Clinical Characteristics and Risk of Hypoxemia Development in Women Infected with SARS-CoV-2 during Pregnancy.
There is limited information on the clinical characteristics and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy. The clinical features and risk factors for hypoxemia development were investigated in pregnant women with coronavirus disease-2019 (COVID-19). From August 2020 to February 2022, we performed a retrospective cohort study of 410 pregnant women with COVID-19. The clinical characteristics and prognoses were compared between pregnant COVID-19 patients requiring oxygen and those who did not. Of 410 patients, 100 (24.4%) required oxygen therapy. Among them, fever [163 (52.6%) vs. 81 (81.0%), p<0.001] and cough [172 (56.4%) vs. 73 (73.0%), p=0.003] were more frequently observed than in non-oxygen group. The proportion of unvaccinated women was higher in oxygen group than in non-oxygen group [264 (85.2%) vs. 98 (98.0%), p=0.003]. During the Omicron wave, patients were more likely to have no oxygen requirement [98 (31.6%) vs. 18 (18.0%), p=0.009]. The risk of hypoxemic respiratory difficulty increased if SARS-CoV-2 infection occurred during the third trimester [adjusted odds ratio (aOR) 5.083, 95% confidence interval (CI): 1.095-23.593, p=0.038] and C-reactive protein (CRP) was elevated (≥1.0 mg/dL) at admission (aOR 5.878, 95% CI: 3.099-11.146, p<0.001). The risk was higher in unvaccinated patients (aOR 5.376, 95% CI: 1.193-24.390, p=0.028). However, the risk was lower in patients during the Omicron wave (aOR 0.498, 95% CI: 0.258-0.961, p=0.038). A quarter of SARS-CoV-2-infected women developed hypoxemic respiratory difficulty during pregnancy. SARS-CoV-2 infection during the third trimester, CRP elevation at admission, and no vaccination increased the risk of hypoxemia in pregnant women.


Nicotiana benthamiana as a model for studying Cryptococcus-plant interaction.
Cryptococcus gattii, an environmental yeast isolated from plants, is one of the agents of cryptococcosis. Here, we aimed to develop a plant model to study C. gattii-plant interaction, since it is unclear how it affects the plant and the yeast. We tested three inoculation methods (scarification, infiltration, and abrasion) in three plant species: Arabidopsis thaliana, Nicotiana tabacum, and N. benthamiana. Cryptococcus gattii was able to grow in all three models, with a peak of yeast cell burden after 7 days, without any pathological effects. Furthermore, the fungal burden was reduced later, confirming that C. gattii is not a phytopathogen. Cryptococcus gattii proliferation was higher in N. benthamiana, which presented an increase in the hydrogen peroxide content, antioxidant system activity, and indoleacetic acid (IAA) production. Cryptococcus gattii colonies recovered from N. benthamiana presented lower ergosterol content, reduced capsule, and increased growth rate in vitro and inside macrophages. In vitro, IAA altered C. gattii morphology and susceptibility to antifungal drugs. We hypothesize that C. gattii can temporarily colonize plant living tissues, which can be a potential reservoir of yeast virulence, with further dissemination to the environment, birds, and mammals. In conclusion, N. benthamiana is suitable for studying C. gattii-plant interaction.


Occurrence and Spatiotemporal Dynamics of Pharmaceuticals in a Temperate-Region Wastewater Effluent-Dominated Stream: Variable Inputs and Differential Attenuation Yield Evolving Complex Exposure Mixtures.
Effluent-dominated streams are becoming increasingly common in temperate regions and generate complex pharmaceutical mixture exposure conditions that may impact aquatic organisms via drug-drug interactions. Here, we quantified spatiotemporal pharmaceutical exposure concentrations and composition mixture dynamics during baseflow conditions at four sites in a temperate-region effluent-dominated stream (upstream, at, and progressively downstream from effluent discharge). Samples were analyzed monthly for 1 year for 109 pharmaceuticals/degradates using a comprehensive U.S. Geological Survey analytical method and biweekly for 2 years focused on 14 most common pharmaceuticals/degradates. We observed a strong chemical gradient with pharmaceuticals only sporadically detected upstream from the effluent. Seventy-four individual pharmaceuticals/degradates were detected, spanning 5 orders of magnitude from 0.28 to 13 500 ng/L, with 38 compounds detected in >50% of samples. "Biweekly" compounds represented 77 ± 8% of the overall pharmaceutical concentration. The antidiabetic drug metformin consistently had the highest concentration with limited in-stream attenuation. The antihistamine drug fexofenadine inputs were greater during warm- than cool-season conditions but also attenuated faster. Differential attenuation of individual pharmaceuticals (i.e., high = citalopram; low = metformin) contributed to complex mixture evolution along the stream reach. This research demonstrates that variable inputs over multiple years and differential in-stream attenuation of individual compounds generate evolving complex mixture exposure conditions for biota, with implications for interactive effects.


Molecular switches for pheromone release from a moth pheromone-binding protein.
Pheromone-binding proteins (PBPs) are involved in the uptake of pheromones from pores on the antennae, transport through an aqueous environment surrounding the olfactory receptor neurons, and fast delivery to pheromone receptors. We tested the hypothesis that a C-terminal segment and a flexible loop are involved in the release of pheromones to membrane-bound receptors. We expressed in Escherichia coli 11 mutants of the PBP from the silkworm moth, BmorPBP, taking into consideration structural differences between the forms with high and low binding affinity. The N-terminus was truncated and His-69, His-70 and His-95 at the base of a flexible loop, and a cluster of acidic residues at the C-terminus were mutated. Binding assays and circular dichroism analyses support a mechanism involving protonation of acidic residues Asp-132 and Glu-141 at the C-terminus and histidines, His-70 and His-95, in the base of a loop covering the binding pocket. The former leads to the formation of a new alpha-helix, which competes with pheromone for the binding pocket, whereas positive charge repulsion of the histidines opens the opposite side of the binding pocket.


The concentrations of clarithromycin and its 14-hydroxy metabolite in sputum of patients with bronchiectasis following single dose oral administration.
Clarithromycin and its metabolite, 14-hydroxy-clarithromycin are active against a wide range of respiratory pathogens. Antibiotics generally penetrate poorly into respiratory secretions which may therefore continue to harbour bacteria following bronchial infection. We have studied sputum and serum concentrations of clarithromycin and 14-hydroxy-clarithromycin in eight patients with idiopathic bronchiectasis without infective exacerbations (five male, three female; mean age 53.3 years). Oral single dose administration of 250 or 500 mg clarithromycin, separated by at least 6 days, was given to each patient. Serum and sputum samples were collected (the latter by physiotherapy at 0, 1, 2, 4, 8, 24 and 0, 4, 8 and 24 h respectively after administration of each dose. Serum sol phase was obtained by high speed centrifugation and concentrations of clarithromycin and 14-hydroxy-clarithromycin were determined by high performance liquid chromatography. Serum Cmax for clarithromycin and 14-hydroxy-clarithromycin were 1.20 mg/L (3 h) and 0.37 mg/L (3.1 h) for clarithromycin (250 mg)) and were 2.78 mg/L (2.5 h) and 0.68 mg/L (2.6 h) for clarithromycin (500 mg) respectively. Sputum Cmax for clarithromycin and 14-hydroxy-clarithromycin were 0.52 mg/L (5 h) and 0.30 mg/L (5.5 h) for clarithromycin (250 mg) and were 1.59 mg/L (5 h) and 0.47 mg/L (5.5 h) for clarithromycin (500 mg) respectively. The sputum/serum percentage ratios at Cmax (sputum) for clarithromycin and 14-hydroxy-clarithromycin were 74.3% and 113.9% (250 mg) and 94.7% and 99.9% (500 mg) respectively. We conclude that oral administration of clarithromycin to patients with bronchiectasis results in rapid penetration into respiratory mucus with persistent drug concentrations that exceed its MIC for many respiratory pathogens.


Novel bacterial vaginosis-associated organisms mediate the relationship between vaginal douching and pelvic inflammatory disease.
We sought to determine whether the relationship between a history of vaginal douching and pelvic inflammatory disease (PID) is mediated by endometrial infection with one or more novel bacterial vaginosis (BV)-associated organisms among Atopobium vaginae, the BV-associated bacterium 1 (BVAB1), neathia (Leptotrichia) amnionii and Sneathia sanguinegens. We first conducted log-binomial regression analyses to identify risk factors for endometrial infection in 535 adolescent and adult women with clinically suspected PID in the PID Evaluation and Clinical Health (PEACH) study. We then examined whether endometrial infection by the BV-associated organisms mediated the association between a history of vaginal douching and histologically confirmed PID using inverse probability weighted marginal structural models. Vaginal douching was significantly associated with endometrial infection with one or more of the targeted BV-associated organisms (relative risk (RR) 1.21, 95% CI: 1.08 to 1.35). The total effect estimate suggested that vaginal douching increased the risk of endometritis by 24% (RR 1.24, 95% CI: 1.03 to 1.49). The controlled direct effect of this association was attenuated with endometrial infection by one or more BV-associated organisms (adjusted RR (aRR) 1.00, 95% CI: 0.57 to 1.74) and endometrial infection by all four BV-associated organisms (aRR 0.95, 95% CI: 0.53 to 1.70) as intermediate variables. Endometrial infection with one or more of the novel BV-associated organisms partially mediated the relationship between vaginal douching and histologically confirmed endometritis in the PEACH study. Frequent vaginal douching may confer risk for endometritis through increasing the risk of endometrial infection by novel-BV-associated organisms. Other potential pathways should be explored.


Surface tension and capillary waves at the nematic-isotropic interface in ternary mixtures of liquid crystal, colloids, and impurities.
In mixtures of thermotropic liquid crystals with spherical poly(methyl methacrylate) particles, self-supporting networklike structures are formed during slow cooling past the isotropic-to-nematic phase transition. Experimental results support the hypothesis that a third component, alkane remnants slowly liberated from the particles, plays a crucial role. A theoretical model, based on the phenomenological Landau-de Gennes, Carnahan-Starling, and hard-sphere crystal theories, is developed to describe the continuous phase separation in a ternary nematic-impurity-colloid mixture. The interfacial tension and the dispersion relation of the surface modes of the nematic-isotropic interface are determined. The colloids decrease the interfacial tension and the damping rate of surface waves, whereas impurities act in an opposite way. This should strongly influence the formation of abovementioned networklike structures and could help explain some of their rheological properties.


