SOX2 expression associates with stem cell state in human ovarian carcinoma.
The SRY-related HMG-box family of transcription factors member SOX2 regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, SOX2 expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies exploring the predictive value of SOX2 protein expression with respect to histopathologic and clinical parameters report contradictory results in individual tumors, indicating that SOX2 may play tumor-specific roles. In this report, we analyze the functional relevance of SOX2 expression in human ovarian carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2 expression increases the expression of CSC markers, the potential to form tumor spheres, and the in vivo tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, SOX2-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that SOX2 associates with stem cell state in ovarian carcinoma and induction of SOX2 imposes CSC properties on SOC cells. We propose the existence of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC.


Why social networks are different from other types of networks.
We argue that social networks differ from most other types of networks, including technological and biological networks, in two important ways. First, they have nontrivial clustering or network transitivity and second, they show positive correlations, also called assortative mixing, between the degrees of adjacent vertices. Social networks are often divided into groups or communities, and it has recently been suggested that this division could account for the observed clustering. We demonstrate that group structure in networks can also account for degree correlations. We show using a simple model that we should expect assortative mixing in such networks whenever there is variation in the sizes of the groups and that the predicted level of assortative mixing compares well with that observed in real-world networks.


Preparation and characterization of polymer nanocomposite containing PMMA, styrene and nanoalumina.
Polymer syrup of polymethyl methacrylate and polystyrene reinforced with 2% non settling nanoalumina particles was prepared by dual initiating system containing benzoylperoxide (BPO), azo-bisisobutyro nitrile (AIBN) and dimethylaniline (DMA). Nanoalumina particles were prepared using autoignition of aluminum nitrate and urea. Nanoalumina particles show the tendency of agglomeration in the polymer matrix because of the presence of hydroxyl groups on its surface. To get better dispersion in polymer matrix, the alumina surface was treated with methacrylol isocyanate, synthesized by the reaction of methacrylol chloride and sodium azide in the presence of dry benzene at 0 degrees C. The polymer syrup prepared this way was applied between two PMMA sheets of 10 cms x 10 cms x 2 mm dimensions each and the composite thus prepared was tested with Bullet Firing Machine as well as Vertical Drop Weight Impact Testing Machine. The impact strength measurements of two plates composite using both these procedures showed that the impact resistance was found to double in case of nanoalumina. The composite of ten layers and of eleven layers was further tested by 0.32 IOF revolver and Sub Machine Gun Carbine 9 mm 1A1 respectively from 10 m distance which produced an ordinary indent with no penetration.


Motifs of VDAC2 required for mitochondrial Bak import and tBid-induced apoptosis.
Voltage-dependent anion channel (VDAC) proteins are major components of the outer mitochondrial membrane. VDAC has three isoforms with >70% sequence similarity and redundant roles in metabolite and ion transport. However, only Vdac2(-/-) (V2(-/-)) mice are embryonic lethal, indicating a unique and fundamental function of VDAC2 (V2). Recently, a specific V2 requirement was demonstrated for mitochondrial Bak import and truncated Bid (tBid)-induced apoptosis. To determine the relevant domain(s) of V2 involved, VDAC1 (V1) and V2 chimeric constructs were created and used to rescue V2(-/-) fibroblasts. Surprisingly, the commonly cited V2-specific N-terminal extension and cysteines were found to be dispensable for Bak import and high tBid sensitivity. In gain-of-function studies, V2 (123-179) was the minimal sequence sufficient to render V1 competent to support Bak insertion. Furthermore, in loss-of-function experiments, T168 and D170 were identified as critical residues. These motifs are conserved in zebrafish V2 (zfV2) that also rescued V2-deficient fibroblasts. Because high-resolution structures of zfV2 and mammalian V1 have become available, we could superimpose these structures and recognized that the critical V2-specific residues help to create a distinctive open "pocket" on the cytoplasmic surface that could facilitate Bak recruitment.


Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells.
Osteopontin is a secreted phosphoglycoprotein that is expressed by a number of normal cells as well as a variety of tumor cells. With respect to breast cancer, osteopontin has been implicated in regulating tumor cell proliferation and migration/metastasis and may serve as a prognostic indicator. However it remains unclear whether osteopontin has the same impact in all breast cancer subtypes and in particular, osteopontin's effects in claudin-low breast cancer are poorly understood. cDNA microarrays and qRT-PCR were used to evaluate osteopontin expression in mammary tumors from MTB-IGFIR transgenic mice and cell lines derived from these tumors. siRNA was then used to determine the impact of osteopontin knockdown on proliferation, apoptosis and migration in vitro in two murine claudin-low cell lines as well as identify the receptor mediating osteopontin's physiologic effects. Osteopontin was expressed at high levels in mammary tumors derived from MTB-IGFIR transgenic mice compared to normal mammary tissue. Evaluation of cell lines derived from different mammary tumors revealed that mammary tumor cells with claudin-low characteristic expressed high levels of osteopontin whereas mammary tumor cells with mixed luminal and basal-like features expressed lower levels of osteopontin. Reduction of osteopontin levels using siRNA significantly reduced proliferation and migration while increasing apoptosis in the claudin-low cell lines. Osteopontin's effect appear to be mediated through a receptor containing ITGAV and not through CD44. Our data suggests that mammary tumors with a mixed luminal/basal-like phenotype express high levels of osteopontin however this osteopontin appears to be largely produced by non-tumor cells in the tumor microenvironment. In contrast tumor cells with claudin-low characteristics express high levels of osteopontin and a reduction of osteopontin in these cells impaired proliferation, survival and migration.


Rheological effects of blood in a nonplanar distal end-to-side anastomosis.
This study investigates rheological effects of blood on steady flows in a nonplanar distal end-to-side anastomosis. The shear-thinning behavior of blood is depicted by a Carreau-Yasuda model and a modified power-law model. To explore effects of nonplanarity in vessel geometry, a curved bypass graft is considered that connects to the host artery with a 90 deg out-of-plane curvature. Navier-Stokes equations are solved using a finite volume method. Velocity and wall shear stress (WSS) are compared between Newtonian and non-Newtonian fluids at different flow rates. At low flow rate, difference in axial velocity profiles between Newtonian and non-Newtonian fluids is significant and secondary flows are weaker for non-Newtonian fluids. At high flow rate, non-Newtonian fluids have bigger peak WSS and WSS gradient. The size of the flow recirculation zone near the toe is smaller for non-Newtonian fluids and the difference is significant at low flow rate. The nonplanar bypass graft introduces helical flow in the host vessel. Results from the study reveal that near the bed, heel, and toe of the anastomotic junction where intimal hyperplasia occurs preferentially, WSS gradients are all very big. At high flow rates, WSS gradients are elevated by the non-Newtonian effect of blood but they are reduced at low flow rates. At these locations, blood rheology not only affects the WSS and its gradient but also secondary flow patterns and the size of flow recirculation near the toe. This study reemphasizes that the rheological property of blood is a key factor in studying hemodynamic effects on vascular diseases.


Parasite diversity of Nyctiphanes simplex and Nematoscelis difficilis (Crustacea: Euphausiacea) along the northwestern coast of Mexico.
The diversity of parasites found on Nyctiphanes simplex and Nematoscelis difficilis (Order Euphausiacea) was compared during 10 oceanographic cruises made off both coasts of the Baja California peninsula, Mexico. We tested the hypothesis that N. simplex has a more diverse parasitic assemblage than N. difficilis because it is a neritic species, has larger population abundance, and tends to form denser and more compact swarms than N. difficilis. These biological and behavioral features may enhance parasite transmission within swarms. We detected 6 types of ectoparasites: (1) epibiotic diatoms Licmophora sp.; (2) Ephelotidae suctorian ciliates; (3) Foettingeriidae exuviotrophic apostome ciliates; (4) an unidentified epicaridean cryptoniscus larvae (isopoda); and 2 castrators: (5) the ectoparasitic Dajidae isopod Notophryxus lateralis and (6) the ellobiopsid mesoparasite Thalassomyces fagei. We also detected 7 types of endoparasites: (1) an undescribed Collinia ciliate (Apostomatida); 3 types of Cestoda: (2) a Tetrarhynchobothruium sp. (Trypanorhyncha), (3) Echinobothrium sp. (Diphyllidea: Echinobothyriidae), and (4) unidentified metacestode; (5) a Trematoda Paronatrema-like metacercaria (Syncoeliidae); (6) the nematode Anisakis simplex (L3); and (7) Polymorphidae acantocephalan larvae (acanthor, acanthella, and cystacanth larval stages). N. simplex is affected by all types of parasites, except the isopod N. lateralis, having a considerably larger parasitic diversity and prevalence rates than N. difficilis, which is only infested with 3 types of ectoparasites and T. fagei. Euphausiid swarming is an adaptive behavior for reproduction, protection against predators, and increased efficiency in food searching, but has a negative effect due to parasitism. Although the advantages of aggregation must overcome the reduction of population and individual fitness induced by parasites, we demonstrated that all types of parasites can affect approximately 14% of N. simplex individuals. Collinia spp. endoparasitoids must occasionally have a significant influence on population mortality with potential epizootic events.


ClNAC100 Is a NAC Transcription Factor of Chinese Fir in Response to Phosphate Starvation.
Phosphate (Pi) deficiency is one of the most limiting factors for Chinese fir growth and production. Moreover, continuous cultivation of Chinese fir for multiple generations led to the reduction of soil nutrients, which hindered the yield of Chinese fir in southern China. Although NAC (NAM, ATAF, and CUC) transcription factors (TFs) play critical roles in plant development and abiotic stress resistance, it is still unclear how they regulate the response of Chinese fir to phosphate (Pi) starvation. Based on Pi-deficient transcriptome data of Chinses fir root, we identified a NAC transcription factor with increased expression under Pi deficiency, which was obtained by PCR and named ClNAC100. RT-qPCR confirmed that the expression of ClNAC100 in the root of Chinese fir was induced by phosphate deficiency and showed a dynamic change with time. It was positively regulated by ABA and negatively regulated by JA, and ClNAC100 was highly expressed in the roots and leaves of Chinese fir. Transcriptional activation assay confirmed that ClNAC100 was a transcriptional activator. The promoter of ClNAC100 was obtained by genome walking, which was predicted to contain a large number of stress, hormone, and growth-related cis-elements. Tobacco infection was used to verify the activity of the promoter, and the core promoter was located between -1519 bp and -589 bp. We identified 18 proteins bound to the ClNAC100 promoter and 5 ClNAC100 interacting proteins by yeast one-hybrid and yeast two-hybrid, respectively. We speculated that AHL and TIFY family transcription factors, calmodulin, and E3 ubiquitin ligase in these proteins might be important phosphorus-related proteins. These results provide a basis for the further study of the regulatory mechanism and pathways of ClNAC100 under Pi starvation.


