Modification of alcohol withdrawal by the A9 allele of the dopamine transporter gene.
Determinants of individual vulnerability to alcohol withdrawal symptoms are largely unknown. Because of the substantial role of monoaminergic transporters in limiting time and space effects of synaptic neurotransmission, the dopamine transporter gene (DAT1; locus symbol: SLC6A3) was studied as a candidate gene possibly related to symptoms of uncomplicated alcohol withdrawal. In 48 chronically intoxicated alcoholics (diagnosed according to ICD-10), withdrawal symptoms were examined and the presence of a variable-number tandem repeat in the 3' untranslated region of the DAT1 gene was determined. Withdrawal syndromes were more pronounced in the 22 patients carrying the nine-copy repeat than in the 26 patients without this variant. Multiple regression analysis revealed that 4% of the variance of withdrawal was explained by this genotype, whereas 16% was due to the amount of alcohol the patients reported having consumed in the month before detoxification. The A9 allele of the dopamine transporter gene is associated with more severe effects of alcohol withdrawal, possibly because of modifications of the brain's capacity to compensate for long-term effects of ethanol on cerebral function.


A Co-infection Model System and the Use of Chimeric Proteins to Study Chlamydia Inclusion Proteins Interaction.
Chlamydia trachomatis is an obligate intracellular bacterium associated with trachoma and sexually transmitted diseases. During its intracellular developmental cycle, Chlamydia resides in a membrane bound compartment called the inclusion. A subset of Type III secreted effectors, the inclusion membrane proteins (Inc), are inserted into the inclusion membrane. Inc proteins are strategically positioned to promote inclusion interaction with host factors and organelles, a process required for bacterial replication, but little is known about Inc proteins function or host interacting partners. Moreover, it is unclear whether each Inc protein has a distinct function or if a subset of Inc proteins interacts with one another to perform their function. Here, we used IncD as a model to investigate Inc/Inc interaction in the context of Inc protein expression in C. trachomatis. We developed a co-infection model system to display different tagged Inc proteins on the surface of the same inclusion. We also designed chimeric Inc proteins to delineate domains important for interaction. We showed that IncD can self-interact and that the full-length protein is required for dimerization and/or oligomerization. Altogether our approach can be generalized to any Inc protein and will help to characterize the molecular mechanisms by which Chlamydia Inc proteins interact with themselves and/or host factors, eventually leading to a better understanding of C. trachomatis interaction with the mammalian host.


Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial.
Previous trials have evaluated the effects of aerobic training alone and of resistance training alone on glycemic control in type 2 diabetes, as assessed by hemoglobin A1c values. However, none could assess incremental effects of combined aerobic and resistance training compared with either type of exercise alone. To determine the effects of aerobic training alone, resistance training alone, and combined exercise training on hemoglobin A1c values in patients with type 2 diabetes. Randomized, controlled trial. 8 community-based facilities. 251 adults age 39 to 70 years with type 2 diabetes. A negative result on a stress test or clearance by a cardiologist, and adherence to exercise during a 4-week run-in period, were required before randomization. Aerobic training, resistance training, or both types of exercise (combined exercise training). A sedentary control group was included. Exercise training was performed 3 times weekly for 22 weeks (weeks 5 to 26 of the study). The primary outcome was the change in hemoglobin A1c value at 6 months. Secondary outcomes were changes in body composition, plasma lipid values, and blood pressure. The absolute change in the hemoglobin A1c value in the combined exercise training group compared with the control group was -0.51 percentage point (95% CI, -0.87 to -0.14) in the aerobic training group and -0.38 percentage point (CI, -0.72 to -0.22) in the resistance training group. Combined exercise training resulted in an additional change in the hemoglobin A1c value of -0.46 percentage point (CI, -0.83 to -0.09) compared with aerobic training alone and -0.59 percentage point (CI, -0.95 to -0.23) compared with resistance training alone. Changes in blood pressure and lipid values did not statistically significantly differ among groups. Adverse events were more common in the exercise groups. The generalizability of the results to patients who are less adherent to exercise programs is uncertain. The participants were not blinded, and the total duration of exercise was greater in the combined exercise training group than in the aerobic and resistance training groups. Either aerobic or resistance training alone improves glycemic control in type 2 diabetes, but the improvements are greatest with combined aerobic and resistance training. ClinicalTrials.gov registration number: NCT00195884.


Genetic control of the cytolytic T lymphocyte response to influenza viruses: H-2 genes influence the response to H-2Kb plus virus.
Genetic control of the cytolytic T lymphocyte responses to influenza virus was examined. Mice bearing the H-2b haplotype and F1 hybrid mice derived from C57BL/6 parents failed to recognize H-2Kb plus type A or type B influenza viruses. Congenic mice that shared H-2Kb but had either H-2Dd of H-2Dq genotypes responded in in vitro secondary cultures to H-2Kb plus virus. Mapping studies suggest the gene(s) controlling the ability to respond to H-2Kb plus virus can be localized in or near the H-2D region. Several interpretations of these observations are discussed.


[Use of omeprazole and esomeprazole in patients suffering from bronchial asthma with associated gastroesophageal reflux disease].
The purpose of this study is a comparative assessment of the clinical efficiency of Omeprazole and Esomeprazole in patients suffering from bronchial asthma (BA) with associated gastroesophageal reflux disease (GERD). 101 patients with BA and associated GERD being under study were divided into three groups depending on the way of application of the anti-reflux therapy. Patients from the I group were administered Omeprazole--20 mg per day, patients from the II group received Omeprazole--mg per day, and patients from the III group were administered Esomeprazole--40 mg per day, the treatment courses of each group amounting to eight weeks. The clinical efficiency indices of pulmonary (CEIP) and esophageal (CEIE) symptoms were calculated when the results of the study were summed. The decrease of CEIP and CEIE against the background of the anti-reflux therapy (for example, the CEIP of patients from the III group decreased from 14.9 +/- 1.5 (before the treatment) to 2.9 +/- 0.6 points following eight weeks of treatment (p < 0.001), and the CEIE decreased from 9.0 +/- 1.2 (before the treatment) to 1.7 +/- 0.3 points following eight weeks of treatment (p < 0.001)) has demonstrated the reliable improvement of the clinical course of BA with associated GERD. We failed to discover any essential differences between the impact of Omeprazole in the dose equal to 40 mg per day and the impact of Esomeprazole in the same dose on the CEIP. Thus, the CEIP amounted to 10.1 +/- 1.2 points in the II group and 8.5 +/- 1.4 points in the III group (p > 0.05) after the fourth week of treatment. At the same time, we have discovered a reliable advantage of Esomeprazole as compared with Omeprazole for the improvement of the CEIE. The therapy of BA with associated GERD with Omeprazole in the dose equal to 40 mg per day or Esomeprazole in the dose equal to 40 mg per day contributes to the reliable improvement of both pulmonary and esophageal symptoms, and application of Esomeprazole results in a faster reduction of bronchial obstruction and gastroesophageal reflux.


Gastric myoelectric and autonomic activities and dyspeptic symptoms in cardiological syndrome X patients.
Syndrome X is defined as anginal chest pain accompanied by objective signs of ischemia on exercise testing but with angiographically normal coronary arteries. The aetiology of this syndrome is still not known. The AIM of this study was to evaluate changes in circadian rhythm of gastric myoelectric activity (MA) and autonomic system (AS) and their correlation with dyspeptic symptoms in SX patients. We studied forty consecutive patients, mean age 46+/-8 yrs with syndrome X and 40 sex-, age- and gender-matched healthy volunteers (47+/-5 yrs). The population of syndrome X patients is heterogeneous combining subgroups with normal and low AS activity with high tonic sympathetic drive. Patients with autonomic dysfunction had a high percent of gastric dysrrhythmia with disturbed sympatho-vagal balance particularly at night. We conclude that dyspeptic symptoms in SX patients with autonomic dysfunction are caused mostly by high adrenergic drive affecting stomach myoelectric activity and inducing gastric dysrrhythmias.


Discovery of indium complexes as water-tolerant Lewis acids.
The work on development of organic reactions that are tolerant to air and moisture, especially that of carbon-carbon bond forming reactions, had only started in the early 1990s. Our laboratory had approached this subject when it was still in its infancy and had developed methodologies for that end. In this article, our decade of work on indium complexes as Lewis acids is summarised.


Ultrasonic texture and volume of testicles in infertile men.
Ultrasound scanning of the testes and surgical biopsy were performed in 95 infertile men to evaluate the use of ultrasound in male infertility. Ultrasonic testicular volume was calculated using three measurements and the formula of an ellipsoid, and the ultrasonic texture was evaluated and given a score from 1 to 5, indicating increasing degrees of irregularity. The median score was 3 (range 1-5), which was higher than previously found in normal men (median score 2; range 1-5; P < 0.0001). The ultrasonic texture score was lower in testes with a uniform pattern of 100% spermatogenic tubules compared with the rest, both for the right (P < 0.001) and for the left (P < 0.0005) testis. Texture score was correlated with the number of obliterated tubules for both testes (P < 0.001). The mean ultrasonic testicular volume of the right testis was 10.30 ml, and that of the left 10.26 ml. Both were smaller compared with the findings in normal men (P < 0.0001). Ultrasonic testicular volume was negatively correlated with texture score (P < 0.001). A positive correlation between ultrasonic volume and sperm count was seen (P < 0.001). Sperm count was negatively correlated with texture score if calculated together with data from 119 men from the general population (P < 0.001). The study shows that ultrasonic volume and texture are valuable parameters in the evaluation of infertile men.


PARTITIONING AROUND MEDOIDS CLUSTERING AND RANDOM FOREST CLASSIFICATION FOR GIS-INFORMED IMPUTATION OF FLUORIDE CONCENTRATION DATA.
Community water fluoridation is an important component of oral health promotion, as fluoride exposure is a well-documented dental caries-preventive agent. Direct measurements of domestic water fluoride content provide valuable information regarding individuals' fluoride exposure and thus caries risk; however, they are logistically challenging to carry out at a large scale in oral health research. This article describes the development and evaluation of a novel method for the imputation of missing domestic water fluoride concentration data informed by spatial autocorrelation. The context is a state-wide epidemiologic study of pediatric oral health in North Carolina, where domestic water fluoride concentration information was missing for approximately 75% of study participants with clinical data on dental caries. A new machine-learning-based imputation method that combines partitioning around medoids clustering and random forest classification (PAMRF) is developed and implemented. Imputed values are filtered according to allowable error rates or target sample size, depending on the requirements of each application. In leave-one-out cross-validation and simulation studies, PAMRF outperforms four existing imputation approaches-two conventional spatial interpolation methods (i.e., inverse-distance weighting, IDW and universal kriging, UK) and two supervised learning methods (k-nearest neighbors, KNN and classification and regression trees, CART). The inclusion of multiply imputed values in the estimation of the association between fluoride concentration and dental caries prevalence resulted in essentially no change in PAMRF estimates but substantial gains in precision due to larger effective sample size. PAMRF is a powerful new method for the imputation of missing fluoride values where geographical information exists.


