Expression and Prognostic Value of Id-4 in Patients with Esophageal Squamous Cell Carcinoma.
Our previous study demonstrated that Id-1 may promote the tumorigenicity of esophageal squamous cell carcinoma (ESCC). Id-4 is another member of Id family, which is rare to be studied in ESCC. In this study, we investigated the expression of Id-4 in human ESCC specimens and determined whether Id-4 expression was associated with the clinicopathologic characteristic and the prognosis of ESCC patients. We examined Id-4 expression using immunohistochemistry in 92 ESCC tissues and adjacent normal tissues. The association between Id-4 expression and clinical parameters and survival was evaluated by statistical analysis. Cox regression analyses were conducted to identify prognostic factors associated with overall survival (OS). In addition, we explored the functional mechanism of Id-4 in ESCC. Id-4 expression was significantly downregulated in ESCC tissues compared with adjacent normal tissues. The expression of Id-4 was associated negatively with pT stage (p=0.002), AJCC stage (p=0.008) and histologic differentiation (p<0.001). OS was more unfavorable in patients with low expression of Id-4 than those with high expression of ESCC patients (p=0.007). In subgroup analysis, low expression of Id-4 could reveal unfavorable OS of patients with pT1b/T2 stage (p=0.024) or with pN0/N1 stage (p=0.004). By univariate analysis, pT stage and Id-4 expression showed statistically significant associations with OS (p=0.025, p=0.01, respectively). By multivariate analysis, Id-4 expression was an independent prognostic factor in ESCC (p =0.038). In addition, we observed that Id-4 could decrease the levels of the p-Smad2, p-Smad3 and TGF-β1 in both Eca109 and TE1 cells, indicating Id-4 may inactivate the TGF-β signaling pathway. Low expression of Id-4 suggested unfavorable prognosis for ESCC patients and could identify the prognosis in patients of early-stage tumors. The potential mechanism for Id-4's tumor suppressor role in ESCC may be related to its inhibitory effect on TGF-β signaling pathway. Thus, we believe that Id-4 may be a promising prognostic marker and a therapeutic target in ESCC.


Stilbenes as κ-selective, non-nitrogenous opioid receptor antagonists.
The natural stilbene pawhuskin A has been shown to function as an opioid receptor antagonist, with preferential binding to the κ receptor. This finding encouraged assembly of a set of analogues to probe the importance of key structural features. Assays on these compounds determined that one (compound 29) shows potent opioid receptor binding activity and significantly improved selectivity for the κ receptor. These studies begin to illuminate the structural features of these non-nitrogenous opioid receptor antagonists that are required for activity.


Clinical Study of Stellate Ganglion Block Combined with General Anesthesia on Hemodynamics, Cognitive Function, and Gastrointestinal Function in Elderly Patients Undergoing Partial Hepatectomy.
Partial hepatectomy under general anesthesia is prone to hemodynamic alterations, and stress reactions are the main contributing factors to postoperative cognitive function in elderly partial hepatectomy patients. Postoperative cognitive dysfunction increases the incidence of postoperative complications and long-term morbidity and mortality in elderly patients. With the increasing trend of aging population and the gradual increase of elderly people undergoing surgical treatment, it is especially important to study the corresponding prevention and treatment measures. In this study, a total of 90 patients with primary liver cancer who received hepatectomy in our hospital from July 2020 to July 2021 were included as the research subject. The changes in hemorheology, stress-related indexes, cognitive function, postoperative pain, and gastrointestinal function were compared between the two groups The results showed that SGB combined with general anesthesia can effectively reduce hemodynamic fluctuations in elderly partial hepatectomy patients, alleviate surgical stress, promote postoperative recovery of cognitive function and gastrointestinal function with high safety, and is worthy of clinical promotion.


Willingness to Take PrEP and Potential for Risk Compensation Among Highly Sexually Active Gay and Bisexual Men.
Once-daily Truvada (Emtricitabine/Tenofovir) as a method of pre-exposure prophylaxis (PrEP) is one of the most promising biomedical interventions to eliminate new HIV infections; however, uptake among gay, bisexual, and other men who have sex with men has been slow amidst growing concern in popular/social media that PrEP use will result in reduced condom use (i.e., risk compensation). We investigated demographic, behavioral, and psychosocial differences in willingness to use PrEP as well as the perceived impact of PrEP on participants' condom use in a sample of 206 highly sexually active HIV-negative gay and bisexual men. Nearly half (46.1 %) said they would be willing to take PrEP if it were provided at no cost. Although men willing to take PrEP (vs. others) reported similar numbers of recent casual male partners (<6 weeks), they had higher odds of recent receptive condomless anal sex (CAS)-i.e., those already at high risk of contracting HIV were more willing to take PrEP. Neither age, race/ethnicity, nor income were associated with willingness to take PrEP, suggesting equal acceptability among subpopulations that are experiencing disparities in HIV incidence. There was limited evidence to suggest men would risk compensate. Only 10 % of men who had not engaged in recent CAS felt that PrEP would result in them starting to have CAS. Men who had not tested for HIV recently were also significantly more likely than others to indicate willingness to take PrEP. Offering PrEP to men who test infrequently may serve to engage them more in routine HIV/STI testing and create a continued dialogue around sexual health between patient and provider in order to prevent HIV infection.


Management of perioperative myocardial ischaemia after isolated coronary artery bypass graft surgery.
Updated knowledge about perioperative myocardial ischaemia (MI) after coronary artery bypass grafting (CABG) and treatment of acute graft failure is needed. We analysed main factors associated with perioperative MI and effects of immediate coronary angiography-based treatment strategy on patient outcome. Among 1119 consecutive patients with coronary artery disease who underwent isolated CABG between January 2011 and December 2015, 43 (3.8%) patients underwent urgent coronary angiography due to suspected perioperative MI. All the data were prospectively collected and retrospectively analysed. The primary endpoint was 30-day mortality; postoperative left ventricular ejection fraction) and major adverse cardiac events were secondary endpoints.ResultsOverall, 30-day mortality in patients with CABG was 1.4% while in patients who developed perioperative MI was 9% (4 patients). Angiographic findings included incorrect graft anastomosis, graft spasm, dissection, acute coronary artery thrombotic occlusion and ischaemia due to incomplete revascularisation. Emergency reoperation (Redo) was performed in 14 (32%), acute percutaneous coronary intervention (PCI) in 15 (36%) and conservative treatment (Non-op) in 14 patients. Demographic and preoperative clinical characteristics between the groups were comparable. Postoperative LVEF was significantly reduced in the Redo group (45% post-op vs 53% pre-op) and did not change in groups PCI (56% post-op vs 57% pre-op) and Non-op (58% post-op vs 57% pre-op). Urgent angiography allows identification of the various underlying causes of perioperative MI and urgent treatment when this is needed. Urgent PCI may be associated with improved clinical outcome in patients with early graft failure.


Effects of morphine on tumour growth.
Endogenous opiate alkaloids, such as morphine, and their peptide counterparts have been implicated in a wide variety of pharmacological and physiological functions. In addition to their use in the treatment of pain, opioids, appears to be important in the growth regulation of normal and neoplastic tissue. This review will focus on the influence of endogenous and exogenous opioids on tumour growth, with emphasis on immunoregulatory and antiproliferative mechanisms.


Outcomes from a One-Week Adapted Sport and Adapted Adventure Recovery Programme for Military Personnel.
The Battle Back Centre offers a bespoke, Self Determination Theory-oriented adapted sport and adventurous training programme centred on experiential learning and reflection to support the recovery of military personnel. To identify the short-term impact of participation in the programme on positive mental health and psychological need satisfaction. Participants were 978 wounded, injured and sick (WIS) personnel classified as: Wounded (battle casualties), Injured (non-battle casualties) and Sick (mental/physical illness). Participants completed the Basic Need Satisfaction in General Scale (Gagné, 2003) and Warwick and Edinburgh Mental Well Being Scale (Tennant et al. 2006) on arrival and course completion. All measures of positive mental health and psychological need satisfaction showed statistically significant increases, with a large effect size, from baseline to course completion (mean ± SD change in positive mental health, competence, autonomy and relatedness were 7.19 ± 9.61, 0.46 ± 0.9, 0.27 ± 0.84, 0.26 ± 0.86, respectively, p < 0.05). While the average magnitude of the intervention effect for positive mental health (16%) is comparable or greater than other reported interventions, changes were achieved in a shorter time. Findings highlight the positive short-term effect adapted sport and adventurous activities have for WIS personnel. Work supported by The Royal British Legion.


Breeding replacement gilts for organic pig herds.
In this study, breeding structures and commercial sow lines were evaluated by economic and genetic simulation studies for their suitability to provide the Dutch organic pig sector with replacement gilts. Sow and litter performance from over 2000 crossbred sows from 2006 to 2007 were collected on 11 to 14 Dutch organic pig herds, respectively, and compared with conventional herds. Results showed that organic herds had lower farrowing rates (3.6% to 7.5%), more live born piglets per litter (0.4% to 1.2%) and higher preweaning mortality rates (7% to 13%) compared to conventional herds. These results were used to simulate economic performance of various combinations of breeding structures and sow lines under organic conditions, under the assumption of absence of genotype-environment interactions. Sow and litter performance data under organic conditions (total piglets born/litter, stillborn piglets/litter, mortality until weaning, lactation length, interval weaning-oestrus and sow culling rate) and the costprice calculation for the Dutch organic pig sector were used as input for the economic simulation studies. The expected genetic progress was simulated for three potential breeding structures of the organic sector: organic breeding herds producing F1 gilts (OrgBS), a flower breeding system (FlowerBS) and a two-line rotation breeding system (RotBS). In FlowerBS, an organic purebred sow line is bred, using on-farm gilt replacement. The OrgBS with a Yorkshire × Landrace cross had the highest margin per sow place (€779), followed by RotBS with Yorkshire × Landrace cross (€706) and FlowerBS with Yorkshire sow line (€677). In case that an organic purebred sow population of 5000 sows would be available, FlowerBS gave the highest genetic progress in terms of cost price reduction (€3.72/slaughter pig per generation), followed by RotBS and OrgBS (€3.60/slaughter pig per generation). For FlowerBS, additional costs will be involved for maintaining a dedicated breeding programme. In conclusion, OrgBS using conventional genetics is economically the most viable option for the organic pig sector. However, this structure has clear disadvantages in terms of risks with regard to disease transmission and market demand. FlowerBS using a dedicated purebred organic line will only be cost-effective if sow population size is sufficiently large. RotBS might be a viable alternative, especially in combination with artificial insemination (AI) boars that are ranked according to an organic selection index. Regardless of breeding structure, the Yorkshire sow line gave the highest prolificacy and the highest economic returns on organic herds.