Recombination and microdiversity in coastal marine cyanophages.
Genetic exchange is an important process in bacteriophage evolution. Here, we examine the role of homologous recombination in the divergence of closely related cyanophage isolates from natural marine populations. Four core-viral genes (coliphage T4 homologues g20, g23, g43 and a putative tail fibre gene) and four viral-encoded bacterial-derived genes (psbA, psbD, cobS and phoH) were analysed for 60 cyanophage isolates belonging to five Rhode Island Myovirus (RIM) strains. Phylogenetic analysis of the 60 concatenated sequences revealed well-resolved sequence clusters corresponding to the RIM strain designations. Viral isolates within a strain shared an average nucleotide identity of 99.3-99.8%. Nevertheless, extensive microdiversity was observed within each cyanophage strain; only three of the 60 isolates shared the same nucleotide haplotype. Microdiversity was generated by point mutations, homologous recombination within a strain, and intragenic recombination between RIM strains. Intragenic recombination events between distinct RIM strains were detected most often in host-derived photosystem II psbA and psbD genes, but were also identified in some major capsid protein g23 genes. Within a strain, more variability was observed at the psbA locus than at any of the other seven loci. Although most of the microdiversity within a strain was neutral, some amino acid substitutions were identified, and thus microdiversity within strains has the potential to influence the population dynamics of viral-host interactions.


Does Periodontal Inflammation Affect Type 1 Diabetes in Childhood and Adolescence? A Meta-Analysis.
The emergence of link between periodontal disease and diabetes has created conditions for analyzing new interdisciplinary approach making toward tackling oral health and systemic issues. As periodontal disease is a readily modifiable risk factor this association has potential clinical implications. The aim of this paper was systematically review the extant literature related to analytics data in order to identify the association between type 1 diabetes (T1DM) in childhood and adolescence with periodontal inflammation. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a database search between 2004 and 2019. A manual search of the literature was conducted as an additional phase of the search process, with the aim of identifying studies that were missed in the primary search. One hundred and thirty-nine records were screened and 10 fulfilled the inclusion criteria. Most studies were of moderate methodological quality. Outcomes included assessments of diabetes and periodontal status. In diabetic populations, compared to healthy subjects, interindividual differences in periodontal status are reflected in higher severity of periodontal inflammation. The most reported barriers to evidence uptake were the intrinsic limits of cross-sectional report data and relevant research, and lack of timely research output. Based on the evidence presented within the literature, the aforementioned biomarkers correlate with poor periodontal status in type 1 diabetic patients. Whilst the corpus of the evidence suggests that there may be an association between periodontal status and type 1 diabetes, study designs and methodological limitations hinder interpretation of the current research.


[Craniopharyngiomas].
Craniopharyngiomas are rare benign epithelial tumors, arising from the pituitary stalk or gland and developing in the sellar and suprasellar region, affecting both adults and children. Incidence is 0.5 to 2 new cases per million inhabitants. Clinical features essentially include visual disturbances, endocrine deficiencies, and neurological signs. Initial signs are often visual loss and increased intracranial pressure in children, growth and pubertal delay in teenagers, visual disturbances or cognitive impairment in adults. Diagnosis is made on MRI and CT scan, demonstrating a sellar or suprasellar tumor, heterogeneous, with frequent calcifications. Craniopharyngiomas can be classified depending on their locations from the sella, the diaphragma sellae, and upon their origins from the pituitary stalk or the infundibulum. They can also be classified depending on the location from the optic chiasm and the third ventricle. This classification allows surgical series comparison, which is of importance since developments and extensions of the tumor can explain surgical difficulties. The management of this lesion is still controversial. Because it is an extra-cerebral benign lesion, the ideal goal of treatment should be complete tumor removal with improvement of altered visual functions, minimal deterioration of endocrine function, and no neuropsychological impairment. But the situation of the tumor, its relationship with third ventricle, hypothalamus, optic tract, vascular structures make its removal often difficult. However, great progresses have been realized in surgical treatment, resulting in a dramatic improvement of the prognosis of craniopharyngiomas. Nowadays, one can expect total removal in 60 to 70% of patients, subtotal removal in 20 to 30%, and partial removal in 10%. When total removal is impossible, radiotherapy may reduce the risk of a poor evolution. Recurrences are a problem in 15% of patients with total removal, 35% in subtotal removal, 70% in partial removal. If radiotherapy has not been performed as first treatment, it is efficient in 80% of recurrences. Long term follow up is necessary in these patients, due to medical management of endocrine, visual and psychological problems, and risk of late recurrence. With close involvement in this management, most of patients may enjoy a good outcome, 80% being able to return to normal active life.


PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex.
PTIP, a protein with tandem BRCT domains, has been implicated in DNA damage response. However, its normal cellular functions remain unclear. Here we show that while ectopically expressed PTIP is capable of interacting with DNA damage response proteins including 53BP1, endogenous PTIP, and a novel protein PA1 are both components of a Set1-like histone methyltransferase (HMT) complex that also contains ASH2L, RBBP5, WDR5, hDPY-30, NCOA6, SET domain-containing HMTs MLL3 and MLL4, and substoichiometric amount of JmjC domain-containing putative histone demethylase UTX. PTIP complex carries robust HMT activity and specifically methylates lysine 4 (K4) on histone H3. Furthermore, PA1 binds PTIP directly and requires PTIP for interaction with the rest of the complex. Moreover, we show that hDPY-30 binds ASH2L directly. The evolutionarily conserved hDPY-30, ASH2L, RBBP5, and WDR5 likely constitute a subcomplex that is shared by all human Set1-like HMT complexes. In contrast, PTIP, PA1, and UTX specifically associate with the PTIP complex. Thus, in cells without DNA damage agent treatment, the endogenous PTIP associates with a Set1-like HMT complex of unique subunit composition. As histone H3 K4 methylation associates with active genes, our study suggests a potential role of PTIP in the regulation of gene expression.


Cardiovascular and connective tissue disorder features in FLNA-related PVNH patients: progress towards a refined delineation of this syndrome.
FLNA Loss-of-Function (LoF) causes periventricular nodular heterotopia type 1 (PVNH1), an acknowledged cause of seizures of various types. Neurological symptoms are inconstant, and cardiovascular (CV) defects or connective tissue disorders (CTD) have regularly been associated. We aimed at refining the description of CV and CTD features in patients with FLNA LoF and depicting the multisystemic nature of this condition. We retrospectively evaluated FLNA variants and clinical presentations in FLNA LoF patient with at least one CV or CTD feature, from three cohorts: ten patients from the French Reference Center for Rare Vascular Diseases, 23 patients from the national reference diagnostic lab for filaminopathies-A, and 59 patients from literature review. Half of patients did not present neurological symptoms. Most patients presented a syndromic association combining CV and CTD features. CV anomalies, mostly aortic aneurysm and/or dilation were present in 75% of patients. CTD features were present in 75%. Variants analysis demonstrated an enrichment of coding variants in the CH1 domain of FLNA protein. In FLNA LoF patients, the absence of seizures should not be overlooked. When considering a diagnosis of PVNH1, the assessment for CV and CTD anomalies is of major interest as they represent interlinked features. We recommend systematic study of FLNA within CTD genes panels, regardless of the presence of neurological symptoms.


Investigation of an outbreak of Clostridium difficile infection in a general hospital by numerical analysis of protein patterns by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
One hundred forty-five cultures of Clostridium difficile, including strains from an apparent nosocomial outbreak of infection, were characterized by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell proteins. Each protein pattern was characterized by the presence of one to three dense bands which were highly reproducible. The first 100 strains (in chronological order) were used as the basis for a numerical analysis which divided the strains into 17 phenons (EP types 1 to 17). The protein patterns of the remaining 45 strains were identified to type by comparing their individual patterns against a data base made up of the protein patterns of the first 100 strains. EP type 1 was the most common, with 70 of 139 (50%) patient isolates having this pattern type, and it accounted for 26 of 35 strains (74%) from patients in a medical teaching ward from which the outbreak was believed to have originated. This type was also found as a high proportion of isolations in a number of other medical and oncology wards, but the majority of these isolates occurred subsequent to the isolations on the initial outbreak ward. This technique can therefore provide a method for tracing the possible spread of epidemic strains in hospitals and other institutions and may contribute to a better understanding of the epidemiology of C. difficile.


[Urinary incontinence restrictions in women's life].
Our purpose with this study was to verify the restriction of the urinary incontinence (UI) in a woman's daily life, considering the type of incontinence, and find out how women deal with that. It is a secondary analysis of data taken from a previous study that were obtained using open and closed questions. Interviews were held with 164 incontinent inpatients of gynecological and urological clinics of two hospital schools in the city of Campinas, in the State of São Paulo, with ages ranging from 25 to 85 years. Of this universe, 104 (64%) indicated one or more restrictions regarding their daily life activities, such as altered sexual (40.9%), social (33.5%), domestic (18.9%) and occupational activities (15.2%). Mixed urinary incontinence and urge incontinence were mentioned as that affected the most women's daily life. The disposable pad system was the most utilized strategy in dealing with UI. It was concluded that UI has a negative impact on the daily life of these women.


Generation of a purely electrostatic collisionless shock during the expansion of a dense plasma through a rarefied medium.
A two-dimensional numerical study of the expansion of a dense plasma through a more rarefied one is reported. The electrostatic ion-acoustic shock, which is generated during the expansion, accelerates the electrons of the rarefied plasma inducing a superthermal population which reduces electron thermal anisotropy. The Weibel instability is therefore not triggered and no self-generated magnetic fields are observed, in contrast with published theoretical results dealing with plasma expansion into vacuum. The shock front develops a filamentary structure which is interpreted as the consequence of the electrostatic ion-ion instability, consistently with published analytical models and experimental results.


