TAG-72-Targeted α-Radionuclide Therapy of Ovarian Cancer Using 225Ac-Labeled DOTAylated-huCC49 Antibody.
Radioimmunotherapy, an approach using radiolabeled antibodies, has had minimal success in the clinic with several β-emitting radionuclides for the treatment of ovarian cancer. Alternatively, radioimmunotherapy with α-emitters offers the advantage of depositing much higher energy over shorter distances but was thought to be inappropriate for the treatment of solid tumors, for which antibody penetration is limited to a few cell diameters around the vascular system. However, the deposition of high-energy α-emitters to tumor markers adjacent to a typical leaky tumor vascular system may have large antitumor effects at the tumor vascular level, and their reduced penetration in normal tissue would be expected to lower off-target toxicity. Methods: To evaluate this concept, DOTAylated-huCC49 was labeled with the α-emitter 225Ac to target tumor-associated glycoprotein 72-positive xenografts in a murine model of ovarian cancer. Results:225Ac-labeled DOTAylated-huCC49 radioimmunotherapy significantly reduced tumor growth in a dose-dependent manner (1.85, 3.7, and 7.4 kBq), with the 7.4-kBq dose extending survival by more than 3-fold compared with the untreated control. Additionally, a multitreatment regime (1.85 kBq followed by 5 weekly doses of 0.70 kBq for a total of 5.4 kBq) extended survival almost 3-fold compared with the untreated control group, without significant off-target toxicity. Conclusion: These results establish the potential for antibody-targeted α-radionuclide therapy for ovarian cancer, which may be generalized to α-radioimmunotherapy in other solid tumors.


Managing severe asthma in adults: lessons from the ERS/ATS guidelines.
To review the latest guidelines on severe asthma. An updated definition of severe asthma is provided together with the evaluation steps necessary to reach a diagnosis of severe asthma. The importance of phenotyping is emphasized, and recommendations are provided for therapies specifically directed for severe asthma. Severe asthma is widely recognized as a major unmet need. It is defined as asthma that requires treatment with high-dose inhaled corticosteroids and a second controller and/or systemic corticosteroid to prevent it from becoming 'uncontrolled' or that remains 'uncontrolled' despite this therapy. Severe asthma is a heterogeneous condition that consists of phenotypes such as eosinophilic asthma. More phenotypes need to be defined. Evaluation of the patient referred to as having severe or difficult-to-control asthma must take into account adherence to treatment, comorbidities and associated factors including side effects from therapies. These need to be addressed. Recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy are presented. Treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty is reviewed and recommendations made. Research efforts into phenotyping of severe asthma will provide both biomarker-driven approaches and newer effective therapies to severe asthma management.


Povidone-Iodine-Based Polymeric Nanoparticles for Antibacterial Applications.
As microbial contamination is becoming more and more serious, antibacterial agents play an important role in preventing and removing bacterial pathogens from microbial pollution in our daily life. To solve the issues with water solubility and antibacterial stability of PVP-I2 (povidone-iodine) as a strong antibacterial agent, we successfully obtain hydrophobic povidone-iodine nanoparticles (povidone-iodine NPs) by a two-step method related to the advantage of nanotechnology. First, the synthesis of poly(N-vinyl-2-pyrrolidone-co-methyl methacrylate) nanoparticles, i.e., P(NVP-MMA) NPs, was controlled by tuning a feed ratio of NVP to MMA. Then, the products P(NVP-MMA) NPs were allowed to undergo a complexation reaction with iodine, resulting in the formation of a water-insoluble antibacterial material, povidone-iodine NPs. It is found that the feed ratio of NVP to MMA has an active effect on morphology, chemical composition, molecular weight, and hydrophilic-hydrophobic properties of the P(NVP-MMA) copolymer after some technologies, such as SEM, DLS, elemental analysis, 1H NMR, GPC, and the contact angle test, were used in the characterizations. The antibacterial property of povidone-iodine NPs was investigated by using Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Pseudomonas aeruginosa (P. aeruginosa) as model bacteria with the colony count method. Interestingly, three products, such as glue, ink, and dye, after the incorporation of povidone-iodine NPs, show significant antibacterial properties. It is believed that, with the advantage of nanoscale morphology, the final povidone-iodine NPs should have great potential for utilization in various fields where antifouling and antibacterial properties are highly required.


Developmental co-ordination disorder in socially disadvantaged Brazilian children.
The consequences of developmental co-ordination disorder (DCD) indicate a need for identification in order to provide adequate intervention. The goals of the study were to investigate DCD prevalence across age bands, gender, race and school performance; the motor difficulties of children with DCD, at-risk and typically developing children in the Movement Assessment Battery for Children (MABC) sub-tests across age bands and gender; and the relationship between motor outcomes, age, gender and socio-economic status (SES) in socially disadvantaged Brazilian children. The MABC was administered to 1056 Brazilian children from 4 to 10 years old. Eighteen per cent of the children were screened as probable DCD (≤5th percentile) and a further 15% as at risk for DCD (>5th and ≤15th percentile). Significantly more children were screened with probable DCD at age 9-10 years (AB3: P = 0.00), whereas at risk classification was equally distributed across age bands (P = 0.12). Boys showed lower prevalence than girls of probable DCD and at risk for DCD (P = 0.04). Children (9-10 years) showed higher motor impairment in the manual dexterity test results. Children with probable DCD and at risk of DCD showed, in general, poor performance in balance and manual dexterity tasks. SES was the strongest predictor of motor outcomes, accounting for 21% of the variance in the MABC percentile scores. The prevalence of probable and at-risk DCD cases as well as the percentage of female were higher than those found in the previous studies, and low SES enhances the risk of poor motor development.


Reversal of sensorimotor gating abnormalities in Fmr1 knockout mice carrying a human Fmr1 transgene.
Fragile X syndrome is caused by a CGG trinucleotide repeat expansion of the FMR1 gene. Individuals with fragile X display several behavioral abnormalities including hyperactivity, social anxiety, autistic-like features, impaired cognitive processing, and impaired sensorimotor gating. The Fmr1KO mouse model of fragile X exhibits several related behavioral phenotypes such as increased activity and altered social interactions. Individuals with fragile X also have impaired sensorimotor gating as measured using the prepulse inhibition of startle response. The authors have recently shown that Fmr1KO mice with a yeast artificial chromosome containing the human FMR1 gene have corrected or overcorrected abnormal behaviors including hyperactivity and altered social interactions. Here the authors present results from a study examining abnormal sensorimotor gating in Fmr1KO mice. Consistent with previous findings, Fmr1KO mice have increased prepulse inhibition. The KO mice with the yeast artificial chromosome containing the human FMR1 gene had levels of prepulse inhibition comparable to WT mice, indicating not only a correction of this phenotype, but also clearly demonstrating that in mice levels of the fragile X mental retardation protein regulate sensorimotor gating.


Role of central venous pressure monitoring in critical care settings.
Central venous pressure (CVP) monitoring is used to assess the fluid status of patients in critical care settings. This article explains CVP monitoring, discussing the rationale for its use, the ways CVP can be measured, and the physiological factors that can affect the reliability and validity of CVP measurement. It also discusses the complications associated with CVP monitoring and the nursing responsibilities in relation to this activity.


Gastric blunt traumatic injuries: A computed tomography grading classification.
To produce a radiological grading of gastric traumatic injuries. In our study, we retrospectively analyzed 32 cases of blunt gastric traumatic injuries and compared computed tomography (CT) data with patients' surgical or medical development. In all cases, a basal phase was acquired, and an intravenous contrast material was administered via an antecubital venous catheter with acquisition in the venous phase (70-90 s). In addition, a further set of delayed scans was performed 4-5 min after the first scanning session, without supplementary intravenous contrast material, to identify or better define areas of active bleeding. All CT examinations were retrospectively reviewed by two radiologists, with more than 5 years of experience in emergency radiology, to detect signs of gastric injuries and/or associated abdominal lesions according to literature data. Specific CT findings for gastric rupture include luminal content extravasation and discontinuity of the gastric wall, while CT findings suggestive of injury consisted of free peritoneal fluid, extraluminal air, pneumatosis, and thickening and hematoma of gastric wall. We found 32 gastric traumatic injuries. In 22 patients (68.8%), the diagnosis was based on the surgical findings; in the other 10 patients (31.2%), the diagnosis was based on the clinical and CT radiological data. We observed discontinuity of the gastric wall and luminal content extravasation in 1 patient (3.1%); in 10 patients (31.2%), there was extra-luminal air in the peritoneum. In 28 patients (87.5%), there was peritoneal fluid, which was blood in 14 patients (hematoma in 11 patients and contrast material extravasation from active bleeding in 3 patients). In 15 patients (46.9%), there was gastric wall thickening. In 3 patients, it was possible to identify a prevalent involvement of the external layer of the gastric wall, whereas, in 2 patients, the inner side of the gastric wall presented with major involvement. In 3 patients (9.4%), pneumatosis of the gastric wall was detected. In 19 (59.4%) patients, the stomach was full. The fundus was the most frequently damaged part of the stomach because it was involved in 17 patients (53.1%). Based on the observed data, we identified four grades of gastric lesions. A radiologic score is helpful for guiding the diagnosis and management (surgical or conservative) of gastric blunt traumatic injuries and stratify patients according to short-term outcomes.


Effect of herbicides on cellulose decomposition by Sporocytophaga myxococcoides.
The effects of 14 herbicides on cellulose decomposition by Sporocytophaga myxococcoides were studied by growing the organism in two different liquid cellulose-mineral salts media in the presence of the test agent and then quantitatively determining the residual cellulose. In the first medium, containing acid-hydrolyzed cellulose, anthrone reagent was used to determine residual carbohydrate. In the second medium, Gooch Pyrex fritted-glass crucibles were used to determine the amount of residual Whatman powdered cellulose. The herbicides used were Atrazine, Simazine, Dacthal, Diuron, Amiben, Banvel-D, Banvel-T,2,3,6-TBA, Dicryl, Maleic Hydrazide, Stam F-34, Zytron, Fenac, and Dalapon. Of these, Zytron appeared to be the most inhibitory to the test bacterium, and was the only compound exhibiting inhibition at a commonly used field rate of application (2 ppm).


