The effect of pregnancy in HIV-infected women.
The diagnosis of HIV in a pregnant women or pregnancy in an HIV-positive woman can be associated with an affective disorder, caring for which can present a major challenge for physicians and health care workers. The associated somatic symptoms can cause serious morbidity. This study aims to explore the mental health of pregnant HIV-infected women. The study took place at the University Teaching Hospital in Lusaka, Zambia and at satellite clinics. Study participants were either pregnant women who were diagnosed with HIV during the course of their pregnancy, or women who knew their HIV-positive status prior to becoming pregnant. A questionnaire was used to assess the psychological state of the women. The majority of women (85%) showed major depressive episodes and had significant suicidal thoughts. About 60% of the women whose HIV was diagnosed during their pregnancy showed signs of somatic illness. Those who knew their HIV status before becoming pregnant did not show severe depressive episodes, but showed anxiety about the HIV status of their babies. This suggests that women who discover their HIV status during the course of their pregnancy are more liable to develop major depressive illness and somatic disorders. Physicians dealing with these women need to be cognisant of the strain HIV can add to pregnancy and of the psychological and psychiatric support they may require.


COVID-19 Trials: Who Participates and Who Benefits?
The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortality from COVID-19 in the United States. Racial and ethnic minority individuals, particularly Black, Hispanic, and Indigenous Americans have experienced higher rates of infection and death than the White population. Although there has been an unprecedented explosion of clinical trials to examine potential therapies, participation by members of these vulnerable communities is crucial to obtaining data generalizable to those communities. We undertook an open-label, factorial randomized clinical trial examining hydroxychloroquine and/or azithromycin for hospitalized patients. Of 53 screened patients, 11 (21%) were enrolled. Ten percent (3/31) of Black patients were enrolled, 33% (7/21) of White patients, and 50% (6/12) of Hispanic patients. Forty-seven percent (25/53) of patients declined participation despite eligibility; 58%(18/31) of Black patients declined participation. Forty percent (21/53) of screened patients were from a nursing facility and 10% (2/21) were enrolled. Enrolled patients had fewer comorbidities than nonenrolled patients: median modified Charlson comorbidity score 2.0 (interquartile range 0-2.5), versus 4.0 (interquartile range 2-6) for nonenrolled patients (P = 0.006). The limitations of the study were the low participation rate and the multiple treatment trials concurrently recruiting at our institution. The high rate of nonparticipation in our trial of nursing facility residents and Black people emphasizes the concern that clinical trials for therapeutics may not target key populations with high mortality rates.


MetaLP: An integrative linear programming method for protein inference in metaproteomics.
Metaproteomics based on high-throughput tandem mass spectrometry (MS/MS) plays a crucial role in characterizing microbiome functions. The acquired MS/MS data is searched against a protein sequence database to identify peptides, which are then used to infer a list of proteins present in a metaproteome sample. While the problem of protein inference has been well-studied for proteomics of single organisms, it remains a major challenge for metaproteomics of complex microbial communities because of the large number of degenerate peptides shared among homologous proteins in different organisms. This challenge calls for improved discrimination of true protein identifications from false protein identifications given a set of unique and degenerate peptides identified in metaproteomics. MetaLP was developed here for protein inference in metaproteomics using an integrative linear programming method. Taxonomic abundance information extracted from metagenomics shotgun sequencing or 16s rRNA gene amplicon sequencing, was incorporated as prior information in MetaLP. Benchmarking with mock, human gut, soil, and marine microbial communities demonstrated significantly higher numbers of protein identifications by MetaLP than ProteinLP, PeptideProphet, DeepPep, PIPQ, and Sipros Ensemble. In conclusion, MetaLP could substantially improve protein inference for complex metaproteomes by incorporating taxonomic abundance information in a linear programming model.


Angular changes and their rates in concurrence to developmental stages of the mandibular second premolar.
In the early developmental stage of the mandibular second premolar (MnP2), it is not unusual to find the tooth extremely angulated to the lower border of the mandible, as seen in the panoramic roentgenogram. On eruption, the tooth, in most cases, is close to being upright. However, impaction or other types of malocclusions due to its ectopic eruption are not rare. This study follows the angular changes of the MnP2 during development. Two hundred two panoramic roentgenograms of 101 patients were retrospectively analyzed. All patients had two sequential films with a minimal time interval of nine months. Each MnP2 was traced, and its developmental stage as well as its angulation to the lower border of the mandible was registered. We found that normally more MnP2 are distally (56.5%) than mesially (25%) inclined. There is a statistically significant difference in the inclination of the teeth during their development from stage D to stage F (D = 75.17 degrees +/- 15.25 degrees, E = 79.35 degrees +/- 12.18 degrees, F = 83.38 degrees +/- 10.79 degrees). The average amount of total angular change rate of the MnP2s from stage D to stage G is 0.09 +/- 0.25 degrees/mo, and the absolute angular change rate is 0.19 +/- 0.25 degrees/mo.


Compound heterozygous mutations in the helicase RTEL1 causing Hoyeraal-Hreidarsson syndrome with Blake`s pouch cyst: a case report.
Telomeres inhibit DNA damage response at the ends of the chromosome to suppress cell cycle arrest as well as ensure genome stability. Dyskeratosis congenita (DC), a telomere-related disease, includes the classical triad involving oral leukoplakia, dysplastic nails, and lacy reticular pigment in the neck and/or upper chest. Hoyeraal-Hreidarrson syndrome (HHS), a severe manifestation of DC, frequently occurs during childhood, and patients with HHS often show short-term survival and thus do not exhibit all mucocutaneous manifestations or syndromic features. We report here a patient with HHS characterized by the proband`s clinical attributes, such as growth delay, bone marrow failure, microcephaly, defects in body development, and the absence of cerebellar hypoplasia combined with Blake`s pouch cyst. By using exome sequencing, novel compound heterozygous mutations (c.1451C > T and c.1266+3del78bp) were detected in the RTEL1 (regulator of telomere elongation helicase 1) gene. The DNA helicase RTEL1 plays a role in genome stability, DNA replication, telomere maintenance, and genome repair. Terminal restriction fragment length analysis revealed a significantly shorter telomere length of the proband. Our findings provided evidence that compound heterozygous RTEL1 mutations cause HHS.


Predictive Analytics to Support Real-Time Management in Pathology Facilities.
Predictive analytics can provide valuable support to the effective management of pathology facilities. The introduction of new tests and technologies in anatomical pathology will increase the volume of specimens to be processed, as well as the complexity of pathology processes. In order for predictive analytics to address managerial challenges associated with the volume and complexity increases, it is important to pinpoint the areas where pathology managers would most benefit from predictive capabilities. We illustrate common issues in managing pathology facilities with an analysis of the surgical specimen process at the Department of Pathology and Laboratory Medicine (DPLM) at The Ottawa Hospital, which processes all surgical specimens for the Eastern Ontario Regional Laboratory Association. We then show how predictive analytics could be used to support management. Our proposed approach can be generalized beyond the DPLM, contributing to a more effective management of pathology facilities and in turn to quicker clinical diagnoses.


Elevated serum C-reactive protein concentration in Bosnian patients with probable Alzheimer's disease.
Studies indicate that inflammatory mechanisms may play an important role in the pathogenesis of Alzheimer's disease (AD). C-reactive protein (CRP), marker and mediator of inflammation, has been detected in lesions typical for the affected areas of AD brain. There have been conflicting reports on serum CRP concentration in AD. Scarce data exist on association of CRP and measures of adiposity in AD patients. Thus, we investigated serum CRP concentration in fifteen overweight institutionalized patients with probable AD and fifteen age-matched control subjects. Body mass index (BMI) and waist/hip ratio (WHR) were calculated for each subject included in the study. Age, systolic and diastolic blood pressure, BMI and WHR did not differ significantly between the two groups. Serum CRP concentration was significantly higher in patients with AD compared to controls (p<0.0001). Although not significant, positive correlations between serum levels of CRP and BMI and WHR were found. Obtained results support the notion that low-grade inflammation is present in patients with AD. Absence of significant association between CRP and measures of total and central adiposity in overweight AD patients needs further investigation and explanation.


Unilateral galactocele following augmentation mammoplasty.
Development of unilateral galactoceles following breast augmentation is reported in 2 young females. Both galactoceles were drained and cultured. In 1 patient the implant was removed and a delayed reinsertion was undertaken. In the second patient the implant was replaced at the time of the drainage procedure. Culture and sensitivity in 1 patient showed no growth and in the second patient revealed Staphylococcus aureus. Although the cause is unknown, galactocele formation may be due to manipulation of breast tissue during surgery. The use of oral contraceptives may also play a role in this process. Hormonal suppression of lactation and removal of the implants may be indicated in these patients. Consideration should be also given to the use of systemic antibiotics directed toward skin pathogens.


Four plasmid genes are required for colicin V synthesis, export, and immunity.
The colicin V production and immunity genes were isolated from plasmid pColV-K30. A HindIII-to-SalI fragment of 9.4 kilobases was cloned into the compatible vectors pBR322 and pACYC184. Mutants defective in colicin production were generated by Tn5 insertions and by constructing deletions in vitro. Physical analysis of these mutations identified a 4.4-kilobase region of this DNA which contains all the plasmid genes (cva) needed for the production of colicin V. The colicin V immunity determinant (cvi) is in a 700-base-pair fragment located within one end of this region. Complementation tests identified three genes, called cvaA, cvaB, and cvaC, required for colicin production. Analysis of the proteins labeled in minicells harboring various Tn5 insertions allowed us to identify protein products for the cvaA and cvaC genes. Mutations in cvaA and cvaB eliminated colicin activity in culture supernatants, but not within the cells. Mutations in cvaC, however, eliminated all detectable activity. From these results we conclude that the cvaC gene codes for the structural gene for colicin V, while cvaA and cvaB are apparently needed for the normal export of the colicin.


