[11C]PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.

Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance-positron emission tomography (MR-PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR-PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.

Comparing right colon adenoma detection rate during water exchange and air insufflation: a double-blind randomized controlled trial.

BACKGROUND: Randomized controlled trials (RCTs) have reported that water exchange (WE) produced the highest adenoma detection rate (ADR) but did not evaluate right colon adenoma detection rate (rADR) as a primary outcome and only one of the trials employed blinded colonoscopists. The aim of our study was to determine whether, compared with air insufflation, WE significantly increases rADR and right colon serrated lesion detection rate (rSLDR) and decreases adenoma miss rate (rAMR). METHODS: This prospective, double-blind RCT was conducted at a regional hospital in Taiwan between December 2015 and February 2020. Standard WE and air insufflation were performed. After cecal intubation, the second blinded endoscopist examined the right colon and obtained rADR (primary outcome) and rSLDR. Then, the primary colonoscopist reinserted the scope to the cecum with WE in both groups and performed a tandem examination of the right colon to obtain rAMR. RESULTS: There were 284 patients (50.9% male, mean age 58.9 ± 9.4 years) who were randomized to WE (n = 144) or air insufflation (n = 140). The baseline characteristics were similar. The rADR (34.7% vs. 22.3%, p = 0.025), Boston Bowel Preparation Scale scores (mean, 2.6 ± 0.6vs. 2.2 ± 0.6, p < 0.001), rSLDR (18.1% vs. 7.1%, p = 0.007), and rAMR (31.5% vs. 45.2%, p = 0.038) were significantly different between WE and air insufflation. CONCLUSIONS: The current study demonstrated a significantly higher rADR and rSLDR with the WE method performed by blinded colonoscopists. The impact of the significant findings in this report on the occurrence of interval cancers deserves to be studied.

Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study.

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12-1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29-3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07-1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06-1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01-19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41-24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.

The dose-response effects of uric acid on the prevalence of metabolic syndrome and electrocardiographic left ventricular hypertrophy in healthy individuals.

BACKGROUND AND AIM: Hyperuricemia (HUA) is associated with the prevalence of metabolic syndrome (MetS) and cardiovascular risks in various populations. HUA is also able to induce cardiomyocyte hypertrophy in mouse models. However, the dose-response effects of serum uric acid (SUA) on the prevalence of MetS and electrocardiographic left ventricular hypertrophy (LVH) are unclear. METHODS AND RESULTS: We retrospectively collected data from 18,932 individuals who underwent an annual health examination between 1/1/2016 and 12/31/2016. We excluded those with systemic diseases or missing questionnaires. The primary study endpoints were the prevalence of MetS and LVH, which were defined by the criteria for the Taiwanese population and the "SPRINT" trial. The cohort consisted of 17,913 individuals with a mean age of 31.2 years (SD 7.4) and a mean body mass index of 24.6 kg/m2 (SD 3.6); 87.1% of the individuals were men. The prevalence rates of HUA, MetS, and LVH were 29.5%, 9.4%, and 0.32%, respectively, in the overall study population. The HUA group was predominantly male and had significantly poorer lifestyle choices and greater laboratory cardiometabolic biomarker values than did the normouricemic group. However, the frequencies of physical activity were comparable between the two groups. After adjusting for confounders, SUA was associated with MetS (OR:1.473, 95% CI:1.408-1.540, P < 0.001) and LVH (OR:1.301, 95% CI:1.064-1.591, P = 0.01). CONCLUSION: We demonstrated that the dose-response effects of SUA are associated with the prevalence of MetS and electrocardiographic LVH in healthy individuals from Taiwan. Based on this evidence, future studies should investigate urate-lowering therapy and cardiovascular benefits in individuals with HUA (ClinicalTrials.gov number NCT03473951).

Intramyocardial bone marrow cell injection does not lead to functional improvement in patients with chronic ischaemic heart failure without considerable ischaemia.

