Comparison of the adjuvanticity of two adjuvant formulations containing de-<Emphasis Type="Italic">O</Emphasis>-acylated lipooligosaccharide on Japanese encephalitis vaccine in mice

Adjuvants are essential vaccine components used to enhance, accelerate, and/or prolong adaptive immunity against specific vaccine antigens. In this study, we compared the adjuvanticity of two adjuvant formulations containing de-O-acylated lipooligosaccharide (dLOS), a toll-like receptor 4 agonist, on the Japanese encephalitis (JE) vaccine in mice. Mice were immunized once or twice at a two-week interval with inactivated JE vaccine in the absence or presence of adjuvant. We found that both the alum- and the liposome-based formulation induced significantly faster and higher serum IgG antibody responses as compared with the non-adjuvanted vaccine after either one or two immunizations. The antibody titers of the mouse immune sera correlated with 50% plaque reduction neutralization test (PRNT₅₀) antibody titers. In addition, the dLOS/liposome formulation was more effective in inducing a Th1-type immune response than the dLOS/alum formulation, as suggested by a strong antigen-specific interferon (IFN)-γ response. Based on these results, we suggest that both alum- and liposome-based adjuvant formulations containing dLOS may be used for the development of JE vaccines with improved immunogenicity.     

Evaluating an owner‐to‐worker training intervention in California nail salons using personal air monitoring

Background

Chemicals in nail products have been linked to numerous health concerns.

Methods

We recruited Vietnamese‐American nail salon owners and workers in California and randomized salons into an intervention or control group. Owners in the intervention group received training and then provided education to workers in their salons on best practices to reduce workplace chemical exposures. Methyl methacrylate (MMA), toluene, and total volatile organic compounds (TVOCs) were measured using personal air monitors worn by workers during the work‐shift.

Results

We enrolled 77 salons (37 intervention and 40 control) and 200 workers. There was no significant intervention effect between the two groups. However, MMA and TVOCs were higher for workers who used gel polish and acrylic nails as well as in busy salons.

Conclusions

Although the intervention did not show reductions in chemical levels, identifying worker tasks and salon characteristics that predict chemical levels can inform future interventions to reduce exposures.

     

Increased frequencies of CD4+ CD25(high) regulatory T cells in acute dengue infection

Dengue virus infection is an increasingly important tropical disease, causing 100 million cases each year. Symptoms range from mild febrile illness to severe hemorrhagic fever. The pathogenesis is incompletely understood, but immunopathology is thought to play a part, with antibody-dependent enhancement and massive immune activation of T cells and monocytes/macrophages leading to a disproportionate production of proinflammatory cytokines. We sought to investigate whether a defective population of regulatory T cells (T reg cells) could be contributing to immunopathology in severe dengue disease. CD4(+)CD25(high)FoxP3(+) T reg cells of patients with acute dengue infection of different severities showed a conventional phenotype. Unexpectedly, their capacity to suppress T cell proliferation and to secrete interleukin-10 was not altered. Moreover, T reg cells suppressed the production of vasoactive cytokines after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T reg cell/effector T cell ratios were increased in patients with acute infection. A strong indication that a relative rise of T reg cell/effector T cell ratios is beneficial for disease outcome comes from patients with mild disease in which this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P = 0.2145). We conclude that although T reg cells expand and function normally in acute dengue infection, their relative frequencies are insufficient to control the immunopathology of severe disease.     

A postural change test improves the prediction of a radiological maxillary sinusitis by ultrasonography in mechanically ventilated patients

