Diversity of Extremely Halophilic Archaeal and Bacterial Communities from Commercial Salts.
Salting is one of the oldest food preservation techniques. However, salt is also the source of living halophilic microorganisms that may affect human health. In order to determine the microbial communities of commercial salts, an investigation were done using amplicon sequencing approach in four commercial salts: Ethiopian Afdera salt (EAS), Ethiopian rock salt (ERS), Korean Jangpan salt (KJS), and Korean Topan salt (KTS). Using domain-specific primers, a region of the 16S rRNA gene was amplified and sequenced using a Roche 454 instrument. The results indicated that these microbial communities contained 48.22-61.4% Bacteria, 37.72-51.26% Archaea, 0.51-0.86% Eukarya, and 0.005-0.009% unclassified reads. Among bacteria, the communities in these salts were dominated by the phyla Proteobacteria, Bacteroidetes, Actinobacteria, and Firmicutes. Of the archaea, 91.58% belonged to the class Halobacteria, whereas the remaining 7.58, 0.83, and 0.01% were Nanoarchaea, Methanobacteria, and Thermococci, respectively. This comparison of microbial diversity in salts from two countries showed the presence of many archaeal and bacterial genera that occurred in salt samples from one country but not the other. The bacterial genera Enterobacter and Halovibrio were found only in Korean and Ethiopian salts, respectively. This study indicated the occurrence and diversity of halophilic bacteria and archaea in commercial salts that could be important in the gastrointestinal tract after ingestion.


How youth-serving organizations enable acquaintance molesters.
In recent years, some of the country's most prominent institutions have been ensnared in child sex abuse scandals. While each abuse incident features its own particular circumstances, institutions that have been the subject of these scandals have displayed similar patterns of organizational behavior that allowed molesting to occur and molesters to escape accountability. We can learn from those patterns to better understand and combat acquaintance molestation in youth-serving organizations. Although sex abuse is an inherent risk in youth work, American youth-serving organizations have responded to this risk largely on a case-by-case basis after abuse incidents have been revealed, rather than through proactive strategies to reduce the risk of abuse and to respond effectively to allegations. An examination of abuse scandals reveals common patterns of behavior among paid and volunteer staff in organizations that did not enact comprehensive, proactive strategies: Faith in the organiation blinded staff to the liklihood of abuse; organizations kept workers ignorant about the extent of the abuse problem; when abuse accusations arose, staff gave the benefit of the doubt to the adult; when abuse accusations were confirmed, staffers did not know how to respond; and not knowing how to resopnd, staff prioritized the protection of the organization. As a result, child molesters have been falsely exonerated or not held accountable, abused children have been disbelieved, and abuse has continued. These organizations inadvertently achieved the opposite of their missions: They enabled child molesters at the expense of children.


Preliminary characterization of the transcriptional and translational products of the Saccharomyces cerevisiae cell division cycle gene CDC28.
The CDC28 gene was subcloned from a plasmid containing a 6.5-kilobase-pair segment of Saccharomyces cerevisiae DNA YRp7(CDC28-3) by partial digestion with Sau3A and insertion of the resulting fragments into the BamHI sites of YRp7 and pRC1. Recombinant plasmids were obtained containing inserts of 4.4 and 3.1 kilobase pairs which were capable of complementing a cdc28(ts) mutation. R-loop analysis indicated that each yeast insert contained two RNA coding regions of about 0.8 and 1.0 kilobase pairs, respectively. In vitro mutagenesis experiments suggested that the smaller coding region corresponded to the CDC28 gene. When cellular polyadenylic acid-containing RNA, separated by agarose gel electrophoresis after denaturation with glyoxal and transferred to nitrocellulose membrane, was reacted with labeled DNA from the smaller coding region, and RNA species of about 1 kilobase in length was detected. Presumably, the discrepancy in size between the R-loop and electrophoretic determinations is due to a segment of polyadenylic acid which is excluded from the R-loops. By using hybridization of the histone H2B mRNAs to an appropriate probe as a previously determined standards, it was possible to estimate the number of CDC28 mRNA copies per haploid cell as between 6 and 12 molecules. Hybrid release translation performed on the CDC29 mRNA directed the synthesis of a polypeptide of 27,000 daltons, as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. This polypeptide was not synthesized when mRNA prepared from a cdc28 nonsense mutant was translated in a parallel fashion. However, if the RNA from a cell containing the CDC28 gene on a plasmid maintained at a high copy number was translated, the amount of in vitro product was amplified fivefold.


Six-color time-resolved Förster resonance energy transfer for ultrasensitive multiplexed biosensing.
Simultaneous monitoring of multiple molecular interactions and multiplexed detection of several diagnostic biomarkers at very low concentrations have become important issues in advanced biological and chemical sensing. Here we present an optically multiplexed six-color Förster resonance energy transfer (FRET) biosensor for simultaneous monitoring of five different individual binding events. We combined simultaneous FRET from one Tb complex to five different organic dyes measured in a filter-based time-resolved detection format with a sophisticated spectral crosstalk correction, which results in very efficient background suppression. The advantages and robustness of the multiplexed FRET sensor were exemplified by analyzing a 15-component lung cancer immunoassay involving 10 different antibodies and five different tumor markers in a single 50 μL human serum sample. The multiplexed biosensor offers clinically relevant detection limits in the low picomolar (ng/mL) concentration range for all five markers, thus providing an effective early screening tool for lung cancer with the possibility of distinguishing small-cell from non-small-cell lung carcinoma. This novel technology will open new doors for multiple biomarker diagnostics as well as multiplexed real-time imaging and spectroscopy.


3D Characterization of Sponge Cake as Affected by Freezing Conditions Using Synchrotron X-ray Microtomography at Negative Temperature.
In this study, the microstructural evolution of a non-reactive porous model food (sponge cake) during freezing was investigated. Sponge cake samples were frozen at two different rates: slow freezing (0.3 °C min-1) and fast freezing (17.2 °C min-1). Synchrotron X-ray microtomography (µ-CT) and cryo-scanning electron microscopy (Cryo-SEM) were used to visualize and analyze the microstructure features. The samples were scanned before and after freezing using a specific thermostated cell (CellStat) combined with the synchrotron beamline. Cryo-SEM and 3D µ-CT image visualization allowed a qualitative analysis of the ice formation and location in the porous structure. An image analysis method based on grey level was used to segment the three phases of the frozen samples: air, ice and starch. Volume fractions of each phase, ice local thickness and shape characterization were determined and discussed according to the freezing rates.


Antibiotic resistance of microbial strains isolated from Korean acne patients.
Over several decades, topical and systemic antibiotics have been the mainstay of treatment for acne vulgaris. The widespread and long-term use of antibiotics in the treatment of acne has resulted in the spread of resistant bacterial strains and treatment failure. We aimed to examine the bacteriology of acne vulgaris and to evaluate its susceptibility to the antibiotics widely used for acne in Korea. We examined the species of bacteria aerobically and anaerobically isolated from 100 Korean acne patients. Among the bacteria isolated, Staphylococcus epidermidis (36 patients) was the most common, followed by Propionibacterium acnes (30 patients). Eleven strains of P. acnes (36.7%) and 25 strains of S. epidermidis (69.4%) were resistant to one or other of the antibiotics tested. A higher proportion of P. acnes isolates were resistant to clindamycin (30%) and erythromycin (26.7%), than to any other antibiotics tested (P = 0.0003). Some S. epidermidis isolates were resistant to tetracycline and doxycycline in addition to clindamycin and erythromycin. In the previous studies, few strains of P. acnes were found to be resistant to any of the antibiotics, but this study shows that antibiotic-resistant strains have been increasing in Korea acne patients.


Heterogeneity in utilization of N-glycosylation sites Asn624 and Asn138 in human lactoferrin: a study with glycosylation-site mutants.
Human lactoferrin (hLF) is a glycoprotein involved in the host defence against infection and excessive inflammation. Our objective was to determine to what extent each of the three sequons for N-linked glycosylation in hLF is actually used. Human kidney-derived 293(S) cell lines expressing recombinant hLF (rhLF) or glycosylation-site mutants were produced. The mutations involved replacement of asparagine residues with glutamine at one or more sequons for N-glycosylation (Asn138, Asn479 and Asn624). Comparative SDS/PAGE analyses of rhLF, mutated rhLF and human-milk-derived (natural) hLF led us to propose that glycosylation of hLF occurs at two sites (at Asn138 and Asn479) in approx. 85% of all hLF molecules. Glycosylation at a single site (Asn479) or at all three sites occurs in approx, 5% and 9% of hLF respectively. The extent of glycosylation at Asn624 was increased to approx. 29% and 40% of Asn479 and Asn138/479 mutant molecules respectively, which indicates that glycosylation at Asn624 in natural hLF might be limited by glycosylation at Asn479. The presence in supernatant of unglycosylated hLF (approx. 60% of the total) after mutations of Asn138 and Asn479 suggests that glycosylation of hLF is not an absolute requirement for its secretion. The pronounced degradation of unglycosylated hLF in supernatant after mutation at all three glycosylation sites (Asn138/479/624 mutant) but not after mutation at both Asn138 and Asn479 suggests that an altered conformation rather than the lack of glycosylation has rendered the Asn138/479/624 mutant susceptible to intra- and/or extra-cellular degradation.


Novel Genetic Constructs for Production of Recombinant HTLV-1/2 Antigens and Evaluation of Their Reactivity to Plasma Samples from HTLV-1-Infected Patients.
Human T-cell leukemia virus type 1 (HTLV-1) can cause life-threatening diseases for which there are no effective treatments. Prevention of HTLV-1 infection requires massive testing of pregnant women, blood for transfusion, and organs for transplantation, as well as safe sex. In this context, serological assays are widely used for monitoring HTLV-1 infections. Despite the necessity for recombinant antigens to compose serological tests, there is little information available on procedures to produce recombinant HTLV-1/2 antigens for serological diagnostic purposes. In this work, we tested a series of genetic constructions to select those more amenable for production in bacterial systems. To overcome the constraints in expressing sections of viral envelope proteins in bacteria, we have used the p24 segment of the gag protein as a scaffold to display the immunogenic regions of gp46 and gp21. Nine recombinant antigenic proteins derived from HTLV-1 and five derived from HTLV-2 were successfully purified. The HTLV-1 antigens showed high efficiency in discriminating HTLV-positive samples from HTLV-negative samples using enzyme-linked immunosorbent assays. Interestingly, HTLV-1-positive samples showed a high level of cross-reaction with HTLV-2 antigens. This finding is explained by the high sequence conservation between the structural proteins of these two highly related viruses. In summary, the results presented in this work provide a detailed description of the methods used to produce recombinant HTLV-1 and HTLV-2 antigens, and they demonstrate that the HTLV-1 antigens show strong potential for serological diagnosis of HTLV-1 infections.


