Comparative study of Kaposi's sarcoma-associated herpesvirus serological assays using clinically and serologically defined reference standards and latent class analysis

Accurate determination of infection with Kaposi's sarcoma-associated herpesvirus (KSHV) has been hindered by the lack of a "gold standard" for comparison of serological assays used to estimate KSHV prevalence in serosurveys conducted in different settings. We have evaluated the performance of five in-house (developed at University College London [UCL], United Kingdom, and at the virology laboratory of the Instituto de Medicine Tropical [IMT] in Sao Paulo, Brazil) and two commercial (ABI and DIAVIR) serological assays to detect antibodies to latency-associated nuclear antigen (LANA) and to lytic KSHV antigens. We used a variety of serum samples assembled to represent populations likely to be at high, intermediate, and low risk of KSHV infection in Brazil. Composite reference standard panels were prepared based on clinical and serological parameters, against which assay performances were assessed using conventional Bayesian statistics and latent class analysis (LCA). Against the clinical reference standard, in-house immunofluorescence assays to detect anti-LANA antibodies (IFA-LANA) produced at UCL and IMT had similar performances, with sensitivities of 61% (95% confidence interval [CI], 48% to 74%) and 72% (95% CI, 58% to 83%) and specificities of 99% (95% CI, 94% to 100%) and 100% (95% CI, 96% to 100%), respectively, and only the IMT IFA-LANA was included in LCA, together with the IMT IFA-lytic and four enzyme-linked immunosorbent assays (ELISAs). The LCA indicated that the IMT whole-virus ELISA performed best (sensitivity, 87% [95% CI, 81% to 91%]; and specificity, 100% [95% CI, 98% to 100%]), confirming the results obtained with the conventional statistical approach. Commercially available ELISA-based tests yielded the lowest specificities using a spectrum of serum samples. The evaluation of KSHV serological assays is warranted before planning serosurveys in various settings.     

Survey on changes in subjective symptoms,onset/trigger factors,allergic diseases,and chemical exposures in the past decade of Japanese patients with multiple chemical sensitivity

Background

Recently, with rapid changes in the Japanese lifestyle, the clinical condition of patients with multiple chemical sensitivity (MCS) may also have undergone change. Thus, we conducted a new survey for subjective symptoms, ongoing chemical exposures, the prevalence of allergic diseases, and presumed onset/trigger factors in patients with MCS and compared results with those of an old survey from ten years ago.

Total syntheses of schizandriside,saracoside and (±)-isolariciresinol with antioxidant activities

Lignans are widely distributed in plants and exhibit significant pharmacological effects, including anti-tumor and antioxidative activities. Here, we describe the total synthesis of schizandriside (1), a compound we previously isolated from Saraca asoca by monitoring antioxidative activity using the 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Starting from a tandem Michael-aldol reaction, the lignan skeleton was synthesized in 6 steps, including a cyclization step. To determine the stereochemistry of 1, we synthesized the natural product (±)-isolariciresinol (18) from alcohol 17. Comparison of the spectral data showed good agreement. Glycosylation was investigated using four different glycosyl donors. Only the Koenigs–Knorr condition using silver trifluoromethanesulfonate with 1,1,3,3-tetramethylurea provided the glycosylated product. Deprotection and purification using reverse-phase high-performance liquid chromatography gave schizandriside (1) and its diastereomer saracoside (2). Synthesized 1, 2 and 18 showed antioxidant activity with IC₅₀?=?34.4, 28.8, 53.0 μM, respectively.     

Dehydropropylpantothenamide isolated by a co-culture of Nocardia tenerifensis IFM 10554T in the presence of animal cells

Journal of Natural Medicines - A new amide, named dehydropropylpantothenamide (1), was obtained by a co-culture of Nocardia tenerifensis IFM 10554T in the presence of the mouse macrophage-like cell...     

Evaluation of QOL After Proximal Gastrectomy Using a Newly Developed Assessment Scale (PGSAS-45)

Background

Proximal gastrectomy with esophagogastrostomy (PGEG) has been widely applied as a comparatively simple method. In this study, we used a questionnaire survey to evaluate the influence of various surgical factors on post-operative quality of life (QOL) after PGEG.

