Pentoxifylline and its association with kaempferol improve NASH-associated manifestation in mice through anti-apoptotic, anti-necroptotic, antioxidant, and anti-inflammatory mechanisms.

OBJECTIVE: Non-alcoholic fatty liver disorders (NAFLD), particularly non-alcoholic steatohepatitis (NASH), have emerged as a leading cause of liver transplantation and mortality. However, the pathophysiology of NASH remains unknown. Oxidative stress, apoptosis, and necroptosis pathways are heavily linked to NASH. Therefore, the current study aimed to investigate the underlying mechanism for Pentoxifylline's (PTX) activity in NASH management, either alone or in combination with Kaempferol (KP). MATERIALS AND METHODS: A total of 32 male C57BL/6J mice were divided into four groups: the mice in the control group were fed a standard chow diet and given a vehicle; the mice in NASH group were maintained on NASH protocol for 25 days; the mice in the PTX group were kept on NASH protocol for 25 days and given PTX (100 mg/kg), and PTX+KP mice group were given NASH protocol along with KP (50 mg/kg) and PTX (100 mg/kg) simultaneously. RESULTS: The LDL-C, total cholesterol, triglycerides, glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), glucose, insulin, and HOMA-IR levels were considerably decreased in the PTX and PTX+KP treated groups. AMP-activated protein kinase (AMPK) Gene expression of the liver was significantly increased in the other treated groups, but peroxisome proliferator-activated receptor (PPAR), phosphorylated mixed lineage kinase-like protein (pMLKL), and sterol regulatory element binding protein 1 (SREBP1) were reduced significantly. Caspase-8 and receptor-interacting serine/threonine protein kinase (RIPK3) protein expression were significantly decreased in the PTX and PTX+KP groups compared to NASH group and nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) immunohistochemistry expression. CONCLUSIONS: Our current study suggests that PTX and its combination with KP have a significant ameliorative effect against NASH via novel mechanisms involving the regulation of apoptosis and necroptosis, as well as decreased oxidative stress, lipogenesis, proinflammatory cytokines, and modulation of histopathological manifestation.

[Profile of the victims of sexual violence in child psychiatry consultation]. / Enfants victimes de violences sexuelles en consultation de pédopsychiatrie.

INTRODUCTION: Child sexual abuse is a major health problem that remains under-declared and under-reported worldwide. In this paper we have taken an interest in establishing the profile of the victims in a clinical population of children consulting for sexual abuse. METHOD: We conducted a descriptive retrospective study in the child and teenager psychiatry department of the Mongi-Slim hospital (Tunis, Tunisia). We included all patients referred for treatment or medical expertise during the period from January 2013 to June 2019 and recorded sociodemographic data and clinical characteristics on pre-established charts from patient files. RESULTS: The total number of consultants was 150 patients with 61,33 % of female subjects (n=92). The average age was 9,9 years old with extremes ranging from 2 to 18 years old. The assault was unique in 62,7 % and happened in a place known by the victim in 47,33 %. Sexual abuse with non-penetrating contact was the most frequent (48 %). The average age at which the first sexual abuse happened was 9 years old. In the vast majority of cases, the abuser was a male. Concerning the identity of the abuser, he was someone of the family in 37,3 % of the cases and in half of these cases, he was the father. In the other cases where the abuser wasn't a family member, the identity was known by the child and/or his family in 48,66 %. A psychiatric diagnosis was made in 58 % of the cases with a percentage of 52,1 % among girls and 60,3 % among boys. Main diagnoses were acute stress disorder in 10,6 %, post trauma stress disorder in 19,3 %, adjustment disorder in14,6 % and a major depressive disorder in 8 %. CONCLUSION: Knowing the profile of victims of child sexual abuse and taking into consideration the social and psychiatric impact can help in adapting the means to intervene properly in order to take care of the victims and prevent such abuse.

How do parents of children with type 1 diabetes mellitus cope and how does this condition affect caregivers' mental health?

