Antimicrobial Resistance and Antibiogram of Thermotolerant Campylobacter Recovered from Poultry Meat in Baghdad Markets, Iraq.

Antimicrobial resistance is a critical public health issue that affects people all over the world. Since bacteria have a proclivity for rapidly acquiring and propagating the resistance gene, antimicrobial-resistant Campylobacter has a negative impact on public health. As a result, the creation of new and highly pathogenic clones is facilitated, making antimicrobial treatment more challenging. This study aimed to determine the antimicrobial resistance pattern (ARP) models, multiple drug resistance (MDR) models, and multiple antibiotic resistance (MAR) index of Campylobacter species isolated from poultry meat sold in Baghdad markets, Iraq. By employing the disc diffusion test, 30 Campylobacter strains from chicken meat, including C. jejuni (n=10) and C. coli (n=20), were exposed to tetracycline (TET), erythromycin, Gentamicin, nalidixic acid, ciprofloxacin, and norfloxacin (NOR). The ARP of the Campylobacter isolates revealed up to five antibiotypes for two species, which revealed resistance to one or more antimicrobials, and 67% of them had MDR resistance to two or more experienced antimicrobials. The NOR-TET model is the most common MDR, having a prevalence of 30% among experienced isolates. In addition, the MAR index, equal to and lower than one, was found in 87% of the isolates. Antibiotic resistance in Campylobacter raises the probability of treatment failure in humans and animals, as well as the propagation of antimicrobial resistance genes. As a result, the presence of Campylobacter in meat could pose a risk of human infection and pollution of the environment.

Bilateral Non-arteritic Anterior Ischaemic Optic Neuropathy as the Presentation of Systemic Amyloidosis.

A 75-year-old hypertensive female with stable idiopathic intermediate uveitis presented with bilateral sequential optic neuropathy with optic disc swelling. The optic neuropathy in the first affected eye (right) was thought to be due to non-arteritic anterior ischaemic optic neuropathy (NAION). Asymptomatic left optic disc swelling was found at routine review 2 months later, and a diagnosis of giant cell arteritis (GCA) was sought. Temporal artery duplex ultrasound showed the "halo sign," but a subsequent temporal artery biopsy showed light-chain (AL) amyloidosis with no signs of giant cell arteritis. In this case, bilateral sequential ischaemic optic neuropathy mimicking non-arteritic anterior ischaemic optic neuropathy was the presenting sign of systemic amyloidosis involving the temporal arteries.

Follow-up of patients with interventional closure of ventricular septal defects with Amplatzer Duct Occluder II.

Nonsurgical closure of congenital ventricular septal defects (VSD) has become increasingly acceptable with the availability of different occlusion systems. Transcatheter device treatment is used for perimembranous and muscular defects. Atrio-ventricular block remains the most troublesome complication of device closure. The aim of this study was to describe our experience with closure of VSD using the Amplatzer Duct Occluder II (ADO II) as an "off-label" approach in children and adults. Between 2004 and 2012 transcatheter closure of 31 VSD (20 perimembranous, 10 muscular VSD and 1 ruptured sinus valsalva) with ADO II was undertaken in patients between 3 months and 55 years of age and with a body weight ranging from 4 to 105 kg in our institution. In 29 of 31 procedures, the defect was successfully closed (93.5%) without any significant complications. No increase of aortic or tricuspid valve regurgitation was found in any after procedure. Small residual shunts were observed immediately after the device implantation, but disappeared during a median follow-up period of 38 months (0.4-63) in 27 of 31 patients. There was no incidence of AV block or other conductance abnormalities during implantation or follow-up. The ADO II device is safe and effective for transcatheter VSD closure, but this is still an "off-label" use. After long-term follow-up in a large number of patients this device may be approved for VSD closure in the future.

Acupuncture in practice: mapping the providers, the patients and the settings in a national cross-sectional survey.