Design and evaluation of mPEG-PLA micelles functionalized with drug-interactive domains as improved drug carriers for docetaxel delivery.
Polymeric micelles are very attractive drug delivery systems for hydrophobic agents, owing to their readily tailorable chemical structure and ease for scale-up preparation. However, the intrinsic poor stability of drug-loaded micelles presents one of the major challenges for most micellar systems in the translation to clinical applications. In this study, a simple, well-defined, and easy-to-scale up 9-Fluorenylmethoxycarbonyl (Fmoc) and tert-butoxycarbonyl (Boc) containing lysine dendronized mPEG-PLA (mPEG-PLA-Lys(FB)2) micellar formulation was designed and prepared for docetaxel (DTX) delivery, in an effort to improve the stability of the micelles, and its physicochemical properties, pharmacokinetics, and anti-tumor efficacy against SKOV-3 ovarian cancer were evaluated. MPEG-PLA-Lys(FB)2 was synthesized via a three-step synthetic route, and it actively interacted with DTX in aqueous media to form stable micelles with small particle sizes (~17-19 nm) and narrow size distribution (PI < 0.1), which can be lyophilized and easily reconstituted in saline without significant change in particle size distribution. In vitro drug-release study demonstrated that mPEG-PLA-Lys(FB)2 micelles achieved delayed and sustained release manner of DTX in comparison with mPEG-PLA micelles. Further in vivo xenograft tumor model in nude mice DTX/mPEG-PLA-Lys(FB)2 micelles demonstrated significantly higher inhibitory effect on tumor growth than the marketed formulation Taxotere. Thus, our system may hold promise as a simple and effective delivery system for DTX with a potential for translation into clinical study.


Congenital desmoid fibromatosis in a Holstein heifer.
An 11-month-old, Holstein heifer was presented for a progressive swelling on the left side of the face that had been present since birth. A diagnosis of fibromatosis was made, based on macroscopic and microscopic examination of the abnormal infiltrative tissue. Because of the poor prognosis the animal was euthanized.


Divergence insufficiency alleviated by posterior fossa decompression with duraplasty in a patient with Chiari type 1.5 malformation.
The authors present a case of Chiari type 1.5 malformation with the uncommon presenting symptoms of esotropia and diplopia due to divergence insufficiency in a 12-year-old girl. Imaging at initial diagnosis revealed cerebellar herniation with extension of the tonsils to the C2 vertebral body, a retroflexed odontoid, and a small cervical syrinx. The patient was initially treated with an uncomplicated Chiari malformation decompression without dural opening. Repeat imaging revealed an adequate decompression. Three months postoperatively the patient's diplopia recurred and she underwent repeat posterior fossa decompression with dural opening and duraplasty. Following repeat decompression with dural opening and duraplasty, the patient's diplopia had not recurred by the 2-year follow-up.https://thejns.org/doi/abs/10.3171/2018.5.PEDS1886.


Fast object imaging and classification based on circular harmonic Fourier moment detection.
Limited by the number of illumination fields and the speed of a spatial light modulator, single-pixel imaging (SPI) cannot realize real-time imaging and fast classification of an object. In this paper, we proposed the circular harmonic Fourier single-pixel imaging (CHF-SPI) for the first time to realize fast imaging and classification of objects. The light field distribution satisfies the circular harmonic Fourier formula, and the light intensity values of the single-pixel detector are equivalent to the circular harmonic Fourier moments. Then the target can be reconstructed under low sampling ratio by inverse transformation. Through simulation and experimental verification, clear imaging can be performed at a sampling ratio of 0.9%. In addition, circular harmonic Fourier moments are used to construct multi-distortion invariant to classify objects with rotation and scale change. The scale change multiples of objects can be calculated and the objects can be classified by using 10 light fields. It is of great significance to classify objects quickly without imaging.


[Surgical therapy of chronic anal fissure--do additional proctologic operations impair continence?].
78 patients with chronic anal fissures have been mainly operated on by lateral internal sphincterotomy (LATS). Continence have been evaluated by questionnaire at least 9 months postoperatively. Patient without any additional proctological operation had minor disturbances of continence in 17%. Patient with additional operations had disturbances of continence in 30%. Especially the subgroup of patients with LATS and haemorrhoidectomy had bad results. In this group only 45% were fully continent.


Peptide-Based Drug-Delivery Systems in Biotechnological Applications: Recent Advances and Perspectives.
Peptides of natural and synthetic sources are compounds operating in a wide range of biological interactions. They play a key role in biotechnological applications as both therapeutic and diagnostic tools. They are easily synthesized thanks to solid-phase peptide devices where the amino acid sequence can be exactly selected at molecular levels, by tuning the basic units. Recently, peptides achieved resounding success in drug delivery and in nanomedicine smart applications. These applications are the most significant challenge of recent decades: they can selectively deliver drugs to only pathological tissues whilst saving the other districts of the body. This specific feature allows a reduction in the drug side effects and increases the drug efficacy. In this context, peptide-based aggregates present many advantages, including biocompatibility, high drug loading capacities, chemical diversity, specific targeting, and stimuli responsive drug delivery. A dual behavior is observed: on the one hand they can fulfill a structural and bioactive role. In this review, we focus on the design and the characterization of drug delivery systems using peptide-based carriers; moreover, we will also highlight the peptide ability to self-assemble and to actively address nanosystems toward specific targets.


Enhanced Thermochemical Stability of CH3NH3PbI3 Perovskite Films on Zinc Oxides via New Precursors and Surface Engineering.
Hydroxyl groups on the surface of ZnO films lead to the chemical decomposition of CH3NH3PbI3 perovskite films during thermal annealing, which limits the application of ZnO as a facile electron-transporting layer (ETL) in perovskite solar cells. In this work, we report a new recipe that leads to substantially reduced hydroxyl groups on the surface of the resulting ZnO films by employing polyethylenimine (PEI) to replace generally used ethanolamine in the precursor solutions. Films derived from the PEI-containing precursors are denoted as P-ZnO and those from the ethanolamine-containing precursors as E-ZnO. Besides the fewer hydroxyl groups that alleviate the thermochemical decomposition of CH3NH3PbI3 perovskite films, P-ZnO also provides a template for the fixation of fullerene ([6,6]-phenyl-C61-butyric acid methyl ester, PCBM) owing to its nitrogen-rich surface that can interact with PCBM. The fullerene was used to block the direct contact between P-ZnO and CH3NH3PbI3 films and therefore further enhance the thermochemical stability of perovskite films. As a result, perovskite solar cells based on the P-ZnO/PCBM ETL yield an optimal power conversion efficiency (PCE) of 15.38%. We also adopt P-ZnO as the ETL for organic solar cells that yield a remarkable PCE of 10.5% based on the PBDB-T:ITIC photoactive layer.


Follow-up of intracranial aneurysms treated with detachable coils: comparison of plain radiographs, 3D time-of-flight MRA and digital subtraction angiography.
All patients with aneurysms treated with Guglielmi detachable coils (GDC) are undergo angiography to assess long-term stability of aneurysm exclusion or to show recurrence of the aneurysm sac, which may require further treatment. We prospectively compared the plain-film appearance of the coil-mass, 3D time-of-flight MR angiography (TOF MRA) and digital subtraction angiography (DSA) for the detection of aneurysm recanalisation during follow-up. We studied 60 patients with 74 intracranial aneurysms treated with Guglielmi detachable coils. We used the unsubtracted image of the angiograms performed at the completion of any embolisation procedure and at follow-up as the plain radiographs. Recanalisation was considered if loosening, compaction or reorientation of the coil mass was apparent. TOF MRA was performed to assess the presence and size of a neck remnant. DSA was regarded as the definitive investigation. Comparison of the techniques showed good agreement as regards aneurysm recanalisation. MRA was more accurate than plain radiography and could replace DSA for long term follow- up. The initial follow-up examination should, however, include both modalities. In cases of contraindications or limitations to MRA, the interval between follow-up angiographic examinations could be increased if there is no change in the plain-film coil-mass appearances.


Batch adsorption study in liquid phase under agitation, rotation, and nanobubbles: comparisons in a multi-parametric study.
Concern for environmental protection has increased throughout the years from a global perspective. To date, the predominance of adsorption as treatment technique in environmental chemistry remains unchallenged. Moreover, the scientific attention for investigating nanobubbles due to their unique properties has turned the search for their application in environmental processes with special emphasis on water treatment. This study is aimed at investigating the effect of rotation on batch adsorption process using commercial activated carbon as adsorbent material, compared with the widely used method of agitation. As liquid medium, deionized water and deionized water enhanced with nanobubbles (of air) were used. The wastewater was simulated by dissolving a common dye as model pollutant, methylene blue, at concentration of 300 mg/L in the tested liquid. The results indicated that the utilization of nanobubbles resulted in an improvement on adsorption rate, compared to the corresponding values of deionized water solutions. These results may lead to promising applications in the future, since just 1 h of operation increases the water purification and thus provides a simply applied, cost-effective, and rapid alternative.


Rhizopogon togasawariana sp. nov., the first report of Rhizopogon associated with an Asian species of Pseudotsuga.
Rhizopogon subgenus Villosuli are the only members of the genus known to form an ectomycorrhizal relationship exclusively with Pseudotsuga. The specificity of this host relationship is unusual in that Rhizopogon is broadly associated with several tree genera within the Pinaceae and relationships with a host genus are typically distributed across Rhizopogon subgenera. Naturally occurring specimens of R. subg. Villosuli have been described only from North American collections, and the unique host relationship with Pseudotsuga is demonstrated only for Rhizopogon associated with P. menziesii (Douglas-fir), the dominant species of Pseudotsuga in North America. Species of Pseudotsuga are naturally distributed around the northern Pacific Rim, and Rhizopogon associates of other Pseudotsuga spp. are not yet described. Here we present the results of field sampling conducted in P. japonica forests throughout the Japanese archipelago and describe Rhizopogon togasawariana sp. nov., which occurs in ectomycorrhizal association with P. japonica. Placement of this new species within R. subg. Villosuli is supported by morphological and molecular phylogenetic analysis, and its implications to Pseudotsuga-Rhizopogon biogeography are discussed.


