Vaccinia‐based influenza vaccine overcomes previously induced immunodominance hierarchy for heterosubtypic protection

Growing concerns about unpredictable influenza pandemics require a broadly protective vaccine against diverse influenza strains. One of the promising approaches was a T cell‐based vaccine, but the narrow breadth of T‐cell immunity due to the immunodominance hierarchy established by previous influenza infection and efficacy against only mild challenge condition are important hurdles to overcome. To model T‐cell immunodominance hierarchy in humans in an experimental setting, influenza‐primed C57BL/6 mice were chosen and boosted with a mixture of vaccinia recombinants, individually expressing consensus sequences from avian, swine, and human isolates of influenza internal proteins. As determined by IFN‐γ ELISPOT and polyfunctional cytokine secretion, the vaccinia recombinants of influenza expanded the breadth of T‐cell responses to include subdominant and even minor epitopes. Vaccine groups were successfully protected against 100 LD₅₀ challenges with PR/8/34 and highly pathogenic avian influenza H5N1, which contained the identical dominant NP₃₆₆ epitope. Interestingly, in challenge with pandemic A/Cal/04/2009 containing mutations in the dominant epitope, only the group vaccinated with rVV‐NP + PA showed improved protection. Taken together, a vaccinia‐based influenza vaccine expressing conserved internal proteins improved the breadth of influenza‐specific T‐cell immunity and provided heterosubtypic protection against immunologically close as well as distant influenza strains.     

Phylogenetic Analyses of HBV Pre-S/S Genes in Mother-Child Pairs with Long-Term Infection by Presumed Vertical Transmission

Vertical transmission from mother to child, the main route of chronic hepatitis B virus (HBV) infection in the East Asia, is considered one of the most important predictors for the response to antiviral therapies as well as its complications such as cirrhosis and hepatocellular carcinoma. Therefore, it is critical in both etiologic and prognostic aspects to confirm whether or not chronic HBV infection is acquired vertically. This study investigated whether mother-to-child infection could be proved by the phylogenetic analyses of HBV pre-S/S genes ever since several decades have elapsed in mother-child pairs with presumed vertical transmission. The pre-S and S regions of HBVs were compared and analyzed phylogenetically in a total of 36 adults (18 mother-child pairs) with chronic HBV infection. All of the isolates of HBV were genotype C and serotype adr. The divergence between mothers and offsprings was 0 to 1.5%. Phylogenetic trees revealed that 17 of 18 pairs (94%) with presumed vertical transmission were grouped into the same cluster. Vertical transmission from mother to child could be strongly suggested even in adults with a history of several decades of HBV infection using the phylogenetic analyses of pre-S and S genes.

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Does Intravenous Ketamine Enhance Analgesia after Arthroscopic Shoulder Surgery with Ultrasound Guided Single-Injection Interscalene Block?: A Randomized,Prospective, Double-Blind Trial

Ketamine has anti-inflammatory, analgesic and antihyperalgesic effect and prevents pain associated with wind-up. We investigated whether low doses of ketamine infusion during general anesthesia combined with single-shot interscalene nerve block (SSISB) would potentiate analgesic effect of SSISB. Forty adult patients scheduled for elective arthroscopic shoulder surgery were enrolled and randomized to either the control group or the ketamine group. All patients underwent SSISB and followed by general anesthesia. During an operation, intravenous ketamine was infused to the patients of ketamine group continuously. In control group, patients received normal saline in volumes equivalent to ketamine infusions. Pain score by numeric rating scale was similar between groups at 1, 6, 12, 24, 36, and 48 hr following surgery, which was maintained lower than 3 in both groups. The time to first analgesic request after admission on post-anesthesia care unit was also not significantly different between groups. Intraoperative low dose ketamine did not decrease acute postoperative pain after arthroscopic shoulder surgery with a preincisional ultrasound guided SSISB. The preventive analgesic effect of ketamine could be mitigated by SSISB, which remains one of the most effective methods of pain relief after arthroscopic shoulder surgery.

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Change of coronary flow velocity during the cold pressor test is related to endothelial markers in subjects with chest pain and a normal coronary angiogram

Background:

Several studies demonstrated that endothelial or atherosclerotic biomarkers, including plasma free insulin‐like growth factor‐I(IGF‐I), soluble CD40 ligand (sCD40L), adiponectin, and leptin have an influence on coronary endothelial function.