BACKGROUND: It has been suggested that bone marrow cell injection may have beneficial effects in patients with chronic ischaemic heart disease. However, previous trials have led to discrepant results of cell-based therapy in patients with chronic heart failure. The aim of this study was to evaluate the efficacy of intramyocardial injection of mononuclear bone marrow cells in patients with chronic ischaemic heart failure with limited stress-inducible myocardial ischaemia. METHODS AND RESULTS: This multicentre, randomised, placebo-controlled trial included 39 patients with no-option chronic ischaemic heart failure with a follow-up of 12 months. A total of 19 patients were randomised to autologous intramyocardial bone marrow cell injection (cell group) and 20 patients received a placebo injection (placebo group). The primary endpoint was the group difference in change of left ventricular ejection fraction, as determined by single-photon emission tomography. On follow-up at 3 and 12 months, change of left ventricular ejection fraction in the cell group was comparable with change in the placebo group (P = 0.47 and P = 0.08, respectively). Also secondary endpoints, including left ventricle volumes, myocardial perfusion, functional and clinical parameters did not significantly change in the cell group as compared to placebo. Neither improvement was demonstrated in a subgroup of patients with stress-inducible ischaemia (P = 0.54 at 3­month and P = 0.15 at 12-month follow-up). CONCLUSION: Intramyocardial bone marrow cell injection does not improve cardiac function, nor functional and clinical parameters in patients with severe chronic ischaemic heart failure with limited stress-inducible ischaemia. CLINICAL TRIAL REGISTRATION: NTR2516.

Discovery and characterization of selective small molecule inhibitors of the mammalian mitochondrial division dynamin, DRP1.

Balanced rates of mitochondrial division and fusion are required to maintain mitochondrial function, as well as cellular and organismal homeostasis. In mammals, the cellular machines that mediate these processes are dynamin-related GTPases; the cytosolic DRP1 mediates division, while the outer membrane MFN1/2 and inner membrane OPA1 mediate fusion. Unbalanced mitochondrial dynamics are linked to varied pathologies, including cell death and neurodegeneration, raising the possibility that small molecules that target the division and fusion machines to restore balance may have therapeutic potential. Here we describe the discovery of novel small molecules that directly and selectively inhibit assembly-stimulated GTPase activity of the division dynamin, DRP1. In addition, these small molecules restore wild type mtDNA copy number in MFN1 knockout mouse embryonic fibroblast cells, a phenotype linked to deficient mitochondrial fusion activity. Thus, these compounds are unique tools to explore the roles of mitochondrial division in cells, and to assess the potential therapeutic efficacy of rebalancing mitochondrial dynamics in pathologies associated with excessive mitochondrial division.

Novel mold-resistant building materials impregnated with thermally reduced nano-silver.

In this study, we evaluated the long-term antifungal effectiveness of 3 types of interior building materials (gypsum board [GB], cement board [CB], and softwood plywood [S-PW]) impregnated with thermally reduced silver nanoparticles supported by titanium dioxide (AgNPs/TiO2 ) under 95% relative humidity for 4 weeks. AgNPs/TiO2 was synthesized at 2 thermal reduction temperatures (TRTs, 120 and 200°C) with 2 different AgNP weight percentages (2 and 5 wt%). Four different silver-loading levels (SLLs, 0.025, 0.05, and 0.5 µg/cm2 and the critical concentration required to inhibit fungal growth on agar plates) and 3 fungal species (Aspergillus niger, Penicillium spinulosum, and Stachybotrys chartarum) were used in the experiments. Higher temperature reduced more ionic Ag+ to metallic Ag0 and increased the dispersion of Ag on TiO2 surface. The 200°C thermally reduced AgNPs/TiO2 demonstrated excellent antifungal efficiency: Mold growth was almost completely inhibited for 28 days at the low SLL of 0.5 µg/cm2 . Additionally, AgNPs/TiO2 exhibited higher antifungal activity on GB and CB than on S-PW. The stepwise regression results indicated that the TRT of AgNPs/TiO2 (ß = -0.739 to -0.51), the SLL (ß = -0.477 to -0.269), and the Ag0 level in the AgNPs (ß = -0.379 to -0.136) were the major factors influencing antifungal activity and TRT might be the most significant one.