Methods

In this post-gastrectomy syndrome assessment study, we analyzed QOL in 2,368 cases. Among these, 193 had undergone proximal gastrectomy and 115 had undergone PGEG. The Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-45 is a questionnaire consisting of 45 items, including the SF-8, the Gastrointestinal Symptom Rating Scale (GSRS), and other symptom items seemed to be specific to post-gastrectomy. The 23 symptom items were composed of seven symptom subscales (SS), including esophageal reflux, abdominal pain, and meal-related distress. These seven SS, total symptom score, ingested amount of food per meal, necessity for additional meals, quality of ingestion SS, ability to work, dissatisfaction with symptoms, dissatisfaction with the meal, dissatisfaction with working, dissatisfaction with daily life SS and change in body weight were evaluated as main outcome measures. In PGEG cases, we evaluated the influence on QOL of various surgical factors, such as procedures to prevent gastroesophageal regurgitation and size of the remnant stomach.

Results

The scores for esophageal reflux and dissatisfaction with the meal were higher in patients who had not undergone an anti-reflux procedure. In most cases, the preserved remnant stomach was more than two-thirds the size of the pre-operative stomach. When comparing patients with a remnant stomach two-thirds the pre-operative size and those with more than three-quarters, the diarrhea SS and necessity for additional meals scores were lower in the group with more than three-quarters. The indigestion, constipation, and abdominal pain subscales, and the total symptom score, were higher in patients who had not undergone pyloric bougie than in those who had.

Conclusion

These results indicated that QOL was better in patients with a large remnant stomach. Procedures to prevent gastroesophageal reflux, and the use of pyloric bougie as a complementary drainage procedure, were considered effective ways to reduce the deterioration of QOL.     

Impact of the Presence and Duration of Donor-Specific Antibodies on Renal Function

Background

Although anti-human leukocyte antigen (HLA) antibodies (DSA) is associated with graft loss, 3 things remain unclear: whether the duration and strength of DSA affect renal function; what mean fluorescence intensity (MFI) cut-off should be used; and whether the DSA effect is additive in case of multiple DSAs.

Methods

A study was made of 63 patients who received living donor kidney transplants with clonal deletion protocol and were followed up for 18 months with reduced doses of immunosuppressants. DSA was tested for monthly, using Luminex Mixed and Single Antigen beads (One Lambda, Inc., Canoga Park, CA, USA). Decrease of estimated glomerular filtration rate (eGFR) was obtained at baseline and 18 months after transplantation. Association of renal damage and DSAs was compared using several DSA models with several MFI cut-offs.

Results

Additive DSA models always showed better association with renal damage than comprehensive models. When calculating the DSA effect in additive models, “proxy-area under the curve” (AUC)—a triangular approximation of the actual AUC—showed better association with renal damage than did DSA duration (R² = 0.105 vs 0.087). Adjusting for other factors, 27% of the variation of GFR change was explained by proxy-AUC. No significant change of association occurred if the MFI cut-off level changed from 1000 to 3000.

Conclusion

Our results support the association of DSA with development of longitudinal renal damage. The clinical interpretation may be similar at MFI cut-offs of 1000, 2000, and 3000. An additive DSA effect may be expected in patients with multiple DSAs. Our study suggests the importance of frequently checking for DSA and reducing their MFI value to minimize renal damage by the antibodies.     

Determinants of reflux perception in patients with non-erosive reflux disease who have reflux-related symptoms on potassium-competitive acid blocker therapy

Esophagus - This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid...     

Histological changes in the human esophagus following triamcinolone injection to prevent esophageal stricture after endoscopic submucosal dissection

Esophagus - Locoregional steroid injection prevents post-endoscopic submucosal dissection (ESD) esophageal stricture, but histological changes that occur following steroid injection in the human...     

Saliva secretion is reduced in proton pump inhibitor-responsive non-erosive reflux disease patients

Esophagus - There is no consensus on the relationship between saliva secretion and non-erosive reflux disease (NERD). In this study, saliva secretion and salivary epidermal growth factor (EGF) in...