The initiation of homologous chromosome synapsis in mouse fetal oocytes is not directly driven by centromere and telomere clustering in the bouquet.
We investigated the behaviour of centromeres and distal telomeres during the initial phases of female meiosis in mice. In particular, we wished to determine whether clustering of centromeres and telomeres (bouquet formation) played the same crucial role in homologous chromosome pairing in female meiosis as it does in the male. We found that synapsis (intimate homologous chromosome pairing) is most frequently initiated in the interstitial regions of homologous chromosomes, apparently ahead of the distal regions. The proximal ends of the chromosomes appear to be disfavoured for synaptic initiation. Moreover, initiation of synapsis occurred in oocytes that showed little or no evidence of bouquet formation. A bouquet was present in a substantial proportion of cells at mid to late zygotene, and was still present in some pachytene oocytes. This pattern of bouquet formation and pairing initiation is in stark contrast to that previously described in the male mouse. We propose that although dynamic movements of centromeres and telomeres to form clusters may facilitate alignment of homologues or homologous chromosome segments during zygotene, in the female mouse positional control of synaptic initiation is dependent on some other mechanism.


Migration of phthalates from PVC toys into saliva simulant by dynamic extraction.
Soft PVC children's products are usually plasticized with phthalates. As young children suck and chew on toys, they extract and ingest certain quantities of the plasticizers. Some phthalates are suspected to affect the kidneys and liver and cause testicular damage. Therefore, the EC has prohibited the sale of toys and childcare articles intended to be placed in the mouth by children <3 years of age made of soft PVC containing >0.1% by weight of six phthalates (1999/815/EC). The aim was to study the materials and plasticizers used in soft children's products. In February 2001, a market surveillance was performed in The Netherlands and 62 soft toys were sampled. Forty-seven of these toys contained plasticized PVC. Diisononylphthalate (DINP) and di(2-ethylhexyl)phthalate (DEHP) were the predominant plasticizers and were usually found in concentrations between 30 and 45% by weight. One teething ring was made of PVC plasticized with 45% by weight of DINP and was not in compliance with Decision 1999/815/EC. The DINP and DEHP migration was determined in saliva simulant using the 'Head over Heels' agitation method. All toys complied with the Scientific Committee on Toxicity, Ecotoxicity and the Environment (SCTEE) guidance release value of 6.7 microg min(-1) 10 cm(-2). The DEHP migration of six toys exceeded the SCTEE guidance release value of 1.7 microg min(-1) 10 cm(-2). Substitutes found for phthalates plasticizers are acetyltributylcitrate, tributylcitrate and diisononyladipate. In addition, other plasticizers and additives were found in minor amounts. The toxicity and the migration behaviour of these substances is less known and requires more attention. To ensure the safety of PVC toys, these substances should also be regulated.


Venous thromboembolism prophylaxis in the pediatric trauma patient.
Although venous thromboembolism (VTE) occurs in less than 1% of hospitalized pediatric trauma patients, care providers must make decisions about VTE prophylaxis on a daily basis. The consequences of VTE are significant; the risks of developing VTE are variable; and the effectiveness of prophylaxis against VTE is not conclusive in children. While the value of VTE prophylaxis is well defined in adult trauma care, it is unclear how this translates to the care of injured children. This review evaluates the incidence and risks of VTE in pediatric trauma and assesses the merits of prophylaxis in children. Pharmacologic prophylaxis against VTE is a reasonable strategy in critically injured adolescent trauma patients. Further study is needed to establish the risks and benefits of VTE prophylaxis across the spectrum of injured children.


Effect of Autologous Platelet Rich Fibrin in Human Mandibular Molar Grade II Furcation Defects- A Randomized Clinical Trial.
The Furcation of multirooted teeth is difficult region to gain access for treatment due to their complex anatomy. Modifications have been made in the periodontal instrument armamentarium to facilitate treatment of furcations. Moreover, many new materials have been introduced to attempt regeneration in the furcation defects. This study evaluated the role of Platelet Rich Fibrin (PRF) in comparison with allograft and Guided Tissue Regeneration (GTR) in the treatment of Grade II mandibular molar furcations. This was a parallel arm prospective randomized, interventional trial (NCT 02430519) conducted on 22 patients, with Grade II mandibular furcation defects. Patients were divided into two equal groups. Group A, were treated by the placement of PRF as a graft and as a membrane while in Group B, the defects were treated by the placement of allograft and Healiguide collagen membrane. Clinical parameters {Plaque Index (PI), Probing Depth (PD), Relative Vertical Clinical Attachment Level (RVCAL), Relative Horizontal Clinical Attachment Level (RHCAL), Gingival Marginal Level(GML), and amount of Bonefill using Radio-Visiography (RVGBF)}, were estimated at baseline and nine months postoperatively. Comparison between the groups was analysed by using independent sample t-test, whereas, paired t-test was used to assess the mean values within the groups. The intergroup comparison for PI, PD, RHCAL, GML, was statistically not significant. Pertaining to RVCAL, there was a statistically significant difference at nine months (p-value=0.04) in Group A. Also, there was a statistically significant difference related to RVGBF (p-value=0.006) in Group A at nine months. The efficacy of PRF should be ascertained by conducting more studies with a larger sample size, on a long term basis, in patients with molar Grade II furcation defects.


[Drug resistance of colon cancer cells to 5-fluorouracil mediated by microRNA-21].
OBJECTIVE To explore downstream regulatory pathway of microRNA-21 (miR-21) in colon cancer cells (RKO) through detecting miR-21 and its target PDCD4, and the influence of miR-21 regulation on the sensitivity of RKO cells to 5-fluorouracil (5-FU). METHODS 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the effect of 5-FU on the viability of RKO cells with knockout of miR-21 or high expression of PDCD4. Real-time was used to determine the expression of PDCD4, ABCC5 and CD44 in RKO cell after knockout of miR-21. RESULTS MTT assay reveals that the IC50 of 5-FU in RKO-WT cells (52.82 ± 0.06 umol/L) was about 67% higher than in miR-21 knockout cells (32.23 ± 0.05 umol/L) (P < 0.05), and the apoptosis ratio elevated after knockout of miR-21. High expression of PDCD4, a target gene of miR-21, can negatively regulate the expression of ABC transporter ABCC5 and the stem cell marker CD44. CONCLUSION MiR-21 can mediate the drug resistance to 5-FU by inhibiting its target PDCD4, which can regulate the expression of ABCC5 and CD44 genes.


Virtual microscopy as a tool for proficiency testing in cytopathology: a model using multiple digital images of Papanicolaou tests.
Modern digital cameras can acquire images from cytologic slides at sufficient resolution to allow for digital enlargement and scrolling on a video monitor, allowing for the simulation of microscopy using a computer. The purpose of this study was to develop a tool for proficiency testing in cytopathology using multiple digital images of Papanicolaou tests. Nine images were photographed from each of 10 Papanicolaou tests at x100 optical magnification, 3400 x 2300-pixel resolution, using a light microscope and a digital camera. All images from each case were tiled in a single canvas with Photoshop 4.0 software. Two cytopathologists and 3 cytotechnologists interpreted these "virtual slides" using a computer and graded diagnostic codes (PAP program, College of American Pathologists). Subjects were retested a year later using the glass slides from the same cases and routine microscopy. Both test results, by diagnostic code, were compared with the McNemar test of symmetry. The 5 test subjects provided 42 and 50 correct diagnostic codes by "virtual microscopy" and light microscopy, respectively. No significant asymmetry in results obtained by virtual microscopy and light microscopy was encountered with the McNemar test of symmetry. All test answers were correctly classified by selection series, using both virtual microscopy and light microscopy, and the responses would have been graded as 100% by current PAP program scoring guidelines. This suggests that virtual microscopy could be used for proficiency testing purposes. A simple virtual microscopy method designed to challenge participants to locate and diagnose cells of interest was effective for the administration of standardized proficiency tests. Virtual microscopy methods that rely on single-plane images to locate and diagnose cells of interest could provide effective proficiency testing tools prior to the development of more computationally intensive systems that represent an entire Papanicolaou test at multiple focal planes.


Molecular Characterization of a New Moniliformis sp. From a Plateau Zokor (Eospalax fontanierii baileyi) in China.
In the present study, a new species of the genus Moniliformis species is described taxonomically in the mitochondrial genomic context. The parasite was found in a plateau zokor captured in a high-altitude area of Xiahe County of Gansu Province, China. The mitochondrial (mt) genome length of this new species was 14,066 bp comprising 36 genes and 2 additional non-coding regions (SNR and LNR), without atp8. The molecular phylogeny inferred by the cytochrome c oxidase subunit I gene (cox1) and the18S ribosomal RNA gene (18S rDNA) sequences showed that the parasite as a sister species to other Moniliformis spp. and was named Moniliformis sp. XH-2020. The phylogeny of the concatenated amino acid sequences of the 12 protein-coding genes (PCGs) showed Moniliformis sp. XH-2020 in the same cluster as Macracanthorhynchus hirudinaceus and Oncicola luehei confirming the cox1 and 18S rDNA phylogenetic inference. In addition, the entire mt genome sequenced in this study represents the first in the order Moniliformida, providing molecular material for further study of the phylogeny of the class Archiacanthocephala. Moreover, the species of this class, use arthropods as intermediate hosts and mammals as definitive hosts and are agents of acanthocephaliasis, a zoonosis in humans. Therefore, this study not only expands the host range among potential wild animal hosts for Archiacanthocephalans which is of great ecological and evolutionary significance but also has important significance for the research of zoonotic parasitic diseases.


Randomized clinical trial of laparoscopic Roux-en-Y gastric bypass versus laparoscopic vertical banded gastroplasty for obesity.
Laparoscopic techniques have been developed for performing Roux-en-Y gastric bypass (LRYGBP) and vertical banded gastroplasty (LVBG) in patients with morbid obesity. It is not certain, however, which is the better technique in non-superobese patients (body mass index less than 50 kg/m(2)). Eighty-three patients (LRYGBP 37, LVBG 46) were assessed in a randomized clinical trial. Perioperative complications were recorded together with preoperative and postoperative respiratory function and mobilization rate. Patients were monitored for 2 years after operation with regard to weight change and the need for remedial surgery. There were no conversions to open surgery. The mean operating time was longer for LRYGBP than LVBG (138 versus 105 min). Five early reoperations were performed after LRYGBP (three for haemorrhage, one for ileus and one suspected leak) and one after LVBG (suspected leak). There were no differences in postoperative respiratory function or mobilization. Weight reduction was greater after LRYGBP (excess weight loss 78.3 versus 62.9 per cent 1 year after surgery, P = 0.009; 84.4 versus 59.8 per cent at 2 years, P < 0.001). Remedial surgical intervention was required in eight patients after LVBG (conversion to Roux-en-Ygastric bypass) and none after LRYGBP. LRYGBP and LVBG were comparable in terms of operative safety and postoperative recovery, but weight reduction was better after LRYGBP.