Risk of developing pressure sore in amyotrophic lateral sclerosis patients - a nationwide cohort study.

BACKGROUND: Prior investigations with few cases have disclosed lack of pressure sore (PrS) formation was characteristic in amyotrophic lateral sclerosis (ALS) patients. However, studies with larger samples are lacking to ascertain this concept. OBJECTIVE: To investigate whether patients with ALS have higher risk of PrS. METHODS: Utilizing a Taiwan National Insurance claims data set with 23 million participants, we extracted 514 patients with ALS and 2056 controls from 1 January 2000 to 31 December 2008. Both groups were followed up until PrS occurrence during study period (2000-2011). The PrS risk was calculated with Cox proportional regression model. RESULTS: The patients with ALS had a greater PrS risk (adjusted hazard ratio [aHR] = 8.82, 95% confidence interval [CI] = 4.90-15.9, P < 0.001) than the controls did. PrS risk was much higher in ALS women (aHR = 26.6, 95% CI = 9.05-78.2, P < 0.001) than in ALS men (aHR = 4.38, 95% CI = 1.99-9.68, P < 0.001). Besides, in people aged 20-54, ALS was linked with a much greater PrS risk (aHR = 27.7, 95% CI = 5.79-132, P < 0.001) than in those aged ≥55 (aHR = 6.10, 95% CI = 3.10-12.0, P < 0.001). CONCLUSIONS: Amyotrophic lateral sclerosis is discovered to be correlated with an enhanced PrS risk. For PrS prevention, it is needed to pay more attention to the management of the patients with ALS, particularly in women and those with relatively younger age. Further investigations are needed to confirm the findings in this study.

Revisits after adenotonsillectomy in children with sleep-disordered breathing: A retrospective single-institution study.

OBJECTIVE: To investigate emergency room (ER) revisits and hospital readmissions following adenotonsillectomy (T&A) in children with sleep-disordered breathing (SDB), and correlations between SDB severity and ER revisits. DESIGN: Retrospective chart review study. SETTING: Tertiary referral centre. PARTICIPANT: 610 consecutive children underwent T&A for treating SDB. MAIN OUTCOME MEASURES: Sleep-disordered breathing severity was defined according to the apnoea-hypopnoea index (AHI) (primary snoring = AHI < 1; mild = AHI 1-5; moderate = AHI 5-10; and severe = AHI > 10). Revisit and readmission patterns within 30 days of the surgery were extracted and analysed. RESULTS: Of these children (mean age = 7.2 years; males = 72%), 49 (8.0%) had first ER revisit, nine (1.5%) had second ER revisits, and one (0.2%) had third ER revisits. Reasons for ER revisits were bleeding related (46%) or non-bleeding related (54%). The timing for revisits was 6.9±1.9 postoperative days for bleeding-related revisits and 9.3±10.0 days for non-bleeding-related revisits. Treatment strategies during these revisits were treat and release in 44 children (74.6%), admission for observation in eight children (13.5%), and admission for surgery in seven children (11.9%). The incidence of ER revisit and hospital readmission was similar among children with all levels of SDB severity. Multivariable logistic regression analysis showed that young children (<3 years) experienced an increased risk of non-bleeding-related revisits (odds ratio [OR] = 4.1). CONCLUSIONS: Children with severe SDB do not experience increased risks of revisit or readmission; however, young children are at increased risk of non-bleeding-related revisits.

[Comparison of clinical outcome between utilized second sacral alar-iliac and iliac screw on kyphoscoliosis patients].