[Preliminary results of submucosal tunneling endoscopic septum division in the treatment of esophageal diverticulum].
To evaluate the safety and efficacy of submucosal tunneling endoscopic septum division (STESD) for escophageal diverticulum. Clinical data of six consecutive patients with symptomatic esophageal diverticula who received STESD in Endoscopy Center of Zhongshan Hospital, Fudan University from April 2016 to November 2016 were analyzed retrospectively. STESD was performed as following: mucosal entry was made 3 cm from the septum of esophageal diverticulum; submucosal tunnel was created towards the septum; after the satisfactory exposure of the septum, endoscopic division was made down to the bottom of the diverticulum; mucosal closure of the tunnel entry was made. The symptoms were scored using a system modified according to Eckardt score, namely dysphagia, heartburn, regurgitation, weight loss and retrosternal pain with each ranging from 0 to 3 (maximum score 15, minimum score 0, the higher the score, the more severe the symptoms). There were four males and two females with median age of 56.5 (range 50-67) years. Four patients were epiphrenic diverticula, and the other two were Zenker's diverticula. Median duration of disease was 2.5 years (range 5 months-29 years). No previous treatment was attempted. All the patients completed STESD successfully. The median septum division length was 2.5(1-4) cm. The median number of metallic clips for mucosal closure was 5(2-6). The median operation time was 51.5 (33-135) min. No major adverse events, such as perforation or bleeding were found in perioperative period. The median time of hospital stay was 5(3-9) days. All the patients had symptom relief after operation. One patient with Zenker's diverticulum reported foreign body sensation after operation and experienced relief two weeks afterwards. During a median follow-up time of 5(4-10) months, the median symptom score of 6 cases was 4.5 (1-13) before and 0.5 (0-4) after operation. The symptom scores went down to zero in 3 patients (preoperative scores 13, 1, 1, respectively), and down to 1 in 2 patients with main symptom of backflow (preoperative scores 5, 4, respectively). One patient with 29 years history of disease did not report obvious improvement in symptoms (preoperative and postoperative scores 5, 4, respectively). Submucosal tunneling endoscopic septum division is efficient and safe to relieve symptomatic esophageal diverticulum in short term.


Physical impairment and body weight history in postmenopausal women: the Women's Health Initiative.
To examine whether weight history and weight transitions over adult lifespan contribute to physical impairment among postmenopausal women. BMI categories were calculated among postmenopausal women who reported their weight and height at age 18 years. Multiple-variable logistic regression was used to determine the association between BMI at age 18 years and BMI transitions over adulthood on severe physical impairment (SPI), defined as scoring <60 on the Physical Functioning subscale of the Rand thirty-six-item Short-Form Health Survey. Participants were part of the Women's Health Initiative Observational Study (WHI OS), where participants' health was followed over time via questionnaires and clinical assessments. Postmenopausal women (n 76 016; mean age 63·5 (sd 7·3) years). Women with overweight (BMI=25·0-29·9 kg/m2) or obesity (BMI≥30·0 kg/m2) at 18 years had greater odds (OR (95 % CI)) of SPI (1·51 (1·35, 1·69) and 2·14 (1·72, 2·65), respectively) than normal-weight (BMI=18·5-24·9 kg/m2) counterparts. Transitions from normal weight to overweight/obese or to underweight (BMI<18·5 kg/m2) were associated with greater odds of SPI (1·97 (1·84, 2·11) and 1·35 (1·06, 1·71), respectively) compared with weight stability. Shifting from underweight to overweight/obese also had increased odds of SPI (1·52 (1·11, 2·09)). Overweight/obese to normal BMI transitions resulted in a reduced SPI odds (0·52 (0·39, 0·71)). Higher weight history and transitions into higher weight classes were associated with higher likelihood of SPI, while transitioning into lower weight classes for those with overweight/obesity was protective among postmenopausal women.


Weak Association Between the Glutamate Decarboxylase 1 Gene (GAD1) and Schizophrenia in Han Chinese Population.
Schizophrenia (SZ) is a complex psychiatric disorder with high heritability, and genetic components are thought to be pivotal risk factors for this illness. The glutamate decarboxylase 1 gene (GAD1) was hypothesized to be a candidate risk locus for SZ given its crucial role in the GABAergic neurotransmission system, and previous studies have examined the associations of single nucleotide polymorphisms (SNPs) spanning the GAD1 gene with SZ. However, inconsistent results were obtained. We hence examined the associations between GAD1 SNPs and SZ in two independent case-control samples of Han Chinese ancestry. Two Han Chinese SZ case-control samples, referred as the discovery sample and the replication sample, respectively, were recruited for the current study. The discovery sample comprised of 528 paranoid SZ cases (with age of first onset ≥ 18) and 528 healthy controls; the independent replication sample contained 1,256 early onset SZ cases (with age of first onset < 18) and 2,661 healthy controls. Logistic regression analysis was performed to examine the associations between GAD1 SNPs and SZ. Ten SNPs covering GAD1 gene were analyzed in the discovery sample, and two SNPs showed nominal associations with SZ (rs2241165, P = 0.0181, OR = 1.261; rs2241164, P = 0.0225, OR = 1.219). SNP rs2241164 was also nominally significant in the independent replication sample (P = 0.0462, OR = 1.110), and the significance became stronger in a subsequent meta-analysis combining both discovery and replication samples (P = 0.00398, OR = 1.138). Nevertheless, such association could not survive multiple corrections, although the effect size of rs2241164 was comparable with other SZ risk loci identified in genome-wide association studies (GWAS) in Han Chinese population. We also examined the associations between GAD1 SNPs and SZ in published datasets of SZ GWAS in East Asians and Europeans, and no significant associations were observed. We observed weak associations between GAD1 SNPs and risk of SZ in Han Chinese populations. Further analyses in larger Han Chinese samples with more detailed phenotyping are necessary to elucidate the genetic correlation between GAD1 SNPs and SZ.


Meeting the needs of a community: teaching evidence-based youth violence prevention initiatives to members of strategic communities.
Youth violence is among the most serious health threats in the nation today. Violence disproportionately affects young people and people of color. Although the national rates of violent injury and homicide have shown a decline in most regions of the United States over the past 15 years, the rates of violence and related injuries among youth remain unacceptably high. The prevention of youth violence has been a priority of health departments nationwide, including the Cook County Department of Public Health. The goal of this project was to provide key community leaders, social service workers, and nurses within suburban Cook County with educational sessions on Blueprints for Violence Prevention, an initiative to promote evidence-based youth violence prevention programs.


Visual selective attention is impaired in children prenatally exposed to opioid agonist medication.
To examine whether prenatal exposure to opioid agonist medication is associated with visual selective attention and general attention problems in early childhood. Twenty-two children (mean age = 52.17 months, SD = 1.81) prenatally exposed to methadone, 9 children (mean age = 52.41 months, SD = 1.42) prenatally exposed to buprenorphine and 25 nonexposed comparison children (mean age = 51.44 months, SD = 1.31) were tested. Visual selective attention was measured with a Tobii 1750 Eye Tracker using a spatial negative priming paradigm. Attention problems were measured using the Child Behavior Checklist. The comparison group demonstrated a larger spatial negative priming effect (mean = 23.50, SD = 45.50) than the exposed group [mean = -6.84, SD = 86.39, F(1,50) = 5.91, p = 0.019, η(2) = 0.11]. No difference in reported attention problems was found [F(1,51) = 1.63, p = 0.21, η(2) = 0.03]. Neonatal abstinence syndrome and prenatal exposure to marijuana were found to predict slower saccade latencies in the exposed group (b = 54.55, SE = 23.56, p = 0.03 and b = 88.86, SE = 32.07, p = 0.01, respectively). Although exposed children did not appear to have attention deficits in daily life, lower performance on the SNP task indicates subtle alteration in the attention system.


Ameloblastic carcinoma: a rare entity.
Ameloblastic carcinoma is a rare aggressive malignant epithelial odontogenic tumour seen in a wide range of age group with no sex predilection. Patient usually presents with a rapidly enlarging swelling. It usually involves the posterior portion of the mandible. Treatment of choice is surgical removal of tumour followed by radiotherapy. We present a case of ameloblastic carcinoma in a 35-year-old man.


Preparation of sodium deoxycholate (DOC) conjugated heparin derivatives for inhibition of angiogenesis and cancer cell growth.
We describe new DOC (sodium deoxycholate)-heparin nanoparticles for in vivo tumor targeting and inhibition of angiogenesis based on chemical conjugation and the enhanced permeability and retention (EPR) effect. Heparin has been used as a potent anticoagulant agent for 70 years, and has recently been found to inhibit the activity of growth factors which stimulate the smooth muscle cells around tumor. From the results, DOC and heparin were conjugated by bonding carboxyl groups of heparin with amine groups of aminated sodium deoxycholate. Larger antitumor effects of the DOC-heparin VI (8.5 mol of DOC coupled with 1.0 mol heparin) were achieved in animal studies, compared to heparin alone. We confirmed that the conjugated heparin retained its ability to inhibit binding with angiogenic factor, showing a significant decrease in endothelial tubular formation. These results provide new insights into the nontoxic anticancer drug carrier as well as the design of multifunctional bioconjugates for targeted drug delivery.


Husbandry and enclosure influences on penguin behavior and conservation breeding.
Multi-zoo comparisons of animal welfare are rare, and yet vital for ensuring continued improvement of zoo enclosures and husbandry. Methods are not standardized for the development of zoo enclosures based on multiple indicators, and case study species are required. This study compares behavior and breeding success to various enclosure and husbandry parameters for the Humboldt penguin, Spheniscus humboldti, for the development of improved enclosure design. Behavioral sampling was completed at Flamingo Land over a period of 8 months. Further data on behavior, enclosure design, and breeding success were collected via questionnaires, visits to zoos, and literature review. Breeding success was primarily influenced by colony age and number of breeding pairs, suggesting an important social influence on reproduction. Across zoos, there was also significant variation in behavior. The proportion of time spent in water varied between zoos (2-23%) and was used as an indicator of physical activity and natural behavior. Regression models revealed that water-use was best predicted by total enclosure area per penguin, followed by land area, with some evidence for positive influence of pool surface area per penguin. Predominantly linear/curvilinear increases in our biological indicators with enclosure parameters suggest that optimal conditions for S. humboldti were not met among the selected zoos. We propose revised minimum conditions for S. humboldti enclosure design, which exceed those in the existing husbandry guidelines. We present a framework for the evaluation of zoo enclosures and suggest that a rigorous scientific protocol be established for the design of new enclosures, based on multivariate methods. Zoo Biol. 35:385-397, 2016. © Wiley Periodicals, Inc.


Geographical distribution of Pseudomonas pseudomallei in China.
1,366 samples of soil and water from southern China coastal provinces were examined for Pseudomonas pseudomallei. Data showed that 58 samples were positive for this bacteria, which is primarily distributed in Hainan Province and the coastal region of mainland. This paper confirmed the environmental presence of P. pseudomallei in China and showed that the distribution of this pathogen has at least reached a latitude of 25.5 degrees north.