Measurement of free radicals and NO by chemiluminescence to identify the reperfusion injury in renal transplantation.
Oxygen free radicals are generated during the reperfusion of ischaemic organs. Several experimental studies have demonstrated that the damage produced by reperfusion can be prevented by a scavenger of free radicals. Furthermore, a significantly improved 5 year graft survival rate after cadaveric renal transplantation has been reported in patients treated with scavengers of free radicals (Land et al., 1993). Therefore, a question remains to be answered: whether a routine monitoring of the radical-mediated reperfusion injury with renal transplantation is useful, and whether there is a necessity for a generalized protective treatment in transplant patients. In a prospective trial, we evaluated a group of eight patients during and after renal cadaveric transplantation (three men, five women), using the chemiluminometric measurement of serum free radicals and NO. The serum quantities of free radicals and NO were significantly increased after reperfusion of the transplant kidney (p < 0.02). The mean time of noticeably increased levels of serum free radicals was 4.8 +/- 1.2 h after reperfusion. The results thus showed an increased liberation of free radicals in the peripheral blood of transplant recipients as possible evidence of free radicals-mediated reperfusion injury in renal transplantation. The generation of free radicals measured by chemiluminescence allow a controlled therapy to decrease the generation of free radicals with antioxidants during the early transplantation period e.g. in older recipients.


Formaldehyde biodegradation and its effect on the denitrification process.
Simultaneous formaldehyde biodegradation and denitrification in batch assays and in a continuous lab-scale reactor were studied. In batch assays, initial biodegradation rates between 0.7 and 3.3 g CKH2O g VSS(-1) d(-1) were obtained at formaldehyde concentrations between 300 and 2150 mg l(-1). The denitrification process was affected by the presence of formaldehyde. The nitrite accumulation increased with the initial formaldehyde concentration. In the continuous reactor, removal efficiencies above 98.5% were obtained at formaldehyde loading rates between 0.37 and 2.96 kg COD m(-3) d(-1) (625-5000 mg CH2O l(-1)). Formaldehyde removal led to the appearance of methanol and formic acid in the medium. Denitrification process was almost complete (around 99.7%) at nitrogen loading rates up to 0.44 kg N-NO3- m(-3) d(-1). Nitrite occasionally appeared in the effluent at concentrations less than 2.9 mg l(-1). The composition of the biogas indicated that denitrification and methanogenesis occurred simultaneously in the same unit.


Chiral Allenes via Alkynylogous Mukaiyama Aldol Reaction.
Herein we describe the development of a catalytic enantioselective alkynylogous Mukaiyama aldol reaction. The reaction is catalyzed by a newly designed chiral disulfonimide and delivers chiral allenoates in high yields and with excellent regio-, diastereo-, and enantioselectivity. Our process tolerates a broad range of aldehydes in combination with diverse alkynyl-substituted ketene acetals. The reaction products can be readily derivatized to furnish a variety of highly substituted enantiomerically enriched building blocks.


The Occlutech Figulla PFO and ASD occluder: a new nitinol wire mesh device for closure of atrial septal defects.
We investigated the safety, feasibility and efficacy of the Occlutech devices for patent foramen ovale (PFO) and atrial septal defect (ASD) closure in a prospective trial. The retention discs of the PFO device (23 x 25 mm, 27 x 30 mm) are connected by a 3 mm waist in the center with only one right atrial side central pin. The left atrial disc is produced either with a single or double flat layer, which allows a significant reduction of meshwork material. The ASD occluder (6-40 mm, 3 mm increments) has only one central pin on the right atrial side. Indications for closure included cryptogenic stroke with evidence of a PFO on transesophageal echocardiography (TEE) or an ASD II. The devices were implanted in 29 patients with PFO and in 12 patients with ASD II (fluoroscopy and TEE). An echocardiographic follow-up examination was performed after 1, 2 and 6 months. The devices were successfully implanted in all 41 patients. There were no periprocedural complications. One patient with ASD II died of recurrent myocardial infarction without evidence of cardioembolic origin. TEE studies showed a residual shunt in 11.2% after 60 days in patients with PFO and a left-to-right shunt in 9.1% of the remaining patients with ASD II. After 180 days only 1 patient with PFO had a right-to-left shunt (3.7%). A residual shunt in the patients with ASD was not observed. The novel Occlutech devices appear to be safe, feasible and effective for PFO and ASD closure, with a significant reduction of the meshwork and absence of left atrial central pin.


Somatic stem cells in the myometrium and in myomas.
The human uterus mainly consists of two layers: an inner endometrium and an outer layer, the myometrium, made of smooth muscle. The uterus is characterized by its unique capacity for regeneration. This capacity permits cyclical regeneration and remodeling of the tissue over the course of a woman's reproductive life. During each menstrual cycle, the endometrium regenerates, and the uterus enlarges to make room for fetal growth. This cyclic physiologic pattern suggests that myometrial stem/progenitor cells are present in the tissue and play a role in myometrial functions. Our group (and others) recently characterized and isolated putative stem/progenitor cells in the myometrium. These findings are permitting a better understanding of myometrial physiology and pathology. We review current studies of myometrial stem/progenitor cells and suggestions that, in combination with hypoxia, these cells may contribute to uterine remodeling during pregnancy and the formation of myomas.


[CLINICAL ASPECTS OF INTRAUTERINE INSEMINATION].
Intrauterine insemination (IUI) is an intervention performed frequently in the treatment of couples suffering from subfertility and women treated using donor sperm. The factors predicting its success include female parameters such as age and ovarian function and male parameters such as sperm quality. However, many details regarding its clinical application such as the methodology of sperm preparation, timing of IUI, the number of inseminations in the same cycle, the recommended number of cycles to be performed and the minimal threshold values of the sperm sample profile required are controversial. The conclusion to be drawn from this literature survey is that there is still lack of sufficient good quality studies performed to allow evidence based recommendations for the performance of IUI.


A case of primary botryoid conjunctival rhabdomyosarcoma.
Rhabdomyosarcoma is the most common childhood primary orbital malignancy, but the occurrence of this tumour in the conjunctiva is rare. A 14-year-old girl presented with a visible case of conjunctival mass in the left eye. The year before, the patient was referred to another hospital for a biopsy of a conjunctival mesenchymal tumour in the same site, which was periodically checked after the excision. We intervened by partially removing the conjunctival mass. The histopathology revealed a botryoid rhabdomyosarcoma. The patient underwent chemotherapy and fractionated radiotherapy. The follow-up after three years revealed that the patient remained clinically tumor-free, with no ocular complication from the radiotherapy. It is evident that by not excising the tumour in its entirety it is therefore possible to preserve the underlying rectus muscles and not interfere with ocular motility. Subsequent radiotherapy and chemotherapy helped to destroy any residual tumour. Alternatively, surgical excision of the mass alone could lead to recurrence of the tumour after some months or years.


Formation of polyelectrolyte-surfactant complexes on surfaces.
The interfacial behavior of polyelectrolytes, mainly cationic with varying content of amphiphilic groups, and their complexes with oppositely charged surfactant are discussed. Both the kinetics and the reversibility aspect of the adsorption are considered. The structure of adsorbed layer formed was found to be dependent not only on the bulk solution phase behavior, but also on the pre-applied conditions, i.e., the path used to obtain a particular solution condition (e.g., by changing pH and concentration of salt, surfactant or polymer). Polyelectrolyte adsorption appears only partly reversible, due to its high affinity to the surface, which slows down the adsorption process. In general, relaxation occurs more easily if the direction of the process is from low to high surface coverage. Association of the surfactant with the polymer, which depends on the surfactant concentration, can completely alter the interfacial behavior. Maximum adsorption occurs generally at a surfactant concentration just before the expected phase separation region, while the complex in some cases could desorb from the surface at high enough surfactant concentration (above the cmc). Different results were obtained for coadsorption of amphiphilic polyelectrolytes when surfactant was added to the preadsorbed polymer layers and when complexes were pre-formed in the solution prior to exposing the surface to the polymer-surfactant solution.


Juvenile arthritis-associated uveitis: visual outcomes and prognosis.
The current issues in the management of uveitis associated with juvenile arthritis revolve mainly around the treatment of mild disease and how to treat patients with more severe disease. The aims of this study were to determine the incidence of uveitis in a cohort of patients with juvenile arthritis as well as the nature of treatment and the risk factors for visual loss. Review of the charts of 71 patients with juvenile arthritis, as defined by the American Academy of Rheumatology, seen between 1992 and 2001 at a combined rheumatology and ophthalmology clinic. Information collected included the patient's sex, age at diagnosis of arthritis and uveitis, and date of diagnosis of arthritis and uveitis. The rheumatologic diagnosis, results of serologic testing, and details of systemic and topical treatments were also recorded. There were 47 girls and 24 boys ranging in age from 16 months to 13 years. The median age at diagnosis of juvenile arthritis was 4 years and 1 month. Twenty-seven patients (38%) had uveitis. The median age at uveitis onset was 5.9 years, with an average interval of 18 months from the diagnosis of arthritis; 11 patients had uveitis at the time of arthritis diagnosis. There was a positive relation between anti-nuclear antibody positivity and the development of uveitis (p < 0.05). Thirteen (48%) of the 27 patients with uveitis had mild anterior segment inflammation, with fewer than 25 cells in the anterior chamber. This group had spontaneous resolution of uveitis without topical therapy. All the patients without uveitis had a final visual acuity of 6/9 or better. Five of the patients with uveitis had a final visual acuity of 6/36 or worse. Cataract was the most common complication affecting visual outcome. Cataract extraction initially improved the visual acuity, but posterior segment complications and glaucoma compromised the final visual outcome. We found an incidence of uveitis of 38% with long-term follow-up of patients with juvenile arthritis; the uveitis was diagnosed an average of 18 months after the arthritis. Almost half of the patients with uveitis had minor anterior segment inflammation. These patients did not receive topical treatment and had good visual outcomes. Patients with uveitis at the time of diagnosis of arthritis tended to have a worse visual prognosis and experienced persistent uveitis despite treatment. In this series, cataract extraction was beneficial in improving visual acuity immediately postoperatively, but posterior segment changes and glaucoma may compromise final visual outcomes.