Cell surface heparan sulfate mediates some adhesive responses to glycosaminoglycan-binding matrices, including fibronectin.
Proteins with affinities for specific glycosaminoglycans (GAC's) were used as probes for testing the potential of cell surface GAG's to mediate cell adhesive responses to extracellular matrices (ECM). Plasma fibronectin (FN) and proteins that bind hyaluronate (cartilage proteo-glycan core and link proteins) or heparan sulfate (platelet factor 4 [PF4]) were adsorbed to inert substrata to evaluate attachment and spreading of several 3T3 cell lines. Cells failed to attach to hyaluronate-binding substrata. The rates of attachment on PF4 were identical to those on FN; however, PF4 stimulated formation of broad convex lamellae but not tapered cell processes fibers during the spreading response. PF4-mediated responses were blocked by treating the PF4-adsorbed substratum with heparin (but not chondroitin sulfate), or alternatively the cells with Flavobacter heparinum heparinase (but not chondroitinase ABC). Heparinase treatment did not inhibit cell attachment to FN but did inhibit spreading. Cells spread on PF4 or FN contained similar Ca2+-independent cell-substratum adhesions, as revealed by EGTA-mediated retraction of their substratum-bound processes. Microtubular networks reorganized in cells on PF4 but failed to extend into the broadly spread lamellae, where fine microfilament bundles had developed. Stress fibers, common on FN, failed to develop on PF4. These experiments indicate that (a) heparan sulfate proteoglycans are critical mediators of cell adhesion and heparan sulfate-dependent adhesion via PF4 is comparable in some, but not all, ways to FN-mediated adhesion, (b) the uncharacterized and heparan sulfate-independent "cell surface" receptor for FN permits some but not all aspects of adhesion, and (c) physiologically compatible and complete adhesion of fibroblasts requires binding of extracellular matrix FN to both the unidentified "cell surface" receptor and heparan sulfate proteoglycans.


Cross-Linking of Doped Organic Semiconductor Interlayers for Organic Solar Cells: Potential and Challenges.
Solution-processable interlayers are important building blocks for the commercialization of organic electronic devices such as organic solar cells. Here, the potential of cross-linking to provide an insoluble, stable, and versatile charge transport layer based on soluble organic semiconductors is studied. For this purpose, a photoreactive tris-azide cross-linker is synthesized. The capability of the small molecular cross-linker is illustrated by applying it to a p-doped polymer used as a hole transport layer in organic solar cells. High cross-linking efficiency and excellent charge extraction properties of the cross-linked doped hole transport layer are demonstrated. However, at high doping levels in the interlayer, the solar cell efficiency is found to deteriorate. Based on charge extraction measurements and numerical device simulations, it is shown that this is due to diffusion of dopants into the active layer of the solar cell. Thus, in the development of future cross-linker materials, care must be taken to ensure that they immobilize not only the host but also the dopants.


Helicobacter rodentium sp. nov., a urease-negative Helicobacter species isolated from laboratory mice.
A spiral-shaped bacterium with bipolar, single, nonsheathed flagella was isolated from the intestines of laboratory mice. The organism grew at 37 and 42 degrees C under microaerobic and anaerobic conditions, did not hydrolyze urea, was weakly positive for catalase and oxidase, reduced nitrate to nitrite, did not hydrolyze indoxyl acetate or hippurate, and was resistant to cephalothin and nalidixic acid. This is the first urease-negative, murine Helicobacter spp. isolated from intestines. Also, Helicobacter pullorum and this bacterium are unique among the genus Helicobacter in having nonsheathed flagella. The new bacterium appears to be part of the normal intestinal flora; although its pathogenic potential is unknown, this organism was also isolated from scid mice with diarrhea that were co-infected with Helicobacter bilis. On the basis of 16S rRNA gene sequence analysis data and biochemical and phenotypic criteria, the new organism is classified as a novel helicobacter, for which we propose the name Helicobacter rodentium. The type strain is MIT 95-1707 (= ATCC 700285).


Management of refractory chylous ascites with peritoneovenous shunts.
The purpose of this study was to define outcome of treatments of refractory chylous ascites using peritoneovenous shunts (PVSs). Clinical data of patients with refractory chylous ascites treated with PVSs between 1992 and 2015 were retrospectively reviewed. The primary end point was clinical benefit, defined as cured, improved, or poor results; secondary end points were complications and reinterventions. Seventeen patients (eight female [47%]; median age, 47 years [range, 19-78 years]) with refractory chylous ascites were studied. This group represented 6% of 284 patients treated for chylous ascites during the study period. The etiology was primary lymphangiectasia in 10 patients (59%) and secondary chylous ascites due to previous surgery, lymphatic obstruction with associated portal hypertension, or malignant tumor in 7 (41%). Eleven patients were treated with LeVeen shunts and six with Denver shunts. Thirty-day mortality, morbidity, and reintervention rates were 5.9%, 18%, and 12%, respectively. Reintervention rate at 6 months was 9.1% with LeVeen shunt, significantly lower than 100% with Denver shunt (P = .001). During a mean follow-up of 5.1 years (range, 17 days-22.7 years), 7 of 11 patients with LeVeen shunt and all 6 patients with Denver shunt required shunt replacement. Median duration of patency was 215 days (range, 2 days-9.0 years) of a total of 25 LeVeen shunts placed in 11 patients and 44 days (range, 6-91 days) of 20 Denver shunts placed in 6 patients. At last follow-up, patency of the LeVeen shunt was 36% (4/11); symptoms improved in 64% of the patients (7/11). Patency rate of Denver shunts was 33% (2/6), and symptoms improved in 33% (2/6). Treatment of refractory chylous ascites continues to be a major challenge. The only currently available PVS, the Denver shunt, had a median patency period of <2 months; it required frequent replacements and resulted in intermittent short-term clinical benefit in one-third of the patients. Improvements in technology to design new shunts, to develop new therapies, or to adopt new techniques to treat chylous ascites are urgently needed.


Pediatric Hodgkin lymphoma: are we over-scanning our patients?
Despite the favorable outcome of most pediatric patients with Hodgkin lymphoma (HL), there is rising concern about risks of carcinogenesis from both diagnostic and therapeutic radiation exposure for patients treated on study protocols. Although previous studies have investigated radiation exposure during treatment, radiation from post-treatment surveillance imaging may also increase the likelihood of secondary malignancies. All diagnostic imaging examinations involving ionizing radiation exposure performed for surveillance following completion of therapy were recorded for 99 consecutive pediatric patients diagnosed with HL from 2000 to 2010. Cumulative radiation dosage from these examinations and the frequency of relapse detection by these examinations were recorded. In the first 2 years following completion of therapy, patients in remission received a median of 11 examinations (range 0-26). Only 13 of 99 patients relapsed, 11 within 5 months of treatment completion. No relapse was detected by 1- or 2-view chest radiographs (n = 38 and 296, respectively), abdomen/pelvis computed tomography (CT) scans (n = 211), or positron emission tomography (PET) scans alone (n = 11). However, 10/391 (2.6%) of chest CT scans, 4/364 (1.1%) of neck CT scans, and 3/47 (6.4%) of PET/CT scans detected relapsed disease. Thus, only 17 scans (1.3%) detected relapse in a total of 1358 scans. Mean radiation dosages were 31.97 mSv for Stage 1, 37.76 mSv for Stage 2, 48.08 mSv for Stage 3, and 51.35 mSv for Stage 4 HL. Approximately 1% of surveillance imaging examinations identified relapsed disease. Given the very low rate of relapse detection by surveillance imaging stipulated by current protocols for pediatric HL patients, the financial burden of the tests themselves, the high cure rate, and risks of second malignancy from ionizing radiation exposure, modification of the surveillance strategy is recommended.


Deficiency of germinal center kinase TRAF2 and NCK-interacting kinase (TNIK) in B cells does not affect atherosclerosis.
Atherosclerosis is the underlying cause of many cardiovascular diseases, such as myocardial infarction or stroke. B cells, and their production of pro- and anti-atherogenic antibodies, play an important role in atherosclerosis. In B cells, TRAF2 and NCK-interacting Kinase (TNIK), a germinal center kinase, was shown to bind to TNF-receptor associated factor 6 (TRAF6), and to be involved in JNK and NF-κB signaling in human B cells, a pathway associated with antibody production. We here investigate the role of TNIK-deficient B cells in atherosclerosis. ApoE-/-TNIKfl/fl (TNIKBWT) and ApoE-/-TNIKfl/flCD19-cre (TNIKBKO) mice received a high cholesterol diet for 10 weeks. Atherosclerotic plaque area did not differ between TNIKBKO and TNIKBWT mice, nor was there any difference in plaque necrotic core, macrophage, T cell, α-SMA and collagen content. B1 and B2 cell numbers did not change in TNIKBKO mice, and marginal zone, follicular or germinal center B cells were unaffected. Total IgM and IgG levels, as well as oxidation specific epitope (OSE) IgM and IgG levels, did not change in absence of B cell TNIK. In contrast, plasma IgA levels were decreased in TNIKBKO mice, whereas the number of IgA+ B cells in intestinal Peyer's patches increased. No effects could be detected on T cell or myeloid cell numbers or subsets. We here conclude that in hyperlipidemic ApoE-/- mice, B cell specific TNIK deficiency does not affect atherosclerosis.


Longstanding proliferation of CD3 negative large granular lymphocytes preceding the development of high grade non-Hodgkin's lymphoma.
A patient with a persistent CD3 negative large granular lymphocyte (LGL) proliferation with immunophenotypic and functional characteristics of natural killer cells is described. The LGL proliferation persisted and six years after diagnosis the patient developed a high grade B cell non-Hodgkin's lymphoma. Molecular studies demonstrated clonal B cell populations in the peripheral blood, distinct from that identified in the lymphoma, both at presentation with non-Hodgkin's lymphoma and at complete remission following combination chemotherapy. It is postulated that T cell dysregulation associated with the CD3 negative LGL proliferation may have led to B cell dysfunction and loss of normal B cell control, with the subsequent development of a clonal B cell lymphoproliferative disorder.


Immune reactions in polysaccharide media. Experiments with specific antibodies of different affinities for serum albumin.
Rabbit antibody fractions of different affinities for human serum albumin were prepared by an immunosorbent technique. The fractions were used in studies on the enhancement of the precipitin reaction by polymers. Dextran increased the immune precipitation to about the same extent regardless of whether antibodies with high and low affinities were used. The effect should considerably facilitate the detection of antibodies with low precipitating ability in immunological assays. The results are discussed in terms of a steric-exclusion mechanism.


