Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus, and neoplastic transformation in glioma.
miR-10b is silenced in normal neuroglial cells of the brain but commonly activated in glioma, where it assumes an essential tumor-promoting role. We demonstrate that the entire miR-10b-hosting HOXD locus is activated in glioma via the cis-acting mechanism involving 3D chromatin reorganization and CTCF-cohesin-mediated looping. This mechanism requires two interacting lncRNAs, HOXD-AS2 and LINC01116, one associated with HOXD3/HOXD4/miR-10b promoter and another with the remote enhancer. Knockdown of either lncRNA in glioma cells alters CTCF and cohesin binding, abolishes chromatin looping, inhibits the expression of all genes within HOXD locus, and leads to glioma cell death. Conversely, in cortical astrocytes, enhancer activation is sufficient for HOXD/miR-10b locus reorganization, gene derepression, and neoplastic cell transformation. LINC01116 RNA is essential for this process. Our results demonstrate the interplay of two lncRNAs in the chromatin folding and concordant regulation of miR-10b and multiple HOXD genes normally silenced in astrocytes and triggering the neoplastic glial transformation.


Fatal injuries of the brain stem and/or upper cervical spinal cord in traffic accidents: nine autopsy cases.
Nine forensic autopsy cases were studied. All had injuries of the brain stem and/or upper cervical spinal cord due to traffic accidents. Among the nine subjects, eight were pedestrians and one was a left, front seat occupant of a vehicle. Examination of these 9 cases revealed that three had ponto-medullary avulsion, two had medullary avulsion and the other four had laceration of the upper cervical spinal cord. Atlanto-occipital dislocation was observed in five cases, and a ring fracture around the foramen magnum in the other two cases. Intraventricular haemorrhage, probably due to tears of the choroid plexus caused by hyperextension or hyperflexion of the head, was found in seven cases. In just one of these seven cases, both of the lateral ventricles were filled with dark red haemocoagulum. Hyperextension is considered to occur more commonly in road trauma cases where the victim is alcoholically intoxicated.


Development of significant disordered eating in an adolescent following gastric bypass surgery.
The development of eating pathology is a concern following bariatric surgery, even in the absence of any pre-surgical psychopathology. No consistent risk factors have emerged in the literature to identify those at greatest risk. However, post-surgical guidelines encourage eating behaviors that would be considered disordered in other contexts. We present a case of an adolescent developing bulimia nervosa following gastric bypass surgery and the escalation of her symptoms from diligently following recommended food behaviors to a full-syndrome clinical eating disorder. We discuss the differences between appropriate post-surgical eating behaviors and disordered eating behaviors. We provide recommendations for clinicians to screen for eating pathology and referrals to an interprofessional treatment team to address eating disordered behaviors and cognitions.


Breast-feeding and maternal smoking in the etiology of Crohn's disease and ulcerative colitis in childhood.
Medical records concerning pediatric or adolescent patients first diagnosed with Crohn's disease or ulcerative colitis in two New York hospitals during a 5-year period (1986 to 1990) were abstracted, and information concerning sex, age, race, birthplace, sibship size, birth order, maternal age at birth, month of birth, duration of breast-feeding, and maternal smoking was recorded. Medical records of patients presenting at the respective pediatric gastroenterology departments immediately before or after the patients with inflammatory bowel disease were seen were also abstracted in order to generate a control series. Data concerning 68 patients with Crohn's disease, 39 patients with ulcerative colitis, and 202 control patients were analyzed through multiple logistic regression. Breast-feeding was negatively associated with Crohn's disease (P approximately 0.04) and ulcerative colitis (P approximately 0.07), with relative risk point estimates around 0.5 and with evidence of duration-dependent trends in both instances. There was no evidence of association of either disease with maternal age at birth, birth order, maternal smoking, or season of birth.


Constitutive nitric oxide synthases are responsible for the nitric oxide production in the ischemic aged cerebral cortex.
Aged brain shows reduced biological plasticity to meet emergency conditions such as ischemia, a process in which nitric oxide (NO) and apoptosis have been shown to play important roles. Using a model of transient global ischemia, we have analyzed the NO system and the p53, bax and bcl-2 response in the cerebral cortex of aged rats. Although immediately after ischemia the NO level is maintained, the reperfusion period increases NO concentrations together with the following: (i) greater bulk-protein nitration mainly due to a 50-kDa immunoreactive band; (ii) an increase in p53 protein; and (iii) an up-regulation of Bax together with a down-regulation of Bcl-2. These results match up with induced endothelial nitric oxide synthase expression immediately after ischemia and in neuronal nitric oxide synthase with the reperfusion. However, inducible nitric oxide synthase was not altered with ischemia/reperfusion. Altogether, these data suggest that NO production in cerebral cortex of aged ischemic animals is due to the constitutive NO synthase isoforms. This response is accompanied by the increased expression of pro-apoptotic proteins.


Malignant melanoma masquerading as Kaposi's sarcoma.
A homosexual HIV-negative man was referred to the genitourinary medicine department with a histological diagnosis of Kaposi's sarcoma. Repeat biopsy confirmed that this was in fact malignant melanoma.


A Systems-Based Map of Human Brain Cell-Type Enriched Genes and Malignancy-Associated Endothelial Changes.
Changes in the endothelium of the cerebral vasculature can contribute to inflammatory, thrombotic, and malignant disorders. The importance of defining cell-type-specific genes and their modification in disease is increasingly recognized. Here, we develop a bioinformatics-based approach to identify normal brain cell-enriched genes, using bulk RNA sequencing (RNA-seq) data from 238 normal human cortex samples from 2 independent cohorts. We compare endothelial cell-enriched gene profiles with astrocyte, oligodendrocyte, neuron, and microglial cell profiles. Endothelial changes in malignant disease are explored using RNA-seq data from 516 lower-grade gliomas and 401 glioblastomas. Lower-grade gliomas appear to be an "endothelial intermediate" between normal brain and glioblastoma. We apply our method for the prediction of glioblastoma-specific endothelial biomarkers, providing potential diagnostic or therapeutic targets. In summary, we provide a roadmap of endothelial cell identity in normal and malignant brain, using a method developed to resolve bulk RNA-seq into constituent cell-type-enriched profiles.


Trans enantiomeric separation of MESA and MOXA, two environmentally important metabolites of the herbicide, metolachlor.
Complete separation of the trans-enantiomers of the two most abundant, persistent polar metabolites of metolachlor, metolachlor ethane sulfonic acid (MESA) and metolachlor oxanilic acid (MOXA), was achieved using UPLC equipped with a reverse phase chiral column and trace detection with an electrospray triple quadrupole mass spectrometer. Various conditions that influenced the separation and instrumental signal were investigated to achieve the optimum separation and instrument response within an analysis time of less than 30 minutes. Different eluting solvent compositions for each metabolite were required for optimized separation of of the 4 enantiomers. Standard curves were responsive to less than 13 ng/mL and 8 ng/mL for the least plentiful MOXA and MESA enantiomers, respectively with a linear coefficient of determination greater than 0.998. Suitability of the method for quantification of the 4 mixed enantiomers of each was demonstrated using natural surface water samples collected from the Choptank River watershed in Eastern Maryland.•LC chiral separation parameters were varied to achieve optimal separation of the major enantiomers of the two metolachlor metabolites.•LC/MS-MS parameters were adjusted to maximize response and minimize analysis time.•Finished methods were used to quantitate enantiomers in archived stream water extracts from agricultural watersheds with corn/soybean production.


Pre-stem cell formation by non-platelet RNA-containing particle fusion.
We found a group of non-platelet RNA-containing particles (NPRCP) in human umbilical cord blood. To understand the origin, characterization and differentiation of NPRCP, we examined cord blood-isolated NPRCP in vitro. The NPRCP range in size from < 1 to 5 μm, have a thin bilayer membrane and various morphological features, contain short RNA and microRNA and express octamer-binding transcription factor 4 (OCT4), sex-determining region Y 2 (SOX2) and DEAD box polypeptide 4 (DDX4). On coculture with nucleated cells from umbilical cord blood, NPRCP fuse to small, active, non-nucleated cells called 'particle fusion-derived non-nucleated cells' (PFDNC). The PFDNC are approximately 8 μm in diameter and are characterized by their twisting movement in culture plates. They can easily move into and out of nucleated cells and finally differentiate into mesenchymal-like cells. In addition, the larger non-nucleated cellular structures that are derived from the aggregation and fusion of multiple NPRCP can further differentiate into large stem cells that also release OCT4- and SOX2-positive non-nucleated small cells. Our data provide strong evidence that NPRCP can fuse into PFDNC, which further differentiate into mesenchymal-like cells. Multiple NPRCP also fuse into other types of large stem cells. We believe that stem cells are derived from NPRCP fusion. There is considerable potential for the use of NPRCP in clinical therapy.


Nitrogen and energy balance in septic and injured intensive care patients: response to parenteral nutrition.
We studied energy and nitrogen balance in 50 intensive care patients with sepsis (n = 18) or multiple trauma (n = 32). Most patients were mechanically ventilated during the study. Within 72h of admission the patients were randomised to receive one of 5 infusion regimens for 48h (group n = 9-11). The control group received hypocaloric glucose, two groups received 1.5g/kg/day of amino-acids, either with hypocaloric glucose on both days or with energy adjusted to pre-nutrition REE on the second day. The fourth group received 0.6g/kg/day of amino-acids and energy at REE, and the fifth group a high nitrogen (18g/day) regimen with a stepwise increase in energy intake from day 1 to day 2. Baseline REE was 118 +/- 18.9% of predicted. No significant differences in REE were observed between the diagnostic groups, treatments or measurements performed during mechanical or spontaneous ventilation. Nitrogen balance in the control group was -250.3 +/- 83.3 mg/kg on day 1 and 218.6 +/- 95.3 mg/kg on day 2. Nitrogen balance remained negative in all groups throughout the study (range of group means-218.6 to -48.5 mg/kg/day). Increasing energy intake equal to prenutrition REE at an amino-acid dosage of 1.5g/kg/day decreased the negative nitrogen balance by 66%. Further increase in energy balance had only a marginal effect on nitrogen balance.