Partial external biliary diversion for intractable pruritus and xanthomas in Alagille syndrome.
Alagille syndrome (AGS) causes intractable pruritus and disfiguring xanthomas because of retained bile acids and cholesterol. This study was performed to determine whether partial external biliary diversion (PEBD) is effective for relief of pruritus and xanthomas in AGS patients who fail conventional medical therapy. Between the years 1985 and 2001, 9 AGS patients underwent PEBD. Complete follow-up data were available for all patients. The average age at PEBD was 4.8 (range 1.4-10) years. The average duration of follow-up was 7.5 (range 0.5-16.0) years. All 9 patients had severe, mutilating pruritus (grade 4) prior to diversion. At 1 year post-PEBD, the average pruritus score was 1.1; 8 patients had only mild scratching when undistracted. Three patients with extensive xanthomas prior to PEBD had complete resolution within 1 year. Mean serum bile salt levels (n = 5) decreased from 136.5 to 37.1 micromol/L and mean cholesterol (n = 7) from 724 to 367 mg/dL 1 year after PEBD. A single 21-year-old patient with PEBD for 14 years experienced an increase in pruritus from grade 1 to grade 4 within 2 months of elective reversal of PEBD. In conclusion, PEBD is effective for treating severe pruritus and hypercholesterolemia in AGS patients without cirrhosis who did not respond to medical therapy. PEBD should be considered as a therapeutic option for these patients before referral for liver transplantation because of morbid complications.


The influence of panic attacks on response to phenelzine and amitriptyline in depressed outpatients.
A total of 169 depressed outpatients completed a 6-week double-blind study designed to compare the relative efficacy of a tricyclic antidepressant (amitriptyline) with a monoamine oxidase inhibitor (phenelzine). Various "target" symptoms reported to predict preferential response to monoamine oxidase inhibitors were assessed. The major finding within the whole patient sample, based on results from serial self-report and interviewer-rated scales, was that phenelzine-treated patients showed greater improvements in anxiety symptoms than did patients treated with amitriptyline. Because of the heterogeneity of the sample, patients were classified into homogeneous subgroups of clinical interest. Data analyses of these subgroups detected important drug treatment differences not discernible by analysis of data from the overall sample. Panic attacks and corresponding anxiety symptoms were reported by about one third of the patients, more often by patients with major depression than with minor depression. Patients who reported "spells of terror or panic" responded preferentially to phenelzine on several measures, particularly on items measuring anxiety. Results suggest that phenelzine may be a preferred drug for treating depressed patients with panic attacks.


[Primary hyperoxaluria type 1 detected by liver biopsy].
PH1 is caused by deficiency of the liver-specific peroxisomal enzyme alanine: glycoxylate aminotransferase (AGT). Early onset with progressive renal failure and systemic oxalosis is typical. We report a case of a 42 year-old man with PH1 in whom liver biopsy and DNA-analysis showed reduced AGT-activity and homozygosity for the polymorphism C154T and the point mutation G630A. The patient seems to respond to pyridoxine treatment. We suggest that clinical suspicion of PH1 be pursued with a diagnostic liver biopsy.


Laboratory study of microphysical and scattering properties of corona-producing cirrus clouds.
Corona-producing cirrus clouds were generated and measured under chamber conditions at the AIDA cloud chamber in Karlsruhe. We were able to measure the scattering properties as well as microphysical properties of these clouds under well-defined laboratory conditions in contrast with previous studies of corona-producing clouds, where the measurements were conducted by means of lidar and in situ aircraft measurements. Our results are in agreement with those of previous studies, confirming that corona-producing cirrus clouds consist of a narrow distribution of small (median Dp=19-32 μm) and compact ice crystals. We showed that the ice crystals in these clouds are most likely formed in homogeneous freezing processes. As a result of the homogeneous freezing process, the ice crystals grow uniformly in size; furthermore, the majority of the ice crystals have rough surface features.


Axial involvement according to ASAS criteria in an observational psoriatic arthritis cohort.
The definition of axial involvement in psoriatic arthritis (PsA) is still under debate. Currently, the axial spondyloarthritis (SpA) criteria defined by Assessment of Spondyloarthritis International Society (ASAS) may be the most adequate.(1) The aims of present study were to assess axial involvement according to ASAS criteria in an observational PsA cohort and define the clinical characteristics more associated with this kind of involvement. Our study included consecutive patients who had a visit in a tertiary Rheumatology centre. All patients included fulfill ClASsification criteria for Psoriatic Arthritis (CASPAR) criteria for PsA and all of them had a recent radiographic assessment of sacroiliitis. Clinical and laboratorial data were taken into account to classify patients as fulfilling or not ASAS criteria for axial SpA. Clinical and demographic data were analyzed about their association with presence of ASAS criteria of axial SpA in an univariable logistic regression analysis. Variables with a p-value <0.05 were re-tested in a multivariable logistic regression. Those variables that maintained statistical significance were tested alone in another multivariable model. Analyses were performed with IBM SPSS Statistics (version 20.0). Regarding the 233 patients included, only 42 patients (19.4%) fulfilled ASAS criteria for axial SpA. However, 22 patients had asymptomatic radiographic sacroiliitis according to modified New York criteria. The prevalence of asymptomatic sacroiliitis was 15.7% between patients without axial symptoms. In multivariable analysis, inflammatory back pain (IBP) [OR=25.111; 95% confidence interval (CI) = 8.770, 71.900, p-value <0.001], presence of HLA-B27 [OR=9.072; 95% CI=2.756, 29.860; p-value <0.001] and male gender [OR=3.767; 95% CI=1.264, 11.232; p-value = 0.017] were associated to axial involvement according to ASAS criteria. Axial SpA ASAS criteria are useful to identify axial involvement in PsA patients. This type of involvement is more common in males, in the presence of HLA-B27 and IBP. Axial disease should be systematically assessed in clinical practice, mainly in patients presenting with this clinical features.


Ghrelin increases the motivation to eat, but does not alter food palatability.
Homeostatic eating cannot explain overconsumption of food and pathological weight gain. A more likely factor promoting excessive eating is food reward and its representation in the central nervous system (CNS). The anorectic hormones leptin and insulin reduce food reward and inhibit related CNS reward pathways. Conversely, the orexigenic gastrointestinal hormone ghrelin activates both homeostatic and reward-related neurocircuits. The current studies were conducted to identify in rats the effects of intracerebroventricular ghrelin infusions on two distinct aspects of food reward: hedonic valuation (i.e., "liking") and the motivation to self-administer (i.e., "wanting") food. To assess hedonic valuation of liquid food, lick motor patterns were recorded using lickometry. Although ghrelin administration increased energy intake, it did not alter the avidity of licking (initial lick rates or lick-cluster size). Several positive-control conditions ruled out lick-rate ceiling effects. Similarly, when the liquid diet was hedonically devalued with quinine supplementation, ghrelin failed to reverse the quinine-associated reduction of energy intake and avidity of licking. The effects of ghrelin on rats' motivation to eat were assessed using lever pressing to self-administer food in a progressive-ratio paradigm. Ghrelin markedly increased motivation to eat, to levels comparable to or greater than those seen following 24 h of food deprivation. Pretreatment with the dopamine D1 receptor antagonist SCH-23390 eliminated ghrelin-induced increases in lever pressing, without compromising generalized licking motor control, indicating a role for D1 signaling in ghrelin's motivational feeding effects. These results indicate that ghrelin increases the motivation to eat via D1 receptor-dependent mechanisms, without affecting perceived food palatability.


An in-depth analysis of theoretical frameworks for the study of care coordination.
Complex chronic conditions often require long-term care from various healthcare professionals. Thus, maintaining quality care requires care coordination. Concepts for the study of care coordination require clarification to develop, study and evaluate coordination strategies. In 2007, the Agency for Healthcare Research and Quality defined care coordination and proposed five theoretical frameworks for exploring care coordination. This study aimed to update current theoretical frameworks and clarify key concepts related to care coordination. We performed a literature review to update existing theoretical frameworks. An in-depth analysis of these theoretical frameworks was conducted to formulate key concepts related to care coordination. Our literature review found seven previously unidentified theoretical frameworks for studying care coordination. The in-depth analysis identified fourteen key concepts that the theoretical frameworks addressed. These were 'external factors', 'structure', 'tasks characteristics', 'cultural factors', 'knowledge and technology', 'need for coordination', 'administrative operational processes', 'exchange of information', 'goals', 'roles', 'quality of relationship', 'patient outcome', 'team outcome', and '(inter)organizational outcome'. These 14 interrelated key concepts provide a base to develop or choose a framework for studying care coordination. The relational coordination theory and the multi-level framework are interesting as these are the most comprehensive.


Partial trisomy 9q resulting from a familial translocation t(9;16)(q32;q24).
Partial Trisomy- 9q was observed in an infant with a multiple malformation syndrome who survived to 18 months. Cytogenetic investigations stimulated by the family history of similarly affected individuals revealed a translocation, t(9;16)(q32;q24), identifiable in four generations of the proband's family. A review of our cases with those reported in the literature reveals clinical similarities. This report sets forth a clinical description of the characteristic phenotype of the 9q partial Trisomy syndrome, including findings at post-mortem, documents multigeneration transmission and discusses this syndrome's clinical overlap with other malformation syndromes.


Radon Levels Measured at a Touristic Thermal Spa Resort in Montagu (South Africa) and Associated Effective Doses.
Radon activity concentrations (in water and in air) were measured at 13 selected locations at the Avalon Springs thermal spa resort in Montagu (Western Cape, South Africa) to estimate the associated effective dose received by employees and visitors. A RAD-7 detector (DURRIDGE), based on alpha spectrometry, and electret detectors (E-PERM®Radelec) were used for these radon measurements. The primary source of radon was natural thermal waters from the hot spring, which were pumped to various locations on the resort, and consequently a range of radon in-water analyses were performed. Radon in-water activity concentration as a function of time (short term and long term measurements) and spatial distributions (different bathing pools, etc.) were studied. The mean radon in-water activity concentrations were found to be 205 ± 6 Bq L (source), 112 ± 5 Bq L (outdoor pool) and 79 ± 4 Bq L (indoor pool). Radon in-air activity concentrations were found to range between 33 ± 4 Bq m (at the outside bar) to 523 ± 26 Bq m (building enclosing the hot spring's source). The most significant potential radiation exposure identified is that due to inhalation of air rich in radon and its progeny by the resort employees. The annual occupational effective dose due to the inhalation of radon progeny ranges from 0.16 ± 0.01 mSv to 0.40 ± 0.02 mSv. For the water samples collected, the Ra in-water activity concentrations from samples collected were below the lower detection limit (~0.7 Bq L) of the γ-ray detector system used. No significant radiological health risk can be associated with radon and progeny from the hot spring at the Avalon Springs resort.