Chemical suppression of an oncogenic splicing variant of AIMP2 induces tumour regression.
AIMP2 (aminoacyl-tRNA synthetase-interacting multifunctional protein 2) is a potent tumour suppressor that induces apoptosis in response to various oncogenic signals. AIMP2-DX2, an exon2-deleted splicing variant of AIMP2, is up-regulated in lung cancer and competitively suppresses the pro-apoptotic activity of AIMP2, resulting in tumorigenesis. In the present study we report that BC-DXI01, a synthetic compound, specifically reduces the cellular levels of AIMP2-DX2 through selective degradation of the AIMP2-DX2 mRNA transcript. We found that BC-DXI01-mediated cell death positively correlates with AIMP2-DX2 expression in the lung cancer cell lines tested. Administration of BC-DXI01 in a AIMP2-DX2-driven tumour xenograft mice model led to reduced tumour sizes and volumes of up to 60% in comparison with vehicle-treated mice group, consistent with decreases in AIMP2-DX2 transcript and protein levels. Taken together, our findings suggest that tumorigenic activity of AIMP2-DX2 can be controlled by the small chemical BC-DXI01, which can selectively suppress the AIMP2-DX2 mRNA transcript.


[Carcinosarcoma of the breast a rare entity with fatal prognosis. One case report].
breast metaplastic carcinomas are a heterogeneous group of neoplasms that exhibit a poor prognosis compared with invasive ductal carcinoma. Correspond less than 1% of all malignant neoplasms of the mammary gland. They usually present as high-grade tumors with a lower rate of lymph node metastases and decreased expression of estrogen and progesterone receptors and Her2 and increased expression of Her1 and Ki-67. we report a 52 year old woman with a breast carcinosarcoma presented with a left breast tumor fungated, ulcerated, polypoid and 18 cm in major diameter with lymph node metastases at diagnosis. She received multimodal management with neoadjuvant chemotherapy, followed by mastectomy and adjuvant chemotherapy; she presented progression of the disease with lung metastases and local massive recurrence, eventually died from complications associated to the disease. metaplastic carcinomas of the breast are extremely rare entities. Due the nature of disease and presentation, the prognosis is poor in these patients. There are several histologic subtypes based on studies of hematoxylin and eosin and immunohistochemical stains. It requires multimodal therapy (surgery, radiotherapy and chemotherapy) for best results.


The interrelationships between electrical stimulation, the environment surrounding the vascular endothelial cells of the skin, and the role of nitric oxide in mediating the blood flow response to electrical stimulation.
Electrical stimulation (ES) is a commonly used modality in physical therapy for treating wounds such as diabetic ulcers and pressure sores but the mechanism of its effect on skin blood flow (BF) has not been determined. Ten subjects were examined during ES of the skin above the quadriceps muscle with biphasic sine wave stimulation at a frequency of 30 Hertz, pulse width 250 microseconds. BF was measured between the electrodes with a Laser Doppler Flow meter. In one series of experiments, N-Nitro-L-Arginine Methyl Ester (L-NAME) was infused to determine the effect of blocking nitric oxide production on the blood flow response to ES. In another series, acetylcholine and epinephrine were infused to determine the effects of the initial blood flow prior to stimulation on the magnitude of the BF response to ES. The apparent mechanism of the increase in blood flow during electrical stimulation seems to be mediated by nitric oxide since the increase in blood flow as a result of stimulation was blocked by L-NAME. Modulation of the vasoconstrictor or vasodilator tone of the skin blood vessels altered the magnitude of the BF response to electrical stimulation; epinephrine blocked the response and acetylcholine increased the response. The BF response to ES is caused by NO and can be modulated by changing the environment of the vascular endothelial cell.


Transpososomes: stable protein-DNA complexes involved in the in vitro transposition of bacteriophage Mu DNA.
We report that two types of stable protein-DNA complexes, or transpososomes, are generated in vitro during the Mu DNA strand transfer reaction. The Type 1 complex is an intermediate in the reaction. Its formation requires a supercoiled mini-Mu donor plasmid, Mu A and HU protein, and Mg2+. In the Type 1 complex the two ends of Mu are held together, creating a figure eight-shaped molecule with two independent topological domains; the Mu sequences remain supercoiled while the vector DNA is relaxed because of nicking. In the presence of Mu B protein, ATP, target DNA, and Mg2+, the Type 1 complex is converted into the protein-associated product of the strand transfer reaction. In this Type 2 complex, the target DNA has been joined to the Mu DNA ends held in the synaptic complex at the center of the figure eight. Supercoils are not required for the latter reaction.


Native Electron Capture Dissociation Maps to Iron-Binding Channels in Horse Spleen Ferritin.
Native electron capture dissociation (NECD) is a process during which proteins undergo fragmentation similar to that from radical dissociation methods, but without the addition of exogenous electrons. However, after three initial reports of NECD from the cytochrome c dimer complex, no further evidence of the effect has been published. Here, we report NECD behavior from horse spleen ferritin, a ∼490 kDa protein complex ∼20-fold larger than the previously studied cytochrome c dimer. Application of front-end infrared excitation (FIRE) in conjunction with low- and high-m/z quadrupole isolation and collisionally activated dissociation (CAD) provides new insights into the NECD mechanism. Additionally, activation of the intact complex in either the electrospray droplet or the gas phase produced c-type fragment ions. Similar to the previously reported results on cytochrome c, these fragment ions form near residues known to interact with iron atoms in solution. By mapping the location of backbone cleavages associated with c-type ions onto the crystal structure, we are able to characterize two distinct iron binding channels that facilitate iron ion transport into the core of the complex. The resulting pathways are in good agreement with previously reported results for iron binding sites in mammalian ferritin.


Age segregation of adolescents in and out of school.
In a naturalistic study of age segregation during adolescence, 403 adolescents making up 153 separate groups were observed in three high schools and seven out-of-school settings. Age segregation was extensive, especially in school, among older adolescents in same-sex groups of friends. More mixed-age association was observed out of school among younger adolescents who were in mixed-sex groups containing relatives. Adolescents were most often observed with friends who were other adolescents, next with adults, and least frequently observed with children. Parents, particularly fathers, were rarely present. It was suggested that age segregation during adolescence is the result of a lack of contact with relatives.


Photo-cross-linking approach to engineering small tyrosine-containing peptide hydrogels with enhanced mechanical stability.
Peptide-based supramolecular hydrogels have been extensively explored in biomaterials owing to their unique bioactive, stimulus-responsive, and biocompatible features. However, peptide-based hydrogels often have low mechanical stability with storage moduli of 10-1000 Pa. They are susceptible to mechanical destruction and solvent erosion, greatly hindering their practical application. Here, we present a photo-cross-linking strategy to enhance the mechanical stability of a peptide-based hydrogel by 10(4)-fold with a storage modulus of ~100 kPa, which is one of the highest reported so far for hydrogels made of small peptide molecules. This method is based on the ruthenium-complex-catalyzed conversion of tyrosine to dityrosine upon light irradiation. The reinforcement of the hydrogel through photo-cross-linking can be achieved within 2 min thanks to the fast reaction kinetics. The enhancement of the mechanical stability was due to the formation of a densely entangled fibrous network of peptide dimers through a dityrosine linkage. We showed that in order to implement this method successfully, the peptide sequence should be rationally designed to avoid the cross talk between self-assembly and cross-linking. This method is convenient and versatile for the enhancement of the mechanical stability of tyrosine-containing peptide-based hydrogels. We anticipate that the photo-cross-linked supramolecular hydrogels with much improved mechanical stability will find broad applications in tissue engineering and drug controlled release.


Dynamic weighting of feature dimensions in visual search: behavioral and psychophysiological evidence.
Dimension-based accounts of visual search and selection have significantly contributed to the understanding of the cognitive mechanisms of attention. Extensions of the original approach assuming the existence of dimension-based feature contrast saliency signals that govern the allocation of focal attention have recently been employed to explain the spatial and temporal dynamics of the relative strengths of saliency representations. Here we review behavioral and neurophysiological findings providing evidence for the dynamic trial-by-trial weighting of feature dimensions in a variety of visual search tasks. The examination of the effects of feature and dimension-based inter-trial transitions in feature detection tasks shows that search performance is affected by the change of target-defining dimensions, but not features. The use of the redundant-signals paradigm shows that feature contrast saliency signals are integrated at a pre-selective processing stage. The comparison of feature detection and compound search tasks suggests that the relative significance of dimension-dependent and dimension-independent saliency representations is task-contingent. Empirical findings that explain reduced dimension-based effects in compound search tasks are discussed. Psychophysiological evidence is presented that confirms the assumption that the locus of the effects of feature dimension changes is perceptual pre-selective rather than post-selective response-based. Behavioral and psychophysiological results are considered within in the framework of the dimension weighting account of selective visual attention.


Regional cerebral blood flow, glucose metabolism, protein synthesis, serum protein extravasation, and content of biochemical substrates in stroke-prone spontaneously hypertensive rats.
Stroke-prone spontaneously hypertensive rats with arterial blood pressure above 210 mmHg were taken for the present study after appearance of neurological symptoms. Regional cerebral blood flow, glucose metabolism, and protein synthesis rate were evaluated on the same brain section by means of triple-labelled autoradiographic techniques. Consecutive sections were used in the pictorial presentation of glucose, ATP, and serum protein extravasation. In addition, NADH-fluorescence was recorded. Two different patterns of hypertension-induced brain lesions could be distinguished: in two animals sharply demarcated cysts were visible in the cortical grey matter. In these animals no regional inhomogeneities of flow and metabolism were present remote from the infarct. In contrast, in three animals cysts were located in the white matter, leading to pronounced hemodynamic and metabolic disturbances throughout the brain. It is concluded that edema-induced brain swelling was the main cause for reduction in blood flow and metabolism.