Background There is relatively limited knowledge about the practitioners who provide acupuncture treatment within the UK, what conditions patients consult for and the treatment provided. Objectives To characterise the conditions treated and by whom, to examine characteristics of the treatment and to explore trends over time. Method A cross-sectional survey of the UK acupuncture practitioners was conducted; 800 practitioners were selected by computer-generated randomisation sequences from the four major UK-based professional associations. Data collected on the practitioners included demographic details, association membership, statutorily regulated status, practice setting, style of acupuncture, diagnostic methods and needle response sought. Practitioners recorded details of their 10 most recent patients, including demographic details, primary reason for consulting and lifestyle advice provided. Results 330 practitioners responded comprising doctors (29%) physiotherapists (29%), nurses (15%) and independent acupuncturists (27%): 62% were women with median age of 48 years. The majority (68%) practiced in independent settings and 42% practiced within the National Health Service. Patients most commonly consulted for low back, neck, shoulder and knee pain, as well as headaches and migraine. Treatment for infertility by independent acupuncturists was found to have increased fivefold in 10 years. Conclusion Acupuncture provides a substantial contribution to the healthcare of the UK, with an estimated 4 million sessions provided annually. The primary complaints for which patients consult reflect the growing evidence base on acupuncture for these conditions. These data provide a basis for decision-making regarding policy and practice.

High frequency of autosomal-recessive DFNB59 hearing loss in an isolated Arab population in Israel.

Autosomal-recessive non-syndromic hearing impairment (DFNB) is usually of prelingual onset with a moderate to profound degree of hearing loss. More than 70 DFNB loci have been mapped and ~40 causative genes have been identified. Non-syndromic hearing impairment caused by mutations of DFNB59 (encoding pejvakin) has been described in a couple of families in which affected individuals presented with either auditory neuropathy or hearing loss of cochlear origin. We have identified and clinically evaluated three consanguineous families of Israeli Arab origin with prelingual non-syndromic hearing impairment and absent otoacoustic emissions in a total of eight affected individuals. All the families originate from the same village and bear the same family name. We have identified a c.406C>T (p.R136X) nonsense mutation in the DFNB59 gene in affected individuals from these families. Among the inhabitants of the village, we found an exceptionally high carrier frequency of ~1 in 12 individuals (7/85; 8.2%). The high prevalence of hearing impairment can be explained by a founder effect and the high consanguinity rate among the inhabitants of this village.

[Iatrogenic pulmonary necrosis due to hyperselective chemotherapy]. / Nécrose pulmonaire iatrogène due à une chimiothérapie hypersélective.

BACKGROUND: The management of cancer requires regular access to the central venous system. We report here, a case of a central venous access system causing pulmonary necrosis and abscess. CASE REPORT: A 48 year old woman with a past history of B-cell lymphoma presented with a relapse of her disease. A subcutaneous central venous access port was placed in the right brachiocephalic area with puncture of the subclavian vein. She received three doses of chemotherapy. Eight days later, she consulted the emergency department on account of right-sided chest pain. Examination revealed a right-sided pleural effusion. The chest x-ray showed the tip of the catheter at the right pulmonary hilum. A CT scan confirmed that the tip of the central venous catheter was located in a branch of the right lower lobe pulmonary artery and was surrounded by consolidation in the right middle and lower lobes. The progress was marked by the development of a lung abscess despite removal of the central venous access system. Subsequent surgery led to satisfactory resolution. CONCLUSION: We report a dramatic case that reminds us that placement of a central venous access system requires a sound technique and regular radiological surveillance.

Lack of interaction of the NMDA receptor antagonists dextromethorphan and dextrorphan with P-glycoprotein.

The anti-N-methyl-D-aspartate (NMDA) effect of dextromethorphan (DEM) seems to be mainly related to the unchanged drug rather than to its more potent metabolite dextrorphan (DOR). The aim of our study was to assess the involvement of P-glycoprotein (P-gp) and pH conditions in the transmembranal transport of these two NMDA antagonists, using a human in vitro Caco-2 cell monolayer model. Transmission electron microscopy, transepithelial electrical resistance, [(3)H]-mannitol permeability, Western blot analysis and the bidirectional transport of the positive controls, rhodamine and digoxine were used to confirm model's integrity and validity. The bidirectional transport of DEM and DOR (1 to 100microM) across the monolayers was investigated in the presence and absence of the P-gp inhibitor cyclosporine A (10microM) at two pH conditions (pH 6.8/7.7-pH 7.4/7.4) and assessed with the specific and more potent P-gp inhibitor GF120918 (4microM). Analytical quantification was achieved using high performance liquid chromatography. At a pH gradient, DEM and DOR were subject to a significant active efflux transport (Papp(B-A) > 2-3x Papp(A-B); p<0.01). However, neither the influx nor the efflux was affected by P-gp inhibitors. At physiological pH, we observed no more efflux of the drugs and no influence of the inhibitors. In conclusion, dextromethorphan and dextrorphan are not P-gp substrates. However, pH-mediated efflux mechanisms seem to be involved in limiting DEM gastrointestinal absorption. The preferential anti-NMDA central effect of DEM appears to be P-gp independent.