A thrombospondin-dependent pathway for a protective ER stress response.
Thrombospondin (Thbs) proteins are induced in sites of tissue damage or active remodeling. The endoplasmic reticulum (ER) stress response is also prominently induced with disease where it regulates protein production and resolution of misfolded proteins. Here we describe a function for Thbs as ER-resident effectors of an adaptive ER stress response. Thbs4 cardiac-specific transgenic mice were protected from myocardial injury, whereas Thbs4(-/-) mice were sensitized to cardiac maladaptation. Thbs induction produced a unique profile of adaptive ER stress response factors and expansion of the ER and downstream vesicles. Thbs bind the ER lumenal domain of activating transcription factor 6α (Atf6α) to promote its nuclear shuttling. Thbs4(-/-) mice showed blunted activation of Atf6α and other ER stress-response factors with injury, and Thbs4-mediated protection was lost upon Atf6α deletion. Hence, Thbs can function inside the cell during disease remodeling to augment ER function and protect through a mechanism involving regulation of Atf6α.


Potent New Targets for Autophagy Enhancement to Delay Neuronal Ageing.
Autophagy is a lysosomal-dependent degradation process of eukaryotic cells responsible for breaking down unnecessary and damaged intracellular components. Autophagic activity gradually declines with age due to genetic control, and this change contributes to the accumulation of cellular damage at advanced ages, thereby causing cells to lose their functionality and viability. This could be particularly problematic in post-mitotic cells including neurons, the mass destruction of which leads to various neurodegenerative diseases. Here, we aim to uncover new regulatory points where autophagy could be specifically activated and test these potential drug targets in neurodegenerative disease models of Drosophila melanogaster. One possible way to activate autophagy is by enhancing autophagosome-lysosome fusion that creates the autolysosome in which the enzymatic degradation happens. The HOPS (homotypic fusion and protein sorting) and SNARE (Snap receptor) protein complexes regulate the fusion process. The HOPS complex forms a bridge between the lysosome and autophagosome with the assistance of small GTPase proteins. Thus, small GTPases are essential for autolysosome maturation, and among these proteins, Rab2 (Ras-associated binding 2), Rab7, and Arl8 (Arf-like 8) are required to degrade the autophagic cargo. For our experiments, we used Drosophila melanogaster as a model organism. Nerve-specific small GTPases were silenced and overexpressed. We examined the effects of these genetic interventions on lifespan, climbing ability, and autophagy. Finally, we also studied the activation of small GTPases in a Parkinson's disease model. Our results revealed that GTP-locked, constitutively active Rab2 (Rab2-CA) and Arl8 (Arl8-CA) expression reduces the levels of the autophagic substrate p62/Ref(2)P in neurons, extends lifespan, and improves the climbing ability of animals during ageing. However, Rab7-CA expression dramatically shortens lifespan and inhibits autophagy. Rab2-CA expression also increases lifespan in a Parkinson's disease model fly strain overexpressing human mutant (A53T) α-synuclein protein. Data provided by this study suggests that Rab2 and Arl8 serve as potential targets for autophagy enhancement in the Drosophila nervous system. In the future, it might be interesting to assess the effect of Rab2 and Arl8 coactivation on autophagy, and it would also be worthwhile to validate these findings in a mammalian model and human cell lines. Molecules that specifically inhibit Rab2 or Arl8 serve as potent drug candidates to modulate the activity of the autophagic process in treating neurodegenerative pathologies. In the future, it would be reasonable to investigate which GAP enzyme can inhibit Rab2 or Arl8 specifically, but not affect Rab7, with similar medical purposes.


Infectious neuropathy.
Infectious neuropathy affects a large number of people worldwide. There is evidence of direct involvement of nerves by the infective agent, from the immune reaction of the patient or secondary to the toxicity of the drugs used during treatment. This group of neuropathies is often treatable or preventable. There is a complex clinical picture of the neuropathy of leprosy, different pathological features and immunological mechanisms. If the skin is unaffected in leprosy it is not always easy to demonstrate that the neuropathy is due to leprosy. Peripheral neuropathy in patients with chronic infection with hepatitis C virus may be due to the virus, the development of vasculitis or direct neurotoxic effects of the treatment. Peripheral neuropathy has become the chief neurological syndrome in individuals infected with HIV-1. The antiretroviral therapies themselves can cause peripheral neuropathies clinically indistinguishable from those caused by the virus. The occurrence of chronic polyneuropathy as a late manifestation in Lyme disease is extremely rare and is not well understood. Although infectious neuropathies are very frequent, mainly in developing countries, further studies are needed to elucidate their mechanisms of action, focusing on preventive interventions.


The complete design in the composite face paradigm: role of response bias, target certainty, and feedback.
Some years ago an improved design (the "complete design") was proposed to assess the composite face effect in terms of a congruency effect, defined as the performance difference for congruent and incongruent target to no-target relationships (Cheung et al., 2008). In a recent paper Rossion (2013) questioned whether the congruency effect was a valid hallmark of perceptual integration, because it may contain confounds with face-unspecific interference effects. Here we argue that the complete design is well-balanced and allows one to separate face-specific from face-unspecific effects. We used the complete design for a same/different composite stimulus matching task with face and non-face objects (watches). Subjects performed the task with and without trial-by-trial feedback, and with low and high certainty about the target half. Results showed large congruency effects for faces, particularly when subjects were informed late in the trial about which face halves had to be matched. Analysis of response bias revealed that subjects preferred the "different" response in incongruent trials, which is expected when upper and lower face halves are integrated perceptually at the encoding stage. The results pattern was observed in the absence of feedback, while providing feedback generally attenuated the congruency effect, and led to an avoidance of response bias. For watches no or marginal congruency effects and a moderate global "same" bias were observed. We conclude that the congruency effect, when complemented by an evaluation of response bias, is a valid hallmark of feature integration that allows one to separate faces from non-face objects.


Fate of antigen-binding cells in unresponsive and immune mice.
Antigen-binding cells (ABC) to the antigen human gamma globulin (HGG) were quantitated in lymphoid tissues of A/J mice at various times after the injection of deaggregated HGG (tolerogen), aggregated HGG (immunogen), or saline. The reaction of lymphoid cells with highly labeled HGG was specific to that antigen since binding could be inhibited by excess unlabeled HGG, but not by unrelated non-cross-reacting proteins. Compared with normal mice, there was a marked decrease in the numbers of ABC in the spleens of unresponsive animals evident as early as 12 h after the injection of tolerogen. A marked increase in ABC was observed in the spleens of immunogen-injected mice, beginning at 24 h and reaching a peak at 3 days. In bone marrow, no difference in the number of ABC was found among the three experimental groups until day 20, when a reduction in ABC was observed only in tolerogen-injected mice. No quantitative difference in the thymuses in the experimental groups could be determined because of the paucity of ABC displayed by normal thymus cells.


Transformation by avian sarcoma viruses leads to phosphorylation of multiple cellular proteins on tyrosine residues.
Phosphoamino acid compositions were determined for 10 size classes of cellular proteins, separated by electrophoresis through one-dimensional sodium dodecyl sulfate-polyacrylamide gels. Phosphotyrosine-containing proteins were observed in uninfected chicken embryo fibroblasts in every size class analyzed, ranging from approximately 20,000 to greater than 200,000 daltons. Transformation of chicken embryo fibroblasts by Rous sarcoma virus or PRC II avian sarcoma virus led to increases in phosphorylation of proteins at tyrosine residues in all of these size classes. A large fraction of the phosphotyrosine-containing protein molecules observed in Rous sarcoma virus-transformed cells was larger than 100,000 daltons with a second broad peak in the 35,000- to 60,000-dalton range. This study suggests that there are a number of substrates of viral or cellular tyrosine-specific protein kinases, which have not yet been identified by other methods.


Advances in paediatric pulmonary vascular disease associated with bronchopulmonary dysplasia.
Pulmonary hypertension (PH) is a common finding in infants with bronchopulmonary dysplasia (BPD). The aim of this review is to describe recent advances in the diagnosis and treatment of PH and discuss whether they will benefit infants and children with BPD related PH. Echocardiography remains the mainstay of diagnosis but has limitations, further developments in diagnostic techniques and identification of biomarkers are required. There are many potential therapies for PH associated with BPD. Inhaled nitric oxide has been shown to improve short term outcomes only. Sidenafil in resource limited settings was shown in three randomized trials to significantly reduce mortality. The efficacy of other therapies including prostacyclin, PDE3 inhibitors and endothelin receptor blockers has only been reported in case reports or case series. Randomized controlled trials with long term follow up are required to appropriately assess the efficacy of therapies aimed at improving the outcome of children with PH.


Medical adjunctive therapy for patients with chronic limb-threatening ischemia: a systematic review.
The aim of this article is to systematically review the literature on medical adjunctive therapy for patients with chronic limb-threatening ischemia (CLTI). MEDLINE, Embase, and Cochrane Database of Systematic Reviews were searched for studies published between January 1st, 2009, and June 1st, 2019. Articles that studied medical treatment of CLTI patients and reported clinical outcomes were eligible. Main exclusion criteria were case reports <20 patients, incorrect publication type, and CLTI caused by Buerger disease. The primary end point was major amputation (above the ankle) in studies with a follow-up of ≥6 months. Secondary end points were other clinical end points such as death and wound healing. Study quality was assessed according to the Downs and Black checklist. Included were 42 articles: four focused on antiplatelet therapy, five on antihypertensive medication, 6 on lipid-lowering therapy, 16 on stem cell therapy, three on growth factors, five on prostanoids, and one study each on cilostazol, glucose-lowering therapy, spinal cord stimulation, sulodexide, and hemodilution. Calcium channel blockers, iloprost, cilostazol, and hemodilution showed significant improvement of limb salvage, but data are limited. Stem cell therapy showed no significant improvement of limb salvage but could potentially improve wound healing. Antiplatelets, antihypertensives, and statins showed significantly lower cardiovascular events rates but not evident lower major amputation rates. The quality of the studies was fair to good. Certain medical therapies serve to improve limb salvage next to revascularization in CLTI patients, whereas others are important in secondary prevention. Because high quality evidence is limited, further research is needed.


