Drug eluting biliary stents to decrease stent failure rates: A review of the literature

Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy.     

Molecular cloning of Proteus mirabilis uroepithelial cell adherence (uca) genes.

Proteus mirabilis bacteria are a common cause of hospital-acquired urinary tract infection. In a previous study, we described a P. mirabilis fimbrial protein, UCA, that adhered to human uroepithelial cells. Genes sufficient for expression of UCA adherence were cloned into Escherichia coli K-12. E. coli bacteria that contained the uca recombinant plasmid adhered to human uroepithelial cells. In addition, the ucaA gene encoding the structural component of UCA pili was subcloned, and its DNA sequence was determined. Amino acid sequence homology (30 to 50%) was found between mature UcaA protein and pilins from pathogenic bacteria representing several genera, including E. coli F17, G, and type 1C pilins, Haemophilus M43 pilin, and a Bordetella pilin.     

Pseudomonas aeruginosa Exoenzyme S Is a Mitogen but Not a Superantigen for Human T Lymphocytes

Virtually all cystic fibrosis (CF) patients become infected with Pseudomonas aeruginosa, and once the infection is established, the organism is rarely cleared. One of the P. aeruginosa virulence factors, exoenzyme S, has been shown to correlate with increased morbidity and mortality both in rat models of chronic pulmonary inflammation and in human CF patients. It has previously been shown that exoenzyme S is a potent stimulus for the proliferation of T cells in greater than 95% of adults, which could contribute to the pathogenesis of CF. The goal of this study was to determine the mechanism of T-cell stimulation by exoenzyme S in an effort to shed light on the immune response and contribute to understanding its role in P. aeruginosa pathogenesis. The current studies demonstrate that exoenzyme S stimulates naive T cells, since fetal blood lymphocytes proliferated and adult lymphocytes that expressed CD45RA proliferated. The percentage of T cells activated by exoenzyme S after a 4-h culture (as measured by CD69 surface expression) was intermediate in magnitude compared to levels induced by a panel of superantigens and mitogens. To determine the mechanism of activation, the requirement for accessory cells was investigated. The proliferative response to exoenzyme S was dependent on the presence of accessory cells but was not blocked by an anti-DR antibody. Exoenzyme S activated both CD4⁺ and CD8⁺ T cells, but CD4⁺ T cells were preferentially activated. The Vβ repertoire of donor T cells showed no preferential activation or preferential expansion after stimulation by exoenzyme S, suggesting that it is not a superantigen. Taken together, our data suggest that exoenzyme S is a T-cell mitogen but not a superantigen. Activation of a large percentage of T lymphocytes by exoenzyme S may produce a lymphocyte-mediated inflammatory response that should be considered in the pathogenesis of CF.     

Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations

Using a new antibody developed against the C-terminus of the cannabinoid receptor (CB1), the immunostaining in the hippocampus revealed additional axon terminals relative to the pattern reported previously with an N-terminus antibody. Due to a greater sensitivity of this antibody, a large proportion of boutons in the dendritic layers displaying symmetrical (GABAergic) synapses were also strongly immunoreactive for CB1 receptors, as were axon terminals of perisomatic inhibitory cells containing cholecystokinin. Asymmetrical (glutamatergic) synapses, however, were always negative for CB1. To investigate the effect of presynaptic CB1 receptor activation on hippocampal inhibition, we recorded inhibitory postsynaptic currents (IPSCs) from principal cells. Bath application of CB1 receptor agonists (WIN55,212-2 and CP55,940) suppressed IPSCs evoked by local electrical stimulation, which could be prevented or reversed by the CB1 receptor antagonist SR141716A. Action potential-driven IPSCs, evoked by pharmacological stimulation of a subset of interneurons, were also decreased by CB1 receptor activation. We also examined the effects of CB1 receptor agonists on Ca2+-independent miniature IPSCs (mIPSC). Both agonists were without significant effect on the frequency or amplitude of mIPSCs. Synchronous gamma oscillations induced by kainic acid in the CA3 region of hippocampal slices were reversibly reduced in amplitude by the CB1 receptor agonist CP 55,940, which is consistent with an action on IPSCs. We used CB1-/- knock-out mice to confirm the specificity of the antibody and of the agonist (WIN55,212-2) action. We conclude that activation of presynaptic CB1 receptors decreases Ca2+-dependent GABA release, and thereby reduces the power of hippocampal network oscillations.     