Relation of parental history of coronary heart disease to obesity in young adults.
To assess the association between obesity and parental coronary heart disease (CHD) history. Analysis of data from an ongoing, large-scale survey on medical status, health behaviour and attitudes. Representative samples of Israeli military personnel upon discharge from compulsory service at age 20-22 y. Overall 14297 men and 11638 women were interviewed and examined upon release from military service between 1989 and 1999. Data on demographic characteristics, family history of CHD, lifestyle, weight and height were collected. Analysis of variance and logistic regression were used. Higher mean body mass index (BMI) and obesity (BMI>30 kg/m(2)) were associated with paternal CHD history in both sexes, and with maternal CHD history among men. Offspring of a parent with a positive CHD history had a higher mean BMI (23.22 vs 22.86 kg/m(2), P<0.001) and were more likely to be obese (5.4 vs 3.7%, P<0.001) than offspring of parents with no history of CHD. Multivariate adjustment for demographic and behavioural variables associated with obesity attenuated the association (adjusted odds ratio for obesity 1.37, 95% confidence interval: 1.15, 1.64). When stratified by sex, this association remained statistically significant only among males. Young adults with a parental history of CHD are more likely to be overweight. This high-risk group should be targeted for early preventive activities.


Who recognizes and chooses behaviors that are best for a relationship? The separate roles of knowledge, attachment, and motivation.
Participants made relationship decisions in several Choose Your Own Adventure-type dating story tasks by choosing between two options at each of 20 points throughout the computerized stories. One option was always the relationship-enhancing option; the other option was detrimental to the relationship. Study 1 included two experimental conditions: Participants were either asked to identify the relationship-enhancing option or to report which option they would actually choose. Individuals high in relationship knowledge were more likely to identify relationship-enhancing behaviors but not more likely to actually choose them. Secure individuals and individuals strongly motivated to have supportive relationships were more likely to identify and to choose relationship-enhancing options. In Study 2 partner supportiveness was manipulated; the fictitious partner was either supportive or nonsupportive. Individuals high in relationship knowledge were better at recognizing when a partner was supportive and when not, whereas attachment anxiety lessened the appreciation of having a supportive partner.


[Age and local changes in the architectonics of the lymphatic bed of the wall of the jejunum and ileum in normal rabbits].
Age and local changes of the lymphatic bed have been studied in the jejunum and ileum preparations obtained from 100 rabbits. The architectonics of the bed is stated to undergo some age and local changes. In fetuses and two-week-old rabbits, chyle sinuses are narrow and all flow into the capillaries of the tela submucosa. In one-month-old animals, the mucosal capillary network is developing and the chyle sinuses flow into it. In six--ten-month-old rabbits, intestinal bed is already formed, the chyle sinuses are wide. Aged changes are represented by a considerably rarefied networks, decrease in the chyle sinuses caliber, deformation of the sinus, capillary and vessel walls. In the jejunum, unlike the ileum, the chyle sinuses are of larger size and have more complex architectonics in the capillary networks of the mucosa and tela submucosa.


Fetal and neonatal hyperthyroidism.
Fetal and neonatal hyperthyroidism are usually produced by transplacental passage of thyroid-stimulating immunoglobulins. Most commonly, the thyroid-stimulating immunoglobulins are a component of active maternal Graves' disease. However, such antibodies may continue to be produced after ablation of the thyroid by surgery, radioiodine, or by the immune mechanisms of Hashimoto's thyroiditis. Other mechanisms that have produced fetal and neonatal hyperthyroidism include activating mutations of the stimulatory G protein in McCune-Albright syndrome and activating mutations of the thyrotropin (TSH) receptor. Fetal hyperthyroidism may be associated with intrauterine growth retardation, nonimmune fetal hydrops, craniosynostosis, and intrauterine death. Features of this condition in the neonate include hyperkinesis, diarrhea, poor weight gain, vomiting, ophthalmopathy, cardiac failure and arrhythmias, systemic and pulmonary hypertension, hepatosplenomegaly, jaundice, hyperviscosity syndrome, thrombocytopenia, and craniosynostosis. The time course of thyrotoxicosis depends on etiology. Remission by 20 weeks is most common in neonatal Graves' disease; remission by 48 weeks is nearly always seen. A subset of these patients may have persistent disease when there is a strong family history of Graves' diseases. Disease persistence is characteristic of patients with activating mutations of the TSH receptor. Treatment of fetal hyperthyroidism comprises administration of antithyroid drugs to the mother. Fetal heart rate and fetal growth should be monitored. Ultrasonography may reveal changes in thyroid size. At times, cordocentesis may be useful for monitoring fetal thyroid function. Hyperthyroid neonates may be treated with antithyroid drugs, beta-adrenergic receptor blocking agents, iodine, or iodinated contrast agents, and at times, with glucocorticoids and digoxin. Nonremitting causes of neonatal hyperthyroidism require ablative treatments such as thyroidectomy.


Systematic review of interventions to repair ascending aortic pseudoaneurysms.
The safety and efficacy of endovascular therapies for ascending aortic pseudoaneurysms (AAPs) are still controversial. We report an endovascular correction of an AAP in a high-risk surgical patient and present the results of a literature review focusing on AAP treatment strategies. A multilingual search of AAP therapy was performed with limiting dates of January 1980 to May 2014. The studies were classified by intervention. A 79-year-old male with a 9 × 10 × 7 cm AAP in the anterior mediastinum was considered too high risk for surgery. An endovascular closure with a 12 mm Amplatzer septal occluder device (St. Jude Medical) was performed, and computed tomography angiography at 3-month follow-up exhibited a thrombosed AAP with minimal residual shunt. In our literature search, we identified 355 cases of AAPs, mostly case reports (91.5%) and a few patient series (8.5%). Surgical correction accounted for 73.8% of the cases, 5% of the patients were conservatively treated or considered too critically ill for any intervention, and 21.2% were treated with endovascular techniques. The most commonly reported endovascular techniques were stent grafts (9.8%) and septal occluder devices (9.8%). Although endovascular closure of AAPs with off-label devices is a reliable option for controlling the expansion and symptoms in high-risk surgical patients, solid data on survival are lacking. Efforts to promote discussion within the heart team to expand the application of endovascular techniques can provide groundbreaking evidence to support the use of endovascular techniques as guideline therapy when facing these complicated cases.


Thermogravimetry-mass spectrometry for carbon nanotube detection in complex mixtures.
In spite of the growth of the carbon nanotube (CNT) industry, there are no established analytical methods with which to detect or quantify CNTs in environmental matrices. Given that CNTs have relatively high thermal stabilities, we investigated the use of thermal techniques to isolate and quantify single wall carbon nanotubes (SWCNTs). Test materials included ten types of commercial SWCNTs, representative biological macromolecules (bovine serum albumin and methylcellulose), soot, natural coastal sediments, and SWCNT-amended sediments. Different SWCNTs exhibited widely diverse degradation temperatures, and thermal analytical methods may require SWCNT-type specific parameters. To improve quantification capabilities, evolved gases were monitored by mass spectrometry. SWCNTs produced diagnostic ion ratios reflective of their high carbon and low hydrogen and oxygen contents. Current detection limits are roughly 4 μg(SWCNT) per sample (e.g., 100 μg(SWCNT) g(-1)(sediment) and 40 mg sample), controlled by interfering ions associated with the instrument's non-airtight design. Although future modifications could improve this limitation, the current method is sufficient for quantifying SWCNTs in laboratories and industrial sites where SWCNTs are handled. Furthermore, the method shows promise to distinguish between incidental (e.g., soot) and engineered (e.g., SWCNTs) nanoparticles, which is not possible with current state-of-the-art techniques.


Structured block placements of hospital pre-registration trainee pharmacists in primary care medical practices across the United Kingdom: Lessons from a pilot scheme.
There is increasing demand for suitably trained pharmacists to undertake clinical roles in primary care general practices across the United Kingdom. This necessitates development of sustainable training opportunities to both better prepare future registrants for such roles and raise awareness of the new career pathway. Educational activity and setting: Hospital pre-registration trainee pharmacists undertook four or eight-week placements in general practice as part of their training year. Trainees attended an introductory session and received educational support tools six weeks prior to their placements. Each trainee had an allocated clinical supervisor in general practice and maintained communication with their hospital tutor. On completion of all placements, trainees and general practice staff were asked to share perceptions and outcomes via online questionnaires. Most trainees reported that the clinical supervision arrangements were satisfactory and found the placement workbook useful for guiding daily activities. Key benefits from the placements included enhanced understanding of the patient journey across healthcare sectors, increased confidence, and raised awareness of general practice as a career option. Main limitations included restricted opportunities to engage in patient-centred activities and lack of integration with general practice teams. All trainees stated that the presence of a general practice pharmacist was essential for learning support. This model demonstrated the feasibility of structured block placements of trainee pharmacists in general practice with identified benefits for trainees and pharmacy workforce requirements. Future research:Identified key limitations to this model need further investigation, to improve the design of future placements.


Long-term treatment with histamine H2-receptor antagonists in Zollinger-Ellison syndrome.
Continuous treatment of three Zollinger-Ellison patients with histamine H2-receptor antagonists for 14, 26 and 31 months resulted in effective relief of complaints and marked reduction in gastric acid secretion. In one of the patients the dose of cimetidine had to be doubled after 15 months of treatment because of a rise in basal gastric acid secretion accompanied by recurrent diarrhea. Fasting and secretin-stimulated serum gastrin levels were not affected by long-term treatment with histamine H2-receptor antagonists. No side-effects were observed in the three patients on long-term treatment.