Bacterial artificial chromosome transgenic analysis of dynamic expression patterns of regulator of G-protein signaling 4 during development. II. Subcortical regions.
A large family of regulator of G protein signaling (RGS) proteins modulates signaling through G-protein-coupled receptors. Previous studies have implicated RGS4 as a vulnerability gene in schizophrenia. To begin to understand structure-function relationships, we have utilized bacterial artificial chromosome (BAC) methods to create transgenic mice that express green fluorescent protein (GFP) under the control of endogenous RGS4 enhancer elements, circumventing the lack of suitable antibodies for analysis of dynamic patterns of expression. This report follows from the accompanying mapping paper in cerebral cortex, with a focus on developmental and mature expression patterns in subcortical telencephalic, diencephalic and brainstem areas. Based on reporter distribution, the data suggest that alterations in RGS4 function will engender a complex phenotype of increased and decreased neuronal output, with developmental, regional, and cellular specificity.


New objective classification system for nuclear opacification.
We have developed an autonomous objective classification scheme for degree of nuclear opacification. The algorithm was developed by using a series of color 35-mm slides acquired with a Topcon photo slit-lamp microscope and use of standard camera settings. The photographs were digitized, and first, and second-order gray-level statistics were extracted from within circular regions of the nucleus. Classifications of severity were performed by using these features as input to a neural network. Training versus classification performance was tested by using photographs of different eyes, and test/retest classification reproducibility was evaluated by using paired photographs of the same eyes. We demonstrate good performance of the classifier against subjective assessments rendered by the Wilmer grading system [Invest. Ophthalmol. Visual Sci. 29, 73 (1988)] and markedly better test/retest reproducibility.


Worldwide legislative challenges related to psychoactive drugs.
The discovery of a "new" psychoactive substance is a relatively exceptional event, while the regulatory response usually involved the assessment of risks to public health and inclusion of the novel substance in the national list of controlled substances. However, in recent years we have witnessed the rapid emergence of new chemical substances, which elude international control and pose a challenge to existing processes and a threat to the credibility of control systems. We currently review and present characteristics of these legal and illegal new substances and issues regarding their global monitoring and regulatory measures already taken, or in the process of being taken, for their control. The concept of prohibition applied in active substance-related legislation is rather hazard ridden as balance is required between the ban on substances of potential therapeutic use and the access on the market of high-risk substances. Current and future laws regarding psychoactive compounds.


"Fundathon": toward massively multiplayer online fundraising games.
Fundraising campaigns could be elaborate local or global contests or games to raise money for good causes--displaying financial results instantly, costing almost nothing, and letting donors, teams and individual fundraisers make their mark.


Antimicrobial Peptides: The Promising Therapeutics for Cutaneous Wound Healing.
Chronic wound infections have caused an increasing number of deaths and economic burden, which necessitates wound treatment options. Hitherto, the development of functional wound dressings has achieved reasonable progress. Antibacterial agents, growth factors, and miRNAs are incorporated in different wound dressings to treat various types of wounds. As an effective antimicrobial agent and emerging wound healing therapeutic, antimicrobial peptides (AMPs) have attracted significant attention. The present study focuses on the application of AMPs in wound healing and discusses the types, properties and formulation strategies of AMPs used for wound healing. In addition, the clinical trial and the current status of studies on "antimicrobial peptides and wound healing" are elaborated through bibliometrics. Also, the challenges and opportunities for further development and utilization of AMP formulations in wound healing are discussed.


LiNbO3 waveguide with embedded Ag nanowire and 3L MoS2 for strong light confinement and ultra-long propagation length in the visible spectral range.
A vertical slot LiNbO3 waveguide with an Ag nanowire and 3L MoS2 embedded in the low-refractive index slot region is proposed for the purpose of improving light confinement. We find that the proposed waveguide has a novel dielectric based plasmonic mode, where local light field is enhanced by the Ag nanowire. The mode exhibits an extremely large figure of merit (FoM) of 6.5×106, one order of magnitude larger than that the largest FoM of any plasmonic waveguide reported in the literature to date. The waveguide also has an extremely long propagation length of 84 cm in the visible wavelength at 680 nm. Furthermore, the waveguide has a low sub-micro bending loss and can be directly connected to all-dielectric waveguides with an extremely low coupling loss. The proposed vertical slot LiNbO3 waveguide is a promising candidate for the realization of ultrahigh integration density tunable circuits in the visible spectral range.


Incidental Finding of Thoracic Aortic Dissection in a Patient Post-Coronary Artery Bypass Graft Surgery.
Thoracic aortic dissection (TAD) is an uncommon but potentially fatal complication of coronary artery bypass graft (CABG). Most patients present to the emergency room with severe chest pain, shortness of breath, or after a syncopal episode. Asymptomatic patients pose a challenge to diagnosis. The authors present a case of an 82-year-old male, who was found to have an incidental finding of a 5-cm ascending aortic aneurysm with an intimal dissection flap four months after CABG. Extensive workup on possible risk factors such as underlying aortic diseases, genetic conditions, and hypertensive crisis proved noncontributory. Aggressive blood pressure control was achieved, and the patient was observed in the intensive care unit before discharge with follow-up. The purpose of this case report is to alert clinicians of TAD after CABG and highlight the importance of developing a protocol for follow-up and monitoring of patients who have undergone CABG, as complications can be asymptomatic. Early and accurate diagnosis of TAD as a complication of CABG is essential to improving survival rates.


Road-safety education: spatial decentering and subjective or objective picture processing.
The current study examined children's ability to analyse pictures of a risky situation, both in relation to the characteristics of the pictures and in relation to the centering/decentering process of cognitive development. Sixty children aged 6, 9 or 11 years were given an objective or subjective version of a story about a risky situation involving road crossing and were asked to reconstruct it by putting six pictures in chronological order. The type of picture series, objective or subjective, had a different effect on the children's understanding and performance, according to the age. The older children were better at ordering the pictures, but on the subjective version only. The picture-version effect on planning time decreased with age; only the younger children took more time to start touching the pictures. On one hand, it is concluded that for the youngest children, objective representations are essential to analysing pictures showing a risk, whereas the oldest children will profit more from a subjective view. On the other hand, subjective representations, which give a more realistic view, provide an excellent tool for testing children's abilities. Subjective representations can be used to detect potentially risky behaviour in virtual situations (static pictures, or multimedia tools), since it permits one to predict at-risk behaviour in the street and to assess the effectiveness of remedial measures.


Polymerization shrinkage and microleakage in Class II cavities of various resin composites.
This study investigated the polymerization shrinkage of restorative materials and microleakage in the proximal box of Class II restorations. Twenty caries free extracted human molars were prepared on the mesial and distal, making 40 slot cavities. Groups (n=10) were classified as: Group 1: Single bond/Filtek Z-250; Group 2: Single Bond/Filtek Flow/Filtek Z-250; Group 3: Admira Bond/Admira; Group 4: Ariston Liner/Ariston. Dentin bonding systems and resin composites were applied according to the manufacturer's instructions. The specimens were stored in distilled water for one week at 37 degrees C, thermocycled (5 degrees-55 degrees C x 2000), stained with 50% aqueous silver nitrate, immersed in a diluted developer solution (24 hours), rinsed and sectioned in two pieces with a low speed saw (Isomet). Dye penetration (Score 0-4) was determined separately at the occlusal enamel margin and cementoenamel junction. The volumetric polymerization shrinkage of materials was determined with the apparatus of Watts and Cash (Watts Cash, 1991) for 300 seconds. Polymerization shrinkage results were as follows: Filtek Flow (3.5% +/- 0.1) > Admira (2.1% +/- 0.1) = Ariston AT (2.3% +/- 0.1) > Filtek Z-250 (1.8% +/- 0.1) (One-way Anova, post hoc Bonferroni test at p = 0.05 level). No statistical difference was found at the enamel margins for any of the materials (Score 0-1). At the cemento-enamel junction, all test groups showed significantly higher microleakage when compared to the enamel margins (Kruskal-Wallis test, Mann-Whitney U). Dye penetration results at dentin were as follows: Filtek Flow + Filtek Z-250 = Admira < Ariston AT = Filtek Z-250. microleakage than the ion-releasing and hybrid composites lined only with bonding agent at the cementoenamel junction in Class II cavities.


Recovery nutrition: timing and composition after endurance exercise.
Consumption of macronutrients, particularly carbohydrate (CHO) and possibly a small amount of protein, in the early recovery phase after endurance exercise can enhance muscle glycogen resynthesis rates. A target of at least 1.2 g x kg body weight(-1) x h(-1) CHO (over several hours) is suggested. This rate of CHO intake could be sustained with liquid, gel, or solid food rich in CHO for maximizing muscle glycogen. Whether the coingestion of protein with CHO compared with isocaloric CHO results in meaningful differences in glycogen replenishment that translate into subsequent performance enhancement is equivocal. Advantages of added protein with CHO in reducing true muscle damage from endurance exercise remain to be verified. There are, however, no apparent contraindications for using milk or specialty CHO/protein/amino acid products either. Future investigations that examine signaling mechanisms within muscle should be conducted in parallel with translational evidence in humans.


Early-Stage, BRCA-Associated Ovarian Cancer Detected by Papanicolaou Smear: A Case Report.
Historically known as a "silent killer", ovarian cancer is often diagnosed at an advanced stage. We describe an unusual case of stage I, ovarian, high-grade serous carcinoma detected by a routine Papanicolaou (PAP) smear, with no abnormal physical, imaging, or laboratory findings. A 53-year-old woman with newly diagnosed triple-negative breast cancer received a screening Pap smear, which showed malignant cells not coming from the breast or uterine cervix. Pelvic examination, cervical biopsy, and gynecologic ultrasonography found no abnormality. Endometrial curettage yielded free-floating adenocarcinoma cells. The immunohistochemical stain result indicated ovary or fallopian tube cancer. Complete cytoreductive surgery was performed, and high-grade serous carcinoma of bilateral ovaries, FIGO stage IB, was diagnosed. Although extremely rare, when malignant cells not originating from the uterine cervix are detected on a Pap smear, it may lead to an early diagnosis of ovarian cancers, and this warrants further comprehensive workup.