Communication Deficits and the Motor System: Exploring Patterns of Associations in Autism Spectrum Disorder (ASD)

Many children with autism spectrum disorder (ASD) have notable difficulties in motor, speech and language domains. The connection between motor skills (oral-motor, manual-motor) and speech and language deficits reported in other developmental disorders raises important questions about a potential relationship between motor skills and speech-language deficits in ASD. To this end, we examined data from children with ASD (n?=?1781), 2–17 years of age, enrolled in the Autism Speaks—Autism Treatment Network (AS-ATN) registry who completed a multidisciplinary evaluation that included diagnostic, physical, cognitive and behavioral assessments as part of a routine standard of care protocol. After adjusting for age, non-verbal IQ, Attention Deficit Hyperactivity Disorder (ADHD) medication use, and muscle tone, separate multiple linear regression analyses revealed significant positive associations of fine motor skills (FM) with both expressive language (EL) and receptive language (RL) skills in an impaired FM subgroup; in contrast, the impaired gross motor (GM) subgroup showed no association with EL but a significant negative association with RL. Similar analyses between motor skills and interpersonal relationships across the sample found both GM skills and FM skills to be associated with social interactions. These results suggest potential differences in the contributions of fine versus gross motor skills to autistic profiles and may provide another lens with which to view communication differences across the autism spectrum for use in treatment interventions.     

Predictive models demonstrate age‐dependent association of subcortical volumes and cognitive measures

Whether brain matter volume is correlated with cognitive functioning and higher intelligence is controversial. We explored this relationship by analysis of data collected on 193 healthy young and older adults through the “Leipzig Study for Mind–Body–Emotion Interactions” (LEMON) study. Our analysis involved four cognitive measures: fluid intelligence, crystallized intelligence, cognitive flexibility, and working memory. Brain subregion volumes were determined by magnetic resonance imaging. We normalized each subregion volume to the estimated total intracranial volume and conducted training simulations to compare the predictive power of normalized volumes of large regions of the brain (i.e., gray matter, cortical white matter, and cerebrospinal fluid), normalized subcortical volumes, and combined normalized volumes of large brain regions and normalized subcortical volumes. Statistical tests showed significant differences in the performance accuracy and feature importance of the subregion volumes in predicting cognitive skills for young and older adults. Random forest feature selection analysis showed that cortical white matter was the key feature in predicting fluid intelligence in both young and older adults. In young adults, crystallized intelligence was best predicted by caudate nucleus, thalamus, pallidum, and nucleus accumbens volumes, whereas putamen, amygdala, nucleus accumbens, and hippocampus volumes were selected for older adults. Cognitive flexibility was best predicted by the caudate, nucleus accumbens, and hippocampus in young adults and caudate and amygdala in older adults. Finally, working memory was best predicted by the putamen, pallidum, and nucleus accumbens in the younger group, whereas amygdala and hippocampus volumes were predictive in the older group. Thus, machine learning predictive models demonstrated an age‐dependent association between subcortical volumes and cognitive measures. These approaches may be useful in predicting the likelihood of age‐related cognitive decline and in testing of approaches for targeted improvement of cognitive functioning in older adults.     

Prevalence and antimicrobial susceptibility pattern of methicillin-resistant Staphylococcus aureus in Assam

Aims:

Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious problem in intensive care units, because of development of multiresistance, and also intrinsic resistance to β-lactam antibiotics. The present study was carried out to investigate the prevalence of MRSA and their rate of resistance to different antistaphylococcal antibiotics.

Materials and Methods:

Between January 2007 and February 2008, the clinical specimens submitted at the microbiology laboratory were processed and all S. aureus isolates were included in this study. All isolates were identified morphologically and biochemically by standard laboratory procedures and antibiotic susceptibility pattern was determined by modified Kirby Bauer disc diffusion method.

Results:

Methicillin resistance was observed in 34.78% of isolates, of which 37.5% were found to be resistant to all commonly used antibiotics. In MRSA isolates, 50% had constitutive resistance, 9.38% had inducible MLS_B resistance and 18.75% had MS phenotype.

Conclusions:

There is a progressive increase in MRSA prevalence in the country but the present rate is still low in comparison to values found in some other institutes. The rate of inducible MLS_B resistance was also lower in comparison with findings from other parts of the country.