Coronary artery spasm is a major cause of sudden cardiac arrest in survivors without underlying heart disease.
The role of coronary spasm in underlying disease-free patients who were resuscitated from sudden cardiac arrest remained uncertain. This study investigated the cause of cardiac arrest, and the etiologic and prognostic differences were compared between patients with underlying heart disease (group I) and those patients without underlying heart disease (group II). Twenty-five survivors of sudden cardiac arrest were classified into two groups according to the presence or absence of underlying heart disease. To investigate the cause of cardiac arrest, we performed ergonovine testing and electrophysiologic study. Fifteen of the patients had underlying heart disease, while 10 did not. Electrophysiologic abnormalities were found in 13 of the 15 patients in group I. In group II, spontaneous attack of coronary spasm occurred in four patients during the observation period, and coronary spasm was induced in three of the remaining six period of 32 +/- 23 months, whereas no patients in group II had recurrence of sudden cardiac arrest at a median follow-up of 32 months (range, 10 to 72 months). Electrophysiologic study identified a potential cause in 13 of 15 patients with underlying heart disease. Coronary spasm was involved in the pathogenesis of sudden cardiac arrest in survivors without identifiable underlying heart disease.


Atypical presentation of HIV seroconversion illness in a young woman.
Early detection and counselling of HIV-infected individuals can have an impact on prevention of HIV transmission. We describe an atypical presentation of an HIV seroconversion illness in a woman.


Duplex Doppler Ultrasound of the Hepatic Artery: A Window to Diagnosis of Diffuse Liver Pathology.
The use of Doppler sonography for evaluation of the liver is well established, and evaluation of the portal and hepatic veins in native livers, as well as the hepatic artery in transplant livers, is a standard part of the examination. Less well known, however, is that assessment hepatic of artery blood flow velocities and waveforms can permit inferences to be made about liver and system pathophysiology even in native livers. This review will illustrate that hepatic parenchymal abnormalities, as well as primary vascular abnormalities both upstream and downstream of the proper hepatic artery, can be inferred from careful interrogation of its Doppler signature during routine abdominal sonography.


Nitrogen input enhances microbial carbon use efficiency by altering plant-microbe-mineral interactions.
Microbial growth and respiration are at the core of the soil carbon (C) cycle, as these microbial physiological performances ultimately determine the fate of soil C. Microbial C use efficiency (CUE), a critical metric to characterize the partitioning of C between microbial growth and respiration, thus controls the sign and magnitude of soil C-climate feedback. Despite its importance, the response of CUE to nitrogen (N) input and the relevant regulatory mechanisms remain poorly understood, leading to large uncertainties in predicting soil C dynamics under continuous N input. By combining a multi-level field N addition experiment with a substrate-independent 18 O-H2 O labelling approach as well as high-throughput sequencing and mineral analysis, here we elucidated how N-induced changes in plant-microbial-mineral interactions drove the responses of microbial CUE to N input. We found that microbial CUE increased significantly as a consequence of enhanced microbial growth after 6-year N addition. In contrast to the prevailing view, the elevated microbial growth and CUE were not mainly driven by the reduced stoichiometric imbalance, but strongly associated with the increased soil C accessibility from weakened mineral protection. Such attenuated organo-mineral association was further linked to the N-induced changes in the plant community and the increased oxalic acid in the soil. These findings provide empirical evidence for the tight linkage between mineral-associated C dynamics and microbial physiology, highlighting the need to disentangle the complex plant-microbe-mineral interactions to improve soil C prediction under anthropogenic N input.


Monitoring and improving acute stroke care: The North Carolina Stroke Care Collaborative.
The North Carolina Stroke Care Collaborative is a stroke care quality-improvement (QI) program that provides performance data to hospitals continuously, allowing for rapid feedback and for development of QI initiatives. Between 2005 and 2012, 89,413 stroke cases were enrolled, and the proportion of patients receiving defect-free care improved from 52% to 79%. However, important areas for improvement remain.


Effect of antimicrobial therapy on progression-free survival of patients with non-small cell lung cancer receiving checkpoint inhibitor- and chemotherapy.
Checkpoint inhibitor therapy (CPI) has significantly changed therapy in non-small cell lung cancer (NSCLC) in recent years. There are some data that the effect of CPI therapy is influenced by the microbiome. Little is known about the influence and timing of antimicrobial therapy (AMT) on the microbiome-mediated effect on CPI therapy. We retrospectively analysed 70 patients (age 68 ± 9.2 years) with NSCLC stage IV. Patients were treated according to the guidelines with either CPI alone (pembrolizumab, nivolumab, atezolizumab) or chemotherapy (platin doublet or docetaxel/nintedanib or pemetrexed). We registered patient's characteristics including presence and timing of AMT. Group 1 consisted of 27 patients with AMT in the month before CPI- or chemotherapy, group 2 was 30 patients with AMT during CPI- or chemotherapy, and group 3 was 43 patients without AMT. Groups 1-3 showed comparable patient characteristics. Using cox-regression analysis, we found that AMT in the month before CPI resulted in a decreased progression-free survival (PFS) compared to patients with CPI and no AMT (14 ± 1.56 vs. 5 ± 0.99, p = 0.005, 95% CI: 0.13-0.67). In patients, who were treated with chemotherapy alone, there was no difference in PFS in those with or without AMT in the month before therapy (5 ± 0.99 vs. 6 ± 0.81 months, p = 0.3). Interestingly, AMT during chemotherapy or CPI therapy showed no effect on PFS. In a real-life setting, we found that AMT reduces PFS when given in the month before CPI therapy. AMT before chemotherapy and during CPI and chemotherapy seems not to influence PFS. The best PFS was seen in patients without AMT before CPI therapy. This implies the need for an even more restrictive use of AMT in the context of patients with NSCLC stage IV disease.


Some aspects of the measurement of phobias and obsessions.
Two assessment schemes for assessing obsessional and phobic disorders are described. The schemes were constructed with the phenomenology and epidemiology of the disorders in mind and were designed for use in the setting of general practice.


Assessment of the optimal cutoff value of fasting plasma glucose to establish diagnosis of gestational diabetes mellitus in Chinese women.
Our aim is to assess the optimal cutoff value of fasting plasma glucose (FPG) in Chinese women at 24-28 weeks' gestation by performing oral glucose tolerance test (OGTT) to improve diagnostic rate of gestational diabetes mellitus (GDM). Data were derived from the Medical Birth Registry of Xiamen. A FPG cutoff value of 5.1 mmol/L confirmed the diagnosis of GDM in 4,794 (6.10%) pregnant women. However, a FPG cutoff value of 4.5 mmol/L should rule out the diagnosis of GDM in 35,932 (45.73%) pregnant women. If we use this cutoff value, the diagnosis of GDM to about 27.3% of pregnant women will be missed. Additionally, a 75-g OGTT was performed in pregnant women with FPG values between 4.5 and 5.1 mmol/L, avoiding the performance of formal 75-g OGTT in about 50.37% pregnant women. Meanwhile, according to maternal age and pre-pregnancy BMI categories, with FPG values between 4.5 mmol/L and 5.1 mmol/L, which had high sensitivity, to improve the diagnostic rate of GDM in all groups. Further researches are needed to present stronger evidences for the screening value of FPG in establishing the diagnosis of GDM in pregnant women.


The THP-1 cell toolbox: a new concept integrating the key events of skin sensitization.
According to the current scientific consensus, one in vitro test is insufficient to cover the key events (KE) defined by the adverse outcome pathway (AOP) for skin sensitization. To address this issue we combined different end points in the same cell line to cover all KEs defined by the skin sensitization AOP. Since dendritic cells (DC) play a key role in the sensitization phase leading to the development of allergic contact dermatitis (ACD), we used THP-1 cells as a surrogate for DC. We measured ROS production and GSH depletion for KE1 (binding to proteins), Nrf2 activation pathway and gene expressions for KE2 (keratinocyte response), phenotype modifications using cell-surface markers and cytokine production for KE3 (DC activation), and T-cell proliferation for KE4 (T-cell activation). These measurements were performed using the THP-1 cell line and an original THP-1/T-cell co-culture system following exposure to a variety of chemicals, including irritant, non-sensitizers, and chemicals sensitizers (pro/prehaptens). Results showed that treatment with sensitizers such as cinnamaldehyde (100 µM) or methylisothiazolinone (150 µM) was able to trigger the three main key events (KE1, KE2, and KE3) of the sensitization phase of ACD in THP-1 cells. In addition, all sensitizers were able to induce T lymphocyte proliferation (KE4), while non-sensitizers and irritants did not. Our study shows for the first time that addressing the four main KE of skin sensitization AOP in a single cell line is an achievable task.


Associations between mental health competence and indicators of physical health and cognitive development in eleven year olds: findings from the UK Millennium Cohort Study.
Positive mental health may support healthy development in childhood, although few studies have investigated this at a population level. We aimed to construct a measure of mental health competence (MHC), a skills-based assessment of positive mental health, using existing survey items in a representative sample of UK children, and to investigate its overlap with mental health difficulties (MHD), socio-demographic patterning, and relationships with physical health and cognitive development. We analysed the UK Millennium Cohort Study (MCS) when children were aged 11 years. Maternal (n = 12,082) and teacher (n = 6739) reports of prosocial behaviours (PS) and learning skills (LS) were entered into latent class models to create MHC measures. Using descriptive statistics, we examined relationships between MHC and MHD, and the socio-demographic patterning of MHC. Associations between MHC and physical health and cognitive development were examined with relative risk ratios [RRR] (from multinomial models): BMI status (healthy weight, overweight, obesity); unintentional injuries since age 7 (none, 1, 2+); asthma symptoms (none, 1, 2+); and tertiles of test scores for verbal ability, spatial working memory and risk-taking. Models were adjusted for potential confounding. Four MHC classes were identified [percentages for maternal and teacher reports, respectively]: high MHC (high PS, high LS) [37%; 39%], high-moderate MHC (high PS, moderate LS) [36%; 26%]; moderate MHC (moderate PS, moderate LS) [19%; 19%]; low MHC (moderate PS, low LS) [8%; 16%]. Higher MHC was less common in socially disadvantaged children. While MHC and MHD were associated, there was sufficient separation to indicate that MHC captures more than the absence of MHD. Compared to children with high MHC, those in other MHC classes tended to have poorer physical health and cognitive development, particularly those with low MHC or high-moderate MHC. For example, children with maternal-report Low MHC were more likely to have experienced 2+ unintentional injuries (RRR: 1.5 [1.1-2.1]) and to have lower verbal ability scores (RRR: 2.5 [1.9-3.2]). Patterns of results were similar for maternal- and teacher-report MHC. MHC is not simply the inverse of MHD, and high MHC is associated with better physical health and cognitive development. Findings suggest that interventions to improve MHC may support healthy development, although they require replication.