Changes in plasma renin activity and plasma aldosterone in the induced paralytic attack of thyrotroxic periodic paralysis.
Changes in serum electrolytes, haematocrit, plasma renin activity and plasma aldosterone induced by glucose and insulin (GI) infusion were serially investigated in seven patients with periodic thyrotoxic paralysis. An attack which developed into complete quadriplegia was induced within 90 min after the beginning of the GI infusion in four out of seven patients. Only a slight paralysis of the legs was produced in another two patients and induction of an attack did not materialize in one. In four patients with complete quadriplegia, the mean values of serum sodium and potassium concentrations, haematocrit, plasma renin activity and plasma aldosterone slightly decreased immediately after the beginning of the GI infusion. Induction of a paralytic attack was not accompanied by any significant changes in serum sodium concentration, haematocrit, plasma renin activity and plasma aldosterone either 15 min before or after the onset of attack, while the serum potassium concentration progressively decreased, and an increase in plasma aldosterone associated with an increase of haematocrit and plasma renin activity reached a peak level at the stage of complete quadriplegia. On the other hand, in the three patients in whom an infusion produced slight or no paralysis of the legs, changes in the serum sodium concentration, haematocrit, plasma renin activity and plasma aldosterone were insignificant and the serum potassium concentration was slightly but insignificantly decreased. These results suggest that hyperaldosteronism may not be a trigger for the induced paralytic attack but a phenomenon secondary to volume depletion and a change in potassium homoeostasis induced by GI infusion.


Experimental cerebral vasospasm after subarachnoid hemorrhage: development and degree of vasospasm.
Vasospasm of the basilar artery in 57 cats was induced by application of fresh blood, or a blood and cerebrospinal fluid (CSF) mixture incubated at 37 degrees C for 2 to 16 days. In animals treated with fresh blood or mixtures incubated for over 15 days, the severity of induced vasoconstriction is slight and duration short. Mixtures incubated 5 to 10 days induced severe and prolonged vasoconstriction. This incubation period for blood and CSF mixtures inducing severe vasospasm coincides with the developmental period of vasospasm after the onset of subarachnoid hemorrhage in our clinical experience. The prolongation of severe vasoconstriction induced by mixtures incubated for 7 days with clotted components is definitely greater than one induced by a mixture without clotted components. This experimental study suggests the existence of a vasospasmogenic substance in the blood in the subarachnoid space. Activity begins about 3 days after subarachnoid hemorrhage, increases strongly at 5 to 10 days, and disappears after 15 days.


Food web persistence in fragmented landscapes.
Habitat destruction, characterized by patch loss and fragmentation, is a key driver of biodiversity loss. There has been some progress in the theory of spatial food webs; however, to date, practically nothing is known about how patch configurational fragmentation influences multi-trophic food web dynamics. We develop a spatially extended patch-dynamic model for different food webs by linking patch connectivity with trophic-dependent dispersal (i.e. higher trophic levels displaying longer-range dispersal). Using this model, we find that species display different sensitivities to patch loss and fragmentation, depending on their trophic position and the overall food web structure. Relative to other food webs, omnivory structure significantly increases system robustness to habitat destruction, as feeding on different trophic levels increases the omnivore's persistence. Additionally, in food webs with a dispersal-competition trade-off between species, intermediate levels of habitat destruction can enhance biodiversity by creating refuges for the weaker competitor. This demonstrates that maximizing patch connectivity is not always effective for biodiversity maintenance, as in food webs containing indirect competition, doing so may lead to further species loss.


PagUNE12 encodes a basic helix-loop-helix transcription factor that regulates the development of secondary vascular tissue in poplar.
Secondary growth in woody plants generates new cells and tissues via the activity of the vascular cambium and drives the radial expansion of stems and roots. It is regulated by a series of endogenous factors, especially transcription factors. Here, we cloned the basic helix-loop-helix (bHLH) transcription factor gene UNFERTILIZED EMBRYO SAC12 (UNE12) from poplar (Populus alba × Populus glandulosa Uyeki) and used biochemical, molecular, and cytological assays to investigate the biological functions and regulatory mechanism of PagUNE12. PagUNE12 mainly localized in the nucleus and possessed transcriptional activation activity. It was widely expressed in vascular tissues, including primary phloem and xylem and secondary phloem and xylem. Poplar plants overexpressing PagUNE12 showed significantly reduced plant height, shorter internodes, and curled leaves compared with wild-type plants. Optical microscopy and transmission electron microscopy revealed that overexpressing PagUNE12 promoted secondary xylem development, with thicker secondary cell walls than wild-type poplar. Fourier transform infrared spectroscopy, confocal Raman microscopy, and 2D Heteronuclear Single Quantum Correlation analysis indicated that these plants also had increased lignin contents, with a lower relative abundance of syringyl lignin units and a higher relative abundance of guaiacyl lignin units. Therefore, overexpressing PagUNE12 promoted secondary xylem development and increased the lignin contents of secondary xylem in poplar, suggesting that this gene could be used to improve wood quality in the future.


Crystallization, X-ray diffraction analysis and preliminary structure determination of the polygalacturonase PehA from Agrobacterium vitis.
Polygalacturonases are pectate-degrading enzymes that belong to glycoside hydrolase family 28 and hydrolyze the alpha-1,4 glycosidic bond between neighboring galacturonasyl residues of the homogalacturonan substrate. The acidic polygalacturonase PehA from Agrobacterium vitis was overexpressed in Escherichia coli, where it accumulated in the periplasmic fraction. It was purified to homogeneity via a two-step chromatography procedure and crystallized using the hanging-drop vapour-diffusion technique. PehA crystals belonged to space group P2(1), with unit-cell parameters a = 52.387, b = 62.738, c = 149.165 A, beta = 89.98 degrees . Crystals diffracted to 1.59 A resolution and contained two molecules per asymmetric unit. An initial structure determination by molecular replacement indicated a right-handed parallel beta-helix fold.


Nonsurgical and nonextraction treatment of a skeletal class III adult patient with severe prognathic mandible.
A patient with a skeletal Class III malocclusion, prognathic mandible, anterior open bite, large tongue, and temporomandibular disorders is presented. Treatment objectives included establishing a stable occlusion with normal respiration, eliminating temporomandibular disorder symptoms, and improving facial esthetics through nonextraction and nonsurgical treatment by creating a favorable perioral environment, restoring the harmony to the tongue and perioral environment, improving masticatory muscle function, and creating adequate tongue space for establishment of normal respiration. The patient was a Japanese adult male, who had previously been advised to have orthognathic surgery, with tongue-size reduction. An expansion plate was used to expand the maxillary dentoalveolar arch. Distalization of the mandibular arch was achieved by reduced excessive posterior vertical dimension, through uprighting and intruding the mandibular posterior teeth and rotating the mandible slightly counter-clockwise. The height of the maxillary alveolar process and the vertical height of symphysis were increased slightly. The functional occlusal plane was reconstructed by uprighting and intruding the posterior teeth with a full-bracket appliance, combined with a maxillary expansion plate, with short Class III and vertical elastics in the anterior area. Myofunctional therapy involved sugarless chewing gum exercises. The excessive posterior vertical occlusal dimension was reduced slightly, creating a small clearance between the posterior maxilla and mandible. At the same time, the interferences in the posterior area were eliminated by the expansion of the maxillary dentoalveolar arch. As a result, the laterally displaced mandible moved to a more favorable jaw relationship, with distalization of the mandibular arch. The functional occlusal plane was reconstructed and an almost-normal overjet and overbite were created. Adequate tongue space for normal respiration was established during the early stage of treatment, by 7 months. A stable occlusion, with adequate posterior support and anterior guidance, was established and maintained at more than 4 years posttreatment.


A computational examination of the two-streams hypothesis: which pathway needs a longer memory?
The two visual streams hypothesis is a robust example of neural functional specialization that has inspired countless studies over the past four decades. According to one prominent version of the theory, the fundamental goal of the dorsal visual pathway is the transformation of retinal information for visually-guided motor behavior. To that end, the dorsal stream processes input using absolute (or veridical) metrics only when the movement is initiated, necessitating very little, or no, memory. Conversely, because the ventral visual pathway does not involve motor behavior (its output does not influence the real world), the ventral stream processes input using relative (or illusory) metrics and can accumulate or integrate sensory evidence over long time constants, which provides a substantial capacity for memory. In this study, we tested these relations between functional specialization, processing metrics, and memory by training identical recurrent neural networks to perform either a viewpoint-invariant object classification task or an orientation/size determination task. The former task relies on relative metrics, benefits from accumulating sensory evidence, and is usually attributed to the ventral stream. The latter task relies on absolute metrics, can be computed accurately in the moment, and is usually attributed to the dorsal stream. To quantify the amount of memory required for each task, we chose two types of neural network models. Using a long-short-term memory (LSTM) recurrent network, we found that viewpoint-invariant object categorization (object task) required a longer memory than orientation/size determination (orientation task). Additionally, to dissect this memory effect, we considered factors that contributed to longer memory in object tasks. First, we used two different sets of objects, one with self-occlusion of features and one without. Second, we defined object classes either strictly by visual feature similarity or (more liberally) by semantic label. The models required greater memory when features were self-occluded and when object classes were defined by visual feature similarity, showing that self-occlusion and visual similarity among object task samples are contributing to having a long memory. The same set of tasks modeled using modified leaky-integrator echo state recurrent networks (LiESN), however, did not replicate the results, except under some conditions. This may be because LiESNs cannot perform fine-grained memory adjustments due to their network-wide memory coefficient and fixed recurrent weights. In sum, the LSTM simulations suggest that longer memory is advantageous for performing viewpoint-invariant object classification (a putative ventral stream function) because it allows for interpolation of features across viewpoints. The results further suggest that orientation/size determination (a putative dorsal stream function) does not benefit from longer memory. These findings are consistent with the two visual streams theory of functional specialization. The online version contains supplementary material available at 10.1007/s11571-021-09703-z.