Contribution of urban runoff in Taipei metropolitan area to dissolved inorganic nitrogen export in the Danshui River, Taiwan.
A previous study has demonstrated that Danshui River has almost the highest dissolved inorganic nitrogen (DIN) yield in the world and exports most of the DIN in the form of ammonium unlike the world's large rivers. However, the DIN sources are poorly constrained. In this study, the contributions of major sources in the Taipei metropolitan area to the DIN export in the Danshui River were investigated. It is observed that ammonium is the major DIN species in the downstream reaches, resulting from the ammonium-dominated inputs of the effluents of wastewater treatment plants (WWTP) and rain water pumping stations (RWPS). DIN concentrations in the downstream (urban) reaches are substantially elevated. The upstream tributaries annually discharge ∼2709 t DIN to the downstream reaches. However, the DIN discharge off the downstream reaches rises to ∼17,918 t, resulting from the contribution of RWPS-collected water, i.e., ∼14,632 t, and the effluents of two WWTP, i.e., ∼577 t. RWPS-collected water inherently contains the contribution of atmospheric deposition, ∼2937 t DIN. This finding implies that ∼11,695 t (∼66 % of the downstream output) DIN flux off the Danshui River is from urban runoff and can be attributed to human activities in the Taipei metropolitan area. To improve the water quality in the Danshui River, water quality controls in urban runoff are important.


Similar biochemical properties of human seminal plasma and epididymal alpha-1,4-glucosidase.
We have studied some characteristics of alpha-1,4-glucosidases in human male reproductive organs in order to obtain information on the origin of the enzyme in seminal plasma. Acid and neutral enzymes could be distinguished on the basis of their selective inhibition either by SDS (acid enzyme) or MTT (neutral enzyme). Only the epididymis contained a significant amount of SDS resistant neutral alpha-1,4-glucosidase which was comparable to what has been isolated in seminal plasma. The similarity of epididymal and seminal plasma neutral enzymes was further confirmed by ultracentrifugation on sucrose density gradients, which permitted a complete separation of neutral (11S) and acid (4S) iso-enzymes. The 11S form was present in epididymis and in seminal plasma, but was totally absent in seminal vesicles, prostates and testis. The epididymal enzyme also had some of the unique characteristics found in the seminal plasma enzyme: it precipitated upon dialysis against distilled water, and its mobility on SDS polyacrylamide gel electrophoresis was identical to that of form 1 in seminal plasma. These results, although they do not constitute absolute proof of the identity of epididymal and seminal plasma alpha-glucosidase, certainly provide strong support for this hypothesis.


Influence of Intimate Partner Violence (IPV) Exposure on Cardiovascular and Salivary Biosensors: Is There a Relationship?
Intimate partner violence (IPV) is a global public health epidemic that initiates/exacerbates health consequences affecting a victim's lifespan. IPV can significantly predispose women to a lifetime risk of developing cardiovascular disease (CVD) due to the effects of stress and inflammation. This study investigates the correlation among IPV exposure, in-vivo CVD events, and inflammatory biomarkers as predictor indices(s) for CVD in female dental patients. Of 37 women enrolled in this study, 19 were African-American (AA) and 18 non-African-American (non-AA) and their ages ranged from 19 to 63 years. IPV-exposure and stress-induced in-vivo CVD events such as Chest Pain (CP) and Heart palpitations were recorded from all enrolled subjects. Cardiovascular events were obtained through surveys by patient self-report. Saliva specimens were obtained from all women and were analyzed for CVD biomarkers using multiplex-ELISA. The prevalence of IPV was 51% (19/37) and statistically equivalent for AA and non-AA. The results show differences in experience of 1) CP (p < 0.01) and 2) heart palpitations (p < 0.02) when IPV + participants are compared with IPV- AA and non-AA cohorts. Of 10 CVD biomarkers analyzed, significant correlations between IPV+ and IPV- subjects were observed for biomarkers that include Interleukin-1β/sCD40L; TNFα/sCD40L; Myoglobin/IL-1β; CRP/sCD40L; CRP/IL-6; CRP/TNFα; TNFα/siCAM; CRP/MMP9; TNF-α/Adiponectin (p < 0.01). Analysis of in vivo CVD status showed that significant race/health disparities exist in IPV + cohorts, as well as increased expression of inflammatory mediators, specifically CRP, IL-1β, IL-6, MMP9. Women who have experienced IPV may be a target cohort for primary prevention of CVD. The use of salivary biomarkers and our protocol may provide a less invasive method to help increase identification of victims at risk for IPV and CVD and potentially decrease other health injuries associated with IPV exposure.


How to Design a Relevant Corpus for Sleepiness Detection Through Voice?
This article presents research on the detection of pathologies affecting speech through automatic analysis. Voice processing has indeed been used for evaluating several diseases such as Parkinson, Alzheimer, or depression. If some studies present results that seem sufficient for clinical applications, this is not the case for the detection of sleepiness. Even two international challenges and the recent advent of deep learning techniques have still not managed to change this situation. This article explores the hypothesis that the observed average performances of automatic processing find their cause in the design of the corpora. To this aim, we first discuss and refine the concept of sleepiness related to the ground-truth labels. Second, we present an in-depth study of four corpora, bringing to light the methodological choices that have been made and the underlying biases they may have induced. Finally, in light of this information, we propose guidelines for the design of new corpora.


Developing Priorities for Palliative Care Research in Advanced Liver Disease: A Multidisciplinary Approach.
Individuals with advanced liver disease (AdvLD), such as decompensated cirrhosis (DC) and hepatocellular carcinoma (HCC), have significant palliative needs. However, little research is available to guide health care providers on how to improve key domains related to palliative care (PC). We sought to identify priority areas for future research in PC by performing a comprehensive literature review and conducting iterative expert panel discussions. We conducted a literature review using search terms related to AdvLD and key PC domains. Individual reviews of these domains were performed, followed by iterative discussions by a panel consisting of experts from multiple disciplines, including hepatology, specialty PC, and nursing. Based on these discussions, priority areas for research were identified. We identified critical gaps in the available research related to PC and AdvLD. We developed and shared five key priority questions incorporating domains related to PC. Conclusion: Future research endeavors focused on improving PC in AdvLD should consider addressing the five key priorities areas identified from literature reviews and expert panel discussions.


The plant cell cycle--15 years on.
The basic components of the plant cell cycle are G1 (postmitotic interphase), S-phase (DNA synthesis phase), G2 (premitotic interphase) and mitosis/cytokinesis. Proliferating cells are phosphoregulated by cyclin-dependent protein kinases (CDKs). Plant D-type cyclins are sensors of the G0 to G1 transition, and are also important for G2/M. At G1/S, the S-phase transcription factor, E2F, is released from inhibitory retinoblastoma protein. Negative regulation of G1 events is through KRPs (Kip-related proteins). Plant S-phase genes are similar to animal ones, but timing of expression can be different (e.g. CDC6 at the start of S-phase) and functional evidence is limited. At G2/M, A-type and the unique B-type CDKs when bound to A, B and D cyclins, drive cells into division; they are negatively regulated by ICK1/2 and perhaps also by WEE1 kinase. In Arabidopsis, a putative CDC25 lacks a regulatory domain. Mitosis depends on correct temporal activity of CDKs, Aurora kinases and anaphase promotion complex; CDK-cyclin B activity beyond metaphase is catastrophic. Endoreduplication (re-replication of DNA in the absence of mitosis) is characterized by E2F expression and down-regulation of mitotic cyclins. Some cell size data support, whilst others negate, the idea of cell size having an impact on development.


Overlapping demyelinating syndrome (Neuromyelitis optica spectrum disorders NMOSD with anti-NMDA receptor encephalitis); A case report.
Neuromyelitis optica spectrum disorder (NMOSD) represents an evolving spectrum of inflammatory demyelinating central nervous system-based autoimmune diseases; while anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is another severe immune-mediated syndrome that occurs in association with IgG antibodies against the GluN1 subunit of the NMDAR and has been predominantly reported in young females (Dalmau et al., 2008 Dec). Although It has been recognized that anti-NMDAR encephalitis can coexist in the same patient who has serological markers of another autoimmune disease (e.g. neuronal autoantibodies and demyelination AQP4 or MOG antibodies) (Titulaer et al., 2014), rare cases are reported with anti-NMDAR encephalitis that overlap with a demyelinating syndrome; such as neuromyelitis optica spectrum disorders associated with Anti- Aquaporin 4 (AQP4) antibodies (Titulaer et al., 2013). We report here an unusual and rare overlapping autoimmune syndrome in a young Omani female who first presented in 2011 with the clinical and radiological presentations of neuromyelitis optica spectrum disorder (NMOSD) and had a complete recovery. Five years later, she was admitted with the diagnosis of anti-NMDAR encephalitis and was found to have positive serum as well as CSF analyses results for AQP4 and anti-NMDAR antibodies. The patient showed significant improvement, for both clinical syndromes with good response to steroid and immunomodulating therapy.


Stability of Self-Assembled Polymeric Micelles in Serum.
The stability of polymeric nanoparticles in serum is critical to their use in drug delivery where dilution after intravenous injection often results in nanoparticle disassembly and drug unloading; however, few investigate this in biologically relevant media. To gain greater insight into nanoparticle stability in blood, the stability of self-assembled polymeric micelles of poly(d,l-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-g-poly(ethylene glycol), P(LA-co-TMCC)-g-PEG, were tested in both serum and individual serum protein solutions. By encapsulating Förster resonance energy transfer pairs and following their release by fluorescence, these micelles demonstrated excellent thermodynamic and kinetic stability in the presence of serum. Further analyses by fast protein liquid chromatography and dynamic light scattering confirmed these data. Moreover, these micelles are compatible with red blood cells, as shown by a hemolysis assay. The stability and compatibility demonstrated in blood suggest that these micelles may be stable in vivo, which is critical for intravenous drug delivery applications. This comprehensive approach to understanding micelle stability and compatibility is broadly applicable.


[Characterization of the genetic diversity of the fish Brycon henni (Characiformes: Characidae) in central Colombia with RAPD markers].
Knowledge on the genetic diversity of wild fish species is essential for conservation and appropriate management of individuals in repopulation programs. In Colombia, Brycon henni has been reported in the Magdalena and Cauca river basins, but the population and range have diminished as a consequence of anthropic activities. In this study, the Random Amplified Polymorphic DNA (RAPD) was used to estimate the actual genetic structure in this species. For the purpose, six sample sites located in the department of Antioquia (Central Chain Mountains of Colombia) were used. Thirty five primers (87.5%), out of forty used, yielded 1 466 reliable and consistent fragments; 417 were considered as unique fragments able to discriminate among the Magdalena (Humarada-1 and Humarada-2) and Cauca (Piedras, La Clara y Guaracfi) river basins samples, suggesting that each is a discrete unit. This diversity suggests that anthropic effects of over fishing, dam building, deforestation and water pollution, have contributed to the isolation of these fish groups on the high mountains. Brycon moorei and Colossoma macropomum, as an interspecific control groups, were placed out of the B. henni general group, confirming their taxonomic classification through morphologic data. The RAPD technique was useful to know the genetic diversity and to discriminate among B. henni populations from different geographic origins, as a basis for an appropriate plan of repopulation, conservation and wildlife management.