Spatial comparison of London's three waves of Spanish Flu.
England and Wales experienced three waves of influenza during the 1918/19 Spanish Flu pandemic. A previous analysis showed that these three waves had fundamentally different spatial and temporal characteristics. This present study compares London's experience of the three waves to discern possible geographic differences on a metropolitan level. Borough mortality data for each wave were normalized and then scaled, with spatial autocorrelation techniques displayed by GIS software and analysed for each wave. Registrar General in England and Wales reporting provided data concerning measures of 'health' and 'wealth' for each metropolitan borough. Spearman's rank correlation determined the correlation of each wave's mortality to each of the other waves including the 'health,' 'wealth' and population density factors. The comparisons showed that there is a spatial difference among the waves. The first two are spatially similar, with both exhibiting 'random' autocorrelation patterns, while the third wave exhibits a 'clustered' pattern. The borough mortality of the first two waves strongly correlated with each other, with both having similar 'health,' 'wealth' and population density factors. However, the third wave's mortality did not correlate with any of the first two and actually behaved in an opposite manner with regard to the 'health,' 'wealth,' and population density factors. These results do not appear in the literature and create new opportunities for research to explain London's mortality during the Spanish Flu pandemic of 1918/19.


Circ_0001658 regulates PI3K/AKT signaling via the miR-671-5p/ITGA2 axis and affects the progress of papillary thyroid carcinoma.
Circular RNAs (circRNAs) are a newly described class of non-coding RNAs that play essential roles in regulating gene expression. However, to date, few studies have examined the roles of circRNAs in papillary thyroid carcinoma (PTC). In this study, we analyzed the expression of circ_0001658 in PTC as well as its functions and associated mechanisms of action in PTC cells. Real-time quantitative polymerase chain reaction was used to determine the expression of circ_0001658, miR-671-5p, and integrin subunit alpha 2 (ITGA2), and western blotting was performed to determine the levels of ITGA2 and phosphatidylinositide 3-kinase/protein kinase B pathway-related proteins in PTC cell lines. Cell Counting Kit-8 and Transwell analyses were conducted to examine the effects of circ_0001658 on PTC cell function following the knockdown of circ_0001658 expression. In addition, the targeting of circ_0001658 and ITGA2 by miR-671-5p was verified using dual-luciferase reporter assays. We demonstrated that circ_0001658 and ITGA2 were significantly up-regulated in PTC tissues and cell lines. Knockdown of circ_0001658 inhibited the growth and metastatic potential of PTC cells. MiR-671-5p targeted both circ_0001658 and ITGA2. Mechanistically, circ_0001658 promoted PTC progression by sponging miR-671-5p, up-regulating ITGA2 expression, and activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. In summary, circ_0001658 is a carcinogenesis-associated circRNA that regulates PI3K/AKT signaling via the miR-671-5p/ITGA2 axis and plays a role in promoting the progression of PTC. Our findings provide a theoretical basis for further molecular biological studies on the treatment of PTC.


Two new European species of the marine genus Tubificoides (Annelida: Clitellata: Naididae) with notes on the morphology of T. pseudogaster (Dahl, 1960).
Two new species of Tubificoides (subfamily Tubificinae), T. charlotteae n. sp. and T. mackiei n. sp., are described based on morphological analyses. Both species were flagged as potentially cryptic in a previous investigation, based on both mitochondrial and nuclear sequence data. Tubificoides charlotteae n. sp., known only from an intertidal site in southern Spain, is characterized by the lack of cuticular papillation, the possession of several needle-like hair chaetae in dorsal bundles, a cone-shaped penis sheath, and a rather large, muscular penial sac. It strongly resembles the north-west European, largely sublittoral species T. amplivasatus, but differs from this species in terms of body size, width of vas deferens, and the shape and size of both the ejaculatory duct and penial sac. Tubificoides mackiei n. sp., collected from the southeast coast of Norway and the west coast of Sweden, is characterized by the lack of cuticular papillae and hair chaetae, and the possession of a rather long penis sheath with a wide terminal opening. It shares several morphological features with the sympatric species Tubificoides pseudogaster, but is distinguished from the latter by the detailed morphology and length of the penis sheaths, the width of the atrium, and the lower maximal number of bifid chaetae in dorsal preclitellar bundles. The utility of an integrative comparative approach, combining molecules and morphology, for the identification and delineation of new taxa within Tubificoides is briefly discussed.


Oxidative stress modulates tyrosine kinase receptor A and p75 receptor (low-affinity nerve growth factor receptor) expression in SHSY5Y neuroblastoma cells.
The interaction of neurotrophins and their tyrosine kinase receptors (trks) is essential for differentiation and survival of brain cells. In Alzheimer's disease (AD), the number of neurotrophins and receptors is markedly decreased. The cause of this reduction is unclear, but the role of beta-amyloid (Abeta) seems central in understanding the mechanisms controlling neurotrophin and trk expression. In the study reported here, we exposed SHSY5Y neuroblastoma cells to Abeta or hydrogen peroxide (H(2)O(2)) and measured the expression of trk-A and p75 at the protein and molecular levels. Both Abeta and H(2)O(2) induced oxidative stress (measured by a decrease in cellular glutathione), which decreased trk-A levels and increased p75 levels, decreased messenger RNA (mRNA) levels of both receptors, and increased nerve growth factor (NGF) secretion. Pretreatment of cells with the antioxidant melatonin returned levels of protein expression, mRNA, and NGF secretion to normal. These results are significant, as they can help in the planning and implementation of AD treatment strategies involving neurotrophins.


The calmodulin-like protein, CML39, is involved in regulating seed development, germination, and fruit development in Arabidopsis.
We show that the calcium sensor, CML39, is important in various developmental processes from seeds to mature plants. This study bridges previous work on CML39 as a stress-induced gene and highlights the importance of calcium signalling in plant development. In addition to the evolutionarily-conserved Ca2+ sensor, calmodulin (CaM), plants possess a large family of CaM-related proteins (CMLs). Using a cml39 loss-of-function mutant, we investigated the roles of CML39 in Arabidopsis and discovered a range of phenotypes across developmental stages and in different tissues. In mature plants, loss of CML39 results in shorter siliques, reduced seed number per silique, and reduced number of ovules per pistil. We also observed changes in seed development, germination, and seed coat properties in cml39 mutants in comparison to wild-type plants. Using radicle emergence as a measure of germination, cml39 mutants showed more rapid germination than wild-type plants. In marked contrast to wild-type seeds, the germination of developing, immature cml39 seeds was not sensitive to cold-stratification. In addition, germination of cml39 seeds was less sensitive than wild-type to inhibition by ABA or by treatments that impaired gibberellic acid biosynthesis. Tetrazolium red staining indicated that the seed-coat permeability of cml39 seeds is greater than that of wild-type seeds. RNA sequencing analysis of cml39 seedlings suggests that changes in chromatin modification may underlie some of the phenotypes associated with cml39 mutants, consistent with previous reports that orthologs of CML39 participate in gene silencing. Aberrant ectopic expression of transcripts for seed storage proteins in 7-day old cml39 seedlings was observed, suggesting mis-regulation of early developmental programs. Collectively, our data support a model where CML39 serves as an important Ca2+ sensor during ovule and seed development, as well as during germination and seedling establishment.


Alterations in Anatomical Covariance in the Prematurely Born.
Preterm (PT) birth results in long-term alterations in functional and structural connectivity, but the related changes in anatomical covariance are just beginning to be explored. To test the hypothesis that PT birth alters patterns of anatomical covariance, we investigated brain volumes of 25 PTs and 22 terms at young adulthood using magnetic resonance imaging. Using regional volumetrics, seed-based analyses, and whole brain graphs, we show that PT birth is associated with reduced volume in bilateral temporal and inferior frontal lobes, left caudate, left fusiform, and posterior cingulate for prematurely born subjects at young adulthood. Seed-based analyses demonstrate altered patterns of anatomical covariance for PTs compared with terms. PTs exhibit reduced covariance with R Brodmann area (BA) 47, Broca's area, and L BA 21, Wernicke's area, and white matter volume in the left prefrontal lobe, but increased covariance with R BA 47 and left cerebellum. Graph theory analyses demonstrate that measures of network complexity are significantly less robust in PTs compared with term controls. Volumes in regions showing group differences are significantly correlated with phonological awareness, the fundamental basis for reading acquisition, for the PTs. These data suggest both long-lasting and clinically significant alterations in the covariance in the PTs at young adulthood.


Strategy for teaching evaluation research in psychiatric/mental health nursing.
The evaluation research course presented in this paper is one strategy for introducing needed evaluation research content at the graduate level in nursing. The course was developed for students who were in their final semester of completing requirements for an MSN degree with a major in psychiatric/mental health nursing. To provide for active involvement in the evaluation research process, students evaluated a psychotherapy group in which they were therapists. The theoretical framework for both class content and the evaluation research project was based on Bloch's extension of Donabedian's approach to evaluation. Using the theoretical framework as a guide, students investigated both process and outcome as well as the relationship between process and outcome. Students reported that the knowledge and skills gained were valuable to their clinical practice. On the other hand, students found the course to be very demanding and difficult to complete in a 15 week period. One unexpected benefit, however, was that the course helped students to understand group process better.


Optimized detection of bacteria in bloodstream infections.
Bloodstream infection (BSI) is a life-threatening condition characterized by the presence of pathogens in the blood. It is associated with increased morbidity and mortality, and has to be treated promptly as mortality increases with every hour of delayed treatment. Therefore, rapid and sensitive diagnosis of BSI is essential. The routine diagnostic method for BSI is blood culture, which can only detect culturable pathogens and takes several days to obtain results. The 16S rRNA gene is present in all bacteria and is commonly used as a target for universal bacterial detection in rapid molecular assays such as PCR. However, molecular detection of the 16S gene is hampered by the large amount of human DNA found in blood samples, making diagnostic results aspecific and less sensitive. We have optimized the selection of PCR primers targeting the 16S rRNA gene to avoid cross-reaction with human DNA background. The developed method increases specificity and sensitivity for pathogen diagnosis, and provides rapid and accurate pathogen detection for rare bacterial DNA in the presence of abundant host DNA.