Objective The aim of this study was to evaluate a postural change test during sinus ultrasound, compared with CT scan, in case of partial sinusogram to differentiate air-fluid level from mucosal thickening. Design Prospective clinical investigation. Setting Medical intensive care unit. Patients 150 intubated patients. Interventions Patients were examined by sinus ultrasound in half-sitting position. A partial sinusogram was defined as the sole visualization of the hyperechogenic posterior wall of the sinus. In this situation, a postural change was performed and ultrasound was achieved in supine position. If the partial sinusogram disappeared when the patient was placed in a supine position (positive test), the partial sinusogram was an air-fluid level. If the partial sinusogram did not disappear (negative test), we considered it as a mucosal thickening. The CT and ultrasound were performed on the same day. Radiological maxillary sinusitis (RMS) on CT was defined as the presence of an air-fluid level. Absence of RMS on CT was defined as normal sinus or as the presence of mucosal thickening. Measurements and results 300 sinuses were examined. A partial sinusogram was found in 90 sinuses and CT scan confirmed the presence of RMS in 55 sinuses (61%). Sensitivity, specificity, positive predictive value, and negative predictive value of postural change test compared with CT were, respectively, 94.6, 85.6, 91.2 and 90.9%. The positive predictive value increased from 61 to 91.2% after the postural change test. Conclusions In case of a partial sinusogram, a postural change increases the accuracy of ultrasound to diagnose RMS.     

Transplantation of hepatitis C virus (HCV) antibody positive,nucleic acid test negative donor kidneys to HCV negative patients frequently results in seroconversion but not HCV viremia

Anecdotal reports have suggested that transplantation of hepatitis C virus (HCV) antibody positive (Ab+)/nucleic acid test negative (NAT?) donor kidneys into HCV negative recipients is not associated with HCV transmission. We reviewed our center's outcomes of 32 HCV negative patients who received kidney allografts from 25 donors who were HCV Ab+/NAT?. The mean recipient age was 56.9 ± 12.1 years and the mean donor age was 41.5 ± 14 years, with a median Kidney Donor Profile Index (KDPI) of 68%. Twelve donors (48%) met Public Health Service (PHS) increased risk status. All patients received antithymocyte globulin induction followed by tacrolimus, mycophenolate mofetil, and steroid maintenance immunosuppression. With a mean follow‐up posttransplant of 10 ± 2.7 months, 1‐ and 3‐ month serum creatinine levels were 1.7 ± 0.8 and 1.3 ± 0.4, respectively, and patient and graft survival rates were 100% and 97%, respectively. Fourteen patients (44%) seroconverted and became HCV Ab+ posttransplant. However, all 32 patients were HCV RNA negative at 1‐ and 3‐ months posttransplant, and 27 and 8 patients tested at 6‐ and 12‐months posttransplant, respectively, remain HCV RNA negative. In conclusion, transplantation of HCV Ab+/NAT? kidneys to HCV negative recipients frequently causes HCV Ab seroconversion but not HCV viremia.     

Transesophageal Pulsed Doppler echocardiography of pulmonary venous flow to assess left ventricular filling pressure in ventilated patients with acute respiratory distress syndrome

OBJECTIVE: To determine whether the systolic fraction (SF) of the pulmonary venous flow (PVF), measured by transesophageal echocardiography (TEE) could be used to estimate the pulmonary artery occlusion pressure (PAOP). DESIGN: Prospective clinical investigation. PATIENTS: Nineteen intubated patients with ARDS. INTERVENTIONS: Doppler examinations with measurement of the SF of the PVF (ie, the systolic velocity-time integral expressed as a fraction of the sum of systolic and early diastolic velocity-time integrals) were performed simultaneously with measurements of PAOP via a right heart catheter at 0 cmH2O PEEP (ZEEP), at PEEP = 8 cmH20 and at PEEP = 16 cmH2O. MEASUREMENTS AND MAIN RESULTS: At ZEEP, PAOP was inversely correlated with the SF of the PVF (r = -.89). The difference of SF between the group with PAOP <18 mm Hg and the group with PAOP > or = 18 mm Hg was statistically significant (P < .05). A SF > or = 55% predicted a PAOP < 15 mm Hg with a positive predictive value of 100% (95% CI = 63-100%). A SF < or = 40% predicted a PAOP > or =18 mm Hg with a positive predictive value of 100% (95% CI = 52-100%). At PEEP = 8 cm H20 (12 patients studied) and at PEEP = 16 cmH2O (10 patients studied), PAOP was inversely correlated with the SF of the PVF: r = -.84, and r = -.85, respectively. CONCLUSION: The SF of the PVF measured by Pulsed Doppler TEE seems to be a valuable index to estimate the left ventricular filling pressure in mechanically ventilated patients with ARDS.     

