Design of a Self-Controlled Dual-Oscillator-Based Supply Voltage Monitor for Biofuel-Cell-Combined Biosensing Systems in 65-nm CMOS and 55-nm DDC CMOS.
A supply voltage monitor (SVM) with self-controlled dual-oscillator-based architecture is proposed herein for biosensing systems combined with a biofuel cell (BFC) in this paper. The output of the BFCs can be used to monitor the biological signals while powering the BFC-combined biosensing systems. Thus, the SVM is designed to convert the change in the supply voltage (V DD) into a code. The architecture of the proposed SVM allows self-controlled periodic operation without external signals. Furthermore, the frequency subtraction technique that uses two oscillators employing gate-leakage-based architecture with different frequency sensitivities to V DD allows accurate code generation with low power consumption and a small circuit area for supply voltage monitoring. The proposed SVM is fabricated using two different CMOS process technologies, including 65-nm CMOS and 55-nm deeply depleted channel (DDC) CMOS. The implementation of the 65-nm CMOS obtains an operating V DD range of 250 mV (0.75-1 V), draws a standby power consumption of 1.4 nW at 0.75-V V DD, exhibits a resolution of 2.4 mV with a nonlinearity error of -8.4/ +12.1 mV, and occupies a circuit area of 0.0047 mm2. Meanwhile, the implementation of the 55-nm DDC CMOS for low-voltage operation achieves an operating V DD range of 300 mV (0.225-0.525 V), draws a standby power consumption of 32.5 nW at 0.25-V V DD, exhibits a resolution of 0.94 mV with a nonlinearity error of -15.2/ +14 mV, and occupies a circuit area of 0.0032 mm2.


Systematic Review on the Content of Outcome Measurement Instruments on Scar Quality.
Measurements of scar quality are essential to evaluate the effectiveness of scar treatments and to monitor scars. A large number of scar scales and measurement devices have been developed, which makes instrument selection challenging. The aim of this study was to provide an overview of the content (ie, included items) of all outcome measurement instruments that measure scar quality in different types of scars (burn, surgical, keloid, and necrotizing fasciitis), and the frequency at which the instruments and included items are used. A systematic search was performed in PubMed and Embase.com up to October 31, 2018. All original studies reporting on instruments that measured at least 1 characteristic of scar quality were included and the instrument's content was extracted. We included 440 studies for data extraction. Included instruments (N = 909) were clinician-reported scales (41%), measurement devices (30%), patient-reported scales (26%), and combined clinician- and patient-reported scales (3%). The Observer scale of the Patient and Observer Scar Assessment Scale, the Cutometer, the Patient Scale of the Patient and Observer Scar Assessment Scale, and the modified Vancouver Scar Scale were the most often used instrument in each of these categories, respectively. The most frequent assessed items were thickness, vascularity, pigmentation, pliability, pain, and itch. The results of this study lay the foundation for our future research, which includes an international Delphi study among many scar experts, and an international focus group study among scar patients, aiming to elucidate how scar quality must be defined and measured from both professional and patient perspectives.


[Oxidative Probing of the G4 DNA Structure by Znp1 Porphyrin within Sequences of MYC and TERT Promotors].
The formation of G4 structures in a DNA double helix competes with the complementary strand interaction. The local environment in DNA can change equilibrium of G4 structures, which are studied on single-stranded (ss) models by classical structural methods. A relevant task is to develop methods for detecting and localizing G4 structures in extended native double-stranded (ds) DNA in the promoter regions of the genome. The ZnP1 porphyrin derivative selectively binds to G4 structures and leads to photo-induced oxidation of guanine in ssDNA and dsDNA model systems. We have shown the oxidative effect of ZnP1 on native sequences of MYC and TERT oncogene promoters, which can form G4 structures. Single-strand breaks in the guanine-rich sequence because of ZnP1 oxidation and subsequent cleavage of the DNA strand with Fpg glycosylase have been identified and assigned to the nucleotide sequence. The detected break sites have been shown to correspond to sequences capable of forming G4 structures. Thus, we have demonstrated the possibility of using porphyrin ZnP1 for the identification and localization of G4 quadruplexes in extended regions of the genome. Here we have shown the novel data on a possibility of folding G4 structures in the presence of complementary strand in native DNA double helix.


A new species of Apteranabropsis Gorochov, 1988 from Guangxi, China (Orthoptera: Anostostomatidae: Anabropsinae: Anabropsini) with key to known species.
This paper describes and illustrates a new species of the genus Apteranabropsis (Anostostomatidae: Anabropsinae) from Guangxi, China, namely Apteranabropsis guangxiensis Bian & Shi sp. nov. A key to all known species of Apteranabropsis is provided.


Retroperitoneal lymphangioleiomyoma with lymph node involvement: A pathologic-radiologic correlation of a rare form of myomelanocytic tumor.
Lymphangioleiomyomatosis (LAM) is a rare and slowly progressive disorder that usually arises in the lung, affects exclusively women in their childbearing years, and typically presents with progressive dyspnea on exertion and pneumothorax. Infrequently, extra-pulmonary LAM can occur in the retroperitoneum, uterine wall, mediastinum and intraperitoneal lymph nodes. Histologically, LAM is characterized by a proliferation of perivascular epithelioid cells (PEC) that express markers for both melanocytes and smooth muscle cells. We report a case of a peripancreatic retroperitoneal mass that was incidentally discovered on magnetic resonance image (MRI) scan of a 38-year-old female. The morphologic findings and the immunohistochemical staining were consistent with a lymphangioleiomyoma. The radiologic and pathologic correlation along with differential diagnosis of this rare entity is discussed.


Characterizing the breast cancer lipidome and its interaction with the tissue microbiota.
Breast cancer is the most diagnosed cancer amongst women worldwide. We have previously shown that there is a breast microbiota which differs between women who have breast cancer and those who are disease-free. To better understand the local biochemical perturbations occurring with disease and the potential contribution of the breast microbiome, lipid profiling was performed on non-tumor breast tissue collected from 19 healthy women and 42 with breast cancer. Here we identified unique lipid signatures between the two groups with greater amounts of lysophosphatidylcholines and oxidized cholesteryl esters in the tissue from women with breast cancer and lower amounts of ceramides, diacylglycerols, phosphatidylcholines, and phosphatidylethanolamines. By integrating these lipid signatures with the breast bacterial profiles, we observed that Gammaproteobacteria and those from the class Bacillus, were negatively correlated with ceramides, lipids with antiproliferative properties. In the healthy tissues, diacylglyerols were positively associated with Acinetobacter, Lactococcus, Corynebacterium, Prevotella and Streptococcus. These bacterial groups were found to possess the genetic potential to synthesize these lipids. The cause-effect relationships of these observations and their contribution to disease patho-mechanisms warrants further investigation for a disease afflicting millions of women around the world.


Immunological mechanisms in glaucoma.
Glaucoma is one of the most frequent causes of blindness worldwide. The elevated intraocular pressure does not explain glaucoma in all patients but can be considered as a risk factor of the disease. There are some evidences that autoimmune mechanisms may be involved in this disorder. This review attempts to demonstrate the findings about autoimmune mechanisms in glaucoma patients. Consistent up- and down-regulations in the autoantibody profiles against ocular antigens are present in glaucoma patients. These changes in natural autoimmunity could be found in independent study populations and might be a promising tool for glaucoma detection.


Diffuse esophageal intramural pseudodiverticulosis and nutcracker esophagus in a 54-year-old man.
Esophageal intramural pseudodiverticulosis, which was first described by Mendl et al. in 1960, is characterized by multiple small flask-shaped outpouchings in the esophageal wall. The pseudodiverticula represent dilated excretory ducts of deep mucous glands in the esophagus. The etiology of this rare condition is unknown. Hiatal hernias, gastroesophageal reflux, esophageal strictures, candida esophagitis, herpes esophagitis, diabetes mellitus, and chronic alcoholism have been found associated with intramural pseudodiverticulosis. We report the second case of esophageal hypermotility in intramural pseudodiverticulosis.


Undernutrition in Crohn's disease: an anthropometric assessment.
Anthropometric measurements of weight, arm-muscle area and arm-fat area were assessed in 106 unselected patients with Crohn's disease, and related to centiles derived from the United States Health and Nutrition Examination Survey of 1971-1974. Results were compared with those obtained in 106 patients with ulcerative colitis and 106 healthy subjects, age and sex-matched with the Crohn's patients. Measurements in healthy subjects and in patients with ulcerative colitis showed a normal centile distribution with the expected proportion falling below the 5th centile. In contrast, a significantly higher proportion of patients with Crohn's disease had measurements below the 5th centile, indicating depleted muscle and fat stores.


Comparison of two gas-liquid chromatographic methods for the determination of nitrazepam in plasma.
Nitrazepam in plasma was determined by gas-liquid chromatography with a nickel-63 electron-capture detector, unchanged by a direct method and also by a hydrolysis method. The extraction in the direct method was carried out with benzenedichloromethane (90:10) and in the hydrolysis method with diethyl ether. The hydrolysis was performed with 6 N sulphuric acid. The hydrolysis product was extracted with toluene-n-heptane-ethyl acetate (80:20:5) directly from acid. Thus the commonly used change in pH was omitted. Nitrazepam concentrations in plasma were determined in 10 healthy volunteers after two oral doses (5 and 10 mg); 0.5 ml of plasma was used for each determination and clonazepam, methylbromazepam and methylnitrazepam were used as internal standards. The recoveries of the methods are almost quantitative (greater than 96%). The two methods are clinically comparable. The high sensitivity and specificity make these methods useful in clinical determinations of nitrazepam in plasma. Advantages and disadvantages of both methods are discussed.


Links between maternal feeding practices and children's eating difficulties. Validation of French tools.
The main objectives of the present study were to validate measures of young children's eating difficulties and maternal feeding practices in a French sample, as well as to assess the links between these practices and children's eating difficulties. Mothers (n=502) of French children aged 20-36 months completed four questionnaires that were validated using a Structural Equation Modelling approach. Links between children and maternal components were investigated using a PLS regression. The Children's Eating Difficulties Questionnaire yielded a 4-dimension solution: Neophobia, Pickiness, Low Appetite and Low Enjoyment in food. The Feeding Style Questionnaire assessed three dimensions: Authoritarian, Authoritative and Permissive Styles. The Feeding Strategy Questionnaire, designed to evaluate strategies used by mothers to make their child taste rejected foods, resulted in four factors: Coercion, Explanation, Contingency and Preference. The Questionnaire relating to Parental Motivations when buying food for children presented a 6-dimension solution: Convenience, Weight-control, Natural, Health-concern, Preference and Price. The factors associated positively with the four dimensions of the Children's Eating Difficulties Questionnaire were on the one hand Permissive Style and Practices to fulfil child's desires, and on the other hand Authoritarian Style, Contingent and Coercive Practices aimed at forcing children to taste rejected foods.