Objective: To compare the clinical outcome and health related quality of life(HRQoL)of patients with degenerative spinal deformity who underwent spino-pelvic fixation utilized second sacral alar-iliac(S(2)AI)with patient utilized traditional iliac screw(IS). Methods: Patients diagnosed as degenerative spinal deformity who underwent spino-pelvic fixation utilized either S(2)AI screw or Iliac screw at Department of Spine Surgery of Drum Tower hospital from January 2013 to January 2016 were retrospectively analyzed. Patients were divided into two groups according to the pelvic fixation technique. Cobb's angle, coronal balance distance(CBD), regional kyphosis(RK), sagittal vertical axis(SVA)were recorded at pre-operation, post-operation and last follow up. The MOS item short from the health survey(SF-36), visual analogue scale(VAS), Oswestry disability index(ODI) were also recorded at pre-operation and last follow up. Five physical examinations were administered to all patient at the last follow up to diagnose sacroiliac joint dysfunction, three tests resulting positive were regarded as dysfunction. Repeated measurement analysis of variance, t-test or non-parametric test was used to analyzed the data, respectively. Results: A total of 22 patients who met the inclusion were recruited in this study. Fourteen patients were utilized S(2)AI screw and 8 patients were utilized iliac screw.There were no significant differences in age, gender, follow up time between two groups. Cobb's angle, CBD, RK, SVA at pre- and post-operation and last follow up showed no significant difference between two groups.SF-36, ODI, VAS at pre-operation and last follow up showed no significant difference between two groups. Compared with baseline, Cobb's angle(44.4°±14.0° vs. 20.2°±7.2° vs. 18.3°±7.1°), C(7)PL-CSVL((25.3±16.0)mm vs. (10.3±5.7)mm vs. (9.2±4.2)mm), RK(33.0°(-12.0°, 50.0°) vs. 20.0°(-33.0°, 8.5°) vs. -19.0°(-29.0°, 19.0°)), SVA((31.5±34.4)mm vs. (12.1±8.4)mm vs. (10.9±7.2)mm), SF36-physical function summary(PCS)(39.8±14.3 vs. 68.2±21.5), SF36-mental component summary(MCS)(44.9±14.8 vs. 73.9±19.9), ODI(37.7±16.9 vs. 19.8±15.8), VAS(4.8±2.1 vs. 1.8±0.9) were significantly improved postoperatively in S(2)AI group(P<0.05). In the IS group, compared with baseline, Cobb's angle(54.3°±18.3° vs. 26.1°±13.2° vs. 25.6°±18.3°), C(7)PL-CSVL((31.0±16.0)mm vs. (13.9±7.0)mm vs. (12.4±6.6)mm), RK (47.0°(15.0°, 57.0°) vs. 4.0°(-10.0°, 16.0°) vs. 7.0°(-9.0°, 12.0°)), SVA((27.1±23.9)mm vs.(13.1±7.5)mm vs. (13.6±6.0)mm), SF36-PCS(29.7±7.1 vs. 61.1±11.2), SF36-MCS(35.9±7.1 vs. 64.0±11.1), ODI(48.6±13.4 vs. 19.0±10.7), VAS(4.9±1.8 vs. 2.6±1.3) were also significantly improved postoperatively(all P<0.05). There were two patients need revision surgery in the IS group due to the instrumentation-related complication. None of the patients in the S(2)AI group needed revision surgery. There were no instances of sacroiliac joint dysfunction in both groups at last follow up. Conclusion: Spino-pelvic fixation utilizing S(2)AI screw could provide similar correction rate to iliac screw and the sacroiliac joint penetration due to S(2)AI won't affect the HRQoL in patient with degenerative deformity who utilized S(2)AI.

In Vitro Activity of Delafloxacin and Microbiological Response against Fluoroquinolone-Susceptible and Nonsusceptible Staphylococcus aureus Isolates from Two Phase 3 Studies of Acute Bacterial Skin and Skin Structure Infections.