Prevalence and predictors of nonfatal myocardial infarction in Jordan.

This study in May 2002, part of the Jordan Department of Statistics national cross-sectional, multistage employment and unemployment survey, measured the prevalence of self-reported myocardial infarction (MI) and the association with modifiable risk factors among Jordanians aged 40+ years. Of 3083 participants, 183 (5.9%) had ever been told by a doctor that they had had a MI. The prevalence varied by age and sex; 128 (69.9%) of the cases were in men. Among males and females, self-reported hypertension and hypercholesterolaemia were significantly associated with MI and diabetes was a significant risk factor for women. There was a significant relationship between current smoking and MI but not with previous smoking. Exercise and body mass index were not statistically significant predictors of MI in both males and females.

Prevalence and predictors of non-fatal myocardial infarction in Jordan

This study in May 2002, part of the Jordan Department of Statistics national crosssectional, multistage employment and unemployment survey, measured the prevalence of selfreported myocardial infarction [MI] and the association with modifiable risk factors among Jordanians aged 40+ years. Of 3083 participants, 183 [5.9%] had ever been told by a doctor that they had had a MI. The prevalence varied by age and sex; 128 [69.9%] of the cases were in men. Among males and females, self-reported hypertension and hypercholesterolaemia were significantly associated with MI and diabetes was a significant risk factor for women. There was a significant relationship between current smoking and MI but not with previous smoking. Exercise and body mass index were not statistically significant predictors of MI in both males and females

Matrix models for childhood infections: a Bayesian approach with applications to rubella and mumps.

Mathematical modelling is an established tool for planning and monitoring vaccination programmes. However, the matrices describing contact rates are based on subjective choices, which have a large impact on results. This paper reviews published models and obtains prior model probabilities based on publication frequency and expert opinion. Using serological survey data on rubella and mumps, Bayesian methods of model choice are applied to select the most plausible models. Estimates of the basic reproduction number R0 are derived, taking into account model uncertainty and individual heterogeneity in contact rates. Twenty-two models are documented, for which publication frequency and expert opinion are negatively correlated. Using the expert prior with individual heterogeneity, R0=6.1 [95% credible region (CR) 4.3-9.2] for rubella and R0=19.3 (95% CR 4.0-31.5) for mumps. The posterior modes are insensitive to the prior for rubella but not for mumps. Overall, assortative models with individual heterogeneity are recommended.

Frequency and significance of antibodies against hepatitis B core (anti-HBc) antigen as the only serological marker for hepatitis B infection in Lebanese blood donors.

During a 2-year period, blood samples from 2505 Lebanese blood donors were chosen at random, at various periods of time at one blood donation centre (Hotel Dieu de France, Beirut, Lebanon) and were screened for markers of HBV infection (HBsAg, anti-HBc and anti-HBs). The study showed HBsAg positivity of 0.6% and an overall exposure rate to HBV of 10.0%. Out of the 2505 blood donors screened, 56 (22%) were found to be 'anti-HBc alone' positive which is almost four times the HBsAg positivity. The 56 'anti-HBc alone' samples were retested by another ELISA kit commercially available and 54 samples were 'anti-HBc alone' positive by both assays. The 54 samples had no serological markers as evidence of infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Only seven (13%) out of the 54 samples were HBV DNA positive by PCR and all were HBV genotype D. All seven HBV DNA-positive samples had HBV DNA levels below 400 copies/ml. Although any circulating HBV DNA among our 'anti-HBc alone' blood donors was below the detection limit of our Amplicor Monitor assay, some of these samples had circulating virus. A national study, where a larger number of blood donors from different blood donation centres across the country will perhaps determine whether screening for anti-HBc in addition to HBsAg detection is needed in Lebanese blood donors.