OBJECTIVE: To evaluate the impact that type 1 diabetes mellitus (T1DM) in children has on parents' mental health and parents' coping with this condition. METHODS: A cross-sectional study involving, at the outpatient examination, 41 caregivers of T1DM patients who had been diagnosed for at least 6 months. We evaluated the parents' coping strategies with the Brief COPE and their depressive and anxiety symptoms with the Hospital Anxiety and Depression Scale (HADS). Glycemic control of patients was assessed using the last glycated hemoglobin (HbA1c) values. RESULTS: The average total score at HADS was 17.62 (SD=6.98). Half of the parents had an anxious score over the cut-off. The more parents were depressed or anxious, the more they used emotion-focused coping (P=0.002 and P=0.00, respectively). The more parents were anxious or depressed, the more they used maladaptive coping strategies such as avoidance and distraction. CONCLUSION: These findings emphasise the key role of healthcare providers in assessing parents' difficulties and taking special care of those who have the most problems.

[Correlates of psychopathic personality traits in a sample of college students in Tunisia]. / Les corrélats des traits de personnalité psychopathiques dans un échantillon d'étudiants universitaires en Tunisie.

BACKGROUND: Although psychopathy and its predictive factors are well documented in clinical samples, studies in non-clinical populations are relatively rare. We proposed to assess psychopathy traits in a population of Tunisian university students and to analyze their predictive factors. METHOD: This was a cross-sectional study of 516 university students enrolled at three major Tunisian universities (Faculty of Humanities and Social Sciences of Tunis, National Engineering School of Tunis, Faculty of Medicine of Tunis). Participants responded to a survey sheet containing sociodemographic data and the Levenson Self-Report Psychopathy Scale. RESULTS: The students were female in 63.2 % of the cases, with a mean age of 22.7years. The socio-economic level was middle class in 62.4% of the cases. More than one-quarter of students (26.7%) consumed tobacco. The majority of students (81.4%) spent their free time on the Internet, while 11.8% participated in associative work. Psychopathy scores were relatively high (mean LSRPS scores=64.8) with no noticeable gender differences. Psychopathic traits were significantly associated with university (P=0.017), maternal occupational status (P=0.038), and tobacco use (P=0.029). In addition, the total psychopathy score was significantly lower among students sharing activities with their families (P=0.044) and among students participating in associational work (P=0.025). The multivariate multiple regression has retained as predictive factors of psychopathic traits the fact of being the eldest of his siblings and the associative work. CONCLUSION: Prevention strategies should be put in place to prevent psychopathy and its individual and social impacts in young adults in general, and in university students in particular, especially promoting associative activity in the university environment which is currently lacking in our context.

Living with type 1 diabetes mellitus: How does the condition affect children's and adolescents' quality of life?

OBJECTIVE: Our study aimed to measure the health-related quality of life (QoL) of Tunisian children and adolescents with type 1 diabetes mellitus (T1MD). METHODS: This cross-sectional study included 48 patients aged 3-18 years with T1MD, diagnosed for at least 6 months, and their parents, who underwent outpatient examinations from September to December 2018. The children's QoL was assessed using the PedQL 3.0 Diabetes Module exploring five dimensions: diabetes symptoms, treatment barriers, treatment adherence, worry, and communication problems. Parents shared their perception of their children's QoL through the PedQL 4.0 parents' report (general health and emotional, social, and scholar functioning). Glycemic control was assessed using the last glycated haemoglobin (HbA1c) values. RESULTS: The patients' average QoL score was 80.52 (±13.61) without significant differences between gender and age. The longer the duration of the disease, the worse the glycemic control. Girls and adolescents seemed to have poorer glycemic control. Boys and adolescents had more difficulties in all aspects of QoL. Parents perceived a worse QoL than that reported by their sons/daughters (72.34±16.42; P=0.006). CONCLUSION: These findings emphasize the importance of an interdisciplinary, biopsychosocial, and family-centered care approach to patients with T1MD.

Properties Investigation of GO/HA/Pt Composite Thin Film.