Massive oral ingestion of elemental mercury.
A 42 year old male, while repairing a sphygmomanometer, intentionally ingested an estimated 3 kg (220 mL) of metallic mercury. During admission, only tremor, irritability, forgetfulness and fatigue were noted. There were no obvious gastrointestinal or hepatic complications. Blood and urine mercury levels were significantly elevated. Most of the metallic mercury was cleared from the gut within 10 days. A few months later, hepatic dysfunction with jaundice developed. Serial investigations did not suggest a viral etiology or alcoholism. Liver function tests and blood and urine mercury levels returned to normal over the next 10 months. The observation suggests that massive and prolonged retention of metallic mercury may facilitate the conversion of metallic, elemental mercury to divalent mercury and its subsequent absorption with development of hepatic dysfunction.


Long-term stability of a TLD-based individual monitoring system.
The thermoluminescence dosemeter (TLD) system at the Individual Monitoring Service (IMS) of the Nuclear Technology Institute (ITN) at the Radiological Protection and Nuclear Safety Department (DPRSN) comprises two 6600 Harshaw readers and the Harshaw 8814 TL card and the holder containing two LiF:Mg,Ti (TLD-100) dosemeters for the evaluation of H(p)(10) and H(p)(0.07). The readers are calibrated on a monthly basis and as part of the quality assurance programme implemented at the IMS a set of dosemeters is issued monthly to the DPRSN's Standard Dosimetry Laboratory for linearity measurements. The results obtained since November 2001 are presented. Fading and sensitivity change experiments are carried out every month covering 8 week periods so that enough time is given to simulate issuing, integrating and receiving times and respective delays. A set of 96 dosemeters organised in eight subsets of 12 are used. In each subset, four dosemeters are irradiated and stored at room temperature (RT), four are not irradiated at all and the last four are irradiated after storage. The 12 dosemeters of each subset are readout at the same time, one per week, covering the 8 week period. The results from the sets irradiated and stored at different periods allowed for the evaluation of fading and sensitivity changes experienced over the whole monitoring period and respective preparation time and readout delays. Time evolution charts of the reader calibration factors, of the linearity parameters and of the evolution of the integrated area in the region of dosimetric interest with storage at RT were obtained. This paper aims to quantify the long-term stability of the TLD system in use at the IMS.


The potential for prostate cancer chemoprevention.
The dramatic international variation in prostate cancer incidence and mortality rates suggests that changeable environmental factors exert an influence. This has prompted a search for ways to prevent the disease. Epidemiologic studies suggest that dietary factors such as the carotenoid lycopene, selenium, vitamin E, and high intake of fat have roles in prostate cancer risk. Several studies show that impairment of androgen synthesis lowers the risk of prostate cancer. 5-alpha-reductase inhibitors such as finasteride have been shown to decrease prostate size by decreasing androgenic stimulation to the prostate. Other promising, but less developed, interventions include vitamin D supplements and modification of diet. Any manipulation to decrease one's relative risk of prostate cancer will by necessity have to be given to a large proportion of men who would never develop prostate cancer even without the intervention. To be acceptable, a successful preventive intervention should have few or no side effects; some additional benefits would be useful. All potential preventive interventions will need to be rigorously evaluated before they can be advocated for prostate cancer prevention.


Cellular hemangiomas ("hemangioendotheliomas") in infants. Light microscopic, immunohistochemical, and ultrastructural observations.
Cellular hemangiomas of infancy, also known as "infantile hemangioendotheliomas," are benign tumors whose dense cellularity may lead to confusion with soft tissue sarcomas. Ultrastructural and immunohistologic study revealed considerable cellular heterogeneity in these lesions despite the monomorphous appearance revealed by routine histologic preparations. Pericytes and endothelial cells are predominant, but fibroblasts and mast cells are regularly present in these tumors. An interstitially located cell of uncertain identification, expressing factor XIIIa and a macrophage marker, not previously noted, comprises an important segment of the cell population. The cell composition reflects the dynamic potential of these lesions, whose natural tendency is to grow, then to become stable, and finally to involute.


Defective expression of T cell-associated glycoprotein in severe combined immunodeficiency.
A T cell surface membrane-associated glycoprotein, Tp40 (40,000 mol wt), also designated as CD-7, was not expressed by the T cells of a patient with severe combined immunodeficiency. In addition to this abnormality, T cell proliferative responses to mitogens were defective and the IL-2 receptor expression was deficient on the patient's T lymphocytes. However, his T cells were found to provide help for the differentiation of normal B cells to Ig-secreting cells. Abundant circulating B cells were detected. These B cells proliferated normally in the presence of anti-mu antibodies and B cell growth factors, but did not differentiate into antibody-secreting cells when provided with the help of normal T cells. In addition, his activated B cells did not proliferate to IL-2 even though IL-2 receptors were expressed. A successful allogeneic histocompatible bone marrow transplantation resulting in T cell engraftment corrected both the T and B cell immunodeficiencies. These findings support the hypothesis that the Tp40 deficiency present in this patient is related to a defect of the T cell precursors, and that Tp40 plays important roles not only essential to T cell interactions but also to certain aspects of T-B cell interaction during the early lymphoid development.


The rebel, the professor, and the entrepreneur: Qualitative study to explore creator stories of FOAM.
The free open access medical education (#FOAMed, or FOAM) movement creates educational content intended to inform medical education and clinical practice and is distributed in an unrestricted fashion (e.g., open access website). The who, what, and in particular the how of FOAM has raised important questions about the sustainability of the movement. We recruited a diverse research team that included educational researchers, FOAM contributors, a business academician, and medical trainees to design and conduct a qualitative study exploring the work of FOAM creators. We analyzed the transcripts of interviews with 11 participants from top FOAM websites in emergency medicine and critical care. The team met frequently to iteratively identify and discuss emergent themes (major and minor) until saturation of concepts was achieved. Creators of FOAM could be categorized using three archetypes: the rebel, the professor, and the entrepreneur. The rebel was categorized as distinctly rejecting "traditional academic structures" yet was compelled to deliver educational content via alternative routes. The professor retained a traditional academic role, instead creating FOAM to supplement academic activities (teaching courses, disseminating scholarship, promotion). Entrepreneurs focused on creating a sustainable entity in an effort to supplement their income and reduce clinical obligations. While all FOAM creators appear unified in their passion to create, promote, and distribute educational material with unfettered access to educators, their motivations for creating content could be differentiated. Given the grassroots nature of FOAM, creators share concerns related to financing, time commitments, and threats to sustainability of these businesses. The longevity of FOAM and what business models are best suited to support them are uncertain. Further exploration of the implications could investigate the best ways to engage with and support the different FOAM creator archetypes and develop models of sustainability.


From non-targeted to targeted GC-MS metabolomics strategy for identification of TCM preparations containing natural and artificial musk.
Moschus is a rare and precious natural medicine. Due to the properties of resources scarcity and expensive price of natural musk, artificial musk has been developed as substitute materials in some prescriptions. Rapid and accurate identification of natural or artificial musk in complex traditional Chinese medicine (TCM) preparations is also a challenge. A strategy from non-targeted to targeted gas chromatography-mass spectrometry (GC-MS) metabolomics was developed for discrimination of natural and artificial musk. Firstly, GC-MS-based non-targeted analysis combined with chemometrics was used to find the potential chemical markers to distinguish natural musk and artificial musk. Subsequently, targeted metabolomics was used to analyze musk in preparations with multiple reaction monitoring (MRM) mode by use gas chromatography coupled with triple quadrupole mass spectrometry (GC-QQQ MS). Two chemical markers named prasterone and androsterone have been selected and could be detected in all Compound Pien Tze Huang preparations (CPZHs) containing artificial musk, while the CPZHs containing natural musk did not detect two markers with S/N (signal to noise ratio) less than 3. Our work provides an applicable approach to select the practical chemical markers for the assessment of musk in preparations to realize the traceability of musk in TCM and improve the quality control of musk-containing preparations.


[The effect of unconscious color hue saturation on emotional state of human].
The aim of the study was to investigate influence of color hue saturation on emotional state of human. We use frontal EEG asymmetry to determine subject's emotional state. Our emotional stimuli summon opposite dynamics of frontal EEG asymmetry. Negative stimuli elicits decreasing of the value of frontal EEG asymmetry and positive stimuli increases the value of frontal EEG asymmetry in fronto-polar and frontal leads. Such dynamics of frontal EEG asymmetry point the emotional experience in accordance the stimulus modality. Blue and red color modification of stimuli leads changes in dynamics of frontal EEG asymmetry during presentation of emotional stimuli and after. In fact, that no one subject gave a report about color difference between stimuli during an experiment, we conclude that influence of color modification was unconscious. Our result shows the possibility of unconscious perception color modification to emotional state of human.


Structural and Functional Differences Between Porcine Aorta and Vena Cava.
Elastin and collagen fibers are the major load-bearing extracellular matrix (ECM) constituents of the vascular wall. Arteries function differently than veins in the circulatory system; however as a result from several treatment options, veins are subjected to sudden elevated arterial pressure. It is thus important to recognize the fundamental structure and function differences between a vein and an artery. Our research compared the relationship between biaxial mechanical function and ECM structure of porcine thoracic aorta and inferior vena cava. Our study suggests that aorta contains slightly more elastin than collagen due to the cyclical extensibility, but vena cava contains almost four times more collagen than elastin to maintain integrity. Furthermore, multiphoton imaging of vena cava showed longitudinally oriented elastin and circumferentially oriented collagen that is recruited at supraphysiologic stress, but low levels of strain. However in aorta, elastin is distributed uniformly, and the primarily circumferentially oriented collagen is recruited at higher levels of strain than vena cava. These structural observations support the functional finding that vena cava is highly anisotropic with the longitude being more compliant and the circumference stiffening substantially at low levels of strain. Overall, our research demonstrates that fiber distributions and recruitment should be considered in addition to relative collagen and elastin contents. Also, the importance of accounting for the structural and functional differences between arteries and veins should be taken into account when considering disease treatment options.


