Predictive Utility of Plasma Amyloid and Tau for Cognitive Decline in Cognitively Normal Adults.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease affecting mostly elderly adults. Recent diagnostic criteria for AD recommend the use of imaging and/or cerebrospinal fluid (CSF) biomarkers together with clinical presentation for a more persuasive diagnosis. The invasiveness and expense of such examinations have led to the search for blood-based biomarkers. The plasma levels of amyloid-ß (Aß) protein and tau peptides have been found to correlate with CSF levels and imaging findings in patients with AD. This study was conducted to explore the predictive utility of plasma Aß1-42 and total tau (t-tau) levels for cognitive decline in healthy adults. METHODS: In this prospective longitudinal study, we enrolled adults aged ≥ 50 years with normal cognition at Taipei Veterans General Hospital from November 2016 to April 2019. Blood samples were collected on recruitment, and plasma Aß1-42 and t-tau levels were quantified through immunomagnetic reduction. Thorough neurophysiological assessment was performed at baseline and at the annual follow-up visit. The participants were divided into two groups according to cognitive decline. The predictive utility of Aß1-42 and t-tau levels was evaluated by receiver operating characteristic curve analysis. RESULTS: Of 60 participants recruited, seven participants progressed to mild cognitive impairment and 53 retained normal cognition on follow-up (average 1.07 ± 0.2 years). The baseline levels of plasma biomarkers (Aß1-42, t-tau, and Aß1-42 × t-tau) were significantly higher in the progressive than in the stable group (p = 0.005, p = 0.007, and p = 0.005, respectively). Higher plasma biomarker levels (Aß1-42 ≥ 16.96 pg/ml and Aß1-42 × t-tau ≥ 382 pg2/ml2) predicted more cognitive decline on annual follow-up visits. CONCLUSION: Plasma Aß1-42 and t-tau levels have predictive utility for cognitive decline, even in subjects with normal cognition. Higher baseline plasma Aß1-42 and t-tau levels may indicate a higher risk of cognitive decline in cognitively normal adults.

A2B5-positive oligodendrocyte precursor cell transplantation improves neurological deficits in rats following spinal cord contusion associated with changes in expression of factors involved in the Notch signaling pathway.

BACKGROUND: Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation. METHODS: OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+ OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation. RESULTS: IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+ OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+ OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation. CONCLUSIONS: A2B5+ OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway.

[Application of molecular analysis in differential diagnosis of ovarian adult granulosa cell tumors].

Objective: To investigate the application value of molecular detection in the differential diagnosis of ovarian adult granulosa cell tumors (AGCT) by analyzing FOXL2, AKT1 and DICER1 mutations in these tumors. Methods: A total of 48 cases of ovarian sex cord-stromal tumor (SCST) were selected from July 2012 to June 2019 in Beijing Obstetrics and Gynecology Hospital, including 21 adult granulosa cell tumors (AGCT), 15 fibromas/fibrothecomas, 8 Sertoli-Leydig cell tumors (SLCT) and 4 other types of ovarian SCST. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for FOXL2, AKT1 and DICER1 genes was performed, followed by sequencing using capillary electrophoresis. Fisher exact test was used to compare the prevalence difference of FOXL2, AKT1 and DICER1 mutations among the groups. P<0.05 was considered significant. Results: Eighteen of the 21 (85.7%) AGCT harbored FOXL2 mutation. Compared with other SCST (13.0%, 3 of 23; including fibromas/fibrothecomas and SLCT), FOXL2 mutation was significantly higher in AGCT (P<0.001). In addition, FOXL2 mutation was also detected in one fibrothecoma, two SLCT and two gynandroblastomas. DICER1 mutation was identified in four of eight SLCT, and these cases were moderately to poorly differentiated. FOXL2 mutation was found in one SLCT with DICER1 mutation. There was no DICER1 mutation in other ovarian SCST. No AKT1 mutation was detected in all the patients. Conclusions: FOXL2 mutation is a highly specific biomarker for adult AGCT and may be helpful to resolve problematic cases. Diagnosis should also be taken into consideration of the clinical and histological features as FOXL2 mutation is also found in other SCST. The detection of DICER1 mutation is helpful for the differential diagnosis of ovarian SLCT. Synchronous DICER1 and FOXL2 mutation in the SLCT has been observed, and its significance needs to be further studied.

[Minimally invasive surgery for centrally located lung cancers].