Targeting gene-virus-mediated manganese superoxide dismutase effectively suppresses tumor growth in hepatocellular carcinoma in vitro and in vivo.
Although the treatment methods for hepatocellular carcinoma (HCC) have made a great progress on patient survival rate and life quality, the HCC recurrence still is very high. To explore the novel effective anticancer strategies for HCC, the Cancer Targeting Gene-Viro-Therapy (CTGVT) strategy was applied through oncolytic virus-delivery antitumor gene. In this article, the dual-regulated oncolytic adenovirus Ad-AFP-E1A-E1B(Δ55kDa)-Mn-SOD (briefly named AD55-Mn-SOD) was constructed using a liver cancer-specific α-fetoprotein (AFP) promoter to control replication-essential E1A gene and deliver the novel tumor suppression gene Manganese superoxide dismutase (Mn-SOD). The results indicated that the constructed AD55-Mn-SOD exerted tumor-specific features, and induced dramatic cytotoxicity in HCC cells in vitro and suppress the HCC xenografted growth in nude mice. Moreover, the anticancer mechanism of AD55-Mn-SOD is due to the activation of caspase apoptotic pathway. These data suggested that AD55-Mn-SOD could become a potential anticancer agent for liver cancer.


The effect of coffee on contralateral suppression of transient evoked otoacoustic emissions.
Background: Coffee is a popular non-alcoholic beverage consumed by humans across the world. It contains caffeine, which is a type of stimulant of the central nervous system. In the auditory system, it has a positive effect on auditory brainstem response and perception of speech in noise. Further, caffeine has an inhibitory effect in the cochlea, but studies have rarely investigated its effect on otoacoustic emissions (OAEs) in humans. OAEs are low-intensity sounds produced by the cochlea, which could be recorded in the ear canal. The present study was carried out to investigate the effect of coffee on transient evoked otoacoustic emission (TEOAE) and contralateral suppression of TEOAE. Method: A total of 52 young adults participated in the study. A cross-over study design was used for the present investigation. The TEOAE and contralateral suppression of TEOAE were recorded before and after consumption of coffee and milk. The contralateral suppression of TEOAE was measured by presenting white noise to the contralateral ear at 40, 50, and 60 dB sound pressure level (SPL). Results: The mean amplitude of TEOAE before and after consumption of coffee was similar in both ears. Further, the mean contralateral suppression of TEOAE was slightly larger after consumption of coffee in both ears. However, the mean difference was not significant in both the ears. Conclusions: Based on the findings of present study, coffee has no significant effect on the amplitude of TEOAE and contralateral suppression of TEOAE.


Choosing Conservative Care in Advanced Chronic Kidney Disease - Patients' Perspectives.
Conservative care (CC) is a viable treatment option for some patients with kidney failure. Choosing between dialysis and CC can be a complex decision, in which involvement of patients is desirable. Gaining insight into the experiences and preferences of patients regarding this decision-making process is an important initial step to improve care. We aimed to identify what is known about the perspective of patients regarding decision-making when considering CC. PubMed, EMBASE and Cochrane databases were systematically searched on 23 February 2023 for qualitative and quantitative studies on patient-reported experiences on decision-making about CC. Data were analysed thematically. Twenty articles were included. We identified three major themes: creating awareness about disease and treatment choice, decision support and motivation to choose CC. Patients were often not aware of the option to choose CC. Patients felt supported by their loved ones during the decision-making process, although they perceived to make the final decision to choose CC themselves. Some patients felt pressured by their healthcare professional to choose dialysis. Reported reasons to choose CC were maintaining quality of life, treatment burden of dialysis, costs and the desire not to be a burden to others. In general, patients were satisfied with their decision for CC. By focussing on the perspective of patients, we identified a wide range of patient experiences and preferences regarding the decision-making process. These findings can help to improve the complex decision-making process between dialysis and CC and to provide patient-centred care.


Effect of Representational Distance between Meanings on Recognition of Ambiguous Spoken Words.
Previous research indicates that mental representations of word meanings are distributed along both semantic and syntactic dimensions such that nouns and verbs are relatively distinct from one another. Two experiments examined the effect of representational distance between meanings on recognition of ambiguous spoken words by comparing recognition of unambiguous words, noun-verb homonyms, and noun-noun homonyms. In Experiment 1, auditory lexical decision was fastest for unambiguous words, slower for noun-verb homonyms, and slowest for noun-noun homonyms. In Experiment 2, response times for matching spoken words to pictures followed the same pattern and eye fixation time courses revealed converging, gradual time course differences between conditions. These results indicate greater competition between meanings of ambiguous words when the meanings are from the same grammatical class (noun-noun homonyms) than they when are from different grammatical classes (noun-verb homonyms).


Otalgia as the sole presenting manifestation of subdural hematoma.
A case is reported of a 57-year-old man with sudden development of nontraumatic left-sided otalgia without any localizing features on otolaryngologic or neurologic examinations. The condition persisted despite empirical antibiotic therapy and simple analgesics. A subsequent computed tomography of the head revealed a subacute left frontoparietal subdural hematoma that was confirmed on magnetic resonance imaging. Neurosurgical drainage was performed with complete symptom resolution. This case report illustrates a possible rare sole presenting manifestation of subdural hematoma. This condition should be considered early in cases of otalgia if no causes are deduced after extensive otolaryngologic evaluation.


Bortezomib for the treatment of mantle cell lymphoma.
To describe the Food and Drug Administration review and marketing approval considerations for bortezomib (Velcade) for the treatment of patients with mantle cell lymphoma. Food and Drug Administration reviewed a multicenter study of bortezomib in 155 patients with progressive mantle cell lymphoma after at least one prior therapy. Seventy-seven percent were stage IV, and 75% had one or more extranodal sites of disease. Prior therapy included an anthracycline or mitoxantrone, cyclophosphamide, and rituximab. Median age was 65 years. All received bortezomib 1.3 mg/m(2) i.v. on days 1, 4, 8, and 11 of each 3-week cycle. The primary end point was response. Response and progression were determined by independent review of serial computed tomography scans using International Lymphoma Workshop Response Criteria. The overall response rate was 31%, including complete response (CR) plus CR unconfirmed (CRu) plus partial response; median response duration was 9.3 months. The CR plus CRu response rate was 8% with a median duration of 15.4 months. Adverse events were similar to those observed previously for bortezomib. The most commonly reported treatment-emergent adverse events were asthenia (72%), peripheral neuropathies (55%), constipation (50%), diarrhea (47%), nausea (44%), and anorexia (39%). The most common adverse event leading to discontinuation was neuropathy. Bortezomib received regular approval for the treatment of patients with mantle cell lymphoma in relapse after prior therapy.


Effects on mouse blastocysts of in vitro exposure to methylnitrosourea and 3-methylcholanthrene.
Mouse blastocysts were exposed in vitro to various concentrations of N-methyl-N-nitrosourea and 3-methylcholanthrene. The incorporation of [3H]thymidine, [3H]uridine, and [3H]leucine into the exposed blastocysts was determined either immediately following exposure or after 18 hr of culture. The concentrations of N-methyl-N-nitrosourea or 3-methylcholanthrene used had no effect on blastocyst viability in either situation. There was a concentration-dependent decrease in the incorporation of the precursors into blastocysts exposed to N-methyl-N-nitrosourea which appears to be more pronounced after 18 hr in culture. This effect was not demonstrated for 3-methylcholanthrene, which requires metabolic activation for reactivity. Blastocysts exposed to N-methyl-N-nitrosourea were injected into the uterine horns of surrogate mothers; a significant increase in the resorption rate of these blastocysts was seen when compared with controls. Similar experiments were performed to determine birth rate. A dose-dependent decrease in birth rate was observed which correlated well with the effects on incorporation of thymidine, uridine, and leucine but not with the effect of implantation rate.


Analysis of 340 Patients with Solid Pseudopapillary Tumors of the Pancreas: A Closer Look at Patients with Metastatic Disease.
Current literature addressing the treatment of solid pseudopapillary neoplasms (SPNs) of the pancreas is limited, particularly for patients with distant metastases. We aimed to define predictive indicators of survival in a large series of patients and assess the outcome of patients with distant metastases. The National Cancer Database was queried for patients diagnosed with SPNs of the pancreas between 1998 and 2011. Single predictor univariate analyses were performed on variables including demographics, tumor characteristics, and surgery outcomes, and multivariate Cox proportional hazards survival analysis was then completed with backward elimination. Overall, 340 patients were identified: 82% were female, median age was 39 years, and 84% had no comorbidities. Patients undergoing any type of surgical resection experienced long-term survival (85% 8-year survival). Patients undergoing surgical resection (n = 296) had superior survival (hazard ratio [HR] 21 for no surgery, p < 0.0001), as did patients treated at academic centers and those with private insurance (HR 3.9, p = 0.009; HR 4.9, p = 0.007). Sex, age, tumor size, presence of lymph node metastases, positive surgical margins, and presence of distant metastases were not significant predictors of survival in multivariate analysis. Of 24 patients with distant metastases, seven were treated surgically and experienced long-term survival similar to that of patients without metastases treated surgically (HR 2, p = 0.48). SPNs of the pancreas are rare neoplasms with excellent overall survival; however, in a low number of patients they metastasize. Of the few patients with metastatic disease selected for resection, most experienced long-term survival.


Association of BLK (rs13277113, rs2248932) polymorphism with systemic lupus erythematosus: a meta-analysis.
The B-cell lymphocyte kinase (BLK) is a src-family protein tyrosine kinase specifically expressed in B-lineage cells that has been implicated in the pathogenesis of systemic lupus erythematosus (SLE) and has been investigated in numerous ethnically diverse studies. However, genetic association studies that have examined the association between BLK gene variants and SLE have produced conflicting results. To shed further light on this issue, we performed a meta-analysis of the association between rs13277113, rs2248932 polymorphism and SLE in different ethnic groups. An updated literature-based meta-analysis of six original articles involving 20,271 control individuals and 11,796 subjects with SLE was conducted. Crude ORs with 95% CIs were used to assess the strength of association between rs13277113, rs2248932 polymorphism and SLE risk. Publication bias was estimated using Egger's linear regression test. The authors assessed the evidence of genotypic association using STATA Version 10.0. The combined overall odds ratio, calculated for SLE and the risk A-allele of rs13277113 was 1.416 (95% CI: 1.358, 1.477). An odds ratio of 1.264 (95% CI: 1.208, 1.322) was found for the T-allele of rs2248932. Significant associations of rs13277113 and SLE were observed for dominant model (AA + AG vs. GG, OR: 1.518; 95% CI: 1.411, 1.632), and recessive model (AA vs. AG + GG, OR: 1.553; 95% CI: 1.461, 1.651); so were rs2248932 and SLE for dominant model (TT + TC vs. CC, OR: 1.342; 95% CI: 1.233, 1.460), and recessive model (TT vs. TC + CC, OR: 1.338; 95% CI: 1.257, 1.424). All of these were conducted in fixed effects model as heterogeneity was not detected. Tests for bias revealed no evidence of biases. On the assessment of available evidence, the authors concluded that moderate evidence exists for an association between the BLK rs13277113, rs2248932 variants and SLE. Therefore, further research is warranted on the role of BLK polymorphisms in the etiology of SLE.