A Novel Pathogenesis-Related Class 10 Protein Gly m 4l, Increases Resistance upon Phytophthora sojae Infection in Soybean (Glycine max [L.] Merr.).
Phytophthora root and stem rot of soybean, caused by Phytophthora sojae (P. sojae), is a destructive disease in many soybean planting regions worldwide. In a previous study, an expressed sequence tag (EST) homolog of the major allergen Pru ar 1 in apricot (Prunus armeniaca) was identified up-regulated in the highly resistant soybean 'Suinong 10' infected with P. sojae. Here, the full length of the EST was isolated using rapid amplification of cDNA ends (RACE). It showed the highest homology of 53.46% with Gly m 4 after comparison with the eight soybean allergen families reported and was named Gly m 4-like (Gly m 4l, GenBank accession no. HQ913577.1). The cDNA full length of Gly m 4l was 707 bp containing a 474 bp open reading frame encoding a polypeptide of 157 amino acids. Sequence analysis suggests that Gly m 4l contains a conserved 'P-loop' (phosphate-binding loop) motif at residues 47-55 aa and a Bet v 1 domain at residues 87-120 aa. The transcript abundance of Gly m 4l was significantly induced by P. sojae, salicylic acid (SA), NaCl, and also responded to methyl jasmonic acid (MeJA) and ethylene (ET). The recombinant Gly m 4l protein showed RNase activity and displayed directly antimicrobial activity that inhibited hyphal growth and reduced zoospore release in P. sojae. Further analyses showed that the RNase activity of the recombinant protein to degrading tRNA was significantly affected in the presence of zeatin. Over-expression of Gly m 4l in susceptible 'Dongnong 50' soybean showed enhanced resistance to P. sojae. These results indicated that Gly m 4l protein played an important role in the defense of soybean against P. sojae infection.


Human Desmoglein-2 and Human CD46 Mediate Human Adenovirus Type 55 Infection, but Human Desmoglein-2 Plays the Major Roles.
Human adenovirus type 55 (HAdV55) represents an emerging respiratory pathogen and causes severe pneumonia with high fatality in humans. The cellular receptors, which are essential for understanding the infection and pathogenesis of HAdV55, remain unclear. In this study, we found that HAdV55 binding and infection were sharply reduced by disrupting the interaction of viral fiber protein with human desmoglein-2 (hDSG2) but only slightly reduced by disrupting the interaction of viral fiber protein with human CD46 (hCD46). Loss-of-function studies using soluble receptors, blocking antibodies, RNA interference, and gene knockout demonstrated that hDSG2 predominantly mediated HAdV55 infection. Nonpermissive rodent cells became susceptible to HAdV55 infection when hDSG2 or hCD46 was expressed, but hDSG2 mediated more efficient HAd55 infection than hCD46. We generated two transgenic mouse lines that constitutively express either hDSG2 or hCD46. Although nontransgenic mice were resistant to HAdV55 infection, infection with HAdV55 was significantly increased in hDSG2+/+ mice but was much less increased in hCD46+/+ mice. Our findings demonstrate that both hDSG2 and hCD46 are able to mediate HAdV55 infection but hDSG2 plays the major roles. The hDSG2 transgenic mouse can be used as a rodent model for evaluation of HAdV55 vaccine and therapeutics.IMPORTANCE Human adenovirus type 55 (HAdV55) has recently emerged as a highly virulent respiratory pathogen and has been linked to severe and even fatal pneumonia in immunocompetent adults. However, the cellular receptors mediating the entry of HAdV55 into host cells remain unclear, which hinders the establishment of HAdV55-infected animal models and the development of antiviral approaches. In this study, we demonstrated that human desmoglein-2 (hDSG2) plays the major roles during HAdV55 infection. Human CD46 (hCD46) could also mediate the infection of HAdV55, but the efficiency was much lower than for hDSG2. We generated two transgenic mouse lines that express either hDSG2 or hCD46, both of which enabled HAd55 infection in otherwise nontransgenic mice. hDSG2 transgenic mice enabled more efficient HAdV55 infection than hCD46 transgenic mice. Our study adds to our understanding of HAdV55 infection and provides an animal model for evaluating HAdV55 vaccines and therapeutics.


Condensation of a nickel tetranuclear cubane into a heptanuclear single-molecule magnet.
A tetranuclear complex, [Ni(4)], with a cubane-like structure synthesized from hexafluoroacetylacetone gives, after drying at high temperature and treatment with pyridine, a heptanuclear nickel(II) complex, [Ni(7)]. The crystal structures of both compounds have been determined by single-crystal X-ray diffraction. Their magnetic properties have been studied by SQUID and μ-SQUID magnetometry as well as by high-frequency EPR spectroscopy (HF-EPR). For [Ni(4)], the temperature dependence of the magnetic susceptibility can be fitted by taking into account strong Ni···Ni ferromagnetic interactions which lead to an S = 4 ground-state spin, in good agreement with the HF-EPR study. For [Ni(7)], the temperature dependence of the magnetic susceptibility shows that the Ni···Ni ferromagnetic interactions are kept within the metal core. However, it was not possible to fit this with a clear set of parameters, and the ground-state spin was undetermined. The field dependence of the magnetization indicates an S = 7 ground-state spin at high field. In contrast, the temperature dependence of the magnetic susceptibility indicates a ground-state spin of S = 6 or even S = 5. These results agree with complicated high-frequency EPR spectra which have been ascribed to the superposition of signals from the ground spin multiplet and from an excited spin multiplet very close in energy, with the excited state having a larger S value than the ground state. Very low temperature studies show that only the heptanuclear complex behaves as a single-molecule magnet.


High-Efficiency and Versatile Approach To Fabricate Diverse Metal-Organic Framework Coatings on a Support Surface as Stationary Phases for Electrochromatographic Separation.
A large number of metal-organic frameworks (MOFs) have exhibited increasingly wide utilization in the field of chromatographic separation owing to their intrinsic fascinating properties. However, the previous studies on supported MOF coating-based chromatographic separation focused only on the synthesis and chromatographic performance of a certain kind of supported MOF coatings as stationary phases using the multiple-step, complicated, and time-consuming modification methods, which severely impeded the widespread application of MOFs in separation science. Herein, a high-efficiency and versatile methodology toward diverse supported MOF coating-based stationary phases to achieve high-efficiency chromatographic separation was first reported based on the immobilized cysteine (Cys)-triggered in situ growth (ICISG) strategy. As a proof-of-concept demonstration, four types of MOF crystals consisting of different ligands and metal ions (Zn2+, Cu2+, Fe3+, and Zr4+) were conveniently and firmly grown on a Cys-modified capillary using the ICISG strategy and employed as the functional stationary phase for electrochromatographic separation. A broad variety of neutral, acidic, and basic compounds were all separated in a highly efficient manner on the developed four MOF-coated columns. The maximum theoretical plate number for Cys-MIL-100(Fe)@capillary was close to 1.0 × 105 plates/m, and the intraday, interday, and column-to-column repeatabilities of retention times for the four MOF-modified columns were all less than 5.25%. More interestingly, the diversified separation performance of the developed MOF-coated columns indicated that the preparation strategy and the skeletal structure of the MOF coating-based stationary phases have a significant influence on the electrochromatographic separation performance and column capacity. Benefiting from the strong universality and high applicability of the developed ICISG strategy, the present study provides an effective route to facilitate the design and fabrication of novel functional MOF-based chromatographic stationary phases.


Synchronous squamous cell carcinoma of the endometrium and endometrioid adenocarcinoma of the ovary.
Synchronous primary endometrial and ovarian cancers are relatively uncommon in general population. The etiology and pathogenesis of this phenomenon remains unclear. The authors' aim was to present a case of synchronous squamous cell carcinoma of the endometrium and endometrioid adenocarcinoma of the ovary and review current literature. The patient, a 64-year-old, nulliparous postmenopausal Greek woman presented with a complaint of abdominal pain and abnormal uterine bleeding. Preoperative computer tomography (CT) of the abdomen and pelvis, and abdominal ultrasound (U/S) revealed an intra-abdominal three cm mass with solid components between the left ovary and small bowel. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH+BS), total omentectomy, pelvic and para-aortic lymph node dissection, and removal of the implant at the serosa of small bowel. Histopathology revealed Stage IA endometrial cancer squamous type and Stage IIIC ovarian cancer of endometrioid-type. Postoperatively the patient underwent adjuvant chemotherapy and radiotherapy. Follow-up of 22 months after initial surgery revealed no evidence of recurrence. The reason for better median overall survival of patients with synchronous primary endometrial and ovarian cancers is not intuitively obvious. Perhaps favourable clinical outcome may be related with the detection of patients at early stage and low-grade disease with an indolent growth rate.


Spontaneously Occurring Formation of Intranuclear and Cytoplasmic Inclusions in Renal Proximal Epithelium Due to Accumulation of D-Amino Acid Oxidase in Wistar Hannover Rats.
Intranuclear and cytoplasmic inclusions in the renal proximal tubular epithelium were observed in nontreated male and female Wistar Hannover rats in a 26-week study (32 weeks of age) and a 104-week study (110 weeks of age). The incidence rates were less than 5% in these two studies. In affected animals, the inclusions were observed in more than 60% of proximal tubular epithelium as various sized (approximately 1-8 μm in diameter) round and eosinophilic materials, but not in distal tubules, Henle's loop, or collecting ducts. Ultrastructurally, inclusions appeared finely granular, homogenous with middle-electron density, and without a limiting membrane. These inclusions were determined to be protein histochemically stained by Azan-Mallory and immunoreactive with an antibody against D-amino acid oxidase (DAO). There was no abnormality in in-life observations or in clinical test values suggestive of renal dysfunction. There were no associated degenerative or inflammatory changes in the kidneys, and no similar inclusions were observed in the other organs. These inclusions are very similar to propiverine hydrochloride (propiverine) and norepinephreine/serotonin reuptake inhibitor-induced inclusions. This is the first report of accumulation of DAO and formation of inclusions occurring spontaneously in rat kidneys. The data are important for toxicological studies using Wistar Hannover rats.