Particle size evaluations using multiwavelength extinction measurements.
As the first phase of a program to develop a lidar method for remote evaluation of mean particle size of stationary source emissions, a data base was experimentally collected consisting of multiple-wavelength extinction coefficients and mean particle sizes of generated aerosols. Extinction data were collected using multi-wavelength (14) transmissometers and a 10-m long aerosol tunnel facility. Generated aerosols consisted of five size fractions of fly ash, three size fractions of silica, and single-size fractions of six other types of particulate material. Particle size evaluations were made by multistage impactor and by air permeability (Fisher) analysis of packed powder. The data base indicates that mean particle size smaller than l-microm diam could be estimated usefully from aerosol extinction measurements using a single-laser lidar system operating at 1.06- and 0.53-microm wavelengths. For larger mean particle sizes the extinction ratio is near unity, and longer wavelength systems are required. The data indicate that a two-laser lidar operating at 10.6 and 0.53 microm could provide estimates of mean particle size to diameters of at least 6 microm.


Diffusion of actin filaments within a thin layer between two walls.
Diffusion of the protein filaments F -actin confined in a thin layer between two walls is studied using the methods of single filament fluorescence imaging and particle tracking. The translational and rotational diffusion coefficients are measured for F -actin of lengths in the range of 1.5-5 microm. The length dependence of the measured diffusion coefficients is consistent with the predicted two-dimensional projection of the diffusion of a cylinder in an unbounded fluid. Fits based on the formulas for diffusion in the bulk fluid yield higher apparent viscosity values than that of the buffer solution by a factor of 2 for a layer thickness between 0.7 and 1.6 microm. We show that the measured results can be accounted for by correction based on the hydrodynamic theory of a long cylinder between confining walls.


Coproduction of Research Questions and Research Evidence in Public Health: The Study to Prevent Teen Drinking Parties.
Community-based participatory research (CBPR) provides a set of principles and practices intended to foster coproduction of knowledge. However, CBPR often has shortcomings when applied to population-level policy and practice interventions, including a focus on single communities and a lack of focus on policy change. At the same time, community trials focused on policy have shortcomings, including lack of stakeholder involvement in framing research questions and modest engagement in study implementation and interpretation and dissemination of results. We describe an attempt to hybridize CBPR and community trials by creating a partnership that included a national membership organization, a coalition advisory board, intervention and delayed intervention communities, and an academic study team, which collaborated on a study of community strategies to prevent underage drinking parties. We use qualitative and quantitative data to critically assess the partnership. Areas where the partnership was effective included (1) identifying a research question with high public health significance, (2) enhancing the intervention, and (3) improving research methods. Challenges included community coalition representatives' greater focus on their own communities rather than the production of broader scientific knowledge. This model can be applied in future attempts to narrow the gap between research, policy, and practice.


Roberts syndrome, normal cell division, and normal intelligence.
Roberts-SC phocomelia syndrome (RS) is an autosomal recessive disorder of symmetric limb defects, craniofacial abnormalities, pre- and postnatal growth retardation, and mental retardation. Patients with RS have been reported to have premature separation of heterochromatin of many chromosomes and abnormalities in the cell-division cycle. No case has been reported who had normal intelligence and normal cell division with typical clinical features of the RS. We report a case of a six-year-old male of clinical and radiologic findings of typical RS with normal cell division and normal intelligence. Although he showed growth retardation, his intelligence was normal. Van Den Berg and Francke later reported that 79 out of 100 cases of Roberts syndrome had premature cell separation (PCS). We think that this case may demonstrate severe expression of the Roberts syndrome even though PCS is not exhibited. The limb involvement of this case was symmetrical, and he showed phocomelia of upper limbs, equinus valgus deformity of ankle, aplasia of fibula, and shortness of fifth toes while his hands and feet were normal with 5 rays each. Craniofacial abnormalities of this case were typical; he showed scaphocephaly, mild hypertelorism, mandibular hypoplasia, dysplastic helix of ear, narrowing of external auditory canal, and cleft palate with wide gap. This report supports the theory that normal intelligence can make social-personal adjustment possible even if all of the stigmata of Roberts syndrome is present.


Mutation of nfxB causes global changes in the physiology and metabolism of Pseudomonas aeruginosa.
Loss-of-function mutations in nfxB lead to up-regulation of mexCD-oprJ expression and, consequently, increased resistance to fluoroquinolone antibiotics. Such nfxB mutants have also been reported to exhibit altered virulence profiles, diminished type III secretion system-dependent cytotoxicity, and impaired fitness. However, it is not clear whether these phenotypes are directly linked to NfxB activity or whether inappropriate expression of the MexCD-OprJ pump has pleiotropic effects, thereby impacting indirectly on the phenotype of the cells. The aim of the current work is to investigate which of these possibilities is correct. We isolated a novel type of nfxB mutant generated by a spontaneous polygenic deletion and show that this mutant is rapidly out-competed when grown in a mixed culture with the wild-type progenitor. This competitive fitness defect only manifested itself during the stationary phase of growth. The endoproteome of the nfxB mutant, assessed using 2D-DiGE (difference gel electrophoresis), showed major alterations compared with the wild-type. Consistent with this, we found that the nfxB mutant was impaired in all forms of motility (swimming, swarming, and twitching) as well as in the production of siderophores, rhamnolipid, secreted protease, and pyocyanin. Further investigation showed that the exoproteome, endometabolome, and exometabolome of the nfxB mutant were all globally different compared with the wild-type. The exometabolome of the nfxB mutant was enriched in a selection of long chain fatty acids raising the possibility that these might be substrates for the MexCD-OprJ pump. The nfxB mutant metabotype could be complemented by expression of nfxB in trans and was abolished in an nfxB mexD double mutant, suggesting that inappropriate overexpression of a functional MexCD-OprJ efflux pump causes pleiotropic changes. Taken together, our data suggest that many of the nfxB mutant phenotypes are not caused by the direct effects of the NfxB regulator, but instead by inappropriate mexCD-oprJ expression. Furthermore, the pleiotropic nature of the phenotypes indicate that these may simply reflect the globally dysregulated physiology of the strain.


Gas-phase pressure measurement using femtosecond laser-induced grating scattering technique.
Gas-phase pressure measurements remain challenging in situations where local pressure rapidly changes or in hostile environments such as turbulent combustion. In this work, we demonstrate the implementation of the recently developed femtosecond laser-induced grating scattering (fs-LIGS) technique for pressure measurement in ambient air. With an overall femtosecond laser pulse energy of 185 μJ, fs-LIGS signals were generated for various gas pressure ranging from 0.2 to 3.0 bar. By theoretically fitting the signal and extracting the time constant of the stationary density modulation damping, the pressure is successfully derived. The derived values were compared to the gauge pressure, which shows a quasi-linear dependence with a slope of 0.96, suggesting the feasibility of the fs-LIGS technique for gas-phase pressure measurements.


Changing Infliximab Prescription Patterns in Inflammatory Bowel Disease: A Population-Based Cohort Study, 1999-2014.
Long-term data on real life use of infliximab (IFX) for inflammatory bowel disease (IBD) are lacking. We studied prescription patterns during the first 16 years following marketing authorization. In a population-based cohort from the North Denmark Region, all IBD patients exposed to IFX during 1999 to 2014 were identified. A total of 623 patients (210 with ulcerative colitis [UC] and 413 with Crohn's disease [CD]) were exposed to IFX. In patients with UC, age at first exposure decreased by 10 months per calendar year (P < 0.05) during the study period. In patients with CD, disease duration at time of first IFX exposure decreased by 7 months per calendar year (P < 0.001). From 2005-2009 to 2010-2014, the proportion of IFX-exposed patients with pancolitis (40% vs 24%, P = 0.04) and the proportion of patients with extensive CD (P = 0.002) decreased. The mean time to discontinuation of IFX remained stable in patients with CD during the study period (2.5-3.0 years) and increased from 0.34 years (2005-2009) to 1.11 years (2010-2015) in patients with UC (P = 0.04). During the first 16 years postmarketing, age at first exposure to IFX decreased in patients with UC, whereas disease duration at time of first exposure decreased in patients with CD. Also, a significant change toward less extensive disease in both UC and CD patients exposed to IFX was observed. Treatment duration in patients with UC increased during the study period, but did not reach the more constant and longer duration of treatment observed in patients with CD.


A 10-year observational single-center study of retroperitoneal unicentric Castleman disease.
Diagnosis of unicentric Castleman disease (UCD) is not easy before the resection and obtainment of pathological result. We retrospectively summarized 10-year experience of clinical evaluation and management for retroperitoneal UCD in Peking Union Medical College Hospital (PUMCH) between December 1, 2009 and December 31, 2019. Seventy two UCD patients with pathological diagnosis after resection were screened out. Among them 25 patients had retroperitoneal UCD. The average age of the 25 patients was 43.80 ± 12.79, and 52.00% were male. No patients had systemic symptoms, and 1 patient got preoperative treatment. The average size of masses was 5.59 ± 2.86 cm. The UCD sites included kidney, adrenal area, perinephric area, pancreas, peripancreatic area, area of descending part of duodenum, periaortic area or beside iliac artery, and others. The masses presented different degree of enhancement on CT scans and hypoecho or isoecho on ultrasound. Increased metabolism could be found on 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT). Some patients had positive results on somatostatin receptor imaging, but none had positive results on 131I-metaiiodo-benzylguanidine (131I-MIBG). Some patients presented the elevated level of interleukin-6 (IL-6), 24hour-urinary catecholamine and tumor markers. All the patients received complete resection of masses and 96.00% had hyaline-vascular type pathology except 1 patient (plasma cell-type). Ninety two percent patients received a long-term follow-up with an average follow-up time of 35.48 ± 33.90 months. No patients died or experienced relapse during follow-up. Differential diagnosis of retroperitoneal UCD may be difficult according to imaging and laboratorial examinations. Differential diagnosis with pheochromocytomas/paragangliomas should be taken into special consideration. Different imaging examinations, such as CT/MRI, 18F-PET/CT, somatostatin receptor imaging and 131I-MIBG, can be combined for differential analysis. Complete resection is the best treatment and could provide a final pathological diagnosis.


SP1-mediated long noncoding RNA POU3F3 accelerates the cervical cancer through miR-127-5p/FOXD1.
Emerging evidence supports the critical roles of long noncoding RNA (lncRNA) in cervical cancer. However, the pathological roles of lncRNA POU3 F3 in the cervical cancer tumorigenesis are still elusive. POU3 F3 was validated to be up-regulated in the cervical cancer tissue specimens and cells comparing with normal controls. Moreover, the ectopic overexpression of POU3 F3 was closely correlated with poor prognosis. In vitro, POU3 F3 promoted the proliferation, invasion of cervical cancer cells. In vivo, POU3 F3 knockdown repressed the tumor growth of cervical cancer cells. The transcriptional expression of POU3 F3 was activated by the transcription factor SP1. Mechanically, POU3 F3 acted as the sponge to target miR-127-5p, while miR-127-5p bind with the 3'-UTR of FOXD1 gene. In conclusion, our data verifies that lncRNA POU3 F3, induced by transcription factor SP1, acts as an oncogene in the cervical cancer tumorigenesis via regulating miR-127-5p/FOXD1 axis, providing a possible therapeutic target for cervical cancer.