The effects of weekly iron supplementation with folic acid, vitamin A, vitamin C on iron status of Indonesian adolescents.
The goal of the study was to determine whether the addition of vitamins A and C and extra folate to the commonly distributed iron-folate supplement administered on a weekly basis would result in improved iron status in anaemic and non-anaemic female adolescents. Subjects (n=84) were selected if their haemoglobin concentration in venous blood was <= 140g/L. Subjects were randomly allocated into 2 groups. One group received 60mg iron, 500m g folic acid, 20 000 IU vitamin A and 60mg vitamin C weekly, while the other group received 60 mg iron and 250m g folic acid weekly for a period of 5 weeks. Before and after treatment, haemoglobin, serum ferritin and body height and weight were determined. All subjects received anthelmintic drugs before supplementation. A complete data set was obtained from 42 young women in the group supplemented with iron, folic acid, vitamin A and vitamin C and from 40 young women in the group supplemented with iron and folic acid. Haemoglobin, mean cell volume and serum ferritin increased significantly in both groups (p<0.05). Among anaemic adolescents, the rise in haemoglobin concentration in the multisupplement group was higher than that in the iron folate group. The result confirms that weekly supplementation is effective in improving iron status in a short time (5 weeks) and that supplementation with vitamins as well as iron results in an additional improvement in haemoglobin concentration.


Histopathological examination of tissue resected during bariatric procedures - to be done or not to be done?
Obesity is one of the major lifestyle diseases and provokes various comorbidities, such as hypertension, type 2 diabetes mellitus, obstructive sleep apnea, and even neoplasms. Bariatric surgery is the most effective treatment of obesity. Since cost-effectiveness has become a major concern, there is a tendency to avoid general histological evaluation of surgical specimens during routine procedures. To evaluate the necessity of histopathological investigation of tissue excised during bariatric surgery and to verify whether the operation should be continued in the case of suspicious macroscopic findings. From January 2013 to December 2016, 1252 patients with obesity were qualified for bariatric procedures. The qualification was performed according to the current European recommendations. Every operation started with an inspection of the peritoneal cavity performed once the abdomen was insufflated. If a macroscopic pathology was found, the specimen was secured for histopathological investigation. Out of 81 (6.47%) patients from whom histopathological samples were collected, 39% (n = 32) showed negative results, and 61% (n = 49) cases showed abnormalities. As it is impossible to exclude the existence of gastric tumors only in preoperative gastroscopy and ultrasonography, especially as there is a higher risk in obese patients, routine histological examination of tissue excised during bariatric procedures should be considered. Since most of the neoplasms were found to be benign, there is no need to abandon the bariatric procedure if a pathology is found and resected. Bariatric surgeons should always focus on thorough examination of the abdominal and the pelvic cavity, especially in female patients.


Simultaneous and cost-effective determination of ethylene glycol and glycolic acid in human serum and urine for emergency toxicology by GC-MS.
A simple, cost-effective, and fast gas chromatography method with mass spectrometry detection (GC-MS) for simultaneous measurement of ethylene glycol, 1,2-propylene glycol and glycolic acid was developed and validated for clinical toxicology purposes. Successful derivatization of glycolic acid with isobutyl chloroformate was achieved directly in serum/urine while glycols are simultaneously derivatized by phenylboronic acid. The entire sample preparation procedure is completed within 10 min. The assay was proved to be quadratic in the range of 50 to 5000 mgL(-1) with adequate accuracy (96.3-105.8%) and precision (CV ≤ 8.9%). The method was successfully applied to quantify the selected compounds in serum of patients from emergency units and the results correlated well with parallel GC-FID measurements (R(2) 0.9933 for ethylene glycol and 0.9943 for glycolic acid).


Multilingual information retrieval in thoracic radiology: feasibility study.
Most essential information contained in the electronic medical record is stored as text, and this imposes several difficulties on automated data extraction and retrieval. Natural language processing is an approach that can unlock clinical information from free texts. The proposed methodology uses the specialized natural language processor MEDLEE developed for the English language. To use this processor on Portuguese medical texts, chest X-ray reports were machine translated (MT) into English. The result of serial coupling of MT and NLP is tagged text that needs further investigation for extracting clinical findings. This experiment's objective was to investigate normal reports and reports with device description on a set of 165 chest X-ray reports. We obtained sensitivity and specificity of 1 and 0.71 for the first condition, and 0.97 and 0.97 for the second. The reference was formed by the opinions of two radiologists. The results of this experiment indicate the viability of extracting clinical findings from chest X-ray reports through coupling MT and NLP.


Assessment of late on-set fetal growth restriction using SMI (superb microvascular imaging) Doppler.
The identification of late-onset fetal growth restriction (FGR) fetuses remains a challenge, given the difficulty to distinguish them from healthy small for gestational age (SGA) fetuses. Given the limitations of conventional Doppler for the identification of placental insufficiency, the appearance of superb microvascular imaging (SMI) Doppler seems promising. Our main objective was to evaluate the diagnostic capability of SMI Doppler for the detection of placental insufficiency findings. A prospective observational study was conducted at a tertiary care center, including 51 patients who had been diagnosed with late on-set SGA or FGR. A placental ultrasonographic evaluation was carried out using SMI Doppler. Patients were sorted into two groups attending to the histologic evaluation of the placentas after delivery: Group 1 (21 cases), Normal group; and Group 2 (30 cases), FGR group. Placentas in the FGR group had lower peak systolic velocity (PV) values of the chorionic plate. The PV of the other vessels were consistently lower in the FGR group that in the normal group, although without reaching statistical significance. The PV of the chorionic plate measured with SMI Doppler, have the capacity to identify placental insufficiency findings. Ultrasonographic placental assessment using SMI Doppler appears to be a useful technique for the evaluation of suspected late on-set placental insufficiency.


Improving RT-LAMP detection of SARS-CoV-2 RNA through primer set selection and combination.
Reverse transcription loop-mediated isothermal amplification (RT-LAMP) has emerged as a viable molecular diagnostic method to expand the breadth and reach of nucleic acid testing, particularly for SARS-CoV-2 detection and surveillance. While rapidly growing in prominence, RT-LAMP remains a relatively new method compared to the standard RT-qPCR, and contribution to our body of knowledge on designing LAMP primer sets and assays can have significant impact on its utility and adoption. Here we select and evaluate 18 LAMP primer sets for SARS-CoV-2 previously identified as sensitive ones under various conditions, comparing their speed and sensitivity with two LAMP formulations each with 2 reaction temperatures. We find that both LAMP formulations have some effects on the speed and detection sensitivity and identify several primer sets with similar high sensitivity for different SARS-CoV-2 gene targets. Significantly we observe a consistent sensitivity enhancement by combining primer sets for different targets, confirming and building on earlier work to create a simple, general approach to building better and more sensitive RT-LAMP assays.


[Prevalence and related factors of carcinoma among population in Macao during 2003 - 2007].
Understanding the prevalence of cancer among Macao residents to better carry out tertiary prevention and control program. Data was gathered from annual reports of Macao Cancer Registry of Health Bureau in 2003 - 2007, and demographic statistics of Statistics and Census Bureau Macau SAR Government in 1997 - 2006. Both International Statistical Classification of Diseases and Related Health Problems 10(th) Revision (ICD-10) were used to classify the diseases and causes of death. Excel 2003 was used for data input and data was analyzed with crude rate, velocity of increase of crude rate and cumulative risk. The average crude incidence rate of cancer was 237.2 per 100 000 among the Macao population, with age standardized incidence rate as 194.4 per 100 000;and crude mortality rate as 101.0 per 100 000. Lower gastrointestinal cancer had the highest crude incidence, with the crude incidence rate of prostate cancer rapidly increasing. Respiratory cancer and breast cancer appeared to be the highest crude incidences in both men and women, with the crude mortality rate (25.0 per 100 000) of respiratory cancer the highest. 72.9% of the tumors occurred at the age of 50 and above. However, 81.1% of the tumors occurred at 50 years old and above in men, with the occurrences of tumors of women distributed more evenly. Breast cancer and epithelial tumor commonly occurred in adolescents and young adults while respiratory cancer mostly seen in adulthood and the elderly. Residents were usually diagnosed of cancer at 61.0 years of age and death occurred at 70.5 year old. The prognosis of cancer of men was worse than women's. The worst prognosis of cancer was seen in liver and esophagus, with death occurred within 1 year after diagnosis was made. Breast cancer had the highest cumulative incidence rate, but respiratory cancer had the highest cumulative mortality rate. Both cumulative rates of incidence and mortality in women were lower than in men. The increase of crude cancer incidence rate was fast among Macao residents, but relatively slow with crude mortality rate. Respiratory and lower gastrointestinal tumors took the majority while prostate and breast cancer were by no means unimportant, which also called for tertiary prevention. People above 50 years old and all males should be listed as target population to receive preventive program on cancer.


Comprehensive Analysis of a tRNA-Derived Small RNA in Colorectal Cancer.
Colorectal cancer often presents as a highly variable disease with myriad forms that are at times difficult to detect in early screenings with sufficient accuracy, for which novel diagnostic methods are an attractive and valuable area of improvement. To improve colorectal cancer diagnosis and prognosis, new biomarkers that can be assembled into a diagnostic panel must be identified, and tRNA-derived small RNAs (tsRNAs) are a particularly interesting and increasingly visible new class of molecules to examine. In this study, small RNA-seq data were profiled for the expression of 104 human tsRNAs in tumor tissue and adjacent normal tissue samples, and a diagnostic model was built based on four differentially expressed tsRNAs: tRF-22-WB86Q3P92, tRF-22-WE8SPOX52, tRF-22-WE8S68L52, tRF-18-8R1546D2. Furthermore, the diagnostic model was validated by two independent validation datasets (AUC was 0.97 and 0.99), and a LASSO model was applied to develop a seven-tsRNA-based risk score model for colorectal cancer prognosis. Finally, a tsRNA-mRNA interaction network was established according to potential mRNA targets predicted by bioinformatic methods. In conclusion, the results suggest that abnormal expression of tsRNA in colorectal cancer may have a functional effect on tumor action and moreover, that some of the tsRNAs identified in this study with diagnostic and prognostic potential could be of clinical significance.


