divided into 12 groups of 10 each. Group I; Vit A for five days. Groups II-IV; Vit C 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. Group V-VII; Vit E at daily doses of 200 iu/kg, 400 iu/kg, 800 iu/kg, respectively. Group VIII and IX; all three vitamins at low and high doses, respectively. Group X; an over-the-counter multivitamin. Group XI; controls group and Group XII; received pure olive oil. All animals (Phases I and II) were exposed to a lethal dose of gamma rays and the survival rates of the animals were monitored and recorded continuously for 16 days after exposure. RESULTS: Phase I: 14 days after irradiation the survival rate for control group was 33.33%, while the survival rates for the 1st to 5th groups were 45.45%, 81.81%, 50%, 57.14%, and 9.09% , respectively. Phase II: The survival rates in the control group and the group that only received pure olive oil, were 50% and 60%, respectively. Survival rate in the animals received Vit C at daily doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, were 90%, 90% and 90%, respectively. Log rank (Mantel-Cox) test showed statistically significant differences between the survival rates in control irradiated mice (no vitamins) and mice received Vit C at daily doses of 200 mg/kg (P=0.042), 400 mg/kg (P=0.042) and 800 mg/kg (P=0.042). CONCLUSION: Altogether, findings of this study showed that even high doses of Vit C can show life-saving radioprotective effects. The significant radioprotective effect of Vit C at doses used in this study, opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life-threatening situations such as exposure to lethal doses of ionizing radiation.  The radioprotective effect of Vit A and Vit E seem to be less efficient compared to that of Vit C.

Effect of treatment willingness on specialist assessment and treatment uptake for hepatitis C virus infection among people who use drugs: the ETHOS study.

Among people who inject drugs (PWID) with chronic HCV, the association between HCV treatment willingness and intent, and HCV specialist assessment and treatment were evaluated. The Enhancing Treatment for Hepatitis C in Opioid Substitution Settings (ETHOS) is a prospective observational cohort. Recruitment was through six opioid substitution treatment clinics, two community health centres and one Aboriginal community controlled health organisation in Australia. Analyses were performed using logistic regression. Among 415 participants (mean age 41 years, 71% male), 67% were 'definitely willing' to receive HCV treatment and 70% reported plans to initiate therapy 12 months postenrolment. Those definitely willing to receive HCV treatment were more likely to undergo specialist assessment (64% vs 32%, P < 0.001) and initiate therapy (36% vs 9%, P < 0.001), compared to those with lower treatment willingness. Those with early HCV treatment plans were more likely to undergo specialist assessment (65% vs 27%, P < 0.001) and initiate therapy (36% vs 5%, P < 0.001), compared to those without early plans. In adjusted analyses, HCV treatment willingness independently predicted specialist assessment (aOR 3.06, 95% CI 1.90, 4.94) and treatment uptake (aOR 4.33, 95% CI 2.14, 8.76). In adjusted analysis, having early HCV treatment plans independently predicted specialist assessment (aOR 4.38, 95% CI 2.63, 7.29) and treatment uptake (aOR 9.79, 95% CI 3.70, 25.93). HCV treatment willingness was high and predicted specialist assessment and treatment. Strategies for enhanced HCV care should be developed with an initial focus on people willing to receive treatment and to increase treatment willingness among those less willing.

Indoor solar thermal energy saving time with phase change material in a horizontal shell and finned-tube heat exchanger.

An experimental as well as numerical investigation was conducted on the melting/solidification processes of a stationary phase change material (PCM) in a shell around a finned-tube heat exchanger system. The PCM was stored in the horizontal annular space between a shell and finned-tube where distilled water was employed as the heat transfer fluid (HTF). The focus of this study was on the behavior of PCM for storage (charging or melting) and removal (discharging or solidification), as well as the effect of flow rate on the charged and discharged solar thermal energy. The impact of the Reynolds number was determined and the results were compared with each other to reveal the changes in amount of stored thermal energy with the variation of heat transfer fluid flow rates. The results showed that, by increasing the Reynolds number from 1000 to 2000, the total melting time decreases by 58%. The process of solidification also will speed up with increasing Reynolds number in the discharging process. The results also indicated that the fluctuation of gradient temperature decreased and became smooth with increasing Reynolds number. As a result, by increasing the Reynolds number in the charging process, the theoretical efficiency rises.