SIGNOR: a database of causal relationships between biological entities.
Assembly of large biochemical networks can be achieved by confronting new cell-specific experimental data with an interaction subspace constrained by prior literature evidence. The SIGnaling Network Open Resource, SIGNOR (available on line at http://signor.uniroma2.it), was developed to support such a strategy by providing a scaffold of prior experimental evidence of causal relationships between biological entities. The core of SIGNOR is a collection of approximately 12,000 manually-annotated causal relationships between over 2800 human proteins participating in signal transduction. Other entities annotated in SIGNOR are complexes, chemicals, phenotypes and stimuli. The information captured in SIGNOR can be represented as a signed directed graph illustrating the activation/inactivation relationships between signalling entities. Each entry is associated to the post-translational modifications that cause the activation/inactivation of the target proteins. More than 4900 modified residues causing a change in protein concentration or activity have been curated and linked to the modifying enzymes (about 351 human kinases and 94 phosphatases). Additional modifications such as ubiquitinations, sumoylations, acetylations and their effect on the modified target proteins are also annotated. This wealth of structured information can support experimental approaches based on multi-parametric analysis of cell systems after physiological or pathological perturbations and to assemble large logic models.


High-level expression of active human cyclooxygenase-2 in insect cells.
Active human cyclooxygenase-2 (Cox-2) was expressed at high levels in insect cells using a recombinant baculovirus. The specific activity of Cox-2 in the microsomes of infected cells was 0.51 mumol O2/min/mg and was comparable to that obtained for partially purified Cox-2 from ovine placenta (0.55 mumol O2/min/mg). The Cox-2 enzyme expressed in insect cells was glycosylated to varying extents and most of the cyclooxygenase activity was in the high-speed microsomal pellet. The insect-cell-expressed enzyme also showed characteristic 15-hydroxyeicosa-tetraenoic acid production after aspirin treatment and had typical inhibition profiles with a number of known nonsteroidal antiinflammatory drugs.


[Reliability of the diagnosis of chronic pancreatitis].
Severe chronic pancreatitis can be easily diagnosed by means of pancreatic function tests and/or imaging procedures, whereas the mild form of the disease or its early stages are more difficult to detect and are often only retrospectively diagnosed. The reliability of imaging procedures depends mainly on the experience of the investigator, whereas the reliability of the pancreatic function tests depends on the patient's compliance. Further diagnostic procedures should be performed in accordance with the mayor symptom. If weight loss, diarrhea and/or steatorrhea dominate, indirect pancreatic function tests are required. Normal results of these tests usually exclude a pancreatogenic origin. If epigastric complaints dominate, ERCP should be performed prior to the indirect pancreatic function tests. If all findings are normal and all other upper abdominal diseases ruled out, but--due to persisting symptoms--chronic pancreatitis is still suspected, a direct function test should be performed to confirm or refute the tentative diagnosis. Chronic pancreatitis may--in its early stage--only involve the small pancreatitic ducts, not visible on ERCP examination, and indirect pancreatic function tests may show falsely normal test results.


A multicompartment vascular model for inferring baseline and functional changes in cerebral oxygen metabolism and arterial dilation.
Functional hemodynamic responses are the composite results of underlying variations in cerebral oxygen consumption and the dilation of arterial vessels after neuronal activity. The development of biophysically based models of the cerebral vasculature allows the separation of the neuro-metabolic and neuro-vascular influences on measurable hemodynamic signals such as functional magnetic resonance imaging or optical imaging. We describe a multicompartment model of the vascular and oxygen transport dynamics associated with stimulus-driven neuronal activation. Our model offers several unique features compared with previous formulations such as the ability to estimate baseline blood flow, volume, and oxygen consumption from functional data. In addition, we introduce a capillary compliance model, arterial and venous oxygen permeability, and model the dynamics of extravascular tissue oxygenation. We apply this model to multimodal optical spectroscopic and laser speckle imaging of the rat somato-sensory cortex during nine conditions of whisker stimulation. By fitting the model using a psuedo-Bayesian framework to incorporate multimodal observations, we estimate baseline blood flow to be 94 (+/-15) mL/100 g min and baseline oxygen consumption to be 6.7 (+/-1.3) mL O(2)/100 g min. We calculate parametric, linear increases in arterial dilation (R(2)=0.96) and CMRO(2) (R(2)=0.87) responses over the nine conditions. Other parameters estimated by the model include vascular transit time and volume reserve, oxygen content, saturation, diffusivity rate constants, and partial pressure of oxygen in the vascular compartments and in the extravascular tissue. Finally, we compare this model to earlier work and find that the multicompartment model more accurately describes the observed oxygenation changes when compared with a single compartment version.


Determining the duration of therapy for patients with community-acquired pneumonia.
Emerging data, including results from two systematic reviews, suggest that with appropriate antimicrobial selection, community-acquired pneumonia (CAP) can be successfully treated in less than 7 days, rather than the 7-14 days frequently utilized. Shorter course therapy has the potential not only to improve efficacy, safety, and compliance, but also to minimize the evolution of resistance. Utilization of procalcitonin as a biomarker in CAP can appropriately influence the duration of therapy without affecting mortality and cure rates. CAP treatment duration can further be reduced successfully into the clinical setting with the assistance of an antibiotic stewardship team.


The impact of NHS Direct on the demand for out-of-hours primary and emergency care.
In order to assess the impact of NHS Direct on out-of-hours primary and emergency care, we sought data on service demand from all GP cooperatives, ambulance services and emergency departments in England, Wales and Scotland. We analysed the impact of NHS Direct on demand, taking advantage of the fact that the service was introduced in waves over a period of 2 years. The results showed that the introduction of NHS Direct was associated with a reduction in calls to GP cooperatives, but with no evident effect on emergency services.


Effect of surface treatments and coffee thermocycling on the color and translucency of CAD-CAM monolithic glass-ceramic.
The effects of surface treatments and coffee thermocycling on the color and relative translucency of a recently introduced computer-aided design and computer-aided manufacturing (CAD-CAM) monolithic glass-ceramic are unknown. The purpose of this in vitro study was to evaluate the effect of coffee thermocycling on the color and relative translucency parameter (RTP) of CAD-CAM monolithic glass-ceramics after different surface treatments. Specimens (1.5-mm-thick) were sectioned from zirconia-reinforced lithium silicate glass-ceramic (ZLS) (n=18) and lithium disilicate glass-ceramic (LDS) blocks (n=18). Two different types of surface treatments (glazing or polishing) were applied to the specimens. The specimens were subjected to 5000 thermocycles in a coffee solution. The color coordinates of specimens were measured before and after coffee thermocycling by using a spectroradiometer, and color differences and relative translucency values were calculated by using CIEDE2000 color difference and RTP formulas. ANOVA was used to analyze the color difference and relative translucency values by using maximum likelihood estimation and the Satterthwaite degrees of freedom methods. Any significant interaction between surface subgroups was further analyzed by using the Tukey-Kramer adjustment (α=.05). Material type had a significant effect on color difference (P=.018). All color difference values of all materials were smaller than the clinical acceptability threshold (<1.8 units). For relative translucency, material (P<.001) and coffee thermocycling had a significant effect (P=.014), and an interaction was found between the surface treatments and materials (P<.001). The Tukey-Kramer test revealed significant differences between glazed and polished subgroups of LDS material, except for ZLS-glazed and ZLS-polished subgroups. Different surface treatments of CAD-CAM monolithic zirconia-reinforced lithium silicate and lithium disilicate glass-ceramics resulted in clinically acceptable color changes after coffee thermocycling. The color changes in all groups, except for LDS-polished, were not perceivable. Lithium disilicate was more translucent than zirconia-reinforced lithium silicate before and after coffee thermocycling. Coffee thermocycling decreased the translucency of both of the materials. Different surface treatments affected the translucency of only lithium disilicate for tested thickness.


Organic and Inorganic Pollutant Concentrations Suggest Anthropogenic Contamination of Soils Along the Manali-Leh Highway, Northwestern Himalaya, India.
Most studies on roadside soil pollution have been performed in areas where petrol is the main fuel. Very little work has been conducted in regions where diesel predominates. We collected soil samples from four sites that span a precipitation gradient along the Manali-Leh Highway in northwestern Himalaya, India. This road traverses rough terrain and most of the vehicles that travel along it are diesel-driven. At each site, we collected samples at incremental distances from the highway (0, 2, 5, 10, 20, and 150 m), and at each distance we collected samples from three depths (3, 9, and 15 cm). We assessed the concentrations of 10 heavy metals (Al, Fe, Cr, Cu, Pb, Ni, Co, Zn, V, and Ba), total sulphur, and total organic carbon (TOC) at each distance, and we measured the concentration of 16 polycyclic aromatic hydrocarbons (PAHs) at 2 m from the highway. Overall, we found that metal concentrations are low and there is no relationship between concentrations and distance from the highway, or depth within the soil profile. Sulphur concentrations, on the other hand, are high in roadside soils and there is a negative relationship between concentration and distance from the highway. PAH concentrations are low, but the proportion of different ringed species suggests that their source is anthropogenic. Correlations between TOC and the various pollutants further suggest that diesel vehicles and potentially biomass combustion are starting to affect the roadside environment in remote northwestern India. We suggest that pollutant concentrations be regularly monitored.


Chitosan-agarose scaffolds supports chondrogenesis of Human Wharton's Jelly mesenchymal stem cells.
Tissue engineering strategies for cartilage aim to restore the complex biomechanical and biochemical properties of the native cartilage. To mimic the in vivo microenvironment, we developed a novel scaffold based on chitosan-agarose (CHAG scaffold) resembling the properties of native cartilage extracellular matrix (ECM) that aids in vitro cartilage formation. The CHAG scaffolds had pore size ranging from 75 to 300 µm and the degradation of 18% over 6 months in PBS. L929 cells and Human Wharton's Jelly-Mesenchymal Stem Cells (HWJ-MSCs) attached well and grew in the CHAG scaffolds. HWJ-MSCs seeded on CHAG scaffolds and cultured in chondrogenic medium were able to differentiate into chondrogenic lineage. Simultaneous supplementation of growth factors (BMP-2, TGF-β3) significantly enhanced chondrogenesis and neo ECM synthesis. CHAG scaffolds seeded with HWJ-MSCs cultured in chondrogenic media supplemented with both BMP-2 and TGF-β3 produced 12.71 ± 1.0 µg GAG/µg DNA compared to the one which received no or either of the growth factors. Our findings suggest that CHAG scaffolds could be used as a biomaterial scaffold for cell mediated repair approaches based on HWJ-MSCs for articular cartilage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1845-1855, 2017.