Subsequent fertility and birth histories of children and adolescents treated with 131I for thyroid cancer.
Forty patients aged 20 years or less who had been treated with 131I after surgery for papillary-follicular thyroid carcinoma were contacted for followup study. Five had died and two were unmarried; the remaining 33 were studied with respect to their subsequent reproductive histories and the health of the offspring. The mean age at the time of the first 131I therapeutic dose was 14.6 years (range 6-20), and the average followup interval, from that first dose until followup, was 18.7 years (range 14-25). The mean total dose of 131I was 196 mCi (range 80-691). The incidences of infertility (12%), miscarriage (1.4%), prematurity (8%), and major congenital anomaly (1.4%) found in this series are not significantly different from those in the general population. Thus, our study offers no overt evidence of genetic damage in children and adolescents treated with high doses of 131I for thyroid carcinoma.


Dose response of elastase-induced emphysema in hamsters.
Elastase-induced emphysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. Single intratracheal injections of 6, 12, or 24 units of porcine pancreatic elastase produced dose-related changes in pulmonary function after 4 wk when compared with sham-injected control animals. Boyle's law end-expiratory volume and residual volume, measured by gas dilution, increased (p less than 0.05) at 12 and 24 units, respectively, whereas vital capacity, determined plethysmographically, and total lung capacity wee increased (p less than 0.05) at all 3 elastase doses. Respiratory system compliance, calculated by a nonlinear least squares regression fit of the deflation pressure-volume curve, increased (p less than 0.05) at 24 units only. The multiple-breath nitrogen washout slope (N2 slope) and the single-breath diffusing capacity for carbon monoxide (DLCO) decreased (p less than 0.05) at all 3 doses of elastase. Both histologic and physiologic evaluation showed dose-related pulmonary impairment. It appears, therefore, that as little as 6 units of elastase produces mild emphysema in hamsters, which is detectable by pulmonary function testing. Of these tests, the DLCO and N2 slope were the most effective in detecting the degree of impairment.


PA-1, a human cell model for multistage carcinogenesis: oncogenes and other factors.
We have developed a cell system which utilizes the human teratocarcinoma cell line PA-1, from which we have characterized four stages of tumor progression. Soon after establishment in culture PA-1 cells revert and are no longer tumorigenic in athymic nude mice. Later, PA-1 cells as they are passaged in culture, become tumorigenic at passage 100. The transition from nontumorigenic to tumorigenic is the result of the biological effects of an activated N-ras oncogene and can be reproduced by transfection of the cloned oncogene into preneoplastic PA-1 cells. Certain preneoplastic cells (prior to passage 100) in this series are susceptible to transformation by single oncogenes while others are not. In studying the basis of this susceptibility to single oncogene induced transformation we have found that somatic cell hybrids between preneoplastic cells which can suppress ras-induced transformation and ras-transformed cells are non-tumorigenic. Therefore, we believe that the progression from ras suppressing to ras susceptibility may be due to the inactivation of a trans-dominant suppressor gene. Our system has identified at least three steps which lead to tumorigenicity; establishment of growth past senesence, activation of a ras oncogene, and inactivation of an oncogene suppressor function. Further genetic alterations are necessary for tumor dissemination and metastasis.


Long-Term Outcome of the Sorin Freedom SOLO Stentless Aortic Valve.
The Sorin Freedom SOLO valve is a third-generation stentless aortic valve which shows beneficial hemodynamic performance compared to stented bioprostheses. Long-term results regarding hemodynamics, the durability of the valve, and patient outcome are scarce, and their acquisition was the aim of this single-center study. Between 2005 and 2006, a total of 68 consecutive patients (30 males, 38 females; mean age at surgery 76.1 ± 6.3 years) underwent aortic valve replacement with a Sorin Freedom SOLO prosthesis. Indications were aortic stenosis (n = 50), aortic regurgitation (n = 1) and mixed lesions (n = 17). Associated procedures were performed in 31 patients (45.6%), most of which were coronary artery bypass grafting (68.8 %). The follow up was performed by telephone interviews, and clinical and echocardiographic examinations. Morbidity, mortality and echocardiographic data were analyzed. The total follow up was 501.1 patient-years, with a mean follow up of 7.4 ± 3.4 years (maximum 11.2 years). The follow up was 100% complete. Hospital mortality was 4.4% (n = 3). Actuarial survival at five and 10 years was 76.5 ± 5.1% and 41.5 ± 6.5%, respectively. Reinterventions were performed in eight patients; these included three reoperations due to endocarditis, four transcatheter aortic valve implantations, and one reoperation due to structural valve deterioration (SVD). The overall freedom from valve reintervention due to SVD at five and 10 years was 97.8 ± 2.2% and 82.9 ± 7.5%, respectively. After eight years, echocardiography demonstrated peak and mean transvalvular gradients of 18 ± 11 and 10 ± 7 mmHg, respectively. The overall effective and indexed aortic valve orifice areas were 1.73 ± 0.58 cm2 and 0.92 ± 0.33 cm2/m2, respectively. At long-term follow up the Sorin Freedom SOLO bioprosthesis was associated with favourable hemodynamic results and survival. Freedom from SVD was not superior to that occurring with stented bioprostheses.


A renewable nanosensor based on a glass nanopipette.
A fluorescent nanosensor based on reporter dye molecules trapped in the tip of a nanopipette has been developed. This 100 nm sized nanosensor has been shown to be capable of measuring local pH and mapping sodium concentration with a temporal resolution of a few milliseconds.


Feeding di-ammonium phosphate as a phosphorous source in finishing lambs reduced excretion of phosphorus in feces without detrimental effects on animal performance.
Phosphorous (P) sources with greater bioavailability might increase animal production efficiency and decrease environmental pollution. The objective of current study was to determine animal performance, nutrient digestibility, blood metabolites and fecal P concentration in finishing lambs fed a diet with either di-calcium phosphate (DCP) or di-ammonium phosphate (DAP) as a P source. Twelve 4-month-old male lambs (initial body weight 24.87±3.4 kg) were randomly allocated to a diet with either DCP or DAP (~261 g/kg of total diet P) fed ad libitum for 93 days. Diets were iso-nitrogenous and iso-energetic and had same calcium (Ca) and P concentrations. The DAP contained 19.7 g/kg of dry matter (DM) Ca, 185.4 g/kg DM P and 14,623 ppm fluorine, while DCP contained 230.3 g/kg DM Ca, 195.2 g/kg DM P and 1,039 ppm fluorine. The diet with DAP contained 60 ppm fluorine while the diet with DCP contained 13 ppm fluorine. Lambs fed the diet with DAP tended to have a greater daily DM intake compared to those fed diet with DCP (p = 0.09). Lambs fed DAP had greater plasma P concentration and alkaline phosphatase activity (p≤0.01) compared with lambs fed DCP. Dry matter and organic matter digestibility of the diets were similar between two treatments at days 60 and 90, while they were greater in lambs fed DCP (p<0.05) at day 30 of the trial. Feeding DAP increased P digestibility (58.7% vs 50.2%; p<0.05) and decreased fecal P concentration in lambs compared with feeding DCP (3.1 vs 3.8 g/kg DM; p<0.05). Providing ~261 g/kg of total diet P as DAP in the diet of finishing lambs improved the bioavailability of P in the body and decreased excretion of P in feces without affecting lamb performance.


Eating behavior and eating disorders: the interface between clinical research and clinical practice.
Cognitive-behavioral therapy (CBT) has been shown to be a highly effective form of treatment for patients with bulimia nervosa and anorexia nervosa. Issues of satiety disturbances, food restriction, and food choice are central to this form of therapy; however, ingestive behavior research that directly addresses these issues in eating disorder patients has often been overlooked by clinicians. These areas of research are reviewed and the implications of the findings for more effective CBT therapy with anorexics and bulimics are discussed.


How I treat bleeding disorder of unknown cause.
Recent studies have demonstrated that only 30% of patients referred for assessment of a possible bleeding tendency will eventually be diagnosed with a mild bleeding disorder (MBD) such as von Willebrand disease (VWD) or platelet function defect (PFD). Rather, most of these patients will be diagnosed with bleeding disorder of unknown cause (BDUC). There remains an important unmet need to define consensus regarding the clinical and laboratory criteria necessary for a formal BDUC diagnosis. Accumulating recent data suggest that BDUC is being diagnosed with increasing frequency. Objective assessment of bleeding phenotype using a standardized bleeding assessment tool (BAT) therefore represents a fundamental first step in the diagnosis of BDUC. Because BDUC is a diagnosis by exclusion, accurate quantification of bleeding phenotype is critical because this will be the primary determinant on which a diagnosis of BDUC is reached. Importantly, BAT scores suggest that patients with BDUC display bleeding phenotypes comparable to those seen in patients with VWD or PFD. Despite the prevalence of BDUC, diagnosis and management of these patients commonly pose significant clinical dilemmas. We consider these challenges in the context of a number of typical case studies, discuss the available evidence, and outline our approach to the management of these patients.


Prognosis of primary sclerosing cholangitis in israel is independent of coexisting inflammatory bowel Disease.
Primary sclerosing cholangitis (PSC) is a rare chronic progressive cholestatic disorder. We assessed its characteristics and natural history in Israel and compared its outcome with respect to coexisting inflammatory bowel disease (IBD). Data on characteristics, course and outcome were retrospectively retrieved on patients diagnosed with PSC from five large Israeli medical centers between 1988 and 2012. Patients with isolated PSC were compared with those with coexisting IBD to identify predictors of outcome. Of 141 patients (56% males) with confirmed PSC, 98 (69.5%) had coexisting IBD. The average age at presentation was 38.8 ± 15.4 years and duration of follow-up was 7.93 ± 6.26 years. The crude estimated point prevalence was 4 cases per 105 persons. Demographics and clinical characteristics were similar among all patients except for symptoms at diagnosis (which were more prevalent among PSC–IBD patients) and utilization of multiple diagnostic modalities (which was more prevalent among isolated-PSC patients). More than one-third of the entire cohort had cirrhosis. A total of 15 patients (10.6%) died and 19 patients (13.5%) developed malignancy during follow-up. Nine patients (6.3%) underwent liver transplantation. Mean survival for the entire cohort was 26.3 ± 1.4 years and mean transplant-free survival was 23.5 ± 1.6 years. Cox proportional hazard regression for transplantation or death revealed two independent risk factors: cirrhosis and malignancy [hazard ratio 4.25 (p = 0.004) and 2.58 (p = 0.046), respectively]. Survival rate of PSC patients in Israel is longer than reported rates worldwide and is independent of coexisting IBD.