High-titer MSCV-based retrovirus generated in the pCL acute virus packaging system confers sustained gene expression in vivo.
Retroviral gene transfer using vectors encoding tumor suppressor genes has been tested repeatedly as a potential anti-tumor therapy. However, most attempts have been hindered by the inability to deliver genes efficiently and to obtain sustained expression in cells growing in vivo. In this paper we describe a method for producing high-titer MSCV virus using the pCL acute retroviral packaging system. This method facilitates the generation of MSCV virus encoding genes that convey the cytostatic or cytocidal phenotypes of benefit in the treatment of cancer. Amphotropic MSCV virus with an average titer of 6 x 10(6) CFU/ml has been routinely produced in this system. We demonstrate that, unlike the pCL retroviral vectors, the MSCV vector is capable of directing sustained in vivo expression of the green fluorescent protein in infected glioma cells following implantation and tumor growth in nude mice.


Effect of ascorbic acid treatment on endothelium-dependent and neurogenic relaxation of corpus cavernosum from middle-aged non-insulin dependent diabetic rats.
The purpose of the present study was to investigate functional responses and nitric oxide synthase activity in the corpus cavernosum of young control, middle-aged control and middle-aged non-insulin dependent diabetic rats. The animal groups were treated with ascorbic acid. Acetylcholine-mediated endothelium-dependent relaxation of cavernosal tissue was significantly attenuated from a maximum of 58.0 +/- 4.1% (1 mmol, n = 10) in young rats to 44.3 +/- 1.6% in aged-matched controls (P < 0.05) and to 23.3 +/- 2.8% in non-insulin-dependent diabetes mellitus rats (P < 0.01). These deficits in acetylcholine responsiveness were completely prevented by ascorbic acid treatment. Non-adrenergic non-cholinergic relaxations evoked by electrical field stimulation (0.5-64.0 Hz) in the corpus cavernosum of middle-aged control and non-insulin dependent (NID) diabetic rats are blunted and were not restored by ascorbic acid. The histochemical findings demonstrated a decrease of nicotinamide adenine dinucleotide phosphate-diaphorase staining in the cavernosal tissue obtained from middle-aged control rats and middle-aged diabetic rats. Partial correction by ascorbic acid may suggest the importance of reactive oxygen species and a therapeutic approach in impotent NID diabetic men.


Role of angiotensin II type 1A receptor phosphorylation, phospholipase D, and extracellular calcium in isoform-specific protein kinase C membrane translocation responses.
The angiotensin II type 1A receptor (AT(1A)R) plays an important role in cardiovascular function and as such represents a primary target for therapeutic intervention. The AT(1A)R is coupled via G(q) to the activation of phospholipase C, the hydrolysis of phosphoinositides, release of calcium from intracellular stores, and the activation of protein kinase C (PKC). We show here that PKCbetaI and PKCbetaII exhibit different membrane translocation patterns in response to AT(1A)R agonist activation. Whereas PKCbetaII translocation to the membrane is transient, PKCbetaI displays additional translocation responses: persistent membrane localization and oscillations between the membrane and cytosol following agonist removal. The initial translocation of PKCbetaI requires the release of calcium from intracellular stores and the activation of phospholipase C, but persistent membrane localization is dependent upon extracellular calcium influx. The mutation of any of the three PKC phosphorylation consensus sites (Ser-331, Ser-338, and Ser-348) localized within the AT(1A)R C-tail significantly increases the probability that persistent increases in diacylglycerol levels and PKCbetaI translocation responses will be observed. The persistent increase in AT(1A)R-mediated diacylglycerol formation is mediated by the activation of phospholipase D. Although the persistent PKCbetaI membrane translocation response is absolutely dependent upon the PKC activity-dependent recruitment of an extracellular calcium current, it does not require the activation of phospholipase D. Taken together, we show that the patterning of AT(1A)R second messenger response patterns is regulated by heterologous desensitization and PKC isoform substrate specificity.


A Multicenter Retrospective Study With a Minimum 5-Year Follow-up Comparing Arthroscopic Bankart Repair and the Latarjet Procedure.
Arthroscopic Bankart repair (ABR) and the Latarjet procedure are surgical techniques commonly used to treat anterior shoulder instability. There is no consensus among shoulder surgeons regarding the indications for choosing one over the other. To compare the results of the Latarjet procedure with those of ABR for the treatment of anterior shoulder instability. Cohort study; Level of evidence, 3. Data on all patients who were treated surgically for recurrent anterior shoulder instability between 2006 and 2011 were retrospectively collected at 4 medical centers. The minimum follow-up was 5 years. Data were retrieved from medical charts, and patients were interviewed to assess their level of satisfaction (range, 0-100), functional outcomes (using the American Shoulder and Elbow Surgeons shoulder score; the Subjective Shoulder Value; and the Disabilities of the Arm, Shoulder and Hand score), and quality of life (using the 12-Item Short Form Health Survey [SF-12]). Information on return to sports activities and postoperative level of activity compared with that of the preinjury state, complications, reoperations, and recurrent instability were recorded and evaluated. A total of 242 patients were included. The Latarjet procedure was performed in 27 shoulders, and ABR was performed in 215 shoulders. Patients in the ABR group had significantly higher rates of redislocation (18.5%; P = .05) and subluxation (21.4%; P = .43) but a lower rate of self-reported apprehension (43.0%; P = .05) compared with patients in the Latarjet group (3.7%, 14.8%, and 63.0%, respectively). There were 5 patients in the ABR group who underwent reoperation with the Latarjet procedure because of recurrent instability. The functional scores in the Latarjet group were better than those in the ABR group. The SF-12 physical score was significantly better in the Latarjet group than in the ABR group (98.1 vs 93.9, respectively; P = .01). Patient satisfaction and subjective scores were similar in both groups. These results support recently published data on the Latarjet procedure that showed its superiority over ABR in midterm stability (dislocations or subluxations). The contribution of self-reported apprehension to the broad definition of stability is not clear, and apprehension rates were not correlated with satisfaction scores or the recurrence of dislocation or subluxation.


Serum calcium levels in various lung diseases.
Calcium levels were determined in sera of patients suffering from various lung diseases. Healthy volunteers served as controls. Significant differences were found between the serum calcium levels of patients with active lung tuberculosis and those of controls (P less than 0.01). After treatment, serum calcium levels decrease to normal values in these patients. It was also found that there were significant differences in serum calcium levels of patients with primary lung carcinoma (P less than 0.01) and of patients with metastatic lung carcinoma as compared to controls (P less than 0.01). On the other hand, normal serum calcium levels were found in patients with pulmonary diseases with or without an infection. In conclusion, it seems likely that a combination of mechanisms plays a role in the pathogenesis of hypercalcaemia in pulmonary tuberculosis and primary and metastatic lung carcinoma.


The use of EEG theta biofeedback in the treatment of a patient with sleep-onset insomnia.
In this report, the treatment of a 42-year-old female with a complaint of chronic sleep-onset insomnia is described. Following the unsuccessful use of relaxation training, treatment consisted of 11 sessions of EEG theta rhythm (4--7 Hz) biofeedback. Theta density and five sleep indices were monitored throughout baseline, placebo, and treatment sessions. A significant increase in theta density was accompanied by reports of a decrease in sleep latency and an increase in total sleep time. This improvement was maintained after withdrawal of medication and at 3-month follow-up.


Analysis of free and total sulfur dioxide in wine by using a gas-diffusion analytical system with pH detection.
The use of sulfur dioxide as preservative in winemaking industry has a direct impact on wine quality. The standard methods to analyze this parameter require several processes and are time consuming. In this paper a simple and rapid analytical method for free and total sulfur dioxide detection is proposed. This method is based on the separation of the analyte from the sample with a permeable gas diffusion membrane and its indirect detection with a pH sensor. The system has been validated and optimized for free sulfur dioxide detection in the range of 1-60mgL-1 and for total sulfur dioxide in the range of 30-300mgL-1 with a limit of detection of 0.5mgL-1. Validation of the system has been carried out using a total of 70 samples of white and red wines and two standard methods, the Ripper and the Paul method. The obtained values have demonstrated a good agreement for both methods.


Total anomalous pulmonary venous connection: helical computed tomography as an alternative to angiography.
Echocardiographic evaluation of the pulmonary veins is inadequate at times. Cardiac catheterization, especially in sick neonates, may be a high-risk procedure. Helical computed tomography with three-dimensional reconstruction is noninvasive but remains an underutilized modality. Between January 2002 and February 2003, 7 computed tomography scans of children 3 weeks to 5 years of age were performed to evaluate the drainage of the pulmonary veins in suspected total anomalous venous drainage. Helical computed tomography (GE High speed Advantage) was performed using 2 mm sections, and rapid bolus hand injections of 2 ml/kg body-weight of nonionic intravenous contrast. Sagittal and coronal reformats, and three-dimensional reconstructions were performed, and reviewed by the radiologist. The findings were discussed with the pediatric cardiologist and surgeon involved in the case. The diagnoses included complex congenital heart disease (n = 5), isolated infradiaphragmatic total anomalous pulmonary venous connections (n = 1), and transposition of the great arteries with total anomalous pulmonary venous connections (n = 1). Cardiac computed tomography accurately demonstrated infradiaphragmatic total anomalous pulmonary venous connections in 4, and supracardiac drainage in 3 patients, in addition to the other cardiac findings. The findings on computed tomography scan correlated with surgical (n = 5) and/or angiographic findings (n = 2) in 7 patients. In sick, high-risk patients, cardiac computed tomography can be considered as an alternative to cardiac catheterization for the evaluation of pulmonary venous drainage.


Prospective evaluation of a regression-determined formula for use in triple procedure surgery.
A surgeon-specific regression equation was applied prospectively to determine the intraocular lens (IOL) power for use in 52 consecutive patients undergoing triple procedure surgery. At their final refraction, 85% (44/52) of these patients could see 20/40 or better. Upon comparing the preoperatively determined refractive goal with that actually obtained, an "ideal" IOL power which would have resulted in the refractive goal was determined. The IOL power selected by the regression formula was within 2 diopters (D) of the ideal IOL power in 67% (35/52) of the cases. For comparison, the power which would have been selected if the Sanders-Retzlaff-Kraff (SRK) or Binkhorst formula was used would have been within 2 D of the ideal IOL power in 62% (SRK, 32/52) and 58% (Binkhorst, 30/52) of the cases. Deviations from the ideal IOL power were predominantly in the undercorrected category for all three formulas evaluated. The authors conclude that even though a surgeon-specific regression formula relying on preoperative axial length performed fully as well as either the SRK or Binkhorst formulas, the choice of which formula to apply remains in the surgeon's hands.