Lower life expectancy among people with an HCV notification: a population-based linkage study.

Among people with hepatitis C virus (HCV) infection, liver disease-related deaths have risen over the last 20 years. Life expectancy has not been estimated in this population. HCV notifications (mandatory notification of anti-HCV-positive serology since 1991) reported to the New South Wales Health Department from 1992 to 2006 were linked to cause of death data. Abridged life tables were constructed from age-specific mortality rates. Life expectancy from ages 18-70 years for non-drug-related mortality causes was estimated using competing risk methods and compared to the general population of Australia. The cohort comprised 81 644 individuals with an HCV notification, with median follow-up of 7.6 years. Median age at notification was 34 years [interquartile range (IQR) 28-42] and 63% were male. Between 1992 and 2006, 4607 deaths occurred. Median age at liver- and drug-related death among males was 51 (IQR 45-66) and 36 (IQR 31-42) years, respectively, and among females was 63 (IQR 49-74) and 36 (IQR 30-41) years, respectively. In each year of follow-up before 2000, 15-21% of deaths were liver- and 30-39% were drug-related. After 2000, liver-related deaths increased to 20-26% of deaths in each year and drug-related deaths decreased to 13-19%. Excluding drug-related causes of death, life expectancy was lowered by an average of 4.2 (SD ± 1.0) and 5.4 (SD ± 0.7) years for males and females, respectively. Among people with an HCV notification, an increasing proportion of deaths are liver-related. Following removal of drug-related mortality, life expectancy in this population remained considerably lower, compared with the general population.

Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity in trained OPA1-deficient mice.

The role of OPA1, a GTPase dynamin protein mainly involved in the fusion of inner mitochondrial membranes, has been studied in many cell types, but only a few studies have been conducted on adult differentiated tissues such as cardiac or skeletal muscle cells. Yet OPA1 is highly expressed in these cells, and could play different roles, especially in response to an environmental stress like exercise. Endurance exercise increases energy demand in skeletal muscle and repeated activity induces mitochondrial biogenesis and activation of fusion-fission cycles for the synthesis of new mitochondria. But currently no study has clearly shown a link between mitochondrial dynamics and biogenesis. Using a mouse model of haploinsufficiency for the Opa1 gene (Opa1(+/-)), we therefore studied the impact of OPA1 deficiency on the adaptation ability of fast skeletal muscles to endurance exercise training. Our results show that, surprisingly, Opa1(+/-) mice were able to perform the same physical activity as control mice. However, the adaptation strategies of both strains after training differed: while in control mice mitochondrial biogenesis was increased as expected, in Opa1(+/-) mice this process was blunted. Instead, training in Opa1(+/-) mice led to an increase in endurance capacity, and a specific adaptive response involving a metabolic remodelling towards enhanced fatty acid utilization. In conclusion, OPA1 appears necessary for the normal adaptive response and mitochondrial biogenesis of skeletal muscle to training. This work opens new perspectives on the role of mitochondrial dynamics in skeletal muscle cells and during adaptation to stress.

A comparison of tissue-engineered bone from adipose-derived stem cell with autogenous bone repair in maxillary alveolar cleft model in dogs.