The trial-packed, heat-processed spare complete denture.
A method has been described to make a second set of complete dentures for a patient. The second set of dentures will reflect relined tissue contours, use of manufactured artificial teeth, and trial-packed, heat-processed denture bases. The new dentures are of equal quality to the original dentures.


Using instrumentation in psychiatric nursing to assess documentation of the nursing process for emergent non-psychiatric patient events.
Ongoing education of experienced psychiatric nurses is imperative given the historically complex health presentations of psychiatric patients. Psychiatric patients tend to have medical co-morbidities and often do not have the financial resources for preventative health care. The hospitalization for acute psychiatric stabilization, is an opportunity for psychiatric nurses to teach and advocate for patients' physiological and psychological health. Documentation of patients' changes in condition and overall clinical presentation, is necessary to ensure patients' health care needs are met.


Bilateral infectious keratitis after a laser in situ keratomileusis enhancement procedure.
We report a case of bilateral infectious keratitis occurring as a complication of bilateral simultaneous laser in situ keratomileusis enhancement procedures. Corneal scraping from the interface of both eyes grew Staphylococcus aureus. The infection cleared after treatment with fortified cefazolin, fortified gentamicin, and ciprofloxacin eyedrops. The patient was left with bilateral paracentral corneal scars. When bilateral surgery is performed, bilateral infection may occur as a rare complication.


Identification of Angiogenesis Rich-Viable Myocardium using RGD Dimer based SPECT after Myocardial Infarction.
Cardiac healing after myocardial ischemia is a complex biological process. Advances in understanding of wound healing response have paved the way for clinical testing of novel molecular imaging to improve clinical outcomes. A key factor for assessing myocardial viability after ischemic injury is the evaluation of angiogenesis accompanying increased expression of integrin αvβ3. Here, we describe the capability of an αvβ3 integrin-targeting SPECT agent, (99m)Tc-IDA-D-[c(RGDfK)]2, for identification of ischemic but viable myocardium, i.e., hibernating myocardium which is crucial to predict functional recovery after revascularization, the standard care of cardiovascular medicine. In vivo SPECT imaging of rat models with transient coronary occlusion showed significantly high uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 in the ischemic region. Comparative measurements with (201)Tl SPECT and (18)F-FDG PET, then, proved that such prominent uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 exactly matched the hallmark of hibernation, i.e., the perfusion-metabolism mismatch pattern. The uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 was non-inferior to that of (18)F-FDG, confirmed by time-course variation analysis. Immunohistochemical characterization revealed that an intense signal of (99m)Tc-IDA-D-[c(RGDfK)]2 corresponded to the vibrant angiogenic events with elevated expression of αvβ3 integrin. Together, these results establish that (99m)Tc-IDA-D-[c(RGDfK)]2 SPECT can serve as a sensitive clinical measure for myocardial salvage to identify the patients who might benefit most from revascularization.


Factors associated with Chinese pregnant women's preference for a cesarean section based on the theory of planned behaviour.
Cesarean delivery on maternal request is one of the important public health issues in China. Our study aimed to apply the theory of planned behaviour to comprehensively determine the factors regarding pregnant women's preference for cesarean section and to provide references for establishing measures to reduce cesarean delivery on maternal request. This cross-sectional analysis was conducted in four women's and children's hospitals in China from May to June 2018. Eligible women arriving for routine antenatal visits at these hospitals were recruited to answer a structured questionnaire. A total of 1853 pregnant women consented to participate in the investigation, with a response rate of 88.75%. Finally, 1677 pregnant women (984 nulliparae and 693 multiparae) were involved in the analysis. Descriptive statistics and logistic regression analyses were used. Of the study participants, 20.39% preferred cesarean section. For both nulliparae and multiparae, those who had lower scores of attitudes towards vaginal delivery, lower scores of childbirth self-efficacy and higher scores of subjective norms were more likely to prefer cesarean section. Pregnant women's birth preferences were significantly associated with their attitudes towards the delivery mode, childbirth self-efficacy and subjective norms, which is consistent with the theory of planned behaviour. Interventions to reduce cesarean delivery on maternal request can be developed based on the theory of planned behaviour.


Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution.
Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene expression. We achieved real-time tracking of CSF-TTR in awake TtrmNeonGreen mice via multi-day intracerebroventricular fiber photometry. Diurnal changes in ChP and CSF TTR levels correlated with CSF thyroid hormone levels. These datasets highlight an integrated platform for investigating diurnal control of brain states by the ChP and CSF.


The non-toxigenic Clostridium difficile CD37 protects mice against infection with a BI/NAP1/027 type of C. difficile strain.
Clostridium difficile CD37, a clinical isolate from the USA, does not produce toxin A, B or binary toxin. The aim of this study was to determine whether strain CD37 can protect mice against infection from a challenge with a toxigenic C. difficile strain. Three groups of mice (n = 10) were pretreated with a antibiotics cocktail for 5 days, switched to sterile water for 2 days, and given one dose of clindamycin (10 mg/kg) one day (day-1) before challenge (day 0) with a toxigenic C. difficile strain. Group 1 (CD37 + UK6) was given 10(7)C. difficile CD37 vegetative cells by gavage twice a day on days -1 and -2, followed by challenge with 10(6) spores of the toxigenic C. difficile UK6 (BI/NAPI/027) on day 0; Group 2 (UK6) was infected with 10(6)C. difficile UK6 spores on day 0; Group 3 (CD37) was challenged with 10(6) CD37 vegetative cells on day 0. Our data show that pre-inoculation of strain CD37 provided mice significant protection (survival, p < 0.001 between groups CD37 + UK6 and UK6) against subsequent infection with the strain UK6, while mice infected with CD37 only did not develop any symptoms of C. difficile infection (CDI). Our results highlight the potential use of CD37 as a therapeutic strain for the prevention of primary and recurrent CDI in humans.


Enteral intestinal alkaline phosphatase administration in newborns decreases iNOS expression in a neonatal necrotizing enterocolitis rat model.
To determine if intestinal alkaline phosphatase (IAP) decreases intestinal injury resulting from experimentally induced necrotizing enterocolitis (NEC). We hypothesized that IAP administration prevents the initial development of NEC related intestinal inflammation. Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day 1 of life. Pre-term pups were exposed to intermittent hypoxia and formula containing LPS to induce NEC. Select NEC pups were given 40, 4 or 0.4 units/kg of bovine IAP (NEC+IAP40u, IAP4u or IAP0.4u) enterally, once daily. Ileal sections were evaluated by real-time PCR (qRT-PCR) for IAP, iNOS, IL-1β, IL-6, and TNF-α mRNA and immunofluorescence for 3-nitrotyrosine (3-NT). Experimentally induced NEC decreased IAP mRNA expression by 66% (p ≤ 0.001). IAP supplementation increased IAP mRNA expression to control. Supplemental enteral IAP decreased nitrosative stress as measured by iNOS mRNA expression and 3-NT staining in the NEC stressed pups (p ≤ 0.01), as well as decreased intestinal TNF-α mRNA expression. In addition, IAP decreased LSP translocation into the serum in the treated pups. We conclude that enterally administered IAP prevents NEC-related intestinal injury and inflammation. Enteral IAP may prove a useful strategy in the prevention of NEC in preterm neonates.


Hepatic gene therapy: efficient retroviral-mediated gene transfer into rat hepatocytes in vivo.
The rat is an excellent model for gene therapy because there are many rat models for human diseases. We have developed a simple and efficient method to deliver genes to the rat liver using recombinant retroviral vectors. A 70% partial hepatectomy followed by retroviral infusion into the portal vein results in 10-15% hepatocyte transduction in vivo. This is 10 times more efficient than in the mouse due partially to the observation that the rat livers have much more synchronous hepatocyte replication after partial hepatectomy. Using a recombinant retroviral vector containing the human alpha 1-antitrypsin cDNA, persistent expression of the human protein in recipient rat plasma was observed for at least six months and at a level that is 10 times greater than the mouse. Thus, rats can serve as an excellent model for gene therapy of metabolic disorders secondary to hepatic deficiencies.


Effects of somatostatin on insulin and glucagon in patients with insulinoma.
Effects of somatostatin on fasting and arginine-or tolbutamide-stimulated insulin release were studied in four patients with insulinoma. Somatostatin (bolus or bolus + infusion) reduced fasting insulin values in all patients; insulin response to tolbutamide was partially reduced in two patients; somatostatin bolus impaired the insulin response to arginine. Fasting glucagon levels and glucagon response to arginine were also reduced by somatostatin. These results indicate the potential usefulness of somatostatin in the diagnosis of insulinoma even if its effect on insulin is only partial.


Impact of stress testing on 30-day cardiovascular outcomes for low-risk patients with chest pain admitted to floor telemetry beds.
The role of immediate stress testing in low-risk patients with a potential acute coronary syndrome has not been rigorously evaluated with respect to impact on 30-day cardiovascular events. We evaluated the impact of inpatient, outpatient, or no stress testing (ETT) on 30-day cardiovascular outcomes. We performed a prospective cohort study in which consecutive patients with chest pain were admitted to a non-intensive-care telemetry bed over 16 months. Patients were identified in the ED, followed daily through hospitalization, and contacted by telephone at 30 days. Patients were excluded if they were admitted to the coronary care unit, died during hospitalization, sustained an acute myocardial infarction (AMI), or received cardiac catheterization before ETT. Patients were stratified according to whether they received an ETT as an inpatient, outpatient, or no ETT. Main outcomes were 30-day cardiac death, AMI, percutaneous interventions (PCI), and coronary artery bypass graft surgery (CABG). Data are presented as percentages with 95% confidence intervals (CI) for main outcomes. A total of 832 patients were admitted 962 times. A total of 205 patients (21%) received an in-house ETT. Seventy-four patients (10%) without an inpatient ETT received an outpatient ETT. At baseline, the groups were similar with respect to likelihood of ischemia based on mean ACI-TIPI score and Goldman risk score. A total of 98% of patients had 30-day follow-up. The cardiovascular outcomes (with 95% confidence interval) for patients with inpatient ETT versus outpatient ETT versus no ETT were as follows: death, 0% (0-1.5%) vs 0% (0-4.1%) vs 1% (0.3-1.7%); AMI, 1% (0.1-2.4%) vs 1.4% (0.1-4.1%) vs 0.3% (0.1-0.7%); PCI, 0.5% (0.1-1.5%) vs 1.3% (0.1-4.1%) vs 0% (0-0.4%); and CABG, 0.5% (0.1-1.5%) vs 0% (0-4.1%) vs 0.2% (0.1-0.4%). There was no statistical difference in 30-day cardiovascular outcomes among patients who received inpatient, outpatient, or no ETT within 30 days. This suggests that patients with chest pain who are admitted to non-intensive-care telemetry (or observation unit) beds might not need stress testing before hospital release.