Musculoskeletal Pain and Cardiovascular Risk in Hispanic/Latino Meatpacking Workers.
Most meatpacking workers have pain affecting their back, arms, and/or wrists from work-related repetitive motions, forceful exertion, and awkward positioning. Chronic musculoskeletal pain is associated with obesity, hypertension, type II diabetes, heart attack, and stroke. Hispanic/Latino workers in the meatpacking industry are a vulnerable population; limited English, lack of health insurance, and fear of deportation often deter them from seeking care where preventable cardiovascular risks might be detected. The purpose of this study was to examine perceived health and actual cardiovascular risk among Hispanic/Latino meatpacking workers with musculoskeletal pain in Nebraska. Structured interviews were used to examine perceived health, awareness of cardiometabolic risk, and capacity for health self-management. Body mass index (BMI), lipids, blood pressure, Hemoglobin A1c (HbA1c), and cardiorespiratory fitness (step test) were used to examine cardiovascular risk. Of those interviewed (n = 39), musculoskeletal pain affected usual life activities in 64% (n = 25) of participants. Of those tested (n = 30), 93% (n = 28) had a BMI > 30 kg/m2, 86% (n = 26) had at least one lipid abnormality, 50% (n = 15) had blood pressure > 120/80 mm Hg, and 43% (n = 13) had an HbA1c > 5.7%. Males had greater fitness than females (p = .03), but also greater lifetime risk of heart attack or stroke compared with females (p = .02). In this sample, cardiovascular risk exceeded that found in the general Hispanic population in the United States. Occupational health nurses can assist workers to be aware of their risk by measuring and providing culturally and linguistically appropriate education on blood pressure, BMI, cholesterol, and HbA1c.


Trends in colorectal cancer screening with home-based fecal occult blood tests in adults ages 50 to 64 years, 2000-2008.
National surveys have reported declines in rates of home-based fecal occult blood test (FOBT) screening for colorectal cancer (CRC) in the last decade. However, socioeconomic status (SES) and racial/ethnic differences in FOBT trends and their changes relative to endoscopic CRC screening have not been evaluated. Data on adults ages 50 to 64 years from the 2000, 2005, and 2008 National Health Interview Surveys were used. Weighted analyses and multivariate logistic regression were used to study trends in the use of FOBT and endoscopic CRC screening during this period. Between 2000 and 2008, significant declines in FOBT prevalence occurred in higher SES groups, but not in lower SES groups (uninsured and publicly insured, those without a usual source of care, lower educated, lower income, and immigrants to the United States) or Hispanics. Endoscopic CRC screening during the period studied consistently increased in all higher SES subgroups. In contrast, few lower SES subgroups (publicly insured, lower educated, near poor individuals, long-term immigrants) and Hispanics experienced increases in CRC endoscopic screening, and these increases were smaller than those observed in higher SES subgroups. Socially and economically disadvantaged groups experienced little or no change in FOBT prevalence, and few of these groups experienced contemporaneous increases in CRC endoscopic screening. These trends suggest the continued availability and acceptance of FOBT in these groups. If national CRC screening goals are to be achieved in populations with lower access to colonoscopy, then annual high-sensitivity FOBT should be promoted as an immediately accessible and viable alternative.


Significance of thyroperoxidase and thyroglobulin antibodies in medically treated Graves' disease.
Thyroperoxidase (TPOAb) and thyroglobulin (TgAb) antibodies are highly prevalent in Graves' disease (GD), but their significance is controversial. We retrospectively analyzed TPOAb and TgAb levels and evolution in 136 patients with newly diagnosed GD between 2000 and 2022, treated with anti-thyroid drugs (ATD) in a block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. At diagnosis, 98 out of 136 (72%) patients were TPOAb positive and 73 out of 136 (54%) patients were TgAb positive. The presence of TPOAb or TgAb antibodies at diagnosis was generally not related to GD presentation and did not influence the risk of relapse (P = 0.304 and P = 0.348, respectively). There was less TED (thyroid eye disease) in TgAb-positive patients than TgAb-negative patients at diagnosis (11 out of 73 (15.1%) versus 21 out of 63 (33.3%) P = 0.012). In contrast, the presence of TPOAb at diagnosis was not associated with TED (P = 0.354). The absence of TgAb at diagnosis (P = 0.05) and time to euthyroidism (P = 0.009), but not smoking or TRAb levels, were associated with TED in multivariate logistic regression. TPOAb and TgAb levels during treatment and after its discontinuation were not predictive of relapse, except for lower titers of TgAb at 18 months in patients who relapsed (P = 0.034). In GD patients treated with a first course of ATD in a B+R regimen we observed lower titers of TgAb at the end of treatment in patients who relapsed and a significant protection against TED in patients with positive TgAb at diagnosis, irrespectively of TPOAb.


Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment.
Bloodstream infections (BSIs) caused by Klebsiella pneumoniae carbapenemases (KPC)-producing K. pneumoniae (KPC-KP) are associated with high mortality rates. We investigated outcomes, risk factors for mortality and impact of appropriate antimicrobial treatment in patients with BSIs caused by molecularly confirmed KPC-KP. All consecutive patients with KPC-KP BSIs between May 2008 and May 2010 were included in the study and followed-up until their discharge or death. Potential risk factors for infection mortality were examined by a case-control study. Case-patients were those who died from the BSI and control-patients those who survived. Appropriate antimicrobial therapy was defined as treatment with in vitro active antimicrobials for at least 48 h. A total of 53 patients were identified. Overall mortality was 52.8% and infection mortality was 34%. Appropriate antimicrobial therapy was administered to 35 patients; mortality due to infection occurred in 20%. All 20 patients that received combination schemes had favourable infection outcome; in contrast, seven of 15 patients given appropriate monotherapy died (p 0.001). In univariate analysis, risk factors for mortality were age (p <0.001), APACHE II score at admission and infection onset (p <0.001) and severe sepsis (p <0.001), while appropriate antimicrobial treatment (p 0.003), combinations of active antimicrobials (p 0.001), catheter-related bacteraemia (p 0.04), prior surgery (p 0.014) and other therapeutic interventions (p 0.015) were significantly associated with survival. Independent predictors of mortality were age, APACHE II score at infection onset and inappropriate antimicrobial treatment. Among them, appropriate treatment is the only modifiable independent predictor of infection outcome.


Defective respiratory rhythmogenesis and loss of central chemosensitivity in Phox2b mutants targeting retrotrapezoid nucleus neurons.
The retrotrapezoid nucleus (RTN) is a group of neurons in the rostral medulla, defined here as Phox2b-, Vglut2-, neurokinin1 receptor-, and Atoh1-expressing cells in the parafacial region, which have been proposed to function both as generators of respiratory rhythm and as central respiratory chemoreceptors. The present study was undertaken to assess these two putative functions using genetic tools. We generated two conditional Phox2b mutations, which target different subsets of Phox2b-expressing cells, but have in common a massive depletion of RTN neurons. In both conditional mutants as well as in the previously described Phox2b(27Ala) mutants, in which the RTN is also compromised, the respiratory-like rhythmic activity normally seen in the parafacial region of fetal brainstem preparations was completely abrogated. Rhythmic motor bursts were recorded from the phrenic nerve roots in the mutants, but their frequency was markedly reduced. Both the rhythmic activity in the RTN region and the phrenic nerve discharges responded to a low pH challenge in control, but not in the mutant embryos. Together, our results provide genetic evidence for the essential role of the Phox2b-expressing RTN neurons both in establishing a normal respiratory rhythm before birth and in providing chemosensory drive.


The extent of food advertising to children on UK television in 2008.
To provide the most comprehensive analysis to date of the extent of food advertising on UK television channels popular with young people following regulatory reform of this type of marketing activity. UK television was recorded 06:00-22:00 h for a weekday and a weekend day every month between January and December 2008 for 14 of the most popular commercial channels broadcasting children's/family viewing. Recordings were screened for advertisements, which were coded according to predefined categories including whether they were broadcast in peak/non-peak children's viewing time. Food advertisements were coded as core (healthy)/non-core (unhealthy)/miscellaneous foods. Food and drinks were the third most heavily advertised product category, and there were a significantly greater proportion of advertisements for food/drinks during peak compared to non-peak children's viewing times. A significantly greater proportion of the advertisements broadcast around soap operas than around children's programmes were for food/drinks. Children's channels broadcast a significantly greater proportion of non-core food advertisements than the family channels. There were significant differences between recording months for the proportion of core/non-core/miscellaneous food advertisements. Despite regulation, children in the UK are exposed to more TV advertising for unhealthy than healthy food items, even at peak children's viewing times. There remains scope to strengthen the rules regarding advertising of HFSS foods around programming popular with children and adults alike, where current regulations do not apply. Ongoing, systematic monitoring is essential for evaluation of the effectiveness of regulations designed to reduce children's exposure to HFSS food advertising on television in the UK.


Quantification of myocardial blood flow by adenosine-stress CT perfusion imaging in pigs during various degrees of stenosis correlates well with coronary artery blood flow and fractional flow reserve.
Only few preliminary experimental studies demonstrated the feasibility of adenosine stress CT myocardial perfusion imaging to calculate the absolute myocardial blood flow (MBF), thereby providing information whether a coronary stenosis is flow limiting. Therefore, the aim of our study was to determine whether adenosine stress myocardial perfusion imaging by Dual Source CT (DSCT) enables non-invasive quantification of regional MBF in an animal model with various degrees of coronary flow reduction. In seven pigs, a coronary flow probe and an adjustable hydraulic occluder were placed around the left anterior descending coronary artery to monitor the distal coronary artery blood flow (CBF) while several degrees of coronary flow reduction were induced. CT perfusion (CT-MBF) was acquired during adenosine stress with no CBF reduction, an intermediate (15-39%) and a severe (40-95%) CBF reduction. Reference standards were CBF and fractional flow reserve measurements (FFR). FFR was simultaneously derived from distal coronary artery pressure and aortic pressure measurements. CT-MBF decreased progressively with increasing CBF reduction severity from 2.68 (2.31-2.81)mL/g/min (normal CBF) to 1.96 (1.83-2.33) mL/g/min (intermediate CBF-reduction) and to 1.55 (1.14-2.06)mL/g/min (severe CBF-reduction) (both P < 0.001). We observed very good correlations between CT-MBF and CBF (r = 0.85, P < 0.001) and CT-MBF and FFR (r = 0.85, P < 0.001). Adenosine stress DSCT myocardial perfusion imaging allows quantification of regional MBF under various degrees of CBF reduction.