A new tool, a better tool? Prevalence and performance of the International Diabetes Federation and the National Cholesterol Education Program criteria for metabolic syndrome in different ethnic groups.
We used a population based study in the Netherlands of 330 Hindustani Surinamese, 586 African Surinamese, and 486 ethnic Dutch (Dutch) to describe the prevalence of the metabolic syndrome (MS) and the association with differences in cardiovascular disease in and between ethnic groups. Fasting blood samples, blood pressure, and anthropometric measurements were obtained. MS was defined according to the criteria of the International Diabetes Federation (IDF) and the criteria of the National Cholesterol Education Program (NCEP). Cardiovascular disease was assessed by the Rose questionnaire and included questions on previous diagnoses of angina pectoris/myocardial infarction, cerebrovascular accident, intermittent claudication. The prevalence of MS (IDF and NCEP) was highest in Hindustani Surinamese men, followed by Dutch and African Surinamese men: 51.0%, 19.4%, and 31.2% (IDF), respectively. Among women, both the Hindustani and African Surinamese participants had a higher prevalence of MS (IDF and NCEP) than the Dutch. The association between the components, MS and cardiovascular disease differed between ethnic groups, in particular among men; OR for MS (NCEP) = 1.0 (0.4-2.7) among Hindustani Surinamese, OR = 4.9 (1.3-18.3) among African Surinamese, and OR = 2.8 (1.1-7.1) among Dutch. However, the differences in MS could not account for the ethnic differences in cardiovascular disease, regardless of the criteria used. The results suggest that, before the criteria can be used to guide practice, they may need to be changed and refined to take into account the differences between ethnic groups as well as the variations by gender.


Cholelithiasis in the Syrian population. A prospective study of 189 patients.
A prospective study of 189 Syrian patients with cholelithiasis was performed to throw light on some features of the disease in Syria. Early or emergency cholecystectomies were performed in 28 percent of all operations, whereas elective operations were carried out in the remaining patients. Explorations of the common bile ducts were performed in 34 patients, only 4 of whom had no stones. Wound and chest infections represented the most common postoperative complications. There was only one postoperative death, which was reportedly due to massive hemorrhage from esophageal varices. Analysis of the stones removed after cholecystectomies revealed that 72.4 percent were of mixed composition, 19.4 percent were pure cholesterol, and 8.2 percent were pigmented stones.


Determination of the effect of abiotic stress on the oxidative potential of edible potato tubers.
Stress factors occurring during the growing season and potato storage, can negatively affect the quality of tubers, including an increased tendency to enzymatic darkening. Abiotic stress due to water shortage is a major factor limiting agricultural production. The purpose of the study was to determine the effect of cultivation technology based on the use of biostimulant, hydrogel and irrigation as well as storage on the propensity to darkening and the content of sugars and organic acids. The results show that genotypic and technological variability in interaction with growing season conditions had a significant (p < 0.05) effect on the oxidative potential (OP) of potato tubers. The Denar cultivar, compared to the 'Gardena', was characterized by a lower tendency to enzymatic darkening. Application of biostimulant and hydrogel generally contributed to lowering the oxidative potential of the tested cultivars. The application of anti-stress agents had no effect on organic acid content. The long-term storage caused an increase in the content of total sugars (TS) (22%), reducing sugars (RS) (49%), chlorogenic acid (ACH) (11%), and loss of ascorbic acid (AA) (6%) in the tubers which contributed to an increase in the oxidative potential of potato tubers (16%). The correlation coefficients obtained (p < 0.05) confirm the dependence of OP on the concentration of organic acids.


Dynamic properties of cortical evoked (10 Hz) oscillations: theory and experiment.
Experiments probed the dynamic properties of stimulus-evoked (approximately 10 Hz) oscillations in somatosensory cortex of anesthetized rats. Experimental paradigms and statistical time series analysis were based on theoretical ideas from a dynamic approach to temporal patterns of neuronal activity. From the results of a double-stimulus paradigm we conclude that the neuronal response contains two components with different dynamics and different coupling to the stimulus. Based on this result a quantitative dynamic model is derived, making use of normal form theory for bifurcating vector fields. The variables used are abstract, but measurable, dynamic components. The model parameters capture the dynamic properties of neuronal response and are related to experimental results. A structural interpretation of the model can be given in terms of the collective dynamics of neuronal groups, their mutual interaction, and their coupling to peripheral stimuli. The model predicts the stimulus-dependent lifetime of the oscillations as observed in experiment. We show that this prediction relies on the basic concept of dynamic bistability and does not depend on the modeling details.


Are neurology residents in the United States being taught defensive medicine?
To study whether and how fear of litigation and defensive medicine are communicated during residency training and to assess whether this affects residents' attitudes. Neurology residents in the US (n=25) and, as a control group, Neurology residents training in Germany (n=42) were asked to rate multiple items regarding litigation, defensive strategies and how often these issues are raised by teaching physicians. Statistic analysis was performed using nonparametric tests. Residents in both countries indicated that litigation is an "important problem", although US residents stated this significantly more often (p<0.001). Initiation of tests motivated mainly by fear of litigation (p=0.004) and explicit teaching of defensive strategies by teaching physicians (p<0.02) were reported more often by US residents. Neurology residents in both the US and Germany perceive a litigational threat, but significantly less so in Germany. This difference may result at least in part from teaching of defensive strategies reported more often in US programs.


Galectin-3 is upregulated in microglial cells in response to ischemic brain lesions, but not to facial nerve axotomy.
We have recently demonstrated that the beta-galactoside-specific lectin galectin-3 is expressed by microglial cells in vitro, but not by normal resting microglia in vivo. In the present study, we have analyzed the expression of galectin-3 by microglia under traumatic conditions in vivo using two experimental rat models which substantially differ in the severity of lesion related to a breakdown of the blood-brain barrier (BBB) and the occurrence of inflammatory processes. These two features are absent after peripheral nerve lesion and present after cerebral ischemia. Here we show that, following facial nerve axotomy under conditions allowing (nerve anastomosis) or not subsequent regeneration (nerve resection), galectin-3 is not expressed by microglia in the corresponding facial nucleus 1-112 days after lesion. Galectin-3 is also absent in microglia at sites of a defective BBB in the normal brain, such as the circumventricular organs. Following experimental ischemia (i.e., permanent occlusion of the middle cerebral artery), in contrast, galectin-3 becomes strongly expressed by activated microglia as early as 48 hours after trauma, as determined by immunohistochemistry and Western blot analysis. Our findings suggest that the expression of galectin-3 by microglia in vivo correlates with the state of microglial activation.


Prognostic Value of Geriatric 8 and Identification of Seniors at Risk for Hospitalized Patients Screening Tools for Patients With Lung Cancer.
Because of the time-consuming aspect of geriatric assessments, cancer specialists are seeking shorter screening tools to distinguish fit and frail patients. We analyzed the predictive value of the Geriatric 8 (G8) and Identification of Seniors at Risk for Hospitalized Patients (ISAR-HP) in elderly patients with lung cancer. From January 2014 to April 2016, the data from patients with lung cancer aged > 70 years at 2 teaching hospitals in the Netherlands were included in a database. The patients were classified as potentially frail if they had a G8 of ≤ 14 or ISAR-HP of ≥ 2. Of the 142 included patients (median age, 77 years; interquartile range, 73-82 years), 108 (76%) were potentially frail. After correction for possible confounders, the potentially frail patients had a significantly greater risk of 1-year mortality (hazard ratio [HR], 4.08; 95% confidence interval [CI] 1.67-9.99; P = .02). Higher disease stage (HR, 1.72; 95% CI, 1.40-2.12; P < .001) was also a significant predictor of mortality; however, initial treatment (standard or otherwise) and age were not. When using both screening instruments separately, an impaired score on the G8 and higher disease stage were the variables remaining in the regression analyses (HR for impaired G8, 3.01; 95% CI, 1.35-6.72; P < .001). Patients with impaired scores on the ISAR-HP and G8 had more geriatric impairments than did patients with only an impaired G8 score. G8 screening is useful for the prognostication of elderly patients with lung cancer and could be used in combination with ISAR-HP to increase specificity at the cost of sensitivity. Using the ISAR-HP as the only screening tool would be insufficient.


Global trends in COVID-19 Alzheimer's related research: a bibliometric analysis.
The COVID-19 pandemic has significantly impacted public health, putting people with Alzheimer's disease at significant risk. This study used bibliometric analysis method to conduct in-depth research on the relationship between COVID-19 and Alzheimer's disease, as well as to predict its development trends. The Web of Science Core Collection was searched for relevant literature on Alzheimer's and Coronavirus-19 during 2019-2023. We used a search query string in our advanced search. Using Microsoft Excel 2021 and VOSviewer software, a statistical analysis of primary high-yield authors, research institutions, countries, and journals was performed. Knowledge networks, collaboration maps, hotspots, and regional trends were analyzed using VOSviewer and CiteSpace. During 2020-2023, 866 academic studies were published in international journals. United States, Italy, and the United Kingdom rank top three in the survey; in terms of productivity, the top three schools were Harvard Medical School, the University of Padua, and the University of Oxford; Bonanni, Laura, from Gabriele d'Annunzio University (Italy), Tedeschi, Gioacchino from the University of Campania Luigi Vanvitelli (Italy), Vanacore, Nicola from Natl Ctr Dis Prevent and Health Promot (Italy), Reddy, P. Hemachandra from Texas Tech University (USA), and El Haj, Mohamad from University of Nantes (France) were the authors who published the most articles; The Journal of Alzheimer's Disease is the journals with the most published articles; "COVID-19," "Alzheimer's disease," "neurodegenerative diseases," "cognitive impairment," "neuroinflammation," "quality of life," and "neurological complications" have been the focus of attention in the last 3 years. The disease caused by the COVID-19 virus infection related to Alzheimer's disease has attracted significant attention worldwide. The major hot topics in 2020 were: "Alzheimer' disease," COVID-19," risk factors," care," and "Parkinson's disease." During the 2 years 2021 and 2022, researchers were also interested in "neurodegenerative diseases," "cognitive impairment," and "quality of life," which require further investigation.


Estimates of Serial Interval and Reproduction Number of Sudan Virus, Uganda, August-November 2022.
We estimated the mean serial interval for Sudan virus in Uganda to be 11.7 days (95 CI% 8.2-15.8 days). Estimates for the 2022 outbreak indicate a mean basic reproduction number of 2.4-2.7 (95% CI 1.7-3.5). Estimated net reproduction numbers across districts suggest a marked spatial heterogeneity.