Effects of indoor air pollution on tribal community in rural India and health risk assessment due to domestic biomass burning: a realistic approach using the lung deposition model.
Indoor air pollution from the combustion of biomass fuel and associated health risks is a critical issue in developing countries. Concentrations of PM2.5 and PM10 are measured in Birbhum, West Bengal, during 2017-2018. PM2.5-bound elemental concentrations of twelve metals are determined in rural kitchens. The results showed higher toxicological risks in BMF (1.15) than the LPG users (0.14). The risk of non-carcinogenic exposure related with dermal contact and ingestion was observed in the acceptable limits (HQ < 1) for all age groups, and the risk associated with inhalation exposure from Cr, Ni, As, and Mn exceeded the acceptable limit. Results also suggest that carcinogenic risks from ingestion and dermal contact are within the acceptable limit (1 × 10-4-1 × 10-6) except Cr and As which were found to exceed the range. The deposition flux (Dφ) for multiple metals in the head airway region, tracheobronchial region, and alveolar regions was found to be higher in teenagers as compared to other groups, whereas the value was lower in infants. Further, it was notified from the Dφ that the metals could pass through the head airways and harm the tracheobronchial tree and alveolar region, increasing the risk of human health.


[Therapeutic concentrations of chlormethiazol in blood and their detection (author's transl)].
Chlormethiazol in body-fluids and tissues is measured with a sensitive gaschromatographic method. The blood-concentration is a reference point for calculating the dosage and effect of chlormethiazol especially in medical questions of behaviour in traffic. The blood levels after a single and also long-term dosage were determined.


Evidence for in vivo mitosis by granule-containing mast cells from canine mastocytomas.
Mast cell accumulations are generally considered to arise almost exclusively from the recruitment of non-granulated, bone-marrow-derived, precursor cells, with the stem cell factor (SCF) reported to play a crucial role in the growth, development and maturation of granulated mast cells within specific tissue sites. In this study dog mastocytoma specimens have been examined by both immunohistochemical and ultrastructural techniques, to demonstrate that fully granulated mast cells are capable of mitotic activity. Observations showing the formation of mitotic spindles, chromosome separation and cytokinesis all support the concept that granulated mast cells are capable of proliferative activity. The ability of mature granulated mast cells to replicate provides an alternative process for local increases in mast cell numbers, at least in canine mast cell tumours. Such observations suggest the possibility that normal or neoplastic human mast cells, fully granulated, have the potential to proliferate in specific tissue sites.


Allergic rhinitis phenotypes based on mono-allergy or poly-allergy.
Allergic rhinitis (AR) is characterized by typical symptoms that are dependent on inflammation. Poly-allergy is a frequent phenomenon. Phenotyping AR represents an up-to-date issue. The aim of this study was to evaluate whether the number of allergies is able to define different phenotypes in patients with AR. 83 patients (43 males, mean age 34.7 years) suffering from AR were evaluated. Sensitization, VAS for nasal symptoms perception, and nasal cytology were evaluated. Poly-allergic patients perceived more severe nasal obstruction than mono-allergic ones (p = 0.0006) as well as they had more frequent sneezing (p < 0.0001). Moreover, poly-allergic patients had a more intense inflammatory infiltrate, concerning both eosinophils (p = 0.0005) and mast cells (p = 0.0001), than mono-allergic patients. The present study demonstrates that the presence of poly-allergy could define a distinct AR phenotype in comparison with mono-allergy. It could be clinically relevant as poly-allergic patients have more intense inflammation and more severe symptoms than mono-allergic ones.


Acute goiter hematoma following blunt neck trauma.
Traumatic hemorrhage into the thyroid gland is rarely reported. We report the case of a 30-year-old man who sustained blunt trauma to his neck, resulting in hemorrhage into a previously existing goiter. The patient's goiter was drained in the hospital. He was doing well at a three-month follow-up.


[Establishment and application of fluorescent quantitative PCR method for detecting human herpes virus type 6].
To establish fluorescent quantitative PCR method for detecting human herpes virus type 6 (HHV6). According to the specific sequence of human herpes virus type 6 genes, the primers and the fluorescent probe (TaqMan) were designed and synthesized. The fragment generated from HHV 6 gene as template was cloned into the pMD18-T vector which was constructed from the pUC 18. And the positive recombinant plasmid was 1:10 diluted and used as standard quantitative template to make the standard curve for sample detection. The standard curve indicated the linear relationship between Ct (cycle threshold) and template concentration. The clinical samples from 135 cases were detected by this system, 16 cases among 135 were positive. The fluorescent quantitative PCR method for the detection of human herpes virus type 6 is simple and accurate, and this method may be helpful to clinical diagnosis.


Spatial dynamics and influencing factors of carbon rebound effect in tourism transport: Evidence from the Yangtze-river delta urban agglomeration.
Economic efficiency gains in tourism are considered a crucial approach to reducing carbon emissions in the tourism sector, especially in tourism transport. However, as a significant source of carbon emissions from tourism activities, the total carbon emissions from tourism transport have not decreased proportionally to the reduction in the intensity, despite China's overall improvement in the tourism economic efficiency. This phenomenon is commonly known as the "rebound effect", which means that although technological progress can achieve emission reductions by efficiency improvement, but it can also indirectly stimulate socio-economic growth and creates new energy demands, results in expected emission reductions being offset by the additional economic growth effect. Based on the multi-source data structure, this paper takes Yangtze-river delta urban agglomeration as an example, quantitatively evaluated the carbon rebound effect of tourism transport through the rebound effect measurement model; simulated the spatiotemporal dynamics evolution pattern of the carbon rebound effect in tourism transport through the spatial kernel density; extracted and identified the dominant factors of carbon rebound effect in tourism transport by the geographic detector. The conclusions summarized as follow: (1) The overall carbon emissions from tourism transport in the agglomeration primarily exhibit a weak rebound effect. (2) The carbon rebound effect is significantly influenced by spatiotemporal factors, which impact its development trend and interaction relations. (3) The level of tourism consumption exerts the greatest influence on the carbon rebound effect of tourism transport, while environmental regulation intensity is commonly employed as a measure to address the rebound effect. This paper aims to enhance the diversity of research on carbon emissions in tourism transport while addressing the existing limitations in spatial-temporal extension. The objective is to restrain the spread of the carbon rebound effect at the regional level, thereby providing a novel decision-making reference for the sustainable development of regional tourism.


Design of chitosan-based nanoparticles functionalized with gallic acid.
Active nanoparticles based on chitosan could be applied as a support for the modulation of gallic acid delivery. In this sense, these nanostructures could be employed in different fields such as food, packaging, and pharmaceutical areas. The design parameters of chitosan-based nanoparticles functionalized with gallic acid (GA) were optimized through RSM by means of the analysis of zeta potential (ZP) and percentage encapsulation efficiency (PEE). The nanoparticles were prepared by ionotropic gelation using tripolyphosphate (TPP), at different combinations of chitosan (CH) concentration, CH:TPP ratio and GA. Global desirability methodology allowed finding the optimum formulation that included CH 0.76% (w/w), CH:TPP ratio of 5 and 37mgGA/gCH leading to ZP of +50mV and 82% of PEE. Analysis through QuickScan and turbidity demonstrated that the most stable nanoparticle suspensions were achieved combining concentrations of chitosan ranging between 0.5 and 0.75% with CH:TPP ratios higher than 3. These suspensions had high stability confirmed by means ZP and transmittance values which were higher than +25mV and 0.21 on average, respectively, as well as nanoparticle diameters of about 140nm. FTIR revealed the occurrence of both hydrogen bond and ionic interactions of CH-TPP which allowed the encapsulation and the improvement of the stability of the active agent.


Overexpression of a mitochondrial ATP synthase small subunit gene (AtMtATP6) confers tolerance to several abiotic stresses in Saccharomyces cerevisiae and Arabidopsis thaliana.
Mitochondrial F(1)F(0)-ATPase is a key enzyme in plant metabolism, providing cells with ATP that uses the transmembrane electrochemical proton gradient to drive synthesis of ATP. A 6 kDa protein (At3g46430) has been previously purified from Arabidopsis thaliana mitochondrial F(1)F(0)-ATPase. In this study, the gene (AtMtATP6; GenBank accession no. AK117680) encoding this protein was isolated from Arabidopsis and characterized. Northern blot analyses showed that the expression of AtMtATP6 gene in Arabidopsis suspension-cultured cells was induced by several abiotic stresses from salts, drought, and cold. Over-expression of AtMtATP6 gene in transgenic yeast and Arabidopsis plants increased the resistance to salts, drought, oxidative and cold stresses. Taken together, our data raise the possibility that induction of the F(1)F(0)-ATPase plays a role in stress tolerance.


Expression of neurofilament proteins in the vestibular ganglion cells of the rat.
Vestibular neurons from adult rats were studied by immunofluorescence microscopy using ten polyclonal and monoclonal antibodies reacting with different subunits of neurofilament (NF) polypeptides. Most antibodies strongly immunolabeled axons and dendrites. With the majority of antibodies the vestibular ganglion cells showed two distinct subpopulations: those with intense immunoreactivity and those without it. The intensely immunoreactive somata, staining with anti-70 kDa and anti-200 kDa NF antibodies but not with anti-150 kDa NF antibodies, comprised 32% of the ganglion cells (range: 27-40%). These cells were larger than the weakly immunoreactive majority of cells. Comparisons of adjacent sections revealed that at least a part of the distinctly immunostained cells were the same regardless of the antibody used. Thus, about one-third of the vestibular ganglion cells seem to form a subpopulation containing 200 kDa and 70 kDa subunits of NF polypeptides. Similar compositions of NF subunits have been demonstrated in such cells as the large dorsal root ganglion cells. The high percentage of neuronal somata with phosphorylated subunits of NF polypeptides demonstrated in this study is exceptional in other normal neurons and has been demonstrated only in experimental models and disease states.