[Fibrinolysis in the therapy of cerebrovascular accident].
Thrombolytic therapy for acute ischemic stroke based on data reported from recent prospective clinical trials was discussed and analyzed. The author presents some conclusions and suggestions for effective stroke management therapy with rtPA, which he believes will be the future of medical treatment of ischemic stroke.


Kids'Cam: An Objective Methodology to Study the World in Which Children Live.
This paper reports on a new methodology to objectively study the world in which children live. The primary research study (Kids'Cam Food Marketing) illustrates the method; numerous ancillary studies include exploration of children's exposure to alcohol, smoking, "blue" space and gambling, and their use of "green" space, transport, and sun protection. One hundred sixty-eight randomly selected children (aged 11-13 years) recruited from 16 randomly selected schools in Wellington, New Zealand used wearable cameras and GPS units for 4 days, recording imagery every 7 seconds and longitude/latitude locations every 5 seconds. Data were collected from July 2014 to June 2015. Analysis commenced in 2015 and is ongoing. Bespoke software was used to manually code images for variables of interest including setting, marketing media, and product category to produce variables for statistical analysis. GPS data were extracted and cleaned in ArcGIS, version 10.3 for exposure spatial analysis. Approximately 1.4 million images and 2.2 million GPS coordinates were generated (most were usable) from many settings including the difficult to measure aspects of exposures in the home, at school, and during leisure time. The method is ethical, legal, and acceptable to children and the wider community. This methodology enabled objective analysis of the world in which children live. The main arm examined the frequency and nature of children's exposure to food and beverage marketing and provided data on difficult to measure settings. The methodology will likely generate robust evidence facilitating more effective policymaking to address numerous public health concerns.


Laparoscopic use of the argon laser in nonendometriotic reproductive pelvic surgery.
The major advantage of the argon laser in laparoscopic reproductive pelvic surgery is the ability to transmit the laser beam along a flexible fiber that can easily be directed at a lesion. Its use has been specifically described for the treatment of endometriosis because the absorption of the argon laser beam (488 + 514 nm) coincides with the pigmented endometriotic implants. It has been suggested that the argon laser would not be as useful in other infertility procedures because the lack of such pigmentation would reduce the lesion's absorption of the laser beam and therefore decrease the laser's efficacy of destruction. The argon laser was used in other kinds of reproductive pelvic surgery in 15 patients over seven months. Procedures performed laparoscopically with the laser were neosalpingostomy, fimbrioplasty, salpingo-oophorolysis, adhesiolysis and ablation of the uterosacral ligaments. Of six patients undergoing laparoscopic surgery with a preoperative diagnosis of pelvic pain, five reported complete resolution of the pain following therapy. There were no intraoperative or postoperative complications. In the short follow-up period, none of the patients conceived. In addition to its use in the treatment of endometriosis, the argon laser, transmitted laparoscopically via a fiber, can be safely used to perform a wide variety of other reproductive pelvic surgical procedures. Its relative efficiency with regard to these procedures, the subsequent pregnancy rates and the laser's ability to ameliorate pelvic pain remain to be established.


Epidemiology of candidemia in Brazil: a nationwide sentinel surveillance of candidemia in eleven medical centers.
Candidemia studies have documented geographic differences in rates and epidemiology, underscoring the need for surveillance to monitor trends. We conducted prospective candidemia surveillance in Brazil to assess the incidence, species distribution, frequency of antifungal resistance, and risk factors for fluconazole-resistant Candida species. Prospective laboratory-based surveillance was conducted from March 2003 to December 2004 in 11 medical centers located in 9 major Brazilian cities. A case of candidemia was defined as the isolation of Candida spp. from a blood culture. Incidence rates were calculated per 1,000 admissions and 1,000 patient-days. Antifungal susceptibility tests were performed by using the broth microdilution assay, according to the Clinical and Laboratory Standards Institute guidelines. We detected 712 cases, for an overall incidence of 2.49 cases per 1,000 admissions and 0.37 cases per 1,000 patient-days. The 30-day crude mortality was 54%. C. albicans was the most common species (40.9%), followed by C. tropicalis (20.9%) and C. parapsilosis (20.5%). Overall, decreased susceptibility to fluconazole occurred in 33 (5%) of incident isolates, 6 (1%) of which were resistant. There was a linear correlation between fluconazole and voriconazole MICs (r = 0.54 and P < 0.001 [Spearman's rho]). This is the largest multicenter candidemia study conducted in Latin America and shows the substantial morbidity and mortality of candidemia in Brazil. Antifungal resistance was rare, but correlation between fluconazole and voriconazole MICs suggests cross-resistance may occur.


Using size-selected gold clusters on graphene oxide films to aid cryo-transmission electron tomography alignment.
A three-dimensional reconstruction of a nano-scale aqueous object can be achieved by taking a series of transmission electron micrographs tilted at different angles in vitreous ice: cryo-Transmission Electron Tomography. Presented here is a novel method of fine alignment for the tilt series. Size-selected gold clusters of ~2.7 nm (Au₅₆₁±₁₄ ), ~3.2 nm (Au₉₂₃± ₂₂ ), and ~4.3 nm (Au₂₀₅₇±₄₅) in diameter were deposited onto separate graphene oxide films overlaying holes on amorphous carbon grids. After plunge freezing and subsequent transfer to cryo-Transmission Electron Tomography, the resulting tomograms have excellent (de-)focus and alignment properties during automatic acquisition. Fine alignment is accurate when the evenly distributed 3.2 nm gold particles are used as fiducial markers, demonstrated with a reconstruction of a tobacco mosaic virus. Using a graphene oxide film means the fiducial markers are not interfering with the ice bound sample and that automated collection is consistent. The use of pre-deposited size-selected clusters means there is no aggregation and a user defined concentration. The size-selected clusters are mono-dispersed and can be produced in a wide size range including 2-5 nm in diameter. The use of size-selected clusters on a graphene oxide films represents a significant technical advance for 3D cryo-electron microscopy.


The Effect of 6 and 12 months Duodenal-Jejunal Bypass Liner Treatment on Obesity and Type 2 Diabetes: a Crossover Cohort Study.
The aim of this research was to study the duodenal-jejunal bypass liner (DJBL) treatment for obesity and type 2 diabetes mellitus (T2DM) in patients after dietary treatment in a cross-over design. DJBL treatment has been proven effective for treatment of obesity and T2DM. However, data on safety and efficacy of a 12-month DJBL treatment is limited. In 2014, our research group reported on a multicenter randomized clinical trial. Patients were randomized to DJBL or dietary treatment (control group). Twenty-eight patients crossed over after their dietary treatment and received up to 12 months of DJBL treatment. Patient visits were conducted at baseline, during DJBL treatment (1 week, 1-6, 9, 12 months) and 6 months after removal of the liner. Patients underwent a standard physical examination, blood sampling, assessment of adverse events, nutritional and diabetes counseling, and a standardized meal tolerance test. Of the 28 patients included in this study, 24 patients completed 6 months of treatment. Eighteen patients were extended to 12 months of DJBL treatment; 13 patients completed this treatment period. After 6 months of DJBL treatment, a significant increase in excess weight loss (EWL) and decrease in weight, BMI, HbA1c, fasting glucose, cholesterol, HDL and LDL improved significantly. After 12 months of DJBL treatment, these parameters stabilized. The DJBL is an effective, minimally invasive treatment option. Even after successful treatment with dietary restrictions, the DJBL is still capable of significantly reducing weight and improving cardiovascular and type 2 diabetes mellitus parameters in obese patients.


Automation in cervical cancer screening. Part 1: fixed cell scanning systems.
Cytology automation is highly desirable if a mass cancer screening system is to be effective, and has been the subject of widespread research and development effort. Several experimental systems have been developed based on fixed cell scanning or flow techniques, but clinical trials have produced disappointing results. The major problem with these early systems has been that of false positive "abnormal cell" signals caused by cell overlaps and artifacts. Most current research is devoted to the development of better techniques for cell presentation, to the improvement of pattern recognition techniques, and to the exploitation of novel cell parameters in flow systems.


Interferometric phase-only optical encryption system that uses a reference wave.
An improved image decryption system is proposed that is based on phase-encoded images and the principle of interference and uses a reference wave. A novel technique for generating intensity patterns from the decrypted phase information consists simply of interfering a reference wave with the wave passing through the encrypted image and a phase-only decrypting key. Optical experiments have confirmed the proposed technique as a simple and robust architecture for optical encryption.


Age-associated alterations in thalamocortical structural connectivity in youths with a psychosis-spectrum disorder.
Psychotic symptoms typically emerge in adolescence. Age-associated thalamocortical connectivity differences in psychosis remain unclear. We analyzed diffusion-weighted imaging data from 1254 participants 8-23 years old (typically developing (TD):N = 626, psychosis-spectrum (PS): N = 329, other psychopathology (OP): N = 299) from the Philadelphia Neurodevelopmental Cohort. We modeled thalamocortical tracts using deterministic fiber tractography, extracted Q-Space Diffeomorphic Reconstruction (QSDR) and diffusion tensor imaging (DTI) measures, and then used generalized additive models to determine group and age-associated thalamocortical connectivity differences. Compared to other groups, PS exhibited thalamocortical reductions in QSDR global fractional anisotropy (GFA, p-values range = 3.0 × 10-6-0.05) and DTI fractional anisotropy (FA, p-values range = 4.2 × 10-4-0.03). Compared to TD, PS exhibited shallower thalamus-prefrontal age-associated increases in GFA and FA during mid-childhood, but steeper age-associated increases during adolescence. TD and OP exhibited decreases in thalamus-frontal mean and radial diffusivities during adolescence; PS did not. Altered developmental trajectories of thalamocortical connectivity may contribute to the disruptions observed in adults with psychosis.