Branching process models for surveillance of infectious diseases controlled by mass vaccination.

Mass vaccination programmes aim to maintain the effective reproduction number R of an infection below unity. We describe methods for monitoring the value of R using surveillance data. The models are based on branching processes in which R is identified with the offspring mean. We derive unconditional likelihoods for the offspring mean using data on outbreak size and outbreak duration. We also discuss Bayesian methods, implemented by Metropolis-Hastings sampling. We investigate by simulation the validity of the models with respect to depletion of susceptibles and under-ascertainment of cases. The methods are illustrated using surveillance data on measles in the USA.

Novel PDGFbetaR antisense encapsulated in polymeric nanospheres for the treatment of restenosis.

Nanospheres composed of the biocompatible and biodegradable polymer, poly-DL-lactide/glycolide and containing platelet-derived growth factor beta-receptor antisense (PDGFbetaR-AS) have been formulated and examined in vitro and in vivo in balloon-injured rat restenosis model. The nanospheres (approximately 300 nm) of homogenous size distribution exhibited high encapsulation efficiency (81%), and a sustained release of PDGFbetaR-AS (phosphorothioated). Cell internalization was visualized, and the inhibitory effect on SMC was observed. Partially phosphorothioated antisense sequences were found to be more specific than the fully phosphorothioated analogs. A significant antirestenotic effect of the naked AS sequence and the AS-NP (nanoparticles) was observed in the rat carotid in vivo model. The extent of mean neointimal formation 14 days after injection of AS-NP, measured as a percentage of luminal stenosis, was 32.21 +/- 4.75% in comparison to 54.89 +/- 8.84 and 53.84 +/- 5.58% in the blank-NP and SC-NP groups, respectively. It is concluded that PLGA nanospheres containing phosphorothioated oligodeoxynucleotide antisense could serve as an effective gene delivery systems for the treatment of restenosis.

The prevalence and expression of inherited connexin 26 mutations associated with nonsyndromic hearing loss in the Israeli population.

Connexin 26 (GJB2) mutations lead to hearing loss in a significant proportion of all populations studied so far, despite the fact that at least 50 other genes are also associated with hearing loss. The entire coding region of connexin 26 was sequenced in 75 hearing impaired children and adults in Israel in order to determine the percentage of hearing loss attributed to connexin 26 and the types of mutations in this population. Age of onset in the screened population was both prelingual and postlingual, with hearing loss ranging from moderate to profound. Almost 39% of all persons tested harbored GJB2 mutations, the majority of which were 35delG and 167delT mutations. A novel mutation, involving both a deletion and insertion, 51del12insA, was identified in a family originating from Uzbekistan. Several parameters were examined to establish whether genotype-phenotype correlations exist, including age of onset, severity of hearing loss and audiological characteristics, including pure-tone audiometry, tympanometry, auditory brainstem response (ABR), and transient evoked otoacoustic emissions (TEOAE). All GJB2 mutations were associated with prelingual hearing loss, though severity ranged from moderate to profound, with variability even among hearing impaired siblings. We have not found a significant difference in hearing levels between individuals with 35delG and 167delT mutations. Our results suggest that, in Israel, clinicians should first screen for the common 167delT and 35delG mutations by simple and inexpensive restriction enzyme analysis, although if these are not found, sequencing should be done to rule out additional mutations due to the ethnic diversity in this region.

The cpc-2 gene of Neurospora crassa encodes a protein entirely composed of WD-repeat segments that is involved in general amino acid control and female fertility.

Phenotypic and molecular studies of the mutation U142 indicate that the cpc-2+ gene is required to activate general amino acid control under conditions of amino acid limitation in the vegetative growth phase, and for formation of protoperithecia in preparation for the sexual phase of the life cycle of Neurospora crassa. The cpc-2 gene was cloned by complementation of the cpc-2 mutation in a his-2ts bradytrophic background. Genomic and cDNA sequence analysis indicated a 1636 bp long open reading frame interrupted by four introns. The deduced 316 amino acid polypeptide reveals 70% positional identity over its full length with G-protein beta-subunit-related polypeptides found in humans, rat (RACK1), chicken, tobacco and Chlamydomonas. With the exception of RACK1 the function of these proteins is obscure. All are entirely made up of seven WD-repeats. Expression studies of cpc-2 revealed one abundant transcript in the wild type; in the mutant its level is drastically reduced. In mutant cells transformed with the complementing sequence, the transcript level, enzyme regulation and female fertility are restored. In the wild type the cpc-2 transcript is down-regulated under conditions of amino acid limitation. With cpc-2 a new element involved in general amino acid control has been identified, indicating a function for a WD-repeat protein that belongs to a class that is conserved throughout the evolution of eukaryotes.