Dominant slowly progressive macular dystrophy.
Twenty-three members of one white family were studied for a new form of dominant slowly progressive macular dystrophy in which visual acuity remained good until the seventh decade. Ten patients had positive signs of this entity. Eight patients had possible early forms. Five had no signs. Several patients had visual acuity fluctuations, documented by their ophthalmologists who saw associated pigment epithelial alterations in some cases. Obvious macular changes included perifoveal pigment epithelial atrophy, posterior pole flecks, and fundus lesions resembling an atrophic form of senile macular degeneration. We suggest a possible hereditary predisposition to senile macular degeneration in our patients.


Effects on mitochondria of mitochondria-induced nitric oxide release from a ruthenium nitrosyl complex.
The ruthenium nitrosyl complex trans-[Ru(NO)(NH(3))(4)(py)](PF(6))(3) (pyNO), a nitric oxide (NO) donor, was studied in regard to the release of NO and its impact both on isolated mitochondria and HepG2 cells. In isolated mitochondria, NO release from pyNO was concomitant with NAD(P)H oxidation and, in the 25-100 microM range, it resulted in dissipation of mitochondrial membrane potential, inhibition of state 3 respiration, ATP depletion and reactive oxygen species (ROS) generation. In the presence of Ca(2+), mitochondrial permeability transition (MPT), an unspecific membrane permeabilization involved in cell necrosis and some types of apoptosis, was elicited. As demonstrated by externalization of phosphatidylserine and activation of caspase-9 and caspase-3, pyNO (50-100 microM) induced HepG2 cell death, mainly by apoptosis. The combined action of the NO itself, the peroxynitrite yielded by NO in the presence of reactive oxygen species (ROS) and the oxidative stress generated by the NAD(P)H oxidation is proposed to be involved in cell death by pyNO, both via respiratory chain inhibition and ROS levels increase, or even via MPT, if Ca(2+) is present.


Circular RNAs as biomarkers for lung cancer.
Lung cancer is the leading cause of death and morbidity from malignant neoplasms worldwide, and its poor prognosis places a heavy burden on patients. A large percentage of lung cancer cases are associated with smoking. A significant number of non-smokers also develop the disease, suggesting an epigenetic and genetic mechanism for the development of lung cancer. The current situation with the diagnosis and treatment of lung cancer remains grim, and effective therapeutic targets and molecular markers are urgently needed. Circular RNAs (circRNAs) are covalently closed non-coding RNAs that have received much attention due to their biological properties such as conservatism, stability, and tissue specificity. Many studies have shown that circRNAs are involved in the regulation of lung cancer through various mechanisms, such as microRNA adsorption, and play an important role in the early diagnosis, treatment, and prognosis of lung cancer. In recent years, it has become increasingly clear that circRNAs are involved in the proliferation, migration, and invasion of lung cancer cells. Differentially expressed circRNAs can be used as non-invasive diagnostic and prognostic markers of lung cancer. This article summarizes the current advances of circRNAs in the diagnosis, treatment and prognosis of lung cancer.


Neuroendocrine and proliferative potential of human intestinal cells during aging.
A population of neuroendocrine cells secreting chromogranin A was verified in the intestine of subjects aged over 60 years. The count of intestinal cells expressing chromogranin A and Ki-67 proliferation protein increases with aging. More intensive expression of chromogranin A and Ki-67 protein in senile age and in long-livers is presumably a compensatory mechanism aimed at the gastrointestinal function maintenance during its age-associated involution.


Role of phytocompounds as the potential anti-viral agent: an overview.
Viral diseases are the most notorious infective agent(s) causing morbidity and mortality in every nook and corner for ages; viruses are active in host cells, and specific anti-virus medicines' developments remain uncanny. In this century of the biological era, human viruses act predominantly as versatile spreaders. The infection of the present COVID-19 virus is up in the air; blithely, the integument of medicinal chemistry approaches, particularly bioactive derived phytocompounds could be helpful to control those human viruses, recognized in the last 100 years. Indeed, natural products are being used for various therapeutic purposes. The major bioactive phytocompounds are chemically containing coumarin, thiosulfonate, steroid, polysaccharide, tannin, lignin, proanthocyanidin, terpene, quinone, saponin, flavonoid, alkaloid, and polyphenol, that are documented for inhibitory action against several viral infections. Mostly, about 20-30% of plants from tropical or temperate regions are known to have some antiviral activity. This comprehensive analysis of bioactive-derived phytocompounds would represent a significant impact and might be helpful for antiviral research and the current state of viral treatments.


Outcomes of Standard Operating Procedures Instituted for Non-COVID Outpatient Department During COVID-19 Pandemic in Rural India.
COVID-19 has emerged as a major health care problem during 2020. The risk of infection and transmission led to imposition of a severe lockdown by the government. The diversion of health care machinery towards the control of transmission, treatment of the infected individuals led to a compromise in delivery of care towards non-COVID ailments. This is truer in rural and unapproachable areas where the health facilities were already in jeopardy. A prospective observational study was conducted from May 2020 to November 2020 at PGIMER satellite center, Sangrur. Standard operating procedures (SOP) were instituted for physical consultation during the COVID-19 pandemic at PGIMER satellite center, Sangrur, a branch of PGIMER, Chandigarh. These were approved by the committee constituted for this purpose. The effectiveness of these SOPs was reported as percentage of healthcare workers who contracted infection for non-COVID OPD. A total of 9963 patients attended the Out Patient Department (OPD). Male to female ratio of the patients was 1.2:1. Maximum (6141) consultations were sought for general physician followed by ophthalmologist (1464). Majority of the consultation were for benign non-communicable disorders. Seventy patients who visited the OPD were referred for COVID-19 testing as they had symptoms of infection. A total of 5 (3.8%) incidents of COVID-19 infection were reported among the healthcare workers at the center. The SOPs proved effective in the delivery of physical care with low occupational hazard to the healthcare workers (HCW).


Reduced bacterial adhesion to heparin-surface-modified intraocular lenses.
Bacterial adherence to intraocular lenses (IOLs) could be the cause of endophthalmitis following cataract surgery and lens implantation. There are previous reports that heparin bound to the surface of poly(methyl methacrylate) (PMMA) IOLs reduces cell adhesion. In this study, the in vitro adherence of Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa to regular PMMA IOLs and to heparin-surface-modified (HSM) PMMA IOLs was investigated. The three bacterial strains attached in significantly lower numbers to HSM-PMMA IOLs than to PMMA IOLs (P < .01). Heparin in solution also inhibited attachment of Staphylococcus epidermidis to regular PMMA IOLs. Heparin may reduce adherence by placing a highly hydrated layer between the bacteria and the IOL surface. Therefore, the use of HSM-PMMA IOLs could diminish the incidence of endophthalmitis.


The Drosophila learning and memory gene linotte encodes a putative receptor tyrosine kinase homologous to the human RYK gene product.
The linotte mutant was isolated on the basis of its learning and memory deficit. Interestingly, linotte individuals carrying a null mutation are viable, indicating that the linotte gene is not required for vital functions. We show here that the linotte gene encodes a putative receptor tyrosine kinase, homologous to the human protein RYK. These products are unique among receptor tyrosine kinases, since they possess a short extra cellular domain, and a modified intracellular catalytic domain. In particular, the subdomains directly involved in ATP binding and phosphotransfer reaction display remarkable variations. These results suggest that linotte is part of a novel signal transduction cascade involved in learning and memory.


Determination of biochemical species on electrophoresis chips with an external contactless conductivity detector.
Contactless conductivity measurements were found to be suitable for the direct detection, i.e., without needing any labels, of a range of biochemically relevant species, namely amino acids, peptides, proteins, immunoglobulin, and DNA. It was also possible to monitor the products of the enzymatic digestion of HSA with pepsin. Detection was carried out on bare electrophoresis chips made from poly(methyl methacrylate) by probing the conductivity in the channel with a pair of external electrodes, which are fixed on the chip holder. Separation efficiencies up to 15,000 plates could be obtained and LODs are in the low muM-range, except for immunoglobulin G (IgG) which could be determined down to 0.4 nM. Linear dynamic ranges of two to three orders of magnitude were obtained for the peptides as examples.


Complexity and spectral analysis of the heart rate variability dynamics for distant prediction of paroxysmal atrial fibrillation with artificial intelligence methods.
Paroxysmal atrial fibrillation (PAF) is a serious arrhythmia associated with morbidity and mortality. We explore the possibility of distant prediction of PAF by analyzing changes in heart rate variability (HRV) dynamics of non-PAF rhythms immediately before PAF event. We use that model for distant prognosis of PAF onset with artificial intelligence methods. We analyzed 30-min non-PAF HRV records from 51 subjects immediately before PAF onset and at least 45min distant from any PAF event. We used spectral and complexity analysis with sample (SmEn) and approximate (ApEn) entropies and their multiscale versions on extracted HRV data. We used that features to train the artificial neural networks (ANNs) and support vector machine (SVM) classifiers to differentiate the subjects. The trained classifiers were further tested for distant PAF event prognosis on 16 subjects from independent database on non-PAF rhythm lasting from 60 to 320 min before PAF onset classifying the 30-min segments as distant or leading to PAF. We found statistically significant increase in 30-min non-PAF HRV recordings from 51 subjects in the VLF, LF, HF bands and total power (p<0.0001) before PAF event compared to PAF distant ones. The SmEn and ApEn analysis provided significant decrease in complexity (p<0.0001 and p<0.001) before PAF onset. For training ANN and SVM classifiers the data from 51 subjects were randomly split to training, validation and testing. ANN provided better results in terms of sensitivity (Se), specificity (Sp) and positive predictivity (Pp) compared to SVM which became biased towards positive case. The validation results of the ANN classifier we achieved: Se 76%, Sp 93%, Pp 94%. Testing ANN and SVM classifiers on 16 subjects with non-PAF HRV data preceding PAF events we obtained distant prediction of PAF onset with SVM classifier in 10 subjects (58+/-18 min in advance). ANN classifier provided distant prediction of PAF event in 13 subjects (62+/-21 min in advance). From the results of distant PAF prediction we conclude that ANN and SVM classifiers learned the changes in the HRV dynamics immediately before PAF event and successfully identified them during distant PAF prognosis on independent database. This confirms the reported in the literature results that corresponding changes in the HRV data occur about 60 min before PAF onset and proves the possibility of distant PAF prediction with ANN and SVM methods.