This study was designed to compare bone regeneration of tissue-engineered bone from adipose-derived stem cell and autogenous bone graft in a canine maxillary alveolar cleft model. In this prospective clinical trial, mesenchymal stem cells (MSCs) were isolated from subcutaneous canine adipose tissue. Undifferentiated cells were incubated with a 3mm×3mm×3mm hydroxyapatite/beta-tricalcium phosphate scaffold, in specific osteogenic medium for 21 days. Four mongrel dogs were prepared by removal of two of the three incisors bilaterally and a 15mm defect in bone was created from crest to nasal floor. After healing, repair was followed by a tissue engineered bone graft from adipose-derived stem cells on one side and corticocancellous tibial auto graft on the other side. Bone regeneration was evaluated by histomorphometry on days 15 and 60 after implantation. The data were analysed with descriptive and t test methods (α=0.05). Bone formation on the autograft sides was higher than on the stem cell sides at 15 and 60 days, 45% and 96% versus 5% and 70%, respectively. Differences between the two groups at 15 and 60 days were significant (p=0.004 and 0.001, respectively). Although autograft is still the gold standard for bone regeneration, tissue engineered bone may provide an acceptable alternative.

Radiography finding in the jaws in children taking bisphosphonate.

BACKGROUND: Bisphosphonates inhibit osteoclasts, prevent bone resorption and decrease bone turnover. This study examined radiography finding in bisphosphonate-associated osteonecrosis of jaws. MATERIALS AND METHODS: This is a retrospective series of 12 clinically diagnosed patients between 7 to 21 year old (average 13 years). They required emergency dental conditions requiring management by dentist: non healing extraction sockets and pain of bone exposure. The panoramic radiography and cone beam computed tomography was performed to assess the problem. Thickening of the lamina dura was observed in 7 patients (58.3 %). But full-thickness sclerosis was seen in 6 patients (50 %). Sclerotic changes in the mandibular canal were noted in 3 patients (25 %). 5 patients (41.6 %) had poorly healing or non-healing of socket in extracted tooth and periapical lucencies. 4 people (33.3 %) had widening of periodontal ligament (PDL) space and osteolysis. Sequestra were seen in 3 persons (25 %). Finally in 2 children (16.6 %) were found oroantral fistula. Only one child (8.3 %) had thickening of soft tissue mid periosteal reaction. RESULTS: Most patients had some degree of osteosclerosis, especially in the area of alveolar bone. Thickening of the lamina dura was also seen in children. Other findings include: osteolysis, sequestra, periosteal new bone formation, widening of PDL,soft tissue thickening, non healing extraction sockets, oroantral fistula and periapical lucencies (P-value < 0.05). CONCLUSION: Common radiographic features in patients taking bisphosphonate, was osteosclerosis. This sclerosis had different views that thickening of the lamina dura and alveolar crest were most common.

An overview of biofilm and its detection in clinical samples.

In many instances, wound colonising-bacteria are thought to be capable of forming biofilms, a significant factor contributing to delays or failure in wound healing. This review summarises the accumulated knowledge of biofilm and addresses the unmet need of biofilm detection in clinical wound samples.

A novel device for automatic withdrawal and accurate calibration of 99m-technetium radiopharmaceuticals to minimise radiation exposure to nuclear medicine staff and patient.

A Joint Automatic Dispenser Equipment (JADE) has been designed and fabricated for automatic withdrawal and calibration of radiopharmaceutical materials. The thermoluminescent dosemeter procedures have shown a reduction in dose to the technician's hand with this novel dose dispenser system JADE when compared with the manual withdrawal of (99m)Tc. This system helps to increase the precision of calibration and to minimise the radiation dose to the hands and body of the workers. This paper describes the structure of this device, its function and user-friendliness, and its efficacy. The efficacy of this device was determined by measuring the radiation dose delivered to the hands of the nuclear medicine laboratory technician. The user-friendliness of JADE has been examined. The automatic withdrawal and calibration offered by this system reduces the dose to the technician's hand to a level below the maximum permissible dose stipulated by the international protocols. This research will serve as a backbone for future study about the safe use of ionising radiation in medicine.

Pseudoaneurysm of mitro-aortic intervalvular fibrosa during the course of mitral valve endocarditis with aorto-left ventricle outflow tract fistula.

