Who were old in the Middle Ages?
Contrary to the accepted view that people in the Middle Ages and the Renaissance were considered old from their forties, in fact they were classified as old between the ages of 60 and 70. In schemes for the division of the life-course into stages old-age begins over a wide range of ages. In some of these schemes it begins indeed, at 40; but in others its onset is at 35, 45, 50, 60, or 72. Several medieval scholars and artists declared at the age of 40 that they were already old; claims are made by such persons even in the nineteenth and twentieth centuries. Yet the same medieval writers in writings written for other purposes, and in other moods would not always present themselves as old though they were older than 40. In all the legislative texts which granted age-linked exemptions from military service, trial by battle, service on the town watches, and various other public duties such as payment of taxes or obligatory work, these were granted to those of 60 or 70 years of age. In various other texts as well, 60 and not 40 is the indicator of old age. Yet this cultural attitude had only limited impact on social reality. In the absence of retirement pensions, what mattered in most people's lives was their functional capacity, rather than strict chronological age.


EhVps23, an ESCRT-I Member, Is a Key Factor in Secretion, Motility, Phagocytosis and Tissue Invasion by Entamoeba histolytica.
The EhVps23 protein, an orthologue of the yeast Vps23 and the mammalian TSG101 proteins, is the single member of the ESCRT-I complex of Entamoeba histolytica identified and characterized until now. EhVps23 actively participates in vesicular trafficking and phagocytosis, which influence several cellular events. In this paper, we investigated the role of EhVps23 in virulence-related functions, including the invasive capacity of trophozoites, using transfected trophozoites. Trophozoites overexpressing the EhVps23 protein (Neo-EhVps23) presented helical arrangements in the cytoplasm, similar to the ones formed by EhVps32 for scission of vesicles. By confocal and transmission electron microscopy, EhVps23 was detected in multivesicular bodies, vesicles, and the extracellular space. It was secreted in vesicles together with other proteins, including the EhADH adhesin. Probably, these vesicles carry molecules that participate in the prey capture or in cell-cell communication. Mass spectrometry of precipitates obtained using α-EhVps23 antibodies, evidenced the presence of proteins involved in motility, phagocytosis, vesicular trafficking and secretion. The study of cellular functions, revealed that Neo-EhVps23 trophozoites exhibit characteristics similar to those described for mammalian transformed cells: they grew 50% faster than the control; presented a significant higher rate of phagocytosis, and migrated five-fold faster than the control, in concordance with the low rate of migration exhibited by Ehvps23-knocked down trophozoites. In addition, Neo-EhVps23 trophozoites produced dramatic liver abscesses in experimental animals. In conclusion, our results showed that EhVps23 overexpression gave to the trophozoites characteristics that resemble cancer cells, such as increased cell proliferation, migration, and invasion. The mutant that overexpresses EhVps23 can be a good study model to explore different events related to the transformation of malignant cells.


[Hemicrania comitata. Critical review and clinical case reports].
The AA. examined 24 subjects suffering from classic or common migraine and 42 subjects with complicated migraine. In 6 cases of complicated migraine, radiologic investigations (cerebral CT scan or scintigraphy) showed ischemic lesions. The AA. discuss their results, on the basis of the most recent acquisitions concerning the pathogenetic mechanisms involved in the complicated migraine; particularly, they dwell upon "the platelet hypothesis".


Arc/Arg3.1 protein expression in dorsal hippocampal CA1, a candidate event as a biomarker for the effects of exercise on chronic stress-evoked behavioral abnormalities.
Chronic stress is a risk factor for behavioral deficits, including impaired memory processing and depression. Exercise is well known to have beneficial impacts on brain health. Mice were forced to treadmill running (4-week) during chronic restraint stress (6h/21d), and then behavioral tests were conducted by Novel object recognition, forced swimming test: FST, sociality test: SI. Dissected brain was stained with anti-calbindin-d28k and anti-Arc antibodies. Also, mice were treated with CX546 intraperitoneally during chronic restraint stress, and behavioral tests were assessed using Morris water maze, FST, and SI. Dissected brain was stained with anti-Arc antibody. The current study demonstrated that chronic stress-induced impairment of memory consolidation and depression-like behaviors, along with the changes in calbindin-d28k and Arc protein levels in the hippocampal CA1 area, were attenuated by regular treadmill running. Further, prolonged ampakine treatment prevented chronic stress-evoked behavioral abnormalities and nuclear Arc levels in hippocampal CA1 neurons. Nuclear localization of Arc protein in hippocampal CA1 neurons, but not total levels, was correlated with behavioral outcome in chronically stressed mice in response to a regular exercise regimen. These results suggest that nuclear levels of Arc are strongly associated with behavioral changes, and highlight the role of exercise acting through an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR)-mediated mechanisms in a chronic stress-induced maladaptive condition.