SFRP2 is a Novel Diagnostic Biomarker and Suppresses the Proliferation of Pituitary Adenoma.
Pituitary adenoma (PA) constitutes one of the most common intracranial tumors. The present study was designed to identify potential diagnostic markers for PA. We used gene expression profiles (GEO: GSE26966 and GEO: GSE63357 datasets) derived from human PA and nontumor samples that were made freely accessible by the gene expression omnibus (GEO) datasets. Differentially expressed genes (DEGs) were screened between 14 normal specimens and 34 PA specimens by the use of the limma package of the R. The diagnostic genes were determined using a LASSO regression model and SVM-RFE analysis. SFRP2 expression in PA cells was analyzed using RT-PCR, and the effect of SFRP2 dysregulation on PA cell proliferation was measured using CCK-8 analysis. In this study, 361 DEGs were identified: 309 genes were downregulated and 52 genes were upregulated. The results of KEGG assays revealed that the 361 DEGs were mainly enriched in the PI3K-Akt signaling pathway, MAPK signaling pathway, growth hormone synthesis, secretion and action, and AGE-RAGE signaling pathway in diabetic complications. Results from the LASSO regression model and the SVM-RFE analysis indicated that LOC101060391 and SFRP2 were diagnostic genes. In contrast to normal tissue, the expressions of LOC101060391 and SFRP2 were much lower in PA samples. According to the ROC assays, high LOC101060391 and SFRP2 expression had an AUC value >0.9 for PA. Upregulation of SFRP2 distinctly inhibited the proliferative capacity of PA cells, as shown by CCK-8 analysis. Furthermore, knockdown of SFRP2 had an influence on cell growth in both the AtT-20 and HP75 cell lines. Taken together, our findings indicate that LOC101060391 and SFRP2 have diagnostic potential for PA. Furthermore, SFRP2 may be an antioncogene and a therapeutic target for PA.


[Anatomy and management of superior petrosal vein in microvascular decompression for trigeminal neuralgia].
Objective: To investigate the characteristics of superior petrosal vein (SPV) and its influence on the surgical field in microvascular decompression (MVD) for trigeminal neuralgia (TN), and to analyze the effect of the surgical treatment of SPV on the surgical approach, indication and prognosis. Methods: The clinical data of 280 patients with trigeminal neuralgia between Jan. 2013 and Jun. 2016 were collected, including the trunks and the branches of SPV, intraoperative electrocoagulation status, the surgery outcome and complications. Results: The petrosal vein during the operation was fully preserved in 152 cases (54.29%). The SPV were completely sectioned in 25 cases (8.92%), while some branches of SPV were sectioned in 103 cases (36.79%). We found that SPV have 1 to 3 trunks, accounted for 67 cases (23.90%), 168 cases (60%), and 45 cases (16.10%), while the SPV with 1 to 4 branches accounted for 17 cases (6.07%), 112 cases (40%), 136 cases (48.57%), and 15 cases (5.36%). The SPV was identified as offending vessel in 17 cases (6.07%). One patient with cutoff SPV trunk encountered cerebellar infarction and recovered completely at 2 weeks after MVD by using intravenous medication. Conclusions: MVD is the recommended treatment method for PTN, mostly SPV is unnecessary to be sectioned completely and small branches of SPV could be sacrificed. Very few patients may develop cerebellar infarction or hematoma.


Cytotoxicity and genotoxicity of butyl cyclohexyl phthalate.
Butyl cyclohexyl phthalate (BCP) is frequently used in personal care products, medical and household applications. The aim of this study is therefore to evaluate possible cytotoxicity and genotoxicity of BCP using in vitro and in vivo assays. The in vitro cytotoxic effect of BCP was investigated on mouse fibroblastic cell line (L929 cells) by MTT assay. The result showed that BCP inhibits cell proliferation in a concentration-dependent manner (IC50 value = 0.29 µg/mL). For genotoxicity assessment, tested concentrations of BCP demonstrated mutagenic activity in the presence of S9 mix with the Salmonella strain TA100 in the Ames test. Results showed that BCP is a secondary mutagenic substance even in low concentrations. The data obtained from 28-days repeated toxicity tests on mice revealed that BCP caused abnormalities of chromosome number, in a dose-dependent manner. Additionally, DNA damage, particularly DNA strand breaks, was assessed by Comet assay. The test result shows that BCP seemed to have genotoxic potential at a high level of exposure.


Interleukin-8 Release Inhibitors Generated by Fermentation of Artemisia princeps Pampanini Herb Extract With Lactobacillus plantarum SN13T.
Some glycosides, which are detected in water extracts from medicinal plants, have been reported to be degraded into their aglycones by incubating with some microorganisms producing β-glucosidase. We have shown that a plant-derived Lactobacillus plantarum SN13T harbors 11 open reading frames (ORFs) encoding the β-glucosidase enzyme and can grow vigorously in several herbal water extracts. In this study, we observed that the water extract from Artemisia princeps Pampanini (AP) fermented with the SN13T strain strongly inhibited the release of interleukin (IL)-8 from the HuH-7 cells, when compared to that without fermentation. Furthermore, we demonstrated that the SN13T strain produced at least two bioactive compounds from some compounds contained in AP extract. In addition, we determined that the two compounds were catechol and seco-tanapartholide C, which dose-dependently inhibited the release of IL-8. Because some sesquiterpene lactones are useful in pharmaceuticals, seco-tanapartholide C may be useful as an anti-inflammatory agent. This study suggests that the fermentation of medicinal herbs with Lb. plantarum SN13T is a significant technique to obtain bioactive compounds having therapeutic potential.


Comparative Analyses of Inflammatory Response and Tissue Integration of 14 Hyaluronic Acid-Based Fillers in Mini Pigs.
Hyaluronic acid (HA)-based dermal fillers have been approved for various clinical indications, both cosmetic and medical. Previous studies that have assessed the performance of HA dermal fillers have primarily focused on evaluating filler durability, and only a few have studied their distribution within the tissues. The present study aimed to compare tissue integration of various types of HA dermal fillers having different clinical indications and varying injection depths. To examine the local inflammatory response and distribution pattern of 14 HA dermal fillers (six Neuramis [NEU], one Belotero [BEL], three Juvéderm [JUV], and four Restylane [RES]), each product was injected intradermally and subcutaneously at the backs of two male miniature pigs. Histopathological evaluation and visual examination of the tissue sections were conducted 1 and 4 weeks after injection. Mean inflammatory cell infiltration scores tended to be lower in response to fillers from the NEU and BEL series than to those from the JUV and RES series after intradermal and subcutaneous injection. Furthermore, the inflammatory response to fillers with higher physicochemical properties specifically designed for injection into deeper layers of the skin tended to be slightly higher than those designated for injection into more superficial layers. There was no significant difference in tissue integration according to clinical indication and injection depth, although fillers from the NEU and BEL series exhibited better tissue integration than those from the JUV and RES series. Our findings not only suggest that the local inflammatory response and tissue integration differ across HA dermal filler products, but also that these parameters could vary according to the recommended clinical indication and injection depth of the products.


Thiazolidinediones and inflammation.
Thiazolidinediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor gamma increasingly used in the treatment of type 2 diabetes. Both in vitro and in vivo studies provide evidence that TZDs have anti-inflammatory properties. TZDs inhibit macrophage activation and decrease inflammatory cytokine expression and release in macrophage and monocyte. In vivo, treatment with TZDs decreases circulating mononuclear cells nuclear NF-kB content while increasing, in the same cells, expression of IkB, an NK-kB inhibitor. Furthermore, TZD treatment results in decreased plasma levels of inflammation and cardiovascular risk markers such as CRP, MMP9, PAI-1 and sCD40 in both obese and type 2 diabetic patients. Finally, TZDs induce synoviocyte apoptosis and reduce secretion of TNFalpha, IL-6 and IL-8 in synoviocyte from rheumatoid arthritis patients. TZDs might thus be considered for use in clinical trials targeting prevention of atherosclerosis and cardiovascular diseases and in pilot trials exploring the possibility that TZDs might help in the treatment of rheumatic diseases.


Hematopoietic growth factors and the treatment of tumor-associated anemias.
Erythropoietin, alone or in combination with colony-stimulating factors, is a promising agent in the treatment of patients with cancer-related 'anemia of chronic disorders', chemo/radiotherapy-induced anemia, or anemia due to myelodysplastic or myeloproliferative syndromes. In the first two groups, at least half of the patients can be expected to respond to erythropoietin alone, with an average response delay of about 4 weeks and maximal responses at weekly doses of approximately 1000 U/kg. In myelodysplastic syndromes, only 10-20% of patients respond to conventional doses of erythropoietin, but doses exceeding 1000 U/kg weekly in combination with granulocyte colony-stimulating factor yield response rates of about 40%. Although these results show that hematopoietic growth factors can be used successfully to treat cancer-related anemias, economic constraints preclude their use at the present time.


Free-standing biomimetic polymer membrane imaged with atomic force microscopy.
Fluid polymeric biomimetic membranes are probed with atomic force microscopy (AFM) using probes with both normal tetrahedrally shaped tips and nanoneedle-shaped Ag(2)Ga rods. When using nanoneedle probes, the collected force volume data show three distinct membrane regions which match the expected membrane structure when spanning an aperture in a hydrophobic scaffold. The method used provides a general method for mapping attractive fluid surfaces. In particular, the nanoneedle probing allows for characterization of free-standing biomimetic membranes with thickness on the nanometer scale suspended over 300-μm-wide apertures, where the membranes are stable toward hundreds of nanoindentations without breakage.