Structural modeling and electrostatic properties of aspartate transcarbamylase from Saccharomyces cerevisiae.
In Saccharomyces cerevisiae the first two reactions of the pyrimidine pathway are catalyzed by a multifunctional protein which possesses carbamylphosphate synthetase and aspartate transcarbamylase activities. Genetic and proteolysis studies suggested that the ATCase activity is carried out by an independently folded domain. In order to provide structural information for ongoing mutagenesis studies, a model of the three-dimensional structure of this domain was generated on the basis of the known X-ray structure of the related catalytic subunit from E. coli ATCase. First, a model of the catalytic monomer was built and refined by energy minimization. In this structure, the conserved residues between the two proteins were found to constitute the hydrophobic core whereas almost all the mutated residues are located at the surface. Then, a trimeric structure was generated in order to build the active site as it lies at the interface between adjacent chains in the E. coli catalytic trimer. After docking a bisubstrate analog into the active site, the whole structure was energy minimized to regularize the interactions at the contact areas between subunits. The resulting model is very similar to that obtained for the E. coli catalytic trimer by X-ray crystallography, with a remarkable conservation of the structure of the active site and its vicinity. Most of the interdomain and intersubunit interactions that are essential for the stability of the E. coli catalytic trimer are maintained in the yeast enzyme even though there is only 42% identity between the two sequences. Free energy calculations indicate that the trimeric assembly is more stable than the monomeric form. Moreover an insertion of four amino acids is localized in a loop which, in E. coli ATCase, is at the surface of the protein. This insertion exposes hydrophobic residues to the solvent. Interestingly, such an insertion is present in all the eukaryotic ATCase genes sequences so far, suggesting that this region is interacting with another domain of the multifunctional protein.


[Isaacs' syndrome. Diagnosis and differential diagnosis of neuromyotonia].
Neuromyotonia is a clinical and electrophysiological syndrome of spontaneous muscle fiber activity due to hyperexcitability of peripheral nerve origin causing generalised, visible myokymia and muscular cramps. Electromyography shows abnormal doublet and triplet discharges of high intraburst frequency as well as myokymic and neuromyotonic discharges. Fasciculations and fibrillation potentials are common. Most commonly, neuromyotonia is an acquired immune-mediated disorder (Isaacs' syndrome) showing elevated antibody levels against presynaptic, voltage-gated, potassium channels. Some of these patients have additional autonomic (hyperhidrosis) and/or CNS symptoms similar to those from limbic encephalitis (referred to then as Morvan's syndrome). We report on a patient with Isaacs' syndrome and discuss the clinical and electrophysiological features, pathophysiology, diagnosis, and differential diagnosis of diseases with peripheral nerve hyperexcitability.


Radish sprouts as an efficient and rapidly available host for an agroinfiltration-based transient gene expression system.
Agroinfiltration, the infiltration of plants with Agrobacterium harboring a plasmid that contains a specific gene, is used to transiently express a gene in a heterologous organism. Using the "Tsukuba system", greater amounts of target protein accumulate compared with usual expression plasmids. Reported host plants, including Nicotiana benthamiana, a common plant for agroinfiltration, need several weeks after sowing to grow enough for infection. To shorten the culture period and, thereby, improve target protein production, we tested sprouts as host plants. Sprouts were grown in the dark to encourage elongation so that vacuum infiltration becomes easier, and this was followed by a few days of exposure to illumination before infection with pBYR2HS-EGFP, the EGFP expression plasmid of the Tsukuba system. Among six tested species of Fabaceae and Brassicaceae, radish showed the highest transient expression. Among six tested radish cultivars, Kaiware, Hakata, and Banryoku provided the best results. Culturing for 5 day, including 1 day of imbibition and 1 to 2 day of exposure to illumination resulted in EGFP fluorescence in 80% of the cotyledon area. Thus, a remarkable amount of EGFP was obtained only 8 day after seed imbibition. The EGFP amount in Kaiware cotyledons was comparable with Rubisco at ∼0.7 mg/g fresh weight. Kaiware sold in supermarkets could also be used, but resulted in lower expression levels.


The roles of myoglobin, MB iso-enzyme of creatine phosphokinase and aspartate aminotransferase in serum in the acute phase of myocardial infarction.
The diagnostic value of serum myoglobin as compared to MB iso-enzyme of creatine phosphokinase and aspartate aminotransferase was investigated in 25 patients admitted on suspicion of acute myocardial infarction with a duration of symptoms less than 6 hours. In group 1 (acute myocardial infarction group), the first blood sample, obtained at a mean time of 3.27 hours after onset of infarction, invariably showed increased myoglobin (mean 2.6-fold normal) whereas MB iso-enzyme of creatine phosphokinase and aspartate aminotransferase were often normal. Peak myoglobin values occurred earlier than peak serum MB iso-enzyme of creatine phosphokinase values. The highest peak values of serum myoglobin were found in patients with extensive myocardial infarction. In group 2 (non-acute myocardial infarction or control group) serial determinations of serum myoglobin, serum MB iso-enzyme of creatine phosphokinase and aspartate aminotransferase were within normal limits. Hence the importance lies with the early detection of serum myoglobin in acute myocardial infarction.


Triamcinolone acetonide facilitates removal of the epiretinal membrane and separation of the residual vitreous cortex in highly myopic eyes with retinal detachment due to a macular hole.
To study the usefulness of intravitreal triamcinolone acetonide injection during vitrectomy in highly myopic eyes with retinal detachment due to a macular hole. Pars plana vitrectomy was performed in 6 patients with retinal detachment resulting from a highly myopic eye with a macular hole. After separation of the posterior hyaloid and removal of any visible epiretinal membrane, triamcinolone acetonide was injected over the posterior pole. Excised specimens were evaluated by transmission electron microscopy. Upon injection of triamcinolone acetonide, the entire epiretinal membrane and residual vitreous cortex could be visualized in all patients. The epiretinal membrane and residual posterior vitreous cortex were completely removed. Successful reattachment was performed without retinal damage in all cases. Electron microscopy revealed a cellular epiretinal membrane within a collagenous matrix lining the smooth internal surface of the internal limiting membrane. No complications related to the use of triamcinolone acetonide were encountered. Intraoperative visualization of the epiretinal membrane and residual posterior vitreous cortex with triamcinolone acetonide was found to be a useful adjunct to vitrectomy. Using triamcinolone acetonide during vitrectomy may facilitate both removal of the epiretinal membrane around the macular hole and separation of the residual vitreous cortex from the retina in highly myopic eyes with retinal detachment.


Inhibitor of DNA-binding family regulates the prognosis of ovarian cancer.
Aim: The mechanistic role of inhibitor of DNA binding or differentiation (ID) family in ovarian cancer (OC) has remained unclear. Materials & methods: We used the Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, SurvExpress, PROGgene V2, TIMER, and FunRich to evaluate the prognostic value of IDs in patients with OC. Results: the mRNA transcripts of all IDs were markedly downregulated in OC compared with normal tissue. The prognostic value of IDs was also explored within the subtypes, pathological stages, clinical stages and TP53 mutational status. The group with low-risk IDs showed relatively good overall survival (OS) compared with the high-risk group. Conclusion: ID1/3/4 may be exploited as promising prognostic biomarkers and therapeutic targets in OC patients.


Free and total plasma theophylline concentrations in chronic airflow obstruction.
It has been suggested that the variability in clinical response between individuals at any given total plasma theophylline concentration may be related to interpatient variability in theophylline plasma protein binding. We therefore measured the plasma protein binding of theophylline in plasma from 39 outpatients with chronic airflow obstruction who were receiving long term oral theophylline treatment. The protein binding was measured at 37 degrees C and pH 7.4 by equilibrium dialysis. Total plasma theophylline concentration was measured by high performance liquid chromatography and the free concentration calculated by multiplying total concentration by the free (unbound) fraction. The total plasma theophylline concentration varied from 0.7 to 22.0 micrograms/ml, mean 10.6 (SD 5.3) micrograms/ml (3.9-121 mumol/l, mean 58.3 (29.2) mumol/l). The free fraction of theophylline varied only from 0.58 to 0.69 (mean 0.626 (0.024] microgram/ml and was not related to the total concentration (r = -0.236, n = 39, p greater than 0.05). There was a very close relationship between free and total plasma concentrations (r = 0.996, n = 39, p less than 0.001). It is concluded that there is little variability in plasma protein binding of theophylline in patients with chronic airflow obstruction. Other factors appear to be responsible for variability between individuals in the response to a given total plasma theophylline concentration.


HGVA: the Human Genome Variation Archive.
High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic data for key reference projects in a clean, fast and integrated fashion. HGVA provides an efficient and intuitive web-interface for easy data mining, a comprehensive RESTful API and client libraries in Python, Java and JavaScript for fast programmatic access to its knowledge base. HGVA calculates population frequencies for these projects and enriches their data with variant annotation provided by CellBase, a rich and fast annotation solution. HGVA serves as a proof-of-concept of the genome analysis developments being carried out by the University of Cambridge together with UK's 100 000 genomes project and the National Institute for Health Research BioResource Rare-Diseases, in particular, deploying open-source for Computational Biology (OpenCB) software platform for storing and analyzing massive genomic datasets.


Generation of an Iba1-EGFP Transgenic Rat for the Study of Microglia in an Outbred Rodent Strain.
Neuroscience has been transformed by the ability to genetically modify inbred mice, including the ability to express fluorescent markers specific to cell types or activation states. This approach has been put to particularly good effect in the study of the innate immune cells of the brain, microglia. These specialized macrophages are exceedingly small and complex, but also highly motile and mobile. To date, there have been no tools similar to those in mice available for studying these fundamental cells in the rat brain, and we seek to fill that gap with the generation of the genetically modified Sprague Dawley rat line: SD-Tg(Iba1-EGFP)Mmmc Using CRISPR-Cas/9 technology, we knocked in EGFP to the promoter of the gene Iba1 With four male and three female founders confirmed by quantitative PCR analysis to have appropriate and specific insertion, we established a breeding colony with at least three generations of backcrosses to obtain stable and reliable Iba1-EGFP expression. The specificity of EGFP expression to microglia was established by flow cytometry for CD45low/CD11b+ cells and by immunohistochemistry. Microglial EGFP expression was detected in neonates and persisted into adulthood. Blood macrophages and monocytes were found to express low levels of EGFP, as expected. Last, we show that EGFP expression is suitable for live imaging of microglia processes in acute brain slices and via intravital two-photon microscopy.