Hydroxyapatite/graphene oxide/platinum (HA/GO/Pt) nanocomposite was synthesized and electrodeposited on a pure zirconium substrate. The coated zirconium was annealed at 200, 300, 400, and 600°C in vacuum furnace in presence of argon gas. The structure and morphology of the coated samples were characterized. Biocompatibility and wear and corrosion resistances of specimens were examined. The result of corrosion tests shows that the graphene into HA/Pt composites significantly improves their corrosion resistance. The wear tests results of uncoated and coated samples before and after annealing show that coated samples annealed at 300°C had better wear resistance compared with uncoated and coated samples at other temperatures. Furthermore, the biocompatibility test shows that the coatings improved the cell attachment and proliferation compared to the pure zirconium substrate.

Sera from different age cohorts in Belgium show limited cross-neutralization between the mumps vaccine and outbreak strains.

OBJECTIVES: Mumps used to affect children between 2 and 15 years old. The mumps-measles-rubella (MMR) vaccine is available, with vaccine coverage rate of about 85% after two vaccine doses. Recently new mumps outbreaks have emerged in highly vaccinated populations; the causes for these new outbreaks are yet unknown. We tested if a difference in seroneutralizing capacity against the vaccine and wild-type viruses existed and if waning immunity could be detected. METHODS: In this study, 570 serum samples (age group 2-3 years (n = 96), 8-9 years (n = 95), 13-14 years (n = 94), 18-20 years (n = 96), 24-26 years (n = 92) and 50 + years (n = 97)) in Belgium were tested in the rapid fluorescent foci inhibition test for their neutralizing capacity against the vaccine and wild-type viruses. RESULTS: Neutralizing antibodies against the vaccine strain were present in 84% (81/97) of the 2-3-year, 74% (70/95) of the 8-9-year, 81% (76/94) of the 13-14-year, 76% (73/96) of the 18-20-year, 67% (62/92) of the 24-26-year and 77% (75/97) of the 50+-year age group serum samples. For all age groups, only about half of these serum samples were also positive for the wild-type virus. The geometric mean titres for the vaccine and wild-type virus for all younger age groups, except for 24-26 years, were significantly different, demonstrating poor in vitro cross-neutralization. CONCLUSIONS: A possible contribution of antigenic differences between the genotype A and G mumps virus as well as other immune factors, in addition to lower-than-optimal vaccination coverage and waning immunity, could explain the poor in vitro cross-neutralization and should be further studied.

Inhibition of MALT1 Decreases Neuroinflammation and Pathogenicity of Virulent Rabies Virus in Mice.

Rabies virus is a neurovirulent RNA virus, which causes about 59,000 human deaths each year. Treatment for rabies does not exist due to incomplete understanding of the pathogenesis. MALT1 mediates activation of several immune cell types and is involved in the proliferation and survival of cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, leading to the expression of immunoregulatory genes. Here, we examined the impact of genetic or pharmacological MALT1 inhibition in mice on disease development after infection with the virulent rabies virus strain CVS-11. Morbidity and mortality were significantly delayed in Malt1-/- compared to Malt1+/+ mice, and this effect was associated with lower viral load, proinflammatory gene expression, and infiltration and activation of immune cells in the brain. Specific deletion of Malt1 in T cells also delayed disease development, while deletion in myeloid cells, neuronal cells, or NK cells had no effect. Disease development was also delayed in mice treated with the MALT1 protease inhibitor mepazine and in knock-in mice expressing a catalytically inactive MALT1 mutant protein, showing an important role of MALT1 proteolytic activity. The described protective effect of MALT1 inhibition against infection with a virulent rabies virus is the precise opposite of the sensitizing effect of MALT1 inhibition that we previously observed in the case of infection with an attenuated rabies virus strain. Together, these data demonstrate that the role of immunoregulatory responses in rabies pathogenicity is dependent on virus virulence and reveal the potential of MALT1 inhibition for therapeutic intervention.IMPORTANCE Rabies virus is a neurotropic RNA virus that causes encephalitis and still poses an enormous challenge to animal and public health. Efforts to establish reliable therapeutic strategies have been unsuccessful and are hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular protease that mediates the activation of several innate and adaptive immune cells in response to multiple receptors, and therapeutic MALT1 targeting is believed to be a valid approach for autoimmunity and MALT1-addicted cancers. Here, we study the impact of MALT1 deficiency on brain inflammation and disease development in response to infection of mice with the highly virulent CVS-11 rabies virus. We demonstrate that pharmacological or genetic MALT1 inhibition decreases neuroinflammation and extends the survival of CVS-11-infected mice, providing new insights in the biology of MALT1 and rabies virus infection.

MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain.

MALT1 is involved in the activation of immune responses, as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. Although MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus, Evelyn-Rotnycki-Abelseth (ERA) virus, and observed increased susceptibility with ERA virus in MALT1-/- mice. Indeed, after intranasal infection with ERA virus, wild-type mice developed mild transient clinical signs with recovery at 35 days postinoculation (dpi). Interestingly, MALT1-/- mice developed severe disease requiring euthanasia at around 17 dpi. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1-/- mice at 10 dpi compared to MALT1+/+ infected mice. At 17 dpi, however, the level of inflammatory cell activation was comparable to that observed in MALT1+/+ mice. Moreover, MALT1-/- mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain.IMPORTANCE Rabies virus is a neurotropic virus which can infect any mammal. Annually, 59,000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular protein involved in innate and adaptive immunity and is an interesting therapeutic target because MALT1-deregulated activity has been associated with autoimmunity and cancers. The role of MALT1 in viral infection is, however, largely unknown. Here, we study the impact of MALT1 on virus infection in the brain, using the attenuated ERA rabies virus in different models of MALT1-deficient mice. We reveal the importance of MALT1-mediated inflammation and T cell activation to control ERA virus, providing new insights in the biology of MALT1 and rabies virus infection.

From Zirconium Nanograins to Zirconia Nanoneedles.

Combinations of three simple techniques were utilized to gradually form zirconia nanoneedles from zirconium nanograins. First, a physical vapor deposition magnetron sputtering technique was used to deposit pure zirconium nanograins on top of a substrate. Second, an anodic oxidation was applied to fabricate zirconia nanotubular arrays. Finally, heat treatment was used at different annealing temperatures in order to change the structure and morphology from nanotubes to nanowires and subsequently to nanoneedles in the presence of argon gas. The size of the pure zirconium nanograins was estimated to be approximately 200-300 nm. ZrO2 nanotubular arrays with diameters of 70-120 nm were obtained. Both tetragonal and monoclinic ZrO2 were observed after annealing at 450 °C and 650 °C. Only a few tetragonal peaks appeared at 850 °C, while monoclinic ZrO2 was obtained at 900 °C and 950 °C. In assessing the biocompatibility of the ZrO2 surface, the human cell line MDA-MB-231 was found to attach and proliferate well on surfaces annealed at 850 °C and 450 °C; however, the amorphous ZrO2 surface, which was not heat treated, did not permit extensive cell growth, presumably due to remaining fluoride.

EVALUATION OF THERMOTOLERANT ACETOBACTER PASTEURIANUS STRAINS ISOLATED FROM MOROCCAN FRUITS CATALYZING OXIDATIVE FERMENTATION AT HIGH TEMPERATURE.

Six strains of acetic acid bacteria were isolated from Moroccan local products and their potential as industrial strains was evaluated in lab-bioreactor. Three of them, namely TAV01, AF01 and CV01, isolated from traditional apple vinegar, apple and cactus fruit, respectively were selected and their responses to high temperature were assessed. Morphological and biochemical identification confirmed that these strains belong to Acetobacter species. Their growth and acetic acid production were compared with the thermoresistant reference strain, Acetobacter senegalensis and mesophilic strains of Acetobacter pasteurianus. The two strains AF01 and CV01 showed abundant growth and noticeable acetic acid production ability at high temperatures (38 to 41°C). A thermophilic character was observed for AF01 strain. Indeed, this bacterium grew better at 38 than 30°C.