Delafloxacin is an investigational anionic fluoroquinolone antibiotic with broad-spectrum in vitro activity, including activity against Gram-positive organisms, Gram-negative organisms, atypical organisms, and anaerobes. The in vitro activity of delafloxacin and the percent microbiological response in subjects infected with fluoroquinolone-susceptible and nonsusceptible Staphylococcus aureus isolates were determined from two global phase 3 studies of delafloxacin versus vancomycin plus aztreonam in patients with acute bacterial skin and skin structure infections (ABSSSI). Patients from 23 countries, predominately the United States but also Europe, South America, and Asia, were enrolled. The microbiological intent-to-treat (MITT) population included 1,042 patients from which 685 S. aureus isolates were submitted for identification and susceptibility testing per CLSI guidelines at the central laboratory (JMI Laboratories, North Liberty, IA). The comparator fluoroquinolone antibiotics included levofloxacin and ciprofloxacin. Nonsusceptibility to these antibiotics was determined using CLSI breakpoints. S. aureus isolates were 33.7% levofloxacin nonsusceptible (LVX-NS). The delafloxacin MIC90 values against levofloxacin-nonsusceptible S. aureus, methicillin-resistant S. aureus (MRSA), and methicillin-susceptible S. aureus isolates were all 0.25 µg/ml. Delafloxacin demonstrated high rates of microbiological response against LVX-NS isolates as well as isolates with documented mutations in the quinolone resistance-determining region (QRDR). S. aureus was eradicated or presumed eradicated in 98.4% (245/249) of delafloxacin-treated patients. Similar eradication rates were observed for delafloxacin-treated subjects with levofloxacin-nonsusceptible S. aureus isolates (80/81; 98.8%) and MRSA isolates (70/71; 98.6%). Microbiological response rates of 98.6% were observed with delafloxacin-treated subjects with S. aureus isolates with the S84L mutation in gyrA and the S80Y mutation in parC, the most commonly observed mutations in global phase 3 studies. The data suggest that delafloxacin could be a good option for the treatment of infections caused by S. aureus isolates causing ABSSSI, including MRSA isolates, where high rates of ciprofloxacin and levofloxacin nonsusceptibility are observed. (The phase 3 studies described in this paper have been registered at ClinicalTrials.gov under identifiers NCT01984684 and NCT01811732.).

Performance of the Pooled Cohort atherosclerotic cardiovascular disease risk score in hepatitis C virus-infected persons.

Chronic hepatitis C virus (HCV) infection has been associated with an increased risk for cardiovascular disease (CVD). The recommended Pooled Cohort atherosclerotic cardiovascular disease (ASCVD) risk equation for estimation of 10-year CVD risk has not been validated in HCV-infected populations. We examined the performance of the ASCVD risk score in HCV-infected persons, using the national Electronically Retrieved Cohort of HCV Infected Veterans to derive a cohort of HCV-infected and uninfected subjects without baseline ASCVD, hepatitis B, or HIV infection, and with low-density lipoprotein cholesterol level<190 mg/dL. Performance of the ASCVD risk equation was assessed by Cox proportional hazard regression, C-statistics and Hosmer-Lemeshow statistic. The cohort included 70 490 HCV-infected and 97 766 HCV-uninfected men with mean age of 55 years, 56% White and 29% Black. Incident CVD event rates were similar between the two groups (13.2 and 13.4 events/1000 person-years), with a higher incidence of coronary heart disease events in the HCV-uninfected group and of stroke events in the HCV-infected group. Adjusting for ASCVD risk score, HCV infection was associated with higher risk for an ASCVD event in the subgroup with baseline ASCVD risk ≥7.5% (HR: 1.19, P<.0001). C-statistics were poor in both the HCV-infected and uninfected groups (0.60 and 0.61, respectively). By Hosmer-Lemeshow test, the ASCVD risk equation overestimated risk amongst lower risk patients and underestimated risk amongst higher risk patients in both the HCV-infected and uninfected groups. Further investigation is needed to determine whether a modified equation to accurately predict ASCVD risk in HCV-infected persons is warranted.

Predictive value of nodal maximum standardized uptake value of pretreatment [18F]fluorodeoxyglucose positron emission tomography imaging in patients with esophageal cancer.