A case of acute myocardial infarction due to coronary spasm in the myocardial bridge.
A 68-year-old Japanese man with acute inferior myocardial infarction underwent emergent coronary angiography which showed a myocardial bridge, but no coronary stenosis, at the infarctrelated artery. A spasm provocation test using intracoronary acetylcholine revealed a total occlusion due to severe spasm at the site of the myocardial bridge. Thus, the myocardial ischemia in this case was caused by the coronary spasm, but not by the limited flow due to the myocardial bridge. Although a beta-blocker is usually the appropriate drug, it should be avoided for coronary spasm. The spasm provocation test is useful to determine the type of medication needed for treatment.


Factors Associated With HIV-Related Stigma Among Indonesian Healthcare Workers: A Cross-Sectional Online Survey.
Despite worldwide advances in HIV care and growing scientific knowledge about HIV, stigma and prejudice continue to hinder people living with HIV/AIDS (PLWHA) from seeking treatment and care. HIV-related stigma among healthcare workers in Indonesia has been investigated and measured in only a few empirical studies. This study was developed to identify factors related to holding stigmatizing attitudes toward PLWHA among professional healthcare providers in Indonesia. A cross-sectional survey approach using convenience and snowball sampling techniques was used. Data were collected in February and March 2022. All of the participants were healthcare workers in Indonesia who had completed an online survey that collected demographic data and measured HIV-related stigma, fear of HIV transmission, and HIV-related knowledge. Bivariate analysis and multiple linear regression were used to investigate the association between the independent and dependent variables. The study enrolled 252 participants, including eight physicians (3.2%), 200 nurses (79.4%), and 44 midwives (17.5%). Over two thirds of the participants (65.1%) had no formal HIV training. Stigmatizing attitudes were associated with lower levels of HIV knowledge ( B = -0.480, p < .01), fear of becoming infected with the HIV virus ( B = 0.354, p < .05), and type of HIV care setting ( B = -2.913, p < .05). Of the three participant categories, physicians had the highest levels of both HIV knowledge and PLWHA-related stigma. The findings indicate many healthcare workers in Indonesia receive limited formal training on HIV, have low levels of HIV knowledge, and fear HIV transmission. Therefore, providing comprehensive and up-to-date education about HIV for health workers and proper personal protective equipment should be incorporated into programs aimed at reducing stigmatizing attitudes against patients with HIV among healthcare workers in Indonesia.


Color variation assay of the anthocyanins from Açai Fruit (Euterpe oleracea): a potential new dye for vitreoretinal surgery.
The goals of this study were to determine the potential for use of the natural anthocyanins from the açai fruit (Euterpe oleracea) during vitreoretinal surgery and the ideal physicochemical properties of the dye. We evaluated the color variations of the dye at different pHs and osmolarities with or without the use of mordants as a potential new tool for internal limiting membrane peeling. The extracts of anthocyanin from the açai fruit were analyzed by spectrophotometry to determine the degree of color variations associated with various pHs and osmolarities. The experiments were conducted in test tubes filled with tryptophan soya media and Petri dishes prepared with agar media. We observed various shades of green, red, and purple in the extracts of the anthocyanin dye at different pHs and osmolarities. The assay to adjust the anthocyanin solution similar to the physiologic retinal environment (osmolarity, 300 mOsm; pH, 7.00) resulted in a shade of purple that may be useful to stain the intraocular microstructures during vitreoretinal surgery. The physicochemical property of the purple anthocyanin solutions from the açai fruit was observed at physiologic pH and osmolarity. Anthocyanins from the açai fruit may be useful to enhance visualization of the intraocular microstructures during vitreoretinal surgery.