Advances in understanding the molecular regulation of cardiac development.
Although impressive progress has been made in the diagnosis and treatment of congenital heart disease, there has been an explosion of new information about the basic molecular mechanisms that control normal heart development and subsequent congenital cardiovascular malformations. Since the advent of targeted null mutations in mice (gene "knockouts"), it has become increasingly evident that defects in the heart and vascular system frequently result from gene alterations and that these defects are often responsible for in utero demise. New genes have been discovered that control looping of the heart, distinguish arteries from veins, and direct formation of the semilunar valve and atrioventricular valves. A pivotal role for several genes expressed by the cardiac neural crest document the importance of these cells in aortic arch selection, in addition to their role in aorticopulmonary septation. In addition, myocardial and endothelial progenitor cells have been isolated from bone marrow stromal cells, and human embryonic stem cells have been successfully isolated, paving the way for developmental approaches to tissue engineering and organ regeneration. Finally, the first successful attempt at in utero manipulation of genes that might palliate certain forms of congenital heart disease has been presented. These recent advances are detailed in this article.


Long-term effects and significant Adverse Drug Reactions (ADRs) associated with the use of Gonadotropin-Releasing Hormone analogs (GnRHa) for central precocious puberty: a brief review of literature.
Central precocious puberty (CPP) is defined as an early pubertal development that occurs before the age of 9 years in boys and 8 years in girls. It results from premature activation of the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone agonists (GnRHa) have been the gold standard therapy for CPP for more than 30 years. These compounds have a high affinity for the pituitary LHRH receptor and are resistant to enzymatic degradation. Through continuous stimulation, GnRHa inhibit the pulsatile secretion of gonadotropin, resulting in hormonal suppression, cessation of pubertal development, and normalization of growth and skeletal maturation rates. The goal of therapy is to halt pubertal progression and delay epiphyseal maturation that leads to improvement of final adult height. There are no widely accepted guidelines for how long to continue treatment with a GnRHa for CPP, and individual practice varies widely. Furthermore, conflicting results have been published on the long-term effects of GnRHa therapy in patients with CPP. Therefore, we reviewed the current literature focusing our attention on the long-term effects and the significant adverse drug reactions (ADRs) observed during treatment with GnRHa in patients with CPP. Our review may provide the necessary data to enable clinicians to administer GnRHa in the safest and most appropriate way. Further studies are necessary to identify the mechanisms of development of potential adverse drug reactions related to GnRHa therapy in CPP.


Clostridium septicum infection and malignancy.
Evidence mounts favoring the relationship, albeit unexplained, between Clostridium septicum infection and malignancy, particularly hematologic or intestinal malignancy. Seven patients with C. septicum gangrene or sepsis have been treated at the Massachusetts General Hospital in the years 1977-79. All of these patients have had associated malignant disease: four patients had colon adenocarcinomas, two patients had acute myeloblastic leukemias, and one patient had breast carcinoma. In six of the seven patients, the malignancy was in an advanced state; the breast carcinoma showed no evidence of recurrence after mastectomy, 17 years earlier. A bowel portal of entry is postulated in five patients. Despite prompt use of appropriate antibiotics, the only survivors were two of the four patients who underwent early extensive debridement. These results suggest that, in the patient with C. septicum infection, malignancy should be sought; that, in the septic patient with known malignancy, C. septicum should be considered; and that, in the absence of external source in the patient with clostridial myonecrosis or sepsis, the cecum or distal ileum should be considered a likely site of infection. Increased awareness of this association between C. septicum and malignancy, and aggressive surgical treatment, may result in improvement in the present 50-70% mortality rate.


Structure of 5 beta-dihydrotestosterone.
17 beta-Hydroxy-5 beta-androstan-3-one, C19H30O2, Mr = 290.45, orthorhombic, P2(1)2(1)2(1), a = 11.7821 (6), b = 21.2184 (8), c = 6.5322 (2) A, V = 1633.0 (2) A3, Z = 4, D chi = 1.181 Mg m-3, lambda(Cu K alpha) = 1.54178 A, mu = 0.58 mm-1, F(000) = 640, T = 293 K, R = 0.033 for 1849 unique observed reflections. The molecular conformation of 5 beta-dihydrotestosterone shows the strong bending typical of 5 beta-steroids: the bowing angle of the A ring, relative to the remainder of the steroid, is 65.1 degrees. Bowing shortens the distance between the terminal O atoms, O(3) and O(17), to 9.824 (2) A which is ca 1 A shorter than was observed in 5 alpha-dihydrotestosterone and testosterone. The effects of both the bowing and the shorter separation between O(3) and O(17) may explain a difference in the affinity of 5 beta-dihydrotestosterone for the dexamethasone binding site on membranes compared to that of the other two compounds. A unique conformational feature of 5 beta-dihydrotestosterone is the flattening of the A ring on the side containing the C(3)--C(4) bond; this may be due to the combination of the 3-oxo substitution and the 5 beta-configuration.


Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9).
ASAP is a newly characterized microtubule-associated protein (MAP) essential for proper cell-cycling. We have previously shown that expression deregulation of human ASAP results in profound defects in mitotic spindle formation and mitotic progression leading to aneuploidy, cytokinesis defects and/or cell death. In the present work we analyze the structure and evolution of the ASAP gene, as well as the domain composition of the encoded protein. Mouse and Xenopus cDNAs were cloned, the tissue expression characterized and the overexpression profile analyzed. Bona fide ASAP orthologs are found in vertebrates with more distantly related potential orthologs in invertebrates. This single-copy gene is conserved in mammals where it maps to syntenic chromosomal regions, but is also clearly identified in bird, fish and frog. The human gene is strongly expressed in brain and testis as a 2.6 Kb transcript encoding a approximately110 KDa protein. The protein contains MAP, MIT-like and THY domains in the C-terminal part indicative of microtubule interaction, while the N-terminal part is more divergent. ASAP is composed of approximately 42% alpha helical structures, and two main coiled-coil regions have been identified. Different sequence features may suggest a role in DNA damage response. As with human ASAP, the mouse and Xenopus proteins localize to the microtubule network in interphase and to the mitotic spindle during mitosis. Overexpression of the mouse protein induces mitotic defects similar to those observed in human. In situ hybridization in testis localized ASAP to the germ cells, whereas in culture neurons ASAP localized to the cell body and growing neurites. The conservation of ASAP indicated in our results reflects an essential function in vertebrates. We have cloned the ASAP orthologs in mouse and Xenopus, two valuable models to study the function of ASAP. Tissue expression of ASAP revealed a high expression in brain and testis, two tissues rich in microtubules. ASAP associates to the mitotic spindle and cytoplasmic microtubules, and represents a key factor of mitosis with possible involvement in other cell cycle processes. It may have a role in spermatogenesis and also represents a potential new target for antitumoral drugs. Possible involvement in neuron dynamics also highlights ASAP as a candidate target in neurodegenerative diseases.


Effects of dietary fibre and exercise on mid-morning diabetic control--a controlled trial.
Twenty-one insulin-dependent diabetic children completed a trial of 4 different breakfasts, given in random order. Three diets differed in fibre content. The fourth diet contained soya beans as part (38%) of the dietary fibre source. Children collected capillary blood samples on to filter paper strips which were analysed for blood glucose content. Each morning the children were asked to exercise vigorously for an hour and to rest for an hour, resulting in comparable rest and exercise periods for each child. Mean initial blood glucose levels on the 4 diets were not significantly different. The low-fibre diet resulted in the highest blood glucose concentrations after breakfast. Blood glucose levels on the high-fibre diet did not differ from those on the medium-fibre diet. The bean diet produced the lowest mean blood glucose level and the smallest reduction in blood glucose level in the hour before lunch. All the children found the bean diet unacceptable but liked the high- and medium-fibre diets, which were as popular as the low-fibre diet. The level of prescribed exercise had no effect on the level of blood glucose. It appears that the potentially major benefits from beans are limited by their unpalatability. The more acceptable cereal fibre produces a smaller but important benefit on morning hyperglycaemia after breakfast.


Changes in anterior chamber biometry and intraocular pressure after uneventful phacoemulsification in non-glaucomatous eyes.
In non-glaucomatous eyes, many factors impact intraocular pressure (IOP) reduction following phacoemulsification. This study aimed to determine the relationship between changes in IOP and alterations in anterior chamber biometric measurements using the Pentacam Scheimpflug anterior segment imaging system before and after uneventful phacoemulsification in non-glaucomatous eyes. This prospective interventional study included patients with ages of 20 - 80 years, no known systemic diseases, and visually significant cataracts necessitating phacoemulsification with posterior chamber intraocular lens implantation. The preoperative and two-month postoperative IOPs were measured using a Goldmann applanation tonometer, and the iridocorneal angle (ICA) in four quadrants (superior, inferior, nasal, and temporal), anterior chamber depth (ACD), and anterior chamber volume (ACV) were measured using the Pentacam. Forty-two eyes of 42 patients with a mean (standard deviation [SD]) age of 56.8 (10.7) years were included; 22 (52%) were men and 20 (48%) were women. The eyes demonstrated statistically significant changes in postoperative IOP, ACD, ACV, and in widening of the ICA (all P < 0.05), with a mean (SD) IOP reduction of 4.5 (2.7) mmHg, ACD deepening of 0.7 (0.6) mm, ACV increase of 33.2 (21.1) mm3, and ICA widening of 7.5o (6.4o), 12.4o (7.7o), 9.1o (7.1o), and 11.5o (6.1o) in the superior, inferior, temporal, and nasal quadrants, respectively. A significant positive correlation was detected between pre- and postoperative IOP (r = + 0.58; P < 0.001) and between pre- and postoperative ACD (r = + 0.50; P < 0.001). Significant negative correlations were detected between preoperative ACV and changes in ACV (r = - 0.42; P < 0.001) and between preoperative ICA and changes in ICA (r = - 0.02; P = 0.001). However, no significant correlations were observed between the changes in IOP and patient age (r = + 0.001; P = 0.957) and axial length of the eye (r = + 0.13; P = 0.221), or changes in ICA (r = - 0.01; P = 0.945), ACD (r = + 0.01; P = 0.945), and ACV (r = - 0.12; P = 0.599). We observed a significant reduction in IOP, widening of the ICA, and increases in ACD and ACV after phacoemulsification; however, there was no significant correlation between changes in IOP and other biometric variables. Further studies are required to determine the exact mechanisms underlying these effects.