We retrospectively reviewed 102 patients with esophageal cancer (97.1% squamous cell carcinoma, 96.1% stage III) received FDG-PET staging and were treated by chemoradiotherapy with or without resection to assess whether the pretreatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) maximum standardized uptake value (SUVmax) of the primary tumor and metastatic lymph nodes can predict the prognosis of patients with esophageal cancer. Receiver operating characteristic analysis was performed to find the cutoff values for primary tumor SUVmax and nodal SUVmax. The influence of clinical factors including primary tumor SUVmax and nodal SUVmax on local progression-free survival, nodal progression-free survival (NPFS), distant metastases-free survival (DMFS), and overall survival (OS) were evaluated using univariate and multivariate analyses. A total of 40 patients received esophagectomy after neoadjuvant chemoradiotherapy (trimodality), while 62 patients received definitive chemoradiotherapy (dCRT). The median follow-up was 26.4 months. The SUVmax of primary tumor had no significant predictive value on all outcomes, while the SUVmax of metastatic lymph nodes had predictive value on several outcomes. High nodal SUVmax (≥7) predicted for worse outcomes than low nodal SUVmax (<7) in the patients who received dCRT (two-year DMFS, 17% vs. 92%, P < 0.001; NPFS, 14% vs. 81%, P = 0.001; OS, 21% vs. 50%, P = 0.003), but not in those received trimodality. On multivariate analysis of patients receiving dCRT, nodal SUVmax was the strongest independent predictor on DMFS (hazard ratio [HR] 13.93, P < 0.001), NPFS (HR 3.99, P = 0.026), PFS (HR 2.90, P = 0.003), and OS (HR 3.80, P = 0.001). High pretreatment nodal SUVmax predicts worse treatment outcomes for the patients treated with dCRT.

Characterization of residual tumours at the primary site in patients with a near pathological complete response after neoadjuvant chemoradiotherapy for oesophageal cancer.

BACKGROUND: A 'surgery as needed' strategy has been proposed for patients with oesophageal cancer who truly achieve a pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT). However, the ability to detect residual disease remains problematic. This study investigated the anatomical locations and pathological characteristics of residual cancer in patients with oesophageal squamous cell carcinoma (SCC) who achieved a near pCR following nCRT. METHODS: Patients with oesophageal SCC who achieved a near pCR after nCRT were eligible. Near pCR was defined as residual cancer in the resection specimen representing less than 10 per cent of the apparent original tumour area. RESULTS: Detailed histopathological reassessment of 76 consecutive patients (mean age 54·4 years) with a near pCR was undertaken. Some 32 patients (42 per cent) with a near pCR had no detectable mucosal lesions. Residual tumour was identified most frequently in the submucosal layer (54, 71 per cent), followed by the mucosa (44, 58 per cent), muscle layer (36, 47 per cent) and adventitia (22, 29 per cent) (P < 0·001). Among patients without ypT1a disease, increasing depth of tumour invasion correlated negatively with the likelihood of mucosal involvement. Of patients with ypT3 disease, 16 of 22 had no detectable cancer located in the mucosa, compared with six of 29 with ypT1b disease (P < 0·001). CONCLUSION: Better tools for predicting pCR are required before considering a 'surgery as needed' approach in the management of oesophageal cancer.

Patient-level analysis of incident vancomycin-resistant enterococci colonization and antibiotic days of therapy.