Patient-Specific Reconstruction Utilizing Computer Assisted Three-Dimensional Modelling for Partial Bone Flap Defect in Hybrid Cranioplasty.
Decompressive craniectomy is a life-saving procedure in the setting of malignant brain swelling. Patients who survive require cranioplasty for anatomical reconstruction and cerebral protection. Autologous cranioplasty remains the commonest practice nowadays, but partial bone flap defects are frequently encountered. The authors, therefore, seek to develop a new technique of reconstruction for cranioplasty candidate with partial bone flap defect utilizing computer-assisted 3D modeling and printing. A prospective study was conducted to evaluate the outcome of a new reconstruction technique that produces patient-specific hybrid polymethyl methacrylate-autologous cranial implant. Computer-assisted 3D modeling and printing was utilized to produce patient-specific molds, which allowed real-time reconstruction of bone flap with partial defect intra-operatively. Outcome assessment for 11 patients at 6 weeks and 3 months post-operatively revealed satisfactory implant alignment with favorable cosmesis. The mean visual analog scale for cosmesis was 91. Mean implant size was 50cm, and the mean duration of intra-operative reconstruction was 30 minutes. All of them revealed improvement in quality of life following surgery as measured by the SF-36 score. Cost analysis revealed that this technique is more cost-effective compared to customized cranial prosthesis. This new technique and approach produce hybrid autologous-alloplastic bone flap that resulted in satisfactory implant alignment and favorable cosmetic outcome with relatively low costs.


Assessing viability and infectivity of foodborne and waterborne stages (cysts/oocysts) of Giardia duodenalis, Cryptosporidium spp., and Toxoplasma gondii: a review of methods.
Giardia duodenalis, Cryptosporidium spp. and Toxoplasma gondii are protozoan parasites that have been highlighted as emerging foodborne pathogens by the Food and Agriculture Organization of the United Nations and the World Health Organization. According to the European Food Safety Authority, 4786 foodborne and waterborne outbreaks were reported in Europe in 2016, of which 0.4% were attributed to parasites including Cryptosporidium, Giardia and Trichinella. Until 2016, no standardized methods were available to detect Giardia, Cryptosporidium and Toxoplasma (oo)cysts in food. Therefore, no regulation exists regarding these biohazards. Nevertheless, considering their low infective dose, ingestion of foodstuffs contaminated by low quantities of these three parasites can lead to human infection. To evaluate the risk of protozoan parasites in food, efforts must be made towards exposure assessment to estimate the contamination along the food chain, from raw products to consumers. This requires determining: (i) the occurrence of infective protozoan (oo)cysts in foods, and (ii) the efficacy of control measures to eliminate this contamination. In order to conduct such assessments, methods for identification of viable (i.e. live) and infective parasites are required. This review describes the methods currently available to evaluate infectivity and viability of G. duodenalis cysts, Cryptosporidium spp. and T. gondii oocysts, and their potential for application in exposure assessment to determine the presence of the infective protozoa and/or to characterize the efficacy of control measures. Advantages and limits of each method are highlighted and an analytical strategy is proposed to assess exposure to these protozoa.


Bouts of steps: The organization of infant exploration.
Adults primarily walk to reach a new location, but why do infants walk? Do infants, like adults, walk to travel to a distant goal? We observed 30 13-month-old and 30 19-month-old infants during natural walking in a laboratory playroom. We characterized the bout structure of walking-when infants start and stop walking-to examine why infants start and stop walking. Locomotor activity was composed largely of brief spurts of walking. Half of 13-month-olds' bouts and 41% of 19-month-olds' bouts consisted of three or fewer steps-too few to carry infants to a distant goal. Most bouts ended in the middle of the floor, not at a recognizable goal. Survival analyses of the distribution of steps per bout indicated that the probability of continuing to walk was independent of the length of the ongoing bout; infants were just as likely to stop walking after five steps as after 50 steps and they showed no bias toward bouts long enough to carry them across the room to a goal. However, 13-month-olds showed an increased probability of stopping after 1-3 steps, and they did not initiate walking more frequently to compensate for their surfeit of short bouts. We propose that infants' natural walking is not intentionally directed at distant goals; rather, it is a stochastic process that serves exploratory functions. Relations between the bout structure of walking and other measures of walking suggest that locomotor exploration is constrained by walking skill in younger infants, but not in older infants.


Drug analysis in necrophagous flies and human tissues.
Necrophagous insects may provide useful information about the time, place and cause of death. In addition, they can serve as reliable alternative specimens for toxicological analysis in cases where human tissue and fluids, normally taken during autopsies, are not available, due to decomposition of the corpse. This paper reports the results of drug analysis of the larvae of two fly families, Calliphoridae and Sarcophagidae, collected from the body of a middle-aged man who had committed suicide approximately three weeks before his corpse was found. Multiple samples of decomposed human tissue, of the blowfly, and of the larval flesh were analysed using gas chromatography/mass spectrometry (GC/MS), and amphetamine was detected in all samples. While the screening results were beyond doubt, the quantitative analysis was less clear, and further research is needed in this area.


Emerging Profiles for Cultured Meat; Ethics through and as Design.
The development of cultured meat has gained urgency through the increasing problems associated with meat, but what it might become is still open in many respects. In existing debates, two main moral profiles can be distinguished. Vegetarians and vegans who embrace cultured meat emphasize how it could contribute to the diminishment of animal suffering and exploitation, while in a more mainstream profile cultured meat helps to keep meat eating sustainable and affordable. In this paper we argue that these profiles do not exhaust the options and that (gut) feelings as well as imagination are needed to explore possible future options. On the basis of workshops, we present a third moral profile, "the pig in the backyard". Here cultured meat is imagined as an element of a hybrid community of humans and animals that would allow for both the consumption of animal protein and meaningful relations with domestic (farm) animals. Experience in the workshops and elsewhere also illustrates that thinking about cultured meat inspires new thoughts on "normal" meat. In short, the idea of cultured meat opens up new search space in various ways. We suggest that ethics can take an active part in these searches, by fostering a process that integrates (gut) feelings, imagination and rational thought and that expands the range of our moral identities.


The Effects of Lexical Pitch Accent on Infant Word Recognition in Japanese.
Learners of lexical tone languages (e.g., Mandarin) develop sensitivity to tonal contrasts and recognize pitch-matched, but not pitch-mismatched, familiar words by 11 months. Learners of non-tone languages (e.g., English) also show a tendency to treat pitch patterns as lexically contrastive up to about 18 months. In this study, we examined if this early-developing capacity to lexically encode pitch variations enables infants to acquire a pitch accent system, in which pitch-based lexical contrasts are obscured by the interaction of lexical and non-lexical (i.e., intonational) features. Eighteen 17-month-olds learning Tokyo Japanese were tested on their recognition of familiar words with the expected pitch or the lexically opposite pitch pattern. In early trials, infants were faster in shifting their eyegaze from the distractor object to the target object than in shifting from the target to distractor in the pitch-matched condition. In later trials, however, infants showed faster distractor-to-target than target-to-distractor shifts in both the pitch-matched and pitch-mismatched conditions. We interpret these results to mean that, in a pitch-accent system, the ability to use pitch variations to recognize words is still in a nascent state at 17 months.


Tuning the Integration Rate of Ce(Ln)O2 Nanoclusters into Nanoparticulated ZrO2 Supports: When the Cation Size Matters.
Three nanostructured catalysts with low total rare earth elements (REEs) content (i.e., 15 mol.%) were prepared by depositing CeO2 or Ln3+-doped CeO2 (Ln3+ = Y3+ or La3+; Ln/Ce = 0.15) on the surface of ZrO2 nanoparticles, as nanometre-thick, fluorite-type clusters. These samples were subjected to successive reduction treatments at increasing temperatures, from 500 to 900 °C. A characterisation study by XPS was performed to clarify the diffusion process of cerium into the bulk of ZrO2 crystallites upon reduction to yield CexZr1-xO2-δ surface phases, and the influence of the incorporation of non-reducible trivalent REE cations, with sizes smaller (Y3+) and larger (La3+) than Ce4+ and Ce3+. For all nanocatalysts, a reduction treatment at a minimum temperature of 900 °C was required to accomplish a significant cerium diffusion. Notwithstanding, the size of the dopant noticeably affected the extent of this diffusion process. As compared to the undoped ZrO2-CeO2 sample, Y3+ incorporation slightly hindered the cerium diffusion, while the opposite effect was found for the La3+-doped nanocatalyst. Furthermore, such differences in cerium diffusion led to changes in the surface and nanostructural features of the oxides, which were tentatively correlated with the redox response of the thermally aged samples.


[Carcinoma spinocellulare and cutaneous T-cell lymphomas].
Two cases of squamous cell carcinoma in patients with cutaneous T cell lymphoma are presented, together with a survey of the rather sparse literature on this subject. The cases presented showed considerable differences in their course. The mutagenic effects of the therapies used against the lymphoma are claimed to be responsible for the development of squamous cell carcinoma in almost all the published reports. However, we think the disturbances of the immune system caused either by the lymphoma itself or by the therapy might be a decisive factor in the development of secondary tumors. This possibility is supported by a comparison of immunosuppressed renal transplant recipients, who frequently develop squamous cell carcinomas of the skin. Frequent clinical follow-up examination of patients with cutaneous T cell lymphomas and early biopsy of suggestive lesions seem mandatory for differentiation between squamous cell carcinomas and tumorous infiltrations of the primary lymphoma. Radical surgical excision, which allows histological examination of the tumor margins, is the therapy of choice for these frequently very aggressive squamous cell carcinomas.


A novel G protein-coupled receptor with homology to neuropeptide and chemoattractant receptors expressed during bone development.
A novel G protein-coupled receptor was isolated from a cDNA derived from the cell line NH15-CA2 and a cDNA library from adult mouse brain using a PCR cloning strategy. The amino acid sequence of the candidate receptor DEZ showed homology to neuropeptide and chemoattractant receptors. Highest overall homology was found with the orphan receptor GPR-1 (65%), the angiotensin II receptor (62%), and the C5a anaphylatoxin receptor (60%). Northern blot analysis of dez revealed a predominant 2.6 kb mRNA species in NH15-CA2 cells. In situ hybridization experiments showed that dez is differentially regulated during development, with a prominent expression in developing osseous and cartilaginous tissue. It was also detectable in the adult parathyroid glands, hinting at a possible function in bone metabolism.