Disruption of MeCP2 attenuates circadian rhythm in CRISPR/Cas9-based Rett syndrome model mouse.
Methyl-CpG-binding protein 2 (Mecp2) is an X-linked gene encoding a methylated DNA-binding nuclear protein which regulates transcriptional activity. The mutation of MECP2 in humans is associated with Rett syndrome (RTT), a neurodevelopmental disorder. Patients with RTT frequently show abnormal sleep patterns and sleep-associated problems, in addition to autistic symptoms, raising the possibility of circadian clock dysfunction in RTT. In this study, we investigated circadian clock function in Mecp2-deficient mice. We successfully generated both male and female Mecp2-deficient mice on the wild-type C57BL/6 background and PER2(Luciferase) (PER2(Luc)) knock-in background using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. Generated Mecp2-deficient mice recapitulated reduced activity in mouse models of RTT, and their activity rhythms were diminished in constant dark conditions. Furthermore, real-time bioluminescence imaging showed that the amplitude of PER2(Luc)-driven circadian oscillation was significantly attenuated in Mecp2-deficient SCN neurons. On the other hand, in vitro circadian rhythm development assay using Mecp2-deficient mouse embryonic stem cells (ESCs) did not show amplitude changes of PER2(Luc) bioluminescence rhythms. Together, these results show that Mecp2 deficiency abrogates the circadian pacemaking ability of the SCN, which may be a therapeutic target to treat the sleep problems of patients with RTT.


Does carbon dioxide retention during exercise predict a more rapid decline in FEV1 in cystic fibrosis?
Carbon dioxide (CO2) retention during exercise is uncommon in mild to moderate lung disease in cystic fibrosis (CF). The ability to deal with increased CO2 is dependent on the degree of airflow limitation and inherent CO2 sensitivity. CO2 retention (CO2R) can be defined as a rise in P(ET)CO2 tension of > or =5 mm Hg with exercise together with a failure to reduce P(ET)CO2 tension after peak work by at least 3 mm Hg by the termination of exercise. To ascertain if carbon dioxide retention during exercise is associated with more rapid decline in lung function. Annual spirometric and exercise data from 58 children aged 11-15 years, with moderate CF lung disease between 1996 and 2002 were analysed. The mean FEV1 at baseline for the two groups was similar; the CO2R group (n = 15) was 62% and the non-CO2 retention group (CO2NR) was 64% (n = 43). The decline in FEV1 after 12 months was -3.2% (SD 1.1) in the CO2R group and -2.3% (SD 0.9) in the CO2NR group. The decline after 24 months was -6.3% (SD 1.3) and -1.8% (SD 1.1) respectively. After 36 months, the decline in FEV1 was -5.3% (SD 1.2) and -2.6% (SD 1.1) respectively. The overall decline in lung function was 14.8% (SD 2.1) in the CO2R group and 6.7% (SD 1.8) in the CO2NR group. Using the primary outcome measure as a decline in FEV(1) of >9%, final multivariate analysis showed that the relative risks for this model were (95% CIs in parentheses): DeltaP(ET)CO2 11.61 (3.41 to 24.12), peak VO2 1.23 (1.10 to 1.43), and initial FEV(1) 1.14 (1.02 to 1.28). Results show that the inability to defend carbon dioxide during exercise is associated with a more rapid decline in lung function.


Neglected Tropical Diseases in the Post-Genomic Era.
Neglected tropical diseases (NTDs) are a group of viral, bacterial, and eukaryotic parasitic diseases that are especially endemic in low-income populations, with a large health and economic impact on both the developing and developed world. The structure and dynamics of the genomes of the organisms causing these diseases, as well as the modes of expression, exchange, and transmission of their genetic information, often deviate from those found in classical, model organism-centric textbooks. We assess the role of basic and applied genetic research in our understanding of key aspects of their biology and evolution, and discuss the impact of novel high-throughput approaches spawned by the post-genomic era on the development of next-generation drugs, vaccines, molecular epidemiology, and/or diagnostic tools for these important pathogens.


Perspectives in targeting miRNA function.
First oligonucleotide analogues that inhibit miRNA function are currently investigated in clinical trials. In addition, several alternative methods are under development that may allow for controlling miRNA function by small molecules-mediated inhibiting of its biogenesis. In this perspectives article, we provide a short overview on recent developments in this field.


Evaluation of tetracycline and fluoroquinolone therapy against Japanese spotted fever: Analysis based on individual data from case reports and case series.
Although approximately 40 years have passed since Japanese spotted fever (JSF) was first reported in Japan, its treatment has not yet been standardised. As in other rickettsial infections, tetracycline (TC) is the first-line treatment, but successful instances of fluoroquinolone (FQ) combination therapy in severe cases have been reported. However, the effectiveness of TC plus FQ combined treatment (TC+FQ) remains controversial. Therefore, the antipyretic effect of TC+FQ was evaluated in this study. A comprehensive search of published JSF case reports was conducted to extract individual patient data. In cases where it was possible to extract temperature data, after homogenising patient characteristics, time-dependent changes in fever type from the date of the first visit was evaluated for the TC and TC+FQ groups. The primary search yielded 182 cases, with individual data evaluations resulting in a final analysis of 102 cases (84 in the TC group and 18 in the TC+FQ group) that included temperature data. The TC+FQ group had significantly lower body temperature compared with the TC group from Days 3 to 4. Although TC monotherapy for JSF can eventually result in defervescence, the duration of fever is longer compared with other rickettsial infections such as scrub typhus. The results suggest that the antipyretic effect of TC+FQ was more effective, with a potential shortening of the duration that patients suffer from febrile symptoms.


CT coronary angiography as an alternative imaging method to ascertain cardiac output and its correlation with echocardiography.
To assess the feasibility and accuracy of cardiac output (CO) obtained using a test bolus in patients scanned with single-source prospective-gated cardiac computed tomography (CT), and comparing it with CO obtained from unenhanced two-dimensional (2D) echocardiography using biplane Simpson's method. In the present study, 100 patients with a mean age of 55 ± 12 years who underwent coronary CT angiography with prospective electrocardiogram (ECG)-gated CT in which the scan delay was evaluated using a test bolus. The time-attenuation curves obtained from the test bolus were used to calculate the CO of the patients. The CO obtained was then compared with that obtained after follow-up 2D echocardiography using biplane modified Simpson method. Linear regression was calculated between the CO and contrast enhancement: CO = -0.16(HUmax) + 7.65. The study showed good correlation between the two methods with r=0.77, p<0.001. On Bland-Altman analysis, no significant difference was noted between the two methods. This less researched method for CO estimation appears feasible; however, the clinical usefulness of this parameter is uncertain in absence of further clinical and reference standard validation.


Influence of the geometry of curved artificial canals on the fracture of rotary nickel-titanium instruments subjected to cyclic fatigue tests.
This study evaluated the influence of different features of canal curvature geometry on the number of cycles to fracture of a rotary nickel-titanium endodontic instrument subjected to a cyclic fatigue test. BioRaCe BR4C instruments (FKG Dentaire, La Chaux-de Fonds, Switzerland) were tested in 4 grooves simulating curved metallic artificial canals, each one measuring 1.5 mm in width, 20 mm in total length, and 3.5 mm in depth with a U-shaped bottom. The parameters of curvature including the radius and arc lengths and the position of the arc differed in the 4 canal designs. Fractured surfaces and helical shafts of the separated instruments were analyzed by scanning electron microscopy. The Student's t test showed that a significantly lower number of cycles to fracture values were observed for instruments tested in canals with the smallest radius, the longest arc, and the arc located in the middle portion of the canal. Scanning electron microscopic analysis of the fracture surfaces revealed morphologic characteristics of ductile fracture. Plastic deformation was not observed in the helical shaft of the fractured instruments. Curvature geometry including the radius and arc lengths and the position of the arc along the root canal influence the number of cycles to fracture of rotary nickel-titanium instruments subjected to flexural load.


Tumor uptake as a function of tumor mass: a mathematic model.
Inverse correlations of tumor uptake (u), measured in percent injected dose per gram, with tumor mass (m) are demonstrated for phospholipid vesicle, nonspecific and specific monoclonal antibody tracers. Correlation coefficients implied u = B mA in 11 different animal experiments. Experimental exponent (A) values lay in the range -0.28-0.64 with a mean of -0.43 while intercept (B) values varied from 3 to 18. Spherical and cylindrical tumor models implied exponents of -0.33 and -0.5, respectively. Comparison of three implantation sites of the human LS174T xenograft revealed a narrow range of exponents (-0.38- -0.46) indicating a consistent geometry for this tumor. Blood flow to the lesion site and inside its volume (as dictated by tumor size) are factors in tumor uptake. Our results indicate that biodistribution data should include the variation of tumor uptake with mass. For less than 10 g lesions, we predict that radiation absorbed dose will be highly dependent upon tumor size.


Gastric carcinogenesis: a comprehensive review of the angiogenic pathways.
Gastric cancer (GC) is undoubtedly one of the most prevalent malignancies worldwide. Since GC is the second leading cause of cancer-related deaths with nearly one million new diagnoses reported every year, there is a need for the development of new, effective treatment strategies of GC. Gastric carcinogenesis is a complex process that is induced by numerous factors and further stimulated by many pro-oncogenic pathways. Angiogenesis is the process of the new blood vessels formation from the already existing ones and it significantly contributes to the progression of gastric tumorigenesis and the growth of the cancerous tissues. The newly formed vessels provide cancer cells with proper nutrition, growth factors, and oxygen supply that are crucial for tumor growth and progression. Tumor-associated vessels differ from the physiological ones both morphologically and functionally. They are usually inefficient and unevenly distributed due to structural transformations. Thus, the development of the angiogenesis inhibitors that possess therapeutic effects has been the main focus of recent studies. Angiogenesis inhibitors mostly affect the vascular endothelial growth factor (VEGF) pathway since it is a major factor that stimulates the pro-angiogenic pathways. The aim of this review was to describe and summarize other promising molecular pathways that might be crucial in further improvements in GC therapies. This article provides an overview of how a meaningful role in tumor progression the angiogenetic process has. Furthermore, this review includes a description of the most important angiogenic factors as well as pathways and their involvement in gastric carcinogenesis.