[Relationship between the pineal body and the hypothalamo-hypophyseal system. V. Melatonin inhibition of the gonadotropic activity of the hypothalamo-hypophyseal system].
Effect of melatonin on the gonadotropic activity of the hypothalamo-hypophysial system was investigated. The following proved to occur under the action of melatonin in sexually immature female rats: reduction of the spontaneous activity of luteinizing hormone (LH), of the LH content in the hypophysis, and of the endogenous luliberin stores in the arcuate nucleus; response of the hypophysis to the exogenous luliberin was also diminished. Single administration of low doses (from 1 to 100 micrograms) of melatonin was accompanied by reduction of cAMP content in the hypophysis and the hypothalamus. LH, luliberin and cAMP were determined by radiochemical methods. The results obtained indicated that the inhibitory influence of the pineal gland on the reproductive system was realized by melatonin, its hormone, through the hypothalamo-hypophysial complex.


The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer.
The peritoneum is one of the most frequent metastatic sites in pancreatic cancer patients, and peritoneal dissemination makes this disease refractory due to aggressive progression and chemoresistance. Although the role of the tumor microenvironment in cancer development is recognized, the correlation between the peritoneal environment and refractoriness of peritoneal dissemination remains unclear. The intraperitoneal tumor-microenvironment and its potential role in the progression of peritoneal dissemination and chemo-refractoriness, focusing especially on macrophages, were investigated. Peritoneal washes were obtained from pancreatic cancer patients, and cellular components were subjected to immunofluorescence assays. The effects of macrophages induced from monocytic THP-1 cells on pancreatic cancer cells were examined in co-culture conditions. The in vivo effects of macrophages on tumor growth and chemo-sensitivity were investigated by subcutaneously or intraperitoneally co-injecting cancer cells with macrophages into mice. CD204-positive macrophages were present along with cancer cells in the peritoneal washes. In in vitro co-culture, tumor-associated macrophages affected pancreatic cancer cells, induced the epithelial-to-mesenchymal transition (EMT), and made them more resistant to chemotherapeutic agents. M2 macrophages promoted growth of both subcutaneous tumors and peritoneal dissemination in mice. Furthermore, co-inoculation of M2 macrophages conferred chemoresistance in the peritoneal dissemination mouse model, which significantly shortened their survival. Intraperitoneal tumor-associated macrophages potentially play an important role in promotion of peritoneal dissemination and chemoresistance of pancreatic cancer via EMT induction.


Demyelinating disease of Schilder type in three young South African children: dramatic response to corticosteroids.
Three young children with the Schilder variant of multiple sclerosis were seen within a 3-year period at our hospital. The diagnosis was made on the basis of the typical (but not pathognomonic) clinical and magnetic resonance imaging (MRI) findings after eliminating other demyelinating and post-infectious disorders of the central nervous system. All three patients were treated with prednisone (2 mg/kg/day), which resulted in complete recovery in one patient and mild and moderate residual hemiparesis in the two other patients, respectively. Corticosteroid therapy was continued until the patients' neurologic condition normalized or no further clinical improvement occurred. No relapses were seen after discontinuation of corticosteroid treatment. Computed tomographic (CT) scan and MRI findings after completion of corticosteroid therapy were equally dramatic and corresponded with the clinical improvement. A strongly positive tuberculin skin test and a positive history of contact with adult tuberculosis in two of our patients raise the possibility of a connection between tuberculosis and Schilder's disease.


Translation and processing of mouse hepatitis virus virion RNA in a cell-free system.
The first event after infection with mouse hepatitis virus strain A59 (MHV-A59) is presumed to be the synthesis of an RNA-dependent RNA polymerase from the input genomic RNA. The synthesis and processing of this putative polymerase protein was studied in a cell-free translation system utilizing 60S RNA from MHV-A59 virions. The polypeptide products of this reaction included two major species of 220 and 28 kilodaltons. Kinetics experiments indicated that both p220 and p28 appeared after 60 min of incubation and that protein p28 was synthesized initially as the N-terminal portion of a larger precursor protein. When the cell-free translation products were labeled with N-formyl[35S]methionyl-tRNAi, p28 was the predominant radioactive product, confirming its N-terminal location within a precursor protein. Translation in the presence of the protease inhibitors leupeptin and ZnCl2 resulted in the disappearance of p28 and p220 and the appearance of a new protein, p250. This product, which approached the maximal size predicted for a protein synthesized from genomic RNA, was not routinely detected in the absence of inhibitors even under conditions which optimized the translation reaction for elongation of proteins. Subsequent chelation of ZnCl2 resulted in the partial cleavage of the precursor protein and the reappearance of p28. One-dimensional peptide mapping with Staphylococcus aureus V-8 protease confirmed the precursor-product relationship of p250 and p28. The results show that MHV virion RNA, like many other viral RNAs, is translated into a large polyprotein, which is cleaved soon after synthesis into smaller, presumably functional proteins. This is in marked contrast to the synthesis of other MHV proteins, in which minimal proteolytic processing occurs.


Screening for osteopenia and osteoporosis: selection by body composition.
There is a great need for simple means of identifying persons at low risk of developing osteoporosis, in order to exclude them from screening with bone mineral measurements, since this procedure is too expensive and time-consuming for general use in the unselected population. We have determined the relationships between body measure (weight, height, body mass index, lean tissue mass, fat mass, waist-to-hip ratio) and bone mineral density (BMD) in 175 women of ages 28-74 years in a cross-sectional study in a county in central Sweden. Dual-energy X-ray absorptiometry was performed at three sites: total body, L2-4 region of lumbar spine, and neck region of the proximal femur. Using multiple linear regression models, the relationship between the dependent variable, BMD, and each of the body measures was determined, with adjustment for confounding factors. Weight alone, in a multivariate model, explained 28%, 21% and 15% of the variance in BMD of total body, at the lumbar spine and at the femoral neck according to these models. The WHO definition of osteopenia was used to dichotomize BMD, which made it possible, in multivariate logistic regression models, to estimate the risk of osteopenia with different body measures categorized into tertiles. Weight of over 71 kg was associated with a very low risk of being osteopenic compared with women weighing less than 64 kg, with odds ratios (OR) of 0.01 (95% confidence interval (CI) 0.00-0.09), 0.06 (CI 0.02-0.22) and 0.13 (CI 0.04-0.42) for osteopenia of total body, lumbar spine and femoral neck, respectively. Furthermore a sensitivity/specificity analysis revealed that, in this population, a woman weighing over 70 kg is not likely to have osteoporosis. Test specifics of a weight under 70 kg for osteoporosis (BMD less than 2.5 SD compared with normal young women) of femoral neck among the postmenopausal women showed a sensitivity of 0.94, a specificity of 0.36, positive predictive value (PPV) of 0.21, and negative predictive value (NPV) of 0.97. Thus, exclusion of the 33% of women with the highest weight meant only that 3% of osteoporotic cases were missed. The corresponding figures for lumbar spine were sensitivity 0.89, specificity 0.38, PPV 0.33, and NPV 0.91. All women who were defined as being osteoporotic of total body weighed under 62 kg. When the intention was to identify those with osteopenia of total body among the postmenopausal women we attained a sensitivity of 0.92 and a NPV of 0.91 for a weight under 70 kg, whereas we found that weight could not be used as an exclusion criterion for osteopenia of femoral neck and lumbar spine. Our data thus indicate that weight could be used to exclude women from a screening program for postmenopausal osteoporosis.


Incidence of New-Onset and Worsening Heart Failure Before and After the COVID-19 Epidemic Lockdown in Denmark: A Nationwide Cohort Study.
The Danish government ordered a public lockdown on March 12, 2020, because of the coronavirus disease 2019 (COVID-19) pandemic. We investigated the immediate consequences of such a lockdown for patients with heart failure (HF). Using the Danish nationwide administrative databases, we investigated the incidence of new-onset HF and hospitalizations for worsening HF before and after the lockdown (January 1 to March 11 versus March 12 to March 31) in 2020 versus 2019. We also investigated the mortality for all patients with HF and in COVID-19-infected patients with HF. Rates of new-onset HF between January 1 and March 11 were comparable for 2020 and 2019 (1.83 versus 1.78 per 10 000 person-years; P=0.19), while hospitalizations for worsening HF were slightly higher in 2020 versus 2019 (1.04 versus 0.93 per 1000 person-years; P=0.02). In the lockdown period, rates of new-onset HF diagnoses (1.26 versus 2.25 per 1000 person-years) and of hospitalizations for worsening HF (0.63 versus 0.99 per 1000 person-years) were significantly lower in 2020 versus 2019 (P for both, <0.0001). Mortality was similar before and after the national lockdown for the population with HF. We observed 90 HF patients with diagnosed COVID-19 infection, of whom 37% (95% CI, 23%-50%) died within 15 days. The number of patients hospitalized with worsening HF or diagnosed with new-onset HF was markedly reduced after lockdown but has not yet impacted mortality in HF patients at a population-based level. However, these data raise concerns for a potential undertreatment of HF currently that may impact prognosis in the longer term.


Are yeasts in vaginal smears intracellular or extracellular?
Using light microscopic cytodiagnosis the only thing that can be said about the position of the yeast cells in relation to the epithelial cells is that the epithelial cells and the parasite are very close to one another. It is not possible to say whether both elements are only temporarily projected above one another or in direct contact. This question can only be answered unequivocally with the aid of the electron microscope. It is possible to verify that the yeast cells, despite their size, are able to invade intact epithelial cells and are capable of reproduction within these same cells.


Extending the "Open-Closed Principle" to Automated Algorithm Configuration.
Metaheuristics are an effective and diverse class of optimization algorithms: a means of obtaining solutions of acceptable quality for otherwise intractable problems. The selection, construction, and configuration of a metaheuristic for a given problem has historically been a manually intensive process based on experience, experimentation, and reasoning by metaphor. More recently, there has been interest in automating the process of algorithm configuration. In this article, we identify shared state as an inhibitor of progress for such automation. To solve this problem, we introduce the Automated Open-Closed Principle (AOCP), which stipulates design requirements for unintrusive reuse of algorithm frameworks and automated assembly of algorithms from an extensible palette of components. We demonstrate how the AOCP enables a greater degree of automation than previously possible via an example implementation.