Glutaric aciduria type 1: clinical, biochemical and molecular findings in patients from Israel.
Glutaric aciduria type 1 (GA1) is a rare cerebral organic aciduria which typically manifests as an acute encephalopathic crisis followed by profound long-term neurological handicap. We report the diagnosis of 12 new patients from a single laboratory in Israel during a 5-year period. Eleven of the 12 were of Palestinian origin, and only two were related. One patient was asymptomatic whilst one was mildly, one moderately and nine severely affected, two of whom had unusual MRI findings. Two patients had normal glutaric acid excretion and normal blood glutarylcarnitine levels yet glutarylcarnitine excretion was increased, indicating its utility as a diagnostic marker. Four novel GCDH mutations (Thr193_Arg194insHis, Asn329Ser, Thr341Pro, Met405Val) and five previously reported mutations (Ser119Leu, Leu283Pro, Ala293Thr, Gly390Arg and Thr416Ile) were identified. Severely and mildly affected or even asymptomatic patients shared the same genotypes (Thr416Ile/Thre416Ile and Aal293Thr/Thr193_Arg194insHis). Knowledge of the responsible mutation enabled successful prenatal diagnosis on chorionic villous DNA in three families. In conclusion, GA1 is genetically heterogeneous and has a relatively high incidence in the Palestinian population, reflecting the historical tradition of marriages within extended kindreds, particularly in isolated villages. Additional genetic and/or environmental factors must account for the phenotypic heterogeneity in patients with the same genotype. The diagnosis was not suspected in the majority of cases despite typical clinical and/or neuroimaging features, suggesting that glutaric aciduria may be under-diagnosed. Greater awareness of glutaric aciduria amongst pediatricians, neonatologists and radiologists is the key to identifying the disorder in the presymptomatic phase and preventing its catastrophic consequences.


To what extent are patients with migraine able to predict attacks?
Premonitory symptoms (PSs) of migraine are those that precede pain in a migraine attack. Previous studies suggest that treatment during this phase may prevent the onset of pain; however, this approach requires that patients be able to recognize their PSs. Our objectives were to evaluate patients' actual ability to predict migraine attacks based on their PSs and analyze whether good predictors meet any characteristic profile. This prospective, observational study included patients with migraine with and without aura. Patients' baseline characteristics were recorded. During a 2-month follow-up period, patients used a mobile application to record what they believed to be PSs and later to record the onset of pain, if this occurred. When a migraine attack ended, patients had to complete a form on the characteristics of the episode (including the presence of PSs not identified prior to the attack). Fifty patients were initially selected. A final total of 34 patients were analyzed, recording 229 attacks. Of whom, 158 (69%) were accompanied by PSs and were recorded prior to the pain onset in 63 (27.5%) cases. A total of 67.6% of the patients were able to predict at least one attack, but only 35.3% were good predictors (>50% of attacks). There were only 11 cases in which a patient erroneously reported their PSs (positive predictive value: 85.1%). Good predictors were not differentiated by any specific clinical characteristic. However, a range of symptoms were particularly predictive; these included photophobia, drowsiness, yawning, increased thirst, and blurred vision. A large majority of patients with migraine experienced a PS and were able to predict at least one attack. Besides, only a small percentage of patients were considered as good predictors; however, they could not be characterized by any specific profile. Nonetheless, when patients with migraine believed that they were experiencing PSs, they were frequently correct.


Polypoid dermal dendrocytic hamartoma in a giant congenital melanocytic nevus.
Giant congenital melanocytic nevus (CMN) might be complicated by the development of several tumor types, mainly melanoma and rhabdomyosarcoma, but also poorly differentiated neoplasms. Striking polypoid exophytic masses occasionally result from neuroectodermal and neuromesenchymal hamartomatous overgrowths, which lends support to the concept of pluripotential melanoblastomatous and neurocristic origin of these lesions. The present report describes what appears to be a unique example of dermal hamartomatous polypoid CD34(+) fibrogenic proliferation devoid of melanin, namely a dendrocytoma, surrounded by the melanocytes from the nevus, located in the skin of the scrotum against a background of giant CMN. The differential diagnosis included dermatofibrosarcoma protuberans, giant-cell fibroblastoma, angiofibroma, Bednar tumor, other types of dermal dendrocytic hamartoma, and neurocristic cutaneous hamartoma. This case lends support to the proposed neurocristic origin of dermal fibrogenic cells.


Purification of canine gut glucagon-like immunoreactivity (GLI) and its insulin releasing activity.
In order to clarify the nature of the biological action of gut glucagon-like immunoreactivity (GLI), GLI was extracted from the mucosa of the canine intestine and purified by gel filtration and affinity chromatography. 1500 gm of the mucosa yielded approximately 7 gm of crude extract of GLI. This crude extract was applied to a column packed with Sephadex G-50 or Bio-Gel P-10 and two peaks were obtained, Peak I and II. Each peak was purified with affinity chromatography, bound to gamma-globulin of anti-glucagon rabbit-serum. In this step, the GLI was purified approximately 80 times in comparison with the crude extract. Peak I or Peak II, as well as pancreatic glucagon, was infused successively into the pancreaticoduodenal artery of the anesthetized dogs. When buffer solution or the Peak I GLI was infused, the plasma immunoreactive insulin in the pancreatic vein did not change significantly. In contrast, both the Peak II and pancreatic glucagon promoted insulin secretion from the pancreas. The results obtained in this experiment demonstrate the promotion of insulin release from the pancreas and suggest an important role of gut GLI in the absorption and metabolic processing of nutrients.


Dioxygen Activation on Cu-MOR Zeolite: Theoretical Insights into the Formation of Cu2O and Cu3O3 Active Species.
The utilization of low-cost and abundant oxygen (O2) as an oxidant in the activation of copper-exchanged zeolites is highly important for the direct, selective oxidation of methane to methanol at low temperatures. While two motifs of active sites, i.e., the [Cu2(μ-O)]2+ and [Cu3(μ-O)3]2+, have been experimentally observed in mordenite (MOR) zeolite, the mechanisms of their formation from the reaction of Cu-MOR with O2 are still unclear. In this study, we performed density functional theory (DFT) calculations for O2 activation over 2[Cu2]2+-MOR and [Cu3O]2+-MOR zeolites. For the reaction on the dicopper species, we found two possible reaction routes: O-O bond cleavage leading to (1) formation of a [Cu2(μ-O)]2+ active species and a trans-μ-1,2-peroxo-Si2 species and (2) simultaneous formation of two [Cu2(μ-O)]2+ active species neighboring to each other. These routes are both exothermic but require completely different O-O bond activation energies. For the reaction on the tricopper species, we suggest a peroxo-Cu3O species as the intermediate structure with two transition states (TSs) involved in the reaction. The first TS where a significant rearrangement of the tricopper site occurs is found to be rate-determining, while the second TS where the peroxo bond is cleaved results in a smaller activation barrier. This reaction, in contrast to the dicopper case, is slightly endothermic. The present study provides theoretical insights that may help design of better Cu-exchanged zeolite catalysts for methane hydroxylation to methanol.


[Eating and ruminating behavior of sheep. 2. Experiments in pregnant and lactating ewes fed with a straw-concentrate mixture].
Fertility oriented ewes in the late stage of gestation and during the lactation period received 19 feeding regimes on the basis of straw-concentrate mixtures, which essentially differed in the feedstuff structure. The ewes fed ad libitum on average used between 5 and 6 hours per day feed intake in the 86 measuring periods. The average daily ruminating time ranged from 398 to 502 minutes. An increasing straw content resulted in significantly longer ruminating periods and a higher number of masticatory movements, additional quotas of long straw had non effect. But even the most unfavourable feeding variants (straw-concentrate mixtures with 40% straw meal treated with NaOH) elicited 21 100 ruminating masticatory movements in 5 hours of ruminating. There were no significant differences between the absolute consumption and ruminating activities in the late stage of gestation and the lactation period; with reference to feed and crude fibre intake the ruminating expenditure in the late stage of gestation was always significantly higher. Rations with a low structural effect resulted in a more unbalanced distribution of consumption and ruminating activities in the course of the day than well structured rations.


Mild nephrogenic diabetes insipidus caused by Foxa1 deficiency.
Foxa1 is a member of the winged helix family of transcription factors and is expressed in the collecting ducts of the kidney. We investigated its potential contribution to renal physiology in Foxa1-deficient mice on a defined genetic background. Foxa1(-/-) mice are dehydrated and exhibit electrolyte imbalance as evidenced by elevated hematocrit and plasma urea levels, hypernatremia, and hyperkalemia. This phenotype is the consequence of decreased urine osmolality secondary to renal vasopressin resistance. Mutations of the human genes encoding the vasopressin 2 receptor and aquaporin 2 cause nephrogenic diabetes insipidus; however, expression of these genes is maintained or increased, respectively, in Foxa1(-/-) mice. Likewise, expression of the genes encoding the Na-K-2Cl cotransporter (NKCC2), the potassium channel ROMK, the chloride channel CLCNKB, barttin (BSND), and the calcium-sensing receptor (CASR), each of which is important in sodium reabsorption in the loop of Henle, is maintained or even increased in Foxa1-deficient mice. Thus, we have shown that Foxa1(-/-) mice represent a new model of nephrogenic diabetes insipidus with unique molecular etiology, and we have identified the first transcription factor whose mutation leads to a defect in renal water homeostasis in vivo.


[Sexual activity in the convalescent from acute myocardial infarct. Bibliographic review].
There is little information in the medical literature about the renewal of sexual activity in patients who have suffered an MI. The knowledge which the internist and the cardiologist have are normally insufficient. The equivalents in energetic cost of a sexual relation of a middle aged adult, are similar to those of: a) a simple Master test of two stairs, b) walking rapidly the length of a street, c) climbing two flights of stairs. d) a test with ergometer to 100 watts or 600 kg-m-m, e) to walk the endles band at 3.5 miles/hour, f) to carry out activities equivalent to 6 cal/min. The average of the maximum cardiac frequency which is reached during coitus is from 115 to 120, equivalent to approximately 4-5 mets., during 20-36 seconds. In the post and preorgasmic period (1 min, before and after) the energetic cost is close to 4 mts. It should be emphasized that there should not exist an exact limit after which the patient who has had an MI is permitted to have sexual relations. The sexual activity should be advised if the patient has satisfactorily passed any of the equivalent tests mentioned above. The cardiologist should know these facts and not wait until the patient asks about them; he should have the initiative to openly discuss them with the patient and his partner from the period interhospitalary convalescence of the MI.