Prostacyclin biosynthesis in vascular endothelium is not inhibited by cyclic AMP. Studies with 3-isobutyl-1-methylxanthine and forskolin.
We have previously reported (Proc. Natl. Acad. Sci. 79, 495-499, 1982) that the cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX), stimulates cyclic AMP accumulation and inhibits prostacyclin (PGI2) production in primary monolayer cultures of human umbilical vein endothelium. The present study was carried out to determine whether these effects are causally related. Incubation of endothelial monolayers with the diterpene, forskolin, increased the intracellular concentration of cyclic AMP by 10-fold. Despite this marked increase in cyclic AMP, neither baseline production of PGI2 nor release in response to stimulation by thrombin or the divalent cation ionophore, A23187, was affected. Both forskolin and isoproterenol were found to potentiate the effect of IBMX on cyclic AMP accumulation without causing further inhibition of PGI2 biosynthesis. Inhibition of cyclic nucleotide phosphodiesterase activity with 2,6-bis-(diethanolamino)-4-piperidinopyrimido-[5,4-d]pyrimidine increased cyclic AMP levels to the same extent as IBMX; however, this agent had no effect on PGI2 biosynthesis. These findings demonstrate that increases in the intracellular concentration of cyclic AMP have no short-term effects on PGI2 biosynthesis in vascular endothelium and suggest that inhibition of PGI2 production by IBMX is the result of some other, cyclic AMP-independent action of the drug.


Lymph node ratio is more predictive than traditional lymph node stratification in lymph node positive invasive breast cancer.
To evaluate the relationships between lymph node ratio (LNR, the ratio of positive lymph nodes in excised axillary lymph nodes) and disease-free survival (DFS) by comparing with traditional absolute positive lymph node number (pN classification) for prediction of breast cancer (BC) progrnosis. We retrospectively reviewed patients who received comprehensive therapy in Department of Breast Surgery, Hubei Cancer Hospital, China from Jan 2002 to Dec 2006 (Group A), and Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, China from Jun 2008 to May 2012 (Group B). Patients were allocated to low-risk (≤0.20), intermediate-risk (> 0.20 but ≤ 0.65), high-risk (>0.65) groups by LNR. The primary endpoint was 5-DFS. A total of 294 patients were included in our study. LNR was verified as a negative prognostic factor for DFS (P= 0.002 in Group A, P< 0.0001 in Group B). Then we found the effects of pN and LNR delamination on disease-free survival (DFS) had statistical significance (P=0.012 for pN and P=0.031 for LNR stratification in Group A, both of them P<0.001 in Group B). Compared to pN staging, LNR staging displayed superior performance in prognosis, the adjusted hazard ratio of recurrence being 2.07 (95%CI, 1.07 to 4.0) for intermediate risk group (P=0.030) and 2.44 (95%CI, 1.21 to 4.92) for high risk group (P=0.013) in Group A. LNR stratification proved an adverse prognostic factor of DFS in lymph nodes positive invasive BC using cut-off values 0.20 and 0.65, and was more predictive than traditional pN classification for 5-DFS.


Electron microscopy study of Q beta replicase.
Purified preparations of Q beta replicase have been studied by electron microscopy using a negative staining technique, and a three-dimensional model of the enzyme molecule has been constructed. The molecule of this four-subunit protein appears to be a compact structure having a size of 100 +/- 10 A; it is subdivided into two unequal bipartite subparticles. The conclusion has been made that all the constituent subunits, including the ribosomal protein Sl, acquire a globular conformation when associated in the replicase complex.


[The prevalence of exposure of children under the age of 18 to second-hand smoke inside motor vehicles].
The objective of the study was to estimate the level of exposure of children under the age of 18 to second-hand smoke (SHS) inside motor vehicles. A prevalence study was conducted on the exposure of children under the age of 18 to SHS in motor vehicles in Lleida (Spain). The population was the users of private motor vehicles. The sample was random, and the data were collected by direct observation. The study variables were: the age and sex of the driver, whether the driver was smoking, and the presence of an exposed passenger under the age of 18. A total of 1600 vehicles were observed, 134 of which (8.4%) were carrying a child. In 8 of these 134 vehicles (6%; 95% CI: 2.5-11.0) a child was exposed to SHS. In all these cases, the driver was a male (P=0.02), and in 75% of cases he was over 40 years old. The rate of child exposure to SHS is very high. There is, therefore, a case for organising campaigns to prevent smoking tobacco inside motor vehicles in the presence of children in Spain.


Exploring sexual dysfunction in care homes.
Sexual needs and sexuality in older adults continues to be a neglected area of clinical intervention, particularly in longer term care settings. This is often due to older adults in long term care beds presenting with increased frailty, and often with significant neurocognitive disorders, making it difficult for care staff to evaluate the capacity of an older adult resident to participate in sexual activities or a sexual relationship. Talking about sexuality, intimacy and sexual health can be embarrassing at any age and sex is often still considered taboo for people who live in care homes. The World Health Organization recently declared that sexual health is a central aspect of life and that each individual has the right to love and be loved, to receive appropriate information and treatment, and to enable intimate relationships and personal control over sexual behavior. This chapter explores sexual behaviors, and barriers to this, in later life, and focuses on the sexual behavior of care home residents with Parkinson's disease. Reasons for sexual dysfunction, potential age-related changes to sexual functioning, along with issues such as changes to body image, intimacy and hyper sexuality, are examined for people with Parkinson's disease. Recommendations for practice are given, and acknowledge that older people may still want to be sexually active or intimate is the first step to addressing the issues and overcoming any barriers.


The Extracellular Matrix of Fungal Biofilms.
A key feature of biofilms is their production of an extracellular matrix. This material covers the biofilm cells, providing a protective barrier to the surrounding environment. During an infection setting, this can include such offenses as host cells and products of the immune system as well as drugs used for treatment. Studies over the past two decades have revealed the matrix from different biofilm species to be as diverse as the microbes themselves. This chapter will review the composition and roles of matrix from fungal biofilms, with primary focus on Candida species, Saccharomyces cerevisiae, Aspergillus fumigatus, and Cryptococcus neoformans. Additional coverage will be provided on the antifungal resistance proffered by the Candida albicans matrix, which has been studied in the most depth. A brief section on the matrix produced by bacterial biofilms will be provided for comparison. Current tools for studying the matrix will also be discussed, as well as suggestions for areas of future study in this field.


A general procedure for estimation of corticosteroid response in individual rats.
A procedure is presented whereby microliter volumes of plasma, obtained rapidly and repeatedly from the tail vein of unanesthetized rats, can be analyzed for corticosterone. Preliminary results suggest that (1) basal levels are considerably lower and (2) the latency to corticosteroid stress response is shorter than previously reported.


Headless compression screw in the neuronavigation-guided and microscope-assisted treatment of spondylolysis.
Since 1968, many surgical techniques used in repairing the pars defect of the vertebra have been reported. Technological advances are giving rise to new ways of obtaining the best outcome using less invasive methods, which are more accurate, simple and effective. To treat cases of spondylolysis such as pseudarthrosis, we used neuro-navigation and microscopy through a 2.5-cm skin incision to approach the pars defect, freshen the fracture and place a type of screw that, until now, has never been used for this purpose. This is a novel technique, which guarantees prolonged compression and sufficient stability to facilitate the prompt healing of the vertebra. We present 2 cases of L5 spondylolysis treated with our technique, a modification of Buck's technique. A detailed description of the screw selection, surgical technical details, follow-up and outcome are discussed.


Fitness of acquired drug resistant Mycobacterium tuberculosis isolates from DOTS compliant patients.
The increasing levels of multi drug resistant tuberculosis (MDRTB) in endemic regions are a cause of concern. When MDR strains exhibit higher fitness they threaten global tuberculosis control. Evaluation of factors other than the particular non-synonymous substitutions that contribute to the fitness of strains may have an important bearing on understanding the spread of the disease. The aim of the study was to determine the fitness of MDRTB strains from TB endemic region, acquiring drug resistance during the course of treatment. Paired isolates of different lineages (one that was drug resistant and one that was drug susceptible) from 5 patients, which acquired resistance during antibiotic treatment and bearing drug resistance mutations in the rpoβ and katG/inhA regions were mixed axenically. Fitness of Mycobacterium tuberculosis (M.tb) strains was evaluated using the difference in generation times of drug resistant and susceptible population obtained by enumeration of CFU. The drug resistant strains bore no significant fitness cost. The selection of specific allelic combinations in multiple drug resistance governing loci may attribute the enhanced/retained fitness of the drug resistant strains.


Transcriptomic changes across vitellogenesis in the black tiger prawn (Penaeus monodon), neuropeptides and G protein-coupled receptors repertoire curation.
The black tiger prawn (Penaeus monodon) is one of the most commercially important prawn species world-wide, yet there are currently key issues that hinder aquaculture of this species, such as low spawning capacity of captive-reared broodstock females and lack of globally available fully domesticated strains. In this study, we analysed the molecular changes that occur from vitellogenesis to spawning of a fully domesticated population of P.monodon (Madagascar) using four tissues [brain and thoracic ganglia (central nervous system - CNS), eyestalks, antennal gland, and ovary] highlighting differentially expressed genes that could be involved in the sexual maturation. In addition, due to their key role in regulating multiple physiological processes including reproduction, transcripts encoding P.monodon neuropeptides and G protein-coupled receptors (GPCRs) were identified and their expression pattern was assessed. A few neuropeptides and their putative GPCRs which were previously implicated in reproduction are discussed. We identified 573 differentially expressed transcripts between previtellogenic and vitellogenic stages, across the four analysed tissues. Multiple transcripts that have been linked to ovarian maturation were highlighted throughout the study, these include vitellogenin, Wnt, heat shock protein 21, heat shock protein 90, teneurin, Fs(1)M3, hemolymph clottable proteins and some other candidates. Seventy neuropeptide transcripts were also characterized from our de novo assembly. In addition, a hybrid approach that involved clustering and phylogenetics analysis was used to annotate all P. monodon GPCRs, revealing 223 Rhodopsin, 100 Secretin and 27 Metabotropic glutamate GPCRs. Given the key commercial significance of P.monodon and the industry requirements for developing better genomic tools to control reproduction in this species, our findings provide a foundation for future gene-based studies, setting the scene for developing innovative tools for reproduction and/or sexual maturation control in P. monodon.