[Principles of translational gene therapy for neuromuscular diseases].
In recent years the theoretical hope has become reality and the first hereditary neuromuscular diseases have become causally treatable. Neuromuscular diseases have thus become the pacemaker of this form of therapy for the whole of neurology. This article describes the principles of precision gene therapy for neurogenetic diseases using examples of neuromuscular diseases. Various strategies of gene therapy have become established and are being tested in preclinical and clinical trials and evaluated as approved forms for long-term efficacy. The aim of every gene therapy is the modification or introduction of the target gene with initiation of a degradation of dysfunctional proteins. Various techniques, such as gene transfer, gene substitution or gene editing in vivo and ex vivo are now usable. For example, a modification of the pre-mRNA using antisense oligonucleotides or RNA interference (siRNA) can be used for exon skipping. An initiation of gene expression to produce the target protein can be based on a modification of the DNA by means of gene replacement, cell-based therapy (iPS cells), regulation by compensatory proteins or pharmacological treatment with so-called small molecules. Each method has advantages and complex disadvantages that must be individually evaluated. Phenotypic peculiarities of a rare disease often only become apparent through specific translational therapy. It is already becoming obvious that a very early point in timing of gene therapy is probably the most effective. Newborn screening is therefore gaining additional importance as early diagnosis can achieve the best possible success of therapies, possibly even preventively.


A gut-restricted glutamate carboxypeptidase II inhibitor reduces monocytic inflammation and improves preclinical colitis.
There is an urgent need to develop therapeutics for inflammatory bowel disease (IBD) because up to 40% of patients with moderate-to-severe IBD are not adequately controlled with existing drugs. Glutamate carboxypeptidase II (GCPII) has emerged as a promising therapeutic target. This enzyme is minimally expressed in normal ileum and colon, but it is markedly up-regulated in biopsies from patients with IBD and preclinical colitis models. Here, we generated a class of GCPII inhibitors designed to be gut-restricted for oral administration, and we interrogated efficacy and mechanism using in vitro and in vivo models. The lead inhibitor, (S)-IBD3540, was potent (half maximal inhibitory concentration = 4 nanomolar), selective, gut-restricted (AUCcolon/plasma > 50 in mice with colitis), and efficacious in acute and chronic rodent colitis models. In dextran sulfate sodium-induced colitis, oral (S)-IBD3540 inhibited >75% of colon GCPII activity, dose-dependently improved gross and histologic disease, and markedly attenuated monocytic inflammation. In spontaneous colitis in interleukin-10 (IL-10) knockout mice, once-daily oral (S)-IBD3540 initiated after disease onset improved disease, normalized colon histology, and attenuated inflammation as evidenced by reduced fecal lipocalin 2 and colon pro-inflammatory cytokines/chemokines, including tumor necrosis factor-α and IL-17. Using primary human colon epithelial air-liquid interface monolayers to interrogate the mechanism, we further found that (S)-IBD3540 protected against submersion-induced oxidative stress injury by decreasing barrier permeability, normalizing tight junction protein expression, and reducing procaspase-3 activation. Together, this work demonstrated that local inhibition of dysregulated gastrointestinal GCPII using the gut-restricted, orally active, small-molecule (S)-IBD3540 is a promising approach for IBD treatment.


Embolic capture angioplasty in peripheral artery interventions.
To report a single-center experience with the Proteus embolic capture angioplasty balloon catheter for the treatment of symptomatic lower extremity peripheral artery disease. Between June 2010 and January 2012, 36 lower extremity lesions were treated in 30 patients (29 men; mean age 65±9 years) with symptomatic peripheral artery disease. Nearly half of the patients had diabetes mellitus. The mean lesion length was 140 mm, and three quarters of the lesions were considered complex owing to severe calcification, chronic total occlusion (≥3 months), in-stent stenosis, and/or length >150 mm. The volume of debris retrieved in the balloon was estimated from the number and size of particles, and a debris score was assigned and classified as low (≤2), moderate (2-4), or high (>4). Immediate procedural success was 86%, and no in-hospital serious adverse events (e.g., death, amputation, or surgical intervention) were reported. Embolic debris was captured in 32 (89%) of 36 cases. Debris scores for totally occluded, long, and in-stent stenotic lesions were 4.8±3.3, 4.6±3.0, and 3.8±2.5, respectively. Angiographic distal embolizations were reported in 2 (5.5%) procedures. Embolic capture angioplasty with the Proteus angioplasty balloon catheter during peripheral artery interventions is technically feasible and captures debris in a large proportion of the cases.


Enterobiasis of the ovary in a patient with cervical carcinoma in situ.
Enterobiasis occurs throughout the female genital tract and may involve peritoneal surfaces. It is generally an incidental finding at surgery or at autopsy but occasionally is symptomatic. Most of the superficial lesions are composed of granulomas with variable fibrosis in which diagnostic eggs are found, often associated with degenerated adult worms. Multiple histologic sections may be required to establish the diagnosis in older lesions. A case of enterobiasis of the ovary in a patient with squamous-cell carcinoma in situ of the cervix is presented. The features of enterobiasis are discussed. The importance of mistaking such lesions for ovarian cancer is discussed.


Halogen-free organophosphorus flame retardants caused oxidative stress and multixenobiotic resistance in Asian freshwater clams (Corbicula fluminea).
Halogen-free organophosphorus flame retardants are widespread in aquatic environments. Although it has been documented that they affect the behavior and reproduction of aquatic species, researches investigating cellular detoxification and the defense system in bivalves are scarce. In this study, adult Asian clams (C. fluminea) were exposed to tris (2-butoxyethyl) phosphate (TBEP) and tributyl phosphate (TBP) at 20, 200, and 2000 μg/L for 28 d. The results showed no noticeable difference in siphoning behavior. However, the siphoning behavior displayed a trend toward a slight decrease in the treatment groups. GR activity was markedly reduced compared with the control groups, whereas the levels of cyp4 significantly increased following the 2000 μg/L TBP treatments (p < 0.05). Moreover, the levels of gsts1 and gstm1 significantly decreased following all TBEP treatments and were significantly inhibited by 20 μg/L TBP (p < 0.05). The adverse effects on antioxidant enzymes suggested that C. fluminea mainly relies on the antioxidant system to reduce damage without an increase in MDA levels following exposure to a low concentration. Moreover, mRNA expression levels of heat shock proteins (hsp 22, 40, 60, 70, and 90) were significantly down-regulated with TBEP and TBP treatments lower than 200 μg/L (p < 0.05), whereas significant up-regulations were observed for hsp 22 and hsp 70 in response to 2000 μg/L TBP treatment (p < 0.05). Up-regulation of ATP-binding cassette (ABC) transporter genes (abcb1 and abcc1) showed that TBEP and TBP could activate the multixenobiotic resistance (MXR) system to discharge xenobiotics in C. fluminea, which kept its shell closed at high concentrations to prevent xenobiotic entry. Our results provide a new insight into the different mechanisms of cellular detoxification and the MXR system of C. fluminea in response to low and high concentrations of TBEP and TBP.


Tumor suppressor bromodomain-containing protein 7 cooperates with Smads to promote transforming growth factor-β responses.
Smad proteins are central mediators in the canonical transforming growth factor-β (TGF-β) signaling pathway in mammalian cells. We report here that bromodomain-containing protein 7 (BRD7) functions as a novel transcription coactivator for Smads in TGF-β signaling. BRD7 forms a TGF-β inducible complex with Smad3/4 through its N-terminal Smad-binding domain. BRD7 simultaneously binds to acetylated histones to promote Smad-chromatin association, and associates with histone acetyltransferase p300 to enhance Smad transcriptional activity. Ectopic expression of BRD7, but not its mutants defective in Smad binding, enhances TGF-β transcriptional, tumor-suppressing and epithelial-mesenchymal transition responses. Conversely, depletion of BRD7 inhibits TGF-β responses. Thus, our study provides compelling evidence for a new function of BRD7 in fine-tuning TGF-β physiological responses.


Osteoarthritis year 2013 in review: biomarkers; reflecting before moving forward, one step at a time.
In 2010, in Osteoarthritis and Cartilage, we published a comprehensive systematic review applying the consensus BIPED criteria (Burden of Disease, Investigative, Prognostic, Efficacy of Intervention and Diagnostic) criteria on serum and urinary biochemical markers for knee and hip osteoarthritis (OA) using publications that were available at that time. It appeared that none of the biochemical markers at that time were sufficiently discriminating to allow diagnosis and prognosis of OA in individual or limited numbers of patients, nor performed so consistently that they could function as primary outcome parameters in clinical trials. Also at present, almost 3 years later, this ultimate goal has not been reached (yet). Frankly, it might be questioned whether we are making the most adequate steps ahead and maybe we have to take a step back to reconsider our approaches. Some reflections are made and discussed: A critical review of molecular metabolism in OA and validation of currently investigated marker molecules in this may be vital and may lead to new and better markers. Creating cohorts in which synovial fluid (SF) is obtained in a systematic way, together with serum and urine, may also bring the field a further step ahead. Thirdly, better understanding of different phenotypes (subtypes) of OA may facilitate identification and validation of biochemical markers. Finally, the systems biology approach as discussed in the last years OA in review on biomarkers, although very complex, might provide steps forward. Looking ahead, we are optimistic but realistic in our expectations, we believe that the field can be brought forward by critically and cautiously reconsidering our approaches, and making changes forward, one step at a time.


Postprandial energy metabolism in the regulation of body weight: is there a mechanistic role for dietary calcium?
There has been much interest in the mechanisms by which calcium may attenuate weight gain or accelerate body fat loss. This review focuses on postprandial energy metabolism and indicates that dietary calcium increases whole body fat oxidation after single and multiple meals. There is, as yet, no conclusive evidence for a greater diet induced thermogenesis, an increased lipolysis or suppression of key lipogenic enzyme systems. There is however convincing evidence that higher calcium intakes promote a modest energy loss through increased fecal fat excretion. Overall, there is a role for dietary calcium in human energy metabolism. Future studies need to define threshold intakes for metabolic and gastrointestinal outcomes.


Anorexigenic effects of GLP-1 and its analogues.
GLP-1 receptors are expressed in the brain, especially in the regions responsible for the regulation of food intake, and intracerebroventricular injection of GLP-1 results in inhibition of food intake. Peripheral administration of GLP-1 dose-dependently enhances satiety and reduces food intake in normal and obese subjects as well as in type 2 diabetic patients. So far, the mechanisms by which GLP-1 exerts its effects are not completely clear. Interactions with neurons in the gastrointestinal tract or possibly direct access to the brain through the blood-brain barrier as observed in rats are possible and discussed in this chapter as well as a novel hypothesis based on the finding that GLP-1 is also expressed in taste cells. Finally, the role of GLP-1 receptor agonists as a possible treatment option in obesity is discussed as well as the role of GLP-1 in the effects of bariatric surgery on adiposity and glucose homeostasis.