Y-stent-assisted coil embolization of anterior circulation aneurysms using two Solitaire AB devices: a single center experience.
Wide-neck intracranial aneurysms remain a challenge to endovascular treatment. We describe our experience in repairing wide-neck aneurysms of the anterior circulation located at arterial branch points using coil embolization assisted by Y-stenting using two Solitaire(®) stents.Six wide-neck intracranial aneurysms located on the middle cerebral artery bifurcation( 3), pericallosal artery( 1), and anterior communicating artery( 2) were repaired by Y-stent-assisted coil embolization using two Solitaire(®) stents. Four cases were incidental findings of aneurysm and two cases were previously treated ruptured aneurysms that had undergone recanalization. All the cases were successfully treated without complications. Follow-up by digital subtraction angiography and magnetic resonance angiography at six months showed the stents to be patent with no recanalization of the aneurysm sacs. Repairing wide-neck aneurysms of the anterior circulation by Y-stent-assisted coil embolization using two Solitaire(®) stents is a simple and safe method of treating complex aneurysms. While the results are promising, larger series with longer term follow-ups are needed to corroborate that this treatment method is superior to other techniques.


Preparation and characterization of nanostructured Pt/TiO2 thin films treated using electron beam.
Pt nanoparticle-doped titanium dioxide (Pt/TiO2) thin films were prepared on a silicon wafer substrate by sol-gel spin coating process. The prepared thin films were treated with electron beam (EB at 1.1 MeV, 100, 200, 300 kGy) at air atmosphere. The effect of EB-irradiation on the composition of the treated thin films, optical properties and morphology of thin films were investigated by various analytical techniques such as X-ray photoelectron spectroscopy (XPS), spectroscopic ellipsometry (SE), X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The crystal structure of the TiO2 layer was found to be an anatase phase and the size of TiO2 particles was determined to be about 13 nm. Pt nanoparticles with diameter of 5 nm were observed on surface of the films. A new layer (presumed to be Pt-Ti complex and/or PtO2 compound) was created in the Pt/TiO2 thin film treated with EB (300 kGy). The transmittance of thin film decreased with EB treatment whereas the refractive index increased.


Development of Pseudomonas aeruginosa Lectin LecA Inhibitor by using Bivalent Galactosides Supported on Polyproline Peptide Scaffolds.
LecA is a galactose-binding tetrameric lectin from Pseudomonas aeruginosa involved in infection and biofilm formation. The emergent antibiotic resistance of P. aeruginosa has made LecA a promising pharmaceutical target to treat such infections. To develop LecA inhibitors, we exploit the unique helical structure of polyproline peptides to create a scaffold that controls the galactoside positions to fit their binding sites on LecA. With a modular scaffold design, both the galactoside ligands and the inter-ligand distance can be altered conveniently. We prepared scaffolds with spacings of 9, 18, 27, and 36 Å for ligand conjugation and found that glycopeptides with galactosides ligands three helical turns (27 Å) apart best fit LecA. In addition, we tested different galactose derivatives on the selected scaffold (27 Å) to improve the binding avidity to LecA. The results validate a new multivalent scaffold design and provide useful information for LecA inhibitor development.


Knockdown of IQGAP1 inhibits proliferation and epithelial-mesenchymal transition by Wnt/β-catenin pathway in thyroid cancer.
Thyroid cancer is the most common endocrine malignant disease with a high incidence rate. The expression of IQGAP1 is upregulated in various cancers, including thyroid cancer. However, the role and underlying mechanism of IQGAP1 in thyroid cancer are still not clear. The expression of IQGAP1 in thyroid cancer tissues and cells was determined by reverse transcription polymerase chain reaction and Western blot analysis. Cells were transfected with different siRNAs using Lipofectamine 2000 or were treated with various concentrations of XAV939. The effects of IQGAP1 knockdown on proliferation and epithelial-mesenchymal transition (EMT) of thyroid cancer cells were determined by MTT assay and Western blot analysis. Animal experiments were performed to investigate the effects of IQGAP1 knockdown on the growth of tumors in vivo. High IQGAP1 expression is found in thyroid cancer tissues and cells. Knockdown of IQGAP1 had inhibitory effects on cell proliferation and EMT, as well as on the Wnt/β-catenin pathway. Additionally, inactivation of the Wnt/β-catenin pathway by XAV939 or si-β-catenin suppressed cell proliferation and EMT. Furthermore, suppression of the Wnt/β-catenin pathway reversed the positive effects of pcDNA-IQGAP1 on cell proliferation and EMT in vitro. Moreover, downregulation of IQGAP1 suppressed tumor growth and EMT in SW579 tumor xenografts through the Wnt/β-catenin pathway in vivo. Our study demonstrated that knockdown of IQGAP1 inhibited cell proliferation and EMT through blocking the Wnt/β-catenin pathway in thyroid cancer.