Sexual Trauma Screening for Men and Women: Examining the Construct Validity of a Two-Item Screen.
The Veterans Health Administration (VHA), the largest integrated healthcare system in the United States, has conducted universal screening for military sexual trauma (MST) to facilitate MST-related care since 2002. VHA defines MST as sexual assault or repeated, threatening sexual harassment that occurred during military service. Evidence of construct validity, the degree to which the screen is measuring what it purports to measure (i.e., MST), was examined using the 23-item Sexual Experiences Questionnaire-Department of Defense (SEQ-DoD). Results showed individuals who endorsed no SEQ-DoD items screened MST negative. Those who had experienced more SEQ-DoD behaviors with greater frequency, and across all four SEQ-DoD domains, were more likely to screen MST positive. Findings were similar for men and women. These findings contribute to the validity evidence for the VHA MST screen.


Outcomes and reliability of the flow coupler in postoperative monitoring of head and neck free flaps.
To assess the accuracy and reliability of the flow coupler relative to the implantable arterial Doppler probe in postoperative monitoring of head and neck free flaps. Retrospective single-institution study, April 2015 to March 2017. Both the venous flow coupler and arterial Doppler were employed in 120 consecutive head and neck free flap cases. When Doppler signal loss occurred, flaps were evaluated by physical exam to determine whether signal loss was a true positive necessitating operating room takeback. Sensitivity, specificity, and false positive rate (FPR) were recorded for each device. Logistic regression was conducted to identify user trends over time. Eleven of 120 patients (9.2%) required takeback, 10 from venous thrombosis and one from arterial thrombosis. Permanent signal loss (PSL) occurred in the flow coupler in all takebacks; PSL occurred in the arterial Doppler only in the case of arterial thrombosis. Salvage rate was 9/11 (81.8%). For the flow coupler, sensitivity was 100%, specificity 86.4%, and FPR 13.6%. For the arterial probe, sensitivity was 9.1%, specificity 97.1%, and FPR 2.9%. A 4.1% decrease in false positives with each additional flow coupler use was observed. Monitoring the vein via flow coupler has high sensitivity in identifying vascular compromise compared to the arterial probe, especially for venous thrombosis. There is moderate FPR; this decreases with increased usage and, when supplemented with physical examination, does not result in unnecessary takebacks. The flow coupler can be a valuable tool in postoperative monitoring of head and neck free flaps. 4. Laryngoscope, 128:812-817, 2018.


A multi-parametric workflow for the prioritization of mitochondrial DNA variants of clinical interest.
Assigning a pathogenic role to mitochondrial DNA (mtDNA) variants and unveiling the potential involvement of the mitochondrial genome in diseases are challenging tasks in human medicine. Assuming that rare variants are more likely to be damaging, we designed a phylogeny-based prioritization workflow to obtain a reliable pool of candidate variants for further investigations. The prioritization workflow relies on an exhaustive functional annotation through the mtDNA extraction pipeline MToolBox and includes Macro Haplogroup Consensus Sequences to filter out fixed evolutionary variants and report rare or private variants, the nucleotide variability as reported in HmtDB and the disease score based on several predictors of pathogenicity for non-synonymous variants. Cutoffs for both the disease score as well as for the nucleotide variability index were established with the aim to discriminate sequence variants contributing to defective phenotypes. The workflow was validated on mitochondrial sequences from Leber's Hereditary Optic Neuropathy affected individuals, successfully identifying 23 variants including the majority of the known causative ones. The application of the prioritization workflow to cancer datasets allowed to trim down the number of candidate for subsequent functional analyses, unveiling among these a high percentage of somatic variants. Prioritization criteria were implemented in both standalone ( http://sourceforge.net/projects/mtoolbox/ ) and web version ( https://mseqdr.org/mtoolbox.php ) of MToolBox.


CT, MR, and CEUS imaging features of recurrent GIST of the pre-sacral space: A case report.
We present the case of a 50-year-old woman affected by a rectal gastrointestinal stromal tumor (GIST), with a recurrence in pre-sacral and pre-coccygeal space after surgery and Imatinib therapy. GISTs are the most common mesenchymal tumors of the gastrointestinal tract and rectal GISTs are rare (only 2% of cases); magnetic resonance and computed tomography are the main imaging techniques for diagnosis and follow-up, while ultrasound and contrast-enhanced ultrasound may be useful to perform a percutaneous biopsy, as in the case presented: the imaging features of the lesion in all these imaging methods are displayed.


HRSBallast: A high-resolution dataset featuring scanned angular, semi-angular and rounded railway ballast.
A high-resolution dataset of digitally scanned railway ballast (HRSBallast) is presented, consisting of 108 individual, digitised samples. The ballast samples were sourced from both a railway test track section located on a heavy haul coal export line in South Africa and a local quarry. The sampled ballast from the field installation represent angular, semi-angular and rounded geometric features depending on the sampled location. The fresh ballast sourced from the quarry was iteratively tested using a hydraulic actuator in a small-scale box test which forms part of a separate research project. The ballast samples were scanned before and after every test to ascertain the changes in geometry, in addition to the loss of material due to attrition. The field and laboratory samples were digitised using a high-resolution, commercial (Visual Simultaneous Localization and Mapping) VSLAM-based scanner with a 40-micrometre accuracy. Samples which were fractured by the hydraulic actuator are also included in the dataset. HRSBallast serves as a reference dataset for granular media (GM) simulations utilizing DEM (discrete element method), degradation or wear modelling, digital assets for the creation of synthetic datasets for deep learning applications, embedded railway instrumentation and video games requiring high-resolution geometry.


International consensus statement on allergy and rhinology: rhinosinusitis 2021.
I. BACKGROUND: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR-RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR-RS-2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence-based findings of the document. ICAR-RS presents over 180 topics in the forms of evidence-based reviews with recommendations (EBRRs), evidence-based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. ICAR-RS-2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence-based management algorithm is provided. This ICAR-RS-2021 executive summary provides a compilation of the evidence-based recommendations for medical and surgical treatment of the most common forms of RS.


Immunophenotypic expression by flow cytometric analysis of cocultured skeletal muscle and bone marrow mesenchymal stem cells for therapy into myocardium.
The product generated by skeletal muscle and bone marrow mesenchymal stem cell cocultures has been demonstrated to improve the functional outcomes after cell therapy in postinfarction or Chagas myocardiopathy. This coculture method allows cell interactions in vitro, diminishing the operational costs of the culture/expansion as well as leading to angiogenesis and myogenesis for regeneration of the injured heart. Flow cytometric analysis may better characterize the cellular types in this model. Our objective was to use flow cytometry to analyze the immunophenotype expressed in this coculture model. The coculture was performed in accordance with Carvalho for 21 days. Flow cytometry was performed before and after coculture to characterize the immunophenotypic profile of cellular subsets, namely, the surface markers CD31, CD34, CD44H, CD45, CD49d, CD54, CD73, CD90, CD105, CD106, Myo-D, M-cadherin, and Connexin-43. Statistics were performed by the nonparametric Friedman test (P < .05) with post-hoc analysis by the nonparametric Wilcoxon test (P < or = .017, Bonferroni correction). The results demonstrated statistical significance for CD45(+) in 89.49% of mononuclear cells, 3.58% in skeletal muscle cells, and 4.74% among cocultured cells (P = .0094); and CD90(+) in 36.18% of mononuclear cells, 6.01% in skeletal muscle cells, and 48.94% among cocultured cells (P = .0420). The cocultured cells expressed the markers CD73(++), CD90(+++), CD45(-), CD34(+), CD105(-/+), CD106(-/+), M-cadherin(-/+), and Connexin-43(-/+). In conclusion, flow cytometric analysis showed a heterogeneous adherent cell population in this coculture model.


Complete, reversible, drug-specific tolerance to stimulation of locomotor activity by caffeine.
The development of tolerance to caffeine-induced stimulation of locomotor activity was evaluated in rats maintained chronically on average daily doses of 160 mg/kg or more of caffeine by the method of scheduled access to drinking water containing the drug. Dose-response curves were determined for caffeine (6.25-100 mg/kg) and d-amphetamine (0.39-6.4 mg/kg) during chronic drug treatment. In addition, the caffeine curve was redetermined 2-3 weeks after removal of the drug from the drinking water. A control group that had scheduled access to drug-free tap water was also tested. Caffeine produced dose-related increases in the locomotor activity of the controls but failed to modify locomotor activity of the chronic caffeine group. In contrast, d-amphetamine increased locomotor activity of both groups comparably. Spontaneous locomotor of the chronic caffeine group was reduced significantly for 4 days after drug-free tap water was substituted for the caffeine solution. The return of spontaneous locomotor activity to baseline values was associated with restored sensitivity to caffeine-induced stimulation of locomotor activity. Thus, chronic administration of caffeine to rats results in the development of tolerance to caffeine-induced stimulation of locomotor activity that is virtually complete, pharmacologically specific, and fully reversible when drug treatment is stopped. Decreases in spontaneous locomotor activity after abrupt termination of chronic caffeine administration follow a time course consistent with a drug withdrawal syndrome.


Drug classification with a spectral barcode obtained with a smartphone Raman spectrometer.
Measuring, recording and analyzing spectral information of materials as its unique finger print using a ubiquitous smartphone has been desired by scientists and consumers. We demonstrated it as drug classification by chemical components with smartphone Raman spectrometer. The Raman spectrometer is based on the CMOS image sensor of the smartphone with a periodic array of band pass filters, capturing 2D Raman spectral intensity map, newly defined as spectral barcode in this work. Here we show 11 major components of drugs are classified with high accuracy, 99.0%, with the aid of convolutional neural network (CNN). The beneficial of spectral barcodes is that even brand name of drug is distinguishable and major component of unknown drugs can be identified. Combining spectral barcode with information obtained by red, green and blue (RGB) imaging system or applying image recognition techniques, this inherent property based labeling system will facilitate fundamental research and business opportunities.


Sudden Unexpected Death Caused by Cardiac Metastasization from Histiocytic Sarcoma.
Haematological malignancies, such as lymphoma and leukaemia, can have a variety of clinical manifestations. The most frequent cause of death from haematological malignancies is multiple organ failure due to neoplastic organ infiltration and/or septic shock. Histiocytic sarcoma (HS) is a rare malignant nodal or extranodal tumour with histiocytic immunophenotype that originates from a lymphohematopoietic precursor. The patients with HS usually have a poor prognosis due to its aggressive clinical behaviour. Rare cases of undiagnosed sudden HS death have been described in the literature. A forensic autopsy of a 46-year-old white male who died at home suddenly and unexpectedly without warning conditions or known diseases. Gross analysis, histology and toxicology were also performed. The diagnosis of HS of the ileum with secondary nodal and cardiac metastatization was made. A prompt diagnosis of HS in life is paramount because it can make a difference in prognostic outcomes.