A proposed common structure of substrates bound to mitochondrial processing peptidase.
Mitochondrial processing peptidase (MPP), a metalloendopeptidase consisting of alpha- and beta-subunits, specifically cleaves off the N-terminal presequence of the mitochondrial protein precursor. Structural information of the substrate bound to MPP was obtained using fluorescence resonance energy transfer (FRET) measurement. A series of the peptide substrates, which have distal arginine residues required for effective cleavage at positions -7, -10, -14, and -17 from the cleavage site, were synthesized and covalently labeled with 7-diethyl aminocoumarin-3-carboxylic acid at the N termini and N,N'-dimethyl-N-(iodoacetyl)-N'-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)ethylenediamine (IANBD) at position +4, as fluorescent donor and acceptor, respectively. When the peptides were bound to MPP, substantially the same distances were obtained between the two probes, irrespective of the length of the intervening sequence between the two probes. When 7-diethylamino-3-(4'-maleimidyl phenyl)-4-methyl coumarin was introduced into a single cysteine residue in beta-MPP as a donor and IANBD was coupled either at the N terminus or the +4 position of the peptide substrate as an acceptor, intermolecular FRET measurements also demonstrated that distances of the donor-acceptor pair were essentially the same among the peptides with different lengths of intervening sequences. The results indicate that the N-terminal portion and the portion around the cleavage site of the presequence interact with specific sites in the MPP molecule, irrespective of the length of the intervening sequence between the two portions, suggesting the structure of the intervening sequence is flexible when bound to the MPP.


S-100 protein in ovarian tumors. A comparative immunohistochemical study of 135 cases.
The distribution of S-100 protein in 135 ovarian tumors, of which 127 were epithelial, was investigated using the immunoperoxidase method. S-100 protein has been demonstrated previously in tumors of various origins. The present study further revealed its characteristic distribution in common epithelial tumors of the ovary. S-100 protein was present in 69% of serous tumors (benign, 50%; borderline, 100%; malignant, 71%), as well as in the serous elements of serous & mucinous mixed tumors (30%). S-100 protein was also demonstrated in 25% of clear cell carcinomas and 29% of endometrioid carcinomas. Interestingly, none of the mucinous tumors were positive for S-100 protein. In addition, the expression of S-100 protein by epithelial ovarian tumors was compared with that of CA 125 and carcinoembryonic antigen (CEA). The distribution of S-100 protein was similar to that of CA 125, since both antigens were frequently present in serous tumors, although their expression patterns were different. On the other hand, S-100 protein-positive cases were almost negative for CEA or vice versa. Our observations indicate that demonstration of S-100 protein in common epithelial tumors of the ovary and comparison of S-100 protein distribution with that of CA 125 and CEA may further clarify the characteristics of common epithelial tumors of the ovary.


Intracerebroventricular delivery of vascular endothelial growth factor in patients with amyotrophic lateral sclerosis, a phase I study.
We studied the feasibility, safety, tolerability and pharmacokinetics of intracerebroventricular delivery of recombinant human vascular endothelial growth factor in patients with amyotrophic lateral sclerosis. In this phase I study in patients with amyotrophic lateral sclerosis, the study drug was delivered using an implantable programmable pump connected to a catheter inserted in the frontal horn of the lateral cerebral ventricle. A first cohort received open label vascular endothelial growth factor (0.2, 0.8 and 2 µg/day), a second cohort received placebo, 0.8 or 2 µg/day of study dug. After the 3-month study period, all patients could participate in an open label extension study. In total, 18 patients with amyotrophic lateral sclerosis, seen at the University Hospitals in Leuven were included. The surgical procedure was well tolerated in most patients. One patient had transient postoperative seizures, due to an ischemic lesion along the catheter tract. The first 3-month study period was completed by 15/18 patients. Administration of 2 µg/day vascular endothelial growth factor resulted in sustained detectable levels in cerebrospinal fluid. A pulmonary embolus occurred in 3 patients, in 1 patient in the first 3-month study, and in 2 patients during the open label extension study. The study drug was well tolerated in the other patients, for up to 6 years in the open label extension study. Our study shows that intracerebroventricular administration of 2 µg/day of vascular endothelial growth factor to patients with amyotrophic lateral sclerosis is feasible, results in detectable cerebrospinal fluid levels and is well tolerated in most patients. The most common serious adverse event was a pulmonary embolus.


Mutations induced by bacteriophage T7 RNA polymerase and their effects on the composition of the T7 genome.
We show here that transcription by the bacteriophage T7 RNA polymerase increases the deamination of cytosine bases in the non-transcribed strand to uracil, causing C to T mutations in that strand. Under optimal conditions, the mutation frequency increases about fivefold over background, and is similar to that seen with the Escherichia coli RNA polymerase. Further, we found that a mutant T7 RNA polymerase with a slower rate of elongation caused more cytosine deaminations than its wild-type parent. These results suggest that promoting cytosine deamination in the non-transcribed strand is a general property of transcription in E. coli and is dependent on the length of time the transcription bubble stays open during elongation. To see if transcription-induced mutations have influenced the evolution of bacteriophage T7, we analyzed its genome for a bias in base composition. Our analysis showed a significant excess of thymine over cytosine bases in the highly transcribed regions of the genome. Moreover, the average value of this bias correlated well with the levels of transcription of different genomic regions. Our results indicate that transcription-induced mutations have altered the composition of bacteriophage T7 genome and suggest that this may be a significant force in genome evolution.


Health evaluation of a pronghorn antelope population in Oregon.
During 1996 and 1997, the U.S. Fish and Wildlife Service conducted a study to determine the cause(s) of population decline and low survival of pronghorn antelope (Antilocapra americana) fawns on Hart Mountain National Antelope Refuge (HMNAR) located in southeastern Oregon (USA). As part of that study, blood, fecal, and tissue samples from 104 neonatal fawns, 40 adult does, and nine adult male pronghorns were collected to conduct a health evaluation of the population. Physiological parameters related to nutrition and/or disease were studied. No abnormalities were found in the complete blood cell counts of adults (n = 40) or fawns (n = 44 to 67). Serum total protein and blood urea nitrogen (BUN) levels were lower compared to other pronghorn populations. Does had mean BUN values significantly lower (P < 0.001) in December 1996 than March 1997. Serum copper (Cu) levels in does (range 0.39 to 0.74 ppm) were considered marginal when compared to domestic animals and other wild ungulates. Fawns had low (0.28 ppm) Cu levels at birth and reached the does' marginal values in about 3 days. Whole blood, serum and liver selenium (Se) levels were considered marginal to low in most segments of the pronghorn population. However, serum levels of vitamin E (range 1.98 to 3.27 microg/ml), as determined from the does captured in March, were apparently sufficient to offset any signs of Se deficiency. No clinical signs of Cu or Se deficiency were observed. Fifty-five of 87 dead fawns were necropsied. Trauma, due to predation by coyotes (Canis latrans), accounted for 62% of the mortality during mid-May to mid-July of each year. Other causes included predation by golden eagles (Aquila chrysaetos) (4%), dystocia (2%), septicemic pasteurellosis (4%), starvation (5%), and unknown (23%). Adult females were tested for serum neutralizing antibodies to Brucella spp. (n = 20, negative), Leptospira interrogans (n = 20, negative), bluetongue virus (n = 20, 35% positive), epizootic hemorrhagic disease virus (n = 20, 30% positive), respiratory syncytial virus (n = 18, negative), parainfluenza virus type 3 (n = 18, 67% positive), infectious bovine rhinotracheitis (n = 18, negative), and bovine viral diarrhea (n = 18, negative). Considering the parameters examined, we found no apparent predisposing factors to mortality including those killed by coyotes, but some nutritional parameters suggest that pronghorns on HMNAR exist on a diet low in protein and Se and marginal in Cu. The effect these factors have on the population is not known.


Virtual reality among the elderly: a usefulness and acceptance study from Taiwan.
Virtual reality (VR) has several applications in the medical domain and also generates a secure environment to carry out activities. Evaluation of the effectiveness of VR among older populations revealed positive effects of VR as a tool to reduce risks of falls and also improve the social and emotional well-being of older adults. The decline in physical and mental health, the loss of functional capabilities, and a weakening of social ties represent obstacles towards active aging among older adults and indicate a need for support. Existing research focused on the effects of VR among older populations, and its uses and benefits. Our study investigated the acceptance and use of VR by the elderly. This pilot study was conducted on 30 older adults who voluntarily participated during March to May 2018. Nine VR applications that promote physical activities, motivate users, and provide entertainment were chosen for this study. Participants were asked to use any one of the applications of their choice for 15 min twice a week for 6 weeks. At the end of 6 weeks, participants were asked to fill out a questionnaire based on the Technology Acceptance Model and a literature review, to evaluate their acceptance of VR technology. Cronbach's alpha reliability analysis was used to test the internal consistency of the questionnaire items. Pearson's product moment correlation was used to examine the validity of the questionnaire. A linear regression and mediation analysis were utilized to identify relationships among the variables of the questionnaire. In total, six male and 24 female participants aged 60~95 years volunteered to participate in the study. Perceived usefulness, perceived ease of use, social norms, and perceived enjoyment were seen to have had significant effects on the intention to use VR. Participants agreed to a large extent regarding the perceived usefulness, perceived enjoyment, and their experience of using VR. Thus, VR was seen to have high acceptance among this elderly population. Older people have positive perceptions towards accepting and using VR to support active aging. They perceived VR to be useful, easy to use, and an enjoyable experience, implying positive attitudes toward adopting this new technology.


Depression, APOE genotype and subjective memory impairment: a cross-sectional study in an African-Caribbean population.
Subjective memory impairment (SMI) is common in older populations but its aetiology and clinical significance is uncertain. Depression has been reported to be strongly associated with SMI. Associations with objective cognitive impairment are less clear cut. Other factors suggested to be associated with SMI include poor physical health and the apolipoprotein E (APOE) epsilon4 allele. Studies of SMI have been predominantly confined to white Caucasian populations. A community study was carried out in a UK African-Caribbean population aged 55-75, sampled from primary care lists. Twenty-three per cent were classified with SMI. Depression was defined using the 10-item Geriatric Depression Scale. Other aetiological factors investigated were education, objective cognitive function, APOE genotype, disablement and vascular disease/risk. The principal analysis was restricted to 243 participants scoring > 20 on the Mini-Mental State Examination (85%). A second analysis included all 290 participants. Depression, self-reported physical impairment and APOE epsilon4 were associated with SMI. The association between SMI and physical impairment was not explained by depression, vascular disease/risk, or disability/handicap. The association between epsilon4 and SMI increased as MMSE scores decreased and was particularly strong in those with depression. The epsilon4 allele was present in 69% (95% CI 41-89%) of those with depression and SMI compared with 28% (20-36%) of those with neither. Depression may not be a sufficient explanation for subjective memory complaints. Memory complaints in the presence of depression are associated with high prevalence of epsilon4 and therefore, presumably, a raised risk of subsequent dementia.