[Characteristics of retinal detachment in eyes with choroidal colobomas].
We reviewed 6 eyes of 6 patients (1 male and 5 females) with retinal detachment associated with choroidal coloboma. Three of these 6 eyes had visible retinal breaks within or at the margin of the coloboma. In one eye, no retinal breaks were noted before or during vitreous surgery, and shallow retinal detachment was localized in the posterior fundus. One eye with bullous retinal detachment with retinal breaks within the coloboma had been having serous retinal detachment localized in the nasal area close to the optic nerve head. In all of these five eyes; vitrectomy, relaxing retinotomy inside the coloboma close to its edges, and cyanoacrylate retinopexy resulted in successful reattachment of the retina. Schisis-like separation similar to that in pit-macular syndrome was noted in the posterior retinal in one eye which had no visible retinal break. Non-rhegmatogenous retinal detachment may exist in association with choroidal colobomas.


Categorical perception of anger and disgust facial expression is affected by non-clinical social anxiety: an ERP study.
Anxiety has been associated with a bias for interpreting threatening information. Faces expressing anger seem to be more easily detected by socially anxious individuals than by non-anxious individuals. Similarly, disgust on a face may also reflect a negative social judgment. We tested the hypothesis that individuals displaying non-clinical social anxiety would be as sensitive to disgust as to anger interpretation by comparing individuals scoring high or low on the fear of social evaluation scale (FNE, Watson and Friend, 1969). Event-related potentials (ERP) were recorded in response to repetitions of a particular facial expression (e.g. anger) and in response to two deviating (rare) stimuli obtained by a morphing procedure, where one depicted the same emotion as the frequent stimulus, while the other depicted a different facial expression (e.g. disgust). The classic effect of categorical perception was reproduced: at a behavioral level, people detected more easily rare faces depicting a different emotion than faces depicting the same emotion. ERP results suggest that deviant faces depicting a different emotion evoked an earlier attentional N2b/P3a wave complex, together with an earlier and enhanced P3b. More interestingly, participants with non-clinical social anxiety manifested a reduced N2b wave when they had to detect a change in intensity of anger presentation. However, these individuals did not show facilitation to disengage from disgust when they have to detect angry faces, which was displayed by control participants. Implications and suggestions for further research about the role played by anger and disgust in psychopathology are outlined.


[Effects of nasogastric and percutaneous endoscopic gastrostomy tube feeding on the susceptibility of pulmonary infection in long-term coma patients with stroke or traumatic brain injury].
Objective: To investigate the effects of nasogastric tube (NGT) and percutaneous endoscopic gastrostomy (PEG) tube feeding on the susceptibility of pulmonary infection in long-term coma patients with stroke or traumatic brain injury. Methods: A total of 295 candidates who were in long-term coma after stroke or traumatic brain injury but without pulmonary infection and eligible for PEG catheterization were screened prospectively between January 2014 and February 2018. The patients were divided into PEG group (86 patients) and NGT group (209 patients) according to the choice of next-of-kin. Data related to the susceptibility of pulmonary infection were collected and analyzed in the two groups one month after the catheterization. Results: After follow-up for one month, compared with NGT group, patients in PEG group had a lower incidence of pulmonary infection (23.3% vs 37.8%, P=0.023), a later occurrence of pulmonary infection (average time: 21 days vs 13 days, P=0.034), and a less severe pulmonary infection (7.0% vs 12.9%, P=0.029). The following characteristics made patients more susceptible to pulmonary infection: age ≥ 70 years (HR=1.619, 95% CI 1.054-2.172), Charlson comorbidity index ≥ 2 points (HR=1.647, 95% CI 1.043-2.485), using of proton pump inhibitor ≥ 7 days (HR=1.725, 95% CI 1.214-2.738), and number of pressure ulcers ≥ 3 (HR=2.109, 95% CI 1.128-3.844). However, serum albumin concentration ≥35 g/L (HR=0.670, 95% CI 0.375-0.963) was a protective factor for pulmonary infections. The number of consistent pathogens cultivated from saliva, gastric juice and sputum simultaneously in NGT and PEG group was 35 strains (27.8%) and 8 strains (13.3%), respectively (P=0.029). The mortality of pulmonary infection was similar in the two groups (3.5% vs 4.3%, P=1.000), but the death due to pulmonary infection in the PEG group occur later (median time: 20 days vs 11 days, P=0.012). Conclusions: PEG feeding was a preferred nutrition way which could reduce the risk of pulmonary infection more effectively than NGT feeding which might favored a retrograde gastro-pulmonary route by which pathogens colonized in stomach migrated to respiratory tract. Patients with characteristics mentioned above had the susceptibility of pulmonary infection, thus risk assessment of pulmonary infection should be conducted before selecting the catheterization method.