Conservative Treatment and Unfavorable Factors to Bone Healing of "Pre-lysis"-Stage Lumbar Spondylolysis in Adolescents.
Retrospective cohort study. To evaluate the clinical outcomes of the conservative treatment of "pre-lysis"-stage lumbar spondylolysis. With the widespread use of magnetic resonance imaging (MRI) for early diagnosis of lumbar spondylolysis, a new disease stage called pre-lysis has emerged, in which intensity change is observed only on MRI without a fracture line on computed tomography. This study aimed to evaluate the clinical outcomes and factors unfavorable to bone healing of the conservative treatment of pre-lysis-stage lumbar spondylolysis. Fifty-three patients with 57 fresh pre-lysis-stage lesions who had completed conservative treatment were included in the study (40 men, 13 women; mean age, 14.3 years). We investigated the rate of bone healing and the relationship between bone healing after conservative therapy and factors such as age, sex, vertebral level, unilateral/bilateral lesions, and presence of spina bifida occulta. The overall bone healing rate was 95% (54/57 lesions). Bilateral lesions had a significantly lower bone healing rate than unilateral lesions (86% vs. 100%, p=0.046). There were no statistically significant differences based on age, sex, vertebral level, or presence of spina bifida occulta. The bone healing rate in unilateral lesions was 100%, which was significantly higher than that in bilateral lesions. It is important to detect and initiate treatment while the lesion is still unilateral, if possible.


Shockwave™ Lithoplasty in Combination With Atherectomy in Treating Severe Calcified Femoropopliteal and Iliac Artery Disease: A Single-Center Experience.
Calcium is a predictor of poor outcome in the treatment of infrainguinal arterial disease. Rotational atherectomy can effectively debulk atherosclerotic calcium but is less likely to significantly modify medial and adventitial calcinosis. Shockwave IVL provides circumferential sonic pressure waves capable of disrupting deeper calcium and theoretically complements the debulking process of atherectomy. We present acute and intermediate outcome data from patients with severe femoral or iliac artery calcified disease treated with the combination of rotational atherectomy and Shockwave IVL at a single center. This is a retrospective study of prospectively collected data on rotational atherectomy (Jetstream (Boston Scientific) and orbital atherectomy (CSI)) from a single operator at a single center with core laboratory analysis of angiographic imaging. All patients that received the combination treatment of rotational atherectomy and Shockwave IVL were included in this study. Patient follow-up was done from medical records with data extracted by an experienced research coordinator. Primary safety endpoint was freedom from major adverse events including major dissection (NHLBI C or higher), perforation, distal embolization, or major amputation defined as amputation above the ankle. Primary effectiveness endpoint was procedural success (≤ 30% residual at end of procedure). 23/24 (95.8%) patients were treated with drug coated balloons (DCB) post combination therapy. Secondary endpoint on follow-up was target lesion revascularization (TLR). A total of 24 patients were included. Mean age was 70.7 ± 9.9 years. Lesions were in the femoropopliteal 79.1%, common femoral 12.5% and iliac 8.3% arteries. 87.0% were claudicants and 58.3% diabetics. Chronic total occlusion was 12.5%, severe calcium 100%, lesion length 84.5 ± 37.1 mm, baseline stenosis 57.1 ± 18.9% and baseline minimal luminal diameter (MLD) 2.2 ± 1.1 mm. Patients were treated with Jetstream (n = 19) or Orbital (n = 5) atherectomy. Embolic filter was used in 58.3% of cases. Post atherectomy stenosis was 36.4 ± 17.5%, post adjunctive IVL 21.1 + 15.7%, and final stenosis 13.0 ± 10.9%. Bailout stenting was 4.6% and primary stenting 13.6% (total stenting rate 18.2%). Final MLD was 4.7 ± 0.8 mm, resulting in an acute gain of 2.5 mm. No infrapopliteal embolization or amputation was noted. At a mean follow up of 591.4 ± 175.2 days, 2 patients died (unrelated to procedure or device). Target lesion revascularization (TLR) at 12 months occurred in 2 patients or 2/22 (9%). At 18-month of follow up TLR occurred in 7/22 (31%) patients. The combination of atherectomy and shockwave IVL followed by adjunctive DCB is safe and appears to be effective in treating severe calcified disease with acceptable TLR on long term follow-up in a population of severe femoropopliteal disease.


Residual quadrupole interaction in brain and its effect on quantitative sodium imaging.
Sodium MRI is particularly interesting given the key role that sodium ions play in cellular metabolism. To measure concentration, images must be free from contrast unrelated to sodium density. However, spin 3/2 NMR is complicated by more than rapid biexponential signal decay. Residual quadrupole interactions (described by frequency ωQ) can reduce Mxy development during RF excitation. Three experiments, each performed on the same four healthy volunteers, demonstrate that residual quadrupole interactions are of concern in quantitative sodium imaging of the brain. The first experiment shows a reliable increase in the rate of excitation 'flipping' (1%-6%), particularly in white matter with tracts running superior-inferior (i.e. parallel to B0). Increased flip-rates imply an associated signal loss and are to be expected when ωQ ~ ω1. The second experiment shows that a prescribed flip-angle decrease from 90° to 20°, with concomitant decrease in TE from 0.25 ms to 0.10 ms and no T1 weighting, results in a 14%-26% saline calibration phantom normalized signal (SN) increase in the white matter regions. The third experiment shows that this (SN) increase is primarily due to a residual quadrupole effect, with a small contribution from T2 weighting. There is an observed deviation from the spin 3/2 biexponential curve, also suggesting ωQ dephasing. Using simulation to explain the results of all three experiments, a model of brain tissue is hypothesized. It includes one pool (50%) with ωQ = 0, and another (50%) in which ωQ has a Gaussian distribution with a standard deviation of 625 Hz. Given the result of the second experiment, it is suggested that the use of reduced flip-angles with large ω1 will provide more accurate measures of sodium concentration than 'standard' methods using 90° pulses. Alternatively, further study of sodium ωQmay provide a means to explore tissue structure and organization.


Variable behavioural phenotypes of patients with monosomies of 15q26 and a review of 16 cases.
Patients with trisomy or tetrasomy of distal 15q show a recognizable overgrowth syndrome, whereas patients with a monosomy of 15q26 share some degree of pre- and postnatal growth retardation, but differ with respect to facial and skeletal dysmorphisms, congenital heart disease and intellectual development. By reviewing 16 cases with losses of 15q26 we found that the size of the deletion was also not a predictor of the breadth of the phenotypic spectrum, the severity of disease or prognosis of the patient. Although monosomies of 15q26 do not represent a classical contiguous gene syndrome, a few candidate genes for selected features such as proportional growth retardation and cardiac abnormalities have been identified. In 11 out of 16 patients with monosomy of distal 15q variable neurobehavioral phenotypes, including learning difficulties, seizures, attention-deficit-hyperactivity disorder, hearing loss and autism, have been found. We discuss clinical ramifications for cases with a loss of 15q26 detected by prenatal array-CGH.


Morphological and molecular characteristics of Milandanielia intermedia (Feider, 1950) (Trombidiformes: Microtrombidiidae) with data on its biology and ecology.
Milandanielia intermedia (Feider, 1950) is re-described. A female from which larvae were obtained by experimental rearing is designated as neotype. Verified diagnoses of active life instars are supplemented with data on habitat preferences, phenology and life cycle. Molecular identification of the species based on its COI sequence is provided.


Osteoresorptive arsenic intoxication.
A 47-year-old woman consulted her dermatologist complaining whole body dermatitis, urticaria and irritating bullous eruptions on the plantar and side surfaces of her feet. She had had multiple hypopigmented spots on her skin since her early adulthood. The patient was treated with topical medication without significant improvement of symptoms. One year later she suffered a myocardial infarction, accompanied by refractory anaemia. At the age of 49, a breast cancer was diagnosed and shortly thereafter her last menstruation occurred. At age 50years, upon complaint of weight loss despite normal food intake, Hashimoto thyroiditis with latent hyperthyroidism, vitamin D insufficiency with secondary hyperparathyroidism, and poikilocytic anaemia with anisochromia, hypochromia, anisocytosis, elliptocytes, drepanocytes, dacryocytes, acanthocytes, echinocytes, schizocytes, stomatocytes and target cells were diagnosed. The osteodensitometric and laboratory examinations revealed osteoporosis with sustained elevation of urinary Dipyridinolin-crosslinks (u-Dpd), and urinary arsenic (u-As) of 500μg/l (equivalent to 0.5 parts per million-ppm, 2.5μg/mg creatinine/dl, u-As: Phosphate of 26μg/mmol; the estimated bone As:P and As/kg body weight were 500μg/g and 11.3mg/kg, respectively). Thalassemia, immunoglobinopathy and iron deficiency were excluded. Supplementation with oral vitamin D and calcium, and antiresorptive therapy with intravenous zolendronate normalised the u-Dpd, significantly decreased the urinary arsenic concentration, and cured the anemia and the urticaria. A diagnosis of osteoresorptive arsenic intoxication (ORAI) was established.


Relationships of leaf diffusion resistance of Populus clones to leaf water potential and environment.
Leaf diffusion resistance (r 1) of the upper and lower leaf surfaces of several Populus clones was related to leaf water potential (ψ1), light intensity, vapor pressure deficit (VPD), and temperature by intrinsicallylinear, logarithmic multiple regression analyses. Regression equations accounted for up to 80% of variation in r 1 data. Light intensity and VPD varied among clones in importance in influencing r 1. Pronounced sensitivity of r 1 of certain clones to VPD was related to drought resistance in their parentage. Increasing r 1 was significantly positively correlated with ψ1, in apparent contradiction to prevailing concepts of stomatal response to water status, and this relationship was probably attributable to effects of other environmental variables on ψ1 and r 1. Leaf resistance decreased after a storm characterized by winds in excess of 160 km·h-1. Cuticular disruption and altered stomatal response may have been responsible for the storminduced r 1 decrease.