Human erythrocyte membrane protein 4.2 is palmitoylated.
Protein 4.2 is a major protein of the human erythrocyte membrane. It has previously been shown to be N-myristoylated. After labeling of intact human erythrocytes with [3H]palmitic acid, radioactivity was found to be associated with protein 4.2 by immunoprecipitation of peripheral membrane proteins extracted at pH 11 from ghosts with anti-(4.2) sera, followed by SDS/PAGE and fluorography. The fatty acid linked to protein 4.2 was identified as palmitic acid after hydrolysis of protein and thin-layer chromatography of the fatty acid extracted in the organic phase. Protein 4.2 could be depalmitoylated with hydroxylamine, suggesting a thioester linkage. Depalmitoylated protein 4.2 showed significantly decreased binding to protein-4.2-depleted membranes, compared to native protein 4.2.


Identifying a New Social Intervention Model of Panic Buying Under Sudden Epidemic.
COVID-19 that broke out at the end of 2019 continues to spread globally, with frequent occurrence of variant disease strains, thus epidemic prevention and control become a kind of routine job. At present, due to the prevention and control measures such as maintaining social distance and community blockades, there is a boom in material purchases in many places, which not only seriously endangers social order and public environmental safety, but also easily leads to the interruption of the supply chain and the shortage of social materials. This article aims to study the intervention methods to curb the spread and spread of panic buying behavior. Firstly, through crawler technology and LDA (Latent Dirichlet Allocation) topic model, this article analyzes the intervention measures taken by various social forces in China to curb the spread of panic buying, and summarizes the multi-channel intervention measures including online and offline forms. Secondly, through the multi-Agent Monte Carlo method, the targeted intervention mechanism is supplemented in each propagation link of the panic buying propagation model, and a new social intervention model of panic buying under sudden epidemic is constructed. Then, through MATLAB modeling and simulation, the main factors affecting panic buying intervention are discussed. The simulation results show that: (1) The single plan with the best intervention effect is the supply monitoring. While the official response can play an immediate inhibitory effect, but it is affected by credibility and timeliness. The intervention effect of psychological counseling is limited, and it generally needs to be used in combination with other measures. (2) The combination strategy with the best intervention effect is "supply monitoring + official response + psychological counseling," and the worst is "information review and guidance + psychological counseling." Supply monitoring is a key measure to curb panic buying. At the same time, "information review and guidance" will have a certain counter-effect in the combined strategy. Finally, the effectiveness and universality of the proposed model are verified by examples of China and Britain.


Functional status and quality of life among breast cancer survivors with heart failure: results of the Medicare Health Outcomes Survey.
The purpose of this population-based study was to examine health-related quality of life (HRQOL) and functional status among breast cancer survivors with heart failure. We examined Medicare Health Outcomes Survey data from women aged 65 and older diagnosed with breast cancer in the past 5 years. Surveys were linked to Surveillance, Epidemiology, and End Results cancer registries. Each woman identified with self-reported heart failure (n = 239) was matched to controls without heart failure (n = 685) using propensity scores. The Short Form-36/Veterans Rand-12 measured eight domains of HRQOL. Functional status impairment was measured by limitations in six activities of daily living (ADLs). Linear models estimated associations between heart failure status and HRQOL. Logistic regression models estimated odds ratios for associations between heart failure and ADL impairment. We examined associations for the total study population and subgroups stratified by cancer stage. Among all study participants, heart failure was associated with significant deficits in every HRQOL domain and impairment in all ADLs (p < 0.01, ORs ranged from 1.74 to 2.47). After stratification by cancer stage, heart failure was associated with physical HRQOL deficits across all cancer stages (physical function, vitality, general health) and mental HRQOL deficits only in women with stage I/II cancer (role-emotional, social function). Women with early stage cancer experienced the greatest HRQOL deficits associated with heart failure. Heart failure in breast cancer survivors is associated with substantial HRQOL deficits and functional status impairment, particularly in early stage cancer. Tailored interventions are needed to improve physical function and mental wellbeing in this high-risk population.


Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) Technology in Fission Yeast.
Shotgun proteomics combined with stable isotope labeling by amino acids in cell culture (SILAC) is a powerful approach to quantify proteins and posttranslational modifications across the entire proteome. SILAC technology in Schizosaccharomyces pombe must cope with the "arginine conversion problem," in which isotope-labeled arginine is converted to other amino acids. This can be circumvented by either using stable isotope-marked lysine only (as opposed to the more standard lysine/arginine double labeling) or using yeast genetics to create strains that only very inefficiently convert arginine. Both strategies have been used successfully in large-scale (phospho)proteomics projects in S. pombe Here we introduce methods for performing a typical SILAC-based experiment in fission yeast, including generation of SILAC-compatible strains, sample preparation, and measurement by mass spectrometry.


Morphology of the membrana limitans.
The morphology of the membrana limitans (ML) was studied by light and electron microscopy to further understand its functional significance. The ML is a porous shield composed of a few to several layers of tightly packed fibrocytes that separate the perilymphatic space of the cochlea and saccule from that of the utricle and canal system. These fibrocytes are thinner on the side of the vestibule. They show many desmosomes and gap junctions and are interspersed with fibrils. The 3-dimensional reconstruction from celloidin sections shows that the ML, as it is viewed from the anterior side, is rectangular in shape, with various surface curvatures and an invagination toward the internal aperture of the vestibular aqueduct. Horseradish peroxidase, a tracer substance, placed on either side of the ML fails to pass to the opposite side. The ML and trabecular meshwork may be a factor contributing to differential sensitivity of cochlear and vestibular sensory cells in the presence of noxious substances.


Adjuvant irradiation for early breast cancer. An on-going controversy.
Adjuvant irradiation has been used in the treatment of breast cancer for over 80 years, but its use has always been, and remains, controversial. It is extremely valuable in the treatment of Stage III and IV breast cancer because of its ability to reduce the local recurrence rate in these late stages down to acceptably low levels; however, to have a significant benefit in Stages I and II, in which the local recurrence rate is only 10% to 20% with mastectomy alone, it should be able to improve survival as well as prevent local recurrence. All of the early trials indicated that adjuvant irradiation neither increased nor decreased survival; however, these trials were flawed by poorly executed randomization processes and/or by the use of radiotherapy that would be considered inadequate by today's standards. The two recent trials, Oslo and Stockholm, which were more stringently randomized and which employed more modern radiotherapy techniques, showed an improved disease-free survival with adjuvant irradiation. Overall, survival, however, was unaffected, save for the small subset of patients with medial tumors and histologically positive axillary nodes. For these patients there was a trend toward survival enhancement by internal mammary node irradiation. All of the trials testing irradiation and surgery against surgery alone have very little relevance in today's adjuvant chemotherapy era; thus, the entire question of survival enhancement by irradiation must be reassessed within the context of adjuvant chemotherapy. Will the combination of adjuvant chemotherapy and irradiation yield a better survival than either adjuvant modality alone? The results of the few prospective trials that have addressed this question are still preliminary, and longer follow-up is necessary before any conclusions can be reached. Also, future studies must be undertaken to address two issues that may be very important when combining chemotherapy and radiotherapy: the sequencing of these two modalities, and the optimum radiotherapy technique for minimizing hematologic suppression.


Real-life effectiveness of 'improved' stoves and clean fuels in reducing PM2.5 and CO: Systematic review and meta-analysis.
2.8 billion people cook with solid fuels, resulting in almost 3 million premature deaths from household air pollution (HAP). To date, no systematic assessment of impacts on HAP of 'improved' stove and clean fuel interventions has been conducted. This systematic review synthesizes evidence for changes in kitchen and personal PM2.5 and carbon monoxide (CO) following introduction of 'improved' solid fuel stoves and cleaner fuels in low- and middle-income countries (LMIC). Searches of published and unpublished literature were conducted through databases and specialist websites. Eligible studies reported mean (24 or 48h) small particulate matter (majority PM2.5) and/or CO. Eligible interventions were solid fuel stoves (with/without chimneys, advanced combustion), clean fuels (liquefied petroleum gas, biogas, ethanol, electricity, solar) and mixed. Data extraction and quality appraisal were undertaken using standardized forms, and publication bias assessed. Baseline and post-intervention values and percentage changes were tabulated and weighted averages calculated. Meta-analyses of absolute changes in PM and CO were conducted. Most of the 42 included studies (112 estimates) addressed solid fuel stoves. Large reductions in pooled kitchen PM2.5 (ranging from 41% (29-50%) for advanced combustion stoves to 83% (64-94%) for ethanol stoves), and CO (ranging from 39% (11-55%) for solid fuel stoves without chimneys to 82% (75-95%) for ethanol stoves. Reductions in personal exposure of 55% (19-87%) and 52% (-7-69%) for PM2.5 and CO respectively, were observed for solid fuel stoves with chimneys. For the majority of interventions, post-intervention kitchen PM2.5 levels remained well above WHO air quality guideline (AQG) limit values, although most met the AQG limit value for CO. Subgroup and sensitivity analyses did not substantially alter findings; publication bias was evident for chimney stove interventions but this was restricted to before-and-after studies. In everyday use in LMIC, neither 'improved' solid fuel stoves nor clean fuels (probably due to neighbourhood contamination) achieve PM2.5 concentrations close to 24-hour AQG limit values. Household energy policy should prioritise community-wide use of clean fuels.


Early glycemia and mortality in critically ill septic patients: Interaction with insulin-treated diabetes.
To investigate the relationship between dysglycemia and hospital mortality in patients with and without a preadmission diagnosis of insulin treated diabetes mellitus (ITDM). An observational multicentre cohort study using the ANZICS-APD database on adult patients admitted to ICU with sepsis between January 1st 2006 and December 31st 2015. Four domains of dysglycemia were investigated (highest, mean and lowest blood glucose levels and glycemic variability: the absolute difference between the highest and lowest level). The association between a preadmission diagnosis of ITDM and hospital mortality in each domain was analysed. We studied 90,644 septic patients including 5127 patients with ITDM. We found that septic ICU patients with ITDM have lower adjusted hospital mortality with higher peak blood glucose levels in the first 24 h while non-ITDM patients have increased mortality (interaction p 0.012). We found that this significant difference was replicated when assessing glycemic variability (interaction p 0.048). Septic patients with a pre-existing diagnosis of ITDM show a different relationship between hospital mortality and highest glucose levels and glycemic variability in the first 24 h than those without ITDM. These findings provide a rationale for an ITDM-specific approach to the management of dysglycemia.