[Research and development thought on biopharmaceutics classification system of Chinese materia medica].
The biopharmaceutics classification system( BCS) is a scientific framework or method for classifying drugs based on drug solubility and permeability,which can be used to provide drug bioavailability-absorption correlation analysis. Based on the characteristics of multi-component and multi-target of traditional Chinese medicine( TCM) as well as the concept,method and technology of BCS,the research group proposed biopharmaceutics classification system of Chinese materia medica( CMMBCS) and carried out research and data accumulation of classical prescriptions. Based on the previous research results,further development ideas under the CMMBCS concept and framework were further proposed in this study. In the course of research,the influence of the intermediate links of the complex interactions of the multi-component environment was omitted,and the component absorption studies on the main clinical effects of prescription ingredients were directly concerned,or the components and data were reversely extracted from the aspects of metabolism,pharmacodynamic pathways and absorption principles. Studies were conducted from two aspects( single component and compound prescription) to comprehensively evaluate the absorption properties of TCM compound. In the research path,the different ways in which Chinese medicine could exert its efficacy were fully considered,and CMMBCS classification and establishment rules were clarified mainly by focusing on the absorption pathway into the blood. Specifically,the network pharmacology and molecular docking technology were used to screen the compound index components of TCM; the absorption rules were studied by the physiologically based pharmacokinetic models and the absorption parameters of CMMBCS were calculated by reverse reasoning. Then the CMMBCS classification of TCM prescription was corrected by studying the efficacy or absorption pathway. In this paper,the theoretical framework and research methodology of CMMBCS were systematically improved based on the establishment of CMMBCS basic theory,the supplementary of drug-oriented research ideas and the application of modern mature Chinese medicine methodology.


Key Roles of p53 Signaling Pathway-Related Factors GADD45B and SERPINE1 in the Occurrence and Development of Gastric Cancer.
p53 can function as an independent and unfavorable prognosis biomarker in cancer patients. We tried to identify the key factors of the p53 signaling pathway involved in gastric cancer (GC) occurrence and development based on the genotype-tissue expression (GTEx) and the Cancer Genome Atlas (TCGA) screening. We downloaded gene expression data and clinical data of GC included in the GTEx and TCGA databases, followed by differential analysis. Then, the key factors in the p53 signaling pathway were identified, followed by an analysis of the correlation between key factors and the prognosis of GC patients. Human GC cell lines were selected for in vitro cell experiments to verify the effects of key prognostic factors on the proliferation, migration, invasion, and apoptosis of GC cells. We found 4,944 significantly differentially expressed genes (DEGs), of which 2,465 were upregulated and 2,479 downregulated in GC. Then, 27 DEGs were found to be involved in the p53 signaling pathway. GADD45B and SERPINE1 genes were prognostic high-risk genes. The regression coefficients of GADD45B and SERPINE1 were positive. GADD45B was poorly expressed, while SERPINE1 was highly expressed in GC tissues, highlighting their prognostic role in GC. The in vitro cell experiments confirmed that overexpression of GADD45B or silencing of SERPINE1 could inhibit the proliferation, migration, and invasion and augment the apoptosis of GC cells. Collectively, the p53 signaling pathway-related factors GADD45B and SERPINE1 may be key genes that participate in the development of GC.


Clinical trials aimed at HIV cure or remission: new pathways and lessons learned.
The main barrier to finding a cure against HIV is the latent HIV reservoir, which persists in people living with HIV (PLWH) despite antiretroviral treatment (ART). Here, we discuss recent findings from interventional studies using mono- and combination therapies aimed at enhancing immune-mediated killing of the virus with or without activating HIV from latency. We discuss latency reversal agents (LRAs), broadly neutralizing antibodies, immunomodulatory therapies, and studies aimed at inducing apoptosis. The landscape of clinical trials for HIV cure and remission has evolved considerably over the past 10 years. Several novel interventions such as immune checkpoint inhibitors, therapeutic vaccines, and broadly neutralizing antibodies have been tested either alone or in combination with LRAs but studies have so far not shown a meaningful impact on the frequency of latently infected cells. Immunomodulatory therapies could work differently in the setting of antigen expression, that is, during active viremia, and timing of interventions could therefore, be key to future therapeutic success. Lessons learned from clinical trials aimed at HIV cure indicate that while we are still far from reaching a complete eradication cure of HIV, clinical interventions capable of inducing enhanced control of HIV replication in the absence of ART might be a more feasible goal.


Long-term visual outcomes of vitrectomy for cystoid macular edema due to nonischemic central retinal vein occlusion.
To report the long-term surgical outcome of vitrectomy for cystoid macular edema due to nonischemic central retinal vein occlusion (CRVO). A retrospective chart review of 25 consecutive eyes (25 patients) with cystoid macular edema due to nonischemic CRVO treated with vitrectomy was performed. All patients underwent a pars plana vitrectomy with the creation of a posterior vitreous detachment if still attached. Simultaneous phacoemulsification with intraocular lens implantation was also performed in phakic eyes. The main outcome measures were best-corrected visual acuity (BCVA) and changes in macular edema shown by contact-lens biomicroscopy. The mean follow-up time was 49 months (range, 16-108). The median BCVA before surgery was 0.31 and the median BCVA at last follow-up was 0.67. The BCVA at the last follow-up improved at least two Snellen lines in 17 (68%), remained unchanged in 4 (16%), and worsened in 4 (16%). The BCVA was 20/40 or better in 3 eyes (12%) preoperatively and in 18 eyes (72%) at the last follow-up. During the follow-up, four patients progressed to ischemic CRVO; one of them had neovascular glaucoma requiring surgical intervention. The data indicate that vitrectomy appears to be a possibly effective treatment in some eyes with cystoid macular edema associated with nonischemic CRVO.


Biofilm diversity, structure and matrix seasonality in a full-scale cooling tower.
Biofilms commonly colonise cooling water systems, causing equipment damage and interference with the operational requirements of the systems. In this study, next-generation sequencing (NGS), catalysed reporter deposition fluorescence in situ hybridisation (CARD-FISH), lectin staining and microscopy were used to evaluate temporal dynamics in the diversity and structure of biofilms collected seasonally over one year from an open full-scale cooling tower. Water samples were analysed to evaluate the contribution of the suspended microorganisms to the biofilm composition and structure. Alphaproteobacteria dominated the biofilm communities along with Beta- and Gammaproteobacteria. The phototrophic components were mainly cyanobacteria, diatoms and green algae. Bacterial biodiversity decreased from winter to autumn, concurrently with an increase in cyanobacterial and microalgal richness. Differences in structure, spatial organisation and glycoconjugates were observed among assemblages during the year. Overall, microbial variation appeared to be mostly affected by irradiance and water temperature rather than the source of the communities. Variations in biofilms over seasons should be evaluated to develop specific control strategies.


Bond strength of composite to astringent-contaminated dentin using self-etching adhesives.
To determine the effects of contamination by ferric sulfate and aluminum chloride astringents on the bond strength of composite bonded to superficial dentin using self-etching adhesives. Freshly extracted human teeth were ground to expose superficial dentin and polished to 600 grit. One of three self-etching adhesive systems and restorative composites were bonded to the specimens, with contamination by one of three astringents and five surface conditions (no contamination, moist dentin control; contaminant, air, adhesive; contaminant, water rinse, air, adhesive; contaminant, water rinse, glycolic acid scrub, rinse, adhesive; contaminant, water rinse, chlorhexadine scrub, rinse, adhesive). Composite was bonded to the surfaces in the shape of an inverted, truncated cone (n = 5, 180 specimens total). Specimens were stored in water at 37 degrees C for 24 hours, then de-bonded in tension with a testing machine at a crosshead speed of 0.5 mm/minute. Tensile bond strengths (MPa) were calculated. Means (SD) were compared using analysis of variance. Significant differences (Fisher's PLSD) were found among all variables. SE and ABF had the highest control values, but were affected most by astringent contamination. Ferric sulfate reduced bond strengths the greatest in most cases, and aluminum chloride putty reduced bond strengths the least. Chlorhexadine rinse was most effective in restoring bond strength values.


Anterior knee pain in children with cerebral palsy.
Anterior knee pain arising from the patellofemoral joint may be a significant problem in the cerebral palsy (CP) population. The aim of this study was to classify patients with anterior knee pain based on etiology and organize orthopaedic management based on this classification. This study was a retrospective chart review of patients with CP and anterior knee pain admitted to the orthopaedic outpatient clinic between 1991 and 2003. Children with CP who had intractable anterior knee pain despite 6 months of conservative treatment with at least 2 years' follow-up were identified and included. The medical records, radiographs, and treatment protocols were screened. Patients were classified into 3 groups according to pathology. Group I consisted of 7 children with patella alta only. Group II consisted of 7 children with patellar inferior pole fractures. Group III consisted of 13 children with subluxated or dislocated patellas. Conservative treatment methods such as anti-inflammatory drugs, local ice packs, stretching exercises, and braces should be the first step in treatment. For those patients in whom conservative treatment was not effective, surgical treatment alternatives were discussed. Knee pain resolved in all patients after surgical treatment of the underlying pathology. Gait analysis can be performed for patients with patellofemoral subluxations to evaluate the rotational malalignment of the tibia and femur. In conclusion, anterior knee pain arising from the patellofemoral joint in patients with CP should be evaluated and treated to prevent future functional deterioration.