Cell type specific expression of secretory TFF peptides: colocalization with mucins and synthesis in the brain.
The "TFF domain" is an ancient cysteine-rich shuffled module forming the basic unit for the family of secretory TFF peptides (formerly P-domain peptides and trefoil factors). It is also an integral component of mosaic proteins associated with mucous surfaces. Three mammalian TFF peptides are known (i.e., TFF1-TFF3); however, in Xenopus laevis the pattern is more complex (xP1, xP4.1, xP4.2, and xP2). TFF peptides are typical secretory products of a variety of mucin-producing epithelial cells (e.g., the conjunctiva, the salivary glands, the gastrointestinal tract, the respiratory tract, and the uterus). Each TFF peptide shows an unique expression pattern and different mucin-producing cells are characterized by their specific TFF peptide/secretory mucin combinations. TFF peptides have a pivotal role in maintaining the surface integrity of mucous epithelia in vivo. They are typical constituents of mucus gels, they modulate rapid mucosal repair ("restitution") by their motogenic and their cell scattering activity, they have antiapoptotic effects, and they probably modulate inflammatory processes. Pathological expression of TFF peptides occurs as a result of chronic inflammatory diseases or certain tumors. TFF peptides are also found in the central nervous system, at least in mammals. In particular, TFF3 is synthesized from oxytocinergic neurons of the hypothalamus and is released from the posterior pituitary into the bloodstream.


Preparation and properties of inhalable nanocomposite particles: effects of the size, weight ratio of the primary nanoparticles in nanocomposite particles and temperature at a spray-dryer inlet upon properties of nanocomposite particles.
Nanoparticles are expected to be applicable to inhalation as carrier but there exist disadvantages because of their size. Their deposition dose to the lung will be small. To overcome this problem and utilize nanoparticles for inhalation, we have prepared nanocomposite particles as drug carriers targeting lungs. The nanocomposite particles are prepared as drug-loaded nanoparticles-additive complex to reach deep in the lungs and to be decomposed into nanoparticles when they deposit into lung. In this study, we examined the effect of preparation condition--inlet temperature, size of primary nanoparticles and weight ratio of primary nanoparticles--on the property of nanocomposite particles. When the size of primary nanoparticles was 400 nm and inlet temperature was 90 degrees C, only the nanocomposite particles containing between 45 and 55% of primary nanoparticles could be decomposed into nanoparticles in water. On the other hand, when the inlet temperature was 80 degrees C, nanocomposite particles were decomposed into nanoparticles independent of the weight ratio of primary nanoparticles. Also, the aerodynamic diameter of the nanocomposite particles was between 1.5 and 2.5 microm, independent of the weight ratio of primary nanoparticles. When the size of primary nanoparticles was 200 nm and inlet temperature was 70 degrees C, nanocomposite particles were decomposed into nanoparticles independent of the weight ratio of primary nanoparticles. Also, the aerodynamic diameters of them were almost 2.0 microm independent of the weight ratio of primary nanoparticles. When the nanocomposite particles containing nanoparticles with the size of 200 nm are prepared at 80 degrees C, no decomposition into nanoparticles was observed in water. Fine particle values, FPF, of the nanocomposite particles were not affected by the weight ratio of primary nanoparticles when they were prepared at optimum inlet temperature.


Supporting the return to work of breast cancer survivors: perspectives from Canadian employer representatives.
PUR POSE: A significant proportion of women with breast cancer want to RTW (return to work) after treatment. Employers play a key role in facilitating RTW for these employees who face distinct challenges. However, the portrait of these challenges remains to be documented from the perspective of employer representatives. The purpose of this article is to describe the perceptions of Canadian employer representatives regarding the management of the RTW of BCSs (breast cancer survivors). Thirteen qualitative interviews were conducted with representatives from businesses of various sizes (< 100 employees, 100-500 employees, > 500 employees). Transcribed data were subjected to iterative data analysis. Three major themes emerged to describe employer representatives' perceptions of managing RTW of BCS. These are (1) providing tailored support; (2) remaining 'human' while managing RTW; and (3) facing the challenges of RTW management after breast cancer. The first two themes were perceived as facilitating RTW. The challenges identified concern uncertainty, communication with the employee, maintaining a supernumerary work position, balancing employee and organizational interests, reconciling with colleagues' complaints, and collaboration among stakeholders. Employers can adopt a humanistic management style by offering flexibility and increased accommodation for BCS who RTW. They can also be more sensitive to this diagnosis, leading some to seek more information from those around them who have experienced it. Employers require increased awareness about diagnosis and side effects, be more confident to communicate, and improved collaboration between stakeholders to facilitate the RTW of BCS. Employers who focus on the individual needs of cancer survivors during RTW can facilitate creative and personalized solutions for a sustainable RTW and help survivors recover their lives after cancer.


Plugging in to Human Memory: Advantages, Challenges, and Insights from Human Single-Neuron Recordings.
We describe single-neuron recordings in the human hippocampal formation, performed in epileptic patients for clinical reasons, and highlight their advantages, challenges, and limitations compared with non-invasive recordings in humans and invasive recordings in animals. We propose a unified framework to explain different findings-responses to novel stimuli, spatial locations, and specific concepts-linking the rodent and human literature regarding the function of the hippocampal formation. Moreover, we propose a model of how memories are encoded in this area, suggesting that the context-independent, invariant coding by concept cells may provide a uniquely human neural mechanism underlying memory representations.


Tooth extraction without discontinuation of oral antithrombotic treatment: A prospective study.
To identify which variable, among those related to surgeries, to patients, or to antithrombotic treatments, could be considered as a bleeding indicator, and to analyze effectiveness of the local hemostatic protocols used, incidence of bleeding and healing index, depending on the number of extracted teeth, and patient antithrombotic treatment. Patients who underwent tooth extractions without interruption or reduction of antithrombotic treatment were prospectively followed. The exact two-tailed Fisher test was used to investigate the relationship between presence/absence of bleeding and type of hemostatic material. The effect of variables on the probability of bleeding and healing index was assessed by means of a multivariate logistic regression. Two hundred and fifty-four procedures were analyzed. The incidence of bleeding was 15.75%. Severe bleeding occurred in only 6 patients (2.34%). The number of involved dental quadrants and pre-surgical antibiotic treatments were found to be positively related with bleeding. The use of vasoconstrictors during surgery resulted in a reduction of healing index scores. Tooth extractions in patients on antithrombotic treatment were found to be free from significant bleeding although the involvement of more than 1 quadrant in the same procedure should be avoided.


Purpura with regular shape in an adolescent: Beware of dermatitis artefacta.
Purpura is common in pediatric patients, mostly diagnosed as IgA-related vasculitis (Henoch-Schönlein purpura), idiopathic thrombocytopenic purpura (ITP), and thrombotic thrombocytopenic purpura (TTP). However, in some cases, for example, cases with dermatitis artefacta, it could puzzle a physician or pediatrician for a long time, with great challenges in diagnosis. We present the case of a 13-year-old boy with recurrent painful purpura on both upper limbs. The physical exam was unremarkable, except for right blepharoptosis and scars from burns. The diagnostic tests were normal. Through repeated communication, the patient was finally diagnosed as having dermatitis artefacta, accompanied by underlying psychological problems. Before dermatitis artefacta was diagnosed, we spent a lot of money and effort on the diagnosis. Therefore, in order to determine the diagnosis as soon as possible and save on unnecessary medical expenses, we propose a rapid process for the diagnosis of purpura of dermatitis artefacta in children.


Failure in neuroprotection of remote limb ischemic postconditioning in the hippocampus of a gerbil model of transient cerebral ischemia.
Remote ischemic postconditioning (RIPoC) has been proven to provide potent protection of the heart and brain against ischemia-reperfusion injury. However, despite the evidence of cerebral protection with RIPoC is compelling, RIPoC-mediated neuroprotection against transient cerebral ischemic insult is still mired in controversy. In this study, we examined the effect of RIPoC induced by sublathal transient hind limb ischemia on neuronal death in the hippocampus following 5 min of transient cerebral ischemia in gerbils. Animals were randomly assigned to sham-, ischemia-, sham plus (+) RIPoC- and ischemia+RIPoC-groups. RIPoC was induced by three cycles of 5-min and 10-min occlusion-reperfusion of both femoral arteries at predetermined points in time (0, 1, 3, 6, 12 and 24h after transient cerebral ischemia). CV staining, F-J B histofluorescence staining and NeuN immunohistochemistry were carried out to examine neuroprotection in the RIPoC-mediated hippocampus 5 days after ischemia-reperfusion. In the ischemia-group, we found a significant loss of pyramidal cells in the stratum pyramidale (SP) of the hippocampal CA1 region at 5 days post-ischemia compared with the sham-group. In all of the ischemia+RIPoC-groups, the loss of pyramidal cells in the CA1 region at 5 days post-ischemia was not different from that in the ischemia-group. Our present findings indicate that RIPoC does not prevent hippocampal CA1 pyramidal cells from neuronal death induced by transient cerebral ischemia.


MutSβ promotes trinucleotide repeat expansion by recruiting DNA polymerase β to nascent (CAG)n or (CTG)n hairpins for error-prone DNA synthesis.
Expansion of (CAG)•(CTG) repeats causes a number of familial neurodegenerative disorders. Although the underlying mechanism remains largely unknown, components involved in DNA mismatch repair, particularly mismatch recognition protein MutSβ (a MSH2-MSH3 heterodimer), are implicated in (CAG)•(CTG) repeat expansion. In addition to recognizing small insertion-deletion loop-outs, MutSβ also specifically binds DNA hairpin imperfect heteroduplexes formed within (CAG)n•(CTG)n sequences. However, whether or not and how MutSβ binding triggers expansion of (CAG)•(CTG) repeats remain unknown. We show here that purified recombinant MutSβ physically interacts with DNA polymerase β (Polβ) and stimulates Polβ-catalyzed (CAG)n or (CTG)n hairpin retention. Consistent with these in vitro observations, MutSβ and Polβ interact with each other in vivo, and colocalize at (CAG)•(CTG) repeats during DNA replication. Our data support a model for error-prone processing of (CAG)n or (CTG)n hairpins by MutSβ and Polβ during DNA replication and/or repair: MutSβ recognizes (CAG)n or (CTG)n hairpins formed in the nascent DNA strand, and recruits Polβ to the complex, which then utilizes the hairpin as a primer for extension, leading to (CAG)•(CTG) repeat expansion. This study provides a novel mechanism for trinucleotide repeat expansion in both dividing and non-dividing cells.