Back-up bone marrow is frequently ineffective in patients with poor peripheral-blood stem-cell mobilization.
To assess hematologic recovery and procedure-related mortality in patients who received high-dose therapy with stem-cell support, in whom the peripheral-blood stem-cell (PBSC) collection fails (CD34+ cells < 1 x 10(6)/kg). The predictive value of granulocyte-monocyte colony-forming cell (GM-CFC) measurements and the value of bone marrow obtained after PBSC collection failure was assessed. The study group comprised 324 consecutive patients mobilized with granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide (273 patients), G-CSF with other chemotherapy (37 patients), and G-CSF alone (14 patients). Between one and four aphereses were performed. In 51 of 324 patients, there was failure to obtain 1 x 10(6)/kg CD34+ cells. Twenty-three patients had greater than 1 x 10(5)/kg GM-CFC; 22 patients proceeded to high-dose therapy. Neutrophil recovery occurred within 21 days, but platelet independence was delayed (> 28 days) in eight patients. Of 28 patients with less than 1 x 10(5)/kg GM-CFC, six received high-dose therapy with PBSC alone and five had delayed engraftment. Twelve patients with less than 1 x 10(5)/kg GM-CFC received high-dose therapy supported by bone marrow collected after PBSC collection failure. Eleven patients were assessable for engraftment; four patients had slow (> 21 days) or delayed (> 28 days) neutrophil recovery and eight patients had delayed platelet recovery. In the group of patients who received less than 1 x 10(5)/kg GM-CFC, there were five procedure-related deaths. This study shows that delayed hematologic recovery is frequent if less than 1 x 10(6)/kg CD34+ cells are infused after high-dose therapy, particularly with GM-CFC less than 1 x 10(5)/kg. The procedure-related mortality in this latter group is high. In most patients whose PBSC collection contains less than 1 x 10(5)/kg GM-CFC, the use of bone marrow cells does not improve engraftment, which suggests that poor PBSC mobilization usually indicates poor marrow function.


Studies on lophocercous cercariae from Bithynia siamensis goniomphalus (Prosobranchia: Bithyniidae).
Cercariae from Bithynia siamensis goniomphalus were studied in an area endemic for opisthorchiasis. Snails emitted different types of cercariae when shedding was induced by illumination. In addition to two lophocercous cercariae, a monostome cercaria (probably Notocotylus sp), two different furcocercariae and a xiphidiocercaria were found. Two similar types of lophocercous cercariae were distinguishable and one could be identified as Opisthorchis viverrini. To date the cercaria of O. viverrini has been regarded as the only lophocercous cercaria in the endemic area of opisthorchiasis. Therefore, differences between these cercariae were further characterized by scanning electron microscopy to enable us to avoid misinterpretations of O. viverrini in Bithynia.


Theoretical Treatment of CH3 NH3 PbI3 Perovskite Solar Cells.
Hybrid halide perovskite solar cells (PSCs) giving over 22 % power conversion efficiencies (PCEs) have attracted considerable attention. Although perovskite plays a significant role in the operation of PSCs, the fundamental theories associated with perovskites have not been resolved in spite of the increase in research. In this Minireview, we assess the current understanding, based on the first-principles calculations, of structural and electronic properties, defects, ionic diffusion, and shift current for CH3 NH3 PbI3 perovskite, and the effect of ionic transport on the hysteresis of current-voltage curves in PSCs. The shift current connected to the possible presence of ferroelectricity is also discussed. The current state-of-the-art and some open questions regarding PSCs are also highlighted, and the benefits, challenges, and potentials of perovskite for use in PSCs are stressed.


Value of General Medical Knowledge Examinations in Performance Assessment of Practicing Physicians With Potential Competence and Performance Deficiencies.
Problems with a physician's performance may arise at any point during their career. As such, there is a need for effective, valid tools and processes to accurately assess and identify deficiencies in competence or performance. Although scores on multiple-choice questions have been shown to be predictive of some aspects of physician performance in practicing physicians, their relationship to overall clinical competence is somewhat uncertain particularly after the first 10 years of practice. As such, the purpose of this study was to examine how a general medical knowledge multiple-choice question examination is associated with a comprehensive assessment of competence and performance in experienced practicing physicians with potential competence and performance deficiencies. The study included 233 physicians, of varying specialties, assessed by the University of California, San Diego Physician Assessment and Clinical Education Program (PACE), between 2008 and 2012, who completed the Post-Licensure Assessment System Mechanisms of Disease (MoD) examination. Logistic regression determined if the examination score significantly predicted passing assessment outcome after correcting for gender, international medical graduate status, certification status, and age. Most physicians (89.7%) received an overall passing assessment outcome on the PACE assessment. The mean MoD score was 66.9% correct, with a median of 68.0%. Logistic regression (P = .038) was significant in indicating that physicians with higher MoD examination scores had an increased likelihood of achieving a passing assessment outcome (odds ratio = 1.057). Physician MoD scores are significant predictors of overall physician competence and performance as evaluated by PACE assessment.


Development of monoclonal antibodies and serological assays including indirect ELISA and fluorescent microsphere immunoassays for diagnosis of porcine deltacoronavirus.
A novel porcine deltacoronavirus (PDCoV), also known as porcine coronavirus HKU15, was reported in China in 2012 and identified in the U.S. in early 2014. Since then, PDCoV has been identified in a number of U.S. states and linked with clinical disease including acute diarrhea and vomiting in the absence of other identifiable pathogens. Since PDCoV was just recently linked with clinical disease, few specific antibody-based reagents were available to assist in diagnosis of PDCoV and limited serological capabilities were available to detect an antibody response to this virus. Therefore, the overall objective of this project was to develop and validate selected diagnostic reagents and assays for PDCoV antigen and antibody detection. The nucleoprotein of PDCoV was expressed as a recombinant protein and purified for use as an antigen to immunize mice for polyclonal, hyperimmune sera and monoclonal antibody (mAb) production. The resulting mAbs were evaluated for use in fluorescent antibody staining methods to detect PDCoV infected cells following virus isolation attempts and for immunohistochemistry staining of intestinal tissues of infected pigs. The same antigen was used to develop serological tests to detect the antibody response to PDCoV in pigs following infection. Serum samples from swine herds with recent documentation of PDCoV infection and samples from expected naïve herds were used for initial assay optimization. The tests were optimized in a checkerboard fashion to reduce signal to noise ratios using samples of known status. Statistical analysis was performed to establish assay cutoff values and assess diagnostic sensitivities and specificities. At least 629 known negative serum samples and 311 known positive samples were evaluated for each assay. The enzyme linked immunosorbent assay (ELISA) showed diagnostic sensitivity (DSe) of 96.1% and diagnostic specificity (DSp) of 96.2%. The fluorescent microsphere immunoassay (FMIA) showed a DSe of 95.8% and DSp of 98.1%. Both ELISA and FMIA detected seroconversion of challenged pigs between 8-14 days post-infection (DPI). An indirect fluorescent antibody (IFA) test was also developed using cell culture adapted PDCoV for comparative purposes. These new, specific reagents and serological assays will allow for improved diagnosis of PDCoV. Since many aspects of PDCoV infection and transmission are still not fully understood, the reagents and assays developed in this project should provide valuable tools to help understand this disease and to aid in the control and surveillance of porcine deltacoronavirus outbreaks.


The personal digital twin, ethical considerations.
The personal digital twin extends to individual persons, a concept that originated in engineering to twin complex machines with a digital simulation containing a model of its functions to monitor its past and present behaviour, and repair, correct, improve or otherwise ensure its optimal operation. Several independent trends in technological developments are seen to converge towards the elaboration of the digital replication of individual human data and life history, notably in health industries. Among the main ones, we consider the ubiquitous distribution of digital assistants, the rapid progress of machine learning concurrent with the exponential growth of 'personal' Big Data and the incipient interest in developing lifelogs. The core hypothesis here is that among the psychological effects of the digital transformation, the externalization of cognitive faculties such as memory, planning and judgement, the decision-making processes located within the human person are also emigrating to digital functions, perhaps as a prelude to a later re-integration within the person via brain-computer interfaces. The paper concludes with ethical considerations about these ongoing developments. This article is part of the theme issue 'Towards symbiotic autonomous systems'.


Validation of three new methods for determination of metal emissions using a modified Environmental Protection Agency Method 301.
Three new methods applicable to the determination of hazardous metal concentrations in stationary source emissions were developed and evaluated for use in U.S. Environmental Protection Agency (EPA) compliance applications. Two of the three independent methods, a continuous emissions monitor-based method (Xact) and an X-ray-based filter method (XFM), are used to measure metal emissions. The third method involves a quantitative aerosol generator (QAG), which produces a reference aerosol used to evaluate the measurement methods. A modification of EPA Method 301 was used to validate the three methods for As, Cd, Cr, Pb, and Hg, representing three hazardous waste combustor Maximum Achievable Control Technology (MACT) metal categories (low volatile, semivolatile, and volatile). The modified procedure tested the methods using more stringent criteria than EPA Method 301; these criteria included accuracy, precision, and linearity. The aerosol generation method was evaluated in the laboratory by comparing actual with theoretical aerosol concentrations. The measurement methods were evaluated at a hazardous waste combustor (HWC) by comparing measured with reference aerosol concentrations. The QAG, Xact, and XFM met the modified Method 301 validation criteria. All three of the methods demonstrated precisions and accuracies on the order of 5%. In addition, correlation coefficients for each method were on the order of 0.99, confirming the methods' linear response and high precision over a wide range of concentrations. The measurement methods should be applicable to emissions from a wide range of sources, and the reference aerosol generator should be applicable to additional analytes. EPA recently approved an alternative monitoring petition for an HWC at Eli Lilly's Tippecanoe site in Lafayette, IN, in which the Xact is used for demonstrating compliance with the HWC MACT metal emissions (low volatile, semivolatile, and volatile). The QAG reference aerosol generator was approved as a method for providing a quantitative reference aerosol, which is required for certification and continuing quality assurance of the Xact.