Unconscious attentional orienting to exogenous cues: A review of the literature.
The present paper reviews research that focuses on the dissociation between bottom-up attention and consciousness. In particular, we focus on studies investigating spatial exogenous orienting in the absence of awareness. We discuss studies that use peripheral masked onset cues and studies that use gaze cueing. The results from these studies show that the classic biphasic pattern of facilitation and inhibition, which is characteristic of conscious exogenous cueing can also be obtained with subliminal spatial cues. It is hypothesized that unconscious attentional orienting is mediated by the subcortical retinotectal pathway. Moreover, a possible neural network including superior colliculus, pulvinar and amygdala is suggested as the underlying mechanism.


Wenckebach periods associated with high grade second degree (2 : 1 and 3 : 1) A-V block.
An electrocardiogram (ECG) of bilateral bundle branch block (BBBB) which may be attributable to a mixture of 2 : 1 and 3 : 1 atrioventricular (A-V) block is described. The irregularity of QRS complexes with left bundle branch block (LBBB) pattern during 2 : 1 A-V block may be ascribable to "Wenckebach periods", which might be due either to A-V nodal or His bundle or bundle branch delay. However, it was impossible to distinguish between them precisely because appropriate His bundle studies were not performed during the active arrhythmic phase. Although the exact mechanism involved were not established with certainty, different rates of recovery in conduction in the bundle branches in association with a marked prolongation of the refractoriness would seem to be the unique feature of this complex arrhythmia. An ECG tracing of BBBB indicating high grade second degree (2 : 1 and 3 : 1) A-V block, in which "spontaneous" occurrence of "Wenckebach periods" with 2 consecutive blocked P waves can be observed during 2 : 1 A-V block, has never been reported previously as far as can be ascertained from published records.


Scanning Spreading Resistance Microscopy: A Promising Tool for Probing the Reaction Interface of Li-Ion Battery Materials.
Imaging of the Li-insertion/extraction [Li-in/out] interface of the electrode materials of Li-ion batteries is essential to reveal their bulk mechanism of electrochemical reaction and phase behavior in the crystal. Generally, the material properties significantly change at this interface. Therefore, direct probing of the changing properties is a promising approach to reliably investigate the Li-in/out interface in the bulk crystal of electrode materials. In this study, we investigated the change in electron conductivity of rutile-TiO2 with Li-insertion and extraction, as a model for the electrochemical interface of a bulk crystal of electrode material. In addition, we probed the interface using logarithm contact resistance [log R (Ω)] imaging via scanning spreading resistance microscopy (SSRM). A distinct Li-in/out interface on the rutile-TiO2(001) wafer was observed using this technique. The imaging resolution of this region was estimated to be approximately 40-50 nm in SSRM images, which was two to three times higher than the resolution of the topographic image (100-150 nm), which was restricted to the curvature radius of the SSRM probe tip. A high spatial resolution was obtained via SSRM imaging because this approach is not influenced by the geometric effects of the surface. This result demonstrated the potential of SSRM imaging for the study of the Li-in/out interface.


Identification of anisakid nematodes from the Southern Baltic Sea using PCR-based methods.
Four common species of Baltic anisakids Anisakis simplex, Hysterothylacium auctum, Contracaecum osculatum from fish (the last one also from the grey seal) and C. rudolphii from cormorants were examined using PCR-RFLP technique for working out the method allowing their identification and differentiation. A fragment of nuclear DNA containing intergenic regions (ITS-1 and ITS-2) of ribosomal DNA together with adjacent sequences of genes coding 18S and 28S rRNA (in total; approximately 1500 bp) was amplified and the products were digested using three endonucleases Hin fI, Hae III and Pvu II. Digestion with Hin fI endonuclease enabled species identification and differentiation between all nematode species studied. Digestion with Hae III endonuclease enabled identification of A. simplex and H. auctum while electrophoretic patterns obtained for both Contracaecum species were similar (differentiation between A. simplex, H. auctum and the genus Contracaecum). Pvu II endonuclease was not suitable to this purpose. On the basis of nucleotide sequences obtained, the pairs of species-specific primers were designed for each species studied. By the use of these pairs of primers the species-specific PCR reactions were carried out. The sizes of specific products were: 486 bp for A. simplex, 491 bp for C. osculatum, 505 bp for C. rudolphii and 663 bp for H. auctum. The methods presented herein can be useful in diagnostics of human anisakidosis, especially when parasites are disrupted.


Asthma severity and PTSD symptoms among inner city children: a pilot study.
Although the association between posttraumatic stress symptoms and asthma severity among children has been hypothesized, it has yet to be explored rigorously. This study sought to describe the posttraumatic stress symptoms of children with asthma and explore the relationship between asthma severity and posttraumatic stress symptoms in an inner city sample with high rates of traumatic exposures. Children aged 7 to 17 years, with a clinician-defined asthma diagnosis, were recruited from an inner city outpatient asthma clinic. Caregivers completed measures assessing the child's asthma and posttraumatic stress symptoms and health care utilization. Children also completed measures of asthma, posttraumatic stress symptoms, and asthma-related quality of life. In all, 24 children-caregiver dyads were enrolled. The sample was 79% male and 83% African American, and the mean age was 11 years. Overall the sample had severe asthma, with 33% having been hospitalized over the past year. In addition, 25% of the sample met Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for the diagnosis of posttraumatic stress disorder, and 74% of the sample experienced a traumatic event. Posttraumatic stress disorder symptoms were found to be significantly related to asthma severity, quality of life, and health care utilization. Assessing for and treating posttraumatic stress symptoms among children with severe asthma may help to improve their asthma course and quality of life. Further research should explore this relationship and related treatment implications.


The decreased circular RNA hsa_circ_0072309 promotes cell apoptosis of ischemic stroke by sponging miR-100.
To investigate the expression of circ_0072309 in patients with ischemic stroke (IS) and in LIFR humanized mice with middle cerebral artery occlusion (MCAO). Further, we explored the underlying mechanism of circ-0072309 in IS. The content of circ-0072309 in serum of patients with IS (n = 70) was measured by qRT-PCR, and the ROC curve was analyzed. LIFR humanized mice were used to measure the content of circ-0072309 in ischemic hemisphere by qRT-PCR and the protein expression of cleaved-caspase-3, cleaved-caspase-8 were detected by Western blot. After that, the expression of miR-100 in serum of patients with IS and in ischemic hemisphere of MCAO mice were detected, and then, we analyzed the correlation between the expression of circ-0072309 and miR-100. The binding sites between circ-0072309 and miR-100 were predicted by online database. We detected whether cric-0072309 bind to miR-100 by Dual-Luciferase report in bEnd2. In addition, bEnd2 was treated with oxygen-glucose deprivation (OGD) to simulate injury of cerebral vascular after cerebral ischemia. After treated with miR-100 mimic or miR-100-inhibitor, we detected the cell survival and rate of cell apoptosis, and the content of cleaved-caspase-3 and caspase-8 protein. The target mRNA of miR-100 was predicted by bioinformatics analysis and analyzed by Dual-Luciferase. After treating bEnd2 with circ-0072309 and miR-100 mimic, we analyzed the cell survival and apoptosis to identify the potential regulatory mechanism. The results of qRT-PCR showed that the expression of circ-0072309 was significantly decreased while the content of miR-100 was significantly increased in the serum of IS patients and in the ischemic hemisphere of MCAO mice. There was a negative correlation between the expression of circ-0072309 and miR-100. The results of Dual-Luciferase showed that circ-0072309 could directly bind to miR-100. After treating bEnd2 with OGD, miR-100-mimic caused a decrease rate of cell survival and an increased rate of apoptosis. Dual-Luciferase showed that miR-100 regulated cell survival and apoptosis by directly binding to mTOR. By comparing treated bEnd2 with circ-0072309, co-transfected bEnd2 with circ-0072309 and miR-100 reduced cell survival and increased apoptosis. According to these results, this study revealed that the circ_0072309-miR-100-mTOR regulatory axis could alleviate IS, and it may be a potential target for the treatment of IS.


Coping after recurrent miscarriage: uncertainty and bracing for the worst.
The aim of this study was to understand how women with single or recurrent miscarriages cope during the waiting periods after miscarriage--waiting for pregnancy or waiting for pregnancy confirmation--and to investigate their perception of a 'positive reappraisal' coping intervention designed for these waiting periods. Positive reappraisal is a cognitive strategy to change the meaning of a situation, specifically reinterpreting the situation in a more positive way. A qualitative methodology was used. Data were obtained from two focus groups comprising nine women with one or more miscarriages. Two core categories, 'uncertainty' and 'bracing', were highlighted during the waiting period for confirmation of an ongoing pregnancy. Women who had experienced a single miscarriage appraised this waiting period as benign and used distraction and coping by social support. Women with recurrent miscarriages could not confidently appraise the waiting period as one that would bring hope or joy and used bracing for the worst as their coping strategy to manage this ambivalence. With this strategy, women tried to control their current emotions, and looked into the future to try to minimise their distress if a further miscarriage occurred. Although all women thought that a 'positive reappraisal' coping intervention would be practical and applicable during waiting periods, only women with recurrent miscarriages actually wanted to use such an intervention. Coping interventions targeting reappraisal of the waiting period stressor situation could help women to cope as they wait for a subsequent pregnancy to be confirmed as ongoing. Coping interventions may need to be tailored, but before any strategy is introduced, further study is needed to identify the most appropriate approach.


Impact of phase lag on synchronization in frustrated Kuramoto model with higher-order interactions.
The study of first order transition (explosive synchronization) in an ensemble (network) of coupled oscillators has been the topic of paramount interest among the researchers for more than one decade. Several frameworks have been proposed to induce explosive synchronization in a network and it has been reported that phase frustration in a network usually suppresses first order transition in the presence of pairwise interactions among the oscillators. However, on the contrary, by considering networks of phase frustrated coupled oscillators in the presence of higher-order interactions (up to 2-simplexes) we show here, under certain conditions, phase frustration can promote explosive synchronization in a network. A low-dimensional model of the network in the thermodynamic limit is derived using the Ott-Antonsen ansatz to explain this surprising result. Analytical treatment of the low-dimensional model, including bifurcation analysis, explains the apparent counter intuitive result quite clearly.


