Discovery of putative salivary biomarkers for Sjögren's syndrome using high resolution mass spectrometry and bioinformatics

The purpose of the current study was to determine if saliva contains biomarkers that can be used as diagnostic tools for Sj?gren's syndrome (SjS). Twenty seven SjS patients and 27 age-matched healthy controls were recruited for these studies. Unstimulated glandular saliva was collected from the Wharton's duct using a suction device. Two μl of salvia were processed for mass spectrometry analyses on a prOTOF 2000 matrix-assisted laser desorption/ionization orthogonal time of flight (MALDI O-TOF) mass spectrometer. Raw data were analyzed using bioinformatic tools to identify biomarkers. MALDI O-TOF MS analyses of saliva samples were highly reproducible and the mass spectra generated were very rich in peptides and peptide fragments in the 750-7,500 Da range. Data analysis using bioinformatic tools resulted in several classification models being built and several biomarkers identified. One model based on 7 putative biomarkers yielded a sensitivity of 97.5%, specificity of 97.8% and an accuracy of 97.6%. One biomarker was present only in SjS samples and was identified as a proteolytic peptide originating from human basic salivary proline-rich protein 3 precursor. We conclude that salivary biomarkers detected by high-resolution mass spectrometry coupled with powerful bioinformatic tools offer the potential to serve as diagnostic/prognostic tools for SjS.     

Reduced memory in fat mass and obesity‐associated allele carriers among older adults with cardiovascular disease

Background: Much attention has been paid to the prevalence and predisposition of the fat mass and obesity‐associated (FTO) gene to obesity, although only a few studies have characterized the extent to which this affects cognitive function. This study examined differences between risk allele carriers (i.e. FTO‐AC/AA) and non‐carriers (i.e. FTO‐CC) on indices of attention/executive function/psychomotor speed, memory, language, and visual‐spatial ability in a sample of older patients with cardiovascular disease. Methods: We recruited 120 older adults from an outpatient cardiology clinic who underwent blood draw and completed neuropsychological testing. Participants were classified into two groups: one for those who were homozygous for the non‐risk‐conferring allele (i.e. FTO‐CC) (n= 49) and the other for those who had at least one copy of the obesity risk‐conferring A allele (i.e. FTO‐AC/AA) (n= 71). Results: Mancova analyses adjusting for age and years of education revealed the FTO‐AC/AA group performed significantly worse on indices of memory (λ= 0.94, F(2, 115) = 3.58, P= 0.03, partial η²= 0.06). Follow‐up tests revealed a significant effect for the FTO‐AC/AA group, relative to the non‐carrier group, on encoding (i.e. California Verbal Learning Test Total Learning) and California Verbal Learning Test long‐delay free recall (P < 0.05). No such differences between FTO carriers and non‐carriers emerged on tests of attention/executive function/psychomotor speed, language, or visual‐spatial ability (P > 0.05 for all). Conclusions: These findings suggest that the FTO risk allele is associated with reduced memory performance, particularly on aspects of memory encoding and delayed recall. To elucidate underlying mechanisms, these findings will need to be replicated in larger samples that utilize neuroimaging.     

A Systematic Review and Meta-Analysis Comparing Laparoscopic Versus Open Gastric Resections for Gastrointestinal Stromal Tumors of the Stomach

Background

This study is a systematic review and meta-analysis that compares the short- and long-term outcomes of laparoscopic gastric resection (LR) versus open gastric resection (OR) for gastric gastrointestinal stromal tumors (GISTs).

Methods

Comparative studies reporting the outcomes of LR and OR for GIST were reviewed.

Results

A total of 11 nonrandomized studies reviewed 765 patients: 381 LR and 384 OR. A higher proportion of high-risk tumors and gastrectomies were in the OR compared with LR (odds ratio, 3.348; 95 % CI, 1.248–8.983; p = .016) and (odds ratio, .169; 95 % CI, .090–.315; p < .001), respectively. Intraoperative blood loss was significantly lower in the LR group [weighted mean difference (WMD), ?86.508 ml; 95 % CI, ?141.184 to ?31.831 ml; p < .002]. The LR group was associated with a significantly lower risk of minor complications (odds ratio, .517; 95 % CI, .277–.965; p = .038), a decreased postoperative hospital stay (WMD, ?3.421 days; 95 % CI, ?4.737 to ?2.104 days; p < .001), a shorter time to first flatus (WMD, ?1.395 days; 95 % CI, ?1.655 to ?1.135 days; p < .001), and shorter time for resumption of oral intake (WMD, ?1.887 days; 95 % CI, ?2.785 to ?.989 days; p < .001). There was no statistically significant difference between the two groups with regard to operation time (WMD, 5.731 min; 95 % CI, ?15.354–26.815 min; p = .594), rate of major complications (odds ratio, .631; 95 % CI, .202–1.969; p = .428), margin positivity (odds ratio, .501; 95 % CI, .157–1.603; p = .244), local recurrence rate (odds ratio, .629; 95 % CI, .208–1.903; p = .412), recurrence-free survival (RFS) (odds ratio, 1.28; 95 % CI, .705–2.325; p = .417), and overall survival (OS) (odds ratio, 1.879; 95 % CI, .591–5.979; p = .285).

Conclusions

LR results in superior short-term postoperative outcomes without compromising oncological safety and long-term oncological outcomes compared with OR.     

Impairments in hippocampal synaptic plasticity following prenatal ethanol exposure are dependent on glutathione levels

Previous studies from our laboratory have shown that prenatal ethanol exposure (PNEE) causes a significant deficit in synaptic plasticity, namely long‐term potentiation (LTP), in the dentate gyrus (DG) region of the hippocampus of male rats. PNEE has also been shown to induce an increase in oxidative stress and a reduction in antioxidant capacity in the brains of both male and female animals. In this study the interaction between LTP and the major antioxidant in the brain, glutathione (GSH), is examined. We show that depletion of the intracellular reserves of GSH with diethyl maleate (DEM) reduces LTP in control male, but not female animals, mirroring the effects of PNEE. Furthermore, treatment of PNEE animals with N‐acetyl cysteine (NAC), a cysteine donor for the synthesis of GSH, increases GSH levels in the hippocampus and completely restores the deficits in LTP in PNEE males. These results indicate that in males GSH plays a major role in regulating LTP, and that PNEE may cause reductions in LTP by reducing the intracellular pool of this endogenous antioxidant. © 2013 Wiley Periodicals, Inc.     

Impact of MammaPrint on Clinical Decision‐Making in South African Patients with Early‐Stage Breast Cancer

The aim of the study was to evaluate the impact of MammaPrint on treatment decision‐making in patients with breast cancer. Clinicopathologic information of all breast cancer patients referred for MammaPrint testing in South Africa was collected from 2007 until 2014. A total of 107 patients (109 tumors) with estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor‐2 negative tumors were selected with tumors ≥10 mm, or when 1–3 nodes were involved without extra‐nodal extension. None of the clinical indicators correlated significantly with the MammaPrint risk classification, which changed the decision for adjuvant chemotherapy in 52% of patients. Of 60 patients who were clinically high risk, 62% had a low‐risk MammaPrint result and of the 47 clinically low ‐risk patients 40% had a high‐risk MammaPrint result. This study indicates that MammaPrint could reduce the need for adjuvant chemotherapy by 17% using the selection criteria stipulated. The significant impact on treatment decisions confirmed the clinical utility of MammaPrint independent of standard clinicopathologic risk factors as supported by long‐term clinical outcome studies.