[Infections by anaerobes in children: frequency of isolation and antimicrobial resistance].
We studied the frequency of isolation and antimicrobial susceptibility of strict anaerobic bacteria isolated in a paediatric hospital. A total of 1,753 samples from purulent material and hemocultures were processed. One hundred and thirty strains were isolated from 95 children: 44 from 48 cases of peritonitis (91.7%), 2 from 8 brain abscesses (25%), 23 from 124 soft tissue abscesses (18.5%), 4 from 64 empyemas or lung abscesses (6.3%) and 22 from 1,509 hemocultures (1.5%). Mixed infection (anaerobic and aerobic bacteria) was detected in 38.5% of the cases; however, in peritonitis 81.3% of the cases showed mixed infection. The more frequently isolated bacteria were: Bacteroides (44.6%), Clostridium (19.2%), Fusobacterium (7.7%) and gram positive cocci (7.7%). Propionibacterium acnes was isolated in 15 specimens; however, most of them were considered as contamination. Bacteroides was isolated more frequently from patients with peritonitis (51.6%). The susceptibility to five antibiotics was tested in 124 strains using the method of serial dilutions in agar plates. The genus Bacteroides showed a high resistance to penicillin (73.1%), moderate to clindamycin (11.5%) and low to cefoxitin, chloramphenicol and metronidazole (6.8%, 2% and 5.8%). The rest of the anaerobic strains tested (other gram negatives and grampositives) were highly sensitive to all the antimicrobials tested, except for clindamycin (26.7% and 36.9% resistance, respectively). Cefoxitin, chloramphenicol and metronidazole had the lower CMI50 and CMI90 for the genus Bacteroides; and for the rest of the bacteria, penicillin had the highest activity (CMI90 less than 0.025). Since the frequency of isolation of anaerobic bacteria in children with severe infections, presumably originated from the digestive tract, paranasal sinus and middle ear is high, anaerobic cultures must be practiced in these patients. Empiric antimicrobial treatment should also be started. This treatment should be with penicillin when the probability of isolation of Bacteroides is low (infections in the face, neck, thorax and soft tissues) and with metronidazole in intraabdominal infections. Because of the severity and probable etiology of brain abscesses, treatment with penicillin and chloramphenicol or metronidazole is recommended in these cases.


A tri-serine cluster within the topoisomerase IIα-interaction domain of the BLM helicase is required for regulating chromosome breakage in human cells.
The recQ-like helicase BLM interacts directly with topoisomerase IIα to regulate chromosome breakage in human cells. We demonstrate that a phosphosite tri-serine cluster (S577/S579/S580) within the BLM topoisomerase IIα-interaction region is required for this function. Enzymatic activities of BLM and topoisomerase IIα are reciprocally stimulated in vitro by ten-fold for topoisomerase IIα decatenation/relaxation activity and three-fold for BLM unwinding of forked DNA duplex substrates. A BLM transgene encoding alanine substitutions of the tri-serine cluster in BLM-/- transfected cells increases micronuclei, DNA double strand breaks and anaphase ultra-fine bridges (UFBs), and decreases cellular co-localization of BLM with topoisomerase IIα. In vitro, these substitutions significantly reduce the topoisomerase IIα-mediated stimulation of BLM unwinding of forked DNA duplexes. Substitution of the tri-serine cluster with aspartic acids to mimic serine phosphorylation reverses these effects in vitro and in vivo. Our findings implicate the modification of this BLM tri-serine cluster in regulating chromosomal stability.


MAP kinase-dependent pathways in cell cycle control.
Mitogen-activated protein kinases such as Erk1 and Erk2 serve as a paradigm for a growing family of proline-directed protein kinases that mediate entry, progression and exit from the cell cycle in diverse eukaryotic cells. These enzymes function within highly conserved modules of sequentially activating protein kinases that transduce signals from diverse extracellular stimuli. In vertebrates, at least three distinct kinases modules have been characterized. Mitogens induce the sequential activation of the kinases Raf1-->Mek1-->Erk2-->Rsk via the G-protein Ras. Stress factors stimulate c-Jun activation through a related kinase pathway involving Mekk-->Sek-->SAPK c-Jun, and hsp27 phosphorylation via the MKK3-->Hog-->MAPKAPK-2 hsp27 route. Genetic and biochemical studies, for example from budding yeast, imply the existence of several related protein kinase modules that can operate in parallel or within integrated systems.


When is bone scintigraphy necessary in the assessment of newly diagnosed, untreated prostate cancer?
To evaluate the utility of bone scintigraphy in the assessment of newly diagnosed, untreated prostate cancer. The probability of a positive bone scan for metastases was analysed for different threshold values of pre-treatment concentrations of prostate specific antigen (PSA), clinical stage, tumour grade based on biopsy, and age in 128 men (mean age 69 years, range 50-90) with newly diagnosed, untreated prostate cancer. The overall survival probabilities estimated from PSA level, extent of bone metastases, tumour grade, clinical stage, and age were calculated using the product-limit method. The positive predictive values of PSA level for bone metastases at thresholds of 10 and 20 ng/mL were poor (27.5 and 47.5%, respectively) whereas similar threshold levels of PSA gave negative predictive values of 100 and 94%, respectively, for a positive bone scan. In a univariate analysis, the overall survival was significantly affected by the extent of bone scan pathology (P < 0.001), the pre-treatment level of PSA (P < 0.001) and tumour grade (P = 0.01), whereas a multivariate analysis identified, in order of significance, tumour grade (P = 0.003), bone scan findings (P = 0.007) and PSA levels (P = 0.03) as independent prognostic factors. Bone scintigraphy seems to be unnecessary in the evaluation of newly diagnosed, untreated prostate cancer in patients with no clinical signs of bone pathology and serum PSA levels of < or = 10 ng/mL. However, the bone scan accurately assesses bone metastases and the prognostic significance of bone scan findings is superior to that of serum PSA level.


The phosphotransferase system of Corynebacterium glutamicum: features of sugar transport and carbon regulation.
In this review, we describe the phosphotransferase system (PTS) of Corynebacterium glutamicum and discuss genes for putative global carbon regulation associated with the PTS. C. glutamicum ATCC 13032 has PTS genes encoding the general phosphotransferases enzyme I, HPr and four enzyme II permeases, specific for glucose, fructose, sucrose and one yet unknown substrate. C. gluamicum has a peculiar sugar transport system involving fructose efflux after hydrolyzing sucrose transported via sucrose EII. Also, in addition to their primary PTS, fructose and glucose are each transported by a second transporter, glucose EII and a non-PTS permease, respectively. Interestingly, C. glutamicum does not show any preference for glucose, and thus co-metabolizes glucose with other sugars or organic acids. Studies on PTS-mediated sugar uptake and its related regulation in C. glutamicum are important because the production yield of lysine and cell growth are dependent on the PTS sugars used as substrates for fermentation. In many bacteria, the PTS is also involved in several regulatory processes. However, the detailed molecular mechanism of global carbon regulation associated with the PTS in this organism has not yet been revealed.


Synthesis of Either C2- or C4'-Alkylated Derivatives of Honokiol and Their Biological Evaluation for Anti-inflammatory Activity.
Honokiol, a biphenolic neolignan isolated from Magnolia officinalis, was reported to have a promising anti-inflammatory activity for the treatment of various diseases. There are many efforts on the synthesis and structure-activity relationship of honokiol derivatives. However, regioselective O-alkylation of honokiol remains a challenge and serves as a tool to provide not only some derivatives but also chemical probes for target identification and mode of action. In this study, we examined the reaction condition for regioselective O-alkylation, in which C2 and C4'-alkylated analogs of honokiol were synthesized and evaluated for inhibitory activity on nitric oxide production and cyclooxygenase-2 expression. Furthermore, we successfully synthesized a potential photoaffinity probe consisting of biotin and benzophenone based on a C4'-alkylated derivative.


Quantitative assessment of leukostasis in experimental hypovolemic-traumatic shock.
Using a hypovolemic-traumatic shock model without reinfusion of shed blood, 111In-oxine-labeled granulocytes were injected to quantify pulmonary leukostasis in dogs. Labeling was facilitated by a non-traumatic and rapid technique for granulocyte processing and a commercially available 111In-oxine solution. Lung biopsy material taken before and after shock showed granulocyte-associated radioactivity to be significantly increased 90 min after the onset of shock. This observation established that pulmonary leukostasis in shock models is not caused solely by reinfusion of shed blood, but rather by humoral factors operative during shock, e.g. by complement activation. The described experimental design should also be useful for in vivo tests of drugs which act on granulocyte function and may have a potential place in the management of shock.


Lipid peroxidation and antioxidative vitamins under extreme endurance stress.
The aim of this study was to examine whether extreme endurance stress of trained athletes can influence lipid peroxidation and muscle enzymes. A randomized and placebo-controlled study was carried out on 24 trained long-distance runners who were substituted with alpha-tocopherol (400 I.U. d-1) and ascorbic acid (200 mg d-1) during 4.5 weeks prior to a marathon race. The serum concentrations of retinol, ascorbic acid, beta-carotene, alpha-tocopherol, malondialdehyde (TBARS) and uric acid as well as glutathione peroxidase (GSH Px) and catalase were measured 4.5 weeks before (A), immediately before (B), immediately after (C) and 24 h after (D) the course. After competition (C) TBARS serum concentrations of the athletes (n = 22) decreased in both groups (P < 0.0001). The ascorbic acid serum concentration increased significantly in the supplemented group from (A) to (B) (P < 0.01), from (B) to (C) (P < 0.001) and in the placebo group a significant increase from (B) to (C) (P < 0.01) was observed. The alpha-tocopherol serum concentration increased significantly in the supplemented group from (A) to (B) (P < 0.001) and from (B) to (C) (P < 0.05). The enzymes glutathione peroxidase (GSH Px) and catalase measured in erythrocytes as well as the serum selenium levels did not show significant differences at any time. A significant increase of CK concentration was observed from (C) to (D) in the supplemented group (P < 0.01) and in the placebo group (P < 0.001). The increase of CK serum concentration is remarkably lower in the supplemented group compared with the placebo group (P < 0.01). It is concluded that endurance training coupled with antioxidant vitamin supplementation reduces blood CK increase under exercise stress.