Craniofacial defects of blastogenesis: duplication of pituitary with cleft palate and orophgaryngeal tumors.
Duplications of organs and/or tissues are rare in morphogenesis and have frequently been attributed to incomplete twinning. To further elucidate the phenotypes associated with organ duplications, we present three infants with duplication of the pituitary gland (DPG). A review of previously reported cases with DPG showed that the commonest additional findings were hypothalamic enlargement, a broad or duplicated sella, cleft palate, hypertelorism, oropharyngeal tumors, agenesis or hypoplasia of the corpus callosum, and abnormalities of vertebrae. DPG and additional malformations constitute a distinct and recognizable pattern of anomalies, which may constitute a polytopic field defect due to splitting of the notochord. However, the precise inductive mechanism resulting in DPG remains unknown.


Radiosensitivity of cloned permanent murine bone marrow stromal cell lines: nonuniform effect of low dose rate.
The x-irradiation biology of supportive stromal cells of the bone marrow microenvironment was investigated by using cloned permanent cell lines that were established from hematopoietically active murine long-term bone marrow cultures. X-irradiation survival curves were derived for each cell line at either 120 cGy/min or clinical low dose rate (LDR) (5 cGy/min) that is used in total body irradiation protocols prior to bone marrow transplantation. Four cell lines, MBA-1, MBA-13, 14F2.1, and D2XRII (Group I) demonstrated a significant increase in D0 at 5 cGy/min (280 cGy, 270 cGy, 210 cGy, and 240 cGy, respectively) compared to 120 cGy/min (215 cGy, 210 cGy, 157 cGy, and 210 cGy, respectively) (p less than 0.05). In contrast, three other clonal cell lines, +/+ #2 cl 4, S1d #3, and GPI alpha-1 (Group II) showed no significant dose rate dependent change in D0 at 5 cGy/min (164 cGy, 174 cGy, and 159 cGy, respectively) compared to 120 cGy/min (159 cGy, 167 cGy, and 143 cGy, respectively). Group I and II cell lines could not be distinguished by differences in synthesis of extracellular matrix proteins including laminin, collagen types I and IV, or histochemically detectable enzymes. Three Group I lines (MBA-1, MBA-13, and D2XRII) and one Group II line, Sld #3, showed decreased support capacity for cocultivated hematopoietic stem cells in vitro. All seven lines had detectable polyA+ mRNA for monocyte colony-stimulating factor (M-CSF) as detected by molecular hybridization; one had detectable levels of polyA+ mRNA for granulocyte-macrophage colony-stimulating factor (GM-CSF) (D2XRII); one, detectable levels of polyA+ mRNA for interleukin 1 (IL-1); and none of the seven had detectable polyA+ mRNA for granulocyte colony-stimulating factor (G-CSF) or IL-3 (multi-CSF). The data indicate that some cells of the hematopoietic microenvironment may not be selectively protected by clinical low dose rate irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)


Pulmonary hypertension, hemolytic anemia, and renal failure. A mitomycin-associated syndrome.
After treatment with mitomycin C, a patient developed pulmonary hypertension with interstitial infiltrates, microangiopathic hemolytic anemia, systemic hypertension, and renal failure with the nephrotic syndrome. Open lung biopsy documented intracapillary fibrin thrombi in the pulmonary vasculature. Renal biopsy documented glomerular and arteriolar changes that were most consistent with a thrombotic-thrombocytopenic-like process. Treatment with corticosteroids, fresh-frozen plasma, and total plasma exchange was ineffective. The patient died six months after the onset. When mitomycin-C therapy is given, the clinician should be aware of the pulmonary, renal, and microangiopathic changes that can be associated with such therapy.


[The role of hepatic stellate cells SSeCKS expression in liver fibrosis].
To investigate the change and effect of SSeCKS (src suppressed c kinase substrates) in the activation of hepatic stellate cells (HSCs). HSCs were isolated from normal rats, the change of SSeCKS mRNA expression on HSCs culture in vitro was determined using real-time PCR, protein level was determined by Western blot and immunofluorescence methods. A rat model of liver fibrosis was established. The expression and location of SSeCKS and alpha-SMA (alpha-smooth muscle actin) in liver tissues were detected by immunofluorescence methods. SSeCKS mRNA expression was low in freshly isolated HSCs cell and the expression increased in activated HSCs in vitro. In liver fibrosis tissue, the number of SSeCKS-positive cells was increased and these cells were distributed along the sinusoids which also contained alpha-SMA positive cells. The expression of SSeCKS was increased in activated HSCs in vitro. Therefore, SSeCKS may be involved in the liver inflammation and fibrosis.


Effect of intrathecal bupivacaine on somatosensory evoked potentials following dermatomal stimulation.
The effect of spinal anesthesia with 3.6 +/- 0.1 ml (mean +/- SEM) of 0.5% bupivacaine on early (less than 150 msec) somatosensory evoked potentials (SEPs) with electrical stimulation of the L1 and S1 dermatomes was examined in 12 patients. The mean level of sensory analgesia (pinprick) was T8,9 +/- 1.0 (+/- SEM) and the mean degree of motor blockade was 1.3 +/- 0.1 (Bromage scale). Intrathecal bupivacaine significantly (P less than 0.05) decreased the amplitude of all SEP components after stimulation of the L1 dermatome and most components during stimulation of the S1 dermatome. Intrathecal bupivacaine also increased the latency of SEPs (P less than 0.05) of both dermatomes. The L1 SEP disappeared in 7 and the S1 SEPs in 5 of the 12 patients during neural blockade. In three patients the SEPs disappeared at both locations. Sensory thresholds increased significantly during blockade. We found no correlation between decrease of amplitude and degree of motor blockade or level of sensory analgesia. Thus, intrathecal plain bupivacaine has a strong depressant effect on the neural afferent transmission as assessed by SEPs. However, despite clinically effective blockade as assessed by pinprick and motor blockade nerve potentials after nociceptive stimulation within the area of sensory block were often able to pass to the cerebral cortex.


Niche shifts and range expansions along cordilleras drove diversification in a high-elevation endemic plant genus in the tropical Andes.
The tropical Andes represent one of the world's biodiversity hot spots, but the evolutionary drivers generating their striking species diversity still remain poorly understood. In the treeless high-elevation Andean environments, Pleistocene glacial oscillations and niche differentiation are frequently hypothesized diversification mechanisms; however, sufficiently densely sampled population genetic data supporting this are still lacking. Here, we reconstruct the evolutionary history of Loricaria (Asteraceae), a plant genus endemic to the Andean treeless alpine zone, based on comprehensive population-level sampling of 289 individuals from 67 populations across the entire distribution ranges of its northern Andean species. Partly incongruent AFLP and plastid DNA markers reveal that the distinct genetic structure was shaped by a complex interplay of biogeography (spread along and across the cordilleras), history (Pleistocene glacial oscillations) and local ecological conditions. While plastid variation documents an early split or colonization of the northern Andes by at least two lineages, one of which further diversified, a major split in the AFLP data correlate with altitudinal ecological differentiation. This suggests that niche shifts may be important drivers of Andean diversification not only in forest-alpine transitions, but also within the treeless alpine zone itself. The patterns of genetic differentiation at the intraspecific level reject the hypothesized separation in spatially isolated cordilleras and instead suggest extensive gene flow among populations from distinct mountain chains. Our study highlights that leveraging highly variable markers against extensive population-level sampling is a promising approach to address mechanisms of rapid species diversifications.


Mirikizumab for the treatment of moderate to severe ulcerative colitis.
Despite a growing number of available therapeutic options for ulcerative colitis (UC), up to 50% of patients do not respond to initial treatment or lose response over time, highlighting the need for novel therapies. The IL-23 pathway has emerged as an important therapeutic target for UC. Mirikizumab is a humanized IgG4 monoclonal antibody against the p19 subunit of IL-23, dosed intravenously during induction and subcutaneously during maintenance. It is effective for the induction and maintenance of remission in moderately to severely active UC, including patients with prior failure of biological or tofacitinib therapy. Like other IL-23 antagonists, mirikizumab has a favorable safety profile. It is the first agent of its class to receive regulatory approval for moderately to severely active UC in Europe.


Apoptosis as the mechanism of the involution of hair follicles in catagen transformation.
Electron microscopy was performed on mouse skin to study the mechanism of the spontaneous involution of hair follicles during catagen. The reduction in follicles size appears to result from cell deletion by apoptosis, a distinct type of cell death with importance in tissue kinetics. These ultrastructural changes have been misinterpreted in the past as autophagic vacuole formation because of the prominent phagocytosis of the apoptotic fragments by adjacent, surviving cells of the hair follicle.


Mast cells inhibit intramacrophage Francisella tularensis replication via contact and secreted products including IL-4.
Francisella tularensis is an intracellular, Gram-negative bacterium that is the causative agent of pulmonary tularemia. The pathogenesis and mechanisms related to innate resistance against F. tularensis are not completely understood. Mast cells are strategically positioned within mucosal tissues, the major interface with the external environment, to initiate innate responses at the site of infection. Mast cell numbers in the cervical lymph nodes and the lungs progressively increased as early as 48 h after intranasal F. tularensis live vaccine strain (LVS) challenge. We established a primary bone marrow-derived mast cell-macrophage coculture system and found that mast cells significantly inhibit F. tularensis LVS uptake and growth within macrophages. Importantly, mice deficient in either mast cells or IL-4 receptor displayed greater susceptibility to the infection when compared with corresponding wild-type animals. Contact-dependent events and secreted products including IL-4 from mast cells, and IL-4 production from other cellular sources, appear to mediate the observed protective effects. These results demonstrate a previously unrecognized role for mast cells and IL-4 and provide a new dimension to our understanding of the innate immune mechanisms involved in controlling intramacrophage Francisella replication.