Cathodoluminescence imaging for identifying uptaken fluorescence materials in Kupffer cells using scanning electron microscopy.
Cathodoluminescence (CL) is the light that is emitted from a material irradiated by an electron beam. The present study was undertaken to show the applicability to biological studies of a scanning electron microscope (SEM) equipped with a high-sensitive cathodoluminescence detection system. For this purpose, we injected inorganic fluorescent powders (P43) suspended in phosphate buffered saline into rat blood circulation, fixed the animals with glutaraldehyde within a day, and observed the hepatic tissues with a SEM. Our instrument enabled the simultaneous collection of both secondary electron (SE) and CL images of these tissues. Backscattered electron (BSE) images of the same portion were also able to be obtained with this microscope. SE and BSE images clearly showed the three-dimensional structure of the hepatic tissues including hepatocytes, Kupffer cells, Ito cells, and sinusoidal epithelial cells, while CL images visualized cathodoluminescence signals emitted from P43 as bright spots. We observed non-coated tissues under a low-vacuum condition and metal-coated tissues under a high-vacuum condition, and found that the high-vacuum observation of metal-coated tissues provided high quality CL images of P43 in the Kupffer cells. The superimposition of the CL images onto the corresponding SE or BSE images revealed that bright spots in the CL images were produced by the fluorescent powders uptaken by Kupffer cells. These findings indicate that the detection of CL as well as SE or BSE signals by SEM all provide us with useful information on the distribution of fluorescent tracers in tissues and cells in three-dimensional images.


Combination Analysis of Metatranscriptome and Metagenome Reveal the Composition and Functional Response of Coral Symbionts to Bleaching During an El Niño Event.
With the abnormal rise in ocean temperatures globally in recent years, coral bleaching is becoming common and serious. However, the response mechanisms and processes of coral symbionts to bleaching are not well understood. In this study, metagenomics and metatranscriptomics were used to explore the composition of coral symbionts and their functions in response to coral bleaching. All four bleaching coral species displayed a significant reduction of the abundance and function of Dinophyceae-like eukaryotes at the DNA and RNA levels. However, different species of bleaching coral have their own characteristic symbiotic components. Bleaching Acropora tenuis and Goniastrea minuta corals exhibited a very high abundance of prokaryotes and associated gene functions, especially for opportunistic bacteria. In contrast, algae and fungi were identified as the main microbial associate components and had relatively high RNA abundance in bleaching Pocillopora verrucosa and Pocillopora meandrina. Different coral species, whether unbleached or bleaching, have the same symbiotic taxa that perform the same biological functions in vivo. Different stages of bleaching, or transitional states, were identified by different genome content and functional gene abundance among bleaching corals. These stages should be considered in future coral bleaching studies to accurately determine symbiont structure and function. An implicit hypothesis is that there is a causal relationship between the stability of eukaryotic communities and coral bleaching.


Neurofibromatosis type 1 and high-grade tumors of the central nervous system.
Neurofibromatosis type 1 (NF1), a common genetic disorder, predisposes patients to the development of both benign and malignant tumors. Although the most common central nervous system (CNS) tumor is a low-grade pilocytic astrocytoma of the optic pathway, there have been sporadic reports of NF1 patients with more aggressive CNS lesions. We investigated the incidence of aggressive CNS lesions in NF1 patients at our institution. We conducted a retrospective review of all patients with NF1 and any CNS tumor being followed in the Children's Memorial Hospital NF1 Clinic. Seven hundred forty patients with a diagnosis of NF1 were identified. Of these, 145 (20%) patients had CNS tumors, 99 (68%) of whom had optic pathway tumors (OPTs). Five patients (3%) were identified as having high-grade tumors, which consisted of anaplastic medulloblastoma (n = 1) and high-grade glioma (n = 4). The mean age at diagnosis of NF1 was 2 years. Three of the five patients had a history of an OPT prior to the development of their high-grade lesions. The clinical courses and treatment of these five patients varied. Currently, two patients are alive and receiving therapy at a mean of 10 months following diagnosis. High-grade CNS tumors may occur in children with NF1. Although tumors in NF patients are generally benign, clinicians should have a high index of suspicion of malignancy in patients whose tumors are in an unusual location or behave in an uncharacteristically aggressive manner.


Optimized protein extraction methods for proteomic analysis of Rhizoctonia solani.
Rhizoctonia solani (Teleomorph: Thanatephorus cucumeris, T. praticola) is a basidiomycetous fungus and a major cause of root diseases of economically important plants. Various isolates of this fungus are also beneficially associated with orchids, may serve as biocontrol agents or remain as saprophytes with roles in decaying and recycling of soil organic matter. R. solani displays several hyphal anastomosis groups (AG) with distinct host and pathogenic specializations. Even though there are reports on the physiological and histological basis of Rhizoctonia-host interactions, very little is known about the molecular biology and control of gene expression early during infection by this pathogen. Proteamic technologies are powerful tools for examining alterations in protein profiles. To aid studies on its biology and host pathogen interactions, a two-dimensional (2-D) gel-based global proteomic study has been initiated. To develop an optimized protein extraction protocol for R. solani, we compared two previously reported protein extraction protocols for 2-D gel analysis of R. solani (AG-4) isolate Rs23. Both TCA-acetone precipitation and phosphate solubilization before TCA-acetone precipitation worked well for R. solani protein extraction, although selective enrichment of some proteins was noted with either method. About 450 spots could be detected with the densitiometric tracing of Coomassie blue-stained 2-D PAGE gels covering pH 4-7 and 6.5-205 kDa. Selected protein spots were subjected to mass spectrometric analysis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Eleven protein spots were positively identified based on peptide mass fingerprinting match with fungal proteins in public databases with the Mascot search engine. These results testify to the suitability of the two optimized protein extraction protocols for 2-D proteomic studies of R. solani.


Wavelet variance analysis for random fields on a regular lattice.
There has been considerable recent interest in using wavelets to analyze time series and images that can be regarded as realizations of certain 1-D and 2-D stochastic processes on a regular lattice. Wavelets give rise to the concept of the wavelet variance (or wavelet power spectrum), which decomposes the variance of a stochastic process on a scale-by-scale basis. The wavelet variance has been applied to a variety of time series, and a statistical theory for estimators of this variance has been developed. While there have been applications of the wavelet variance in the 2-D context (in particular, in works by Unser in 1995 on wavelet-based texture analysis for images and by Lark and Webster in 2004 on analysis of soil properties), a formal statistical theory for such analysis has been lacking. In this paper, we develop the statistical theory by generalizing and extending some of the approaches developed for time series, thus leading to a large-sample theory for estimators of 2-D wavelet variances. We apply our theory to simulated data from Gaussian random fields with exponential covariances and from fractional Brownian surfaces. We demonstrate that the wavelet variance is potentially useful for texture discrimination. We also use our methodology to analyze images of four types of clouds observed over the southeast Pacific Ocean.


Effects of physical activity and depressive symptoms on cognitive function in older adults: National Health and Nutrition Examination Survey.
Population aging is a growing phenomenon, with cognitive impairment becoming a prevalent issue among the elderly. This study aimed to investigate the impact of physical activity and depressive symptoms on cognitive function in older adults using a nationally representative data set of U.S. older adults aged ≥ 60 years. The study comprised 2713 participants aged ≥ 60 from the National Health and Nutrition Examination Survey 2011-2014. Participants were classified into two groups: Cognitive impairment and No-Cognitive impairment, determined by the results of the Digit Symbol Substitution Test (DSST). Physical activity (PA) was assessed using the Global Physical Activity questionnaire (GPAQ), while depressive symptoms were evaluated using the Patient Health Questionnaire (PHQ-9). Logistic regression analysis examined the relationship between physical activity, depressive symptoms and cognitive function. Multifactorial logistic regression analysis showed that high levels of physical activity were found to be significantly associated with a lower risk of cognitive impairment compared to low levels of physical activity [OR = 0.789, 95% CI:0.632 ~ 0.986, P = 0.037]. On the other hand, the presence of major depressive symptoms was significantly associated with a higher risk of cognitive impairment compared to the absence of depressive symptoms [OR = 3.482, 95% CI: 2.278 ~ 5.324, P < 0.001]. Participants in the recreational physical activity group exhibited higher Cognitive scores (P < 0.001), indicating better cognitive functioning. High levels of Physical activity were independently associated with a lower incident cognitive impairment. Additionally, the severity of depression was positively correlated with an increased risk of cognitive impairment.


Impact of seaweed beachings on dynamics of δ(15)N isotopic signatures in marine macroalgae.
A fine-scale survey of δ(15)N, δ(13)C, tissue-N in seaweeds was conducted using samples from 17 sampling points at two sites (Grandcamp-Maisy (GM), Courseulles/Mer (COU)) along the French coast of the English Channel in 2012 and 2013. Partial triadic analysis was performed on the parameter data sets and revealed the functioning of three areas: one estuary (EstA) and two rocky areas (GM(∗), COU(∗)). In contrast to oceanic and anthropogenic reference points similar temporal dynamics characterized δ(15)N signatures and N contents at GM(∗) and COU(∗). Nutrient dynamics were similar: the N-concentrations in seawater originated from the River Seine and local coastal rivers while P-concentrations mainly from these local rivers. δ(15)N at GM(∗) were linked to turbidity suggesting inputs of autochthonous organic matter from large-scale summer seaweed beachings made up of a mixture of Rhodophyta, Phaeophyta and Chlorophyta species. This study highlights the coupling between seaweed beachings and nitrogen sources of intertidal macroalgae.


[Why does the human immunodeficiency virus (HIV) invade the nervous system?].
Human Immunodeficiency Virus (HIV) has neurotropic effects that are independent of the well-known lymphotropism. They have been proved by various techniques, but their pathogenesis is not clear. It is remarkable that the neuropathological features do not correlate with the degree of the clinical symptomatology. HIV antigens and antibodies are demonstrable within the central nervous system by immunological tests. The macrophages transport the virus across the blood-brain barrier and are responsible for its persistence in that location. Different cell types, especially of the subcortical areas, have HIV-receptive CD4 molecules. These markers may be identical with the receptors for endogenous neuropeptides and it is likely that viral proteins are causing a competitive inhibition of these mostly neurotrophic factors. This interference is discussed as one of the main reasons of HIV dementia.