Water in bacterial biofilms: pores and channels, storage and transport functions.
Bacterial biofilms occur in many natural and industrial environments. Besides bacteria, biofilms comprise over 70 wt% water. Water in biofilms occurs as bound- or free-water. Bound-water is adsorbed to bacterial surfaces or biofilm (matrix) structures and possesses different Infra-red and Nuclear-Magnetic-Resonance signatures than free-water. Bound-water is different from intra-cellularly confined-water or water confined within biofilm structures and bacteria are actively involved in building water-filled structures by bacterial swimmers, dispersion or lytic self-sacrifice. Water-filled structures can be transient due to blocking, resulting from bacterial growth, compression or additional matrix formation and are generally referred to as "channels and pores." Channels and pores can be distinguished based on mechanism of formation, function and dimension. Channels allow transport of nutrients, waste-products, signalling molecules and antibiotics through a biofilm provided the cargo does not adsorb to channel walls and channels have a large length/width ratio. Pores serve a storage function for nutrients and dilute waste-products or antimicrobials and thus should have a length/width ratio close to unity. The understanding provided here on the role of water in biofilms, can be employed to artificially engineer by-pass channels or additional pores in industrial and environmental biofilms to increase production yields or enhance antimicrobial penetration in infectious biofilms.


Conserved genetic determinant of motor organ identity in Medicago truncatula and related legumes.
Plants exhibit various kinds of movements that have fascinated scientists and the public for centuries. Physiological studies in plants with the so-called motor organ or pulvinus suggest that cells at opposite sides of the pulvinus mediate leaf or leaflet movements by swelling and shrinking. How motor organ identity is determined is unknown. Using a genetic approach, we isolated a mutant designated elongated petiolule1 (elp1) from Medicago truncatula that fails to fold its leaflets in the dark due to loss of motor organs. Map-based cloning indicated that ELP1 encodes a putative plant-specific LOB domain transcription factor. RNA in situ analysis revealed that ELP1 is expressed in primordial cells that give rise to the motor organ. Ectopic expression of ELP1 resulted in dwarf plants with petioles and rachises reduced in length, and the epidermal cells gained characteristics of motor organ epidermal cells. By identifying ELP1 orthologs from other legume species, namely pea (Pisum sativum) and Lotus japonicus, we show that this motor organ identity is regulated by a conserved molecular mechanism.


[INFORMED CONSENT FOR SURGERY: WHAT'S REALLY GOING ON THERE?]
The process of "informed consent" is currently being evaluated by the Ministry of Health, with the intent to recommend steps to improve patients' and doctors' satisfaction. Following the committee meetings, we decided to initiate an evaluation of the patient's perceptions regarding technical and logistic aspects of the process. To learn about patients' perceptions on the informed consent process, by evaluating different aspects and variables. One hundred patients who underwent an "informed consent" process, followed by general surgery, were interviewed using a formulated call-script. All the patients had surgery at Ramat Hayal Hospital during January 2020. All the interviewed patients reported that their surgeon was the one who participated in the informed consent process. The majority of the patients (70%) reported that the meeting lasted between 10-20 minutes. Only 35% of the patients reported that the surgeon used auxiliary materials during the meeting. Almost all patients (96-99%) noted that the explanations delineated by the surgeon during their meeting were clear, satisfactory, and congruent with their real experiences of their surgery. Based on the results of this study, we confirm that the informed consent process for patients having surgery at the Ramat Hayal Hospital, is adequate and follows the recommendations of the law. Analyzing our data by the funding agent did not disclose meaningful differences except regarding the use of auxiliary materials. This issue will be examined in a future study. These study results show a high compliance with the informed consent process in accordance with the law and MOH regulations.