Medical student self-assessment narratives: perceived educational needs during fourth-year emergency medicine clerkship.
The educational needs of medical students in the 4th-year of training are not well defined in the literature. The specific aim of this investigation is to characterize the perceived educational needs of 4th-year medical students during an Emergency Medicine clerkship. This was a thematic analysis of informed self-assessment narratives. The writings were performed by medical students during an Emergency Medicine clerkship from July 2010 through May 2011. Themes and subthemes that emerged were assessed for frequency of occurrence. Qualitative analysis of 203 narratives revealed 13 themes and 55 subthemes. Patient care (50%), history taking (44%), and physical examination (29%) were the themes most commonly noted as strengths. Medical decision making/plan of care (44%), differential diagnosis (37%), presentation skills (32%), and knowledge base (27%) were the themes most commonly noted as weaknesses. All themes were described as strengths by some students and weaknesses by others; however, trends were apparent in the analysis. Fourth-year medical students rotating on an Emergency Medicine clerkship perceive an educational need to improve medical decision making/plan of care. Self-assessment narratives reveal trends in strengths and weaknesses but also highlight the importance of recognizing students as unique learners with individualized needs.


[Current treatment concepts for olecranon and prepatellar bursitis in Austria].
The limited evidence available on the diagnosis and treatment of olecranon and prepatellar bursitis indicates nationally varying treatment approaches. Therefore the aim of this study was to survey the current treatment concepts of olecranon and prepatellar bursitis in Austria. An online questionnaire comprising of demographic data, questions regarding diagnostics and differentiation between septic bursitis (SB) and non-septic bursitis (NSB) as well as two case reports for therapy appraisal were sent to members of the Austrian Society of Orthopaedics and Orthopaedic Surgery (ÖGO) and the Austrian Society of Traumatology (ÖGU). The overall response rates were 46 % (ÖGU)/12 % (ÖGO). Differentiation between SB and NSB was predominantly based on medical history/clinical presentation (ÖGU: 100 %/ÖGO: 84 %) and blood sampling (ÖGU: 82 %/ÖGO: 77 %). 64/36 % of surveyed members of ÖGO/OGU performed a bursal aspiration. 95/55 % of Austrian ÖGU opinion leaders favoured a surgical treatment approach in cases of SB/NSB. Conversely, ÖGO members rather favoured a conservative treatment approach (28/27 %). Significant differences were found between ÖGO and ÖGU, with the latter favouring a surgical treatment approach in cases of SB and NSB. However, the international literature argues for a conservative treatment approach. Further high quality research is needed to establish an evidence-based treatment approach.


Particle size distribution of aerosols and associated heavy metals in kitchen environments.
Mass size distributions of total suspended particulate matter (TSPM) was measured from Sep 2002 to April 2003 in indoor kitchen environments of five locations in Jawaharlal Nehru University (JNU), New Delhi, with the help of a high volume cascade impactor. Particulate matters were separated in five different size ranges, i.e. >10.9 microm, 10.9-5.4 microm, 5.4-1.6 microm, 1.6-0.7 microm and <0.7 microm. The particle size distribution at various sites appears to follow uni-modal trend corresponding to fine particles i.e. size range <0.7 microm. The contributions of fine particles are estimated to be approximately 50% of TSPM and PM10.9, while PM10.9 comprises 80% of TSPM. Good correlations were observed between various size fractions. Regression results reveal that TSPM can adequately act as a surrogate for PM10.9 and fine particles, while PM10.9 can also act as surrogate for fine particles. The concentrations of heavy metals are found to be dominantly associated with fine particles. However, the concentration of some metals and their size distribution, to some extent is also site specific (fuel type used).


Ultrasound localization microscopy and functional ultrasound imaging reveal atypical features of the trigeminal ganglion vasculature.
The functional imaging within the trigeminal ganglion (TG) is highly challenging due to its small size and deep localization. This study combined a methodological framework able to dive into the rat trigeminal nociceptive system by jointly providing 1) imaging of the TG blood vasculature at microscopic resolution, and 2) the measurement of hemodynamic responses evoked by orofacial stimulations in anesthetized rats. Despite the small number of sensory neurons within the TG, functional ultrasound imaging was able to image and quantify a strong and highly localized hemodynamic response in the ipsilateral TG, evoked not only by mechanical or chemical stimulations of corneal nociceptive fibers, but also by cutaneous mechanical stimulations of the ophthalmic and maxillary orofacial regions using a von Frey hair. The in vivo quantitative imaging of the TG's vasculature using ultrasound localization microscopy combined with in toto labelling reveals particular features of the vascularization of the area containing the sensory neurons, that are likely the origin of this strong vaso-trigeminal response. This innovative imaging approach opens the path for future studies on the mechanisms underlying changes in trigeminal local blood flow and evoked hemodynamic responses, key mechanisms for the understanding and treatment of debilitating trigeminal pain conditions.


Cyclodextrin glucanotransferase: fundamentals and biotechnological implications.
Cyclodextrin glucanotransferase (CGTase) is an extracellular enzyme of the GH13 α-amylase family that catalyzes a unique intramolecular reaction known as cyclization to transform α-1, 4-glucans and similar starches into cyclodextrins. They also catalyze intermolecular transglycosylation reactions namely coupling, disproportionation, and some hydrolyzing effects on starch. The monomeric structures of the CGTase exhibit five domains (A, B, C, D, and E domains) with different molecular weights and amino acid sequences depending on the source. Among bacteria, Bacillus genus covers approximately 90% of the CGTase producers, while other genera like Klebsiella, Paenibacillus, and Thermoanaerobacter also shown decent contributions in recent studies. CGTase production is highly supported by alkaliphilic bacteria under submerged fermentation rather than solid-state fermentation. The bacterial sources, biochemical properties, production conditions, and structure of CGTases are compiled in this review. Cyclodextrins have the unique property of making inclusion complexes with various compounds, hence widely used in the food, pharmaceutical, cosmetics, laundry, and chemical sectors. This review presents a comprehensive view of CGTase produced by Bacillus spp., and other bacterial genera like Klebsiella, Paenibacillus, and Microbacterium. It also gives insight of the properties and recent biotechnological applications of cyclodextrins. KEY POINTS: • Transglycosylation reactions catalyzed by CGTase and their structural properties. • Comparative data of CGTase production by various genera and Bacillus spp. • Structures, properties, and applications of different cyclodextrins.


Spontaneous healing of rectal penetration by SpaceOAR® hydrogel insertion during permanent iodine-125 implant brachytherapy: A case report.
Radiation therapy with permanent iodine-125 implant brachytherapy is well established for curable prostate cancer. To maximize the therapeutic potential of brachytherapy, delivered radiation doses have been increased accompanied by refined intraoperative procedures of radioactive seeds placement. However, dose escalation is a double-edged sword in prostate brachytherapy; it could induce rectal toxicity, yet is successful in curable treatment in prostate cancer. To reduce irradiation of the rectum, the SpaceOAR® system has been used to inject synthetic polyethylene glycol hydrogel between the prostate and the rectum. The present report describes a case of spontaneous healing of rectal penetration associated with SpaceOAR® hydrogel.


Multivariate prognostic evaluation of the mitotic activity index and fibrotic focus in node-negative invasive breast cancers.
We validated with univariate and multivariate (Cox) analysis, the prognostic value of the mitotic activity index (MAI), the fibrotic focus (FF) and other prognosticators in 448 patients with lymph node-negative (LN-) invasive breast cancer <55 years without adjuvant systemic treatment (72.5 months median follow-up, range 4-119). Of these patients, 24.8% developed distant and 1.6% loco-regional recurrence. FF showed excellent inter-observer reproducibility (kappa = 0.93). Strong prognosticators were MAI, grade, nuclear atypia, FF and the St. Gallen criterion (SG). The subgroup with excellent survival selected by SG was only 16% of all patients, implying over-treatment of more than 70% of all LN- patients when using SG as adjuvant therapy selection criterion. If MAI <10, 13% showed distant metastases, contrasting with 41% if MAI > or = 10. FF was prognostic in the ductal and mixed ductal cancers, but not in the lobular and other subtype cancers. Patients with invasive (mixed) ductal cancers with FF absent, FF < 1/3 or FF > 1/3 of the tumour area, had distant metastasis rates of 17%, 35% and 48%; in MAI < 10 and FF absent, FF < 1/3 or FF > 1/3, metastasis rates were 11%, 13% and 42% and if MAI > or = 10, metastasis rates were 31%, 48% and 50%, respectively. In the 12 patients with MAI < 10 and a large FF > 1/3, event-free survival was similar to patients with MAI > or = 10. With multiple regression MAI < 10 versus > or = 10 is the strongest prognosticator (also stronger than the SG). The FF may be important as it has additional prognostic value to the MAI in the small subgroup of invasive ductal or mixed-ductal breast cancer patients with combined MAI < 10 and an FF > 1/3 of the tumour area.


Structure of partially denatured Escherichia coli 23 S ribosomal RNA determined by electron microscopy.
The secondary structure of 23 S ribosomal RNA was analyzed by electron microscopy after partial denaturation. A reproducible pattern of loops was seen when molecules were spread for electron microscopy in 50% formamide solutions containing various concentrations of Mg2+ and Na+. Some loops were stabilized more than others by Na+ or by Mg2+; but in general, small amounts of Mg2+ (0.5 to 1.0 mM) markedly stabilized all the major loops, as did much greater amounts of Na+ (100 mM). However, at all levels of Mg2+ examined, increasing levels of Na+ destabilized loop structures. These data are consistent with the known salt dependence of double-stranded DNA and transfer RNA structure. The four most frequently observed loops correspond, within the limits of measurement error, to the major loops in the secondary structure models of Noller et al. (1981) and Glotz et al. (1981). These four loops are, in length and position of their midpoints along the 23 S rRNA molecule: 490 +/- 50 at 250 +/- 40; 350 +/- 50 at 1860 +/- 80; 400 +/- 70 at 2330 +/- 150; and 570 +/- 100 at 2350 +/- 100. Three of the four have base-paired stems with delta G0 values among the lowest of all the loops in the two indirect models. At least two are also among the most stable loops found in computer searches of the 23 S rRNA sequence for dyad symmetry. These results demonstrate that partial denaturation mapping can both identify prominent features of secondary structure in rRNA and estimate their relative stability.