Regulation of thrombin generation at cell surfaces.
A complex series of reactions are involved in the assembly, function, and regulation of the prothrombinase complex. Since the enzyme is multicomponent in nature and each component is required for catalytic function, modulation of enzymatic activity can be achieved in a variety of ways. In addition, since complex assembly so profoundly affects reaction rates, mechanisms that perturb complex formation either positively or negatively have a profound effect on thrombin generation and its local physiologic effects. All of the cells that support prothrombinase assembly and hence thrombin generation respond to thrombin in a variety of ways. Thrombin selectively binds to thrombomodulin and heparin-like molecules expressed on the endothelial cell surface. Thrombin induces the release (and possible synthesis of) prostacyclin, plasminogen activator inhibitor, platelet-derived growth factor, and interleukin-1 and inhibits the release of plasminogen activator from vascular endothelium. Interleukin-1 is a potent mediator of inflammatory phenomena as well as an inducer of tissue factor synthesis in vascular endothelium. With respect to platelets, thrombin selectively binds and stimulates the platelet release reaction and subsequent aggregation. The thrombin-induced release of platelet-derived growth factor from both platelets and vascular endothelium may play a role in inflammation, wound healing, and atherogenesis. Thrombin itself is a potent mitogen of mesenchymal cells, and more recently has been shown to be not only a chemoattractant, but also a mitogen for monocytes. Thrombin also appears to bind selectively to monocytes and in so doing induces release of interleukin-1. Thrombin affects a myriad of cellular responses related to hemostasis, thrombosis, inflammation, would repair, and atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Internalization of Mycobacterium bovis, Bacillus Calmette Guerin, by bladder cancer cells is cytotoxic.
Instillation of Bacillus Calmette Guerin (BCG) into the bladder is the standard treatment for superficial bladder cancer. It leads to a local inflammatory response due to the release of cytokines and influx of immune cells to the tumor site. Although the presence of an intact immune system is an essential criterion for successful therapy, attachment of the bacteria to the bladder urothelial is just as important. The purpose of our study is to determine the role of bacterial internalization by epithelial cells. Transfection of the alpha5 integrin gene into the BCG unresponsive bladder cancer cell line, RT4, caused an increase in bacterial uptake and also increased cell death. Treatment of cells with cycloheximide did not prevent bacterial internalization but blocked its cytotoxic effect suggesting that unlike cell death, the process of bacterial internalization does not require new protein synthesis. Our data also show that the bacteria secretory products can prevent its own internalization. The extract prepared from lyophilized BCG altered the phosphorylation status of the focal adhesion kinase which is responsible for cellular endocytosis. Therefore, bacterial phosphatases may be present in the bacterial extract. Their activity may inhibit BCG internalization. Thus washing the reconstituted bacteria to remove the enzymes before instillation into the bladder might improve the therapeutic outcome of intravesical BCG therapy.


Electronic health records and malpractice claims in office practice.
Electronic health records (EHRs) may improve patient safety and health care quality, but the relationship between EHR adoption and settled malpractice claims is unknown. Between June 1, 2005, and November 30, 2005, we surveyed a random sample of 1884 physicians in Massachusetts to assess availability and use of EHR functions, predictors of use, and perceptions of medical practice. Information on paid malpractice claims was accessed on the Massachusetts Board of Registration in Medicine (BRM) Web site in April 2007. We used logistic regression to assess the relationship between the adoption and use of EHRs and paid malpractice claims. The survey response rate was 71.4% (1345 of 1884). Among 1140 respondents with data on the presence of EHR and available BRM records, 379 (33.2%) had EHRs. A total of 6.1% of physicians with an EHR had a history of a paid malpractice claim compared with 10.8% of physicians without EHRs (unadjusted odds ratio, 0.54; 95% confidence interval, 0.33-0.86; P = .01). In logistic regression analysis controlling for sex, race, year of medical school graduation, specialty, and practice size, the relationship between EHR adoption and paid malpractice settlements was of smaller magnitude and no longer statistically significant (adjusted odds ratio, 0.69; 95% confidence interval, 0.40-1.20; P = .18). Among EHR adopters, 5.7% of physicians identified as "high users" of EHR had paid malpractice claims compared with 12.1% of "low users" (P = .14). Although the results of this study are inconclusive, physicians with EHRs appear less likely to have paid malpractice claims. Confirmatory studies are needed before these results can have policy implications.


Do Disruptions in the Circadian Timing System Contribute to Autonomic Dysfunction in Huntington's Disease?
Huntington's disease (HD) patients suffer from a progressive neurodegenerative disorder that inflicts both motor and non-motor symptoms. HD is caused by a CAG repeat expansion within the first exon of the huntingtin (HTT) gene that produces a polyglutamine repeat that leads to protein misfolding, soluble aggregates, and inclusion bodies detected throughout the body. Both clinical and preclinical research indicate that cardiovascular dysfunction should be considered a core symptom in at least a subset of HD patients. There is strong evidence for dysautonomia (dysfunctional autonomic nervous system, ANS) in HD patients that can be detected early in the disease progression. The temporal patterning of ANS function is controlled by the circadian timing system based in the anterior hypothalamus. Patients with neurodegenerative diseases including HD exhibit disrupted sleep/wake cycle and, in preclinical models, there is compelling evidence that the circadian timing system is compromised early in the disease process. Here we review data from preclinical models of HD that explore the intersection between disruption of circadian rhythms and dysautonomia. This work will lead to new therapeutic strategies and standards of care for HD and other neurodegenerative diseases.


Mycophenolate mofetil-induced colitis with graft versus host disease-like features in a liver transplant recipient.
Mycophenolate mofetil (MMF) is a commonly used immunosuppressive drug in the management of transplant recipients. Gastrointestinal (GI) toxicity (diarrhea) is the most frequently reported adverse event in MMF-treated transplant patients. MMF-induced Graft versus Host Disease has rarely been reported in literature. We report a case of MMF-induced colitis with Graft versus Host Disease-like features, to highlight the importance of high clinical suspicion for its diagnosis, and that appropriate management in such a setting can reduce morbidity and mortality. We also review the relevant literature.


Trial of intravesical versus extravesical ureteroneocystostomy in renal transplant recipients.
We carried out a trial to evaluate the complication rate of intravesical (LP) versus extravesical (Lich) ureteroneocystostomy in recipients of renal transplantation. Ureteric stenosis was the predominant complication in the LP technique, which was more difficult to correct. Complications by the Lich technique were urinary leaks, which were managed successfully by prolonged bladder drainage. We conclude that the Lich technique is simpler to perform and avoids the complication of ureteric stenosis, and should therefore be the procedure of choice for ureteric implantation in recipients of renal transplants.


Distraction arthroplasty compared to other cartilage preservation procedures in patients with post-traumatic arthritis: a systematic review.
Post-traumatic arthritis (PTA) is characterized by the deterioration of articular cartilage temporally associated with an articular injury. With a paucity of literature comparing joint preservation techniques, we performed a systematic review of the literature intending to describe and summarize the results of ankle distraction arthroplasty as it compares with studies on tibio-talar microfracture, allograft, and autograft for ankle joint preservation in the post-traumatic population under 50 years of age. Research databases were searched and abstracts screened for relevance on our topic of interest. Abstracts meeting screening criteria with high interobserver reliability underwent full-manuscript review and coding for pertinent citation, study level, treatment, and outcome variables. Outcome variables for patient-reported pain scales, validated outcome measurement tools, radiographic progression, reoperation/re-treatment rates, and complication rates were recorded. Out of 105 unique citations, 10 publications were included. The distraction arthroplasty studies had 36 out of 181 patients requiring reoperation for complications (19.9%), while other joint-preserving procedures studies had 40 out of 177 patients requiring reoperations for complications (22.6%). Clinical outcome scores at mean follow-up time ranging from 2 to 10 years between studies were similar. Reported results for a variety of cartilage preservation procedures, including distraction arthroplasty, are satisfactory and reoperation rates for complication are similar. Limitations in available data and underlying study quality affect synthesis of the results therein. While distraction arthroplasty is an option for cartilage preservation in patients with PTA of the ankle, the technique is highly specialized which may affect the external validity. III.


Failure to pass meconium.
Failure to pass meconium during the first twenty-hours of life is a cardinal sign of a congenital low alimentary tract obstruction. This review article discusses a systematic approach when confronting such problem to help clinicians arrive to a correct diagnosis. Prenatal and postnatal diagnosis, imaging investigation, differential diagnosis and management of the more common causes of failure to pass meconium are reviewed.


Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations.
Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency of phenylalanine hydroxylase. This deficiency leads to the accumulation of Phe and its metabolites in tissues and body fluids of PKU patients. The main signs and symptoms are found in the brain but the pathophysiology of this disease is not well understood. In this context, metabolic alterations such as oxidative stress, mitochondrial dysfunction, and impaired protein and neurotransmitters synthesis have been described both in animal models and patients. This review aims to discuss the main metabolic disturbances reported in PKU and relate them with the pathophysiology of this disease. The elucidation of the pathophysiology of brain damage found in PKU patients will help to develop better therapeutic strategies to improve quality of life of patients affected by this condition.


Contextual Facilitators and Maintaining of Compassion-Based Care: An Ethnographic Study.
Compassion is an important part of nursing. It fosters better relationships between nurses and their patients. Moreover, it gives patients more confidence in the care they receive. Determining facilitators of compassion are essential to holistic care. The purpose of this study was to explore these facilitators. This ethnographic study was conducted in 2014-2015 with 20 nurses, 12 patients, and 4 family members in the medical and surgical wards. Data collection was done through observations and in-depth semi-structured interviews with purposive sampling. The study was carried out in 15 months. Data analysis was performed using constant comparison based on Strauss and Corbin. Data analysis defined three main themes and eight subthemes as the fundamentals of compassion-based care. Nurses' personal factors with subcategories of personality, attitudes, and values and holistic view; and socio-cultural factors with subcategories of kindness role model, religious, and cultural values are needed to elicit compassionate behaviors. Initiator factors, with subcategories of patient suffering, patient communication demands, and patient emotional and psychological necessity are also needed to start compassionate behaviors. The findings of this study showed that nurses' communication with patients is nurse's duty in order to understand and respect the needs of patients. Attention should be paid to issues relating to compassion in nursing and practice educational programs. Indeed, creating a care environment with compassion, regardless of any shortcomings in the work condition, would help in the development of effective nursing.