Hyperpolarized 83Kr MRI of lungs.
Hyperpolarized (hp) (83)Kr (spin I=9/2) is a promising gas-phase contrast agent that displays sensitivity to the surface chemistry, surface-to-volume ratio, and surface temperature of the surrounding environment. This proof-of-principle study demonstrates the feasibility of ex vivo hp (83)Kr magnetic resonance imaging (MRI) of lungs using natural abundance krypton gas (11.5% (83)Kr) and excised, but otherwise intact, rat lungs located within a custom designed ventilation chamber. Experiments comparing the (83)Kr MR signal intensity from lungs to that arising from a balloon with no internal structure inflated to the same volume with krypton gas mixture suggest that most of the observed signal originated from the alveoli and not merely the conducting airways. The (83)Kr longitudinal relaxation times in the rat lungs ranged from 0.7 to 3.7s but were reproducible for a given lung. Although the source of these variations was not explored in this work, hp (83)Kr T(1) differences may ultimately lead to a novel form of MRI contrast in lungs. The currently obtained 1200-fold signal enhancement for hp (83)Kr at 9.4T field strength is found to be 180 times below the theoretical upper limit.


On the origin of ultraslow spontaneous Na+ fluctuations in neurons of the neonatal forebrain.
Spontaneous neuronal and astrocytic activity in the neonate forebrain is believed to drive the maturation of individual cells and their integration into complex brain-region-specific networks. The previously reported forms include bursts of electrical activity and oscillations in intracellular Ca2+ concentration. Here, we use ratiometric Na+ imaging to demonstrate spontaneous fluctuations in the intracellular Na+ concentration of CA1 pyramidal neurons and astrocytes in tissue slices obtained from the hippocampus of mice at postnatal days 2-4 (P2-4). These occur at very low frequency (∼2/h), can last minutes with amplitudes up to several millimolar, and mostly disappear after the first postnatal week. To further investigate their mechanisms, we model a network consisting of pyramidal neurons and interneurons. Experimentally observed Na+ fluctuations are mimicked when GABAergic inhibition in the simulated network is made depolarizing. Both our experiments and computational model show that blocking voltage-gated Na+ channels or GABAergic signaling significantly diminish the neuronal Na+ fluctuations. On the other hand, blocking a variety of other ion channels, receptors, or transporters including glutamatergic pathways does not have significant effects. Our model also shows that the amplitude and duration of Na+ fluctuations decrease as we increase the strength of glial K+ uptake. Furthermore, neurons with smaller somatic volumes exhibit fluctuations with higher frequency and amplitude. As opposed to this, larger extracellular to intracellular volume ratio observed in neonatal brain exerts a dampening effect. Finally, our model predicts that these periods of spontaneous Na+ influx leave neonatal neuronal networks more vulnerable to seizure-like states when compared with mature brain.NEW & NOTEWORTHY Spontaneous activity in the neonate forebrain plays a key role in cell maturation and brain development. We report spontaneous, ultraslow, asynchronous fluctuations in the intracellular Na+ concentration of neurons and astrocytes. We show that this activity is not correlated with the previously reported synchronous neuronal population bursting or Ca2+ oscillations, both of which occur at much faster timescales. Furthermore, extracellular K+ concentration remains nearly constant. The spontaneous Na+ fluctuations disappear after the first postnatal week.


Activated carbons-preparation, characterization and their application in CO2 capture: A review.
In this paper, we provide a comprehensive review of the latest research trends in terms of the preparation, and characteristics of activated carbons regarding CO2 adsorption applications, with a special focus on future investigation paths. The reported current research trends are primarily closely related to the synthesis conditions (carbonization and physical or chemical activation process), to develop the microporosity and surface area, which are the most important factors affecting the effectiveness of adsorption. Furthermore, we emphasized the importance of regeneration techniques as a factor determining the actual technological and economic suitability of a given material for CO2 capture application. Consequently, this work provides a summary and potential directions for the development of activated carbons (AC). We attempt to create a thorough theoretical foundation for activated carbons while also focusing on identifying and specific statements of the most relevant ongoing research scope that might be advantageous to progress and pursue in the coming years.


Enhanced synaptic inhibition disrupts the efferent code of cerebellar Purkinje neurons in leaner Cav2.1 Ca 2+ channel mutant mice.
Cerebellar Purkinje cells (PCs) encode afferent information in the rate and temporal structure of their spike trains. Both spontaneous firing in these neurons and its modulation by synaptic inputs depend on Ca(2+) current carried by Ca(v)2.1 (P/Q) type channels. Previous studies have described how loss-of-function Ca(v)2.1 mutations affect intrinsic excitability and excitatory transmission in PCs. This study examines the effects of the leaner mutation on fast GABAergic transmission and its modulation of spontaneous firing in PCs. The leaner mutation enhances spontaneous synaptic inhibition of PCs, leading to transitory reductions in PC firing rate and increased spike rate variability. Enhanced inhibition is paralleled by an increase in the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) measured under voltage clamp. These differences are abolished by tetrodotoxin, implicating effects of the mutation on spike-induced GABA release. Elevated sIPSC frequency in leaner PCs is not accompanied by increased mean firing rate in molecular layer interneurons, but IPSCs evoked in PCs by direct stimulation of these neurons exhibit larger amplitude, slower decay rate, and a higher burst probability compared to wild-type PCs. Ca(2+) release from internal stores appears to be required for enhanced inhibition since differences in sIPSC frequency and amplitude in leaner and wild-type PCs are abolished by thapsigargin, an ER Ca(2+) pump inhibitor. These findings represent the first account of the functional consequences of a loss-of-function P/Q channel mutation on PC firing properties through altered GABAergic transmission. Gain in synaptic inhibition shown here would compromise the fidelity of information coding in these neurons and may contribute to impaired cerebellar function resulting from loss-of function mutations in the Ca(V)2.1 channel gene.


Overexpression of the WAPO-A1 gene increases the number of spikelets per spike in bread wheat.
Two homoeologous QTLs for number of spikelets per spike (SPS) were mapped on chromosomes 7AL and 7BL using two wheat MAGIC populations. Sets of lines contrasting for the QTL on 7AL were developed which allowed for the validation and fine mapping of the 7AL QTL and for the identification of a previously described candidate gene, WHEAT ORTHOLOG OF APO1 (WAPO1). Using transgenic overexpression in both a low and a high SPS line, we provide a functional validation for the role of this gene in determining SPS also in hexaploid wheat. We show that the expression levels of this gene positively correlate with SPS in multiple MAGIC founder lines under field conditions as well as in transgenic lines grown in the greenhouse. This work highlights the potential use of WAPO1 in hexaploid wheat for further yield increases. The impact of WAPO1 and SPS on yield depends on other genetic and environmental factors, hence, will require a finely balanced expression level to avoid the development of detrimental pleiotropic phenotypes.


Ventral cervical fusion at multiple levels using free vascularized double-islanded fibula - a technical report and review of the relevant literature.
Reconstruction of the cervical spine using free vascularized bone flaps has been described in the literature. The reports involve either one level or, when multiple levels, they describe en bloc resection and reconstruction. Stabilization of different levels with a preserved intermediate segment with a single vascularized flap has not been described. We report on the case of a 55-year-old man, who had been operated several times using conventional techniques for cervical myelopathy and instability, who presented to us with severe neck pain. Diagnostic procedures showed pseudarthrosis of C3/4 and stress-overload of the C3/4 and C5/6 segments. The C4/5 fusion was adequately rigid, but avascular. We performed anterior cervical fusion at the C3/4 and C5/6 levels with a vascularized fibula flap modified as a double island. The rigidly fused C4/5 block was preserved and vascularized with the periosteum bridging the two fibular islands. The method and technique are described in detail. Fusion was adequate. Donor site morbidity was minimal and temporary. The patient is symptom free to date (25 months). The suggested method provides the possibility of vertebral fusion at different levels using a single vascularized flap. The indications for this procedure are (1) repeated failure of conventional methods, (2) established poor bone healing and bone non-union with avascular grafts and (3) a well-fused or preserved intermediate segment. The relevant literature is reviewed.


Ethnic and sex differences in the association of child maltreatment and depressed mood. The HELIUS study.
Maltreatment in childhood increases the risk of depression later in life. The influence of ethnicity and sex on this relationship is less well understood. This paper examines ethnic and sex differences in rates of child maltreatment (CM) and depressed mood in adulthood and investigates whether the association between CM and depressed mood in adulthood is influenced by ethnicity and sex. Baseline data from the multiethnic HELIUS study (Amsterdam, the Netherlands) was analyzed and consisted of 22,551 participants aged 18-70 years from Dutch, African Surinamese, South Asian-Surinamese, Turkish, Moroccan, or Ghanaian ethnic backgrounds. Physical, sexual and psychological abuse, and emotional neglect in childhood were self-reported and depressed mood was measured using the Patient Health Questionnaire-9. Logistic regression analyses demonstrated that emotional neglect and psychological abuse both have significant positive relationships with depressed mood. Furthermore, these associations were consistent across ethnic groups. The addition of ethnicity-by-maltreatment interaction terms to a main effects model revealed that Ghanaians who reported physical abuse in childhood were the only ethnic group with significantly increased odds for depressed mood (OR = 2.62, p = .001), with the same being true for Moroccans who experienced sexual abuse in childhood (OR = 1.91, p = .008). No sex differences were found in the relationships between CM and depressed mood. The association between different types of CM and depressive symptoms may not always be uniform across ethnic groups. Greater understanding of the nuances present in these relationships is required to develop effective prevention and intervention strategies for multiethnic populations.


Effects of toluene inhalation on pulmonary host defenses of mice.
The potential hazards of exposure to vapor-phase toluene on pulmonary host defenses were evaluated. Mice exposed to concentrations ranging from 2.5-500 ppm, including the threshold limit value level of 100 ppm, exhibited increased susceptibility to respiratory infection with Streptococcus zooepidemicus. The no-measurable-effect level for single, as well as for 5 exposures was 1 ppm. Significantly decreased pulmonary bactericidal activity was observed after single exposures to 500, 250, 100 and 2.5 ppm toluene, and after 5 daily 3-h exposures to 1.0 ppm of toluene. A 20-exposure study with toluene at 1 ppm produced no changes in either of the 2 assays.


