Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508 culture-supernatant ameliorate obesity by inducing thermogenesis in obese-mice.

Excessive body fat and the related dysmetabolic diseases affect both developed and developing countries. The aim of this study was to investigate the beneficial role of a bacterial culture supernatant (hereafter: BS) of Lactobacillus and Bifidobacterium and their potential mechanisms of action on white-fat browning and lipolysis. For selection of four candidates among 55 Lactic acid producing bacteria (LAB) from human infant faeces, we evaluated by Oil Red O staining and Ucp1 mRNA quantitation in 3T3-L1 preadipocytes. The expression of browning and lipolysis markers was examined along with in vitro assays. The possible mechanism was revealed by molecular and biological experiments including inhibitor and small interfering RNA (siRNA) assays. In a mouse model, physiological, histological, and biochemical parameters and expression of some thermogenesis-related genes were compared among six experimental groups fed a high-fat diet and one normal-diet control group. The results allow us to speculate that BS treatment promotes browning and lipolysis both in vitro and in vivo. Moreover, the BS may activate thermogenic programs via a mechanism involving PKA-CREB signaling in 3T3-L1 cells. According to our data, we can propose that two LAB strains, Bifidobacterium longum DS0956 and Lactobacillus rhamnosus DS0508, may be good candidates for a dietary supplement against obesity and metabolic diseases; however, further research is required for the development as dietary supplements or drugs.

Diagnostic performance of interferon-gamma release assay for diagnosis of tuberculous pericarditis: A meta-analysis.

BACKGROUND: The diagnosis of tuberculous pericarditis is difficult to set, not only for its non-specific clinical presentation, but also for the lack of useful diagnostic tests. We comprehensively evaluate the overall diagnostic accuracy of Interferon-gamma release assays (IGRA) upon tuberculous pericarditis by meta-analysis. METHODS: We searched PubMed, Embase and Cochrane Library database from the earliest available date of indexing through April 30, 2019. The study quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS2) checklist. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-) and constructed summary receiver operating characteristic curves parameters. RESULTS: Across six results from five studies (415 patients), the pooled sensitivity for IGRA methods was 0.94 (95% confidence interval [CI]; 0.87-0.98) with heterogeneity (χ2  = 69.9, P = .01) and a pooled specificity of 0.94 (95% CI; 0.75-0.94) without heterogeneity (χ2  = 41.1, P = .13). Likelihood ratio (LR) syntheses gave an overall positive likelihood ratio (LR+) of 16.8 (95% CI; 8.0-35.4) and negative likelihood ratio (LR-) of 0.06 (95% CI; 0.03-0.13). The pooled diagnostic odds ratio was 278 (95% CI; 114-6806). CONCLUSIONS: Interferon-gamma release assays demonstrated good sensitivity and specificity for diagnosis of tuberculous pericarditis. At present, the literature regarding remains the use of IGRA for diagnosis of tuberculous pericarditis still limited; thus, further large multicenter studies would be necessary to substantiate the diagnostic accuracy of IGRA test for the diagnosis of tuberculous pericarditis.

Phase lag entropy as a hypnotic depth indicator during propofol sedation.

Phase lag entropy, an electro-encephalography-based hypnotic depth indicator, calculates diversity in temporal patterns of phase relationship. We compared the performance of phase lag entropy with the bispectral index™ in 30 patients scheduled for elective surgery. We initiated a target-controlled infusion of propofol using the Schnider model, and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation scale every 30 s with each stepwise increase in the effect-site propofol concentration. Phase lag entropy and bispectral index values were recorded. The correlation coefficient and prediction probability between phase lag entropy or bispectral index and the sedation level or effect-site propofol concentration were analysed. We calculated baseline variabilities of phase lag entropy and bispectral index. In addition, we applied a non-linear mixed-effects model to obtain the pharmacodynamic relationships among the effect-site propofol concentration, phase lag entropy or bispectral index and sedation level. As sedation increased, phase lag entropy and bispectral index both decreased. The prediction probability values of phase lag entropy and bispectral index for sedation levels were 0.697 and 0.700 (p = 0.261) and for the effect-site concentration of propofol were 0.646 and 0.630 (p = 0.091), respectively. Baseline variability in phase lag entropy and bispectral index was 3.3 and 5.7, respectively. The predicted propofol concentrations, using the Schnider pharmacokinetic model, producing a 50% probability of moderate and deep sedation were 1.96 and 3.01 µg.ml-1 , respectively. Phase lag entropy was found to be useful as a hypnotic depth indicator in patients receiving propofol sedation.