Minimally invasive surgery helps enhance postoperative recovery and improve quality of life of the patients by minimizing surgical trauma and decreasing incisional pain. Minimally invasive pulmonary resection, including both video-assisted thoracoscopic surgery and robotic surgery, is mainly used for surgical management of peripheral early stage lung cancers. Because of tumor location, lymph node involvement, and treatment modalities, surgery for central lung cancers is often technically demanding. Open thoracotomy is still the dominant approach for these tumors, especially when complex procedures such as sleeve lobectomy or pneumonectomy are needed. With the advent of surgical techniques, minimally invasive techniques have started to be tried in treatment of central lung cancers. Initial results have proven their feasibility and safety in sleeve lobectomy and pneumonectomy, showing a great potential of minimally invasive surgery in the future. Further study is necessary to prove its functionally superiority and oncological equivalence to open surgery, so that more lung cancer patients could benefit for minimally invasive surgery.

Updating maintenance energy requirement for the current sheep flocks and the associated effect of nutritional and animal factors.

There is evidence indicating that using the current UK energy feeding system to ration the present sheep flocks may underestimate their nutrient requirements. The objective of the present study was to address this issue by developing updated maintenance energy requirements for the current sheep flocks and evaluating if these requirements were influenced by a range of dietary and animal factors. Data (n = 131) used were collated from five experiments with sheep (5 to 18 months old and 29.0 to 69.8 kg BW) undertaken at the Agri-Food and Biosciences Institute of the UK from 2013 to 2017. The trials were designed to evaluate the effects of dietary type, genotype, physiological stage and sex on nutrient utilization and energetic efficiencies. Energy intake and output data were measured in individual calorimeter chambers. Energy balance (Eg) was calculated as the difference between gross energy intake and a sum of fecal energy, urine energy, methane energy and heat production. Data were analysed using the restricted maximum likelihood analysis to develop the linear relationship between Eg or heat production and metabolizable energy (ME) intake, with the effects of a range of dietary and animal factors removed. The net energy (NEm) and ME (MEm) requirements for maintenance derived from the linear relationship between Eg and ME intake were 0.358 and 0.486 MJ/kg BW0.75, respectively, which are 40% to 53% higher than those recommended in energy feeding systems currently used to ration sheep in the USA and the UK. Further analysis of the current dataset revealed that concentrate supplement, sire type or physiological stage had no significant effect on the derived NEm values. However, female lambs had a significantly higher NEm (0.352 v. 0.306 or 0.288 MJ/kg BW0.75) or MEm (0.507 v. 0.441 or 0.415 MJ/kg BW0.75) than those for male or castrated lambs. The present results indicate that using present energy feeding systems in the UK developed over 40 years ago to ration the current sheep flocks could underestimate maintenance energy requirements. There is an urgent need to update these systems to reflect the higher metabolic rates of the current sheep flocks.

Risk of post-contrast acute kidney injury in emergency department patients with sepsis.

INTRODUCTION: Although computed tomography (CT) is a useful tool for exploring occult infection in patients with sepsis in the emergency department, the potential nephrotoxicity of contrast media is a major concern. Our study aimed to investigate the association between use of contrast-enhanced CT and the risks of acute kidney injury and other adverse outcomes in patients with sepsis. METHODS: In total, 587 patients with sepsis who underwent CT scan (enhanced CT group: 105, non-enhanced CT group: 482) from January 2012 to December 2016 at a tertiary referral centre were enrolled in this retrospective analysis, and propensity score matching was performed to minimise the selection bias. The length of stay, incidences of acute kidney injury and emergent dialysis, and short-term mortality were compared between the two groups. RESULTS: Compared with patients in the non-enhanced CT group, patients in the contrast-enhanced CT group did not have increased risks of acute kidney injury (odds ratio [OR]=1.38, 95% confidence interval [CI]=0.55-3.43; P=0.489), emergent dialysis (OR=1.31, 95% CI=0.47-3.68; P=0.602), or short-term mortality (OR=0.90, 95% CI=0.48-1.69; P=0.751). In addition, there was no significant difference in the median length of hospital stay between survivors in the two groups (20 vs 19 days, P=0.742). CONCLUSIONS: Intravenous contrast administration during CT scanning was not associated with prolonged length of hospital stay in patients with sepsis in an emergency setting. Moreover, the use of contrast-enhanced CT was not associated with increased risks of acute kidney injury, emergent dialysis, or short-term mortality.

[Clinicopathological features of ovarian Brenner tumors].