Contact phase of blood coagulation in cardiogenic pulmonary oedema (CPO) and adult respiratory distress syndrome (ARDS).
In order to assess the role of the kallikreinkinin (k-k) system in the pathogenesis of pulmonary oedema, we studied the contact phase factors of blood coagulation, as well as the haemodynamics and blood gas changes in 34 patients with pulmonary oedema, 23 of them with Adult Respiratory Distress Syndrome (ARDS) and 11 with cardiogenic pulmonary oedema (CPO). We have verified significant differences in the haemodynamic pattern and blood gases between the two groups of patients, which corroborate the previously established differences between both types of pulmonary oedema. Our results reveal k-k system activation in ARDS patients, with a significant fall in factor XII (p less than 0.05), prekallikrein (p less than 0.01), alpha-2-macroglobulin (p less than 0.01) and high molecular - weight kininogens (p less than 0.005), with a rise in C1-esterase inhibitor (p less than 0.001) in comparison with patients with CPO. All of the CPO patients had normal prekallikrein levels, whereas 15 out 23 ARDS cases (65%) had decreased prekallikrein values. Our results suggest that the k-k system activation could play a role in the pathogenesis of ARDS. Estimation of prekallikrein levels may be helpful in the differential diagnosis of ARDS.


Current and Emerging Options in the Management of EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Considerations in the Elderly.
The elderly population with cancer is increasing worldwide. Currently, the median age at lung cancer diagnosis is approximately 70 years. Clinicians are increasingly dealing with a population of elderly non-small-cell lung cancer patients characterised by relevant co-morbidities and ageing-related characteristics, making treatment choice more challenging. Robust evidence demonstrated that activating mutations in the epidermal growth factor receptor (EGFR) gene are the best predictor for sensitivity to EGFR tyrosine kinase inhibitors. Nine large phase III trials conducted in both the Asian and Caucasian populations demonstrated that gefitinib, erlotinib and afatinib are superior to standard platinum-based chemotherapy as front-line treatment and subgroup analyses confirmed the superiority of erlotinib or gefitinib over chemotherapy in the second-line setting. Although no large phase III trials have been specifically conducted in EGFR mutation-positive (EGFR (mut+)) elderly non-small-cell lung cancer patients, available data, coming from subgroup analysis, retrospective series or small prospective phase II trials, replicated in the elderly the results observed in the general population, thus suggesting that age per se does not represent a criterion for treatment selection. In addition, the favourable toxicity profile of EGFR-tyrosine kinase inhibitors makes these agents the preferred option in such a group of patients, for which concomitant medications are often required.


Electrical ablation of atrial muscle. I. Early and late anatomic observations in canine atria.
Electrode catheter ablation (ECA) of atrial muscle may be a useful technique for the treatment of drug-refractory supraventricular tachycardias originating in the right atrial free wall (RAFW). We performed this study in order to determine: (1) the safety of electrical shocks applied to the RAFW and (2) the early and late anatomic effects of ECA. Twelve beagle puppies, ranging in age from 2.0 to 7.5 months and weighting 2.3 to 8.0 kg, underwent electrical ablation of the RAFW, using energy doses of 100 to 400 J. At the highest energy doses tested (400 J), one puppy died of refractory ventricular fibrillation and one of low cardiac output. Atrial perforation and cardiac tamponade occurred in two puppies, each of which received one shock of 200 J. The area of myocardial damage following ECA shocks of 150 J was greater than for shocks of 100 J, 94 +/- 14 vs 56 +/- 11 mm2, respectively (p less than 0.02). Acutely, ECA produced transmural hemorrhagic necrosis. Eleven weeks after electrical ablation, atrial fibrosis was apparent at the site of ablation. In conclusion, ECA may be used to fulgurate atrial tissue in the RAFW. We recommend 150 J as a safe upper limit in small subjects, although higher energy doses may not produce cardiac perforation or adverse hemodynamic effects in larger subjects.


Second generation of hydroxyethylamine BACE-1 inhibitors: optimizing potency and oral bioavailability.
BACE-1 inhibition has the potential to provide a disease-modifying therapy for the treatment of Alzheimer's disease. Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable.


Inhibition of meiotic divisions of rat spermatocytes in vitro by polycyclic aromatic hydrocarbons.
The toxic effects of polycyclic aromatic hydrocarbons (PAH) on spermatogenic cells undergoing meiotic division were investigated in vitro. Toxicity was assayed as alterations in cell nucleus morphology and cell survival and by DNA flow cytometry. Benzo[a]pyrene (BP) and 7,12-dimethylbenz[a]anthracene (DMBA) inhibited the progression of spermatocytes through meiotic division and were highly cytotoxic at concentrations higher than 1 microM. These results were obtained upon addition of a drug-metabolizing system, indicating that the seminiferous tubules lack the enzymes required for the initiation of PAH metabolism. The spindle poisons, e.g., vincristine and Colcemid, a group of direct-acting agents, affected spermatogenesis during meiotic division in a manner similar to that observed with PAH. In contrast, adriamycin did not inhibit meiotic division, although it did induce the formation of meiotic micronuclei as a result of chromosome breakage. It is concluded that low concentrations, i.e., 0.1 microM of PAH, strongly inhibit meiotic division, presumably after metabolic activation to reactive molecules functionally resembling direct-acting alkylating agents. High concentrations of PAH are cytotoxic.


The effect of intravenous premedication with lorazepam (ativan), pentobarbitone or diazepam on recall.
Sixty-nine patients undergoing regional anaesthesia were premedicated with either lorazepam (1, 2, 3 or 5 mg), diazepam (5 or 10 mg), pentobarbitone (50 mg) or placebo given i.v., on a double-blind, randomized basis. A simple yet rigorous protocol was used to test the effect of these drugs on anterograde recall. Lorazepam 3 and 5 mg was found to affect anterograde recall significantly. None of the other drugs tested affected recall.


Effects of sodium butyrate and dimethylsulfoxide on human pancreatic tumor cell lines.
The effects of 1 mM sodium butyrate or 2% dimethylsulfoxide (DMSO) on three human pancreatic tumor cell lines were examined. The cell lines tested were MIA PaCa-2, PANC-1 and CAPAN-1. Both butyrate and DMSO inhibited the ability of all three lines to form colonies in soft agar. These results suggest that the use of these agents provides a model system for the study of the molecular changes involved in human pancreatic cancer. In butyrate all the cell lines showed a marked increase in cellular levels of alkaline phosphatase, while growth in DMSO led to a reduction in most cases. DMSO caused a rapid reduction in the attachment of all three cell lines to collagen substrates, while butyrate had no effect. These results illustrate the fact that although both butyrate and DMSO appear to greatly reduce the parameters correlated with tumorigenicity of human pancreatic cancer cells, the mechanisms involved may be very different.


Effects of using cane and vestibular rehabilitation on the walking function in elderly patients with dizziness.
Adults over the age of 65 years with balance disorders are at about twice the risk of falls, compared with those without balance disorders. Falls contribute to about 74% of the proximal femoral fractures commonly seen in the elderly. Since balance disorders are more prevalent in older adults than in younger adults, it is important to deal with balance disorders in older adults to prevent falls and the resulting deterioration in their ADL (activity of daily living). In this study, we investigated the effects of vestibular rehabilitation (VR) and cane use on improving gait and balance in patients aged over 65 years with balance disorder. Patients aged over 65 years presenting to the Department of Otolaryngology at St. Marianna University School of Medicine between July 1 and November 1, 2018, with symptoms of dizziness for ≥ 3 months and a Japanese translation of the Dizziness Handicap Inventory score of ≥ 26 were included in the study. We quantitatively analyzed their gait before and after VR, and with and without the use of a cane. A total of 21 patients participated in the study (14 women; mean age 73.9 ± 6.9 years). Before VR, using a cane made no difference to step length or walking speed. After VR, using a cane increased step length from 50.5 cm (95% confidence interval [CI], 47.4-53.7 cm) to 52.0 cm (95% CI, 48.9-55.1 cm) (p = 0.039). There was no change in walking speed. A comparison of walking assessment results while using a cane before and after VR showed that step length increased from 49.9 cm (95% CI, 46.6-53.2 cm) to 52.0 cm (95% CI, 48.9-55.1 cm) (p = 0.005), and walking speed increased from 90.5 cm/s (95% CI, 82.7-98.4 cm/s) to 96.1 cm/s (95% CI, 88.3-103.9 cm/s) (p = 0.005). Walking speed and step length with the use of a cane significantly improved following VR. VR and cane use may act synergistically to improve walking.


Microbiology of osteomyelitis in patients infected with the human immunodeficiency virus.
Osteomyelitis rarely develops in patients infected with the human immunodeficiency virus despite their immunosuppressed state. In the limited literature available on this subset of patients, the role of opportunistic micro-organisms is controversial. Our purpose is to describe the microbiologic features of osteomyelitis. This is a retrospective review of 20 patients infected with the human immunodeficiency virus who were admitted to our musculoskeletal infection ward with the diagnosis of osteomyelitis. Eleven patients (55%) were intravenous drug users. Medical comorbidities were present in 14 of 20 patients (70%), including tuberculosis in five patients and hepatitis C in three patients. The mean CD4 count was 269/mm (range, 20-539/mm). Osteomyelitis was monomicrobial in 10 patients (50%) and polymicrobial in seven patients (35%) whereas in three patients no organism was cultured. The most common pathogen was Staphylococcus aureus, present in 10 patients (50%). No mycobacterial or fungal pathogens were identified. Infection recurred in 3 of 14 patients (21%) that were available for followup. Despite their immunocompromised status, patients infected with the human immunodeficiency virus did not develop osseous infections with opportunistic pathogens. Staphylococcus aureus was the most common pathogen found; however, a considerable proportion of infections were polymicrobial.