Gastric tube necrosis following minimally invasive oesophagectomy is a learning curve issue.

INTRODUCTION: Gastric tube necrosis following oesophagectomy is thought to have an increased association with a minimally invasive technique. Some suggest gastric ischaemic preconditioning may reduce ischaemic complications. We discuss our series of 155 consecutive minimally invasive oesophagectomies (MIOs), including a number of cases of gastric tube ischaemia, of which 4 (2.6%) developed conduit necrosis. METHODS: Data were collected prospectively of MIOs carried out by a single surgeon between 2005 and 2011. Cases of gastric tube necrosis were identified. RESULTS: Overall, 155 patients were identified. The inpatient mortality rate was 2.6%. Gastric tube necrosis occurred in four patients (2.6%). An ultrasonic dissector injury to the gastroepiploic arcade had occurred in two cases. In another case, the gastric tube was strangulated in the hiatus. In the remaining case, no clear mechanical cause was identified. All 4 cases occurred within the first 73 cases. The gastric tube necrosis rate of the first 50 cases versus cases 51-155 was 4% and 2% respectively (p=0.5948). The anastomotic leak rate in these two cohorts was 18% and 7% respectively (p=0.0457). There was a significant reduction in overall gastric tube complications from 22% to 10% following the learning curve of the initial 50 cases (p=0.0447). CONCLUSIONS: In our series, gastric tube necrosis appears to be a learning curve issue. Prophylactic measures such as ischaemic preconditioning become less relevant as the operating surgeon's experience increases. Instead, meticulous attention to preserving the gastroepiploic arcade, avoidance of tension in the tube and careful positioning of the gastric conduit through an adequately sized hiatus are key factors.

High frequency of carbapenem-resistant Acinetobacter baumannii in patients with diabetes mellitus in Saudi Arabia.

Carbapenem-resistant Acinetobacter baumannii is becoming increasingly prevalent in patients with diabetes mellitus in the Middle East. We examined the relationship of these bacteria and their resistance mechanisms to the diabetic disease status of patients in Saudi Arabia. Susceptibilities of 271 isolates to carbapenems, tigecycline and colistin were determined, followed by detection of carbapenemase genes. A blaVIM gene was detected in ~95 % of isolates; blaOXA-23 and blaOXA-40 genes were also prevalent. Diabetic patients were significantly more likely to carry carbapenem-resistant isolates. Carbapenem-resistant A. baumannii is a serious problem in diabetic patients, and molecular detection of resistance mechanisms in these isolates is required.

Klebsiella pneumoniae susceptibility to biocides and its association with cepA, qacΔE and qacE efflux pump genes and antibiotic resistance.

BACKGROUND: Although antiseptics are some of the most widely used antibacterials in hospitals, there is very little information on reduced susceptibility to these biocides and its relationship with resistance to antibiotics. AIM: To determine the relationship between reduced susceptibility to biocides and the carriage of antiseptic resistance genes, cepA, qacΔE and qacE, as well as identifying the role of efflux pumps in conferring reduced susceptibility. METHODS: Susceptibility was assessed for five biocides: chlorhexidine, benzalkonium chloride, Trigene, MediHex-4, Mediscrub; and for 11 antibiotics against 64 isolates of Klebsiella pneumoniae. Susceptibility to all compounds was tested by the agar double dilution method (DDM) and the effect of efflux pumps on biocides determined by repeating the susceptibility studies in the presence of the efflux pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP). The presence of the cepA, qacΔE and qacE genes was identified by polymerase chain reaction. FINDINGS: The bacteria were not widely antibiotic resistant though a few showed reduced susceptibility to cefoxitin, chloramphenicol and rifampicin and later-generation cephalosporins but not to carbapenems. Biocide susceptibility, tested by DDM, showed that 50, 49 and 53 strains had reduced susceptibility to chlorhexidine, Trigene and benzalkonium chloride, respectively. The antiseptic resistance genes cepA, qacΔE and qacE were found in 56, 34 and one isolates respectively and their effects as efflux pumps were determined by CCCP (10 mg/L), which decreased the minimum inhibitory concentrations (MICs) of chlorhexidine and Medihex-4 by 2-128-fold but had no impact on the MICs of benzalkonium chloride, Trigene and Mediscrub. CONCLUSION: There was a close link between carriage of efflux pump genes, cepA, qacΔE and qacE genes and reduced biocide susceptibility, but not antibiotic resistance, in K. pneumoniae clinical isolates.