Objective: To investigate the clinicopathological characteristics and diagnosis of ovarian Brenner tumors. Methods: Forty-seven cases of ovarian Brenner tumors were enrolled from January 2012 to May 2018 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University. Clinical data, imaging examination, histopathological characteristics and immunohistochemical phenotype were analyzed. Results: The age of the patients ranged from 30-73 years and the mean age was 55 years. Thirty-nine patients (83.0%) were postmenopausal. Forty cases (85.1%) of the Brenner tumors were benign, five (10.6%) borderline and two (4.3%) malignant. Usual tumor markers of ovarian carcinoma, including CA199 and CA125 were normal or mild elevated in the 47 cases. Imaging before surgery was not specific to Brenner tumors. Microscopically, benign Brenner tumors were composed of nests of bland, transitional-type cells within a fibromatous stroma. In our 5 cases of borderline Brenner tumors, mildly atypical transitional-type cells were projected into the cyst lumens and lack of stromal invasion. In 2 cases of malignant Brenner tumors, different degrees of nuclear atypial transitional-type cells exhibited stromal invasion. Immunohistochemical stains for CK7, GATA3, p63 and CK5/6 were positive in all cases. Ki-67 was less than 5% in Brenner tumors, and up to 20%-30% in malignant Brenner tumors. Conclusion: Brenner tumors are mostly seen in postmenopausal patients and are usually benign. Imaging examination and usual ovarian tumor markers do not provide diagnostic value. Diagnosis and classification of Brenner tumors depend on histopathological evaluation.

[KRAS mutations analysis in mucinous epithelial lesions of the endometrium].

Objective: To investigate the frequency of KRAS mutation in mucinous epithelial lesions of the endometrium, and analyze the correlation between KRAS mutation and the clinicopathologic features. Methods: The cohort included forty-three cases of mucinous epithelial lesions of the endometrium selected from July 2015 to October 2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed, followed by sequencing using capillary electrophoresis. The Fisher exact test was used to compare the prevalence of KRAS mutation among the different groups. Results: The patients'age ranged from 33 to 77 years [mean (55.12±9.34) years, median 55 years]. None of the eight cases of endometrial hyperplasia with mucinous differentiation without atypia showed KRAS mutation. The frequency of KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation (EAHMD), 6/15 in endometrioid carcinoma with mucinous differentiation (ECMD) and 8/9 in mucinous carcinoma (MC), respectively. The differences were statistically significant between MC versus EC (P<0.01) and MC versus ECMD (P<0.05). Conclusion: The high frequency of KRAS mutation in EAHMD, ECMD and MC indicates that KRAS mutational activation is implicated in the pathogenesis of endometrial mucinous carcinoma.

[Association between the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity and invasive measured left atrial pressure in patients with atrial fibrillation and preserved left ventricular ejection fraction].

Objective: To evaluate the association between the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity (E/E') and left atrial pressure (LAP) estimated from invasive catheter measurements in patients with atrial fibrillation (AF). Methods: A total of 46 consecutive patients with non-valvular AF and preserved left ventricular ejection fraction (LVEF) admitted in our department to receive the first radiofrequency ablation from May to July 2017 were included. All patients underwent echocardiography at 24-48 hours before radiofrequency ablation, and LAP was invasively measured during the ablation procedure. According to mean LAP, patients were divided into 2 groups of normal LAP (LAP≤12 mmHg(1 mmHg=0.133 kPa, n=31) and elevated LAP (LAP>12 mmHg, n=15). Linear correlation analysis was used to evaluate the relationship between E/E' and LAP. Results: E/E' correlated well with LAP (septal E/E' (E/E'(sep)), r= 0.397, P=0.006; lateral E/E' (E/E'(lat)), r=0.433, P=0.003; mean E/E' (E/E'(mean)), r=0.431, P=0.003). Using receiver operating characteristic analysis, the optimal cut-off for E/E'(sep) was 12.5 (sensitivity 73.3%, specificity 67.7%), E/E'(lat) was 10.8 (sensitivity 80.0%, specificity 77.4%), E/E'(mean) was 11.0 (sensitivity 86.7%, specificity 64.5%) to predict mean LAP>12 mmHg. Conclusion: E/E', especially the E/E'(lat), is positively correlated with LAP in patients with AF and preserved LVEF, and may be used to estimate the diastolic function in AF patients with preserved LVEF.

[Inflammatory myofibroblastic tumor of the paranasal sinus：three cases report].

The clinical manifestations of paranasal sinusitis were similar to those of chronic sinusitis. The main manifestations were recurrent nasal congestion,nasal obstruction,such as invasion of the surrounding tissue,local compression. Clinical manifestations were usually nonspecific. CT imaging could display the size,range of the tumor and its relationship with the surrounding tissues. Inflammatory myofibroblastic tumor is a low-grade malignant tumor and frequently misdiagnosed. Diagnosis depends on the pathological examination.Complete surgical resection is the preferred method of treatment. Adjuvant treatment included radiotherapy,chemotherapy and hormone therapy. recurrence and death was not uncommon.

Effects of pelvic floor muscle exercise on faecal incontinence in rectal cancer patients after stoma closure.