Time course of phorbol-12-myristate-13-acetate (PMA)-induced down-regulation of topoisomerase II in human leukemia cells.
The time course of the down-regulation of topoisomerase II associated with phorbol-induced differentiation was quantified in two human HL-60 leukemia cell lines. In the line sensitive to phorbol-induced differentiation (S cells), immunoreactive topoisomerase II levels did not begin to fall until 12 hr following exposure of the cells to phorbol ester. Thereafter, levels declined over the next 36 hr. By contrast, phorbol treatment of the phorbol ester tolerant cell line (PET cells) produced a transient decrease in topoisomerase II only to be followed by a recovery to pretreatment levels. The patterns of the alterations in topoisomerase II mRNA levels mirrored those of the alterations in immunoreactive topoisomerase II. Unexpectedly, nuclear run-on studies revealed that transcriptional start sites were not reduced in either cell line following their exposure to phorbol esters. These data suggest that the down-regulation of topoisomerase II is a consequence rather than a cause of phorbol-induced differentiation in HL-60 cells. Furthermore, this down-regulation is not mediated by a decrease in the number of topoisomerase II transcription sites.


Time course of NT-proBNP levels after acute ischemic stroke.
Studies suggest that N-terminal-pro-brain natriuretic peptide (NT-proBNP) can be a biomarker of cardioembolic stroke. However, the best time to measure it after stroke is unknown. We studied the time course of NT-proBNP in patients with ischemic stroke. Consecutive acute ischemic stroke patients were admitted over 10 months to a Stroke Unit. Stroke type was classified according to TOAST. Blood samples were drawn within 24, 48, and 72 hours after stroke. Friedman test was used to compare NT-proBNP values across the 3 times in all, cardioembolic and non-cardioembolic stroke patients. Post hoc analysis with Wilcoxon signed-rank tests was conducted with a Bonferroni correction. Mann-Whitney test was used to compare median values of NT-proBNP between cardioembolic and non-cardioembolic stroke patients. ROC curves were drawn to determine NT-proBNP accuracy to diagnose cardioembolic stroke at 24, 48, and 72 hours after stroke onset. One hundred and one patients were included (29 cardioembolic) with a mean age of 64.5±12.3 years. NT-proBNP values for cardioembolic stroke were significantly higher (P < 0.001) than for non-cardioembolic stroke in the 3 time points. NT-proBNP was highest in the first 24-48 h after ischemic stroke and decreased significantly 72 h after stroke onset. The area under the curve for the three time points was similar. NT-proBNP levels were highest in the first 2 days after ischemic stroke and declined significantly thereafter. However, the area under the curve for the three time points was similar. The first 72 hours after ischemic stroke have a similar diagnostic accuracy to diagnose cardioembolic stroke.


Antileishmanial, cellular mechanisms, and cytotoxic effects of green synthesized zinc nanoparticles alone and in combined with glucantime against Leishmania major infection.
We decided to investigate the antileishmanial, cellular mechanisms, and cytotoxic effects of green synthesized Zinc nanoparticles (ZnNPs) alone and combined with glucantime against Leishmania major infection. The effect of green synthesized ZnNP on L. major amastigote was studied through macrophage cells. The mRNA expression level of iNOS and IFN-γ followed by the exposure of J774-A1 macrophage cells to ZnNPs was assessed by Real-time PCR. The Caspase-3-like activity of promastigotes exposed to ZnNPs was studied. Effects of ZnNPs alone and combined with glucantime (MA) were studied on cutaneous leishmaniasis in BALB/c mice. ZnNPs displayed the spherical shape with sizes ranging from 30 to 80 nm. The obtained IC50 values for ZnNPs, MA, and ZnNPs + MA were 43.2, 26.3, and 12.6 µg/mL, respectively; indicating the synergistic effects of ZnNPs in combination with MA. CL lesions had completely improved in the mice received with ZnNPs in combination with MA. The mRNA expression level of iNOS, TNF-α, and IFN-γ was dose-dependently (p < 0.01) upregulated; whereas it was downregulated in IL-10. ZnNPs markedly stimulated the caspase-3 activation with no significant toxicity on normal cells. Based on these in vitro and in vivo results, green synthesized ZnNPs, mainly along with MA, showed that has the potential to be introduced as a new drug for CL therapy. Triggering of NO production, and inhibition of infectivity rate are revealed as mechanisms of action ZnNPs on L. major. But, supplementary investigations are necessary to clear the efficacy and safety of these agents.


Long-Term Effects of Proximal Splenic Artery Embolization on Splenic Volume and Platelet Count.
The spleen is the most commonly injured visceral organ in blunt abdominal trauma. Post-splenectomy infection risk has led to the shift toward spleen preserving procedures and splenic artery embolization (SAE) is now the treatment of choice for hemodynamically stable patients with splenic injury. This study aims to assess the long-term effect of SAE on splenic volume and platelet count. Using CPT codes, 66 patients who underwent SAE were identified, and 14 of those who had the necessary imaging and laboratory follow-up were included in the study. Indications for SAE were portal hypertension in 8 patients, bleeding in 4 patients, and thrombocytopenia in 1, and one patient had a separate indication. Splenic volume was calculated by automated volumetric software (Aquarius, TeraRecon, Inc.). Paired t-tests were performed to compare splenic volume and platelets before and after SAE. Fourteen patients (7 males, 7 females) with a mean age of 51 ± 11.95 years underwent SAE and were followed by a repeat computed tomography scan at an average of 733.57 days. Nine SAEs were performed using vascular plugs, 3 using micro coils, and 2 out of that were with Gelfoam slurry, and 2 using coils only. All embolizations were technically successful with complete cessation of flow. Mean splenic volumes pre- and post-SAE were 903.5 ± 523.73 cm3 and 746.5 ± 511.95 cm3, respectively, representing a mean decrease of 8.31% compared to baseline [P = 0.346]. Minimum platelet counts (x103) pre-SAE (within 3 months) and post-SAE (2 weeks to 3 months after the procedure) were 55.79 ± 57.11 and 116 ± 145.40, respectively. The minimum platelet count showed a statistically significant mean increase of 134.92% (P = 0.033). The splenic volume is not altered significantly by SAE in the long term. Similarly, the platelet count is also not significantly altered at 3 months follow-up. This study, although small, suggests that SAE is a safe intervention that can preserve splenic volume and function in the long term.


Developing an experimental model for surgical drainage investigations: an initial report.
We sought to pilot and initiate validation of a surgical drainage model. We designed a laboratory model to compare Jackson-Pratt surgical drains using 3 soups to emulate body fluids of serous, purulent, and necrotic debris. Each drain was trialed with each of the 3 fluids. Time and completeness of drainage were recorded. A survey of surgical residents and faculty was performed for convenience sampling. Under serous conditions, the round Jackson-Pratt drained the cavity quicker, but left a larger residual volume of fluid. Under purulent conditions, the round Jackson-Pratt was slower and drained less fluid. With debris fluid, the round Jackson-Pratt was quicker with less residual fluid whereas the flat type clogged each time. Survey results showed adequate concordance with surgeons in agreement on soup choice. The Jackson-Pratt drains perform differently depending on the drainage situation. The surgical community requires improved drain data to drive practice patterns.


Myotoxicity induced by Cerastes cerastes venom: Beneficial effect of heparin in skeletal muscle tissue regeneration.
Myonecrosis is a relevant tissue damage induced by snakes of Viperidae family often leading to permanent tissue and function loss and even amputation. The aim of this study was to evaluate the effect of heparin on skeletal muscle tissue regeneration after Cerastes cerastes envenomation. Mice received either the venom (1 LD50) by i.m. route, or the venom followed, by heparin administration by i.v. route at 15 min and 4 h. Obtained results showed that Cerastes cerastes venom induced deep tissue structure alterations, characterized mainly by edema, hemorrhage, myonecrosis and inflammation. Myotoxicity was correlated with increased CK levels in sera, concomitant with their decrease in muscle tissue homogenates. Muscle wet weight was restored within 2 weeks after heparin treatment and 28 days in the envenomed group. Heparin treatment significantly decreased MPO activity, suggesting an anti-inflammatory effect. NO, HGF, VEGF and G-CSF levels were increased after heparin administration. These mitogenic factors constitute potent stimuli for satellite and endothelial cells improving, thus, muscle regeneration. This study showed that muscle tissue recovery was significantly enhanced after heparin treatment. Heparin use seems to be a promising therapeutic approach after viper envenomation.


Oxytocin and Social Adaptation: Insights from Neuroimaging Studies of Healthy and Clinical Populations.
Adaptation to the social environment is critical for human survival. The neuropeptide oxytocin (OT), implicated in social cognition and emotions pivotal to sociality and well-being, is a promising pharmacological target for social and emotional dysfunction. We suggest here that the multifaceted role of OT in socio-affective processes improves the capability for social adaptation. We review OT effects on socio-affective processes, with a focus on OT-neuroimaging studies, to elucidate neuropsychological mechanisms through which OT promotes social adaptation. We also review OT-neuroimaging studies of individuals with social deficits and suggest that OT ameliorates impaired social adaptation by normalizing hyper- or hypo-brain activity. The social adaption model (SAM) provides an integrative understanding of discrepant OT effects and the modulations of OT action by personal milieu and context.


Synergistic stimulating effect between cyclic AMP and phorbol ester on plasminogen activator inhibitor type 2 production in human promyelocytic leukemia cell line PL-21.
We investigated the effect of agents which raise intracellular cyclic AMP (cAMP) and protein kinase C activators on the production of plasminogen activator inhibitor type-2 (PAI-2) by cultured human promyelocytic leukemia cell line, PL-21. As previously reported, PMA, a protein kinase C activator, showed a strong stimulating effect on the PAI-2 production. 1-oleoyl-2-acetyl-sn-glycerol (OAG), another synthetic protein kinase C activator, also showed a stimulating effect, which was, however, much less than that of PMA. The agents which raise intracellular cAMP, dibutyryl cAMP, 8-bromo cAMP, prostaglandin E1, and 3-isobutyl-1-methyl-xanthine, little increased the PAI-2 production when tested alone, but showed significant synergistic effects with PMA or OAG. The synergistic effect between PMA and dibutyryl cAMP was further verified by SDS-PAGE followed by immunoblotting using a monoclonal antibody against the PAI-2. It is interesting that the up-regulation of PAI-2 by cAMP and the synergistic effect with PKC activators forms a contrast to the previous reported bi-directional regulation of endothelial PAI-1 secretion by PKC activator and cAMP.