Responses of directionally selective neurons of the frog tectum mesencephali, their adaptation and extrapolation features.
Tectal directionally selective neurons were investigated in frogs. The highest measure of agreement in the character of response and dynamics of latent periods of neuron pairs was found with interelectrode distances of up to 300 mu, a fact which is evidently connected with the dimensions of the zones of ramification of the afferent fibers. Adaptation and extrapolation properties were discovered for most neurons and they were more marked in the nuclear layers of the tectum than in the fibrous layers. The more stable responses of neurons in the fibrous layers indicate the possible representation there of branches of fibers of the retinal ganglion cells, whereas neurons with high adaptivity (novelty neurons) are located in the nuclear layers.


Survival outcomes of robotic-assisted laparoscopy versus conventional laparoscopy and laparotomy for endometrial cancer: A systematic review and meta-analysis.
Robotic-assisted laparoscopy (RALS) has gained widespread acceptance in the field of gynecological oncology. However, whether the prognosis of endometrial cancer after RALS is superior to conventional laparoscopy (CLS) and laparotomy (LT) remains inconclusive. Therefore, the aim of this meta-analysis was to compare the long-term survival outcomes of RALS with CLS and LT for endometrial cancer. A systematic literature search was conducted on electronic databases (PubMed, Cochrane, EMBASE and Web of Science) until May 24, 2022, followed by a manual search. Based on inclusion and exclusion criteria, publications investigating long-term survival outcomes after RALS vs CLS or LT in endometrial cancer patients were collected. The primary outcomes included overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and disease-free survival (DFS). Fixed effects models or random effects models were employed to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs) as appropriate. Heterogeneity and publication bias were also assessed. RALS and CLS had no difference in OS (HR = 0.962, 95% CI: 0.922-1.004), RFS (HR = 1.096, 95% CI: 0.947-1.296), and DSS (HR = 1.489, 95% CI: 0.713-3.107) for endometrial cancer; however, RALS was significantly associated with favorable OS (HR = 0.682, 95% CI: 0.576-0.807), RFS (HR = 0.793, 95% CI: 0.653-0.964), and DSS (HR = 0.441, 95% CI: 0.298-0.652) when compared with LT. In the subgroup analysis of effect measures and follow-up length, RALS showed comparable or superior RFS/OS to CLS and LT. In early-stage endometrial cancer patients, RALS had similar OS but worse RFS than CLS. RALS is safe in the management of endometrial cancer, with long-term oncological outcomes equivalent to CLS and superior to LT.


Identification of cells from fetal bladder epithelium in human amniotic fluid.
Cultured human amniotic fluid cells consist of five different types of cytokeratin-positive epithelial cells, E-1 to E-5, differing by their size, growth morphology, and cytokeratin pattern, according to our earlier investigations. Using anticytokeratin antibodies in indirect immunofluorescence (IIF) microscopy, we show in this study that cultured urine cells contain four of the cell types found in amniotic fluid. In addition, we used two urothelium-specific antibodies, anti-UMA and anti-Las-86, in combination with cytokeratin antibodies to distinguish urothelium-derived cells in amniotic fluid and urine cell cultures. Two of the epithelial cell types were found to express urothelial antigens and thus to originate from the transitional bladder epithelium. These cells were found in 26 of the 33 amniotic fluid cell cultures and in nine of the ten urine cell cultures.


The combination of infrared and microwave radiation to quantify trace elements in organic samples by ICP OES.
Sample-decomposition methods using microwave radiation in closed systems have been commonly used in the analysis of inorganic constituents; however, these methods are limited to small amounts of organic samples. This work proposes the combined use of infrared radiation and microwave radiation (IR-MW) to increase the amount of organic samples digested. The determination of Al, Ca, Cu, Fe, K, Mg, Mn, Na, P and Zn in human-feed samples was accomplished by ICP OES. The results were in agreement with those obtained from conventional decomposition by microwave radiation (closed system). The results obtained using the proposed IR-MW system for standard reference material (whole milk powder, NIST 8435) were also compared. Agreements of 85-100% were obtained for Al, Ca, Cu, Fe, K, Mg, Na, P and Zn in the standard reference material. The IR-MW system is simple to implement and cheap because it uses commercially available infrared lamps and allows the use of infrared radiation in the microwave-digestion vessel. Additionally, it is possible to reach better precision in the analysis of the human-feed samples using the IR-MW system. The proposed method also allows total digestion of large sample amounts or samples rich in organic compounds can also be performed in the IR-MW system using small volumes of nitric acid.


Tooth agenesis: An overview of diagnosis, aetiology and management.
Patients with one or more developmentally absent teeth are routinely encountered in dental practice. Tooth agenesis can be associated with significant functional, aesthetic and psycho-social problems. The present article provides an overview of the prevalence and aetiology of tooth agenesis, as well as the condition's clinical characteristics and management options with reference to the evidence base. A timely diagnosis can facilitate the appropriate planning and management which might not be straightforward, and patient care will likely require multi- and inter-disciplinary input. It is critical that dental care practitioners are aware of the clinical characteristics and management options for tooth agenesis.


Comparative effects of native insulin and insulin-dextran complexes on the metabolism of adipose tissue.
Insulin-dextran complexes have been prepared and their biological activities compared to that of native insulin. Complexes referred to as T-70 had a molecular weight of about 450 000, T-2000 being more than 2 million. Insulin-dextran T-70 was stable and no release of free insulin from the complex was observed upon its incubation with adipose tissue. Insulin-dextran T-70 mimicked the effects of native insulin upon adipose tissue metabolism. It also lowered blood sugar. These effects necessitated, on an insulin molar basis, concentrations of the complex that were 10-times greater than those needed for native insulin. Maximal concentrations of insulin complex T-70 or native insulin elicited similar quantitative effects. This suggested that when the concentration of insulin-dextran T-70 was high enough, the complex occupied a sufficient number of receptor sites to produce maximal stimulation of the tissue. In contrast, insulin-dextran T-2000 was barely effective, indicating that, probably due to its size, it was unable to reach receptor sites. The size, stability and metabolic effects of insulin-dextran T-70 observed in this study give additional support to the concept that insulin action is probably mediated via a series of events initiated at the level of the plasma membrane of adipocytes.


Plasmodium falciparum: discovery of peroxidase active organelles.
Staining with 3,3' diaminobenzidine tetrahydrochloride (DAB) is a common method used for the detection of peroxidases. Using this histochemical staining method in conjunction with transmission electron microscopy, we observed oxidation of DAB that was localized to a discrete set of organelles displaying morphological similarity to small (75-90 nm diameter) versions of higher eukaryotic microbodies or peroxisomes. These single membrane bounded organelles were characterized by an asymmetrical matrix capable of oxidizing DAB to an electron dense inclusion. Oxidation of DAB was further found to be dependent upon hydrogen peroxide (H2O2) as a substrate. Given a lack of peroxisomal import proteins and enzymes, it is unlikely that these represent conventional peroxisomes. Rather, they likely represent specialized organelles containing endogenous peroxidase or pseudo-peroxidase activity.


Repurposing of Various Current Medicines as Radioprotective Agents.
The side effects of ionising radiation include skin changes, dry mouth, hair loss, low blood count, and the mutagenic effect on normal cells when utilized in radiotherapy for cancer treatment. These radiations can cause damage to the cell membrane, lipids, proteins, and DNA and generate free radicals. Evidence reports stated that radiotherapy accounts for 17-19% of secondary malignancies, labelling this treatment option a double-edged sword. Radioprotective molecules are used for mitigating radiotherapy's side effects. These agents show free radical scavenging, antioxidant, collagen synthesis inhibition, protease inhibition, immune stimulation, increased cytokine production, electron transfer, and toxicity reduction properties. The most frequently used amifostine has an array of cancer applications, showing multitarget action as nephroprotective to cisplatin and reducing the chances of xerostomia. Many other agents, such as metformin, edaravone, mercaptopropionylglycine, in specific diseases, such as diabetes, cerebral infarction, cystinuria, have shown radioprotective action. This article will discuss potentially repurposed radioprotectors that can be used in the clinical setting, along with a brief discussion on specific synthetic agents like amifostine and PrC-210. Rigorous literature search using various electronic databases, such as PubMed, ScienceDirect, Scopus, EMBASE, Bentham Science, Cochrane Library, etc., was made. Peer-review research and review papers were selected, studied, reviewed, and analysed. Safety and risk-free treatment can be guaranteed with the repurposed agents. Agents like metformin, captopril, nifedipine, simvastatin, and various others have shown potent radioprotective action in various studies. This review compiled repurposed synthetic radioprotective agents.


Assessment of the diagnostic accuracy of the TDx-FLM II to predict fetal lung maturity.
Because respiratory distress syndrome (RDS) affects 1% of live births, accurate and rapid assessment of markers of fetal lung maturity is critical to clinicians in deciding whether to deliver a preterm infant. Our objective was to determine the optimal diagnostic cutoff value for the TDx-FLM II assay (Abbott Laboratories) for predicting clinically significant RDS. Amniotic fluid TDx-FLM II data were collected retrospectively over 4 years. Women were included in the study if they had delivered within 72 h of TDx-FLM II testing and both the mother and infant charts could be reviewed. Women who had been treated with steroids and delivered unaffected infants were excluded from the analysis. The diagnosis of RDS was defined as infants who either were treated with surfactant and/or were placed on a ventilator and/or required continuous positive airway pressure for >1 day. A total of 185 women met all entry criteria (15 RDS, 170 non-RDS). A cutoff value for a mature result of >or=45 mg/g gave a sensitivity of 100% (95% confidence interval, 82-100%) and a specificity of 90% (95% confidence interval, 78-89%). The TDx-FLM II appears to predict clinically significant RDS when a cutoff of >or=45 mg/g is used for mature results. Further studies will be required to confirm these findings.


Biomechanical basis of optimal scoliosis surgical correction.
For an optimal approach to surgical correction of scoliosis, it was deemed desirable to biomechanically simulate the set of corrective forces applied by alternative internal fixation systems, so as to determine and apply the internal fixation system producing the best correction under safe levels of forces applied by the fixation systems to the spinal structures. To this end, we have developed, and presented here, (1) a spinal finite-element model relating the applied corrective forces to the corrected spinal configurations, (2) a method for determining the stiffness of the patient's spine prior to surgery, (3) computerized finite-element analysis simulation of alternative internal correction-fixation systems, so as to determine the most efficacious system, (4) instrumentations for surgically implementing the recommendations of the surgical simulation analysis and (5) comparisons of the model-simulated and surgically-obtained corrected spinal configurations. These procedures together constitute the biomechanical foundations of scoliosis surgical correction.