[Pathological examination of breast biopsy specimens].
No differences for long-term disease free survival could be found between breast conserving surgery and mastectomy. Most importantly is the fact that this therapy presents a significantly higher risk for local recurrence. The characterisation of this risk is one of the most important things to do. These findings result in a widespread change in treatment of breast cancer patients. Consequently an increase in interdisciplinary working between radiologists, surgeons and pathologists could be found. Histological examinations are necessary for diagnosis and exactly evaluation of the tumor extension. Microscopic evaluation of the resection margin is of most important interest, because there is a direct connection between local recurrence and tumor infiltration of the resection margin. We performed our investigations by the use of a standardized complete embedding method with the possibility of three-dimensional reconstruction, on a cohort of 280 patients. Additionally this method allowed the detection of all relevant findings on one hand and on the other hand an evaluation of all resection margins. Our results showed a breast conserving therapy including tumor free margins was performed in 67% of the patients. But there was a second resection necessary in 57% of the cases. An extensive tumor distribution as the detection of multifocal tumor spread was the reason for mastectomy in 33%. Our findings point out the necessarily of the histological examination in the line of the complete embedding method of the breast biopsy material in order to analyse the tumor including resection margin evaluation.


Brugada electrocardiographic pattern induced by fever.
Brugada syndrome is a major cause of sudden death in young adults. Fever has been described to induce a Brugada-type electrocardiogram in asymptomatic patients with a negative family history, to disclose Brugada syndrome and to increase the risk of death and induce T wave alternans in patients with diagnosed Brugada syndrome. Risk stratification is challenging and demands a careful evaluation. Here we present 2 case reports and review the literature.


Genetic Characterization of a Stable F' lac Plasmid.
A mutant F' plasmid has been isolated in a strain of Salmonella typhimurium harboring F(ts114)lac. This mutant, designated FlacS, exhibits unique genetic stability in strains of S. typhimurium and Escherichia coli. It shows no thermolability and is lost at frequencies of 20 to 100 times less than the wild-type F'lac (F42) in the same genetic backgrounds. The FlacS is also insensitive to conventional plasmid curing agents, whereas both F(ts114)lac and F42 are readily cured. The nature of the mutation(s) conferring stability to the FlacS is unclear, but plasmid linkage has been established. The high frequency of conjugal transfer of the FlacS and its behavior in recombination-deficient strains of S. typhimurium and E. coli argue against its stability being due to stable chromosomal integration. The FlacS is also capable of transferring chromosomal markers in S. typhimurium and E. coli mating systems. No major differences in chromosomal mobilization have been observed among F42, F(ts114)lac, and FlacS donors of either genus.


[Comparison of various methods of surgical hernia repair].
Over the last 15 years, a number of different procedures for hernia repair have been developed. Apart from the open techniques, with or without the use of a prosthetic mesh or mesh plug, endoscopic procedures such as transabdominal preperitoneal (TAPP), and totally endoscopic preperitoneal (TEPP), hernioplasty are now established operations. In the present paper, the common open surgical procedures are compared with the minimally invasive repairs with regard to practicability, postoperative wound pain and complications, mobilization, recurrence rates and cosmesis. In the view of the authors, the standard method for inguinal hernial repair is the open Lichtenstein procedure or the Rutkow patch and plug method.


The nutritional consequences of foraging in primates: the relationship of nutrient intakes to nutrient requirements.
Many studies have examined the proportion of time that primates devote to feeding on various types of food, but relatively little is known about the intake rates associated with each food. However, the nutritional consequences of foraging can only be interpreted by comparing nutrient intakes with estimated nutrient requirements. The energy available to primates from ingested foods will depend both on the composition of the food and the extent to which various constituents, including fibre fractions, are digested. Both human and non-human primates have relatively low requirements for protein as a consequence of slow growth rates, small milk yields and relatively dilute milk. Because the nutrient demands of growth and reproduction are spread out over time, it appears that primates do not need to seek out foods of particularly high nutrient density, except perhaps during weaning. Although food selection in some species of primates appears to be correlated with the protein concentration of foods, it is unlikely that high dietary protein levels are required, at least when foods of balanced amino acid composition (such as leaves) are included in the diet.


Proximate, intermediate, and distal predictors of under-five mortality in Chad: analysis of the 2014-15 Chad demographic and health survey data.
Under-five mortality in Chad reached a minimum value of 119 deaths per 1000 live births in 2018, compared with a maximum of 250 in 1972. Despite this decline in the mortality trend, for every six children in Chad, one dies before the age of five. This study, therefore, investigated the proximate, intermediate, and distal determinants of under-five mortality in Chad. We used data from the 2014-15 Chad's Demographic and Health Survey. Data of 7782 children below 5 years were used for the study. Both descriptive and multivariable hierarchical logistic regression analyses were performed. Statistical significance was declared at p < 0.05. Under-five mortality was found to be 130 deaths per 1000 live births in Chad, with variations across the various population sub-groups. For distal predictors, the likelihood of death was higher in children born in the FChari Baguirmi region (AOR = 3.83, 95% CI: 1.81-8.14). Children whose mothers belonged to the Baguirmi/Barma ethnic group (AOR = 8.04, 95% CI: 1.75-36.99) were more likely to die before the age of five. On the contrary, the likelihood of under-five mortality was low among children born in rural areas (AOR = 0.73, 95% CI: 0.55-0.97). With the intermediate predictors, the likelihood of under-five deaths was higher among children whose mothers had no formal education (AOR = 1.72, 95% CI: 1.06-2.77). Regarding the proximate predictors, the odds of under-five deaths was higher among male children (AOR = 1.03, 95% CI: 1.05-1.63) and first rank children (AOR = 1.58, 95% CI: 1.13-2.21). The study found that the determinants of under-five mortality in Chad are region of residence, place of residence, ethnicity, education, sex of child, and birth rank. These findings show that both socio-economic and proximate factors explain the disparities in under-five mortality in Chad. The identification of these factors can be pivotal towards the design of evidence-based interventions intended to improve child survival. Therefore, improving maternal education while refocusing and re-packaging existing strategies to target selected sub-regional populations with high under-five mortality is urgently required.


[Excessive computer usage in adolescents--results of a psychometric evaluation].
Excessive computer and video game playing among children is being critically discussed from a pedagogic and public health point of view. To date, no reliable data for this phenomenon in Germany exists. In the present study, the excessive usage of computer and video games is seen as a rewarding behavior which can, due to learning mechanisms, become a prominent and inadequate strategy for children to cope with negative emotions like frustration, uneasiness and fears. In the survey, 323 children ranging in age from 11 to 14 years were asked about their video game playing behavior. Criteria for excessive computer and video game playing were developed in accordance with the criteria for dependency and pathological gambling (DSM-IV, ICD-10). Data show that 9.3% (N = 30) of the children fulfill all criteria for excessive computer and video game playing. Furthermore, these children differ from their class mates with respect to watching television, communication patterns, the ability to concentrate in school lectures and the preferred strategies coping with negative emotions. In accordance with findings in studies about substance-related addiction, data suggest that excessive computer and video game players use their excessive rewarding behavior specifically as an inadequate stress coping strategy.


Properties and substrate specificities of the phenylalanyl-transfer-ribonucleic acid synthetases of Aesculus species.
1. Phenylalanyl-tRNA synthetases have been partially purified from cotyledons of seeds of Aesculus californica, which contains 2-amino-4-methylhex-4-enoic acid, and from four other species of Aesculus that do not contain this amino acid. The A. californica preparation was free from other aminoacyl-tRNA synthetases, and the contaminating synthetase activity in preparations from A. hippocastanum was decreased to acceptable limits by conducting assays of pyrophosphate exchange activity in 0.5m-potassium chloride. 2. The phenylalanyl-tRNA synthetase from each species activated 2-amino-4-methylhex-4-enoic acid with K(m) 30-40 times that for phenylalanine. The maximum velocity for 2-amino-4-methylhex-4-enoic acid was only 30% of that for phenylalanine with the A. californica enzyme, but the maximum velocities for the two substrates were identical for the other four species. 3. 2-Amino-4-methylhex-4-enoic acid was not found in the protein of A. californica, so discrimination against this amino acid probably occurs in the step of transfer to tRNA, though subcellular localization, or subsequent steps of protein synthesis could be involved. 4. Crotylglycine, methallylglycine, ethallylglycine, 2-aminohex-4,5-dienoic acid, 2-amino-5-methylhex-4-enoic acid, 2-amino-4-methylhex-4-enoic acid, beta-(thien-2-yl)alanine, beta-(pyrazol-1-yl)alanine, phenylserine and m-fluorophenylalanine were substrates for pyrophosphate exchange catalysed by the phenylalanyl-tRNA synthetases of A. californica or A. hippocastanum. Allylglycine, phenylglycine and 2-amino-4-phenylbutyric acid were inactive.


Temperature and moisture conditions for life in the extreme arid region of the Atacama desert: four years of observations including the El Niño of 1997-1998.
The Atacama along the Pacific Coast of Chile and Peru is one of the driest and possibly oldest deserts in the world. It represents an extreme habitat for life on Earth and is an analog for life in dry conditions on Mars. We report on four years (September 1994-October 1998) of climate and moisture data from the extreme arid region of the Atacama. Our data are focused on understanding moisture sources and their role in creating suitable environments for photosynthetic microorganisms in the desert surface. The average air temperature was 16.5 degrees C and 16.6 degrees C in 1995 and 1996, respectively. The maximum air temperature recorded was 37.9 degrees C, and the minimum was -5.7 degrees C. Annual average sunlight was 336 and 335 W m(-2) in 1995 and 1996, respectively. Winds averaged a few meters per second, with strong föhn winds coming from the west exceeding 12 m s(-1). During our 4 years of observation there was only one significant rain event of 2.3 mm, which occurred near midnight local time. We suggest that this event was a rainout of a heavy fog. It is of interest that the strong El Niño of 1997-1998 brought heavy rainfall to the deserts of Peru, but did not bring significant rain to the central Atacama in Chile. Dew occurred at our station frequently following high nighttime relative humidity, but is not a significant source of moisture in the soil or under stones. Groundwater also does not contribute to surface moisture. Only the one rain event of 2.3 mm resulted in liquid water in the soil and beneath stones for a total of only 65-85 h over 4 years. The paucity of liquid water under stones is consistent with the apparent absence of hypolithic (under-stone) cyanobacteria, the only known primary producers in such extreme deserts.