Vancomycin-resistant enterococci (VRE) infections are a public health threat associated with increased patient mortality and healthcare costs. Antibiotic usage, particularly cephalosporins, has been associated with VRE colonization and VRE bloodstream infections (VRE BSI). We examined the relationship between antimicrobial usage and incident VRE colonization at the individual patient level. Prospective, weekly surveillance was undertaken for incident VRE colonization defined by negative admission but positive surveillance swab in a medical intensive care unit over a 17-month period. Antimicrobial exposure was quantified as days of therapy (DOT)/1000 patient-days. Multiple logistic regression was used to analyse incident VRE colonization and antibiotic DOT, controlling for demographic and clinical covariates. Ninety-six percent (1398/1454) of admissions were swabbed within 24 h of intensive care unit (ICU) arrival and of the 380 patients in the ICU long enough for weekly surveillance, 83 (22%) developed incident VRE colonization. Incident colonization was associated in bivariate analysis with male gender, more previous hospital admissions, longer previous hospital stay, and use of cefepime/ceftazidime, fluconazole, azithromycin, and metronidazole (P < 0·05). After controlling for demographic and clinical covariates, metronidazole was the only antibiotic independently associated with incident VRE colonization (odds ratio 2·0, 95% confidence interval 1·2-3·3, P < 0·009). Our findings suggest that risk of incident VRE colonization differs between individual antibiotic agents and support the possibility that antimicrobial stewardship may impact VRE colonization and infection.

Association of hepatitis B virus infection with decreased ischemic stroke.

OBJECTIVES: Inflammatory processes (both infections and autoimmune diseases) may cause endothelial dysfunction and arterial atherosclerosis, subsequently increasing the risk of acute ischemic stroke (AIS). In this investigation, we analyzed the association between hepatitis B virus (HBV) infection and AIS risk. METHODS: A Taiwan national insurance claims data set of 1,000,000 patients was used to extract 22,303 patients with HBV and 89,212 randomly selected sex- and age-matched controls from the beginning of 2000 to the end of 2006. Both groups were followed up until the appearance of AIS or the end of 2011. AIS risk was measured using the Cox proportional regression model. RESULTS: After adjusting for the relevant covariates, the HBV group exhibited a lower AIS risk (adjusted hazard ratio [aHR] = 0.77, 95% confidence interval [CI]: 0.66-0.89) compared with the controls at the end of follow-up. Under the condition of no comorbidities, patients with HBV had a lower AIS risk compared with the controls (aHR = 0.65, 95% CI: 0.48-0.87). In 3 age-stratified subgroups, HBV was correlated with a significantly diminished risk of AIS (age ≤ 49 years: aHR = 0.57, 95% CI: 0.39-0.82; age 50-64 years: aHR = 0.65, 95% CI: 0.53-0.80; age ≥ 65 years: aHR = 0.96, 95% CI: 0.76-1.23). CONCLUSION: HBV was correlated with a reduced risk of AIS development. Although a decrease in AIS risk was noted in the patients with HBV, preventing the development of AIS in this population warrants further attention.

Comprehensive analysis of RHD splicing transcripts reveals the molecular basis for the weak anti-D reactivity of Del -red blood cells.

BACKGROUND: Of the Rh blood type, Del is a rare variant that elicits the weakest anti-D reactivity. In this study, we revisit the genetic changes of Del allele and characterise the RHD splicing transcripts to realise the molecular basis of Del formation in the Taiwanese population. STUDY DESIGN AND METHODS: The RHD exons from Del and D-positive individuals were amplified by polymerase chain reaction (PCR) using different primer pairs followed by sequencing analyses. In addition, full-length RHD transcripts were reversed transcribed and amplified by nested-PCR. The type and frequency of the RHD splicing transcripts were analysed after sequencing the PCR products that were subcloned into a cloning vector. RESULTS: All Del individuals had a characteristic 1227G>A mutation. No deletion of the exon sequences was found. At least nine types of RHD splicing transcripts including exons 7/8/9 deletion, 7/9 deletion, 8/9 deletion, 9 deletion, 2/3/7/9 deletion, 2/3/7/8/9 deletion, exons 7/8/9 deletion with replacement of exon 3 with RHCE exon 3, exon 9 deletion with cryptic insertion of 170 bp of intron 7 and exons 7/8/9 deletion with cryptic insertion of 117 bp of intron 3 were identified in the Del -RBC. These aberrant splicing transcripts led to production of frame shift or truncated D antigen. Notably, no full-length RHD transcript was identified in the Del -RBC. CONCLUSION: The RHD 1227G>A mutation contributes to the molecular basis of Del phenotype in the Taiwanese population. The point mutation results in aberrant frame shift or exon deletion transcripts and generates D protein with weak antigen presenting function.