Base-By-Base: single nucleotide-level analysis of whole viral genome alignments.
With ever increasing numbers of closely related virus genomes being sequenced, it has become desirable to be able to compare two genomes at a level more detailed than gene content because two strains of an organism may share the same set of predicted genes but still differ in their pathogenicity profiles. For example, detailed comparison of multiple isolates of the smallpox virus genome (each approximately 200 kb, with 200 genes) is not feasible without new bioinformatics tools. A software package, Base-By-Base, has been developed that provides visualization tools to enable researchers to 1) rapidly identify and correct alignment errors in large, multiple genome alignments; and 2) generate tabular and graphical output of differences between the genomes at the nucleotide level. Base-By-Base uses detailed annotation information about the aligned genomes and can list each predicted gene with nucleotide differences, display whether variations occur within promoter regions or coding regions and whether these changes result in amino acid substitutions. Base-By-Base can connect to our mySQL database (Virus Orthologous Clusters; VOCs) to retrieve detailed annotation information about the aligned genomes or use information from text files. Base-By-Base enables users to quickly and easily compare large viral genomes; it highlights small differences that may be responsible for important phenotypic differences such as virulence. It is available via the Internet using Java Web Start and runs on Macintosh, PC and Linux operating systems with the Java 1.4 virtual machine.


Assisted reproductive techniques for hybridization of camelids.
The camelid family comprises the Old World camelids (or dromedary and Bactrian camels) and the New World camelids (namely the llamas, alpacas, guanacos and vicunas). Although the species within each group can hybridize among themselves to produce fertile offspring, it is only recently that a hybrid between New and Old World camelids has been reported. To create this hybrid, semen was collected from male camels by artificial vagina (AV) and inseminated into female guanacos (n = 9) and llamas (n = 3) at the appropriate stage of their follicular wave cycle. Similarly, guanaco and llama semen was collected, also by AV, and inseminated into female camels (n = 42). Although several conceptions occurred, only one hybrid (camel sire x guanaco dam) continued to term and was born alive after 328 days of gestation, and another is pregnant at the time of writing (camel sire x llama dam). Further studies are presently being carried out using extraspecific embryo transfer to try and improve the success rate of live offspring being born. Female guanacos (n = 4) are treated with hormones to stimulate their ovaries to produce several follicles before being inseminated with camel semen. Of the 12 camel recipients that have to date received hybrid embryos (camel sire x guanaco dam), 10 conceived, but 9 of these subsequently aborted between 30 and 365 days and only one recipient was still pregnant at the time of writing.


Ultrafast Intersystem Crossing in Epigenetic DNA Nucleoside 2'-Deoxy-5-formylcytidine.
DNA methylation and demethylation are the key steps in epigenetics. Emerging studies have demonstrated that these two processes play crucial roles in mammalian development and pathogenesis. Epigenetic modified cytosine and its further oxidative products, including 5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine, are called the "new four bases of DNA". The appearance of such new epigenetic bases can complicate DNA photodamage and repairing mechanism because they could have drastically different excited-state dynamics compared to canonical DNA nucleobases. In this study, excited-state dynamics of three demethylated nucleosides in buffer solution at physiological pH were investigated by femtosecond to microsecond time-resolved spectroscopy. Distinct excited-state dynamics are found in these demethylated nucleosides. For 2'-deoxy-5-formylcytidine (5fdCyd), direct observation of ultrafast intersystem crossing to the triple state with a 69% quantum yield is presented. Meanwhile, the triplet-state energy of 5fdCyd can transfer to the ambient molecular oxygen and generate destructive singlet oxygen. On the other hand, no such observation is seen in 2'-deoxy-5-hydroxymethylcytidine (5hmdCyd) and 2'-deoxy-5-carboxycytidine (5cadCyd), and these two bases show ultrafast internal conversion similar to that in 5-methylcytidine and cytidine. These results indicate that 5fdCyd is an effective internal triplet photosensitizer in DNA, and it could act as a new hot spot in DNA photodamage.


Fabrication of multiplex quasi-three-dimensional grids of one-dimensional nanostructures via stepwise colloidal lithography.
By using O2-plasma etched monolayers of hexagonally close-packed latex spheres as masks for metal vapor deposition, we successfully demonstrate a stepwise colloidal lithography to stepwise grow highly ordered multiplex quasi-three-dimensional grids of metallic one-dimensional nanostructures, e.g., nanowires and nanorods. The success of the present approach is centered at manipulation of the incidence angle of metal vapor beams with respect to the normal direction of colloidal masks and particularly the azimuth angle phi of the projection of the vapor beam incidence on the masks with respect to the vector from one sphere to the nearest neighbors. Stepwise deposition of different metals by regularly varying phi allows consecutively stacking of 1D nanostructures into multiplex quasi-3D grids. This stepwise angle-resolved colloidal lithography should provide a significant nanochemical complement of conventional lithographic techniques, enabling us to easily fabricate sophisticated 3D nanostructures with defined vertical and lateral heterogeneity.


Interleukin-18 promoter polymorphisms in Egyptian patients with rheumatoid arthritis.
The aim of this study was to investigate the association of interleukin-18 (IL-18) promoter single nucleotide polymorphisms (SNPs) at - 607 and - 137 regions with risk for rheumatoid arthritis (RA) and their association with activity and severity of the disease. The study included 80 RA patients and 80 age and sex matched healthy subjects. Forty RA patients and 40 control subjects were randomly chosen to measure their serum IL-18 levels. IL-18 SNPs at - 607 and - 137 regions were analyzed using polymerase chain reaction-sequence specific polymorphism (PCR-SSP) analysis. The frequency of -137CC genotype was significantly lower in RA patients than controls (OR = 0.23, 95% CI 0.07-0.72, p = 0.012), while the -607C/A genotypes (CC, CA, AA) showed insignificant differences between patients and controls. No association was found between erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin (HB), DAS 28 and X ray grades and -607C/A and - 137G/C genotypes. Serums levels of IL-18 were not significantly different among individuals with different IL-18 -607 and -137 genotypes. It is concluded that RA is negatively associated with IL-18 -137CC SNP, and that IL-18 607-SNPs may not be a risk factors for RA in Egyptian patients with no specific genotype association with disease activity or severity. No specific genotype was associated with higher IL-18 serum levels.


Isolation and characterization of EPD1, an essential gene for pseudohyphal growth of a dimorphic yeast, Candida maltosa.
Additional copies of the centromeric DNA (CEN) region induce pseudohyphal growth in a dimorphic yeast, Candida maltosa (T. Nakazawa, T. Motoyama, H. Horiuchi, A. Ohta, and M. Takagi, J. Bacteriol. 179:5030-5036, 1997). To understand the mechanism of this transition, we screened the gene library of C. maltosa for sequences which could suppress this morphological change. As a result, we isolated the 5' end of a new gene, EPD1 (for essential for pseudohyphal development), and then cloned the entire gene. The predicted amino acid sequence of Epdlp was highly homologous to those of Ggp1/Gas1/Cwh52p, a glycosylphosphatidylinositol-anchored protein of Saccharomyces cerevisiae, and Phr1p and Phr2p of Candida albicans. The expression of EPD1 was moderately regulated by environmental pH. A homozygous EPD1 null mutant showed some morphological defects and reduction in growth rate and reduced levels of both alkali-soluble and alkali-insoluble beta-glucans. Moreover, the mutant could not undergo the transition from yeast form to pseudohyphal form induced by additional copies of the CEN sequence at pH 4 or by n-hexadecane at pH 4 or pH 7, suggesting that EPD1 is not essential for yeast form growth but is essential for transition to the pseudohyphal form. Overexpression of the amino-terminal part of Epd1p under the control of the GAL promoter suppressed the pseudohyphal development induced by additional copies of the CEN sequence, whereas overexpression of the full-length EPD1 did not. This result and the initial isolation of the 5' end of EPD1 as a suppressor of the pseudohyphal growth induced by the CEN sequence suggest that the amino-terminal part of Epd1p may have a dominant-negative effect on the functions of Epd1p in the pseudohyphal growth induced by the CEN sequence.


[Human oocyte freezing in Spain: comment on the Real Decree 120/2003].
This work analyzes some scientific, ethic and legal aspects about the freezing of human ovocites in Spain. Inside the context of the Law 35/1998 of Assisted Reproduction Techniques, it is analyzed the Royal Decree 120/2003 which regulates the authorization of controlled experiences with reproductive aims. These experiences investigate the fecundation of ovocites or ovaric tissue previously frozen. It is also studied the inform made through parliament by the General Court of Judicial Power and it is also valued the importance of the terms "experience", "investigation" and "project" used in the legal text.


Memorial consequences of environmental context change in children and adults.
Changing environmental context during encoding can influence episodic memory. This study examined the memorial consequences of environmental context change in children. Kindergartners, first and fourth graders, and young adults studied two lists of items, either in the same room (no context change) or in two different rooms (context change), and subsequently were tested on the two lists in the room in which the second list was encoded. As expected, in adults, the context change impaired recall of the first list and improved recall of the second. Whereas fourth graders showed the same pattern of results as adults, in both kindergartners and first graders no memorial effects of the context change arose. The results indicate that the two effects of environmental context change develop contemporaneously over middle childhood and reach maturity at the end of the elementary school days. The findings are discussed in light of both retrieval-based and encoding-based accounts of context-dependent memory.


PYY in the expanding pancreatic epithelium.
Gut peptide YY (PYY) plays an important role in regulating metabolism and is expressed during the ontogeny of the pancreas. However, its biological role during endocrine cell formation is not fully understood, and its role, if any, during pancreatic regeneration in the adult has not yet been explored. The knowledge of factors involved in beta cell renewal in adult animals is clearly relevant for the design of treatment strategies for type 1 diabetes. We therefore sought to determine if observations during fetal pancreas formation also apply to pancreatic growth in adult animals. Indeed, we have found marked expansion of the PYY-expressing population during pancreatic regeneration. In addition, we demonstrate the presence of cells co-expressing PYY and the critical pancreatic transcription factor pancreatic duodenal homeobox1 (PDX-1). Interestingly, these cells also co-expressed specific islet hormones during pancreatic development and re-growth, suggesting a developmental relationship. Furthermore, we have found that PYY can act in concert with IGF-1 to stimulate cellular responsiveness in pancreatic epithelial cells in vitro. Our data suggest that PYY may be a mediator of islet cell development, as well as a cofactor for growth factor responses, not only during fetal pancreas formation but also during regeneration in adult animals.