Evaluation of matrix effects for pesticide residue analysis by QuEChERs coupled with UHPLC-MS/MS in complex herbal matrix.
Matrix effects (MEs) can heavily affect the accuracy and reproducibility of a pesticide residue analysis method, especially in complex matrices such as herbs. Therefore, it is of great importance to assess MEs of pesticides in herbal matrices. In this research, the MEs of 28 pesticides and their metabolites in five types of herbs representing different medicinal parts were evaluated by UHPLC-MS/MS analysis after QuEChERs pretreatment. Suppression MEs were found for most organophosphorus and carbamate pesticides while enhancement MEs were observed for sulfonylurea. Besides, stronger inhibition effects were observed for early or late elution pesticides and in matrices of Lonicerae japonicae flos and Perillae folium. Some pesticides were observed with enhancement MEs in Astragali radix. These results indicated that MEs were mainly affected by the retention time of the analytes, the ionization mode of the precursor ions, the overall structure of the compounds, and the chemical composition of the matrices.


Transcatheter Aortic Valve Replacement in Asia: Present Status and Future Perspectives.
Over the last decade, based on evidence from multiple randomized clinical trials, transcatheter aortic valve replacement (TAVR) has become the established treatment for patients with symptomatic severe aortic stenosis. Despite the overwhelming expansion of TAVR in Western countries, the initial uptake and widespread adoption of this procedure have been relatively delayed in Asian countries, owing to the high cost of devices; limited local health and reimbursement policies; and lack of specific training/proctoring program, specialized heart team, or dedicated infrastructure. Furthermore, it has not yet been determined whether there are substantial interracial and ethnic differences in the clinical characteristics, comorbidities, and anatomic features, as well as procedural and long-term outcomes, in patients receiving TAVR. In this review, we provide not only a comprehensive look at the current status and outcomes of TAVR in Asian populations compared with those of Western populations but also a perspective on the future of TAVR in Asia.


Toxicity studies on dermal application of plant extract of Plumbago zeylanica used in Ethiopian traditional medicine.
Plant-based therapeutic preparations are cyclically returning to complement dermatologic therapy, however, data on the toxicity profile of such plants are lacking. In the present study, Plumbago zeylanica, a medicinal plant commonly used in Ethiopia for skin diseases was subjected to a systematic dermatotoxicity study. To this effect, the dermatotoxicity of 80% methanol extract of the root part of Plumbago zeylanica was investigated in animals following standard procedures for irritation, sensitization, acute toxicity and repeated toxicity tests. Extraction of plant material with 80% methanol resulted in 9.45% of crude extract of Plumbago zeylanica. The skin irritation test on rabbits showed Plumbago zeylanica extract to be a moderate irritant, with a primary irritation index of 2.00. Sensitization test on mice by the Mouse Ear Swelling Test method revealed the extract to be non-sensitizer in a dose range of 4-10mg/ml and the percent responder was zero. Acute dermal toxicity test on rats did not produce any overt signs of toxicity, except that there was a weight gain difference between the test and control groups of female rats. This was not, however, supported by other parameters, like the absolute and relative organ weights. Repeated dose toxicity test was associated with increased relative testis weight (P<0.05) as well as higher values for Blood urea nitrogen and K+ (P<0.05) in both sexes with the highest dose (1000 mg/kg) group, although histopathological analyses failed to lend support to these observations. Taken together, the dermatotoxicity test results from this study suggest that Plumbago zeylanica toxic effects might be limited to effects like moderate irritation.


Circulating circTOLLIP serves as a diagnostic biomarker for liquid biopsy in non-small cell lung cancer.
Circular RNAs (CircRNAs) have been found to possess vital functions in tumorigenesis of various cancer types, including non-small cell lung cancer (NSCLC). The aim of this study was to identify and explore the diagnostic values of the newly found Toll interacting protein (TOLLIP)-derived circRNA (circTOLLIP) for liquid biopsy in NSCLC. RNase R and actinomycin D assays were conducted to confirm the existence and stability of circTOLLIP. RT-qPCR was performed to identify the expression levels of circTOLLIP in NSCLC tumor tissues, whole blood, and cell lines. The diagnostic values were evaluated by receiver operating characteristic (ROC) curve analysis. CircTOLLIP was screened as a candidate biomarker and was found to be significantly down-regulated in both NSCLC tissues and cell lines. Interestingly, circulating circTOLLIP was also lower-expressed in the whole blood of patients with NSCLC compared to that of patients with benign lung disease and healthy controls. Importantly, the circulating circTOLLIP represented better diagnostic values in comparison to the traditional tumor markers (NSE, CYFR21-1, and CA72-4), and showed higher stability even though the whole blood was exposed to various tough conditions. Our findings indicate that circTOLLIP can be used as a non-invasive biomarker to distinguish early-stage NSCLC from benign lung diseases and from healthy controls, suggesting the potential application of circTOLLIP for liquid biopsy in NSCLC.


RNA-binding protein FXR1 drives cMYC translation by recruiting eIF4F complex to the translation start site.
Fragile X-related protein-1 (FXR1) gene is highly amplified in patients with ovarian cancer, and this amplification is associated with increased expression of both FXR1 mRNA and protein. FXR1 expression directly associates with the survival and proliferation of cancer cells. Surface sensing of translation (SUnSET) assay demonstrates that FXR1 enhances the overall translation in cancer cells. Reverse-phase protein array (RPPA) reveals that cMYC is the key target of FXR1. Mechanistically, FXR1 binds to the AU-rich elements (ARE) present within the 3' untranslated region (3'UTR) of cMYC and stabilizes its expression. In addition, the RGG domain in FXR1 interacts with eIF4A1 and eIF4E proteins. These two interactions of FXR1 result in the circularization of cMYC mRNA and facilitate the recruitment of eukaryotic translation initiation factors to the translation start site. In brief, we uncover a mechanism by which FXR1 promotes cMYC levels in cancer cells.


EZH2 serves as a promising therapeutic target for fibrosis.
Fibrosis affects the function of many organs and tissues, and its persistent development can lead to tissue sclerosis and cancer, even leading to death further. Recent studies suggested that enhancer of zeste homolog 2 (EZH2), a major regulator of epigenetic repression, played an important role in the occurrence and development of fibrosis through gene silencing or transcriptional activation. As the most studied and powerful pro-fibrotic cytokine closely related to EZH2, TGF-β1 was primarily involved in the regulation of fibrosis along with the typical Smads and non-Smads signaling pathways. In addition, EZH2 inhibitors demonstrated inhibitory effects in several types of fibrosis. This review summarized the relationship underlying the action of EZH2, TGF-β1/Smads, and TGF-β1/non-Smads with fibrosis and described the research progress of EZH2 inhibitors in the treatment of fibrosis.


The role of vegetable and fruit consumption and other habits on survival following the diagnosis of oral cancer: a prospective study in Spain.
The authors carried out a hospital-based prospective study to evaluate the role of behavioral and clinical risk factors, occurring before and after diagnosis, on the prognosis of 146 patients with newly diagnosed oral cancer using Cox models. High weekly intake of vegetables before and after diagnosis were both associated with lower recurrence rates, longer overall survival and longer oral cancer survival. Diagnostic delay was associated with an increased risk of recurrence and oral cancer mortality. Patients presenting with pharyngeal pain or a mucosal lesion had a longer oral cancer survival than patients presenting with other symptoms. Quitting tobacco and alcohol consumption before and after diagnosis were both associated with a lower recurrence and/or better survival, but the effects were not statistically significant. This study suggests that high consumption of vegetables before and after diagnosis of oral cancer may reduce the risk of recurrence, overall mortality and cancer mortality in oral cancer patients.


The effects of teaching medical students psychotherapy skills in the outpatient department.
A psychiatric clerkship which emphasizes a clinical exposure to the conduct of outpatient psychodynamic psychotherapy is described and evaluated. Compared to more traditional inpatient based clerkships, an outpatient psychotherapy-oriented clerkship attracts significantly greater numbers of students. In addition, medical students taking such a rotation rate its educational value on its completion significantly more positively compared to other clerkship sites. Finally, students taking the psychotherapy oriented clerkship opt for psychiatry as a specialty significantly more frequently than students taking the more traditional clerkships. The impact of such a learning experience on interpersonal skills with non-psychiatric, medical patients is also discussed.


Natural radioactivity of groundwater in Vendian deposits in St. Petersburg Region.
The study is focused on the hydrogeological conditions and the chemistry of groundwater of the Vendian aquifer in the western part of the Leningrad oblast (Karelian Isthmus and the area near Sosnovy Bor town) and St. Petersburg City, where groundwater features higher radioactivity, but nevertheless it is used for drinking water supply. Data on the radiological characteristics, which have been determined in the estimation of the quality of groundwater used for drinking are generalized and analyzed. These characteristics include the gross alpha and gross beta activity and the specific activity of natural radionuclides 222Rn, 226Ra, 228Ra, 210Pb, 210Po, 238U, and 234U. The data were subjected to statistical and correlation analysis to determine the hygienic criteria for the use of groundwater of this aquifer for drinking water supply and to study the sources and the processes of formation of the natural radiological background. Groundwater quality standards were shown to be exceeded in the majority of the analyzed wells. The brackish water in the southern, deeper, part of the aquifer system was shown to have higher radioactivity and relatively high concentrations of 226Ra, 228Ra, 210Pb, and 210Po, compared with fresh water in the northern part of the territory, of which higher, though nonuniform, 222Rn activity is typical. Relationships between the radiation characteristics of groundwater are considered along with the causes of formation of groundwater radionuclide composition as a result of the higher radioactivity of the host deposits and the chemistry of groundwater; changes in the radiological and hydrochemical background groundwater characteristics from the north to the south are characterized in accordance with the subsidence of the aquifer system and an increase in the stagnation of the hydrochemical regime. The analysis of the well-known relationship between the concentrations of radium isotopes in groundwater, uranium and thorium isotopes in the host rocks, and groundwater residence time in the aquifer, along with the comparison of the available field data with calculation results, suggested the conclusion that the concentration of uranium in the water-bearing rocks in the major portion of the area under consideration is higher than its regional mean values.


Tolerogenic dendritic cells generated with IL-10/TGFβ1 relieve immune thrombocytopenia in mice.
Activated platelet-specific autoreactive T cells play a key role in the pathophysiology of immune thrombocytopenia (ITP). Tolerogenic dendritic cells (tDCs) that induce T cells tolerance to platelet autoantigens are a promising strategy for specific cellular therapy in autoimmunity. In this study, we generated three kinds of GPIIb-specific tDCs stimulated by IL-10 (10-DCs), TGFβ1 (T-DCs), or a combination of IL-10 and TGFβ1 (10T-DCs), respectively, and compared their phenotypes and biological function. Our data demonstrate that GPIIb-specific 10T-DCs induced the weakest memory lymphocytes responses and exhibited stronger tolerogenic potential than others, making them suitable for tolerance inducing therapies. Furthermore, in ITP mice model we found that 10T-DCs abrogated the decrease in platelet counts and the increase in serum IFN-γ level, confirming the in vivo tolerogenic potential of 10T-DCs. Our study provides a promising strategy for ITP intervention in the clinic by the induction of platelet-specific immune tolerance.