The crystal structure of augmenter of liver regeneration: A mammalian FAD-dependent sulfhydryl oxidase.
The crystal structure of recombinant rat augmenter of liver regeneration (ALRp) has been determined to 1.8 A. The protein is a homodimer, stabilized by extensive noncovalent interactions and a network of hydrogen bonds, and possesses a noncovalently bound FAD in a motif previously found only in the related protein ERV2p. ALRp functions in vitro as a disulfide oxidase using dithiothreitol as reductant. Reduction of the flavin by DTT occurs under aerobic conditions resulting in a spectrum characteristic of a neutral semiquinone. This semiquinone is stable and is only fully reduced by addition of dithionite. Mutation of either of two cysteine residues that are located adjacent to the FAD results in inactivation of the oxidase activity. A comparison of ALRp with ERV2p is made that reveals a number of significant structural differences, which are related to the in vivo functions of these two proteins. Possible physiological roles of ALR are examined and a hypothesis that it may serve multiple roles is proposed.


Factor VIII inhibitors in mild and moderate-severity haemophilia A. UK Haemophilia Centre Directors Organisation.
Twenty six patients with mild or moderate haemophilia A and inhibitors are described. The inhibitor was detected at a median age of 33 years, after a median of 5.5 bleeding episodes. This usually following intensive replacement therapy. The median presenting inhibitor titre was antihuman 11.6 BU/ml, antiporcine 1.45 BU/ml. Plasma basal factor VIII level declined from a median of 0.08 IU/ml to 0.01 IU/ml following the inhibitor development. This caused spontaneous bleeding in 22 and a bleeding pattern similar to acquired haemophilia in 17. Bleeding was often severe and caused two deaths. The inhibitor disappeared spontaneously, or following immune tolerance induction, in 16 cases after a median of 9 months (range 0.5-46), with a return to the original baseline VIIIC level and bleeding pattern accompanied inhibitor loss. The inhibitor persisted in the remainder of the cases over a median period of 99 months (range 17-433 months) of follow-up. Inhibitors are an uncommon complication of mild haemophilia which frequently persist and may be associated with severe, life-threatening, haemorrhage. Forty-one percent of treated haemophilic family members had a history of factor VIII inhibitors, suggesting a familial predisposition to develop inhibitors in these kindreds. Sixteen patients from 11 families were genotyped. Seven different missense mutations affecting the light chain were detected and two in the A2 domain. Five patients from three families had a mutation causing a substitution of Trp2229 by Cys in the C2 domain which appears to predispose to inhibitor formation since 7 of the 18 affected individuals have a history of inhibitor development.


Cystic fibrosis lung transplantation.
This review summarizes recently published investigations on issues pertaining to cystic fibrosis (CF) lung transplantation. We specifically focus on indications and candidate selection as well as infectious and noninfectious issues specific to CF lung transplant recipients. Recent studies have focused on candidate adequacy in high-risk CF patients. We review the current literature on individuals who develop respiratory failure requiring mechanical ventilation and those patients with a pretransplant diagnosis of pulmonary hypertension. Furthermore, the management of peri-operative infectious issues is reviewed including recurrent infections with multidrug-resistant bacterial, mycobacterial, and fungal organisms. Other CF-specific issues addressed include common comorbidities such as CF-related diabetes, gastroesophageal reflux, CF liver disease, and bone metabolism. Lung transplantation is a limited, but potentially life-saving therapeutic option for patients with CF. Optimal candidate selection and awareness of CF-specific issues in the pretransplant and posttransplant setting may lead to better long-term outcomes.


PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation.
Phosphatase of regenerating liver 3 (PRL3) is overexpressed in a variety of tumors, and high levels of PRL3 expression are associated with tumorigenesis and metastasis. Consistent with an oncogenic role for PRL3, we show that ectopic PRL3 expression promotes cell proliferation and invasion. However, little is known about the molecular basis for PRL3 function. Obtaining this knowledge is vital for understanding PRL3-mediated disease processes and for the development of novel anticancer therapies targeted to PRL3. Here we report that up-regulation of PRL3 activates the Src kinase, which initiates a number of signal pathways culminating in the phosphorylation of ERK1/2, STAT3, and p130(Cas). The activation of these pathways likely contributes to the increased cell growth and motility of PRL3 cells. We provide evidence that PRL3 induces Src activation through down-regulation of Csk, a negative regulator of Src. Importantly, Src activation and Csk down-regulation are also observed in colon cancer cells expressing a higher level of PRL3. Thus, we have revealed a biochemical mechanism for the PRL3-mediated cell invasion and proliferation in which elevated PRL3 expression causes a reduction in Csk level, leading to Src activation.


Development of Clinical Vignettes to Describe Alzheimer's Disease Health States: A Qualitative Study.
To develop clinical descriptions (vignettes) of life with Alzheimer's disease (AD), we conducted focus groups of persons with AD (n = 14), family caregivers of persons with AD (n = 20), and clinicians who see persons with AD in their practices (n = 5). Group participants read existing descriptions of AD and commented on the realism and comprehensibility of the descriptions. We used thematic framework analysis to code the comments into themes and develop three new vignettes to describe mild, moderate, and severe AD. Themes included the types of symptoms to mention in the new vignettes, plus the manner in which the vignettes should be written. Since the vignette descriptions were based on focus group participants' first-hand knowledge of AD, the descriptions can be said to demonstrate content validity. Members of the general public can read the vignettes and estimate their health-related quality-of-life (HRQoL) as if they had AD based on the vignette descriptions. This is especially important for economic evaluations of new AD medications, which require HRQoL to be assessed in a manner that persons with AD often find difficult to undertake. The vignettes will allow the general public to serve as a proxy and provide HRQoL estimates in place of persons with AD.


[Persistence of antibodies three years after vaccination with the 23-valent pneumococcal vaccine].
To study the persistence of antibodies after primary immunization with the 23-valent pneumococcal vaccine in children with nephrotic syndrome. Sera from 14 of 26 children with nephrotic syndrome were obtained 3 years after vaccination. We used an ELISA method to measure IgG antibody levels to pneumococcal serotypes 14, 23F, 3 and 6B. Antibody levels before vaccination, 1 month and 3 years after vaccination were compared. Significant increases in specific antibody concentrations were observed 30 days after vaccination for all serotypes except serotype 3. Differences in response according to serotype were found. The highest serological response was observed for serotype 14 (78.5 % of the patients showed a good-to-moderate response). Three years after vaccination antibody levels were significantly decreased (27.3 % of children for serotype 14, 46.2 % for serotype 23F and 50 % for serotype 6B). The 23-valent pneumococcal vaccine is immunogenic in children aged more than 2 years with nephrotic syndrome. Response varied according to serotype. Persistence of vaccine-induced antibodies is short-term, with low antibody levels 3 years after immunization. The results of this study suggest that these patients require revaccination 3 years after the first dose.


Adenosine A1 receptor-mediated inhibition of vasopressin action in inner medullary collecting duct.
We examined the effects of adenosine and adenosine analogues on arginine vasopressin (AVP)-induced increases in osmotic water permeability (Pf; micron/s) and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat inner medullary collecting ducts (IMCDs). When added to the bath, the A1 receptor agonist N6-cyclohexyladenosine (CHA) produced a rapid and reversible inhibition of AVP-stimulated (10 pM) Pf (1,781 +/- 195 to 314 +/- 85 microns/s at 0.3 microM CHA; n = 9). The inhibitory effect of CHA was concentration dependent, with a 50% inhibitory concentration of 10 nM. The effect of CHA was inhibited by prior exposure of IMCDs to the A1 receptor antagonist 1,3-dipropylxanthine-8-cyclopentylxanthine (DP-CPX; 1 microM) or by preincubation with pertussis toxin. CHA had no effect on cAMP-induced increases in Pf. In addition to CHA, adenosine and the nonselective agonist 5'-(N-ethylcarboxamido)-adenosine (NECA) inhibited AVP-dependent Pf by > or = 70%, whereas the A2 receptor agonist CGS-21680 had no effect. Luminal adenosine (0.1 mM) had no effect on basal or AVP-stimulated Pf. CHA, NECA, and adenosine but not CGS-21680 inhibited AVP-stimulated cAMP accumulation in a concentration-dependent manner (50% inhibitory concentrations 0.1-300 nM). The inhibitory effect of CHA on AVP-stimulated cAMP accumulation was attenuated by DPCPX. We conclude that adenosine, acting at the basolateral membrane, inhibits AVP action in the IMCD via interaction with A1 receptors. The inhibition occurs proximal to cAMP generation and likely involves an inhibitory G protein.


Functional cDNA clones of the human respiratory syncytial (RS) virus N, P, and L proteins support replication of RS virus genomic RNA analogs and define minimal trans-acting requirements for RNA replication.
The RNA-dependent RNA polymerase of human respiratory syncytial (RS) virus was expressed in a functional form from a cDNA clone. Coexpression of the viral polymerase (L) protein, phosphoprotein (P), and nucleocapsid (N) protein allowed us to develop a system for expression and recovery of replicable RS virus RNA entirely from cDNA clones. cDNA clones of the N, P, and L genes were constructed in pGEM-based expression plasmids and shown to direct expression of the appropriate polypeptides. Two types of RS virus genomic RNA analogs were expressed from an intracellular transcription plasmid that directed the synthesis of RNAs with defined 5' and 3' ends. One analog included the authentic 5' and 3' termini of the genome, and the second contained the authentic 5' terminus and its complement at the 3' terminus as found in copyback defective interfering RNAs of other negative-strand RNA viruses. Both types of genomic analogs were encapsidated and replicated in cells expressing the RS virus N, P, and L proteins. Omission of any of the three viral proteins abrogated replication, thereby defining the N, P, and L proteins as the minimal trans-acting proteins required for RNA replication. This system has the advantages that expression occurs at a level sufficient to allow direct biochemical analysis of the products of RNA replication and that neither the use of reporter genes nor wild-type RS helper virus is required. These features allow analysis of both cis- and trans-acting factors involved in the control of replication of RS virus RNA.