Building an outpatient imaging center: A case study at genesis healthcare system, part 2.
In the second of 2 parts, this article will focus on process improvement projects utilizing a case study at Genesis HealthCare System located in Zanesville, OH. Operational efficiency is a key step in developing a freestanding diagnostic imaging center. The process improvement projects began with an Expert Improvement Session (EIS) on the scheduling process. An EIS session is a facilitated meeting that can last anywhere from 3 hours to 2 days. Its intention is to take a group of people involved with the problem or operational process and work to understand current failures or breakdowns in the process. Recommendations are jointly developed to overcome any current deficiencies, and a work plan is structured to create ownership over the changes. A total of 11 EIS sessions occurred over the course of this project, covering 5 sections: Scheduling/telephone call process, Pre-registration, Verification/pre-certification, MRI throughput, CT throughput. Following is a single example of a project focused on the process improvement efforts. All of the process improvement projects utilized a quasi methodology of "DMAIC" (Define, Measure, Analyze, Improve, and Control).


Satellite DNA sequences in the human acrocentric chromosomes: information from translocations and heteromorphisms.
Satellite III DNA has been located by in situ hybridization in chromosomes 1, 3--5, 7, 9, 10, 13--18, 20--22, and Y and ribosomal DNA (rDNA) in the acrocentric chromosomes 13--15, 21, and 22. In the acrocentric chromosomes, the satellite DNA is located in the short arm. Here we report comparisons by in situ hybridization of the amount of satellite DNA in Robertsonian translocation and "normal variant" chromosomes with that in their homologs. In almost all dicentric Robertsonian translocations, the amount of satellite DNA is less than that in the normal homologs, but it is rarely completely absent, indicating that satellite DNA is located between the centromere and the nucleolus organizer region (NOR) and that the breakpoints are within the satellite DNA. The amount of satellite DNA shows a range of variation in "normal" chromosomes, and this is still more extreme in "normal variant" chromosomes, those with large short arm (p+ or ph+) generally having more satellite DNA than those with small short arms (p- or ph-). The cytological satellites are heterogeneous in DNA content; some contain satellite DNA, others apparently do not, and the satellite DNA content is not related to the size or intensity of fluorescence of the satellites. The significance of these variations for the putative functions of satellite DNA is discussed.


Studies on the synthesis of sterol carrier protein-2 in rat adrenocortical cells in monolayer culture. Regulation by ACTH and dibutyryl cyclic 3',5'-AMP.
The effects of ACTH or dibutyryl cyclic AMP (Bt2cAMP) on the synthesis of sterol carrier protein-2 (SCP2) have been studied in rat adrenocortical cells in monolayer culture. Radiolabeling of total cellular proteins with [35S]methionine and immunoprecipitation with antibodies directed against rat liver SCP2, followed by polyacrylamide gel electrophoresis and fluorography, showed a 3-4-fold increase in the rate of synthesis of SCP2 in cells treated for 48 h with ACTH (1 microM) or Bt2cAMP (0.1 mM). The induction of SCP2 synthesis depended upon the concentrations of ACTH or Bt2cAMP with an ED50 of 8 and 100 nM, respectively, and increased linearly with time between 12 and 48 h of treatment. Immunoprecipitation of SCP2 synthesized in a rabbit reticulocyte in vitro translation system programmed with RNA isolated from cells treated with ACTH or Bt2cAMP revealed increased synthesis of SCP2 compared to RNA from control cells. The immunoprecipitable rat adrenal SCP2, synthesized in a cell-free translation system, showed mobility corresponding to Mr of 14,400 upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was clearly larger than immunodetectable SCP2 synthesized in cultured adrenal cells (Mr = 11,300). The electrophoretic mobilities of rat liver SCP2 synthesized in cultured cells and in a cell-free translation system were the same as the respective forms from rat adrenal. It is concluded that the synthesis of SCP2 in rat adrenocortical cells is induced by ACTH and that the induction is mediated by cAMP and may involve increased levels of translatable mRNA encoding a higher molecular weight precursor form of SCP2, which presumably undergoes post-translational processing yielding the mature form.


Evolutionary Computing Enriched Computer-Aided Diagnosis System for Diabetic Retinopathy: A Survey.
Complications caused due to diabetes mellitus result in significant microvasculature that eventually causes diabetic retinopathy (DR) that keeps on increasing with time, and eventually causes complete vision loss. Identifying subtle variations in morphological changes in retinal blood vessels, optic disk, exudates, microaneurysms, hemorrhage, etc., is complicated and requires a robust computer-aided diagnosis (CAD) system so as to enable earlier and efficient DR diagnosis practices. In the majority of the existing CAD systems, functional enhancements have been realized time and again to ensure accurate and efficient diagnosis of DR. In this survey paper, a number of existing literature presenting DR CAD systems are discussed and analyzed. Both traditional and varoius evolutionary approaches, including genetic algorithm, particle swarm optimization, ant colony optimization, bee colony optimization, etc., based DR CAD have also been studied and their respective efficiencies have been discussed. Our survey revealed that evolutionary computing methods can play a vital role for optimizing DR-CAD functional components, such as proprocessing by enhancing filters coefficient, segmentation by enriching clustering, feature extraction, feature selection, and dimensional reduction, as well as classification.


[How I explore ... differential diagnosis of a red eye].
As a common reason for consultation, red eye can be a symptom of benign diseases, such as conjunctivitis, subconjunctival hemorrhage, dry eye syndrome,..., which can be managed by the general practitioner or internist. Conversely, more serious pathologies require a ophthalmologist management: these are keratitis, uveitis, acute glaucoma attack, or endophtalmitis. This article is intended to help practitioner to guide diagnosis when he's faced with a red eye.


Age and sex as moderators of the placebo response – an evaluation of systematic reviews and meta-analyses across medicine.
Predictors of the placebo response (PR) in randomized controlled trials (RCT) have been searched for ever since RCT have become the standard for testing novel therapies and age and gender are routinely documented data in all trials irrespective of the drug tested, its indication, and the primary and secondary end points chosen. To evaluate whether age and gender have been found to be reliable predictors of the PR across medical subspecialties, we extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine) known for high PR rates. The literature database used contains approximately 2,500 papers on various aspects of the genuine PR. These 'meta-analyses' were screened for statistical predictors of the PR across multiple RCT, including age and gender, but also other patient-based and design-based predictors of higher PR rates. Retrieved papers were sorted for areas and disease categories. Only 15 of the 75 analyses noted an effect of younger age to be associated with higher PR, and this was predominantly in psychiatric conditions but not in depression, and internal medicine but not in gastroenterology. Female gender was associated with higher PR in only 3 analyses. Among the patient-based predictors, the most frequently noted factor was lower symptom severity at baseline, and among the design- based factors, it was a randomization ratio that selected more patients to drugs than to placebo, more frequent study visits, and more recent trials that were associated with higher PR rates. While younger age may contribute to the PR in some conditions, sex does not. There is currently no evidence that the PR is different in the elderly. PR are, however, markedly influenced by the symptom severity at baseline, and by the likelihood of receiving active treatment in placebo- controlled trials.


Papillary thyroid carcinoma in Denmark, 1943--1968.
The material presented dates from a nationwide Cancer Registry, and covers all cases of papillary thyroid carcinoma (T.C.) diagnosed in Denmark from 1943 to 1968, including those based on postmortem examinations. Direct comparison with clinical data from hospitals elsewhere will therefore tend to show less favorable results. In general, Danish cases show a higher average age than those from American hospitals. For the younger age groups this may to some extent be explained by the fact that therapeutic x-irradiation of the thymus during childhood has never been practiced in Denmark. However, the later occurrence in life of Danish cases and the less favorable prognosis might suggest a failure to realize the malignant character of the lesion in the earlier part of its course, and a variable experience on the part of the surgeons and the variety of institutions from which the material was collected. The age-adjusted incidence rate, the mortality, and complications are discussed. It is concluded that the prognosis may be improved considerably by more extensive operations on the thyroid gland, avoiding complications such as paralysis of the recurrent laryngeal nerve and tetany. The surgical efforts should be supplemented with suppression of the TSH production. In the present retrospective study it was not possible to report 20- and 30-year survival rates. This is a task for the future, as is the planning of prospective studies which, in the case of a disease as rare as papillary T.C., should be established on an international basis.


Excited-state properties and transitions of fluorescent 8-vinyl adenosine in DNA.
8-vinyl-adenosine (8VA) is a new fluorescent nucleoside analogue with improved spectroscopic properties as compared to 2-aminopurine (2AP). To further understand its photophysics, we analyzed by the time-dependent density functional theory and the configuration interaction single method, the electronic properties, and transitions of 8VA in its free form and stacked with one or two flanking bases. For free 8VA, the predicted excited-state energy gaps, absorbance peak position, and oscillator strength were found to be in excellent agreement with the experimentally determined ones. Moreover, its high fluorescence quantum yield was found to be associated with the dipole-allowed S1 --> S0 transition. Stacking of 8VA with C, T, or A in dimers or trimers resulted in fluorescence quenching through mechanisms that depend on the nature and relative orientation of the flanking base(s). When 8VA is stacked with T, quenching mainly results from nonradiative relaxation to low-lying dark excited state(s) that do not exist in free 8VA. When 8VA is stacked with A, quenching results mainly from mixing of the molecular orbitals in the ground state. Both types of quenching are thought to accompany the stacking of 8VA with C. In addition, the C-8VA-C trimer was found to exhibit a low-lying S1 emissive state that may generate an increased fluorescence quantum yield and lifetime. The predicted photophysical properties of the trimers are highly consistent with the spectroscopic data of a series of 15-mer oligonucleotides differing only by the nature of the residues flanking the central 8VA.


[Suicide in Portugal].
Firstly suicide and parasuicide are defined and their respective characteristics are described. Some classifications of suicide and suicidal behaviors are analysed, mainly those which emphasize the clinical aspects. Certain models which undertake to explain the suicide are briefly reviewed, namely those which see the suicide as a deviant behaviour as well as those which see the suicide as a disease. Some epidemiologic features of suicide and parasuicide in Europe are reported, with special emphasis on Portugal. Suicidal risk factors, namely biomedical, psychological, social, cultural, environmental and symptomatic are analysed. The predictive evaluation of suicide is pointed out and some suicide prevention strategies are discussed. Finally the dependence of suicide on individual life cycles, on psychological, social and cultural conditions and on cultures and societies cycles is considered.