Modulation of cell-mediated cytotoxicity function after alteration of fatty acid composition in vitro.
Fatty acids incorporated into cytotoxic T lymphocytes (CTL) during in vitro stimulation can enhance or inhibit the subsequent expression of cell-mediated cytotoxicity, depending on the class of fatty acid. Unsaturated fatty acids enhance cytolysis, whereas saturated fatty acids inhibit it. The effects of fatty acids on cytolysis can be mediated in the absence of cell division, thus eliminating relative clonal amplification or contraction as a basis for the observed effects. Nevertheless, the net result of fatty acid alteration is an increase (unsaturated fatty acids) or decrease (saturated fatty acids) in the frequency, in the treated immune population, of CTL capable of lysing target cells. These observations are best explained by a model in which fatty acid incorporated into cell membrane phospholipids results in a direct recruitment into or out of the pool of CTL within the immune population capable of lysing target cells under the conditions employed to assay cytotoxicity.


[Analyzing the coronary heart disease mortality decline in a Mediterranean population: Spain 1988-2005].
To examine the extent to which the decrease in coronary heart disease mortality rates in Spain between 1988 and 2005 could be explained by changes in cardiovascular risk factors and by the use of medical and surgical treatments. We used the previously validated IMPACT model to examine the contributions of exposure factors (risk factors and treatments) to the main outcome, changes in the mortality rates of death from coronary heart disease, among adults 35 to 74 years of age. Main data sources included official mortality statistics, results of longitudinal studies, national surveys, randomized controlled trials, and meta-analyses. The difference between observed and expected coronary heart disease deaths in 2005 was then partitioned between treatments and risk factors. From 1988 to 2005, the age-adjusted coronary heart disease mortality rates fell by almost 40%, resulting in 8530 fewer coronary heart disease deaths in 2005. Approximately 47% of the fall in deaths was attributed to treatments. The major treatment contributions came from initial therapy for acute coronary syndromes (11%), secondary prevention (10%), and heart failure (9%). About 50% of the fall in mortality was attributed to changes in risk factors. The largest mortality benefit came from changes in total cholesterol (about 31% of the mortality fall) and in systolic blood pressure (about 15%). However, some substantial gender differences were observed in risk factor trends with an increase in diabetes and obesity in men and an increase in smoking in young women. These generated additional deaths. Approximately half of the coronary heart disease mortality fall in Spain was attributable to reductions in major risk factors, and half to evidence-based therapies. These results increase understanding of past trends and will help to inform planning for future prevention and treatment strategies in low-risk populations.


Comparisons of contact lens, foil, fiber and skin electrodes for patterns electroretinograms.
Pattern electroretinograms are small physiologic signals that require good patient cooperation and long recording times, particularly when conditions are not optimal. Six electrodes were compared to evaluate their efficacy. Pattern electroretinograms were recorded in eight healthy volunteers to high-contrast, pattern-reversal checks (40' width) with Burian-Allen, DTL fiber, C-glide, gold foil, HK loop and skin electrodes. Raw data for 320 reversals were analyzed off-line to evaluate signal amplitude, quality, P50 and N95 peak times, artifact rate and electrical noise. Insertion time, impedance and subjective comfort were also assessed. The Burian-Allen contact lens electrode gave the largest signal and lowest impedance but was the least comfortable and had the highest artifact rate (p < 0.01). A skin electrode on the lower eyelid produced the smallest pattern electroretinogram with the poorest quality (p < 0.05). The four other electrodes were foil or fiber electrodes in contact with the tear film, conjunctiva and/or the inferior cornea. The signal from these showed only minor differences. When electrodes are compared for pattern electroretinograms recording, the foil and fiber electrodes do not differ substantially but contact lens and skin electrodes show substantial disadvantages.


Chlamydial genital infection in Algiers: a sero-epidemiological survey.
Using a microimmunofluorescence test, the prevalence of antichlamydial immunoglobulin (Ig) G in 720 people in Algiers was studied. 34 (36%) of women with low genital infection, 28 (30%) of 91 patients attending a cancer screening clinic, and 44 (100%) of prostitutes had antichlamydial IgG at a titre greater than or equal to 1:16. Among 180 women seeking a rubeola test, 48 (26.6%) had IgG titres greater than or equal to 1:16. 144 infants less than 3 months old were also tested and 16.6% of them had IgG titres greater than or equal to 1:160; 20 (20.7%) of 97 men with chronic urethritis had IgG titres greater than or equal to 1:16. Antibody titres suggesting active disease in prostitutes, patients attending the cancer screening clinic and women with low genital infection were found in 95%, 11% and 17% respectively.


Lactobacillus rhamnosus supplementation ameliorates high fat diet-induced epigenetic alterations and prevents its intergenerational inheritance.
Multiple studies have reported the epigenetic inheritance of parental metabolic traits could increase the risk of developing metabolic disorders in offsprings. L. rhamnosus (LR) as a probiotic has been found to be beneficial in metabolic diseases. Current study was aimed to explore the effects of LR on high-fat diet induced epigenetic alterations and their transgenerational inheritance. Prediabetes was induced in SD rats by feeding HFD for 16 weeks, followed by LR supplementation for 12 weeks, and were put on mating. Biochemical parameters and histopathological changes were assessed in both F0 and F1 generations. Epigenetic alterations were assessed in liver and paternal sperms using Western blotting and qRT-PCR. HFD fed animals displayed alterations in metabolic indices and histopathological features in liver and pancreas which were more prominent in males. These alterations were also inherited to male offsprings. LR supplementation reversed these metabolic and histological alterations in F0 animals and also prevented their intergenerational inheritance. At molecular level, LR supplementation reversed the alterations in miRNA (miR-155-5p, miR-26a-5p, miR-21-5p, miR-200c-3p, and miR-let7a-5p) expression, DNMT1 expression and the histone modification landscape within liver involving H3K36me2, H3K79me2 and H3K27me3 histone marks. Furthermore, expression of the mentioned miRNAs was found to be altered in the sperms of F0 males which was partly restored by LR supplementation. Present study indicates that parental HFD-induced prediabetes can transfer the altered epigenetic memory to offspring. Parental LR supplementation can erase this memory and protect the offspring from intergenerational transfer of pathological traits.


The role of energy, political stability, and real income on achieving carbon neutrality: asymmetric evidence.
Apart from business considerations stemming from the marketplace, businesses, individuals, and the economy at large, political decisions also play a role on environmental quality. Governments make a series of policies that impact private businesses, sectors, the environment, and the economy at large. In this paper, we test the asymmetric role of political risk on CO2 emissions, while controlling for renewable energy, non-renewable energy, and real income: policy toward environmental sustainability objectives in the context of Turkey. To realize the motive of this study, we capture the asymmetric effect of the regressors by adopting the nonlinear autoregressive distributed lag method (NARDL). This research adds to the environmental literature in terms of methodological and empirical. Methodologically, the study shows that a nonlinear relationship exists among the variables, and it has a significant impact on environmental sustainability targets. The outcome of the NARDL indicates that the increasing political risk, non-renewable energy, and economic growth follow a trajectory trend on carbon emissions, which is unsustainable in Turkey, but renewable energy is sustainable. Moreover, decreasing real income and non-renewable energy decreases carbon emissions. This research also deployed the frequency domain test to capture the causal association of the concerned variables and the outcome indicates political risk, renewable energy, non-renewable energy use, and real income are predictors of CO2 in Turkey. From this result, policies geared toward promoting a sustainable environment were formulated.


Zen meditation and access to information in the unconscious.
In two experiments and two different research paradigms, we tested the hypothesis that Zen meditation increases access to accessible but unconscious information. Zen practitioners who meditated in the lab performed better on the Remote Associate Test (RAT; Mednick, 1962) than Zen practitioners who did not meditate. In a new, second task, it was observed that Zen practitioners who meditated used subliminally primed words more than Zen practitioners who did not meditate. Practical and theoretical implications are discussed.


Modeling growth, lipid accumulation and lipid turnover in submerged batch cultures of Umbelopsis isabellina.
The production of lipids by oleaginous yeast and fungi becomes more important because these lipids can be used for biodiesel production. To understand the process of lipid production better, we developed a model for growth, lipid production and lipid turnover in submerged batch fermentation. This model describes three subsequent phases: exponential growth when both a C-source and an N-source are available, carbohydrate and lipid production when the N-source is exhausted and turnover of accumulated lipids when the C-source is exhausted. The model was validated with submerged batch cultures of the fungus Umbelopsis isabellina (formerly known as Mortierella isabellina) with two different initial C/N-ratios. Comparison with chemostat cultures with the same strain showed a significant difference in lipid production: in batch cultures, the initial specific lipid production rate was almost four times higher than in chemostat cultures but it decreased exponentially in time, while the maximum specific lipid production rate in chemostat cultures was independent of residence time. This indicates that different mechanisms for lipid production are active in batch and chemostat cultures. The model could also describe data for submerged batch cultures from literature well.


Down regulation of NDUFS1 is involved in the progression of parenteral-nutrition-associated liver disease by increasing Oxidative stress.
Parenteral nutrition (PN)-associated liver disease (PNALD) is a common and life-threatening complication of patients receiving PN. However, its definitive pathology remains unclear. Ubiquinone oxidoreductase core subunit S1 (NDUFS1), which is the largest core subunit of mitochondrial complex I, could alter the mitochondrial reactive oxygen species (ROS) formation. The purpose of this study was to investigate the role of NDUFS1 in the pathogenesis of PNALD and its underlying mechanism. We performed hepatic proteomics analysis of PNALD patients, and established a PNALD rat model to verify the role of oxidative stress, NDUFS1, pyrin inflammasome, and IL-1β in the progression of PNALD. Proteomics analysis revealed the NDUFS1 expression was decreased in PNALD patients, and the differentially espressed proteins were involved in mitochondrial respiratory chain complex Ⅰ. Treatment with MitoQ or overexpression of NDUFS1 can alleviate the progression of PNALD by reducing oxidative stress. The expression of pyrin, caspase-1, and IL-1β was increased in PN rats. Pharmacological antagonism of pyrin by colchicine can alleviate liver injury and hepatic steatosis. NDUFS1 prevents PNALD pathogenesis by regulating oxidative stress. Pyrin inflammasome and IL-1β may participate in the process of PNALD development by suppressing the transcription of MTTP and impairing the secretion of VLDL. Oxidative stress reduction may be employed as a strategy in the prevention and treatment of PNALD.