Characterization of an IgA receptor from group B streptococci: specificity for serum IgA.
Some strains of group B streptococci express a cell surface protein which binds IgA. This report describes some properties of such an IgA receptor and compares it with a previously described IgA receptor from group A streptococci. The group B receptor was released in an almost pure form from bacteria incubated at elevated pH, and could be isolated by IgA-Sepharose affinity chromatography. The sequence of the N-terminal 19 amino acid residues was unique. The receptor preferentially binds IgA of human origin, as shown in immunoblotting experiments with purified IgA from nine different species. The affinity constant of the purified receptor for serum IgA was determined to be 3.5 x 10(8) M-1, but for secretory IgA it was too low to allow determination. This result indicates that secretory component and/or J chain interferes with the binding of IgA to this type of bacterial receptor, which may be one of the physiological functions of these polypeptides. A reduction in affinity was also observed for another complexed form of IgA, alpha 1-microglobulin-IgA. The group B receptor is antigenically unrelated to the IgA receptor from group A streptococci (protein Arp), but competitive inhibition experiments indicate that they bind to the same region in IgA. The implications of these findings, and the biological role of bacterial IgA receptors, are discussed.


Prenatal testing for Down syndrome: comparison of screening practices in the UK and USA.
Prenatal testing for Down Syndrome is a topic covered in every genetic counselor's training as it constitutes the main workload of genetic counselors in prenatal settings. Most Western countries nowadays offer some type of testing for Down Syndrome. However, practices vary according to country with regards to what tests are offered, insurance coverage and the legal situation concerning the option of terminating an affected pregnancy. In view of the growing interest in international genetic counseling issues, this article aims to compare prenatal testing practices in two English-speaking countries: the United Kingdom and the United States of America. A case will be presented to highlight some of the differences in practice. The topic underlines important implications for genetic counseling practice, such as patients' understanding of testing practices, risk perception, counseling provision and impact of prenatal testing results.


Genetic variation in Wnt/β-catenin and ER signalling pathways in female and male elite dancers and its associations with low bone mineral density: a cross-section and longitudinal study.
The association of genetic polymorphisms with low bone mineral density in elite athletes have not been considered previously. The present study found that bone mass phenotypes in elite and pre-elite dancers are related to genetic variants at the Wnt/β-catenin and ER pathways. Some athletes (e.g. gymnasts, dancers, swimmers) are at increased risk for low bone mineral density (BMD) which, if untreated, can lead to osteoporosis. To investigate the association of genetic polymorphisms in the oestrogen receptor (ER) and the Wnt/β-catenin signalling pathways with low BMD in elite and pre-elite dancers (impact sport athletes). The study included three phases: (1) 151 elite and pre-elite dancers were screened for the presence of low BMD and traditional osteoporosis risk factors (low body weight, menstrual disturbances, low energy availability); (2) a genetic association study was conducted in 151 elite and pre-elite dancers and age- and sex- controls; (3) serum sclerostin was measured in 101 pre-elite dancers and age- and sex-matched controls within a 3-year period. Eighty dancers revealed low BMD: 56.3% had at least one traditional osteoporosis risk factor, whereas 28.6% did not display any risk factor (37.2% revealed traditional osteoporosis risk factors, but had normal BMD). Body weight, menstrual disturbances and energy availability did not fully predict bone mass acquisition. Instead, genetic polymorphisms in the ER and Wnt/β-catenin pathways were found to be risk factors for low BMD in elite dancers. Sclerostin was significantly increased in dancers compared to controls during the 3-year follow-up (p < 0.05). Elite and pre-elite dancers demonstrate high prevalence of low BMD, which is likely related to genetic variants at the Wnt/β-catenin and ER pathways and not to factors usually associated with BMD in athletes (body weight, menstrual disturbances, energy deficiency).


Design criteria: tests used to assess platelet function.
A brief overview of platelet function tests used in the past to assess relations between dietary fatty acids and thrombogenicity reveals problems that need to be recognized and addressed before planning future studies. Implementation of new strategies that integrate new technologies with measures of two or more markers of platelet activity may be more successful in predicting the thrombotic potential of dietary fatty acids.


Dental implants: materials and design considerations.
Although the biologic principles underlying successful clinical implants are still not completely understood, it is clear that both physical and chemical attributes of the material may influence the clinical outcome. Knowledge of the stresses and strains in an implant system and superstructure is still incomplete, but micromotion at the interface must be avoided for bone fixation. The composition and topography of the implant surface influence the cellular events at the bone-biomaterial interface. These surface parameters require definition to interpret the tissue response to a particular material. Hydroxyapatite-coated surfaces are an example of a variable implant modality that has resulted in variable clinical performance. The clinician should consider all the available information on material and design before embarking on extensive clinical trial.


First Report of Laurel Wilt Disease Caused by Raffaelea lauricola on Spicebush in Louisiana.
In the past two decades, laurel wilt disease has significantly affected members of the Lauraceae in the southeast United States, causing widespread mortality of native redbay (Persea borbonia (L.) Spreng), and incidence of infections in avocado (Persea americana Mill.), sassafras (Sassafras albidum L.) and swamp bay (Persea palustris [Raf.] Sarg.) (Fraedrich et al., 2008, 2015, Olatinwo, et al. 2019). Laurel wilt is a vascular disease caused by Raffaelea lauricola (T.C. Harr., Fraedrich & Aghayeva), a fungus vectored by a non-native ambrosia beetle Xyleborus glabratus Eichhoff (Fraedrich et al. 2008). In August 2020, we investigated the mortality of a spicebush shrub (Lindera benzoin L.) (3.8 cm diameter at root collar, two m height) located ca. 17 mi northeast of Colfax, Grant Parish, Louisiana (31.750263° N, -92.643694° W). Evaluation of the dead shrub revealed brown, persistent foliage, and black vascular discoloration of the sapwood, typical symptoms of laurel wilt (Fig. S1). Although, beetle holes were observed on the sapwood, no beetle was found in galleries at the time. In the laboratory, a fungus consistently isolated from surface-sterilized sapwood tissues plated on potato dextrose agar (PDA) was identified as R. lauricola based on the morphological characteristics of the isolate (i.e., mucoid growth, conidiophores, and oblong/ovoid shape conidia [Harrington et al. 2008]). The fungal isolate was denoted as SB1. The identity of the fungus was confirmed by positive PCR amplification of the large subunit ribosomal RNA gene region using species-specific primers; rab-lsu-rl_F: CCCTCGCGGCGTATTATAG and rab-lsu-rl_R: GCGGGGCTCCTACTCAAA (Olatinwo, unpublished). The sequence of the isolate SB1 (GenBank Accession no. MW207371) showed 100% homology to the R. lauricola strain CBS 127349 sequence (GenBank Accession no. MH877933). The pathogenicity of SB1 on spicebush was evaluated on four healthy shrubs (average: 1 m height and 40 mm in diameter) at the location from which the original detection was made. Stems of two spicebush shrubs were inoculated with SB1 agar plugs from a 14-day old culture on PDA, while plain PDA plugs were used on the remaining two shrubs as non-inoculated controls. Agar plugs were placed in 5 mm (0.2 in) diameter hole punched on the bark with cork-borer as described by Mayfield et al (2008). After six weeks, the R. lauricola inoculated shrubs were wilted with noticeable blackened tissue discoloration in the sapwood, while the control trees remained healthy (Fig. S2). Raffaelea lauricola was re-isolated from tissue of the two inoculated, symptomatic shrubs, but not from the control trees. The sequence of the re-isolated R. lauricola isolate, denoted as SB3 (GenBank Accession no. MW207372), showed 100% homology to the R. lauricola strain CBS 127349 and isolate SB1. This first documentation of laurel wilt on spicebush in Louisiana is significant because, spicebush berries, leaves, and twigs are food sources for forest animals, birds, and insects including whitetail deer and spicebush swallowtail (Papilio troilus L.). Since its first report on sassafras in 2014 (Fraedrich et al. 2015), laurel wilt has spread across Louisiana on sassafras and swamp bay (Olatinwo et al. 2019) and has been confirmed in14 parishes. This report shows the relentless nature of the disease, as the pathogen moves from one vulnerable host to the next, expanding into new locations and threatening forest ecosystems across the southern United States.


Circulating myeloid and plasmacytoid dendritic cells after allergen inhalation in asthmatic subjects.
Dendritic cells are key contributors to initiation and maintenance of T-cell immunity to inhaled allergen. The purpose of this study was to enumerate the changes in peripheral blood myeloid (mDCs) and plasmacytoid dendritic cells (pDCs), the DCs expressing chemokine receptor 6 (CCR6) and chemokine receptor 7 (CCR7), following diluent and allergen inhalation in asthmatic subjects. Peripheral blood was obtained from 16 allergic asthmatic subjects before and at 0.5, 1, 2, 3, 4, 6, 24, and 48 h after inhaled diluent and allergen challenges. Dendritic cells were enumerated using flow cytometry. Allergen inhalation significantly reduced mDCs at 6 h (21.3 +/- 2.0 vs 15.0 +/- 1.8/microl blood; P < 0.05) and 24 h (21.5 +/- 3.4 vs 16.4 +/- 2.4/microl blood; P < 0.05) after challenge. Circulating pDCs were significantly lower than baseline up to 24 h after both allergen and diluent challenges. There was a significant efflux of CCR6(+) mDCs from peripheral blood at 6 h and CCR6(+) pDCs at 4 h after allergen challenge, when compared with diluent. There was no difference in the number of circulating CCR7(+) mDCs or pDCs after diluent or allergen challenges. Peripheral blood mDCs and CCR6(+) mDCs, but not pDCs, are reduced up to 24 h after allergen inhalation. Thus, allergen inhalation causes trafficking of immature CCR6(+) DCs from blood into the airway, while that of the trafficking of the mature CCR7(+) DCs from the airways into the regional lymph nodes probably occurs through the lymphatic system.


Sucrose counteracts the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.
Polyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance. We fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein∶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state. The background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.