Risk factors for motor complications in female patients with Parkinson's disease.
To investigate the risk factors of motor complications in female patients with Parkinson's disease (PD) and the correlation between the occurrence of motor complications and sex hormone levels. According to the occurrence and types of motor complications, 103 female PD patients were divided into two groups: patients with or without the wearing-off phenomenon, patients with or without dyskinesia. Binary logistic regression analysis was performed respectively to screen for the risk factors of the wearing-off phenomenon and dyskinesia in female PD patients. Among 103 female PD patients, 44 (42.72%) had motor complications. Patients with the wearing-off phenomenon and patients with dyskinesia had higher prolactin levels than patients without the wearing-off phenomenon and patients without dyskinesia, respectively. However, the difference was no longer significant when the two groups were corrected for multiple comparisons (P < 0.0028). Multivariate analysis found that younger age at onset and higher Hoehn-Yahr (H&Y) stage were identified as independent risk factors for the wearing-off phenomenon and younger age of onset was an independent risk factor for dyskinesia in female PD patients (P < 0.05). Female PD patients have a higher incidence of motor complications. Younger age of onset and higher H&Y stage were the risk factors of the wearing-off phenomenon, and younger onset age was the risk factor of dyskinesia in female PD patients. There may be a certain correlation between the occurrence of motor complications and sex hormone levels in female PD patients, which requires further verification.


Long-term high-altitude hypoxia increases plasma nitrate levels in pregnant ewes and their fetuses.
The study was designed to determine whether moderate chronic hypoxia changes plasma nitrate concentrations in nonpregnant and pregnant, near-term ewes and their fetuses. Pregnant ewes were put into either a normoxic control group or a chronically hypoxic group maintained at high altitude (3820 m, PaO 2 60 mm Hg) from day 30 of gestation. On day 140 blood samples were collected from the maternal jugular vein and from the fetal umbilical artery and vein. Blood samples were also obtained from normoxic nonpregnant adult ewes and nonpregnant adult ewes exposed to high-altitude hypoxia for 110 days. Plasma nitrate concentrations were determined through chemiluminescence assay. Within normoxic groups plasma nitrate concentrations of pregnant, near-term ewes were significantly elevated compared with those of nonpregnant ewes (17.4 +/- 0.3 vs 6.8 +/- 0.4 micromol/L, P <.0001). Fetal umbilical arterial and venous plasma nitrate concentrations did not differ from each other in the normoxic group (44.7 +/- 4.2 and 44.0 +/- 4.3 micromol/L, respectively) but were significantly higher than those of their mothers (P <.0001). Compared with normoxic groups, pregnant ewes with chronic hypoxia showed significantly increased plasma nitrate concentrations (30.9 +/- 1.8 micromol/L, P <.001), as did their fetuses (arterial 146.1 +/- 14.7 micromol/L, venous 154.5 +/- 14.6 micromol/L, P <.0001), but nonpregnant ewes with chronic hypoxia did not (7.5 +/- 0.3 micromol/L, P >.05). We conclude that (1) production of endogenous nitric oxide is increased by pregnancy in sheep and is higher in the fetus than in the mother, and (2) moderate chronic hypoxia selectively augments nitric oxide production in the pregnant ewe's circulation and, even more profoundly, in the fetal lamb's circulation.


KORA-gen--resource for population genetics, controls and a broad spectrum of disease phenotypes.
KORA-gen is a resource for genetic epidemiological research, based on the KORA platform (Cooperative Health Research in the Region of Augsburg). Biosamples and phenotypic characteristics as well as environmental parameters of 18,000 adults from Augsburg and the surrounding counties are available. The age range of the participants was 25 to 74 years of recruitment and is 30 to 90 years in 2005. KORA-gen can be used by external partners. Interested parties can inform themselves interactively via internet about the available data and the rules of access. The genotypic data base is a common resource of all partners.


Caution regarding the specificities of pan-cancer microbial structure.
Results published in an article by Poore et al. (Nature. 2020;579:567-574) suggested that machine learning models can almost perfectly distinguish between tumour types based on their microbial composition using machine learning models. Whilst we believe that there is the potential for microbial composition to be used in this manner, we have concerns with the paper that make us question the certainty of the conclusions drawn. We believe there are issues in the areas of the contribution of contamination, handling of batch effects, false positive classifications and limitations in the machine learning approaches used. This makes it difficult to identify whether the authors have identified true biological signal and how robust these models would be in use as clinical biomarkers. We commend Poore et al. on their approach to open data and reproducibility that has enabled this analysis. We hope that this discourse assists the future development of machine learning models and hypothesis generation in microbiome research.


An unusual mechanism of spinal cord injury due to active neck stretching and its functional implications.
Spinal cord injury without radiological abnormality is a rare entity and has not been reported to occur secondary to active neck stretching. The case report highlights the possible mechanisms of injury and functional outcomes of multidisciplinary rehabilitation.


Selective cholinergic lesions in the rat nucleus basalis magnocellularis with limited damage in the medial septum specifically alter attention performance in the five-choice serial reaction time task.
Selective immunotoxic cholinergic lesions in the nucleus basalis magnocellularis (NBM) impair visuospatial attention performance in a 5-choice serial reaction time task (5-CSRT task). The features of the reported deficits, however, do not perfectly match among studies, in which some lesions may have been too weak while others largely encroached onto the septal region. Using the 5-CSRT task, we therefore re-assessed the effects of NBM lesions that produced minimal septal damage. Long-Evans adult male rats were trained to stable 5-CSRT task performance (stimulus duration: 0.5 s) and subsequently subjected to intra-NBM injections of 192 IgG-saporin (200 ng/side). The lesions induced more than 90% loss of choline acetyltransferase-positive neurons in the NBM vs. only 28% in the medial septum. The decrease of the optical density of acetylcholinesterase reaction products was significant in the cortex (-91%), not in the hippocampus. In the 5-CSRT task, the lesions resulted in increased omissions (from 10% to 30%) and decreased correct responses (from 80% to 60%), with negligible or no effects on all other usually collected variables. This deficit disappeared with lengthened stimulus duration (i.e. 0.5-1 and then 5 s). Furthermore, overall performance levels decreased when the stimulus duration was shortened (i.e. 0.5-0.2 s) or its intensity attenuated, and rats with cholinergic lesions remained consistently impaired vs. controls. These results show that disruption of sustained visual attention functions by damage to the NBM cholinergic neurons can be evidenced despite weak or no effects on variables accounting for motivational, locomotion- or impulsivity-related biases. Discrepancies with previously reported results are discussed in terms of differences in lesion extent/specificity and training levels.


Inhibition of human islet amyloid polypeptide aggregation and cellular toxicity by oleuropein and derivatives from olive oil.
Loss of β-cell function and β-cell death is the key feature of type 2 diabetes mellitus (T2DM). One hypothesis for the mechanism of this feature is amyloid formation by the human islet amyloid polypeptide (hIAPP). Despite the global prevalence of T2DM, there are no therapeutic strategies for the treatment of or prevention of amylin amyloidosis. Clinical trials and population studies indicate the healthy virtues of the Mediterranean diet, especially the extra virgin olive oil (EVOO) found in this diet. This oil is enriched in phenolic compounds shown to be effective against several aging and lifestyle diseases. Oleuropein (Ole), one of the most abundant polyphenols in EVOO, has been reported to be anti-diabetic. Some of Ole's main derivative have attracted our interest due to their multi-targetted effects, including interference with amyloid aggregation path. However, the structure-function relationship of Ole and its metabolites in T2DM are not yet clear. We report here a broad biophysical approach and cell biology techniques that enabled us to characterize the different molecular mechanisms by which tyrosol (TYR), hydroxytyrosol (HT), oleuropein (Ole) and oleuropein aglycone (OleA) modulate the hIAPP fibrillation in vitro and their effects on cell cytotoxicity. The OleA formed by enolic acid and hydroxytyrosol moiety was found to be more active than the Ole and HT at low micromolar concentrations. We further demonstrated that OleA inhibit the cytotoxicity induced by hIAPP aggregates by protecting more the cell membrane from permeabilization and then from death. These findings highlight the benefits of consuming EVOO and the great potential of its polyphenols, mainly OleA. Moreover, they support the possibility to validate and optimize the possible pharmacological use of EVOO polyphenols for T2DM prevention and therapy and also for many other amyloid related diseases.


Palladium-catalyzed propargylic substitution with phosphorus nucleophiles: efficient, stereoselective synthesis of allenylphosphonates and related compounds.
A new, efficient method is developed, based on a palladium(0)-catalyzed reaction of propargylic derivatives with various phosphorus nucleophiles, to produce allenylphosphonates and their analogues with defined stereochemistry in the allenic and the phosphonate moiety.


A validation of the religious and spiritual struggles scale among young people living with HIV in Zimbabwe: Mokken scale analysis and exploratory factor analysis.
Religious/spiritual convictions and practices can influence health- and treatment-seeking behavior, but only few measures of religiousness or spirituality have been validated and used outside of the US. The Religious and Spiritual Struggles scale (RSS) measures internal and external conflict with religion and spirituality and has been validated mainly in different high-income contexts. The aim of this study was the validation of the RSS in the Zimbabwean context and among young people living with human immunodeficiency virus (YPLHIV) aged 14-24. Data collection with an Open Data Kit (ODK) questionnaire with 804 respondents took place in 2021. The validation was performed by confirmatory factor analysis (CFA), using statistical equation modeling (SEM), and Mokken scale analysis (MSA). After the low confirmability of the original scale sub-dimensions exploratory factor analysis (EFA) was applied. The EFA resulted in four new sub-domains that were different from the original six domains in the RSS but culturally more relevant. The new sub-domains are significantly related to health. The findings support the validity and relevance of the RSS and the new sub-domains in this context. As our study was limited to YPLHIV, further validation of the RSS among different population groups and contexts in the sub-Saharan region is encouraged.


Benign juvenile focal muscular atrophy of upper extremities--a familial case.
A 53-year-old man and his 18-year-old son, both suffering from benign focal muscular atrophy of upper extremities are described. To our knowledge this is the first familial case of this disease in Caucasians.