Quantized pumping and topology of the phase diagram for a system of interacting bosons.
Interacting lattice bosons at integer filling can support two distinct insulating phases, which are separated by a critical point: the Mott insulator and the Haldane insulator [E. G. Dalla Torre, E. Berg, and E. Altman, Phys. Rev. Lett. 97, 260401 (2006).]. The critical point can be gapped out by breaking lattice inversion symmetry. Here, we show that encircling this critical point adiabatically pumps one boson across the system. When multiple chains are coupled, the two insulating phases are no longer sharply distinct, but the pumping property survives. This leads to strict constraints on the topology of the phase diagram of systems of quasi-one-dimensional interacting bosons.


Morphological, biophysical and synaptic properties of glutamatergic neurons of the mouse spinal dorsal horn.
Interneurons of the spinal dorsal horn are central to somatosensory and nociceptive processing. A mechanistic understanding of their function depends on profound knowledge of their intrinsic properties and their integration into dorsal horn circuits. Here, we have used BAC transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the vesicular glutamate transporter (vGluT2) gene (vGluT2::eGFP mice) to perform a detailed electrophysiological and morphological characterisation of excitatory dorsal horn neurons, and to compare their properties to those of GABAergic (Gad67::eGFP tagged) and glycinergic (GlyT2::eGFP tagged) neurons. vGluT2::eGFP was detected in about one-third of all excitatory dorsal horn neurons and, as demonstrated by the co-expression of vGluT2::eGFP with different markers of subtypes of glutamatergic neurons, probably labelled a representative fraction of these neurons. Three types of dendritic tree morphologies (vertical, central, and radial), but no islet cell-type morphology, were identified in vGluT2::eGFP neurons. vGluT2::eGFP neurons had more depolarised action potential thresholds and longer action potential durations than inhibitory neurons, while no significant differences were found for the resting membrane potential, input resistance, cell capacitance and after-hyperpolarisation. Delayed firing and single action potential firing were the single most prevalent firing patterns in vGluT2::eGFP neurons of the superficial and deep dorsal horn, respectively. By contrast, tonic firing prevailed in inhibitory interneurons of the dorsal horn. Capsaicin-induced synaptic inputs were detected in about half of the excitatory and inhibitory neurons, and occurred more frequently in superficial than in deep dorsal horn neurons. Primary afferent-evoked (polysynaptic) inhibitory inputs were found in the majority of glutamatergic and glycinergic neurons, but only in less than half of the GABAergic population. Excitatory dorsal horn neurons thus differ from their inhibitory counterparts in several biophysical properties and possibly also in their integration into the local neuronal circuitry.


Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms.
Aneurysms and dissections affecting thoracic aorta are associated with smooth muscle cell (SMC) dysfunction. NO/cGMP signaling pathway in smooth muscle cells has been shown to be affected in sporadic thoracic aortic aneurysms. We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. We found that aortic tissue obtained from Marfan, tricuspid and bicuspid thoracic aneurysms expressed lower levels of PDE5 mRNA compared to control aortas. In particular, we found that affected aortas showed lower levels of all the PDE5A isoforms, compared to control aortas. Transfection of vascular SMCs (VSMCs) with NOTCH3 activated domain (NICD3) induced the expression of PDE5A1 and A3 protein isoforms, but not that of the corresponding mRNAs. VSMC stimulation with GSNO, a nitric oxide analogue or with 8-br-cGMP, but not with 8-br-cAMP, up-regulated PDE5 and NOTCH-3 protein levels, indicating a negative feedback loop to protect the arterial wall from excessive relaxation. Finally, we found that PDE5 is expressed early during human aorta development, suggesting that if loss of function mutations of PDE5 occur, they might potentially affect aortic wall development.


A bio-inspired neural environment to control neurons comprising radial glia, substrate chemistry and topography.
Achieving alignment of cells is key to the success of regenerative strategies of neural tissue. We report a high-throughput method to investigate neural cell response to surface chemistry overlaid orthogonally onto a gradient of gradually changing groove widths. Using a bio-inspired approach wherein radial glial cells, which naturally guide neurons in the developing brain, enhance the attachment and directional outgrowth of neurons, we show the differences in the interaction and cellular response of glia, neurons and co-cultured cells. Radial glia were found to preferentially reside in grooves of width 6-35 μm with greater alignment to grooves <10 μm on the hydrophobic and hydrophilic extremes of chemistry. When neurons were sequentially cultured after radial glia, they showed enhanced alignment compared to when they were cultured alone, for all chemistries and groove widths. This is not dependent on co-localisation of the neurons with glia suggesting the radial glial cells pre-condition the substrate giving rise to enhanced attachment and alignment of subsequently cultured neurons. The results indicate a dependence of both primary radial glia and neuron responses on surface chemistry and micro-groove width. Grooved surfaces (width 5-10 μm) of mid-range wettability show the greatest potential to significantly enhance axonal alignment and, therefore, potential regeneration, when pre-conditioned by radial glia, highlighting the importance of surface engineering for neural scaffolds.


Role of Foxp3 gene in maternal susceptibility to pre-eclampsia - a study from South India.
Pre-eclampsia (PE) is a multifactorial pregnancy-specific vascular disorder characterized by hypertension and proteinuria and affects around 3-8% of pregnancies worldwide. Defective placentation during the early stage of pregnancy most likely in combination with maternal and environmental factors could lead to systemic inflammation, endothelial dysfunction and the manifestation of the clinical symptoms. Inadequate number of regulatory T cells (Tregs) or their functional deficiency is linked with infertility, miscarriage and PE. It is well identified that forkhead box P3 (Foxp3) gene is a master control gene for the development and function of Tregs that play an important role in the maintenance of self-tolerance and mediate maternal tolerance to the foetus. The main objective of this study was to assess the maternal susceptibility to PE with respect to a deletion mutation in exon-2 and -3279 C > A polymorphism (rs3761548) in the promoter region within the Foxp3 gene in a total of 282 PE patients and 215 normal pregnant women. The results showed that exon-2 deletion mutation is present in 1.06% of patients and none in the controls, indicating that it was not a common gene polymorphism associated with PE. With respect to rs3761548, the C allele frequency was observed to be higher in patients than in controls (49% versus 27%; OR = 2.81, P < 0.01). In conclusion, our results are suggestive of A allele to be protective against PE and C allele as predisposing in a dose-dependent manner in our population.


Interdisciplinary education for community health: the case for nursing and social work collaboration.
A nurse educator and a social work educator developed an interdisciplinary team-taught course in community health for both social work and nursing students. This account of their experience elaborates the implications of interdisciplinary education for the student learning experience including theory and practice content, socialization, and transition; faculty development; and the larger university community. Although this particular instance is limited to baccalaureate education, the authors underscore the potential of interdisciplinary course work for the enrichment of all levels of nursing and social work education.


Amphotericin B selection of mutant Chinese hamster cells with defects in the receptor-mediated endocytosis of low density lipoprotein and cholesterol biosynthesis.
This paper describes a rapid and efficient two-step procedure for the isolation of mutant cells with defects in receptor-mediated endocytosis. The procedure takes advantage of two fungal metabolites, compactin (ML236B), a potent inhibitor of cholesterol biosynthesis, and amphotericin B, a polyene antibiotic that forms toxic complexes with sterols in membranes. Mutagen-treated Chinese hamster ovary cells were preincubated overnight in a medium containing mevalonate, low density lipoprotein (LDL), and compactin (Mev/LDL/Com). At the end of the preincubation period, wild-type cells were cholesterol replete while mutant cells that could not utilize the cholesterol in LDL were cholesterol deficient. Subsequent incubation with amphotericin B for 6 hr killed most of the wild-type cells. After a second round of Mev/LDL/Com-amphotericin B selection, endocytosis-defective clones appeared at a frequency of approximately equal to 2.6 X 10(-5). Some of these clones expressed LDL receptor-defective phenotypes and fell into one of two previously defined classes of mutation. Sensitivity of the mutants to infection by vesicular stomatitis virus suggested that the mutations do not disrupt the coated pit-coated vesicle pathway of endocytosis. Minor modifications in the Mev/LDL/Com-amphotericin B selection permit the isolation of cholesterol auxotrophs and might allow the isolation of conditional-lethal mutations. Because LDL can be coupled to ligands that bind to receptors other than the LDL receptor, Mev/LDL/Com-amphotericin B selection may permit the isolation of mutant cells with defects that specifically disrupt other endocytic pathways.


Intestinal parasitism in Malayan aborigines (Orang Asli).
Surveys were conducted in the southern Malay peninsula to assess intestinal parasitism in the aboriginal ethnic minority groups. Faecal specimens from 1 273 persons were examined by the thiomersal-iodine-formol direct-smear technique. Prevalences are reported and, for helminth infections, data on worm burdens. The state of sanitation in each of 9 cultural-ecological groups was assessed by means of a simplified system of scoring for variables. Particular attention was paid to relationships between cultural and ecological factors, sanitation, and observed patterns of intestinal parasitism. The author also discusses the fact that the number of parasitic species diminishes in habitats simplified by man, whereas an increase occurs in the prevalence and intensity of the more adaptable species that persist in ecosystems of low complexity.