Target-Activated DNA Polymerase Activity for Sensitive RNase H Activity Assay.

Herein, the ribonuclease H (RNase H) activity assay based on the target-activated DNA polymerase activity is described. In this method, a detection probe composed of two functional sequences, a binding site for DNA polymerase and a catalytic substrate for RNase H, serves as a key component. The detection probe, at its initial state, suppresses the DNA polymerase activity, but it becomes destabilized by RNase H, which specifically hydrolyzes RNA in RNA/DNA hybrid duplexes. As a result, DNA polymerase recovers its activity and initiates multiple primer extension reactions in a separate TaqMan probe-based signal transduction module, leading to a significantly enhanced fluorescence "turn-on" signal. This assay can detect RNase H activity as low as 0.016 U mL-1 under optimized conditions. Furthermore, its potential use for evaluating RNase H inhibitors, which have been considered potential therapeutic agents against acquired immune deficiency syndrome (AIDS), is successfully explored. In summary, this approach is quite promising for the sensitive and accurate determination of enzyme activity and inhibitor screening.

Initial Unilateral Exposure to Deep Brain Stimulation in Treatment-Resistant Depression Patients Alters Spectral Power in the Subcallosal Cingulate.

Background: High-frequency Deep Brain Stimulation (DBS) of the subcallosal cingulate (SCC) region is an emerging strategy for treatment-resistant depression (TRD). This study examined changes in SCC local field potentials (LFPs). The LFPs were recorded from the DBS leads following transient, unilateral stimulation at the neuroimaging-defined optimal electrode contact. The goal was identifying a putative electrophysiological measure of target engagement during implantation. Methods: Fourteen consecutive patients underwent bilateral SCC DBS lead implantation. LFP recordings were collected from all electrodes during randomized testing of stimulation on each DBS contact (eight total). Analyses evaluated changes in spectral power before and after 3 min of unilateral stimulation at the contacts that later facilitated antidepressant response, as a potential biomarker of optimal contact selection in each hemisphere. Results: Lateralized and asymmetric power spectral density changes were detected in the SCC with acute unilateral SCC stimulation at those contacts subsequently selected for chronic, therapeutic stimulation. Left stimulation induced broadband ipsilateral decreases in theta, alpha, beta and gamma bands. Right stimulation effects were restricted to ipsilateral beta and gamma decreases. These asymmetric effects contrasted with identical white matter stimulation maps used in each hemisphere. More variable ipsilateral decreases were seen with stimulation at the adjacent "suboptimal" contacts, but changes were not statistically different from the "optimal" contact in either hemisphere despite obvious differences in impacted white matter bundles. Change in theta power was, however, most robust and specific with left-sided optimal stimulation, which suggested a putative functional biomarker on the left with no such specificity inferred on the right. Conclusion: Hemisphere-specific oscillatory changes can be detected from the DBS lead with acute intraoperative testing at contacts that later engender antidepressant effects. Our approach defined potential target engagement signals for further investigation, particularly left-sided theta decreases following initial exposure to stimulation. More refined models combining tractography, bilateral SCC LFP, and cortical recordings may further improve the precision and specificity of these putative biomarkers. It may also optimize and standardize the lead implantation procedure and provide input signals for next generation closed-loop therapy and/or monitoring technologies for TRD.

Observation of coherent elastic neutrino-nucleus scattering.

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ confidence level, using a low-background, 14.6-kilogram CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.

Minimally Invasive Transforaminal Lumbar Interbody Fusion in the Outpatient Setting.

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) has been shown to have long-term clinical outcomes similar to those with open TLIF and decreased perioperative morbidity. This study assessed whether this procedure can be safely performed in outpatient settings. Ninety-six consecutive patients undergoing 1- or 2-level MIS-TLIFs were retrospectively reviewed. They were divided into inpatient and outpatient cohorts (36%). All had a minimum of 2 years of follow-up. Patient demographics, comorbidities, complications, and readmissions were examined. Early postoperative complications were stratified into wound related, infection, neurologic, implant related, and vascular injuries. Patients in the outpatient cohort were significantly younger, had lower American Society of Anesthesiologists physical status scores, and had lower Charlson Comorbidity Index scores than patients in the inpatient cohort. There were no statistically significant differences in overall postoperative complication rates, readmission rates, or final Oswestry Disability Index or visual analog scale scores between the 2 cohorts. The clinical outcomes of the outpatient TLIF procedure were similar to those of the inpatient procedure and it had an acceptable complication rate. [Orthopedics. 2016; 39(6):e1218-e1222.].