Absence of a disinhibition effect of alcohol on food consumption.
Alcohol is frequently mentioned as a disinhibitor of restrained eating behavior although only a small number of studies have investigated this disinhibition effect. The present study was conducted to fill this gap. A total of 116 female college students participated in a questionnaire-based assessment and a taste-test experiment. Before the taste test, half of the participants consumed a preset amount of alcohol-laced orange juice, the other half were given plain orange juice. The dependent variable was the amount of savory crackers eaten during the taste test. The Dutch Eating Behavior Questionnaire (DEBQ), the Three-Factor Eating Questionnaire (TFEQ), and the Restraint Scale (RS) were used to measure eating behavior dimensions, which formed the independent variables in various regression analyses. No disinhibition effect was found. On the contrary, participants scoring high on restraint (DEBQ, TFEQ) proved to consume even less food than those having lower scores. Participants that rated high on the scales measuring tendency toward overeating consumed more food than participants with low scores. These results support earlier contentions that the validity of the Restraint Theory's statement that dieting leads to overeating is questionable.


Shift of activity from attention to motor-related brain areas during visual learning.
With practice, we become increasingly efficient at visual object comparisons. This may be due to the formation of a memory template that not only binds individual features together to create an object, but also links the object with an associated response. In a longitudinal fMRI study of object matching, evidence for this link between perception and action was observed as a shift of activation from visual-attentive processing areas along the posterior intraparietal sulcus to hand-sensory and motor-related areas.


Response to important considerations when assessing the effect of essential fatty acids on cognitive performance.
In this letter, we respond to the comments raised by Visaria et al. in their letter to the editor about the publication "Association of dietary ω-3 and ω-6 fatty acids intake with cognitive performance in older adults: National Health and Nutrition Examination Survey (NHANES) 2011-2014". We have further adjusted for some key covariates as the authors mentioned in the letter and performed sensitivity analysis by excluding vegetarians considering the bioavailability of fatty acids from different sources. In conclusion, the results were basically consistent with our previous results, which showed that the results were stable and reliable. We hope that our study could be helpful in further studies delineating the various intricacies of fatty acid nutrition and metabolism and control for covariates.


Mutagenic effect of argemone oil in Oryza sativa L.
In view of the large scale adulteration of edible oils with Argemone oil, a study was undertaken to test its mutagenicity on rice seed. In treatment with screw-pressed oil a marked reduction in seed germination and high chlorophyll mutation and mutant frequencies were observed. In sequential treatments between gamma rays and Argemone oil both mutation and mutant frequencies were significantly higher than that of individual treatments. This study clearly indicates that Argemone oil is a potent mutagen with serious implications for the genetic hygiene of human beings.


Determinants of childbirth care quality along the care continuum in limited resource settings: A structural equation modeling analysis of cross-sectional data from Burkina Faso and Côte d'Ivoire.
Despite the important increase in in-facility births, perinatal mortality rates have remained high and slow to decrease in many developing countries. This situation is attributed to poor childbirth care quality. The reason why women delivering in health facilities do not always receive care of an adequate standard is unclear. We assessed the determinants of childbirth care quality along the care continuum by means of different approaches. A health facility-based cross-sectional study with a direct observation of health care workers' practices while caring for mother-newborn pairs was carried out in Burkina Faso and Côte d'Ivoire. The performance of a set of essential best practices (EBPs) was assessed in each birth event at the admission, prepushing and immediate postpartum stages. A quality score, in the form of the additive sum of EBPs effectively delivered, was computed for each stage. We used negative binomial regression models and a structural equation modeling analysis to assess the determinants of care quality at each stage and the relationships of the quality delivered at the different stages, respectively. A total of 532 and 627 mother-newborn pairs were evaluated in Burkina Faso and Côte d'Ivoire, respectively. In both countries, delivery care quality varied significantly at all stages between health districts. Predelivery care quality was consistently higher in referral hospitals than in primary health care facilities (incident rate ratio (IRR) = 1.02, p < 0.05, and IRR = 1.10, p < 0.05, respectively, for Burkina Faso and Côte d'Ivoire). Quality at admission was poorer among nurses than among midwives in Burkina Faso (IRR = 0.81, p < 0.001). Quality at the admission and predelivery stages was positively correlated with immediate postpartum care quality (β = 0.48, p < 0.001, and β = 0.29, p < 0.001, respectively). Quality improvement strategies must target both providers and health facilities, and different inputs are needed depending on the stage in the care continuum.


Amplification pattern of 12q13-q15 genes (MDM2, CDK4, GLI) in urinary bladder cancer.
The chromosomal region 12q13-q15 is recurrently amplified in bladder cancer. Putative target genes located in this region include MDM2, CDK4, and GLI. To evaluate the involvement of these genes in bladder cancer, we screened a tissue microarray (TMA) containing 2317 samples by fluorescence in situ hybridization (FISH). Amplification was found for MDM2 in 5.1%, for CDK4 in 1.1%, and for GLI in 0.4% of interpretable tumors. Among tumors having amplification of at least one of these 12q13-q15 genes, 76.6% had amplification of MDM2 alone and 6.4% had amplification of CDK4 alone. Coamplifications were seen of MDM2 and CDK4 in 10.6%, and of CDK4 and GLI in 6.4%. Neither coamplifications of all three genes nor isolated GLI amplifications were found. These data suggest a prominent role of MDM2 as a 12q13-q15 amplification target in bladder cancer. However, independent CDK4 amplifications do also occur suggesting either two non-overlapping amplification sites or else a minimal overlapping region between MDM2 and CDK4 perhaps containing another yet unknown oncogene. The frequency of amplification increased significantly from stage pTa to pT1-4 (P<0.04) and from low to high grade (P<0.005). These data are consistent with a high level of genetic instability in invasively growing and high-grade bladder tumors.


Geriatric Psychiatry Across the Spectrum: Medical Student, Resident, and Fellow Education.
The older adult population in the United States is poised to reach 83.7 million by 2050, and up to 20% will suffer from cognitive and mental illnesses. We do not have the workforce available to meet this need; therefore, general psychiatrists will care for many older psychiatric patients. Enhancing learning opportunities during general medical education and residency could improve the knowledge of general psychiatrists and encourage recruitment into geriatric psychiatry. This article outlines geriatric psychiatry education in medical school, residency, and geriatric psychiatry fellowship with suggestions for recruitment into the field, along with recommendations for enhanced learning for general psychiatrists.


A pilot study of a longitudinal mindfulness curriculum in undergraduate medical education.
To support student well-being, a mindfulness curriculum in undergraduate medical education was launched at our university in 2014. We describe the program and report 3-year results. Medical students responded to online questionnaires on mindfulness (Freiburg Mindfulness Inventory), empathy (Jefferson Scale of Physician Empathy), resilience (Connor-Davidson Resilience Scale) and perceived stress (Perceived Stress Scale) and were surveyed for demographics, home practice, and subjective experience at curriculum launch and yearly for 3 years. In respondents, high stress (19.2 (SD=6)) and low resilience (71.2 (SD=12.5)) scores were seen throughout training. Scores for mindfulness correlated positively with those for empathy (r=.217 p < 0.01) and resilience (r = .539, p < 0.01), and negatively with stress scores (r = -.380, p < 0.01). While overall scale scores did not statistically change after curriculum implementation, statistically significant increases were seen in mindfulness (12%, p = 0.008), empathy (5%, p = 0.045), and resilience scores (12%, p = 0.002) with a trend toward lower stress scores (8%, p =0.080) in respondents who felt they applied the curriculum principles. Two hours of reported home practice per week was associated with statistically significant changes (14% increased mindfulness scores p < 0.001; 6% increased empathy scores p < 0.001, 10% increased resilience scores p = 0.003; 11% decreased stress scores p = 0.008). Despite positive program evaluations for both mandatory and elective sessions, student attendance at elective sessions was low. A mindfulness curriculum integrated into formal undergraduate medical education is feasible. Benefits may be confined to those students who apply curriculum principles and practice regularly. Further study is needed.Résumé. Pour soutenir le bien-être des étudiants, un cursus de méditation pleine conscience dans le cadre du programme de doctorat en médecine a été lancé à notre université en 2014. Nous décrivons le programme et communiquons les résultats après trois ans. Des étudiants en médecine ont répondu à des questionnaires en ligne sur la pleine conscience (inventaire de pleine conscience de Freiburg), l'empathie (Échelle de Jefferson sur l'empathie du médecin), la résilience (échelle de résilience de Connor-Davidson) et le stress perçu (échelle du stress perçu) et ont été interrogés pour les caractéristiques démographiques, la pratique de la méditation pleine conscience à domicile et l'expérience subjective au moment du lancement du cursus et, ensuite, annuellement pendant trois ans. Chez les répondants, un degré de stress élevé (19,2 (ET=6)) et une faible résilience (71,2 (ET=12,5)) ont été observés tout au long de la formation. Il y avait une corrélation positive entre les la pleine conscience et l'empathie (r=0,17, p<0,01) et de la résilience (r=0,539, p<0,01), et négative avec le stress (r=-0,380, p<0,01). Alors que les résultats globaux ne changent pas statistiquement après la mise en œuvre du cursus, des augmentations statistiquement significatives ont été observées pour la pleine conscience (12%, p=0,008), l'empathie (5%, p=0,045) et la résilience (12%, p=0,002) avec une tendance vers des résultats inférieurs pour le stress (8%, p=0,080) chez les répondants qui estimaient avoir appliqué les principes du programme. On retrouvait des changements significatifs chez les répondants qui rapportaient avoir pratiqué deux heures par semaine à domicile (résultats accrus de 14% pour la pleine conscience (p<0,001), de 6% pour l'empathie (p<0,001) et de 10% pour la résilience (p= 0,003), et réduits de 11% pour le stress (p=0,008)). Malgré des évaluations de programme positives pour les sessions obligatoires et optionnelles, l'assiduité des étudiants aux sessions optionnelles était faible. Un cursus de méditation pleine conscience intégré dans des études formelles de doctorat en médecine est faisable. Les avantages peuvent être confinés aux étudiants qui appliquent les principes du programme et qui le pratiquent sur une base régulière. D'autres études sont requises.


Transient occlusion of an Angioguard protection system by massive embolization during angioplasty of a degenerated aortocoronary saphenous vein graft.
Distal embolization is the most important complication of balloon dilatation of degenerated saphenous vein grafts. We describe a case of massive embolization associated with transient occlusion in which larger distal embolization and myocardial infarction were avoided despite transient but complete occlusion of a filter protection system (Angioguard).