The copycat phenomenon after two Finnish school shootings: an adolescent psychiatric perspective.
Two school shootings with altogether 18 victims took place in Finland in November 2007 and September 2008. Homicides and suicides are both associated with the copycat phenomenon. The aim of the present study was to characterize adolescent copycats who had threatened to carry out a school massacre. The nation-wide study evaluated 77 13- to 18-year-old adolescents who were sent for adolescent psychiatric evaluations between 8.11.2007 and 30.6.2009, one of the reasons for evaluation being a threat of massacre at school. The medical files of the copycats were retrospectively analysed using a special data collection form. Data on demographics, family- and school-related issues, previous psychiatric treatment and previous delinquency, current symptoms, family adversities and psychiatric diagnoses were collected. The severity of the threat expressed and the risk posed by the adolescent in question were evaluated. The Psychopathy Checklist Youth Version was used to assess psychopathic traits. All of the copycats were native Finns with a mean age of 15.0 years. Almost two thirds of them had a history of previous mental health treatment before the index threat. Almost two thirds of the copycats suffered from anxiety and depressive symptoms, and almost half of the sample expressed either suicidal ideation or suicidal plans. Behavioural problems including impulse control problems, aggressive outbursts, the destruction of property as well as non-physical and physical violence against other persons were common. The diagnosis groups highlighted were behavioural and emotional disorders, mood disorders as well as schizophrenia-related disorders. The prevalence of pervasive developmental disorders was high. Only one of the copycats was assessed as expressing high traits of psychopathy. The copycats with school massacre threats were characterized with a high prevalence of mental and behavioural disorders. Like actual school shooters, they showed psychotic symptoms and traumatic experiences, but unlike the shooters, the copycats were not psychopathic.


Cannabinoid hyperemesis syndrome: potential mechanisms for the benefit of capsaicin and hot water hydrotherapy in treatment.
Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation. Putative mechanisms responsible for the benefit of hot water hydrotherapy are also investigated. An extensive search of PubMed, OpenGrey, and Google Scholar from inception to April 2017 was performed to identify known and theoretical thermoregulatory mechanisms associated with the endocannabinoid system. The searches resulted in 2417 articles. These articles were screened for relevant mechanisms behind capsaicin and heat activation having potential antiemetic effects. References from the selected articles were also hand-searched. A total of 137 articles were considered relevant and included. Capsaicin: Topical capsaicin is primarily used for treatment of neuropathic pain, but it has also been used successfully in some 20 cases of cannabinoid hyperemesis syndrome. The pharmacokinetics and pharmacodynamics of capsaicin as a transient receptor potential vanilloid 1 agonist may explain this effect. Topical capsaicin has a longer half-life than oral administration, thus its potential duration of benefit is longer. Capsaicin and transient receptor potential vanilloid 1: Topical capsaicin binds and activates the transient receptor potential vanilloid 1 receptor, triggering influx of calcium and sodium, as well as release of inflammatory neuropeptides leading to transient burning, stinging, and itching. This elicits a novel type of desensitization analgesia. Transient receptor potential vanilloid 1 receptors also respond to noxious stimuli, such as heat (>43 °C), acids (pH <6), pain, change in osmolarity, and endovanilloids. The action of topical capsaicin may mimic the effect of heat-activation of transient receptor potential vanilloid 1. Endocannabinoid system and transient receptor potential vanilloid 1: Cannabinoid hyperemesis syndrome may result from a derangement in the endocannabinoid system secondary to chronic exogenous stimulation. The relief of cannabinoid hyperemesis syndrome symptoms from heat and use of transient receptor potential vanilloid 1 agonists suggests a complex interrelation between the endocannabinoid system and transient receptor potential vanilloid 1. Temperature regulation: Hot water hydrotherapy is a mainstay of self-treatment for cannabinoid hyperemesis syndrome patients. This may be explained by heat-induced transient receptor potential vanilloid 1 activation. "Sensocrine" antiemetic effects: Transient receptor potential vanilloid 1 activation by heat or capsaicin results in modulation of tachykinins, somatostatin, pituitary adenylate-cyclase activating polypeptide, and calcitonin gene-related peptide as well as histaminergic, cholinergic, and serotonergic transmission. These downstream effects represent further possible explanations for transient receptor potential vanilloid 1-associated antiemesis. These complex interactions between the endocannabinoid systems and transient receptor potential vanilloid 1, in the setting of cannabinoid receptor desensitization, may yield important clues into the pathophysiology and treatment of cannabinoid hyperemesis syndrome. This knowledge can provide clinicians caring for these patients with additional treatment options that may reduce length of stay, avoid unnecessary imaging and laboratory testing, and decrease the use of potentially harmful medications such as opioids.


Well-founded practice or personal preference: a comparison of established techniques for measuring ulnar variance in healthy children and adolescents.
Ulnar variance is a clinical measure used to determine the relative difference in length between the radius and ulna. We aimed to examine consistency in ulnar variance measurements and normative data in children and adolescents using the perpendicular and the Hafner methods. Two raters measured ulnar variance on hand radiographs of 350 healthy children. Participants' mean calendar and skeletal ages were 12.3 ± 3.6 and 12.0 ± 3.7 years, 52% were female. Raters used the perpendicular method, an adapted version of the perpendicular method (in which the distal radial articular surface is defined as a sclerotic rim) and the Hafner method, being the distance between the most proximal points of the ulnar and radial metaphyses (PRPR) and the distance between the most distal points of both (DIDI). Intraclass correlation coefficients (ICCs) for intermethod consistency and inter- and intrarater agreement were calculated using a two-way ANOVA model. Variability and limits of agreement were determined using the Bland-Altman method. The interrater ICC was 0.75 (95% CI, 0.61-0.84) for the adapted perpendicular method, 0.88 (95% CI, 0.80-0.93) for PRPR, and 0.94 (95% CI, 0.90-0.97) for DIDI. The intermethod consistency ICC was 0.60 (95% CI, 0.48-0.70) for perpendicular versus PRPR and 0.60 (95% CI, 0.49-0.70) for perpendicular versus DIDI. The intrarater ICC was 0.88 (95% CI, 0.70-0.95) for perpendicular, 0.90 (95% CI, 0.83-0.94) for PRPR, and 0.81 (95% CI, 0.69-0.89) for DIDI. The perpendicular method was not useable in 38 cases (skeletal age ≤ 9 years) and the Hafner method in 79 cases (skeletal age ≥ 12 years). The perpendicular and Hafner methods show moderate intermethod consistency. The Hafner method is preferred for children with skeletal ages < 14 years, with good to excellent inter- and intrarater agreement. The adapted perpendicular method is recommended for patients with skeletal ages ≥ 14 years. • The perpendicular method for measuring ulnar variance requires extended instructions to ensure good interrater agreement in pediatric and adolescent patients. • The Hafner method is recommended for ulnar variance measurement in children with unfused growth plates and up to a skeletal age of 13 years, and the perpendicular method is recommended for children with fused growth plates and from skeletal age 14 and older. • The mean ulnar variance measured in this study for each skeletal age group (range, 5-18 years) is provided, to serve as a reference for future ulnar variance measurements using both methods in clinical practice.


Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications.
The rising epidemic of diabetes is a pressing issue in clinical medicine worldwide from both healthcare and economic perspectives. This is fueled by overwhelming increases in the incidence and prevalence of obesity. Obesity and diabetes are characterized by both insulin resistance and endothelial dysfunction that lead to substantial increases in cardiovascular morbidity and mortality. Reciprocal relationships between insulin resistance and endothelial dysfunction tightly link metabolic diseases including obesity and diabetes with their cardiovascular complications. Therefore, therapeutic approaches that target either insulin resistance or endothelial dysfunction alone are likely to simultaneously improve both metabolic and cardiovascular pathophysiology and disease outcomes. Moreover, combination therapies with agents targeting distinct mechanisms are likely to have additive or synergistic benefits. Conventional therapies for diabetes and its cardiovascular complications that are both safe and effective are insufficient to meet rising demand. Large, robust, epidemiologic studies demonstrate beneficial metabolic and cardiovascular health effects for many functional foods containing various polyphenols. However, precise molecular mechanisms of action for food polyphenols are largely unknown. Moreover, translation of these insights into effective clinical therapies has not been fully realized. Nevertheless, some functional foods are likely sources for safe and effective therapies and preventative strategies for metabolic diseases and their cardiovascular complications. In this review, we emphasize recent progress in elucidating molecular, cellular, and physiological actions of polyphenols from green tea (EGCG), cocoa (ECG), and citrus fruits (hesperedin) that are related to improving metabolic and cardiovascular pathophysiology. We also discuss a rigorous comprehensive approach to studying functional foods that is essential for developing novel, effective, and safe medications derived from functional foods that will complement existing conventional drugs.


Reasons to Write in Grade 6 and Their Association With Writing Quality.
Writing is a particularly complex and demanding task that needs to be mastered to assure students' success at school. In the last decades, the scientific community has been unanimous about the involvement of cognitive and motivational processes in the learning of writing. However, little is still known about some motivation-related processes, such as the reasons why students write. Therefore, this study analyzed the role of motivation in writing in developing writers, by examining the motives to write of 321 sixth graders. We used the Writing Motivation Questionnaire, which is a new instrument tapping the following motivations for writing: curiosity, involvement, grades, competition, social recognition, emotional regulation, and relief from boredom. Findings confirmed the multidimensional nature of motivations to write and supported the validity and reliability of the instrument. Also, results revealed that the strongest motives to write were grades and curiosity, and that curiosity and social recognition were significant predictors of writing quality, above and beyond attitudes and self-efficacy. Together these findings confirm the key role of motivation in writing and provide validity evidence of the Writing Motivation Questionnaire. This seems a useful tool to better understand the motivational processes involved in learning to write. However, despite the increasing research investment in this area, it is still important to carry out further studies that may contribute to the enrichment of the field of writing motivation.


Newly Diagnosed Lung Cancer: Which Molecular Tests Are Needed for Optimal Treatment Decision Making?
The management of advanced non-small-cell lung cancer (NSCLC) has changed dramatically over the past few years due to our expanded knowledge of the molecular basis of lung cancer (driver mutations and immune targets) and drugs that affect these pathways, namely targeted agents and checkpoint inhibitors. Consequently, it is important to test patients with newly diagnosed advanced NSCLC for potentially significant molecular abnormalities prior to the initiation of treatment. This requires close coordination between the surgical pathologist, the molecular pathologist, and the medical oncologist to ensure that the biopsy specimen is used judiciously to get all necessary information. In this article, I suggest an approach to the diagnostic evaluation of patients with newly diagnosed advanced NSCLC, in an attempt to identify the best treatment options for each.