Diffusivity of cerebellar hemispheres enables discrimination of cerebellar or parkinsonian multiple system atrophy from progressive supranuclear palsy-Richardson syndrome and Parkinson disease.
To explore the usefulness of histogram analysis of mean diffusivity (MD) derived from diffusion-weighted imaging of large infratentorial structures to distinguish parkinsonian syndromes. Local research ethics committee approval and informed consent were obtained. Ten patients with Parkinson disease (PD), nine with the parkinsonian variant of multiple system atrophy (MSA-P), seven with the cerebellar variant of MSA (MSA-C), 17 with progressive supranuclear palsy-Richardson syndrome (PSP-RS), and 10 healthy subjects were recruited. Histograms of MD values were generated for all pixels in the whole infratentorial compartment and separately for the whole brainstem, vermis, and cerebellar hemispheres. To assess the differences in MD values among groups, the Kruskal-Wallis test was used, followed by the Mann-Whitney U test for pairwise comparisons. All P values resulting from pairwise comparisons were corrected with the Bonferroni method. MSA-P and MSA-C groups had higher median MD values (P < .01) in the brainstem and cerebellum when compared with other groups; this finding was in line with the known consistent neurodegenerative damage in posterior cranial fossa structures in these diseases. Median MD values from cerebellar hemispheres were used to discriminate patients with MSA-C and those with MSA-P from patients with PD and those with PSP-RS (P < .01; sensitivity, specificity, and positive predictive value equaled 100%). Furthermore, patients with PSP-RS had significantly higher MD values in the vermis than did healthy subjects (P < .05) and patients with PD (P < .001). These findings support the clinical usefulness of diffusion imaging in the differential diagnosis of parkinsonism, suggesting that the minimally operator-dependent histogram analysis of the infratentorial structures and particularly of the whole cerebellar hemispheres can be used to distinguish patients with MSA-P and those with MSA-C from patients with PSP-RS and those with PD.


Pneumoperitoneum does not influence trocar site implantation during tumor manipulation in a solid tumor model.
The purpose of this study was to assess tumor implantation at abdominal wound sites following manipulation of a solid abdominal tumor. GW-39 human colon cancer cells were injected into the omentum of golden Syrian hamsters. At 2 weeks, an omental tumor was harvested and animals were randomized to bivalve (A), crush (B), strip (C), or excision (D), with or without pneumoperitoneum. Four 5-mm trocars were inserted into the abdomen, and the tumor was reinserted through the midline, swept through four quadrants, and removed. The incision was closed and pneumoperitoneum at 7 mmHg was maintained for 10 min. Tumor implantation at wound sites was documented at 7 weeks. Implantation at trocar sites was 53 and 49% with and without pneumoperitoneum in the manipulated groups (A, B, C), respectively (p = 0.993). Implantation at trocar sites was reduced in the control group (D) at 9 and 10% with and without pneumoperitoneum, respectively (p < 0.001). Tumor implantation at trocar sites is due to spillage of tumor during manipulation and not to pneumoperitoneum.


Parental Messages about Substance Use in Early Adolescence: Extending a Model of Drug-Talk Styles.
This study extends a typology of parent-offspring drug talk styles to early adolescents and investigates associations with adolescent substance use. Data come from a self-report survey associated with a school-based, 7th grade drug prevention curriculum. Mixed methods were used to collect data across four measurement occasions spanning 30 months. Findings highlight the frequencies of various drug-talk styles over time (i.e., situated direct, ongoing direct, situated indirect, ongoing indirect, never talked), messages adolescents hear from parents, and comparisons of alcohol, cigarette, and marijuana use by drug-talk style. This study advances an understanding of parent-adolescent communication about substances and holds practical implications for drug prevention efforts.


The effectiveness of subgingival irrigant ozone-based as adjuvant for non-surgical periodontal therapy in the treatment of chronic periodontitis: a review.
The aim of this review was to establish the efficacy of Ozone therapy (OT) in Periodontal disease's (PD) tratment. An electronic search of publications was established from two electronic databases: PubMed and Web of Science. The search strategy used a combination of controlled vocabulary and freetext words. Inclusion and exclusion criteria were defined by the authors before the start of the study. The inclusion criteria were: all studies published in English language; studies in vivo on humans; studies analyzing the correlation between PD and OT. The search resulted in 102 titles. Only 9 articles were included in the quantitative analysis. By the analyzed studies a strictly connection is still not evincible. More clinical trials are recommended to investigate the role of ozone, in its various types of topical administration, as a valid subgingival irrigant to achieve the goal of periodontal tissue health.


DNA damage-induced Bcl-xL deamidation is mediated by NHE-1 antiport regulated intracellular pH.
The pro-survival protein Bcl-xL is critical for the resistance of tumour cells to DNA damage. We have previously demonstrated, using a mouse cancer model, that oncogenic tyrosine kinase inhibition of DNA damage-induced Bcl-xL deamidation tightly correlates with T cell transformation in vivo, although the pathway to Bcl-xL deamidation remains unknown and its functional consequences unclear. We show here that rBcl-xL deamidation generates an iso-Asp(52)/iso-Asp(66) species that is unable to sequester pro-apoptotic BH3-only proteins such as Bim and Puma. DNA damage in thymocytes results in increased expression of the NHE-1 Na/H antiport, an event both necessary and sufficient for subsequent intracellular alkalinisation, Bcl-xL deamidation, and apoptosis. In murine thymocytes and tumour cells expressing an oncogenic tyrosine kinase, this DNA damage-induced cascade is blocked. Enforced intracellular alkalinisation mimics the effects of DNA damage in murine tumour cells and human B-lineage chronic lymphocytic leukaemia cells, thereby causing Bcl-xL deamidation and increased apoptosis. Our results define a signalling pathway leading from DNA damage to up-regulation of the NHE-1 antiport, to intracellular alkalanisation to Bcl-xL deamidation, to apoptosis, representing the first example, to our knowledge, of how deamidation of internal asparagine residues can be regulated in a protein in vivo. Our findings also suggest novel approaches to cancer therapy.


Coupled-map-lattice model for spontaneous pore formation in anodic oxidation.
We construct a coupled map lattice model for spontaneous pore formation in anodic oxidation in two dimensions and perform numerical simulations, after we explain steady flat solutions, their linear stability, and a single pore solution for a model of Parkhutik and Shershulsky.


The U.S. Dairy Forage Research Center (USDFRC) Condensed Tannin NMR Database.
This Perspective describes a solution-state NMR database for flavan-3-ol monomers and condensed tannin dimers through tetramers obtained from the literature to 2015, containing data searchable by structure, molecular formula, degrees of polymerization, and 1H and 13C chemical shifts of the condensed tannins. Citations for all literature references are provided and should serve as valuable resource for scientists working in the field of condensed tannin research. The database will be periodically updated as additional information becomes available, typically on a yearly basis and is available for use, free of charge, from the U.S. Dairy Forage Research Center (USDFRC) Website.


Comparison of blood group versus HLA-dependent transplantation and its influence on donor kidney survival.
The advantages of organ allocation based on human leukocyte antigen (HLA) typing are controversial. This evaluation compares the results of HLA-dependent and non-HLA-dependent allocation in the transplantation of donor kidneys. Seventy-seven donor kidney pairs explanted locally between 1984 and 1994 were examined. One half of each pair was transplanted locally in Bonn on the basis of criteria including blood group, waiting time and currently negative cross-match. The other half of these pairs was allocated in accordance with the Eurotransplant (ET) criteria. Cold ischaemia time was an average of 14.02 h in Bonn vs. 24.18 h in the ET group (P<0.0001). The number of HLA mismatches was calculated and, for example, for locus A it was 1.13 in Bonn vs. 0.73 in the ET group (P=0.0003). One-year graft survival for the locally transplanted kidneys was 92.2% and, for the ET kidneys, 90.9%. Five-year survival was 79.5% vs. 81.7%, respectively. Patient survival after 1 year was 100% vs. 97.4%, and after 5 years, 93.4% vs. 93.1%. The results show that it is possible to provide patients with a locally allocated kidney graft that enables good function after a short waiting period. This procedure avoids long cold ischaemia time and long waiting periods.


[Randomized controlled trial on haiguiyuyang capsule in the treatment of duodenal ulcer].
To assess the efficacy and safety of haiguiyuyang capsule in the treatment of duodenal ulcer (also diagnosed as weiwan pain and hanrecuoza syndrome according to the theory of TCM). This is a multi-center clinical trial cooperatively conducted from May 2003 to March 2004 in accordance to the principle of informed consent, to the criteria for subject inclusion, exclusion, discontinuation, and to the relevant guidelines for evaluating the therapeutic effects of new TCM drugs. The design of double-blind, double-dummy and randomized controlled trial was adopted. 438 patients were randomized to the Test group (n = 330, treated with haiguiyuyang capsule) and to the Control group (n = 108, treated with ranitidine). The therapeutic course for both groups was 6 weeks. Regarding the efficacy in treating duodenal ulcer, in the Test group, the Marked Efficacy Rate was 66.37% and the Total Efficacy Rate was 82.13%; in the Control group, the Marked Efficacy Rate was 68.61% and the Total Efficacy Rate was 93.34%; there was no significant difference between the two groups (P>0.05). Regarding the efficacy in treating the syndrome diagnosed by TCM, in the Test group, the Marked Efficacy Rate was 70.31% and the Total Efficacy Rate was 93.34%; in the control group, the rates were 71.29% and 91.66% respectively; there was no significant difference between the two groups (P>0.05). Besides, regarding the abatement of distention and fullness of stomach after treatment, the haiguiyuyang capsule was better than ranitidine (P<0.05). No adverse side-effect was observed. The efficacy of haiguiyuyang capsule in treating duodenal ulcer is similar to that of ranitidine. No obvious adverse effect of it was observed in this trial.


The value of ultrasound in the child with an acute urinary tract infection.
To assess the value of an ultrasound examination in children with a proven urinary tract infection. The results of renal ultrasound and 99mTc-dimercapto-succinic acid (DMSA) studies were compared in 112 children with a first documented symptomatic Escherichia coli urinary tract infection. Ultrasound was particularly effective in detecting the presence of obstruction, renal swelling and parenchymal change consistent with acute pyelonephritis. However, ultrasound failed to detect half of the kidneys with photon deficient areas on 99mTc DMSA scan and was unreliable in detecting the presence of scarring. An ultrasound examination alone should not be relied on in the child with an acute urinary tract infection.


Systematic review of ethnomedicine, phytochemistry, and pharmacology of Cyperi Rhizoma.
Cyperi Rhizoma (CR) is the dry rhizome of Cyperus rotundus L., a Cyperaceae plant. It has a long history of clinical medication and is known as the "holy medicine" of gynecology. CR smells sweet and bitter. It has the effect of soothing the liver and relieving depression, regulating qi, regulating meridian and relieving pain. It can be used to treat liver qi stagnation, chest pain, spleen and stomach qi stagnation, hernia pain, irregular menstruation and other diseases. At present, the main chemical constituents isolated from CR are volatile oil, flavonoids and terpenes. Modern pharmacological studies have shown that CR has a wide range of pharmacological activities, including antidepressant, hypoglycemic, antioxidant, anti-inflammatory, antipyretic and analgesic effects. In this paper, the botany, traditional application, phytochemistry, pharmacological effects, processing and other aspects of CR are reviewed. At the same time, the shortcomings of current research of CR are discussed in depth, and the possible solutions are put forward in order to find a breakthrough point for future research of CR.