Hypothesis:

The aim of the present study was to investigate whether change of coronary flow velocity of the distal left anterior descending artery (LAD) during the cold pressor test (CPT) with transthoracic Doppler echocardiography (TTE) was associated with these biomarkers in subjects with chest pain and a normal coronary angiogram.

Methods:

In 190 subjects (mean age, 54±11 years; male:female, 113:77) with chest pain and a normal coronary angiogram, peak diastolic velocity (PDV) of the distal LAD during the CPT with TTE was assessed. Acetylcholine provocation test was performed in 58 subjects (mean age, 51±10 years) who were clinically suspected of vasospasm. CPT%PDV was defined as the percent change in PDV during the CPT. Associations between CPT%PDV and clinical parameters were analyzed.

Results:

According to multiple regression analysis, CPT%PDV was associated with plasma free IGF‐I in the entire study population (β=0.295, P<0.001 in all subjects; β=0.341, P=0.001 in males; β=0.243, P=0.037 in females; β=0.303, P=0.002 in nonsmokers; and β=0.256, P=0.047 in smokers), and sCD40L in males (β=?0.269, P=0.008)and smokers (β=?0.261, P=0.046). Subjects with vasospasm to intracoronary acetylcholine had lower plasma free IGF‐I(6.9±3.3 vs 8.9±3.4, P=0.026) and CPT%PDV (8.8±24.9 vs 52.7±26.0, P<0.001) than the others. Plasma adiponectin and leptin were not associated with CPT%PDV.

Conclusions:

Change of coronary flow velocity assessed using the CPT with TTE may be related to endothelial markers, especially plasma free IGF‐I. © 2011 Wiley Periodicals, Inc. Additional Supporting Information may be found in the online version of this article. The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

Morphology of the zygomaticus minor and its relationship with the orbicularis oculi muscle

The aim of this study was to examine in detail the anatomic variations in the orbicularis oculi muscle (OOc) and relationship of the zygomaticus minor muscle (ZMi) with the OOc, thereby providing an anatomic basis for explaining facial animation and attachment to the periorbital muscle. Sixty-one hemifaces from embalmed Korean adult cadavers (34 males, 27 females; age range, 45-85 years; mean age, 62.6 years) were used in this study. The prevalence of cases in which the ZMi did not run straight from the upper lip, rather running straight to the corner of the levator labii superioris, was 36.1% (22/61), because the origin of ZMi covered the inferior border of the OOc. The prevalence of mixing of the belly of the orbital part of the outer edge of the OOc with the ZMi was 88.5%, and that of blending of the ZMi band into the lower inner corner of the OOc was 55.7%. The area of blending of the OOc and ZMi was located 17.8 mm down from the Frankfort plane and 8.9 mm lateral to the vertical line between the lateral canthus and the Frankfort plane in the lateral part of the OOc. At this position, the mixed belly extends medially for a distance of 16 mm. This research has identified the exact location where the ZMi and OOc blend and determined the relationship between the ZMi and the suborbicularis oculi fat. This result will be given as basic data for understanding facial expressions and for performing composite rhytidectomy.     

Medial muscular band of the orbicularis oculi muscle

Despite the importance of anatomic variations in the muscular bands around the orbicularis oculi muscle (OOc), little is known about them. The morphology and variations therein of the medial muscular band of the OOc were thus examined in the current study. Sixty-one hemifaces of Korean cadavers were dissected to enable examination of the anatomic organization of the muscles around the OOc. A medial muscular band of the OOc was observed in 40 cases (65.6%). Three patterns of attachment were found. In type A (14 cases, 23%), it attached to the frontal belly without being attached to the medial canthal tendon; in type B (14 cases, 23%), it originated from the medial canthal tendon at the lower portion of the OOc and inserted into the cheek skin, and in type C (12 cases, 19.7%), it was also observed to insert into the cheek skin and attach to the frontal belly without being attached to the medial canthal tendon. The distance between the inferior edge of the OOc and the subnasale was 16.3 (SD, 4.3) mm and 14.5 (SD, 4.4) mm in cases with and without a medial muscular band, respectively. A space was observed on the inferolateral side of the OOc in about 67.2% of cases. These findings regarding the medial muscular band of the OOc increase further the anatomic variations associated with this region. In addition, it appears that this medial muscular band of the OOc can help to prevent drooping of the OOc.