The preoperative and postoperative oxidative status of children with chronic adenotonsillar hypertrophy.
This study aimed to evaluate the preoperative and postoperative oxidative status of children with chronic adenotonsillar hypertrophy. The study comprised 25 patients with indications for tonsillectomy and/or adenoidectomy following a diagnosis of chronic adenotonsillar hypertrophy and 25 age-gender matched control patients were included to the study. Blood samples were taken from the patients preoperatively and at four weeks postoperatively. Preoperative and postoperative serum total oxidant (TOS) and total antioxidant (TAS) levels were measured and the oxidative stress index (OSI) was calculated. The serum total oxidant level and oxidant stress index values in the preoperative and postoperative periods of the patients were found to be significantly high compared to those of the control group. While the preoperative serum total oxidant level values were found to be significantly high compared to the postoperative values, no statistical significance was found between the total antioxidant and oxidative stress index values. The development of chronic adenotonsillar hypertrophy plays a role in oxidative status and therefore, to neutralize high levels of oxidants in patients, the use of antioxidants for a period preoperatively and postoperatively is thought to be necessary.


Europium-directed self-assembly of a luminescent supramolecular gel from a tripodal terpyridine-based ligand.
Eu(III), the last piece in the puzzle: Europium-induced self-assembly of ligands having a C(3)-symmetrical benzene-1,3,5-tricarboxamide core results in the formation of luminescent gels. Supramolecular polymers are formed through hydrogen bonding between the ligands. The polymers are then brought together into the gel assembly through the coordination of terpyridine ends by Eu(III) ions (blue dashed arrow: distance between two ligands in the strand direction).


Early glottic cancer: surgery or radiation therapy?
From 1970 to 1979 at the University Otorhinolaryngological Clinic, at the Radiology Institute of the University and at the Radiation Therapy Department of the Hospital of Florence, 385 early glottic cancers were treated: 300 by surgery and 85 with radiation therapy as the primary therapy. The policy of treatment in this period was in most cases surgery; those patients who could not be operated were treated with radiation therapy. The local control actuarial rates at 5 years were 85%, 70% and 65% for the T1a, T1b and T2 patients treated by surgery, and 86%, 83% and 57% for those treated with radiation therapy. Considering the surgical salvage, the actuarial results at 5 years were 95%, 86% and 71% for the group treated by surgery, and 86%, 90% and 69% for the one treated with radiotherapy. The crude results at 3 and 5 years with an analysis of failures according to treatment modalities are also reported. In our experience, cordectomy can be the treatment of choice in T1a glottic cancer, whereas radiation therapy offers better results in the T1b forms. Treatment policy is more questionable in the T2 cases.


Comparison of ELISA and HI for detection of antibodies against Wesselsbron disease virus.
A two-graph Receiver Operating Characteristic analysis was done to determine the optimal cut-off value of an indirect enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to Wesselsbron disease (WSL) virus. When ELISA and haemagglutination-inhibition (HI) results of WSL-positive and WSL-negative control sheep sera were compared, the sensitivity of ELISA was 97.9% and that of HI, 87.5%, while the specificity of ELISA and HI were 95.7% and 100%, respectively. The ELISA's superior sensitivity was confirmed by the results of the two assays performed on a simulated range of low-positive sera, which showed that the ELISA was able to detect WSL-antibody levels at least ten times lower than those the HI could. The ELISA was also less cross-reactive than the HI to guinea-pig antisera against nine flaviviruses relevant to southern Africa. The combination of the ELISA's ability to test untreated sera in single dilution and its superior sensitivity and lower cross-reactivity as compared to that of the traditional HI, makes it the assay of choice for automation and large-scale screening of animals for antibodies to WSL virus.


A compact and stable incidence-plane-rotating second harmonics detector.
We describe a compact and stable setup for detecting the optical second harmonics, in which the incident plane rotates with respect to the sample. The setup is composed of rotating Fresnel rhomb optics and a femtosecond ytterbium-doped fiber laser source operating at the repetition frequency of 10 MHz. The setup including the laser source occupies an area of 1 m2 and is stable so that the intensity fluctuation of the laser harmonics can be less than 0.2% for 4 h. We present the isotropic harmonic signal of a gold mirror of 0.5 pW and demonstrate the integrity and sensitivity of the setup. We also show the polarization-dependent six-fold pattern of the harmonics of a few-layer WSe2, from which we infer the degree of local-field effects. Finally, we describe the extensibility of the setup to investigate the samples in various conditions such as cryogenic, strained, ultrafast non-equilibrium, and high magnetic fields.


Involvement of finger domain and kringle 2 domain of tissue-type plasminogen activator in fibrin binding and stimulation of activity by fibrin.
Human tissue-type plasminogen activator (t-PA) catalyses the conversion of inactive plasminogen into active plasmin, the main fibrinolytic enzyme. This process is confined to the fibrin surface by specific binding of t-PA to fibrin and stimulation of its activity by fibrin. Tissue-type plasminogen activator contains five domains designated finger, growth factor, kringle 1, kringle 2 and protease. The involvement of the domains in fibrin specificity was investigated with a set of variant proteins lacking one or more domains. Variant proteins were produced by expression in Chinese hamster ovary cells of plasmids containing part of the coding sequence for the activator. It was found that kringle 2 domain only is involved in stimulation of activity by fibrin. In the absence of plasminogen and at low concentration of fibrin, binding of t-PA is mainly due to the finger domain, while at high fibrin concentrations also kringle 2 is involved in fibrin binding. In the presence of plasminogen, fibrin binding of the kringle 2 region of t-PA also becomes important at low fibrin concentrations.


Transcription and processing of the gene for spinach chloroplast threonine tRNA in a homologous in vitro system.
An in vitro system was established to study the transcription and processing of threonine tRNA using spinach chloroplast enzyme extract. Experiments using a series of 5' deletion mutants demonstrated that the transcription of trnT gene required no 5' upstream promoter elements. Four plasmid DNA templates containing trnT were constructed for tRNA processing assay. The processing reaction was carried out either with exogenously added precursor-tRNAs made by T7 RNA polymerase or with RNAs synthesized by the transcription activity in the same processing enzyme extract. Both assays demonstrated that the 5' and 3' ends of mature tRNA were processed endonucleolytically and the processing of the 5' end preceded the maturation of the 3' end. The activity of nucleotidyl transferase that adds CCA nucleotides to the 3' end of tRNA was also observed. The use of a coupled transcription and processing system provides us with a better insight to the tRNA processing mechanism of the chloroplast.


Very mild stroke patients benefit from intravenous tissue plasminogen activator without increase of intracranial hemorrhage.
Intravenous recombinant tissue plasminogen activator (IV rt-PA) is an effective medication currently used to treat acute ischemic stroke within three hours of symptom onset in patients with an identifiable clinical deficit measured using the National Institute of Health Stroke Scale (NIHSS). We compared the outcomes of 27 identified patients with an NIHSS of 6 or less who received IV rt-PA for acute ischemic stroke treatment within three hours of symptom onset in our center with 24 historic controls from the nationally available National Institute of Neurological Disorders and Stroke (NINDS) study database. The mean initial NIHSS was not significantly different in patients and control groups (mean +/- SD: 4.52 +/- 1.25 and 4.71 +/- 1.4) (P = 0.45). The mean modified Rankin score (mRS) at the time of discharge in patients and control group were 0.78 +/- 1.19 and 1.75 +/- 1.75, respectively. The mRS at discharge demonstrated a statistically significant (P < 0.03) improved clinical outcome for IV rt-PA treated group. The rate of intracranial hemorrhage (ICH) in the IV rt-PA group and control group was not significantly different (P = 1, odds ratio: 0.88, CI: 0.05-14.09). This retrospective study demonstrates that administering intravenous rt-PA to patients with a very mild stroke (NIHSS of 6 or less) can lead to improved clinical outcome when compared to patients with similar NIHSS who have not received similar treatment.


The stroop color-word interference test as an indicator of ADHD in poor readers.
The performance on the Stroop Color-Word Interference Test of 36 boys with Attention Deficit Hyperactivity Disorder (ADHD) was compared with performances of a matched control sample. The control group outperformed their counterparts on the control and interference conditions of the Stroop test, suggesting ADHD-specific executive and reading deficits. When individuals with both ADHD and reading disorders were excluded from the analysis, the authors found a significant difference between the ADHD group and the control group on the color-word test, indicating that poor reading skills may produce false negatives on the Stroop test. However, fast and slow readers with ADHD did not perform differently from each other on the color-word test. The authors postulated the existence of two different causes of reading problems: phonological deficits and attentional deficits.


E-Cigarettes and the Drug Use Patterns of Adolescents.
This study examines the role of e-cigarettes in the drug use patterns of adolescents. Of specific interest is whether adolescent e-cigarette users fall into a group of (1) youth who do not use traditional drugs of abuse or (2) polysubstance users. Using latent class analysis, we identify major "classes" of substance users on the basis of recent use of e-cigarettes, alcohol, marijuana, cigarettes, and prescription drugs. Analyses are conducted separately for adolescents in 8th, 10th, and 12th grades. Data come from 16 615 participants in the 2014 Monitoring the Future survey. Youth who do not use traditional drugs of abuse account for about 50% of e-cigarette users in 8th grade, 35% in 10th grade, and 17% in 12th grade. These youth come from a large "low-level users" group found in each grade, characterized by low probability of use for all substances (e-cigarette probability in this group for 8th graders = .046; 10th graders = .071; 12th graders = .027). Other e-cigarette users come from a smaller, "poly-users" group found in each grade, characterized by high-to-moderate probabilities (.83-.21) of using e-cigarettes and other substances. Specific to 12th grade is a third, additional polysubstance group characterized by high likelihood of e-cigarette use (.93). The proportion of e-cigarette users who do not use traditional drugs of abuse is larger at younger ages. Longitudinal panel studies starting at 8th and 10th grades may best inform the current debate on whether e-cigarette use is a risk or protective factor for future transition to the use of other substances. The proportion of e-cigarette users who do not use traditional drugs of abuse is larger at younger ages. Longitudinal panel studies starting at 8th and 10th grades may best inform the current debate on whether e-cigarette use is a risk or protective factor for future transition to the use of other substances.