Removal of methyl violet from aqueous solution by perlite.
The use of perlite for the removal of methyl violet from aqueous solutions at different concentration, pH, and temperature has been investigated. Adsorption equilibrium is reached within 1 h. The capacity of perlite samples for the adsorption of methyl violet was found to increase with increasing pH and temperature and decrease with expansion and increasing acid-activation. The adsorption isotherms are described by means of the Langmuir and Freundlich isotherms. The adsorption isotherm was measured experimentally at different conditions and the experimental data were correlated reasonably well by the adsorption isotherm of Langmuir. The order of heat of adsorption corresponds to a physical reaction. It is concluded that the methyl violet is physically adsorbed onto the perlite. The removal efficiency (P) and dimensionless separation factor (R) have shown that perlite can be used for removal of methyl violet from aqueous solutions, but unexpanded perlite is more effective.


Enhancing mothers' interactions with toddlers who have sensory-processing disorders.
The objective of the current study was to examine the effects of a brief Mediational Intervention for Sensitizing Caregivers (the MISC-SP) designed to enhance the quality of mothers' interaction with their toddlers who have sensory processing disorders (SPD). The basic assumption was that quality parent-child interactions can serve as a protective factor moderating the potential negative effects of toddlers' sensory processing and regulation difficulties on their development. The effects of the intervention were compared to those of another intervention designed to enhance children's sensory functioning (the SI group) and to a control group receiving no intervention. Participants were 86 toddlers (12-18 months old) with SPD and their mothers, who were randomly assigned to the aforementioned three research groups. Following the intervention period, mothers in the MISC-SP group showed more sensitive behavior, supported their toddlers' communication behavior better, and used teaching behaviors more appropriately than did mothers in the two other groups.


Protein restriction during puberty alters nutritional parameters and affects ovarian and uterine histomorphometry in adulthood in rats.
In a large part of the population inefficient ingestion of proteins, whether for cultural, aesthetic or economic reasons, is a global concern. Low-protein diets can cause severe functional complications, mainly during the development and maturation of organs and systems, including the female reproductive system. The present study investigated the effect of nutritional protein restriction during puberty on the oestrous cycle and expression of sex steroid receptors (AR, ERα e ERβ) in ovarian and uterine tissues of adult rats. Protein restriction promoted lower body weight gain, feed efficiency and higher caloric intake. There was an increase in the oestrus phase arrest without changing the total length of the oestrous cycle. The consumption of low-protein diet also reduced the thickness of the uterine endometrium (uterine epithelium and endometrial stroma) in addition to increasing the number of primary and atretic follicles in the ovaries. Furthermore, the low-protein diet reduced the levels of androgen receptor (AR) and increased the oestrogen receptor β (ERβ) in the ovary, while no significant changes were observed in the uterus. Our study reinforces the importance of adequate protein intake during puberty, since physiological changes in this developmental period interfere with the histomorphometry of the ovaries and uteri, possibly resulting in impaired folliculogenesis and fertility in the reproductive period.


A Pan-Cancer Analysis on the Systematic Correlation of MutS Homolog 2 (MSH2) to a Malignant Tumor.
MutS homolog 2 (MSH2) is a crucial participant in human DNA repair, and lots of the studies functionally associated with it were begun with hereditary nonpolyposis colorectal cancer (HNPCC). MSH2 has also been reported to take part in the progresses of various tumors' formation. With the help of GTEx, CCLE, and TCGA pan-cancer databases, the analysis of MSH2 gene distribution in both tumor tissues and normal control tissues was carried out. Kaplan-Meyer survival plots and COX regression analysis were conducted for the assessment into the MSH2's impact on tumor patients' clinical prognosis. In an investigation to the association of MSH2 expression with immune infiltration level of various tumors and a similar study on tumor immune neoantigens, microsatellite instability was subsequently taken. It was found that high expression of MSH2 is prevalent in most cancers. MSH2's efficacy on clinical prognosis as well as immune infiltration in tumor patients revealed a fact that expression of MSH2 in prostate adenocarcinoma (PRAD), brain lower-grade glioma (LGG), breast-invasive carcinoma (BRCA), and head and neck squamous cell carcinoma (HNSC) posed a significant correlation with the immune cell infiltration level of patients. Likewise as above, MSH2's expression comes in a similar trend with tumor immune neoantigens and microsatellite instability. MSH2's expression in the majority of tumors is a direct factor to the activation of tumor-associated pathways as well as immune-associated pathways. MSH2's early screening or even therapeutic target role for sarcoma (SARC) diagnosis is contributing to the efficiency of early screening and overall survival in SARC patients.


Membrane contact probability: An essential and predictive character for the structural and functional studies of membrane proteins.
One of the unique traits of membrane proteins is that a significant fraction of their hydrophobic amino acids is exposed to the hydrophobic core of lipid bilayers rather than being embedded in the protein interior, which is often not explicitly considered in the protein structure and function predictions. Here, we propose a characteristic and predictive quantity, the membrane contact probability (MCP), to describe the likelihood of the amino acids of a given sequence being in direct contact with the acyl chains of lipid molecules. We show that MCP is complementary to solvent accessibility in characterizing the outer surface of membrane proteins, and it can be predicted for any given sequence with a machine learning-based method by utilizing a training dataset extracted from MemProtMD, a database generated from molecular dynamics simulations for the membrane proteins with a known structure. As the first of many potential applications, we demonstrate that MCP can be used to systematically improve the prediction precision of the protein contact maps and structures.


The effects of age-related macular degeneration on work productivity: A meta-analysis.
Age-related macular degeneration (AMD) is one of the leading causes of vision loss and blindness in older adults. Given the aging population in developed countries and the increased participation of older adults in the labour market, this paper aims to understand the impact of AMD on workplace productivity. Economic studies, comparative studies, observational studies, cohort studies, case series, randomized control trials, clinical trials, multicenter studies from MEDLINE, EMBASE, and CINHAL, as well as grey literature, were systematically searched to obtain all relevant literature. Duplicate records were removed, and two independent reviewers screened records for relevance. After screening, a risk of bias assessment was carried out. Data were extracted and a meta-analysis was performed using STATA 15.0. Fixed-effect and random-effect models were computed based on heterogeneity. Seven studies consisting of 3,060,864 subjects from 5 different countries were included in this systematic review. Mean wages lost due to impaired work productivity ranged from $1,395 to $55,180. The mean unemployment rate attributed to AMD ranged from 5.50% to 77.00%. Meta-analysis results indicated a significant unemployment rate (SMD = 0.44, CI: [0.27, 0.62]). Patients with AMD experience impaired work productivity as demonstrated by the wages lost and significantly higher rates of unemployment.


An Exploration of the Effect of Hemodynamic Changes Due to Normal Aging on the fNIRS Response to Semantic Processing of Words.
Like other neuroimaging techniques assessing cerebral blood oxygenation, near-infrared spectroscopy (NIRS) has been applied in many neurocognitive studies. With NIRS, neural activation can be explored indirectly via hemodynamic changes in the imaged region. In studies of aging, changes in baseline physiology and brain anatomy confound NIRS measures seeking to investigate age-related changes in neuronal activity. The field is thus hampered by the complexity of the aging process itself, and statistical inferences from functional data acquired by optical imaging techniques must be interpreted with care. Multimodal integration of NIRS with both structural and baseline physiological assessments is crucial to avoid misinterpreting neuroimaging signals. In this study, a combination of two different optical techniques, anatomical MRI and Arterial Spin Labeling (ASL), was used to investigate age-related changes in activation during a lexical-semantic processing task. Quantitative analysis revealed decreased baseline oxyhemoglobin and cerebral blood flow in the older adults. Using baseline physiology measures as regressors in the investigation of functional concentration changes when doing analyses of variance, we found significant changes in task-induced areas of activity. In the right hemisphere, more significant age-related activity was observed around the junction of the inferior frontal gyrus and inferior precentral sulcus, along with engagement of Wernicke's area. In the left hemisphere, the degree and extent of frontal activation, including the dorsolateral prefrontal cortex and inferior frontal gyrus, differed between age groups. Measuring background physiological differences and using their values as regressors in statistical analyses allowed a more appropriate, age-corrected understanding of the functional differentiations between age groups. Age-corrected baselines are thus essential to investigate which components of the NIRS signal are altered by aging.


Hormonal control of collagen metabolism. Part II.
Natural and synthetic glucocorticoids are known to effect collagen metabolism. This influence is responsible for several side-effects of a long term therapy with glucocorticoids. Molecular mechanisms of these phenomena are complex, and are only partially elucidated. It has been found that glucocorticoids decrease amount of mRNA coding procollagen chains. Posttranslational modifications including hydroxylation of proline and lysine residues and glycosylation of hydroxylysine residues in procollagen are depressed by glucocorticoids. This is caused by depressed activity of the specific enzymes of intracellular stages of collagen biosynthesis. Extracellular maturation of collagen is affected by steroids but changes reported depend upon rate of the collagen turnover. The effect of glucocorticoids on collagen degradation is a subject of controversy; there are a few data that the hormones decrease activity of collagenolytic enzymes. Possible indirect mechanisms of effect of glucocorticoids on the collagen metabolism include modulatory role of these hormones in inflammatory cell activity as well as a release of various humor mediators. Pathophysiological aspect of hormonal regulation of collagen metabolism by glucocorticoids in hepatic and pulmonary fibrosis as well as keloids are also reviewed.


Colonic lesion characterization in inflammatory bowel disease: A systematic review and meta-analysis.
To perform a systematic review and meta-analysis for the diagnostic accuracy of in vivo lesion characterization in colonic inflammatory bowel disease (IBD), using optical imaging techniques, including virtual chromoendoscopy (VCE), dye-based chromoendoscopy (DBC), magnification endoscopy and confocal laser endomicroscopy (CLE). We searched Medline, Embase and the Cochrane library. We performed a bivariate meta-analysis to calculate the pooled estimate sensitivities, specificities, positive and negative likelihood ratios (+LHR, -LHR), diagnostic odds ratios (DOR), and area under the SROC curve (AUSROC) for each technology group. A subgroup analysis was performed to investigate differences in real-time non-magnified Kudo pit patterns (with VCE and DBC) and real-time CLE. We included 22 studies [1491 patients; 4674 polyps, of which 539 (11.5%) were neoplastic]. Real-time CLE had a pooled sensitivity of 91% (95%CI: 66%-98%), specificity of 97% (95%CI: 94%-98%), and an AUSROC of 0.98 (95%CI: 0.97-0.99). Magnification endoscopy had a pooled sensitivity of 90% (95%CI: 77%-96%) and specificity of 87% (95%CI: 81%-91%). VCE had a pooled sensitivity of 86% (95%CI: 62%-95%) and specificity of 87% (95%CI: 72%-95%). DBC had a pooled sensitivity of 67% (95%CI: 44%-84%) and specificity of 86% (95%CI: 72%-94%). Real-time CLE is a highly accurate technology for differentiating neoplastic from non-neoplastic lesions in patients with colonic IBD. However, most CLE studies were performed by single expert users within tertiary centres, potentially confounding these results.