The mitro-aortic intervalvular fibrosa (MAIVF) connects the anterior mitral leaflet to the posterior portion of the aortic annulus. The pseudoaneurysm of MAIVF is one of the uncommon but catastrophic complications of native or prosthetic aortic valve endocarditis or chest trauma. We report a case of infective endocarditis of mitral valve complicated by development of pseudoaneurysm of MAIVF, and fistulous formation causing massive shunt flow from the ascending aorta above the non-coronary cusp to the left ventricle outflow tract.

A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics.

Glutamate excitotoxicity leads to fragmented mitochondria in neurodegenerative diseases, mediated by nitric oxide and S-nitrosylation of dynamin-related protein 1, a mitochondrial outer membrane fission protein. Optic atrophy gene 1 (OPA1) is an inner membrane protein important for mitochondrial fusion. Autosomal dominant optic atrophy (ADOA), caused by mutations in OPA1, is a neurodegenerative disease affecting mainly retinal ganglion cells (RGCs). Here, we showed that OPA1 deficiency in an ADOA model influences N-methyl-D-aspartate (NMDA) receptor expression, which is involved in glutamate excitotoxicity and oxidative stress. Opa1(enu/+) mice show a slow progressive loss of RGCs, activation of astroglia and microglia, and pronounced mitochondrial fission in optic nerve heads as found by electron tomography. Expression of NMDA receptors (NR1, 2A, and 2B) in the retina of Opa1(enu/+) mice was significantly increased as determined by western blot and immunohistochemistry. Superoxide dismutase 2 (SOD2) expression was significantly decreased, the apoptotic pathway was activated as Bax was increased, and phosphorylated Bad and BcL-xL were decreased. Our results conclusively demonstrate that not only glutamate excitotoxicity and/or oxidative stress alters mitochondrial fission/fusion, but that an imbalance in mitochondrial fission/fusion in turn leads to NMDA receptor upregulation and oxidative stress. Therefore, we propose a new vicious cycle involved in neurodegeneration that includes glutamate excitotoxicity, oxidative stress, and mitochondrial dynamics.

Resistance carrying plasmid in a traumatic wound.

OBJECTIVE: To isolate and identify antibiotic-resistant bacteria from the exudate of a complex wound and determine if antibiotic resistance genes are chromosomal or plasmid borne. METHOD: Antibiotic resistant bacteria from wound exudate of a single clinical sample were selected on agar media with ampicillin. A single colony was further screened for resistance to kanamycin by antibiotic-supplemented agar and to other antibiotics by an automated Phoenix instrument. Identification of the isolate was carried out by biochemical profiling and by 16S rDNA analysis. RESULTS: Approximately 51% of total bacteria in the wound exudate with identical colony morphotype were resistant to 100 microg/ml of ampicillin. A single colony from this population also demonstrated resistance to 50 microg/ml of kanamycin on kanamycin-supplemented agar. Further antimicrobial sensitivity testing by the Phoenix instrument indicated resistance to inhibitory concentrations of amoxicillin-clavulanate, ampicillin-sulbactam, cefazolin, gentamicin, nitrofurantoin, tobramycin, and trimethoprim-sulfamethoxazole. Biochemical and 16S rDNA analysis identified this bacterial isolate as a member of genus Enterobacter. A plasmid preparation from this isolate successfully transferred ampicillin and kanamycin resistance to E. coli competent cells. E. coli transformants displayed two resistance phenotypes and the plasmids from these transformants displayed two different restriction type patterns, with one correlating to ampicillin and kanamycin resistance and the other only to ampicillin resistance. CONCLUSION: A multiple antibiotic-resistant Enterobacter spp. from the wound fluid of a clinical sample was found to carry an antibiotic-resistant plasmid in a closely related species E. coli. The presence of antibiotic resistance plasmid in Enterobacteria that are part of the normal microbial flora of the human gut and skin could lead to the spread of resistance phenotype and emergence of antibiotic resistant pathogens. This study suggests normal human microbial fl ora could be a potential reservoir for resistance genes.