Unique features of non-obstructive emphysema and pure airway obstruction.

SETTING: Emphysema without airway obstruction or airway obstruction without emphysema are often detected clinically, although they are commonly co-existent. We therefore tested the hypothesis that non-obstructive emphysema and pure airway obstruction have unique features. METHODS: A case-control observation study was undertaken retrospectively in a patient cohort at a single centre. Among 2662 subjects who underwent chest computed tomography and pulmonary function tests, we enrolled 90 patients with non-obstructive emphysema, 119 with pure airway obstruction, 81 with obstructive emphysema and 2031 subjects as normal controls. The features of the four groups were analysed and compared. RESULTS: Higher serum homocysteine (13.4 ± 7.4 vs. 11.6 ± 4.6 mol/l), higher rate of osteoporosis (15.8% vs. 4.5%), higher leukocyte count, higher male ratio, lower serum albumin and lower body mass index were observed in subjects with non-obstructive emphysema than in controls (P < 0.05). In multiple logistic regression analysis of groups without airway obstruction, osteoporosis, hyperhomocysteinaemia, hypoalbuminaemia and higher leukocyte count were independent factors associated with non-obstructive emphysema (P < 0.05). CONCLUSION: Hyperhomocysteinaemia, hypoalbuminaemia, osteoporosis and higher leukocyte count were independent predictors of non-obstructive emphysema.

Less commonly used and emerging clinical applications of SPECT-CT in benign and malignant disease.

The emergence of hybrid imaging, combining anatomical computed tomography (CT) and functional single-photon emission computed tomography (SPECT), has greatly expanded the armoury available to image disease. Integrated SPECT-CT is a dual-modality technique, which improves the sensitivity and specificity of existing radionuclide studies and enables characterization of equivocal findings detected by conventional imaging. There is a wide range of established and emerging clinical applications for SPECT-CT, which were reviewed in detail at a symposium organized by the British Institute of Radiology in March 2012. A series of articles were commissioned as an adjunct to the symposium and to raise awareness of the clinical utility of this technique. The focus of this article is on less commonly used and emerging clinical applications of hybrid SPECT-CT in a spectrum of benign and malignant conditions. The article will illustrate the incremental value of the technique in a variety of clinical applications.

Feasibility and test-retest reliability of an electroencephalography-based brain mapping system in children with cerebral palsy: a preliminary investigation.

OBJECTIVE: To investigate the feasibility and test-retest reliability of a novel electroencephalography (EEG)-based brain mapping system in healthy children and children with cerebral palsy (CP). DESIGN: Correlation statistics. SETTING: University brain mapping and neurorehabilitation laboratory. PARTICIPANTS: A convenience sample of children (N=12; 5 healthy children, mean ± SD, 12.6±0.89y; 7 children with CP, mean ± SD, 9.71±1.1y) participated in the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Mu band (8-12Hz) power values in event-related spectral perturbation maps during reach and grasp hand movements were repeatedly measured on 2 separate occasions (2h apart). Intraclass correlation coefficient (ICC(1,2)) tests were computed to determine test-retest reliability at the standard level of significance (P<.004). In addition, the feasibility of the system was determined by evaluating potential differences in the cortical activation areas obtained from topographical maps during actual reach and grasp motor tasks between healthy children and children with CP. RESULTS: The test-retest reliability results showed excellent reliability between the repeated measures, ranging from .93 (P=.000) to .99 (P=.000). Our EEG brain mapping system was capable of distinguishing differences in the cortical activity power (mu band power spectra) between healthy children and children with CP. CONCLUSIONS: To our knowledge, this study is the first evidence demonstrating the feasibility and reliability of the EEG brain mapping system. Clinically, this system provides important insights into neuroplasticity associated with motor recovery after treatment and can also be used as real-time neurofeedback or noninvasive neuromodulation in the course of neurologic rehabilitation.

A wristwatch in the esophagus associated with esophageal perforation: report of an intriguing case.