Time, uncertainty, and suboptimal choice.
Under certain conditions, pigeons prefer information about whether food will be forthcoming at the end of an interval to a higher chance of obtaining the food. In the typical protocol, choosing one option (Informative) is followed by one of two 10-s long terminal-link stimuli: SG always ending in food or SR never ending in food, with SG occurring only 20% of the trials. The other option (Non-informative) is also followed by one of two 10-s long terminal-link stimuli: SB or SY, both ending in food 50% of the trials. Although the Informative option yields food with a lower probability than the Non-informative (0.2 vs. 0.5), pigeons prefer it. To determine whether such preference occurs because SG and SR disambiguate the trial outcome immediately upon choice, we delayed the moment the disambiguation took place in two experiments. In Experiment 1, when the Informative option was chosen, SG always ensued for t seconds of the terminal-link, and then the standard contingencies followed. Experiment 2 was similar, except that SR always ensued for t seconds. Across conditions, t varied from 0 to 10sec. In both experiments, preference for the Informative option decreased with t, but the effect was stronger in Experiment 1. We discuss the implication of these findings for functional and mechanistic models of suboptimal choice.


A unifying representation of ventricular volumetric indexes.
We studied volumetric characteristics of the ventricle in various hearts covering a wide (patho)physiological range, using the individual operating point at basal conditions. The aim of this analysis is to formulate a unifying relationship between volumetric parameters which will be applicable to cardiac ventricles regardless of underlying pathology. Analyzing our own measurements as well as additional data published elsewhere indicates that end-systolic volume (ESV) versus end-diastolic volume (EDV) yields a high linear population based correlation coefficient. This analytical expression can subsequently be used for the evaluation of clinically relevant derived indexes. For example, the new approach permits estimation of important physiological quantities such as stroke work and myocardial oxygen consumption, while isopleths and regions with equal ejection fraction can all be inscribed as linear relationships within a single graph. Based on statistical considerations, we demonstrate that in terms of correlation this new graphical representation is superior to the curve relating output (stroke volume) to input (preload) of the ventricle. We conclude that the ESV versus EDV representation facilitates insight into cardiac volumetric behavior and permits prediction of clinically relevant cardiodynamic effects, as produced by ventricular dimensional changes, for example induced by surgical or pharmacological intervention, or by the progression of cardiac disease.


[Retardation of human drug-resistant HL-60 cell in G1 phase and induction of sensitive cell to apoptosis by cyclosporine A].
To further study the relationship between resistance to apoptosis and drug resistance in harringtonine-resistant HL-60 cells (HR20), cyclosporine A (CsA) 20, 10 micrograms.ml-1 was shown to induce the sensitive HL-60 cells to apoptosis, showing a typical DNA "ladder" band. But the same concentrations of CsA retarded the HR20 cells in G1 phase and could not induce the cells to apoptosis. The cellular daunorubicin accumulation increased when HR20 cells were treated with low concentration of CsA and the reversal of drug resistance by CsA was unrelated to the retardation of cell cycle progression. High phosphorylation of about 50 kDa protein occured when HR20 cells were treated with CsA 10 micrograms.ml-1. The results domonstrate that cyclosporine A retarded the harringtonine-resistant HL-60 cells in G1 phase but induced HL-60 cells to apoptosis, and the retardation was unrelated to drug resistance.


Impact of the hybridization form of the coordinated nitrogen atom on the electrocatalytic water oxidation performance of copper complexes with pentadentate amine-pyridine ligands.
The field of molecular catalysts places a strong emphasis on the connection between the ligand structure and its catalytic performance. Herein, we changed the type of coordinated nitrogen atom in pentadentate amine-pyridine ligands to explore the impact of its hybridization form on the water oxidation performance of copper complexes. In the electrochemical tests, the copper complex bearing dipyridine-triamine displayed an apparently higher rate constant of 4.97 s-1, while the copper complex with tripyridine-diamine demonstrated overpotential reduction by 56 mV and better long-term electrolytic stability.


Bioremediation of Hexavalent Chromium by Chromium Resistant Bacteria Reduces Phytotoxicity.
Chromium (Cr) (VI) has long been known as an environmental hazard that can be reduced from aqueous solutions through bioremediation by living cells. In this study, we investigated the efficiency of reduction and biosorption of Cr(VI) by chromate resistant bacteria isolated from tannery effluent. From 28 screened Cr(VI) resistant isolates, selected bacterial strain SH-1 was identified as Klebsiella sp. via 16S rRNA sequencing. In Luria-Bertani broth, the relative reduction level of Cr(VI) was 95%, but in tannery effluent, it was 63.08% after 72 h of incubation. The cell-free extract of SH-1 showed a 72.2% reduction of Cr(VI), which indicated a higher activity of Cr(VI) reducing enzyme than the control. Live and dead biomass of SH-1 adsorbed 51.25 mg and 29.03 mg Cr(VI) per gram of dry weight, respectively. Two adsorption isotherm models-Langmuir and Freundlich-were used for the illustration of Cr(VI) biosorption using SH-1 live biomass. Scanning electron microscopy (SEM) analysis showed an increased cell size of the treated biomass when compared to the controlled biomass, which supports the adsorption of reduced Cr on the biomass cell surface. Fourier-transform infrared analysis indicated that Cr(VI) had an effect on bacterial biomass, including quantitative and structural modifications. Moreover, the chickpea seed germination study showed beneficial environmental effects that suggest possible application of the isolate for the bioremediation of toxic Cr(VI).


MiR-153-3p Suppresses Cell Proliferation, Invasion and Glycolysis of Thyroid Cancer Through Inhibiting E3F3 Expression.
The aim was to research the role of miR-153-3p and E2F3 in the development of thyroid tumors. A total of 91 thyroid cancer patients were involved. The role of miR-153-3p in THCA cell lines and Nthy-ori3-1 cell line was researched. qPCR was used to detect miR-153-3p and E2F3 expression. MiR-153-3p mimic, inhibitor, siE2F3 or corresponding controls were transfected in cells. CCK8 was used to verify the proliferation. Cell cycle and apoptosis was detected by flow cytometry. Transwell assay was applied for migration and invasion, and glycolysis was monitored. The binding of miR-153-3p and E2F3 was predicted by targetscan database, and verified by luciferase reporter and RNA-pull down assay. Western blot was used to detect E2F3 expression. Rescue assay was undertaken to verify the effect of siE2F3 on miR-153-3p inhibitor. Moreover, the effect of miR-153-3p mimic on tumor volume and weight was measured. IHC assay was processed to E2F3 and Ki67 expression, and TUNEL assay was used for apoptosis. MiR-153-3p expressed lower in thyroid tumors and cells. The level of miR-153-3p was negatively related with TNM stage. MiR-153-3p inhibited cell proliferation, invasion migration, and induced cycle arrest and apoptosis. Moreover, it negatively regulated E2F3. siE2F3 rescued effects of miR-153-3p inhibitor in all above biological processes in thyroid cancer cells. MiR-153-3p inhibited tumor growth. Moreover, it inhibited E2F3 and Ki67 expression, and also increased apoptosis in vivo. MiR-153-3p suppresses cell proliferation, invasion and glycolysis of thyroid cancer through inhibiting E3F3 expression, which may be a biomarker for thyroid cancer diagnose.


Impact of diabetes and its treatment on cognitive function among adolescents who participated in the Diabetes Control and Complications Trial.
The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13-19 years at entry in the Diabetes Control and Complications Trial (DCCT). This was a longitudinal study involving 249 patients with type 1 diabetes who were between 13 and 19 years old when they were randomly assigned in the DCCT. Scores on a comprehensive battery of cognitive tests obtained during the Epidemiology of Diabetes Interventions and Complications follow-up study, approximately 18 years later, were compared with baseline performance. We assessed the effects of the original DCCT treatment group assignment, mean A1C values, and frequency of severe hypoglycemic events on eight domains of cognition. There were a total of 294 reported episodes of coma or seizure. Neither frequency of hypoglycemia nor previous treatment group was associated with decline on any cognitive domain. As in a previous analysis of the entire study cohort, higher A1C values were associated with declines in the psychomotor and mental efficiency domain (P < 0.01); however, the previous finding of improved motor speed with lower A1C values was not replicated in this subgroup analysis. Despite relatively high rates of severe hypoglycemia, cognitive function did not decline over an extended period of time in the youngest cohort of patients with type 1 diabetes.


PIAS-1 is a checkpoint regulator which affects exit from G1 and G2 by sumoylation of p73.
p73 is a recently described member of the p53 family, and, like p53, it undergoes a number of posttranslational modifications. Here we show, by yeast two-hybrid screening, pull-down assays, and coimmunoprecipitation, that p73alpha, -beta, and -gamma bind to the protein inhibitor of activated STAT-1 (PIAS-1) and that this binding stabilizes p73. PIAS-1 also sumoylates p73alpha, although not the C-terminally truncated isoforms p73beta and -gamma, and this requires the RING finger domain of PIAS-1. The DeltaNp73alpha isoform can also bind, and be sumoylated by, PIAS-1. PIAS-1-mediated sumoylation decreases p73 transcriptional activity on several target promoters, such as Bax. p73 is colocalized in the nucleus with PIAS-1, and sumoylated p73 is located exclusively in the nuclear matrix. PIAS-1 is expressed predominantly during S phase, and PIAS-1 overexpression reduces p73-mediated transcription of p21, with a reduction of cells in G(1) and cell cycle reentry. Inhibition of endogenous PIAS-1 by RNA interference reduces the proportion of cells in S phase and induces G(2) arrest. These data suggest that PIAS-1, acting partly through binding and sumoylation of p73, is an important component of the cell cycle machinery.


Acute manipulation of diacylglycerol reveals roles in nuclear envelope assembly & endoplasmic reticulum morphology.
The functions and morphology of cellular membranes are intimately related and depend not only on their protein content but also on the repertoire of lipids that comprise them. In the absence of in vivo data on lipid asymmetry in endomembranes, it has been argued that motors, scaffolding proteins or integral membrane proteins rather than non-lamellar bilayer lipids such as diacylglycerol (DAG), are responsible for shaping of organelles, local membrane curvature and fusion. The effects of direct alteration of levels of such lipids remain predominantly uninvestigated. Diacylglycerol (DAG) is a well documented second messenger. Here we demonstrate two additional conserved functions of DAG: a structural role in organelle morphology, and a role in localised extreme membrane curvature required for fusion for which proteins alone are insufficient. Acute and inducible DAG depletion results in failure of the nuclear envelope (NE) to reform at mitosis and reorganisation of the ER into multi-lamellar sheets as revealed by correlative light and electron microscopy and 3D reconstructions. Remarkably, depleted cells divide without a complete NE, and unless rescued by 1,2 or 1,3 DAG soon die. Attenuation of DAG levels by enzyme microinjection into echinoderm eggs and embryos also results in alterations of ER morphology and nuclear membrane fusion. Our findings demonstrate that DAG is an in vivo modulator of organelle morphology in mammalian and echinoderm cells, indicating a fundamental role conserved across the deuterostome superphylum.