Surgical techniques for spinopelvic reconstruction following total sacrectomy: a systematic review

Purpose

To identify all available reconstruction methods for a total sacrectomy. Secondarily, we aimed to evaluate outcomes based on different interventions.

Methods

We searched PubMed to identify sacral resections for tumors requiring internal fixation for stabilization. Demographic information, fixation techniques and postoperative outcomes were abstracted.

Results

Twenty-three publications (43 patients) met inclusion criteria from an initial search of 856 (κ 0.93). Mean age was 37 years and follow-up was 33 months. Fixation methods included a combination of spinopelvic fixation (SPF), posterior pelvic ring fixation (PPRF), and/or anterior spinal column fixation (ASCF). For the purposes of analysis, patients were segregated based on whether they received ASCF. Postoperative complications including wound/instrument infections, GI or vascular complications were reported at a higher rate in the non-ASCF group (1.63 complications/patient vs. 0.7 complications/patient). Instrument failure was seen in 5 (16.1 %) out of the 31 patients with reported outcomes. Specifically, 1 out of 8 patients (12.5 %) with ASCF compared with 4 out of 23 patients (17.4 %) without ASCF had hardware failure. At final follow-up, 35 of 39 patients were ambulating.

Conclusion

While surgical treatment of primary sacral tumors remains a challenge, there have been advances in reconstruction techniques following total sacrectomy. SPF has shifted from intrapelvic rod and hook constructs to pedicle and iliac screw–rod systems for improved rigidity. PPRF and ASCF have adapted for deficiencies in the posterior ring and anterior column. A trend toward a lower rate of hardware failure emerged in the group utilizing anterior spinal column support. Despite a more involved reconstruction with ASCF, surgical complications such as infection rates and blood loss were lower compared to the group without ASCF. While we cannot definitively say one system is superior to the other, based on the data gleaned from this systematic review, it is our opinion that incorporation of ASCF in reconstructing the spinopelvic junction may lead to improved outcomes. However, most importantly, we recommend that the treating surgeon operate on patients requiring a total sacrectomy based on his or her level of comfort, as these cases can be extremely challenging even among experts.     

α-Glucosidase inhibition, 15-lipoxygenase inhibition,and brine shrimp toxicity of extracts and isolated compounds from Terminalia macroptera leaves

Context: Terminalia macroptera Guill. &; Perr. (Combretaceae), a tree that grows in West Africa, has been used in traditional medicine against a variety of diseases such as hepatitis, gonorrhea, skin diseases, and diabetes.

Objective: To investigate enzyme inhibitory activity against α-glucosidase and 15-lipoxygenase (15-LO) and toxicity against brine shrimp of extracts and compounds from T. macroptera leaves.

Materials and methods: Methanol extract, ethyl acetate, and butanol extracts obtained from the methanol extract, six isolated polyphenols (chebulagic acid, chebulic acid trimethyl ester, corilagin, methyl gallate, narcissin, and rutin), and shikimic acid were evaluated for enzyme inhibition and toxicity.

Results: In enzyme inhibition assays, all extracts showed high or very high activity. Chebulagic acid showed an IC₅₀ value of 0.05?µM towards α-glucosidase and 24.9?±?0.4?µM towards 15-LO, in contrast to positive controls (acarbose: IC₅₀?201?±?28?µM towards α-glucosidase, quercetin: 93?±?3?µM towards 15-LO). Corilagin and narcissin were good 15-LO and α-glucosidase inhibitors, as well, while shikimic acid, methyl gallate, and chebulic acid trimethyl ester were less active or inactive. Rutin was a good α-glucosidase inhibitor (IC₅₀ ca. 3?µM), but less active towards 15-LO. None of the extracts or the isolated compounds seemed to be very toxic in the brine shrimp assay compared with the positive control podophyllotoxin.

Conclusion: Inhibition of α-glucosidase in the gastrointestinal tract may be a rationale for the medicinal use of T. macroptera leaves against diabetes in traditional medicine in Mali. The plant extracts and its constituents show strong inhibition of the peroxidative enzyme 15-LO.     

Cyclic Penta- and Hexaleucine Peptides without N-Methylation Are Orally Absorbed

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