Association between the thoroughness of the histopathological examination and survival in patients with esophageal squamous cell carcinoma who achieve pathological complete response after chemoradiotherapy.

The College of American Pathologists guidelines recommend examining at least four representative tumor blocks for determining pathological T stage in patients with primarily resected esophageal cancer. Whether the same pathological requirements are adequate in patients undergoing esophagectomy following neoadjuvant chemoradiotherapy (nCRT) remains unclear. We hypothesized that current examination protocols may underestimate the presence of microscopical residual disease after nCRT, potentially leading to under-staging. We retrospectively reviewed the records of patients with esophageal squamous cancer (ESCC) who were diagnosed as having pathological complete response (pCR) following nCRT. The thoroughness of the pathological examination in pCR patients was examined using (i) the number of blocks examined in suspicious tumor area (≤4 vs. >4), and (ii) the block quotient (calculated as the pretreatment tumor length divided by the number of blocks examined in suspicious tumor area). A total of 91 patients were enrolled. The mean number of blocks used to confirm pCR was 4.8 (range: 2-14). The 5-year overall survival (OS) and disease-free survival (DFS) in the entire cohort were 55% and 65%, respectively. Multivariate analyses identified the block quotient as the only independent predictor of OS and DFS. Receiver operating characteristic curve analysis indicated an optimal cutoff value of 1.4 for the block quotient. Among the patients who achieved pCR, the 5-year DFS differed significantly between subjects with a low (≤1.4) or high (>1.4) block quotient (76% vs. 47%, respectively, P = 0.03). The block quotient (calculated by the pretreatment tumor length divided by the number of blocks) - which reflects the meticulousness of the histopathological examination for confirming pCR - is associated with survival in ESCC patients.

Electro-optically spectrum tailorable intracavity optical parametric oscillator.

We report a unique, pulsed intracavity optical parametric oscillator (IOPO) whose output spectrum is electro-optically (EO) tailorable based on an aperiodically poled lithium niobate (APPLN) working simultaneously as an optical parametric gain medium and an active gain spectrum filter in the system. We have successfully obtained from the IOPO the emission of single to multiple narrow-line signal spectral peaks in a near-infrared (1531 nm) band simply by electro-optic control. The power spectral density of the EO tailored signal can be enhanced by up to 10 times over the original (nontailored) signal.

Genetic and mechanistic evaluation for the weak A phenotype in Ael blood type with IVS6 + 5G>A ABO gene mutation.

BACKGROUND AND OBJECTIVES: Ael is a rare blood type that is characterized by weak agglutination of RBCs when reacts with anti-A antibody in adsorption-elution test. Although IVS6 + 5G→A mutation is known to associate with the Ael blood type, genetic and mechanistic evaluation for the weak agglutination of Ael with IVS6 + 5G→A mutation has not yet been completely addressed. MATERIALS AND METHODS: In this study, five cases of confirmed Ael individuals were analysed. The cDNAs for the A(el) alleles were obtained by cloning method for sequence analyses. The erythroleukemia K562 cells were used as the cell study model and were transfected with the A(el) expression construct. Flow cytometry analysis was then performed to determine the levels of surface antigen expression. RESULTS: The results indicated that IVS6 + 5G→A attributes to all cases of Ael . RT-PCR analyses revealed the presence of at least 10 types of aberrant A(el) splicing transcripts. Most of the transcripts caused early termination and produced non-functional protein during translation. Nevertheless, the transcript without exons 5-6 was predicted to generate functional Ael glycosyltransferase lacking 57 amino acids at the N-terminal segment. When the exons 5-6 deletion transcript was stably expressed in the K562 cells, weak agglutination of the cells can be induced by adding anti-A antibody followed by adsorption-elution test. CONCLUSION: This study demonstrates that aberrant splicing of A transcripts contributes to weak A expression and the weak agglutination of Ael -RBCs, adding to the complexity for the regulatory mechanisms of ABO gene expression.