Rapid acquisition of decreased carbapenem susceptibility in a strain of Klebsiella pneumoniae arising during meropenem therapy.

A strain of Klebsiella pneumoniae (K1) was isolated from a catheterized patient with a urinary tract infection. The patient was subsequently treated with meropenem, after which K. pneumoniae (K2) was once again isolated from the patient's urine. Susceptibility testing showed that strain K1 was fully susceptible to carbapenem antibiotics with the exception of ertapenem, to which it exhibited intermediate resistance, whilst K2 was resistant to ertapenem and meropenem. From pulsed-field gel electrophoresis profiling both strains exhibited identical banding patterns. Both contained CTX-M-15, OXA-1, SHV-1 and TEM-1 ß-lactamase genes following PCR analyses. Outer membrane protein analysis demonstrated that K1 and K2 lacked an OMP of c. 40 kDa, with an additional OMP of c. 36 kDa missing from K2. Mutation studies showed that the K2 OMP phenotype could be selected by single-step carbapenem-resistant mutants of K1. Expression of transcriptional activator ramA and efflux pump component gene acrA were up-regulated in both strains by RT-PCR. Neither strain expressed ompK35, but ompK36 was found in both. Sequence analysis revealed gene sequences of ompK35, ompK36 and ramR in both strains; notably, ramR contained a mutation resulting in a premature stop codon. Transconjugation studies demonstrated transfer of a plasmid into E. coli encoding the CTX-M-15, TEM-1 and OXA-1 ß-lactamases. We concluded that the carbapenem-resistant phenotype observed from this patient was attributable to a combination of CTX-M-15 ß-lactamase, up-regulated efflux and altered outer membrane permeability, and that K2 arose from K1 as a direct result of meropenem therapy.

First report of a novel extended-spectrum beta-lactamase KOXY-2 producing Klebsiella oxytoca that hydrolyses cefotaxime and ceftazidime.

Klebsiella oxytoca strains MU946294N and MB193997E were isolated from patients in Scotland. Strain MU946294N was resistant to pencillins, monbactams and cephalosporins. Isolate MB193997E displayed a ß-lactam resistance phenotype consistent with chromosomal ß-lactamase overproduction. No bla(TEM), bla(SHV) or bla(CTX-M) genes could be amplified in either strain; however, amplification by PCR was found with primers for the bla(OXY-2) gene. This ß-lactamase gene in MU946294N differed by one mutation from the all other bla(OXY) genes previously reported, with an amino acid substitution Alanine237 Threonine enhancing the binding of cefotaxime. Strain MB193997E showed mutations at positions 255 and 283, neither of which affect function. Based on rpoB and gyrA characterization, both strains were assigned to the KoII phylogenic group but they were completely dissimilar from each other by PFGE. This study is the first to report the substitution of Alanine to Threonine at position 237 in a OXY- 2 ß-lactamase and this enhances resistance to cefotaxime.

Effect of frameshift mutagen acriflavine on control of resistance genes in Acinetobacter baumannii.