Janus kinase inhibitors in systemic lupus erythematosus: implications for tyrosine kinase 2 inhibition.
Aberrant activation of the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is common in systemic lupus erythematosus (SLE), conferring immune-mediated properties in target tissues. Multiple cytokines activate different combinations of JAKs and STATs to alter the cell fate of target tissue and induce end-organ damage. Thus, the simultaneous blockade of several different cytokines by small molecules acting downstream intracellular signalling has gained traction. JAK inhibitors have been approved for the treatment of several rheumatic diseases, yet hitherto not for SLE. Nevertheless, JAK inhibitors including tofacitinib, baricitinib, and deucravacitinib have shown merit as treatments for SLE. Tofacitinib, a JAK1/3 inhibitor, reduced cholesterol levels, improved vascular function, and decreased the type I interferon signature in SLE patients. Baricitinib, a JAK1/2 inhibitor, demonstrated significant improvements in lupus rashes and arthritis in a phase 2 and a phase 3 randomised controlled trial, but the results were not replicated in another phase 3 trial. Deucravacitinib, a selective tyrosine kinase 2 (TYK2) inhibitor, yielded greater response rates than placebo in a phase 2 trial of SLE and will be investigated in larger phase 3 trials. TYK2 is activated in response to cytokines actively involved in lupus pathogenesis; this review highlights the potential of targeting TYK2 as a promising therapy for SLE.


Seed from the upper devonian.
We present evidence proving the existence of seeds in the Upper Devonian and extending the known age of seed plants from the Lower Carboniferous (Mississippian) into the Upper Devonian.


Identification of molecularly defined Staphylococcus aureus strains using matrix-assisted laser desorption/ionization time of flight mass spectrometry and the Biotyper 2.0 database.
Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) has recently been introduced for bacterial identification. To our knowledge, this is the first study where the Biotyper 2.0 database (Bruker Daltonics) has been applied for bacterial identification in a local strain collection of molecularly defined Staphylococcus aureus. We showed that the accuracy of the Biotyper 2.0-based identification for 602 molecularly defined strains of S. aureus, irrespective of meticillin resistance, was equivalent to that of the molecularly defined reference even at a score cut-off value of 2. Also, 412 isolates of 20 different species of non-S. aureus staphylococci were all correctly identified to species level compared to the molecularly defined reference. Moreover, the MALDI-TOF MS-based S. aureus identification approach was clearly faster than more time-consuming methods such as a molecular identification approach.


The 50-kDa primase subunit of Drosophila melanogaster DNA polymerase alpha. Molecular characterization of the gene and functional analysis of the overexpressed protein.
The gene encoding the 50-kDa subunit of Drosophila melanogaster DNA polymerase alpha has been cloned. A comparison of the predicted polypeptide sequence of the Drosophila protein with the equivalent subunits from mouse and yeast suggests that they are closely related and defines three conserved regions which are likely to be important for enzyme activity. The expression patterns of both the 50-kDa protein and its transcript (a single RNA message of 1.6 kilobases) throughout development are consistent with a role of the protein in DNA replication. When overexpressed and purified the 50-kDa subunit displays DNA primase activity. The products of the reaction, mainly oligoribonucleotides 12-14 nucleotides in length, plus dimers and some trimers, are similar to those synthesized by either the intact DNA polymerase alpha, or the biochemically isolated primase heterodimer. The isolated primase also shows similar sensitivity to antibodies, magnesium and monovalent cations, and the same nucleotide requirements as complexed forms of the primase. The isolated subunit, however, is more thermally labile, suggesting a role for the additional subunits in DNA polymerase alpha in stabilizing the primase activity of the 50-kDa primase subunit.


Intentionally remembering or forgetting own- and other-race faces: Evidence from directed forgetting.
People are better at remembering faces of their own relative to another ethnic group. This so-called own-race bias (ORB) has been explained in terms of differential perceptual expertise for own- and other-race faces or, alternatively, as resulting from socio-cognitive factors. To test predictions derived from the latter account, we examined item-method directed forgetting (DF), a paradigm sensitive to an intentional modulation of memory, for faces belonging to different ethnic and social groups. In a series of five experiments, participants during learning received cues following each face to either remember or forget the item, but at test were required to recognize all items irrespective of instruction. In Experiments 1 and 5, Caucasian participants showed DF for own-race faces only while, in Experiment 2, East Asian participants with considerable expertise for Caucasian faces demonstrated DF for own- and other-race faces. Experiments 3 and 4 found clear DF for social in- and outgroup faces. These results suggest that a modulation of face memory by motivational processes is limited to faces with which we have acquired perceptual expertise. Thus, motivation alone is not sufficient to modulate memory for other-race faces and cannot fully explain the ORB.


Protein hydrolysates from anchovy waste: purification and chemical characterization.
The aim of this study is to prompt the recovery of industrial by-products through the production of new functional foods; it takes advantage from new throughput technologies with low environmental impact and high economic sustainability. In the field of fish processing, in order to recover the worthy protein-rich fish waste, residues from the production of Anchovies (Engraulis encrasicolus) have been converted into hydrolysate through enzymatic treatment. The obtained hydrolysate product showed a promising biological and nutritional content made by differently sized peptides and free amino acids endowed with assessed benefic effects. The study showed the possibility to produce a dry powder with an activity water (aw) of 0.3-0.5 and an essential amino acids (EAA) fraction of 42.0% over the total amino acids (TAAs). These results pave the way to the smart recovery of commercial products featured by high nutritional value, either as stand-alone items or as components of functional foods.


Metabolic disturbances and defects in insulin secretion in rats with streptozotocin-nicotinamide-induced diabetes.
Rats with diabetes induced by streptozotocin (STZ) and nicotinamide (NA) are often used in animal studies concerning various aspects of diabetes. In this experimental model, the severity of diabetes is different depending on doses of STZ and NA. Moreover, diabetic changes in rats with STZ-NA-induced diabetes are not fully characterized. In our present study, metabolic changes and insulin secretion were investigated in rats with diabetes induced by administration of 60 mg of STZ and 90 mg of NA per kg body weight. Four to six weeks after diabetes induction, insulin, glucagon and some metabolic parameters were determined to evaluate the severity of diabetes. Moreover, insulin secretory capacity of pancreatic islets isolated from control and diabetic rats was compared. It was demonstrated that administration of 60 mg of STZ and 90 mg of NA per kg body weight induced relatively mild diabetes, since insulin, glucagon and other analyzed parameters were only slightly affected in diabetic rats compared with control animals. In vitro studies revealed that insulin secretory response was preserved in pancreatic islets of diabetic rats, however, was lower than in islets of control animals. This effect was observed in the presence of different stimuli. Insulin secretion induced by 6.7 and 16.7 mmol/l glucose was moderately reduced in islets of diabetic rats compared with control islets. In the presence of leucine with glutamine, insulin secretion appeared to be also decreased in islets of rats with STZ-NA-induced diabetes. Insulinotropic action of 6.7 mmol/l glucose with forskolin was also deteriorated in diabetic islets. Moreover, it was demonstrated that at a non-stimulatory glucose, pharmacological depolarization of plasma membrane with a concomitant activation of protein kinase C evoked significant rise in insulin release in islets of control and diabetic rats. However, in diabetic islets, this effect was attenuated. These results indicate that impairment in insulin secretion in pancreatic islets of rats with mild diabetes induced by STZ and NA results from both metabolic and nonmetabolic disturbances in these islets.


Mechanisms for Color Convergence in a Mimetic Radiation of Poison Frogs.
In animals, bright colors often evolve to mimic other species when a resemblance is selectively favored. Understanding the proximate mechanisms underlying such color mimicry can give insights into how mimicry evolves-for example, whether color convergence evolves from a shared set of mechanisms or through the evolution of novel color production mechanisms. We studied color production mechanisms in poison frogs (Dendrobatidae), focusing on the mimicry complex of Ranitomeya imitator. Using reflectance spectrometry, skin pigment analysis, electron microscopy, and color modeling, we found that the bright colors of these frogs, both within and outside the mimicry complex, are largely structural and produced by iridophores but that color production depends crucially on interactions with pigments. Color variation and mimicry are regulated predominantly by iridophore platelet thickness and, to a lesser extent, concentration of the red pteridine pigment drosopterin. Compared with each of the four morphs of model species that it resembles, R. imitator displays greater variation in both structural and pigmentary mechanisms, which may have facilitated phenotypic divergence in this species. Analyses of nonmimetic dendrobatids in other genera demonstrate that these mechanisms are widespread within the family and that poison frogs share a complex physiological "color palette" that can produce diverse and highly reflective colors.


A 'brain tumor' in an intravenous drug abuser.
A male intravenous drug abuser who was infected with hepatitis B and C, presented with a slowly progressive hemiplegia. Contrast enhanced computerized tomography of the head showed a solitary ring-enhanced mass with surrounding edema. Clinically brain tumor was suspected but a brain biopsy confirmed cerebral toxoplasmosis. An HIV test was not considered until the result of brain biopsy. He also had lymphopenia and positive serum toxoplasma antibody. His subsequent HIV test was positive. He deteriorated after a brain biopsy. Empirical antitoxoplasma treatment is recommended in HIV-positive patients with ring-enhanced lesions with surrounding edema and with positive toxoplasma serology. Cerebral toxoplasmosis is still the commonest cerebral opportunistic infection in HIV-infected patients even though the incidence has declined with the use of antiretroviral therapy. It is often diagnosed in those patients as an initial presentation of HIV infection or in those who failed to attend for disease monitoring. Clinical features and differential diagnosis of cerebral toxoplasmosis in immunocompromised patients are discussed.


Concise, stereoselective approach to the spirooxindole ring system of citrinadin A.
The spirooxindole ring system of citrinadin A has been synthesized with excellent control over the absolute stereochemistry at the spirocenter. The key step involves a novel diastereoselective DMDO-mediated oxidative rearrangement employing an 8-phenylmenthol chiral auxiliary on the indole nitrogen.