Foreign bodies in the esophagus are commonly seen in emergency medicine. We report here on a very rare case of a working wristwatch in the esophagus, which was successfully extracted by surgical intervention along with primary repair of the perforated cervical esophagus through a transcervical incision. This watch was impacted for 4 days in the cervical esophagus of an adult schizophrenic patient and resulted in cervical esophageal perforation associated with acute deep neck infection.

Hamstring contractures in children with spastic cerebral palsy result from a stiffer extracellular matrix and increased in vivo sarcomere length.

Cerebral palsy (CP) results from an upper motoneuron (UMN)lesion in the developing brain. Secondary to the UMNl esion,which causes spasticity, is a pathological response by muscle - namely, contracture. However, the elements within muscle that increase passive mechanical stiffness, and therefore result in contracture, are unknown. Using hamstring muscle biopsies from pediatric patients with CP (n =33) and control (n =19) patients we investigated passive mechanical properties at the protein, cellular, tissue and architectural levels to identify the elements responsible for contracture. Titin isoform, the major load-bearing protein within muscle cells, was unaltered in CP. Correspondingly, the passive mechanics of individual muscle fibres were not altered. However, CP muscle bundles, which include fibres in their constituent ECM, were stiffer than control bundles. This corresponded to an increase in collagen content of CP muscles measured by hydroxyproline assay and observed using immunohistochemistry. In vivo sarcomere length of CP muscle measured during surgery was significantly longer than that predicted for control muscle. The combination of increased tissue stiffness and increased sarcomere length interact to increase stiffness greatly of the contracture tissue in vivo. These findings provide evidence that contracture formation is not the result of stiffening at the cellular level, but stiffening of the ECM with increased collagen and an increase of in vivo sarcomere length leading to higher passive stresses.

Role of hepatitis B virus X repression of C/EBPbeta activity in the down-regulation of glutathione S-transferase A2 gene: implications in other phase II detoxifying enzyme expression.

1. A genome-wide in silico screening rendered the genes of phase II enzymes in the rat genome whose promoters contain the putative DNA elements interacting with CCAAT/enhancer binding protein (C/EBP) and NF-E2-related factor (Nrf2). The hepatitis B virus X (HBx) protein strongly modulates the transactivation and/or the repression of genes regulated by some bZIP transcription factors. 2. This study investigated the effects of HBx on the induction of phase II enzymes with the aim of elucidating the role of HBx interaction with C/EBPbeta or Nrf2 bZIP transcription factors in hepatocyte-derived cells. 3. Immunoblot and reporter gene analyses revealed that transfection of HBx interfered with the constitutive and inducible GSTA2 transactivation promoted by oltipraz (C/EBPbeta activator), but not that by tert-butylhydroquinone (t-BHQ, Nrf2 activator). Moreover, HBx transfection completely inhibited GSTA2 reporter gene activity induced by C/EBPbeta, but failed to inhibit that by Nrf2. 4. Gel shift assays identified that HBx inhibited the increase in C/EBPbeta-DNA complex formation by oltipraz, but not the increase in Nrf2-DNA complex by t-BHQ. Immunoprecipitation and immunoblot assays verified the direct interaction between HBx and C/EBPbeta. Moreover, chromatin immunoprecipitation assays confirmed HBx inhibition of C/EBPbeta binding to its binding site in the GSTA2 gene promoter. HBx repressed the induction of other phase II enzymes including GSTP, UDP-glucuronyltransferase 1A, microsomal epoxide hydrolase, GSTM1, GSTM2, and gamma-glutamylcysteine synthase. 5. These results demonstrate that HBx inhibits the induction of phase II detoxifying enzymes, which is mediated by its interaction with C/EBPbeta, but not Nrf2, substantiating the specific role of HBx in phase II detoxifying capacity.

Mucosal prior to systemic application of recombinant adenovirus boosting is more immunogenic than systemic application twice but confers similar protection against SIV-challenge in DNA vaccine-primed macaques.

We investigated the immunogenicity and efficacy of a bimodal prime/boost vaccine regimen given by various routes in the Simian immunodeficiency virus (SIV) rhesus monkey model for AIDS. Twelve animals were immunized with SIV DNA-vectors followed by the application of a recombinant adenovirus (rAd5) expressing the same genes either intramuscularly (i.m.) or by oropharyngeal spray. The second rAd5-application was given i.m. All vaccinees plus six controls were challenged orally with SIVmac239 12 weeks post-final immunization. Both immunization strategies induced strong SIV Gag-specific IFN-gamma and T-cell proliferation responses and mediated a conservation of CD4(+) memory T-cells and a reduction of viral load during peak viremia following infection. Interestingly, the mucosal group was superior to the systemic group regarding breadth and strength of SIV-specific T-cell responses and exhibited lower vector specific immune responses. Therefore, our data warrant the inclusion of mucosal vector application in a vaccination regimen which makes it less invasive and easier to apply.