The positive-acting sulfur regulatory protein CYS3 of Neurospora crassa: nuclear localization, autogenous control, and regions required for transcriptional activation.

The positive-acting global sulfur regulatory protein, CYS3, of Neurospora crassa turns on the expression of a family of unlinked structural genes that encode enzymes of sulfur catabolism. CYS3 contains a leucine zipper and an adjacent basic region (b-zip), which together constitute a bipartite sequence-specific DNA-binding domain. Specific anti-CYS3 antibodies detected a protein of the expected size in nuclear extracts of wild-type Neurospora under conditions in which the sulfur circuit is activated. The CYS3 protein was not observed in cys-3 mutants. Nuclear extracts of wild type, but not cys-3 mutants, also showed specific DNA-binding activity identical to that obtained with a CYS3 protein expressed in Escherichia coli. A truncated CYS3 protein that contains primarily the b-zip domain binds to DNA with high specificity and affinity in vitro, yet fails to activate gene expression in vivo, and instead inhibits the function of the wild-type CYS3 protein. Amino-terminal, carboxyterminal, and internal deletions as well as alanine scanning mutagenesis were employed to identify regions of the CYS3 protein that are required for its trans-activation function. Regions of CYS3 carboxy terminal to the b-zip motif are not completely essential for function although loss of an alanine-rich region results in decreased activity. All deletions amino terminal to the b-zip motif led to a complete loss of CYS3 function. Alanine scanning mutagenesis demonstrated that an unusual prolinerich domain of CYS3 appears to be very important for function and is presumed to constitute an activation domain. It is concluded that CYS3 displays nuclear localization and positive autogenous control in Neurospora and functions as a trans-acting DNA-binding protein.

The DNA-binding domain of the Cys-3 regulatory protein of Neurospora crassa is bipartite.

Cys-3, the major sulfur regulatory gene of Neurospora crassa, encodes a regulatory protein that is capable of sequence-specific interaction with DNA. The interaction is mediated by a region within the CYS3 protein (the bzip region) which contains a potential dimer-forming surface, the leucine zipper, and an adjacent basic DNA contact region, NH2-terminal to the leucine zipper. To investigate the bipartite nature of the bzip region, a series of cys-3 mutants obtained by oligonucleotide-directed mutagenesis were expressed and tested for dimer formation as well as DNA binding and in vivo function. The results demonstrate that CYS3 protein exists as a dimer in the presence and absence of the target DNA and that dimerization of CYS3 is mediated strictly by the leucine zipper, which is required for both cys-3 function in vivo and DNA-binding activity in vitro. Furthermore, a truncated CYS3 protein corresponding to just the bzip region was found to mediate dimer formation and to possess DNA-binding activity. A CYS3 mutant protein with a pure methionine zipper showed significant, although reduced, function in vivo and in vitro.

Mutational analysis of the DNA-binding domain of the CYS3 regulatory protein of Neurospora crassa.

cys-3, the major sulfur regulatory gene of Neurospora crassa, activates the expression of a set of unlinked structural genes which encode sulfur catabolic-related enzymes during conditions of sulfur limitation. The cys-3 gene encodes a regulatory protein of 236 amino acid residues with a leucine zipper and an upstream basic region (the b-zip region) which together may constitute a DNA-binding domain. The b-zip region was expressed in Escherichia coli to examine its DNA-binding activity. The b-zip domain protein binds to the promoter region of the cys-3 gene itself and of cys-14, the sulfate permease II structural gene. A series of CYS3 mutant proteins obtained by site-directed mutagenesis were expressed and tested for function, dimer formation, and DNA-binding activity. The results demonstrate that the b-zip region of cys-3 is critical for both its function in vivo and specific DNA-binding in vitro.