The purpose of this study was to examine the effects of pelvic floor muscle exercise (PFME) on the faecal incontinence (FI) of rectal cancer patients following stoma closure. Participants were randomly distributed into an exercise group (n = 27) and non-exercise group (n = 26). An experimental design and longitudinal approach were implemented for data collection. Baseline data were collected at 1 day before discharge, and then PFME was taught before the patients were discharged from the hospital. We collected data and followed up with the patients at their pre-discharge visit and at 1, 2, 3, 6 and 9 months after discharge. The Cleveland Clinic Faecal Incontinence (CCI) score was used to measure patient outcome. PFME proved to effectively decrease the degree of FI in stoma closure recipients. The FI score of the exercise group significantly decreased from 8.37 to 2.27 after PFME compared with that of the non-exercise group (from 8.54 to 2.58). The generalised estimation equation tests showed that both group and time were significantly different. The tests also indicated that although PFME appeared to hasten the decline of incontinence, this effect was no longer detectable at 9 months; thus, it may be an effective intervention for FI when implemented up to half a year after discharge.

Proteomic analysis of susceptibility in intestinal stromal tumors.

We analyzed the susceptibility of intestinal stromal tumors using cell culture and proteomics. Human SGC7901 gastric cells were selected and divided into a blank control group (untransfected SGC7901 cells), a negative control group [SGC7901 cells transfected with negative interference control-small interfering RNA (siRNA)], and a COOH-terminus tensin-like molecule (CTEN)-siRNA-1 group (SGC7901 cells transfected with CTEN-siRNA-1). The cells were successfully transfected and subjected to analyses of cell proliferation, cell cycle, cell invasion, CTEN expression, and proteomics. The percentages of cells in the G0/G1, S, and G2/M phases were similar in the three groups (P > 0.05), and the OD values were also similar at 24, 48, and 72 h (P > 0.05). Compared with the levels in the blank and negative control groups, CTEN protein in the CTEN-siRNA-1 group decreased by 66 and 65%, respectively, and significantly fewer cells in the CTEN-siRNA-1 group were capable of invasion (P < 0.05). Proteomic analysis showed that in the CTEN-siRNA-1 group, 283 proteins were upregulated and 242 were downregulated; from these, the expression levels of E-cadherin and ERK proteins changed significantly. Silencing the expression of CTEN in intestinal stromal tumor cells reduces their invasion capability. Moreover, silencing CTEN at different stages can also regulate the expression levels of E-cadherin and ERK proteins.

Reduction in greenhouse gas emissions from sewage sludge aerobic compost in China.

Sewage sludge is an important contributor to greenhouse gas (GHG) emissions and the carbon budget of organic solid waste treatment and disposal. In this case study, total GHG emissions from an auto-control sludge compost system, including direct and indirect emissions and replaceable reduction due to sludge compost being reused as fertilizer, were quantified. The results indicated that no methane generation needed to be considered in the carbon debit because of the advantages of auto-control for monitoring and maintenance of appropriate conditions during the composting process. Indirect emissions were mainly from electricity and fossil fuel consumption, including sludge transportation and mechanical equipment use. Overall, the total carbon replaceable emission reduction owing to sludge being treated by composting rather than landfill, and reuse of its compost as fertilizer instead of chemical fertilizer, were calculated to be 0.6204 tCO2e t(-1) relative to baseline. Auto-control compost can facilitate obtaining certified emission reduction warrants, which are essential to accessing financial support with the authentication by the Clean Development Mechanism.

Use of antispastic nicardipine and nitroglycerin (NG) cocktail solution increases graft flow during off-pump coronary artery bypass grafting.

AIM: NG solution composed of nicardipine and nitroglycerin is a new anti-spastic solution for arterial grafts. We investigated its efficacy on the left internal thoracic artery (LITA) during off-pump coronary artery bypass grafting (OPCAB). METHODS: The free flow of LITA in 41 OPCAB patients was measured. The patients were divided to four groups: LITA pedicle wrapped with normal saline (Group I, N.=10) or NG (Group II, N.=11); or in addition to wrapping, 2 cc NG (Group III, N.=10) or normal saline (Group IV, N.=10) injected into LITA. After 30 min, the distal end free flow and the graft flow by an ultrasound probe were measured. RESULTS: The free flow significantly increased in Group II (30.0±4.7 vs. 21.6±4.5 cc/min, P=0.007) and III (70.0±11.5 vs. 24.5±6 cc/min, P=0.001) but not in Group I (20.8±4.7 vs. 19.4±4.1 cc/min, P=0.33) or IV (35.8±7.5 vs. 29±9.2 cc/min, P=0.06) with significant differences between the Group III to all other groups (P=0.016-0.001). The graft flow by ultrasound probe was significantly higher in Group III (41.2±6.2 cc/min) than that in Group IV (24.1±3.1 cc/min, P=0.028). CONCLUSION: Use of NG solution for LITA graft preparation is a choice of antispastic protocol. NG solution used either topically or intraluminally significantly increases the blood flow of IMA grafts with the best effect obtained by intraluminal injection. The present study provides an additional anti-spastic method by using second generation of calcium antagonists and nitric oxide donor in coronary artery bypass surgery.