Reagent- and Metal-Free Anodic C-C Cross-Coupling of Aniline Derivatives.
The dehydrogenative cross-coupling of aniline derivatives to 2,2'-diaminobiaryls is reported. The oxidation is carried out electrochemically, which avoids the use of metals and reagents. A large variety of biphenyldiamines were thus prepared. The best results were obtained when glassy carbon was used as the anode material. The electrosynthetic reaction is easily performed in an undivided cell at slightly elevated temperature. In addition, common amine protecting groups based on carboxylic acids were employed that can be selectively removed under mild conditions after the cross-coupling, which provides quick and efficient access to important building blocks featuring free amine moieties.


Severe combined immunodeficiency: a case series from a paediatric hospital in Kenya.
Severe Combined Immunodeficiency (SCID) involves the lymphocyte lineage and mimics Human Immunodeficiency Virus (HIV) disease common in our region, making it difficult to diagnose and manage effectively. SCID in East Africa stands underdiagnosed because of lack of awareness and diagnostic resources. A case series of three SCID patients admitted to a Tertiary Paediatric Centre in Kenya between 2016 and 2019. The clinical presentations, laboratory findings, management and outcome for each were studied. Three cases were diagnosed between the ages of 4 to 15 months. Two of them were male and one was a female. All had a history of previous sibling death. There was no parental consanguinity. All presented with pneumonia. One of them had vaccine acquired Rotavirus infection and a persistent generalised maculopapular rash. The T, B cell profile was T- B- in two and T- B+ in one case and the immunoglobulins were reduced in all. All the cases were fatal. Thus, Primary immunodeficiency disorders are prevalent in East Africa. A proper clinical history, examination and laboratory tests like a haemogram, peripheral blood film can aid to suspect and diagnose SCID even with limited resources.


Protamine assembled in multilayers on colloidal particles can be exchanged and released.
Biocomposite thin films assembled on colloidal particles by means of layer-by-layer adsorption have been suggested as drug carriers and diagnostic devices. Protamine (PRM)/dextransulfate (DXS) and protamine/bovine serum albumine (BSA) multilayers were fabricated on colloidal silica and subsequently investigated by means of fluorescence activated cell sorting (FACS) and microelectrophoresis. Fluorescein labeled polyelectrolytes were embedded at different positions in the multilayers as a marker for layer growth. FACS showed that PRM and DXS formed regular growing stable multilayers, yet adsorbed PRM can be nevertheless exchanged with PRM in solution during layer formation and also after the multilayer formation has been completed. Up to 90% of the PRM pool was available for exchange. PRM together with BSA as demonstrated by SFM did not form multilayers under the applied conditions although the zeta-potential, commonly used as an indicator for stepwise adsorption, observed characteristic alternations. The capability of bound PRM to exchange with PRM in solution is attributed to its relatively small size. The demonstrated exchange may have importance in designing multilayers with smart release features. Furthermore, FACS proved to be a rather suitable means to quantify the aggregation behavior during coating and washing. Singulets, doublets, triplets, and aggregates of higher order could be clearly resolved. The aggregation of particles coated with PRM/DXS layers was higher than that of silica particles coated with PAH/PSS layers. In the first case about 50% of all recorded events are attributed to aggregats, while the PAH/PSS coating produced only about 10% aggregates.


Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran.
Beta-thalassaemia is a congenital haemolytic anaemia characterized by partial (intermedia, TI) or complete (major, TM) deficiency in the production of beta-globin chains. The primary aim of this study was to determine the prevalence of thromboembolic events in patients with beta-thalassaemia. To achieve this, a multiple choice questionnaire was sent to 56 tertiary referral centres in eight countries (Lebanon, Italy, Israel, Greece, Egypt, Jordan, Saudi Arabia and Iran), requesting specific information on patients who had experienced a thromboembolic event. The study demonstrated that thromboembolic events occurred in a clinically relevant proportion (1.65%) of 8,860 thalassaemia patients (TI - 24.7% or TM - 75.3%) from the Mediterranean and Iran. Thromboembolism occurred 4.38 times more frequently in TI than TM (p < 0.001), with more venous events occurring in TI and more arterial events occurring in TM. Thrombosis in thalassaemia was also more common in females, splenectomized patients and those with profound anaemia (haemoglobin <9 g/dl). Due to the increased risk of thromboembolic events, the rationale for splenectomy should perhaps be re-assessed and the role of transfusion therapy for the prophylaxis of thrombosis, among other complications, be evaluated prospectively.


Plasma YKL-40 levels correlate with the severity of coronary atherosclerosis assessed with the SYNTAX score.
Introduction YKL‑40 is a protein released locally by inflammatory cells. Thus, it may constitute a biomarker of inflammatory conditions, such as atherosclerosis. Objectives The aim of the study was to determine YKL‑40 levels in patients with ischemic heart disease and to analyze the correlation of this biomarker with the severity of coronary atherosclerosis. Patients and methods The study included 158 patients: 52 with stable ischemic heart disease and 67 with acute coronary syndrome: ST‑segment elevation myocardial infarction (STEMI; n = 47) or non-ST‑segment elevation myocardial infarction (NSTEMI; n = 20). The control group included 39 individuals without abnormalities in coronary vessels. We evaluated plasma YKL‑40 levels and their correlation with the severity of coronary atherosclerosis assessed with the SYNTAX score. Results Patients with myocardial infarction had higher plasma YKL‑40 levels than those with stable ischemic disease (median [range], 235.3 [161.6-366.1] ng/ml vs 61.2 [53.1-83.1] ng/ml; P <0.001) or controls (median [range], 235.3 [161.6-366.1] ng/ml vs 55.7 [51.2-75.2] ng/ml; P <0.001). No differences were found in YKL‑40 concentrations between STEMI and NSTEMI patients (median [range], 263 [150.3-363.7] ng/ml and 214.9 [163.4-367.6] ng/ml, respectively; P = 0.7). The SYNTAX score in patients with ischemic heart disease correlated positively with YKL‑40 concentrations (R = 0.34; P <0.001). Conclusions YKL‑40 can be considered a potential biomarker of coronary atherosclerosis severity.


First Report of Cucurbit Chlorotic Yellows Virus affecting Watermelon in USA.
Watermelon (Citrullus lanatus) is a high nutrient crop, high in vitamins and very popular in the U.S and globally. The crop was harvested from 101,800 acres with a value of $560 million in the U.S (USDA-NASS, 2020). California, Florida, Georgia and Texas are the four-leading watermelon-producing states in the U.S. During the fall season of 2020, plants in two North Florida watermelon fields, one in Levy County (~20 acres) and one in Suwannee County (~80 acres) with varieties Talca and Troubadour, respectively, exhibited viral-like symptoms. The fields had 100% disease incidence that led to fruit quality issues and yield losses of 80% and above. Symptoms observed in the watermelon samples included leaf crumpling, yellowing and curling, and vein yellowing similar to that of single/and or mixed infection of cucurbit leaf crumple virus (CuLCrV; genus: Begomovirus, family: Geminiviridae), cucurbit yellow stunting disorder virus (CYSDV; genus: Crinivirus, family: Closteroviridae) and squash vein yellowing virus (SqVYV; genus: Ipomovirus, family: Potyviridae), although the vine decline symptoms often associated with SqVYV infection of watermelon were not observed. All three viruses are vectored by whiteflies and previously described in Florida (Akad et al., 2008; Polston et al., 2008; Adkins et al., 2009). To confirm the presence of these viruses, RNA was isolated from 20 symptomatic samples using the RNeasy Plant Mini Kit (Qiagen, USA) as per protocol. This was followed by RT-PCR (NEB, USA) using gene-specific primers described for CuLCrV, CYSDV and SqVYV (Adkins et al., 2009). Amplicons of expected sizes were obtained for all the viruses with the infection of CuLCrV in 17/20, CYSDV in 16/20, and SqVYV in 8/20 samples. In addition, the presence of cucurbit chlorotic yellows virus (CCYV; genus: Crinivirus, family: Closteroviridae) in mixed infection was confirmed in 4/20 samples (3 leaves and 1 fruit) by RT-PCR with primers specific to the CCYV coat protein (CP), heat shock protein 70 homolog (HSP70h) and RNA dependent RNA polymerase (RdRp) designed based on the available CCYV sequences (Sup Table. 1). The RT-PCR amplification was performed using a symptomatic watermelon sample and the amplicons of RdRp, HSP70h and CP were directly sequenced by Sanger method, and the sequences of the amplicons were deposited in GenBank under the accession number: MW527462 (RdRp, 952 bp), MW527461 (HSP70h, 583 bp) and MW527460 (CP, 852 bp). BLASTn analysis demonstrated that the sequences exhibited an identity of 99% to 100% (RdRp and HSP70h, 100%; and CP, 99%) with the corresponding regions of the CCYV isolate Shanghai from China (accession number: KY400636 and KY400633). The presence of CCYV was further confirmed in the watermelon samples by ELISA (Loewe, Germany) using crude sap extracted from the RT-PCR-positive, symptomatic watermelon samples. CCYV was first identified in Kumamoto, Japan in 2004 on melon plants (Gyoutoku et al. 2009). The CCYV was previously reported on melon from Imperial Valley, California (Wintermantel et al., 2019), and more recently on squash in Tifton, Georgia (Kavalappara et al., 2021) and cantaloupe in Cameron, Texas (Hernandez et al., 2021). To our knowledge, this is the first report of CCYV on field watermelon production in the U.S. Continued monitoring of the CCYV in spring and fall watermelon crop, and cucurbit volunteers and weeds will be critical toward understanding the spread of this virus and its potential risk to watermelon in Florida and other regions of the U.S.