Microvascular autologous transplantation of partial submandibular gland for severe keratoconjunctivitis sicca.
To evaluate the feasibility of microvascular autologous transplantation of partial submandibular gland (SMG) to prevent or reduce epiphora in severe keratoconjunctivitis sicca (KCS). A total of 39 patients with KCS, covering 42 eyes, were randomised to undergo transplantation of partial or total SMG from January 2006 to December 2009. Clinical data of survival rate of transplanted SMG, ophthalmologic features of best-corrected visual acuity, Schirmer test results, break-up time (BUT) of tear film, fluorescence staining, incidence of postoperative epiphora and frequency of subsequent surgery were compared between two groups. Total SMG transplantation was performed in 22 eyes, and partial SMG transplantation was performed in the other 20 eyes. All transplanted SMGs survived. Microvascular crisis occurred in one case of partial SMG transplantation, but the gland survived after exploration to remove the venous thrombus. Obstruction of the ductal orifice in one case of partial SMG transplantation was resolved by reconstruction of the ductal orifice. Symptoms of dry eyes disappeared, and patients were able to discontinue use of artificial tears. Severe epiphora occurred in 6 eyes undergoing partial SMG transplantation and in 19 eyes undergoing total SMG transplantation (p<0.01). Surgical reduction was performed in 6 eyes undergoing partial SMG transplantation and 18 eyes undergoing total SMG transplantation (p<0.01). Microvascular transplantation of partial SMG is feasible and effective for severe KCS and does not decrease the survival rate of transplanted SMG. For ample SMGs with normal function, transplantation of partial SMG alleviates the symptoms of dry eye and significantly reduces the incidence of severe postoperative epiphora.


The effect of mystery shopper reports on age verification for tobacco purchases.
Mystery shops involving attempted tobacco purchases by young buyers have been implemented in order to monitor retail stores' performance in refusing underage sales. Anecdotal evidence suggests that mystery shop visits with immediate feedback to store personnel can improve age verification. This study investigated the effect of monthly and twice-monthly mystery shop reports on age verification. Mystery shoppers visited 45 Walgreens stores 20 times. The stores were randomly assigned to 1 of 3 conditions. Control group stores received no feedback, whereas 2 treatment groups received feedback communications on every visit (twice monthly) or on every second visit (monthly) after baseline. Logit regression models tested whether each treatment group improved verification rates relative to the control group. Postbaseline verification rates were higher in both treatment groups than in the control group, but only the stores receiving monthly communications had a significantly greater improvement compared with the control group stores. Verification rates increased significantly during the study period for all 3 groups, with delayed improvement among control group stores. Communication between managers regarding the mystery shop program may account for the delayed age-verification improvements observed in the control group stores. Encouraging interstore communication might extend the benefits of mystery shop programs beyond those stores that receive this intervention.


Peaks of in situ N2 O emissions are influenced by N2 O-producing and reducing microbial communities across arable soils.
Agriculture is the main source of terrestrial N2 O emissions, a potent greenhouse gas and the main cause of ozone depletion. The reduction of N2 O into N2 by microorganisms carrying the nitrous oxide reductase gene (nosZ) is the only known biological process eliminating this greenhouse gas. Recent studies showed that a previously unknown clade of N2 O-reducers (nosZII) was related to the potential capacity of the soil to act as a N2 O sink. However, little is known about how this group responds to different agricultural practices. Here, we investigated how N2 O-producers and N2 O-reducers were affected by agricultural practices across a range of cropping systems in order to evaluate the consequences for N2 O emissions. The abundance of both ammonia-oxidizers and denitrifiers was quantified by real-time qPCR, and the diversity of nosZ clades was determined by 454 pyrosequencing. Denitrification and nitrification potential activities as well as in situ N2 O emissions were also assessed. Overall, greatest differences in microbial activity, diversity, and abundance were observed between sites rather than between agricultural practices at each site. To better understand the contribution of abiotic and biotic factors to the in situ N2 O emissions, we subdivided more than 59,000 field measurements into fractions from low to high rates. We found that the low N2 O emission rates were mainly explained by variation in soil properties (up to 59%), while the high rates were explained by variation in abundance and diversity of microbial communities (up to 68%). Notably, the diversity of the nosZII clade but not of the nosZI clade was important to explain the variation of in situ N2 O emissions. Altogether, these results lay the foundation for a better understanding of the response of N2 O-reducing bacteria to agricultural practices and how it may ultimately affect N2 O emissions.


Assessment of microleakage of cervical restorations.
Cervical lesions restored with composite resin seem to be more susceptible to marginal leakage, because the gingival margin is usually placed in cementum and/or dentin. The purpose of this study was to evaluate the effectiveness of five dentinal bonding agents, four composite resins and a glass ionomer cement in eliminating marginal gaps in an extraoral model. This study was accomplished using extracted human teeth and dye penetration method. The results indicated that none of the available dentinal bonding agents was able to eliminate marginal gaps completely. The cavities restored with the two component type dentinal adhesives leaked less than the negative control, glass ionomer cement.


Inspissated secretions: a life-threatening complication of prolonged noninvasive ventilation.
Noninvasive Ventilation is frequently initiated in an attempt to avoid the complications of invasive mechanical ventilation. The optimal duration of this strategy is unclear, as prolonged noninvasive ventilation has associated complications. This case report illustrates the development of life-threatening inspissated secretions precipitating airway obstruction as a consequence of prolonged noninvasive ventilation.


Review: Microextraction Technique Based New Trends in Food Analysis.
Food chemistry is the study and classification of the quality and origin of foods. The identification of definite biomarkers and the determination of residue contaminants such as toxins, pesticides, metals, human and veterinary drugs, which are a very common source of food-borne diseases. The food analysis is continuously demanding the improvement of more robust, sensitive, highly efficient, and economically beneficial analytical approaches to promise the traceability, safety, and quality of foods in the acquiescence with the consumers and legislation demands. The traditional methods have been used at the starting of the 20th century based on wet chemical methods. Now it existing the powerful analytical techniques used in food analysis and safety. This development has led to substantial enhancements in the analytical accuracy, precision, sensitivity, selectivity, thereby mounting the applied range of food applications. In the present decade, microextraction (micro-scale extraction) pays more attention due to its futures such as low consumption of solvent and sample, throughput analysis easy to operate, greener, robotics, and miniaturization, different adsorbents have been used in the microextraction process with unique nature recognized with wide range applications.


Isomer- and sex-specific bioactivation of mononitrotoluenes. Role of enterohepatic circulation.
2-Nitrotoluene (2NT) induces DNA repair in the in vivo-in vitro hepatocyte unscheduled DNA synthesis assay in male, but not female, Fischer-344 rats. 3-Nitrotoluene (3NT) and 4-nitrotoluene (4NT) are inactive in both sexes. The structurally related rat hepatocarcinogen, 2,6-dinitrotoluene, which also displays a sex-specific toxicity, requires biliary excretion for bioactivation. Therefore, the role of enterohepatic circulation in the development of the isomer- and sex-specific hepatic bioactivation of the mononitrotoluenes was studied in male and female Fischer-344 rats. Male rats excreted 28.6, 10.8, and 9.8% of a dose (200 mg/kg) of 2NT, 3NT, or 4NT, respectively, in the bile 12 hr after the dose. Female rats excreted 9.6, 4.3, and 1.3% of a dose of 2NT, 3NT, or 4NT, respectively, in the bile 12 hr after the dose. Of the 2NT-related material excreted in the bile, 77% in males (22.0% of the dose) and 86% in females (8.3% of the dose) was 2-nitrobenzyl glucuronide. Of the 3NT-related material excreted in the bile, 28% in males (2.8% of the dose) and 16% in females (0.7% of the dose) was 3-nitrobenzyl glucuronide. Of the 4NT-related material excreted in bile, 9% in males (0.9% of the dose) and 7% in females (0.1% of the dose) was 4-nitrobenzyl glucuronide. Inhibition of enterohepatic circulation by bile duct cannulation resulted in a decrease in hepatic macromolecular covalent binding by 98, 75, and 78% in male rats, and by 85, 44, and 45% in female rats after 2NT, 3NT, or 4NT, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular Engineering of Perylene Diimide Polymers with a Robust Built-in Electric Field for Enhanced Solar-Driven Water Splitting.
The built-in electric field of the polymer semiconductors could be regulated by the dipole moment of its building blocks, thereby promoting the separation of photogenerated carriers and achieving efficient solar-driven water splitting. Herein, three perylene diimide (PDI) polymers, namely oPDI, mPDI and pPDI, are synthesized with different phenylenediamine linkers. Notably, the energy level structure, light-harvesting efficiency, and photogenerated carrier separation and migration of polymers are regulated by the orientation of PDI unit. Among them, oPDI enables a large dipole moment and robust built-in electric field, resulting in enhanced solar-driven water splitting performance. Under simulated sunlight irradiation, oPDI exhibits the highest photocurrent of 115.1 μA cm-2 for photoelectrochemical oxygen evolution, which is 11.5 times that of mPDI, 26.8 times that of pPDI and 104.6 times that of its counterparts PDI monomer at the same conditions. This work provides a strategy for designing polymers by regulating the orientation of structural units to construct efficient solar energy conversion systems.


Bayesian methods for searching for optimal rules for timing intercourse to achieve pregnancy.
With societal trends towards increasing age at starting a pregnancy attempt, many women are concerned about achieving conception before the onset of infertility, which precedes menopause. Couples failing to conceive a pregnancy within 12 months are classified as clinically infertile, and may be recommended for assisted reproductive therapy (ART). Because many ART procedures are expensive and may convey an increased risk of adverse outcomes for the offspring, it is advantageous to decrease time to pregnancy by natural methods. One possibility is to intentionally time intercourse during the days of the menstrual cycle having the highest conception probabilities. This article proposes a Bayesian decision theoretic approach for searching for optimal rules for timing intercourse based on cycle day, secretions and other information. Good rules result in high conception probabilities while requiring minimal targeted intercourse. A biologically based statistical model is used to relate cycle day and biomarkers to the conception probability. A stochastic search procedure is then developed to search for rules with high expected utility, and the methods are applied to data from a recent Italian study.