Evidence for altered upper extremity muscle synergies in chronic stroke survivors with mild and moderate impairment.
Previous studies indicate that motor coordination may be achieved by assembling task-dependent combinations of a few muscle synergies, defined here as fixed patterns of activation across a set of muscles. Our recent study of severely impaired chronic stroke survivors showed that some muscle synergies underlying isometric force generation at the hand are altered in the affected arm. However, whether similar alterations are evident in stroke survivors with lesser impairment remains unclear. Accordingly, we examined muscle synergies underlying spatial patterns of elbow and shoulder muscle activation recorded during an isometric force target matching protocol performed by 16 chronic stroke survivors, evenly divided across mild and moderate impairment levels. We applied non-negative matrix factorization to identify the muscle synergies and compared their structure across groups, including previously collected data from six age-matched control subjects and eight severely impaired stroke survivors. For all groups, EMG spatial patterns were well explained by task-dependent combinations of only a few (typically 4) muscle synergies. Broadly speaking, elbow-related synergies were conserved across stroke survivors, regardless of impairment level. In contrast, the shoulder-related synergies of some stroke survivors with mild and moderate impairment differed from controls, in a manner similar to severely impaired subjects. Cluster analysis of pooled synergies for the 30 subjects identified seven distinct clusters (synergies). Subsequent analysis confirmed that the incidences of three elbow-related synergies were independent of impairment level, while the incidences of four shoulder-related synergies were systematically correlated with impairment level. Overall, our results suggest that alterations in the shoulder muscle synergies underlying isometric force generation appear prominently in mild and moderate stroke, as in most cases of severe stroke, in an impairment level-dependent manner.


Membrane turnover in rod photoreceptors: ensheathment and phagocytosis of outer segment distal tips by pseudopodia of the retinal pigment epithelium.
We have documented the ultrastructural changes that occur within the photoreceptor outer segment and the retinal pigment epithelium (RPE) during photosensitive membrane turnover. We employed an in vitro eyecup preparation from Xenopus laevis in which a large shedding event was induced by adding the excitatory amino acid L-aspartate (Greenberger & Besharse 1985; J. comp. Neurol. 239, 361-372). We found that during L-aspartate-induced shedding the RPE cells formed, on their apical domains, previously undescribed processes that were directly involved in disc phagocytosis. These processes are structurally similar to processes formed by macrophages during phagocytosis and are accordingly referred to as pseudopodia. Pseudopodia were distinguishable from the apical villous process normally extended from the RPE in that they were closely applied to the surface of the outer segment, had a cytoplasmic matrix of low electron density that was devoid of most cellular organelles and were enriched in thin (7 nm diameter) filaments. Filament size, specific pseudopodial staining with the actin-specific probe rhodamine phalloidin and inhibition of pseudopod formation by cytochalasin D suggested that the thin filaments were composed of actin. Pseudopodial formation also occurs during a normal light-initiated shedding event. However, the low frequency of shedding, the asynchrony of the individual shedding events and the transient appearance of the pseudopodia prevented a full appreciation of their role during normal disc shedding. Associated with massive shedding and pseudopodial formation, there was an increased adherence between retina and RPE. During L-aspartate treatment, the apical portions of the RPE cells partitioned with the distal outer segment during retinal isolation. This effect was directly related to the development of pseudopodia and may reflect alteration of surface features of the rod outer segment (ROS)-RPE interface related to phagocytosis. Our observations show that transiently forming pseudopodia are the organelles of phagocytosis and that they may play a role in disc detachment as well.


Distribution of blood group antigens A, B, H, Lewisa, and Lewisb in human normal, fetal, and malignant colonic tissue.
In humans, most blood group substances (BGS) are expressed throughout the fetal colon but are absent from the distal portion of adult colon. Cancers of the distal colon frequently reexpress BGS thereby suggesting that these antigens behave as oncofetal antigens at this organ site. We used a sensitive immunoperoxidase method with monoclonal antibodies directed against blood groups A, B, O (H), Lewisa and Lewisb to systematically evaluate BGS expression in fetal colon, normal adult colon from immediate autopsies of kidney donors, mucosa adjacent to cancer (transitional mucosa) and colorectal cancer tissues. In normal colon, BG-A, B, H, and Lewisb were expressed in proximal but not distal colon, whereas Lewisa was distributed uniformly throughout the colon. In colon cancer, and fetal colon, the proximal-distal gradient of BG-A, B, H, and Lewisb expression was abolished because of enhanced distal expression of these antigens. In cancer tissues, three patterns of altered BGS expression emerged: (a) incompatible expression of BG-A or BG-B (over 50% of patients); (b) deletion of BGS; and (c) precursor BG-H accumulation (80% of 25 tumors). BGS staining of transitional mucosa closely resembled that of the adjacent tumor except that no examples of BGS deletion were encountered in transitional mucosa. The goblet cell secretory vacuole accounted for most of the BGS expression in normal colon, but cancer cells demonstrated differentiation-dependent antigenic expression such that well-differentiated tumors expressed BGS on cell apical membranes and glandular contents, but poorly differentiated cancers exhibited diffuse cytoplasmic staining. These findings confirm the oncofetal nature of BGS in distal colon cancer, and provide immunohistochemical evidence for a diverse repertoire of altered antigen expression in colon cancer. Further investigation is needed to elucidate the possible genetic and biochemical mechanisms involved.


Broad-spectrum suppression of innate immunity is required for colonization of Arabidopsis roots by the fungus Piriformospora indica.
Piriformospora indica is a root-colonizing basidiomycete that confers a wide range of beneficial traits to its host. The fungus shows a biotrophic growth phase in Arabidopsis (Arabidopsis thaliana) roots followed by a cell death-associated colonization phase, a colonization strategy that, to our knowledge, has not yet been reported for this plant. P. indica has evolved an extraordinary capacity for plant root colonization. Its broad host spectrum encompasses gymnosperms and monocotyledonous as well as dicotyledonous angiosperms, which suggests that it has an effective mechanism(s) for bypassing or suppressing host immunity. The results of our work argue that P. indica is confronted with a functional root immune system. Moreover, the fungus does not evade detection but rather suppresses immunity triggered by various microbe-associated molecular patterns. This ability to suppress host immunity is compromised in the jasmonate mutants jasmonate insensitive1-1 and jasmonate resistant1-1. A quintuple-DELLA mutant displaying constitutive gibberellin (GA) responses and the GA biosynthesis mutant ga1-6 (for GA requiring 1) showed higher and lower degrees of colonization, respectively, in the cell death-associated stage, suggesting that P. indica recruits GA signaling to help establish proapoptotic root cell colonization. Our study demonstrates that mutualists, like pathogens, are confronted with an effective innate immune system in roots and that colonization success essentially depends on the evolution of strategies for immunosuppression.


Antiviral activity and its mechanism of guanine 7-N-oxide on DNA and RNA viruses derived from salmonid.
Guanine 7-N-oxide produced by Streptomyces sp. was found to inhibit in vitro the replication of herpes virus (Oncorhynchus masou virus, OMV), rhabdo virus (infectious hematopoietic necrosis virus, IHNV) and a bi-segmented double-strand virus (infectious pancreatic necrosis virus, IPNV) derived from salmonids with IC50 values of about 10 micrograms/ml, 20 micrograms/ml and 32 micrograms/ml, respectively. The agent was not toxic for the host cells (chinook salmon embryo, CHSE-214) at the IC50 concentrations. Labeling of IHNV viral RNA and host cellular DNA and RNA with [3H]uridine and [3H]thymidine during drug treatment showed that guanine 7-N-oxide did not reduce the incorporation of these precusors into RNA and DNA. The anti-IHNV activity of guanine 7-N-oxide was enhanced synergistically by neplanocin A, an inhibitor of RNA methylation. The mechanism of action of guanine 7-N-oxide is discussed, in regard to maturation of viral messenger RNA including capping.


Polymorphic integrations of an endogenous gammaretrovirus in the mule deer genome.
Endogenous retroviruses constitute a significant genomic fraction in all mammalian species. Typically they are evolutionarily old and fixed in the host species population. Here we report on a novel endogenous gammaretrovirus (CrERVγ; for cervid endogenous gammaretrovirus) in the mule deer (Odocoileus hemionus) that is insertionally polymorphic among individuals from the same geographical location, suggesting that it has a more recent evolutionary origin. Using PCR-based methods, we identified seven CrERVγ proviruses and demonstrated that they show various levels of insertional polymorphism in mule deer individuals. One CrERVγ provirus was detected in all mule deer sampled but was absent from white-tailed deer, indicating that this virus originally integrated after the split of the two species, which occurred approximately one million years ago. There are, on average, 100 CrERVγ copies in the mule deer genome based on quantitative PCR analysis. A CrERVγ provirus was sequenced and contained intact open reading frames (ORFs) for three virus genes. Transcripts were identified covering the entire provirus. CrERVγ forms a distinct branch of the gammaretrovirus phylogeny, with the closest relatives of CrERVγ being endogenous gammaretroviruses from sheep and pig. We demonstrated that white-tailed deer (Odocoileus virginianus) and elk (Cervus canadensis) DNA contain proviruses that are closely related to mule deer CrERVγ in a conserved region of pol; more distantly related sequences can be identified in the genome of another member of the Cervidae, the muntjac (Muntiacus muntjak). The discovery of a novel transcriptionally active and insertionally polymorphic retrovirus in mammals could provide a useful model system to study the dynamic interaction between the host genome and an invading retrovirus.


Effects of atrial natriuretic factor on blood pressure and the renin-angiotensin-aldosterone system.
Atrial natriuretic factor (ANF) antagonizes vasoconstriction induced by numerous smooth muscle agonists and also lowers blood pressure in intact animals. ANF has particularly marked relaxant effects on angiotensin II-contracted vessels in vitro. Sensitivity to the blood pressure-lowering effect of ANF in vivo appears to be enhanced in renin-dependent models of renovascular hypertension compared with other experimental hypertensive models. The depressor action of low, possibly physiological doses of ANF in two-kidney, one-clip Goldblatt rats is due to a decrease in total peripheral resistance. On the other hand, high doses of ANF can lower cardiac output, particularly in volume-expanded models such as deoxycorticosterone-salt hypertension. ANF markedly inhibits renin secretion in intact animals, probably via increased glomerular filtration rate and load of sodium chloride to the macula densa. This effect is masked when renal perfusion is impaired (e.g., via unilateral renal artery constriction), in which case ANF may stimulate renin secretion slightly. ANF also reduces plasma aldosterone in vivo and inhibits basal and agonist-induced aldosterone release from isolated adrenal cortical cells. This effect appears to be especially marked for angiotensin-induced aldosterone production in vivo and in vitro. These findings indicate that ANF has potentially important interactions with the renin-angiotensin-aldosterone system and suggest a role for ANF in the homeostatic control of blood pressure as well as of extracellular fluid volume.