The Natural History of Sport-Related Concussion in Collegiate Athletes: Findings from the NCAA-DoD CARE Consortium.
Sport-related concussion is recognized as a significant injury with variable recovery rates. This study defined the acute natural history of sport concussion in male and female collegiate athletes participating in a broad array of sports. We conducted a prospective, longitudinal investigation among collegiate student athletes (n = 34,709) from 30 academic institutions. Primary outcomes included the time (days) from injury until initiation of a return to participation (RTP) protocol and time from injury until medical clearance for unrestricted RTP. Concussed athletes (n = 1751, 19.2 years, 63.2% male) participating in 22 different sports began the RTP protocol in a median 6.4 (IQR 3.7-11.8) days. Time to initiate the RTP protocol was lengthened by less frequent post-injury assessments, greater initial post-injury symptom severity, limited contact sports participation, practice/training injuries, and three or more prior concussions. The median total RTP duration was 12.8 (IQR 8.7-20.1) days. Total RTP duration was shorter with ADHD medication usage, males, and greater assessment frequency; while greater initial post-injury symptom severity, practice-/training-related injuries, and three or more prior concussions had longer recoveries. Although median recovery times are consistent with previous guidelines, it was not until 1 month post-injury that a preponderance of collegiate athletes were cleared to begin the RTP protocol (92%) or cleared for unrestricted sport participation (85%). Intrinsic and extrinsic factors had a small effect, altering recovery trajectories by up to 2 days, suggesting a largely unified approach to post-injury monitoring and management across all athletes. These data represent a shift from previous classification parameters of normal clinical recovery.


Cerebral Perfusion Imaging for Intravenous Thrombolysis Treatment.
Intravenous thrombolysis is the cornerstone of acute ischemic stroke treatment. However, the benefits of recanalization and reperfusion must be balanced against the risk of intracranial hemorrhage. Time from symptom onset was previously the most important selection tool for identifying patients who would benefit from treatment without prohibitive risk for secondary hemorrhage. Enhanced techniques in noncontrast computed tomography followed by computed tomography and magnetic resonance perfusion imaging led to the expansion of treatment eligibility for intravenous thrombolysis. Perfusion imaging allows for more precise evaluation of tissue at-risk to identify patients who would benefit from treatment many hours beyond symptom onset.


The mettle of moral fundamentalism: a reply to Robert Baker.
This article is a reply to Robert Baker's attempt to rebut moral fundamentalism, while grounding international bioethics in a form of contractarianism. Baker is mistaken in several of his interpretations of the alleged moral fundamentalism and findings of the Advisory Committee on Human Radiation Experiments. He also misunderstands moral fundamentalism generally and wrongly categorizes it as morally bankrupt. His negotiated contract model is, in the final analysis, itself a form of the moral fundamentalism he declares bankrupt.


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After 1933 many scientists and university teachers were obliged to relinquish their posts in the universities of Germany because of national-socialist laws. Organizations-in-aid like the Academic Assistance Council in Great Britain tried to 'defend science and learning' raising funds and finding new openings for the expelled academics. But as immigration laws were tight and jobs were scarce in the host countries the AAC and the other organizations had to select the most qualified from among the applicants for support. -- The questions the article tries to answer are: What kind of criteria were applied in this selection? Who were the experts? How were the placements made? How did the applicants react to the decisions? Taking for example the AAC, it examines measures to assist a group of scientists who, having tried to settle down in England, finally emigrated to Turkey.


Yoga of Immortals Intervention Reduces Symptoms of Depression, Insomnia and Anxiety.
Background: Depression, anxiety, and disordered sleep are some common symptoms associated with sub-optimal mental health. During the COVID-19 pandemic, mental health issues have grown increasingly more prevalent in the population. Due to social distancing and other limitations during the pandemic, there is a need for home-based, flexible interventions that can improve mental health. The Yoga of Immortals (YOI) mobile application provides a structured intervention that can be used on any mobile device and applied from the user's home. Methods: A total of 1,505 participants were enrolled in the study and used the YOI app for an 8-week period. Participants were asked to fill out three questionnaires: The Patient Health Questionnaire, 8 items (PHQ-8), the Generalized Anxiety Disorder questionnaire (GAD-7) and the Insomnia Severity Index (ISI). These three items were completed by 1,297 participants a total of four times: before starting YOI, two more times during use, and a fourth time after the 8-week usage period. Changes in PHQ8, GAD7 and ISI in participants were compared to a control group, who did not use the YOI app but completed all questionnaires (590 controls finished all questionnaires). Results: Participants reported significant decreases in depression and anxiety-related symptoms. Compared to baseline, PHQ-8 scores decreased 50% on average after the 8-week period. GAD-7 scores also decreased by 40-50% on average, and ISI scores decreased by 50%. These changes were significantly greater (p < 0.05) than that observed in the control group. Participants who reported a previous diagnosis of depression and generalized anxiety reported significantly larger decreases in PHQ-8 and GAD-7 as compared to participants with no prior diagnosis (p < 0.05). Conclusions: Regular use of the YOI intervention over an 8-week period led to significant decreases in symptoms of both depression and anxiety, as well as alleviation of insomnia.


Toxoplasma gondii in domestic and wild animals from forest fragments of the municipality of Natal, northeastern Brazil.
Toxoplasmosis stands out as a global disease that has felines as definitive hosts. In the municipality of Natal, Rio Grande do Norte State, Brazil, two parks are notable for their ecological and social importance. This study aimed to investigate the presence of Toxoplasma gondii in short hair cats, bats and small non-volant mammals in these two ecological reserves. Altogether, biological samples were obtained from 154 mammals, 92 wild animals from both areas and 62 domestic cats of the Parque da Cidade. In total, 22 (53.7%) non-volant wild mammals, 11 (21.5%) bats and 28 (52.8%) cats were positive for IgG anti-T. gondii antibodies using the Modified Agglutination Test (≥ 25). It was possible to detect the presence of T. gondii DNA, by means of a molecular amplification of a B1 gene fragment (155bp), in 92 tissue samples from wild animals, including Didelphis albiventris, Monodelphis domestica, Artibeus lituratus, Carollia perspicillata and Glossophaga soricina. Of the 62 cats examined by the same molecular method, T. gondii DNA could be detected in 4 cats. In this study, it was observed the circulation of T. gondii in wild species and domestic cats, demonstrating the involvement of wild and domestic animals in the cycle of T. gondii.


Longitudinal mental health service and medication use for ADHD among Puerto Rican youth in two contexts.
The study describes prevalence and rates of services and medication use and associated factors over time among Puerto Rican youths with attention-deficit/hyperactivity disorder (ADHD). Longitudinal data are obtained on Puerto Rican children ages 5 through 13 years in the south Bronx in New York (n = 1,138) and two metropolitan areas in Puerto Rico (n = 1,353). The Diagnostic Interview Schedule for Children-IV is the diagnostic tool. Five composite measures of risk factors: negative family influences, ineffective structuring, environmental risks, child risks, and maternal acceptance are constructed to relate services and medication use to risk variables. ADHD prevalence is similar in Puerto Rico and the south Bronx. Overall mental health services, medication, and psychostimulant use is lower in Puerto Rico across three time points. Most participants never received treatment at any time point. More environmental risks, negative child traits, and low maternal warmth are associated with more services, even after adjusting for comorbidity. When risk variables are controlled, the effects of ADHD on services use decrease. Previous treatment is a strong predictor of subsequent treatment. Rates of services and medication use are lower in Puerto Rico. Context seems to be more important than ethnicity in predicting mental health services and medication use among Puerto Rican children with ADHD. Other psychiatric diagnoses and general risk variables are important correlates of services and medication use.


β -[18F]Fluoro Azomycin Arabinoside (β -[18F]FAZA): Synthesis, Radiofluorination and Preliminary PET Imaging of Murine A431 Tumors.
1-α-D-(5-Deoxy-5-[18F]fluoroarabinofuranosyl)-2-nitroimidazole([18F] FAZA) is a PET radiotracer that demonstrates excellent potential in imaging regional hypoxia, and is clinically used in diagnosing a wide range of solid tumors in cancer patients. [18F]FAZA, however, is radiofluorinated in only moderate recovered radiochemical yield (rRCY, ~12%). It is postulated that the relative stability of the C1' β-anomeric bond at C5' will make 1-β-D-(5-fluoro-5-deoxyarabinofuranosyl)-2-nitroimidazole (β-FAZA), the β-conformer of FAZA, an attractive candidate for clinical hypoxia imaging. The principle goals were to synthesize β-FAZA and β-Ac2TsAZA, the radiofluorination precursor, to establish the radiofluorination chemistry leading to β-[18F]FAZA, and to investigate the biodistribution of β-[18F]FAZA in an animal tumor-bearing model using PET imaging. The appropriately-protected furanose sugar was coupled with 2-nitroimidazole to afford 1-β-D-(2,3-di-O-acetylarabinofuranosyl)-2-nitroimidazole (β-Ac2AZA). Fluorination of β-Ac2AZA with DAST, followed by alkaline hydrolysis, afforded β-FAZA (21%). The radiolabeling synthon, 1-β-D-(5-O-toluenesulfonyl-2,3-di-O-acetylarabinofuranosyl)-2-nitroimidazole (β-Ac2TsAZA), on radiofluorination using the 18F/K222 complex under various reaction conditions, followed by base-catalyzed deacetylation, afforded β-[18F]FAZA. β-[18F]FAZA was radiochemically stable for at least 8 h when stored in aqueous ethanol (8%) at 22 °C. A preliminary PET imaging-based biodistribution study of β-[18F]FAZA was performed in A431 tumor-bearing nude mice. β-FAZA and β-Ac2TsAZA were synthesized in satisfactory yield. Radiochemistry of [18F]FAZA was established. PET images showed strong uptake in hypoxic regions of the tumor. The synthesis of β-FAZA and β-[18F]FAZA are reported. Radiofluorination of β-Ac2TsAZA and the deprotection of β-Ac2[18F]FAZA were facile, but led to a more complex mixture of radiofluorinated by-products than observed with the corresponding precursor of α-[18F]FAZA. PET images were indicative of hypoxia-selective accumulation of β-[18F]FAZA in tumor.


Generalization of word retrieval following semantic feature treatment.
The effectiveness of a Semantic Feature Treatment (SFT) at increasing word retrieval accuracy of untreated words was examined in relation to the influence of the number of shared features with treated words. Generalization of these improvements to discourse was also examined. Three adults with chronic aphasia completed 12 SFT sessions. Generalization to untreated words with many shared features (SFs) and with no shared features (NSFs), as well as generalization to discourse tasks, was analyzed. All participants improved in word retrieval accuracy for treated words. Accuracy of retrieving untreated words improved for two participants. Retrieval accuracy for untreated words with SF improved more than for words with NSF. Generalization of improvements to discourse tasks occurred for two participants. SFT improves word retrieval accuracy for some people with aphasia during confrontation naming and discourse tasks. Generalization may be slightly higher for untreated words with SFs than untreated words with NSFs. Future research is needed to further investigate the effect shared features have on generalization of improvements, and to determine candidacy for SFT.