Acinetobacter baumannii is a Gram-negative pathogenic bacterium that often exhibits a multidrug-resistant phenotype causing infections at various sites of the body and increasingly leading to septicaemic shock. This study evaluated the role of acriflavine, a frameshift mutagen, on the movement of insertion sequence ISAba1 in clinical isolates of A. baumannii, with the focus on changes in expression levels of the bla(ADC) and bla(OXA-51-like) genes. Resistance profiles were assessed with consideration of ISAba1 acting as a promoter upstream of the bla(ADC) or bla(OXA-51-like) gene. ISAba1 movement was observed in the acriflavine mutants Ab153M and Ab1225M. Ab153M exhibited an increase in the MIC values of carbapenems and ceftazidime, with ISAba1 gained upstream of the bla(ADC) and bla(OXA-51-like) genes, correlating with an increase in gene expression. Reduced expression of the 17, 23 and 25 kDa outer-membrane proteins (OMPs) was also observed in Ab153M. There was a significant decrease in MIC values of carbapenems with the loss of ISAba1 upstream of the bla(ADC) and bla(OXA-51-like) genes in strain Ab1225M, and a significant decrease in bla(OXA-51-like) gene expression and, to a lesser extent, in bla(ADC) expression. Ab1225M and a serially subcultured Ab1225 strain (Ab1225s) exhibited overexpression of the 17, 23, 25 and 27 kDa OMPs. There was a decrease in MIC values of the carbapenems and piperacillin/tazobactam but not of ceftazidime in Ab1225s, which had ISAba1 upstream of the bla(ADC) and bla(OXA-51-like) genes. A significant decrease in bla(OXA-51-like) expression was observed in Ab1225s, whereas the expression of bla(ADC) was similar to that in the Ab1225 parental strain. The attenuation in this strain may be due to overexpression of OMPs and it is clear that, even if ISAba1 is present upstream of an antibiotic resistance gene, it may not necessarily contribute towards the overexpression of antibiotic resistance genes (bla(OXA-51-like) in Ab1225s). Movement of the IS element within the A. baumannii chromosome may be an important regulatory mechanism employed by the bacterium under particular stress conditions, and the ability to upregulate the expression of antibiotic resistance genes is likely to be an important factor in the pathogenicity of this bacterium.

Prevalence of transferable blaCTX-M-15 from hospital- and community-acquired Klebsiella pneumoniae isolates in Scotland.

OBJECTIVES: This study was performed to investigate the prevalence and genetic characteristics of transferable bla(CTX-M-15) from hospital- and community-acquired Klebsiella pneumoniae isolates in Scotland. METHODS: A total of 219 clinical isolates of K. pneumoniae collected in 2006 and 2007 at the Royal Infirmary of Edinburgh, Scotland, were tested for antimicrobial susceptibility by the agar double dilution method. PCR and sequencing were used to detect bla(CTX-M), bla(TEM), bla(SHV) and qnr genes. Clonality of the isolates was assessed by PFGE. RESULTS: Sixteen (7.3%) isolates were found to be producers of CTX-M-15 extended-spectrum ß-lactamases (ESBLs), of which two isolates (12.5%) were reported to be from patients with community-acquired infections. The ISEcp1 was detected by sequencing 48 nucleotides upstream of bla(CTX-M-15) in all isolates but one. A total of one to two plasmids, ranging in size from ~40 to 210 kb, were observed per strain. By a PCR-based replicon typing method, plasmids carrying bla(CTX-M-15) were assigned to IncFII or IncN types. Sequencing and PCR analysis revealed the presence of complex class 1 integrons in all isolates but one. Two isolates positive for class 1 integrons were positive for class 2 integrons as well. Five different clones of CTX-M-15-producing isolates were identified by PFGE. CONCLUSIONS: This work reports the emergence of hospital- and community-acquired CTX-M-type enzymes in the Edinburgh area of Scotland.

Acute superior vena cava obstruction following Ivor-Lewis oesophagectomy.

A 53 year old man developed upper body swelling, hypotension, anuria and a metabolic acidosis within 24 h following an Ivor-Lewis oesophagectomy. His co-morbidities included hypertension, hypercholesterolaemia, ischaemic heart disease and he was a smoker. He did not have radiotherapy but had received neo-adjuvant chemotherapy through an in-dwelling right subclavian central venous catheter. Azygous vein ligation during oesophagectomy resulted in acute upper body venous hypertension and signs of hypovolaemic shock which were attributed to undiagnosed thrombotic occlusion of the superior vena cava. The patient was anticoagulated and made a full recovery after a period of stay in intensive care.