UmTea1, a Kelch and BAR domain-containing protein, acts at the cell cortex to regulate cell morphogenesis in the dimorphic fungus Ustilago maydis.
The spatial organization of a cell is crucial for distribution of cell components and for cell morphogenesis in all organisms. Ustilago maydis, a basidiomycete fungus, has a yeast-like and a filamentous form. The former buds once per cell cycle at one of the cell poles, and can use the same site repeatedly or choose a new site at the same pole or opposite pole. The filamentous form consists of a long apical cell with short septate basal compartments lacking cytoplasm. It grows at the apex and can reverse growth forming a new growth zone at the basal end. We are interested in understanding how these different morphologies are generated. Here we present identification and characterization of U. maydis Tea1, a homologue of the fission yeast cell end marker Tea1. We demonstrate that UmTea1, a Kelch domain protein, interacts with itself and is an important determinant of the site of polarized growth: tea1 mutants bud simultaneously from both cell poles and form bifurcate buds. UmTea1 also regulates septum positioning, cell wall deposition, cell and neck width, coordination of nuclear division and cell separation, and localization of sterol-rich membrane domains. Some of these functions are shared with UmTea4, another cell end marker. We show that Tea1::GFP localizes to sites of polarized or potential polarized growth and to the septation site in the yeast-like form. Additionally, localization of Tea1::GFP as rings along the filament suggests that the filament undergoes septation. We hypothesize that Tea1 may act as a scaffold for the assembly of proteins that determine the site of polarized growth.


A method to analyze the cord geometrical uncertainties during head and neck radiation therapy using cone beam CT.
We developed a method to analyze quantitatively the residual cord geometrical uncertainties after image registration during head and neck radiation therapy by using sequential cone beam CT (CBCT). The geometrical centroid line of cervical spinal canal was computed to serve as a cord surrogate. We found that the cord motions were non-uniform from C1 to C6, and that the patterns of motion were variable across patients. This method has potential applications in monitoring cord setup accuracy and in designing treatment margins.


Emotions experienced at event recall and the self: Implications for the regulation of self-esteem, self-continuity and meaningfulness.
The intensity of positive affect elicited by recall of positive events exceeds the intensity of negative affect elicited by recall of negative events (fading affect bias, or FAB). The research described in the present article examined the relation between the FAB and three regulatory goals of the self: esteem, continuity and meaningfulness. The extent to which an event contributed to esteem (Study 1), continuity (Study 2) or meaningfulness (Study 3) was related to positive affect at event recall provoked by positive memories and to negative affect at event recall provoked by negative memories. The relation between affect experienced at recall and the three regulatory goals was bidirectional. The results showcase how individuals use recall for self-regulatory purposes and how they implement self-regulatory goals for positive affect.


[Computer-assisted management of depots for blood products in health establishments].
To manage the filing of blood components at the hospital of the city of Bayeux, the laboratory uses Cursus, a dedicated software for haemovigilance. Benefits for using this software at different steps of the blood bank management are: simplification, security and harmonization of practices during receipt and issurance of blood components, securing recordings with the use of bar codes for patient identification and blood components listing, implementation of a computerized tracking system for transfusion, traceability, limitation of written documents and availability of statistics on the management of the depot.


Effect of the homogeneity of the column set on the performance of a simulated moving bed unit. II. Experimental study.
Previous studies of the simulated moving bed (SMB) process assume identical characteristics of all the columns incorporated in a given unit. Due to the practical impossibility to manufacture identical columns, numerical applications of the theory to modeling and optimization use for each of the needed column parameter the average value for the entire column set. In this study, the effects of these simplifications on the actual productivity of the SMB process are evaluated by making exact calculations, i.e., by taking the differences in the porosity values into account. We apply a revised set of separation conditions previously introduced and derived from the equilibrium theory. Earlier theoretical results are compared to experimental results obtained in the study of the enantiomeric separation of Tröger's base on Chiralpak AD. Due to the nonLangmuirian character of the adsorption isotherms of these two compounds on the packing material used, the separation area cannot be determined analytically. As an alternative, a reliable numerical algorithm was used to scan a wider region and to define the separation area. The form of this area depends on the applied porosity values. A UV detector and a laser polarimeter located at one node of the SMB monitor on-line the internal concentration profiles. Excellent agreement between the calculated and the experimentally determined concentration profiles was obtained under nonlinear conditions. The influence of column-to-column variations on the performance of the SMB process was found to be more significant under nonlinear than under linear conditions.


Uninfected red cells from malaria-infected blood: alteration of fatty acid composition involving a serum protein: an in vivo and in vitro study.
Alteration of uninfected erythrocytes from Plasmodium (the malaria parasite)-infected blood remained an open question. In this study we compared the in vivo fatty acid compositions of control and uninfected monkey erythrocytes. A large (40%) increase in the linoleic acid level was observed, which was recovered mostly in neutral lipids. An in vitro system was developed to study medium-mediated alterations of cultured erythrocytes by Plasmodium falciparum. The increase in the linoleate level was reproduced in vitro and was also localized in the neutral lipid fraction, especially in triacylglycerols. Studies using proteolytic digestion and heat denaturation showed that a heat-labile serum protein is indispensable for the increase in the linoleate level of red cells treated with the supernatant of P. falciparum cultures. Both the function and the mechanism of this modification of uninfected erythrocytes still remain unknown.


An additional 2'-ribofuranose residue at a specific position of the DNA primer prevents Its elongation by HIV-1 reverse transcriptase.
Oligodeoxynucleotides containing 2'-O-beta-D-ribofuranosyladenosine were prepared and used as modified primers in RNA-templated DNA synthesis catalyzed by HIV reverse transcriptase. It was shown that the additional 2'-ribofuranose residue in specific position of primer prevents its elongation.


Identification and mutational analysis of continuous, immunodominant epitopes of the major oyster allergen Crag 1.
Shellfish, including oysters, often cause allergic reactions in children and adults. Oysters are inevitably consumed because of its delicacy and nutritional benefit, leading to frequent occurrence of severe clinical symptoms observed in patients with oyster hypersensitivity. We aimed to identify the immunodominant epitopes of oyster tropomyosin and crucial amino acids for IgE binding, which will help us to further understand the immunochemical characteristics of Cra g 1. The potential epitopes were predicted by immunoinformatics tools and the resultant immunodominant epitopes were identified by inhibition ELISA with pooled sera and individual serum from oyster allergic patients. Surprisingly, homologous substitution of multiple amino acids led to obviously decrease affinity of IgE antibodies, but this manner did not abrogate binding completely. Five major linear epitopes were evenly distributed on the surface of homology-based Cra g 1 model and hydrophilic residues appeared to be the most important for IgE binding. These results not only offer a better understanding of the molecular mechanism of interaction between Cra g 1 and oyster-specific IgE but also have significance in clinical diagnosis and immunotherapy.


Outcomes of skin cancer excision in frail patients: A retrospective cohort study.
Non-melanoma skin cancer (NMSC) is the most common cancer type and incidence increases with age. As a consequence, an increasing number of frail patients are being referred for consideration of skin cancer surgery. However, some of these patients may not live long enough to experience benefit from surgery, while being at risk of postoperative complications. To investigate the treatment burden of surgical excision of skin cancers in frail individuals. We conducted a single-center retrospective cohort study analyzing outcomes of skin cancer excision in frail versus non-frail patients. Eighty-eight patients were included. The complication rate was higher in frail versus non-frail patients: 12 (27.9%) versus 9 (18.8%), with 5 unplanned postoperative hospital attendances leading to 3 hospital admissions in the frail cohort. Nine patients in the frail group (21%) died within 6 months of their procedure versus no deaths in the non-frail group (p < 0.001 Fisher's Exact test), with no deaths attributed to skin cancer. Treatment-related complications and mortality are common in frail patients after surgical excision of skin lesions clinically suspicious for skin cancer. Careful consideration should be given, and patients should be adequately counseled about treatment risks and alternative management options, including active surveillance, in particular, if the lesions are expected to remain asymptomatic.


Some enzyme histochemical characteristics of the human hippocampus.
The histochemical distribution of acetylcholinesterase (AChE) and alpha-glycerophosphate dehydrogenase (alpha-GPDH) was studied in the area dentata and hippocampus proper of the human brain. Although differences did exist, there were many features in common with the distribution of these two enzymes in the rat and guinea pig. The laminar chemoarchitectonic picture was not as distinct in the human brain as in the rat and guinea pig. Most of the AChE reaction products were confined to the neuropil, with the strongest staining intensity in supra- and infrapyramidal zones. The layer of mossy fibres (stratum lucidum), was characteristically pale. On the other hand, AChE-positive cell bodies were observed in the hilus of the area dentata and a few scattered cells in the hippocampus proper. The AChE reaction products were sparse in the pyramidal cells, conforming similar observations in the rat and guinea pig. Based on our previous description of the AChE-positive cell bodies and fibres in the human septum and a considerable body of experimental material obtained in the rat, it is suggested that most of the AChE in the dentate area and the hippocampus proper is confined to terminals of cholinergic septal efferents in both man and other species. alpha-GPDH was particularly reactive in the cell layers, hilus fasciae dentatae and the layer of mossy fibers. These observations are similar to those described for the rat and guinea pig. They indicate, furthermore, a particular metabolic property common to the archicortex of man and other species.


Pulmonary embolectomy.
Embolectomy was carried out in eight patients with pulmonary emboli. Angiographic diagnosis was obtained in six, and in two cases pulmonary angiography could not be done because of the very critical condition of the patients. In the latter two, diagnosis was made based only on clinical findings. Two patients died in the operating room (25 percent). Six patients were discharged in good condition. It is emphasized that pulmonary embolectomy should be done in cases of pulmonary emboli when a clinical status of shock is present (systolic blood pressure less than 80 mm of mercury and the patient in low cardiac output syndrome) and when there is no response to medical treatment regardless of the degree of obstruction in the pulmonary arterial tree.