Morphologic features of uterine leiomyomas associated with hereditary leiomyomatosis and renal cell carcinoma syndrome: a case report.
Patients with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome are prone to develop smooth muscle tumors of the uterus and skin and also renal carcinomas. The morphologic features of renal tumors that arise in the setting of HLRCC are well described, the hallmark feature being the presence of prominent eosinophilic nucleoli surrounded by a clear halo. Renal tumors associated with HLRCC are aggressive and often present late with high-stage disease. Early detection of patients with HLRCC could lead to surveillance for renal carcinomas. Women with HLRCC often present at a young age with uterine leiomyomas and frequently undergo hysterectomy as a result. HLRCC associated uterine leiomyomas show nuclear features similar to those described in HLRCC associated renal tumors. Therefore, presence of these nuclear features in uterine smooth muscle tumors may aid in early detection of HLRCC, resulting in surveillance for renal carcinoma. We present a case of a 32-year-old woman who underwent hysterectomy for uterine fibroids and subsequently presented 5 years later with high-stage renal carcinoma. Histologic evaluation of uterine leiomyomas and renal carcinoma revealed identical nuclear features, that is, prominent nucleoli with perinucleolar halos, raising the possibility of HLRCC. Subsequent testing confirmed a fumarate hydratase mutation. The presence of above-described nuclear features in uterine leiomyomas should raise the possibility of HLRCC.


Interpreting estimates of heritability--a note on the twin decomposition.
While most outcomes may in part be genetically mediated, quantifying genetic heritability is a different matter. To explore data on twins and decompose the variation is a classical method to determine whether variation in outcomes, e.g. IQ or schooling, originate from genetic endowments or environmental factors. Despite some criticism, the model is still widely used. The critique is generally related to how estimates of heritability may encompass environmental mediation. This aspect is sometimes left implicit by authors even though its relevance for the interpretation is potentially profound. This short note is an appeal for clarity from authors when interpreting the magnitude of heritability estimates. It is demonstrated how disregarding existing theoretical contributions can easily lead to unnecessary misinterpretations and/or controversies. The key arguments are relevant also for estimates based on data of adopted children or from modern molecular genetics research.


[Current status of pharmacologic treatment of arrhythmia].
Arrhythmias result from alterations in the electrophysiological properties of the heart: excitability, automatism, conduction, refractory period, and repolarization. These properties depend on the cellular membrane voltage. This voltage is a consequence of macromolecular tunnels permitting the flow of electrical charged particles and the action of the electrogenic pumps against electrochemical gradients. The voltage alterations in the membrane give rise to arrhythmogenic mechanisms resulting of automatism alterations or disorders in conduction, producing re-entry or circus movement. The medical treatment must be based on a correct integral diagnosis, knowledge of the trigger and maintenance mechanisms of the arrhythmia as well as on the pharmacology of the drug. The antiarrhythmic drug classifications are useful for didactic purposes but may be of little use in medical practice. In supraventricular arrhythmias, the mechanisms are known and can be identified; the re-entry pathways are also known and the electrophysiological mechanisms are normal, therefore the response to the drugs is predictable. In contrast, in ventricular arrhythmias, the mechanisms are variable, the circuits are very difficult to identify and involve healthy and sick tissues. The therapeutic indication is very difficult and incorrect in many occasions. It is possible that, in the future, the study of hereditary arrhythmias could be the basis for a better understanding of these problems.


Band structure and near infrared quantum cutting investigation of GdF3:Yb3+, Ln3+ (Ln = Ho, Tm, Er, Pr, Tb) nanoparticles.
A series of GdF3:Yb(3+), Ln(3+) (Ln = Ho, Tm, Er, Pr, Tb) nanoparticles were prepared by a simple and green hydrothermal method without any additives, which exhibited an ellipse-like shape with a diameter of 63 nm and a length of 101 nm on average. To prove the existence (or not) of near infrared quantum cutting for various lanthanide ion couples (Yb/Ho; Yb/Tm; Yb/Er; Yb/Pr; Yb/Tb) in one host lattice (GdF3), the measured luminescence spectra and decay lifetimes of these samples were analysed. Furthermore, the band structures and densities of state of GdF3 were also studied with the help of first-principles calculations, and the direct band gap of GdF3 was estimated to be 7.443 eV wide. Based on this, detailed processes and possible mechanisms of the luminescence phenomena are discussed. GdF3:Yb(3+), Ln(3+) nanoparticles may have potential applications in modifying the solar spectrum to enhance the efficiency of silicon solar cells.


Seeing is Believing? Evidence from Property Prices in Inundated Areas.
We use hedonic property models to estimate the changes in implicit flood risk premium following a large flood event. Previous studies have used flood hazard maps to proxy flood risk. In addition to knowing whether a property lies in the floodplain, we use a unique data set with the flood inundation map. We find that the price discount for properties in the inundated area is substantially larger than in comparable properties in the floodplain that did not get inundated. This suggests that, in addition to capturing an information effect, the larger discount in inundated properties reflects potential uninsurable flood damages, and supports a hypothesis that homeowners respond better to what they have visualized ("seeing is believing").


A retrospective study of predictive factors for effective aripiprazole augmentation of antidepressant therapy in treatment-resistant depression.
Several studies have evaluated the efficacy and tolerability of aripiprazole for augmentation of antidepressant therapy for treatment-resistant depression (TRD). Here, we investigated the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder and the clinical predictors of treatment efficacy in a Japanese population. Eighty-five depressed Japanese patients who underwent aripiprazole augmentation therapy after failing to respond satisfactorily to antidepressant monotherapy were included in the study. Treatment responses were evaluated based on Clinical Global Impression Improvement scores assessed 8 weeks after initiation of aripiprazole administration. We compared demographic and diagnostic variables, psychiatric medication variables, and clinical variables between remission and nonremission groups. The aripiprazole augmentation remission rate was 36.5%. Multiple logistic regression analysis indicated that aripiprazole augmentation was significantly more effective for bipolar depression than for major depressive disorder, and both absence of comorbid anxiety disorders and current episode duration >3 months were significantly associated with the efficacy of aripiprazole augmentation. Polarity of depression, comorbidity of anxiety disorders, and current episode duration may predict the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder. Among them, comorbidity of anxiety disorders was significantly related to the efficacy for TRD including only major depressive disorder. Additional studies are needed to examine the association between the efficacy of aripiprazole augmentation and bipolarity, and these findings should be validated further in a prospective study.


Molecular diagnosis of CMV infection in fetal aborted tissues in the region of Thrace.
To detect the incidence of CMV infection in spontaneous abortion in Thrace. Genetic material from 143 fetuses aged from 11 to 39 weeks was examined. The material originated from various regions of Thrace. All fetuses and the respective placentas underwent routine histopathology. DNA was isolated from sections of paraffinized tissues. Detection of CMV in the DNA genomic samples was performed using a commercial PCR-based detection kit. From the 143 fetuses that were examined, two were found to be CMV positive. Pathological findings related to inflammatory corruptions were observed in the placentas of 97 embryos, including the CMV infected ones. This study indicates CMV-DNA infection in 1.4% of aborted fetuses. CMV infection incidence in aborted fetuses is similar to this reported in other European regions. The molecular technique of PCR applied on paraffin-embedded biopsy material is proven to be an accurate, valid and fast method for investigating the CMV infection in aborted fetuses.


Life span of patients with Eisenmenger syndrome is not superior to that of patients with other causes of pulmonary hypertension.
Patients with Eisenmenger syndrome (ES) carry a better prognosis from diagnosis than patients with other causes of pulmonary hypertension (PH), but their life span has not yet been clarified. To clarify both survival from diagnosis and life span in ES, and in closed shunt with pulmonary arterial hypertension (PAH), as compared with other causes of PH. Data on all adult patients with PH attending our centre over the past decade was collected. Outcome was defined as death or transplantation. We studied 149 patients, including 30 (20%) patients with ES and 12 (8%) patients with closed shunt with PAH. Median age at diagnosis was lower for patients with ES and closed-shunt with PAH compared to patients with other causes of PH (P<0.001 and P=0.008 respectively). Median follow-up was 4.25 years. Survival from diagnosis was longer in ES compared to other causes of PH (logrank; P=0.02) and similar between closed-shunt with PAH and other causes of PH (logrank; P=0.3). Survival rates at 3, 6 and 9 years from diagnosis were: 73%, 50% and 47% for ES, 75%, 25% and 0% for closed-shunt with PAH, 65%, 23% and 9% for other causes of PH. Life span was similar in those three groups (logrank; P=0.2 and P=0.7, respectively). Life span is similar in patients with ES, with a closed-shunt associated with PAH, and in patients with other causes of PH.


Pathways to women's crime: differences among women convicted of drug, violence and fraud offenses.
The current study was conducted on 60 Israeli female inmates. Our aim was to examine the differences among women convicted for drug, violence, and fraud offenses by socio-demographic variables and self-control and aggression levels. Results revealed that the drug group was characterized by measures attributed to chronic delinquency, and the fraud group was found to fit the pathway to low crime. At the same time, the violence group was not characterized by any of these patterns. The findings were discussed in relation to their theoretical contribution and applicability.


Economic Value Estimation of the Natural Heritage of the Tatra National Park.
The aim of the study is to determine the economic value of the Tatra National Park. The willingness to pay approximation was used. Additionally, a questionnaire survey was applied in order to collect data. It contained a hypothetical event, and respondents expressed their willingness to pay an annual entry fee to the Tatra National Park in exchange for a guarantee of stopping the interference to its integrity. The total number of respondents was 921. The results show that the income level has a positive impact on respondents' willingness to pay for entry to the Tatra National Park. With the increase of fee, the willingness to pay for entry to the Tatra National Park decreased by 2.2% for every additional price increase. The resulting value of the Tatra National Park, with the limits of the presented research mentioned in the paper, is approximately 17.5 million €.


MRI assessment of cardiac tumours: part 1, multiparametric imaging protocols and spectrum of appearances of histologically benign lesions.
Cardiac magnetic resonance imaging (MRI) is the reference standard technique for assessment and characterization of a suspected cardiac tumour. It provides an unrestricted field of view, high temporal resolution and non-invasive tissue characterization based on multi-parametric assessment of the chemical micro-environment. MRI exploits differences in hydrogen proton density in conjunction with T1 and T2 relaxation properties of different tissues to help differentiation normal from abnormal and benign from malignant lesions. In this article we review specific cardiac MRI techniques, tumour protocol design and the appearance of the spectrum of histologically benign tumours.