Prolonged survival of vaccinated macaques after oral SIVmac239 challenge regardless of viremia control in the chronic phase.

To evaluate the efficacy of a multigenic vaccine and its protective immunity in the SIVmac239 challenge model, 12 rhesus macaques were divided into two groups. The vaccine group was intramuscularly immunized with multigenic DNA and recombinant adenovirus vaccine, while the control group received buffers. At 16 weeks after the last immunization, all macaques were challenged orally with pathogenic SIVmac239. The mean plasma SIV RNA loads of the vaccine group were significantly lower than those of the placebo control group up to 16 weeks post-challenge. The vaccine-induced Gag-specific IFN-gamma ELISPOT T cell responses inversely correlated with the viral loads before the chronic phase. Two out of six vaccinated macaques with strong and sustained Gag-specific T cell responses showed viremia control and maintained CD4+ T cell percentage. However, the other four vaccinated macaques showed high viral loads and reduced level of CD4+ T cell percentages during the chronic phase, comparable to those in control macaques. Five out of six vaccinated macaques survived for more than 72 weeks, while five out of six controls died of an AIDS-related disease. Therefore, the vaccination conferred not only reduction of viral loads in a portion of vaccinated macaques (2/6), but also prolonged survival of all vaccinated macaques regardless of viremia control. Our results further suggest that new experimental approaches may be needed to assess protective effects from AIDS-associated disease in the immunized macaques after oral SIV challenge.

Comparison of plantar pressure distribution patterns between foot orthoses provided by the CAD-CAM and foam impression methods.

Foot orthotic treatment is one of the major conservative methods used to handle foot problems. Total plantar contact foot orthoses are used to reduce and redistribute peak pressures. For the fabrication of a total plantar contact foot orthosis, the computer-aided design and computer-aided manufacturing (CAD-CAM) method has been applied. In this study, the plantar foot-orthosis interface pressure data during walking were collected by the Novel Pedar-mobile in-shoe plantar pressure measuring system. The data were collected under three conditions: (i) Flat insole, (ii) foot orthosis provided by the CAD-CAM method, and (iii) foot orthosis provided by the foam impression method. The Swiss Comfort CAD-CAM foot orthotics system was used in this study. For conditions (ii) and (iii), foot shapes were collected in partial weight bearing and subtalar neutral conditions. Thirty normal subjects were recruited for this study. The plantar foot surface was divided into eight plantar foot regions and then was investigated. These regions included the heel, the medial and lateral arches, the medial, mid and lateral forefoot, the hallux, and the lateral toes. The results showed that the orthoses provided by both the CAD-CAM and foam impression methods could decrease the peak pressure and the maximum force in the heel region, and increase the peak pressure and the maximum force in the medial arch region. Both orthoses redistributed the peak pressure and the maximum force from the heel to the medial arch region. The peak pressure in the mid forefoot region was different between the orthoses provided by the CAD-CAM and foam impression methods.

Phase II enzyme induction by alpha-lipoic acid through phosphatidylinositol 3-kinase-dependent C/EBPs activation.