Toward Reproducible Results from Targeted Metabolomic Studies: Perspectives for Data Pre-processing and a Basis for Analytic Pipeline Development.
Contemporary metabolomics experiments generate a rich array of complex high-dimensional data. Consequently, there have been concurrent efforts to develop methodological standards and analytical workflows to streamline the generation of meaningful biochemical and clinical inferences from raw data generated using an analytical platform like mass spectrometry. While such considerations have been frequently addressed in untargeted metabolomics (i.e., the broad survey of all distinguishable metabolites within a sample of interest), this methodological scrutiny has seldom been applied to data generated using commercial, targeted metabolomics kits. We suggest that this may, in part, account for past and more recent incomplete replications of previously specified biomarker panels. Herein, we identify common impediments challenging the analysis of raw, targeted metabolomic abundance data from a commercial kit and review methods to remedy these issues. In doing so, we propose an analytical pipeline suitable for the pre-processing of data for downstream biomarker discovery. Operational and statistical considerations for integrating targeted data sets across experimental sites and analytical batches are discussed, as are best practices for developing predictive models relating pre-processed metabolomic data to associated phenotypic information.


Blue-light irradiation up-regulates the ent-kaurene synthase gene and affects the avoidance response of protonemal growth in Physcomitrella patens.
We report a novel physiological response to blue light in the moss Physcomitrella patens . Blue light regulates ent -kaurene biosynthesis and avoidance response to protonemal growth. Gibberellins (GAs) are a group of diterpene-type plant hormones biosynthesized from ent-kaurenoic acid via ent-kaurene. While the moss Physcomitrella patens has part of the GA biosynthetic pathway, from geranylgeranyl diphosphate to ent-kaurenoic acid, no GA is found in this species. Caulonemal differentiation in a P. patens mutant with a disrupted bifunctional ent-copalyl diphosphate synthase/ent-kaurene synthase (PpCPS/KS) gene is suppressed under red light, and is recovered by application of ent-kaurene and ent-kaurenoic acid. This indicates that derivatives of ent-kaurenoic acid, not GAs, might act as endogenous developmental regulators. Here, we found unique responses in the protonemal growth of P. patens under unilateral blue light, and these regulators were involved in the responses. When protonemata of the wild type were incubated under blue light, the chloronemal filaments grew in the opposite direction to the light source. Although this avoidance was not observed in the ent-kaurene deficient mutant, chloronemal growth toward a blue-light source in the mutant was suppressed by application of ent-kaurenoic acid, and the growth was rescued to that in the wild type. Expression analysis of the PpCPS/KS gene showed that the mRNA level under blue light was rapidly increased and was five times higher than under red light. These results suggest that regulators derived from ent-kaurenoic acid are strongly involved not only in the growth regulation of caulonemal differentiation under red light, but also in the light avoidance response of chloronemal growth under blue light. In particular, growth under blue light is regulated via the PpCPS/KS gene.


KIAA0319 Genotype Predicts the Number of Past Concussions in a Division I Football Team: A Pilot Study.
This candidate gene study evaluated the relationship of a past history of concussion with single nucleotide polymorphisms (SNPs) in nine genes in a small cohort (N = 87) of a nationally ranked Division I football team. Genes and SNPs studied were selected based on their published connection to brain injury and brain development, as well as impulsivity. We used multinomial logistic regression analysis (MLRA) to quantify how well genotype predicted the number of previously diagnosed concussions (three categories: none, one, two or more), while covarying race and number of years participating in football. The rs4504469 SNP for KIAA0319 was the only locus that significantly predicted number of previously diagnosed concussions (p = 0.005, meeting Bonferroni correction for multiple comparisons). The KIAA0319 results raise the hypothesis that having the CT or TT genotype of KIAA0319 may be predictive of a lower incidence of previously diagnosed concussion. This finding raises a number of hypotheses for future pre-clinical research, particularly whether alterations in neural organization related to KIAA0319 rs4504469 lead to reduced susceptibility for lasting head trauma, or greater resilience in the face of repeated subconcussive injury.


AKT1 Gene Polymorphisms and Obstetric Complications in the Patients with Schizophrenia.
We performed a genetic association study with schizophrenic patients to investigate whether the V-akt murine thymoma viral oncogene homolog 1 (AKT1) gene plays a role in obstetric complications. One-hundred-eighty patients with schizophrenia (male, 113; female, 67) were included. All patients fulfilled DSM-IV criteria for schizophrenia. Obstetric complications were measured by the Lewis scale. Prenatal and perinatal information was retrospectively collected from the patients' mothers. We selected six single nucleotide polymorphisms (SNPs) for the AKT1 gene: SNP1 (rs3803300), SNP2 (rs1130214), SNP3 (rs3730358), SNP4 (rs 1130233), SNP5 (rs2494732), and SNPA (rs2498804). The genotype data were analyzed for an association with the Lewis total score in terms of allele, genotype, and haplotype distribution. The mean total Lewis scores were 1.30+/-1.61 for males and 1.54+/-1.87 for females. Higher total score tended to be correlated with an earlier age of onset of schizophrenia in females. In the total sample, no SNP was associated with obstetric complications. However, the additional analyses for male and female subgroups found a significant association between SNPA and SNP4 and Lewis score in females (p=0.02 for SNPA, p=0.04 for SNP4). The SNP5-SNPA haplotype showed a positive association with obstetric complications (p=0.03) in the female patient group. We found an association between SNPs in the AKT1 gene and total Lewis score measuring obstetric complications in female patients with schizophrenia. Because these findings did not survive a correction for multiple testing, the significance should be interpreted carefully and replication studies are required.


Transforaminal lumbar interbody fusion and posterior lumbar interbody fusion utilizing BMP-2 in treatment of degenerative spondylolisthesis: neither safe nor cost effective.
With the rise of health care costs, there is increased emphasis on evaluating the cost of a particular surgical procedure for quality adjusted life year (QALY) gained. Recent data have shown that surgical intervention for the treatment of degenerative spondylolisthesis (DS) is as cost-effective as total joint arthroplasty. Despite these excellent outcomes, some argue that the addition of interbody fusion supplemented with bone morphogenetic protein (BMP) enhances the value of this procedure. This review examines the current research regarding the cost-effectiveness of the surgical management of lumbar DS utilizing interbody fusion along with BMP. Posterolateral spinal fusion with instrumentation for focal lumbar spinal stenosis with DS can provide and maintain improvement in self-reported quality of life. Based on the available literature, including nonrandomized comparative studies and case series, the addition of interbody fusion along with BMP does not lead to significantly better clinical outcomes and increases costs when compared with more routine posterolateral fusion techniques. To enhance the value of the surgical management for DS, costs must decrease or there should be substantial improvement in effectiveness as measured by clinical outcomes. To date, there is insufficient evidence to support the use of interbody fusion devices along with BMP to treat routine cases of focal stenosis accompanied by DS, which are routinely adequately treated utilizing posterolateral fusion techniques.


[Progress and challenges facing user acceptance in the implementation and qualification of the Unified Health System in Primary Healthcare: a review of the bibliographical output in Brazil].
The public policies adopted by the Unified Health System (SUS) in Brazil have gone through successive transformations, striving to reassert health as a universal right. The user acceptance of the guidelines of the National Humanization Policy for Care and Management of the SUS - Humanize SUS - is taking shape and relevance in Primary Healthcare (PHC) to ensure humanized access and resolution of the health demands of users and communities in Brazil. A critical analysis of the bibliographical output in Brazil from 1989 to 2009 was conducted regarding acceptance of implementation and qualification of SUS in PHC. The databases consulted were SciELO, Lilacs and Medline. The results revealed progress in broadening access to PHC services and health professionals more sensitive to the needs of users and communities. However, lack of coordination in integrated networks, excess demand, the hegemonic biomedical model, lack of training and democratic and reflexive spaces to reorganize the work process have been raising increasingly more incisive questions about the potential of this guideline for the implementation and qualification of SUS.


Macro-to-micro links in the relation between income inequality and mortality.
A growing literature points to links between income inequality and mortality. Any examination of the link should distinguish, both theoretically and empirically, between shifts in inequality that result from changes in the bottom and top of the income distribution. When state-level data from the U.S. censuses of 1980 and 1990 were used to measure differences in mortality, the results indicated that inequality measures reflecting depth of poverty show stronger correlations with mortality than do inequality measures reflecting heights of affluence. In addition, longitudinal data from the Panel Study of Income Dynamics were used to related state-level inequality measures to individual-level data on mortality. This comparison revealed significant associations between degree of income inequality in state of residence and individual risk of death only for nonelderly individuals with middle-class incomes in 1990.


High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of Common Variable Immune Deficiency (CVID).
We previously developed GoMiner, an application that organizes lists of 'interesting' genes (for example, under-and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. The original version of GoMiner was oriented toward visualization and interpretation of the results from a single microarray (or other high-throughput experimental platform), using a graphical user interface. Although that version can be used to examine the results from a number of microarrays one at a time, that is a rather tedious task, and original GoMiner includes no apparatus for obtaining a global picture of results from an experiment that consists of multiple microarrays. We wanted to provide a computational resource that automates the analysis of multiple microarrays and then integrates the results across all of them in useful exportable output files and visualizations. We now introduce a new tool, High-Throughput GoMiner, that has those capabilities and a number of others: It (i) efficiently performs the computationally-intensive task of automated batch processing of an arbitrary number of microarrays, (ii) produces a human-or computer-readable report that rank-orders the multiple microarray results according to the number of significant GO categories, (iii) integrates the multiple microarray results by providing organized, global clustered image map visualizations of the relationships of significant GO categories, (iv) provides a fast form of 'false discovery rate' multiple comparisons calculation, and (v) provides annotations and visualizations for relating transcription factor binding sites to genes and GO categories. High-Throughput GoMiner achieves the desired goal of providing a computational resource that automates the analysis of multiple microarrays and integrates results across all of the microarrays. For illustration, we show an application of this new tool to the interpretation of altered gene expression patterns in Common Variable Immune Deficiency (CVID). High-Throughput GoMiner will be useful in a wide range of applications, including the study of time-courses, evaluation of multiple drug treatments, comparison of multiple gene knock-outs or knock-downs, and screening of large numbers of chemical derivatives generated from a promising lead compound.