Improved diagnostic performance of susceptibility-weighted imaging with compressed sensing-sensitivity encoding and neuromelanin-sensitive MRI for Parkinson's disease and atypical Parkinsonism.
To verify the diagnostic performance of the loss of nigrosome-1 on susceptibility-weighted imaging (SWI) with compressed sensing-sensitivity encoding (CS-SENSE) and neuromelanin on neuromelanin-sensitive (NM) magnetic resonance imaging (MRI) for the diagnosis of Parkinson's disease (PD) and atypical Parkinsonism. A total of 195 patients who underwent MRI between October 2019 and February 2020, including SWI, with or without CS-SENSE, and NM-MRI, were reviewed retrospectively. Two neuroradiologists assessed the loss of nigrosome-1 on SWI and neuromelanin on the NM-MRI. The result of N-3-fluoropropyl-2-beta-carbomethoxy-3-beta-(4-iodophenyl) nortropane positron-emission tomography (PET) was set as the reference standard. When CS-SENSE was applied for nigrosome-1 imaging on SWI, the non-diagnostic scan rate was lowered significantly from 19.3% (17/88) to 5.6% (6/107; p=0.004). Diagnosis of PD and atypical Parkinsonism based on the loss of nigrosome-1 on SWI and based on NM-MRI showed good diagnostic value (area under the curve [AUC] 0.821, 95% confidence interval [CI] = 0.755-0.875: AUC 0.832, 95% CI = 0.771-0.882, respectively) with a substantial inter-reader agreement (κ = 0.791 and 0.681, respectively). Combined SWI and neuromelanin had a similar discriminatory ability (AUC 0.830, 95% CI = 0.770-0.880). Similarly, the diagnosis of PD was excellent. CS-SENSE may add value to the diagnostic capability of nigrosome-1 on SWI to reduce the nondiagnostic scan rates. Furthermore, loss of nigrosome-1 on SWI or volume loss of neuromelanin on NM-MRI may be helpful for diagnosing PD.


Cerebral white matter hyperintensities in the prediction of cognitive decline and incident dementia.
Cerebral white matter hyperintensities (WMH), detected in vivo with magnetic resonance imaging (MRI), are commonly used to assess cerebrovascular burden in cognitive impairment. However, the association between WMH and cognition is not consistent across the literature. The present review examines evidence from published longitudinal studies. We reviewed the PubMed data base from January 1990 to March 2013 and included studies investigating the association of WMH with (1) the risk of dementia in the general population, (2) the risk of conversion to dementia in the mild cognitive impairment (MCI) population, and (3) cognitive decline in the general population. WMH were associated with all types of dementia in the general population, but not in MCI patients. Results are discrepant for global decline. WMH appear to be early predictors of the risk of dementia, but this association appears to be modulated by cognitive reserve, age and the spatial distribution of lesions. There are, however, some limits in the use of WMH as a marker of vascular burden. In addition to their ischaemic origin, WMH may be the result of co-occurring morbidity. Further research is needed to elucidate to what extent WMH actually reflect vascular risk to evaluate the likely efficacy of interventions specifically targeting WMH reduction.


The water diuretic effect of the alpha-2 adrenoceptor agonist, AGN 190851, is species-dependent.
The effect of the novel alpha-2 adrenoceptor agonist, AGN 190851, was evaluated for its diuretic action in the rat, dog and cynomolgus monkey and its ability to inhibit vasopressin-stimulated cyclic AMP accumulation in rat and dog cortical collecting tubules in vitro. The data indicate that in the rat, AGN 190851 resulted in a dose-dependent water diuresis, which was accompanied by an increase in blood pressure and osmolar clearance. In addition, AGN 190851 resulted in a dose-dependent inhibition of vasopressin-stimulated cyclic AMP accumulation in rat cortical collecting tubules in vitro. In contrast, AGN 190851 was unable to cause either a water diuresis in conscious dogs or inhibit vasopressin-stimulated adenylate cyclase activity in canine tissue in vitro. In the lightly anesthetized cynomolgus monkey, AGN 190851 also failed to alter renal function significantly. Administration of the vasopressin receptor antagonist, SK&F 105494, to either dogs or cynomolgus monkeys demonstrated that antagonism of the vasopressin V2 receptor could result in a brisk water diuresis in both species. The data demonstrate that alpha-2 adrenoceptors can functionally antagonize vasopressin antidiuretic activity in the rat, but not in the dog or cynomolgus monkey.


Impact of a children's health insurance program on newly enrolled children.
Although there is considerable interest in decreasing the number of US children who do not have health insurance, there is little information on the effect that health insurance has on children and their families. To determine the impact of children's health insurance programs on access to health care and on other aspects of the lives of the children and their families. A before-after design with a control group. The families of newly enrolled children were interviewed by telephone using an identical survey instrument at baseline, at 6 months, and at 12 months after enrollment into the program. A second group of families of newly enrolled children were interviewed 12 months after the initial interviews to form a comparison sample. The 29 counties of western Pennsylvania, an area with a population of 4.1 million people. A total of 887 families of newly enrolled children were randomly selected to be interviewed; 88.3% agreed to participate. Of these, 659 (84%) responded to all 3 interviews. The study population consists of 1031 newly enrolled children. The children were further classified into those who were continuously enrolled in the programs. The 330 comparison families had 460 newly enrolled children. The following access measures were examined: whether the child had a usual source of medical or dental care; the number of physician visits, emergency department visits, and dentist visits; and whether the child had experienced unmet need, delayed care, or both for 6 types of care. Other indicators were restrictions on the child's usual activities and the impact of being insured or uninsured on the families. Access to health care services after enrollment in the program improved: at 12 months after enrollment, 99% of the children had a regular source of medical care, and 85% had a regular dentist, up from 89% and 60%, respectively, at baseline. The proportion of children reporting any unmet need or delayed care in the past 6 months decreased from 57% at baseline to 16% at 12 months. The proportion of children seeing a physician increased from 59% to 64%, while the proportion visiting an emergency department decreased from 22% to 17%. Since the comparison children were similar to the newly enrolled children at enrollment into the insurance programs, these findings can be attributed to the program. Restrictions on childhood activities because of lack of health insurance were eliminated. Parents reported that having health insurance reduced the amount of family stress, enabled children to get the care they needed, and eased family burdens. Extending health insurance to uninsured children had a major positive impact on children and their families. In western Pennsylvania, health insurance did not lead to excessive utilization but to more appropriate utilization.


The sequence of the nucleocapsid protein (N) gene of Piry virus: possible domains in the N protein of vesiculoviruses.
A number of independent cDNA clones of the Piry virus N gene message were identified and sequenced. From the resulting sequences and previously published data, we derived the sequence of the mRNA for this protein. Sequence similarities of the translated region of Piry virus with that of other viruses suggest that Piry virus is as distantly related to Chandipura virus as it is to the vesicular stomatitis viruses of Indiana and New Jersey serotypes. Based on the relative conservation of the amino acid sequence of the nucleocapsid protein of these vesiculoviruses, the N protein can be subdivided into at least three regions, possibly indicative of functional domains.


The role of positive nerve root sedimentation sign in the treatment of patients undergoing lumbar disc herniation.
To investigate the efficacy of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of patients who were diagnosed with lumbar disc herniation (LDH) with positive nerve root sedimentation sign (NRSS). A total of 86 patients who underwent LDH were recruited and divided into NRSS-positive group (n = 49) and NRSS-negative group (n = 37). The visual analog scale (VAS), Japanese Orthopaedic Association (JOA), and Oswestry disability index (ODI) were used to evaluate the low back pain and functional recovery and were compared between the two groups. There were no significant differences in the demographic parameters between the two groups. The average area of the dural sac compression in the NRSS-positive group was significantly higher than that in the NRSS-negative group. Patients with a positive NRSS showed a better low back pain relief than those with a negative NRSS at 1 week and 1 month after surgery. The JOA and ODI in the NRSS-positive group were better than those in the NRSS-negative group at 3 months and 6 months postoperatively. The apparent efficiency of JOA and the excellent and good rate of ODI in the negative group was lower than that in the positive group at 6 months after surgery. Patients undergoing LDH with a positive NRSS showed better pain relief and functional recovery than those with a negative NRSS. The present study suggested that NRSS might be a valuable sign and associated with better clinical outcomes in patients undergoing LDH with the treatment of PTED.


Interaction of smoking and aging on emphysema and small airways disease in asymptomatic healthy men by CT-based parametric response mapping analysis.
To explore whether small airway disease and emphysema were affected by the interaction between smoking and aging on chest computed tomography (CT) images of asymptomatic healthy men analysed using a quantitative imaging tool parametric response mapping (PRM). In this retrospective study, 95 asymptomatic healthy men underwent biphasic chest CT. The PRM classifies lung as a percentage of normal (PRMNormal%), functional small airway disease (PRMfSAD%), and emphysema (PRMEmph%). The patients were divided into groups based on their age and smoking status. Multiple linear regression analysis was applied to explore the factors influencing lung injury. Simple effects analysis was performed to explore the interaction between different age groups and smoking status. The interaction between aging and smoking significantly affected PRMfSAD% and PRMEmph% (p<0.001). The age range 60-69 and smoking were associated with increased PRMfSAD% and PRMEmph% (p<0.05). Futher stratification into different age subgroups showed that smoking was associated with increased PRMfSAD% and PRMEmph% in the 50-59 year age group. Besides, smoking in the 50-59 and 60-69 years group was associated with decreased PRMNormal%, while smoking in the 60-69 years group did not significantly influence the prevalence of PRMfSAD% and PRMEmph% (p>0.05). PRM reveals the interplay between smoking and aging in the development of lung injury in asymptomatic healthy men. Aging and smoking are important factors of emphysema and small airway disease in the 50-69 years group. In the 60-69 years group, aging poses a greater risk of lung injury compared to smoking.