1. alpha-Lipoic acid (alpha-LA) activates antioxidant pathways and exerts insulin-like actions via phosphatidylinositol 3-kinase (PI3K), and previous studies from the authors' laboratory support the essential role of PI3K-dependent CCAAT/enhancer binding protein (C/EBP) activation in antioxidant defence responses. 2. The study investigated whether alpha-LA treatment promoted phase II antioxidant gene induction through C/EBP activation and, if so, whether combined treatment of alpha-LA and insulin synergistically increased target gene expression. 3. alpha-LA treatment induced GSTA2 in H4IIE cells in a concentration- and time-dependent manner. In cells transfected with the regulatory region of the GSTA2 gene, alpha-LA treatment increased luciferase reporter-gene activity. Immunoblot, immunocytochemistry, and gel shift assays identified the nuclear translocation and DNA binding of C/EBPalpha and C/EBPbeta, but not C/EBPdelta, in alpha-LA-treated cells. Deletion of the C/EBP binding site abolished the ability of alpha-LA to promote the luciferase gene activity. 4. alpha-LA, when combined with low concentrations of insulin, transactivated the GSTA2 gene to a greater extent compared with alpha-LA or a higher concentration of insulin treatment alone. Combined treatment of alpha-LA with insulin not only potentiated insulin signalling, but also enhanced PI3K-dependent activation of C/EBPalpha and C/EBPbeta forms. alpha-LA in combination with insulin substantially increased haemoxygenase-1, microsomal epoxide hydrolase and beta-nicotinamide adenine dinucleotide phosphate (NADPH) quinone oxidoreductase expression, verifying the enhanced induction of other phase II enzymes. A dominant negative C/EBP transfection experiment indicated that GSTA2 gene induction by simultaneous treatment of alpha-LA and insulin was also dependent on C/EBPs. 5. The results demonstrate that alpha-LA induces phase II enzymes via PI3K-dependent C/EBPalpha and C/EBPbeta activation, and enhances the ability of insulin to promote target gene induction.

Momilactone B, an allelochemical of rice hulls, induces apoptosis on human lymphoma cells (Jurkat) in a micromolar concentration.

Although momilactone B has been studied as an allelochemical of rice (Oryza sativa L.), to date we have no report showing the effect of momilactone B on mammalian cells. This study was undertaken to examine whether this allelochemical has anticancer activity on cancer cells. We show here that momilactone B at micromolar doses has antitumor efficacy by inducing apoptosis in several blood cancer cells including human leukemic T cells. In addition, our study elucidated that anticancer activity of momilactone B on human leukemic T cells resulted from the induction of apoptosis via caspase and mitochondria. From these results, momilactone B can be considered as a novel therapeutic strategy for human leukemic T cells from its direct apoptosis-inducing activity.

An anatomical study of the insertion of the zygomaticus major muscle in humans focused on the muscle arrangement at the corner of the mouth.

BACKGROUND: The aim of this study was to clarify the arrangement of the zygomaticus major muscle by means of topographic examination, and to evaluate the anatomical variations in the insertion of the zygomaticus major at the perioral region. METHODS: After a detailed dissection in the modiolar region, the insertion area of the zygomaticus major was observed in 70 embalmed cadavers. RESULTS: At the perioral region of the dissected specimens, the anatomical aspects of the muscular arrangement and attachment of the zygomaticus major muscle were classified into four categories. In type I, the superficial muscle band of the zygomaticus major is blended and interlaced with the levator anguli oris, whereas the fibers of the deep muscle band blend into the buccinator, passing deeper to the levator anguli oris; this was the situation most commonly encountered (54.3 percent). It was found that the insertion of the zygomaticus major was divided into superficial and deep bands (types I and IV) [42 cases (60 percent)] and into three layers of superficial, middle, and deep fibers (type II) [17 cases (24.3 percent)]. The others were cases where the zygomaticus major was inserted deep into the levator anguli oris as a single muscle band (type III) [11 cases (15.7 percent)]. CONCLUSION: The arrangement and insertion patterns of the zygomaticus major in this study are expected to provide critical information for surgical planning for the procedure of facial reanimation surgery.

Atraumatic oral spray immunization with replication-deficient viral vector vaccines.

The development of needle-free vaccines is one of the recently defined "grand challenges in global health" (H. Varmus, R. Klausner, R. Klausner, R. Zerhouni, T. Acharya, A. S. Daar, and P. A. Singer, Science 302:398-399, 2003). To explore whether a natural pathway to the inductive site of the mucosa-associated lymphatic tissue could be exploited for atraumatic immunization purposes, replication-deficient viral vector vaccines were sprayed directly onto the tonsils of rhesus macaques. Tonsillar immunization with viral vector vaccines encoding simian immunodeficiency virus (SIV) antigens induced cellular and humoral immune responses. Viral RNA levels after a stringent SIV challenge were reduced, providing a level of protection similar to that observed after systemic immunization with the same vaccines. Thus, atraumatic oral spray immunization with replication-deficient vectors can overcome the epithelial barrier, deliver the vaccine antigen to the mucosa-associated lymphatic tissue, and avoid induction of tolerance, providing a novel approach to circumvent acceptability problems of syringe and needle vaccines for children and in developing countries.