Significant association of DRD2 enhancer variant rs12364283 with heroin addiction in a Pakistani population.

The dopamine D2 receptor encoded by DRD2 has been implicated in multiple psychiatric disorders, mediated at least in part by two intronic variants affecting mRNA splicing, rs1076560 and rs2283265, and a less frequent enhancer variant, rs12364283, which increases DRD2 mRNA expression. This study tests whether these functionally validated variants confer susceptibility toward heroin addiction in a Pakistani population. A total of 540 heroin addicts and 467 healthy controls were genotyped, basic allele and genotype tests were performed. Neither rs1076560 nor rs2283265 significantly associated with heroin addiction. The enhancer rs12364283 occurs more frequently in heroin-dependent cases than controls (MAF 13% vs. 7%, respectively), revealing significant association with heroin addiction (p = 3.0E-06, OR 2.1). This study identifies rs12364283 of DRD2 as a potential risk factor for heroin addiction in the Pakistani study population. This enhancer variant had been shown to increase DRD2 mRNA expression, a possible factor in increased vulnerability to heroin addiction. Further studies are needed to validate this association of rs12364283.

Partial thickness wound: Does mechanism of injury influence healing?

Wound healing is a complex multistep process which is temporally and spatially controlled. In partial thickness wounds, regeneration is possible from the stem cells in the edges of the wound and from the remnants of the epidermal appendages (such as hair follicles and sebaceous glands). This study examines whether the mechanism of injury influences healing of wounds of similar depth. Burn and excisional wounds were created on the back of Hampshire pigs and harvested at 7, 14, 28, 44, 57 and 70days after injury and processed for histology and immunohistochemistry. Quantitative analysis of re-epithelialisation, inflammatory response and thickness of the scar and semi-quantitative analyses of the architecture of the resultant scar were performed and subjected to statistical analysis. Results demonstrated a higher number of neutrophils, macrophages and lymphocytes present in the burn on day 7 compared to the excisional wounds. The inflammatory profile of burn wounds was higher than that of excisional wounds for the first month after injury albeit less marked than on day 7 after injury. Re-epithelialisation was markedly advanced in excisional wounds compared to burn wounds at day 7 after injury, corresponding to the higher number of hair follicles in the underlying dermis of excisional wounds at this time point. The thickness of the neo-epidermis increased with time and at day 70 after wounding, the neo-epidermis of the burn was significantly thicker than the neo-epidermis of the excisional scar. Interestingly, following partial thickness excision of skin, there was neo-dermal reformation albeit with an altered architecture, lacking the normal basket-weave pattern of collagen. The thickness of the dermis of partial thickness excisional scar was greater than that of the adjacent unwounded skin. The neo-dermis of the burn scar was even thicker, with the collagen arranged more compactly and disorganised compared to excisional scar and normal skin. This study provides evidence that the mechanism of injury does influence wound healing and the resultant scarring.

Complete Genome Sequence Analysis and Characterization of Selected Iron Regulation Genes of Pasteurella Multocida Serotype A Strain PMTB2.1.

Although more than 100 genome sequences of Pasteurella multocida are available, comprehensive and complete genome sequence analysis is limited. This study describes the analysis of complete genome sequence and pathogenomics of P. multocida strain PMTB2.1. The genome of PMTB2.1 has 2176 genes with more than 40 coding sequences associated with iron regulation and 140 virulence genes including the complete tad locus. The tad locus includes several previously uncharacterized genes such as flp2, rcpC and tadV genes. A transposable phage resembling to Mu phages was identified in P. multocida that has not been identified in any other serotype yet. The multi-locus sequence typing analysis assigned the PMTB2.1 genome sequence as type ST101, while the comparative genome analysis showed that PMTB2.1 is closely related to other P. multocida strains with the genomic distance of less than 0.13. The expression profiling of iron regulating-genes of PMTB2.1 was characterized under iron-limited environment. Results showed significant changes in the expression profiles of iron-regulating genes (p < 0.05) whereas the highest expression of fecE gene (281 fold) at 30 min suggests utilization of the outer-membrane proteins system in iron acquisition at an early stage of growth. This study showed the phylogenomic relatedness of P. multocida and improved annotation of important genes and functional characterization of iron-regulating genes of importance to the bacterial growth.

Migration of indwelling central venous catheter and fatal hydrothorax.

Central venous catheter complications can be related to insertion, indwelling, or extraction. Most of the times, immediate complications are anticipated and managed; whereas, delayed complications can go unnoticed. In the case discussed here, migration and dislodgement of catheter tip resulted in delayed hydrothorax and sudden death of a 9-month-old female infant.

Endovascular repair in penetrating aortoesophageal foreign body injury.

Foreign body ingestion in adults is not as common as in children. Sharp foreign body ingestion is even rarer; however, it may result in perforation, inflammation, or fistula formation at various gastrointestinal levels. In our case, the patient was unaware of the foreign body ingestion and presented with retrosternal chest pain, odynophagia, and occasional choking. Endoscopy and computed tomography thorax scan revealed a piece of chicken bone penetrating the aorta through the esophageal wall. No signs of mediastinitis were found. The foreign body was retrieved endoscopically with simultaneous endovascular stent repair of the aorta. Postoperative recovery was uneventful. There is an associated high morbidity and mortality in such cases, mandating long-term follow-up.

Long term video/EEG prevents unnecessary vagus nerve stimulator implantation in patients with psychogenic nonepileptic seizures.

OBJECTIVE: Psychogenic nonepileptic seizures (PNES) are common paroxysmal events that mimic and can often be misdiagnosed as epileptic seizures. PNES account for 10 to 40% of patients referred to epilepsy centers. Patients with uncontrolled PNES are at times subjected to vagus nerve stimulator (VNS) implantation. We report a series of such referred patients studied with video/EEG monitoring at our institution. METHODS: We evaluated patients who were implanted with a VNS by their primary neurologist for refractory seizures and who were referred to the Vanderbilt University epilepsy monitoring unit for a second opinion. The presumed diagnosis of epilepsy was based on abnormal routine EEG studies obtained by their primary neurologist. We evaluated these patients and recorded their typical spells between 2005 and 2009. We describe the results of 13 patients with VNS who were found to have PNES. The total number of patients with a VNS studied during this time was 60. RESULTS: None of the patients had undergone prior long-term video/EEG monitoring to document the nature of their events. A total of 13 patients with an implanted VNS had exclusive PNES, 9 women and 4 men with a mean age of 38.2±10.4 years. Mean age at seizure onset was 28.5±15.4 years. Patients were taking two to four antiepileptic medications in addition to VNS at the time of video/EEG monitoring. The average latency from the time of VNS implantation to the confirmatory diagnosis was 2.8 years. One to ten (median=3) of these patients' typical seizures were recorded during video/EEG monitoring. All patients were subsequently discharged off antiepileptic medications, and five of these patients were discharged home with the VNS turned off. CONCLUSION: A VNS may be implanted inappropriately in patients with PNES. As video/EEG monitoring may help in excluding the diagnosis of PNES and preventing unnecessary VNS implants, it should be a requirement before VNS implantation.