[The progress and prospect of prepulse inhibition in autism].
Prepulse inhibition (PPI) is suppression of the startle reflex when an intense startling stimulus is preceded by a weaker sensory stimulus (the prepulse). It is an operational measurement of sensorimotor gating mechanism to help human adapt to complex environment. This weak prepulse protect central cognitive processing by damping the effect of intense stimuli. Autistics cannot select out behaviorally important information from a lot of irrelevant resources and reflect abnormal gating mechanism and attentional abnormalities. Previous studies have not made agreement on whether autistic patients demonstrated deficits in PPI, because the results depend on age, sex, severity of the disease as well as the experimental parameters used. Moreover, these studies have not covered whether autistics have suffered deficits in higher-order processing. In this review, the "top-down" modulation of selective attention and subjective emotion are introduced into the PPI experiment. We also introduce fear conditioning and perceived spatial separation paradigm to further explore the interaction between autistic cognitive process and gating mechanism.


Hospital revival and the board.
Hospitals in dire financial straights must act decisively, but are they making the right decisions? The board has a different leadership role in a financial turnaround.


Taxonomy-guided selection of Paraburkholderia busanensis sp. nov.: a versatile biocontrol agent with mycophagy against Colletotrichum scovillei causing pepper anthracnose.
This study introduces a novel approach based on the taxonomy-guided selection of bacterial biocontrol agents from a known beneficial taxonomic group. Following 16S rRNA screening, we focused on the genus Paraburkholderia, which harbors strains with large genomes and versatile benefits to plants. A strain designated P39 was selected, identified, and characterized for its biocontrol activity against Colletotrichum scovillei. Strain P39 exhibited antagonism against C. scovillei by producing compounds, including volatiles, with antifungal activity, both in vitro and on pepper fruits. Genomic, physiological, and biochemical analyses revealed that the selected strain represents a novel species, named Paraburkholderia busanensis. Genomic analyses provided insights into the fitness and biocontrol activities of the selected strains. Moreover, P39 displays mycophagy, consuming fungal mycelia and transforming them into bacterial biomass, particularly in nutrient-poor media supplemented with fungal mycelia. The genome harbored chitin and N-acetylglucosamine utilization genes, suggesting a proposed pathway for the utilization of fungal cells as a nutrient source. Microscopic observations further supported the ability of this strain to rupture and damage fungal hyphae, depriving them of their cellular constituents. This study successfully demonstrated the implementation of a taxonomy-guided approach for the selection of bacterial strains for biocontrol. These findings contribute to our understanding of biocontrol strategies, bacteria-fungi interactions, and the identification of Paraburkholderia busanensis sp. nov. as a potential candidate for the biocontrol of pepper anthracnose. Additionally, this strain serves as a valuable resource for antifungal compounds and volatiles, and for the study of bacteria-fungal interactions and mycophagy. IMPORTANCE Traditional control methods for postharvest diseases rely on fungicides, which cause human health and environmental concerns. This study introduces a taxonomy-guided strategy for selecting biocontrol agents. By focusing on Paraburkholderia group, which harbors diverse plant-beneficial strains, the inadvertent selection of harmful strains was circumvented, thereby obviating the need for laborious in vitro screening assays. A highly promising candidate, strain P39, has been identified, exhibiting remarkable biocontrol activity against Colletotrichum scovillei. Through comprehensive genomic, physiological, and biochemical analyses, P39 was characterized as a novel species within the Paraburkholderia genus and designated Paraburkholderia busanensis. Moreover, these findings deepen our understanding of bacterial-fungal interactions, as they elucidate a potential pathway for the utilization of fungal chitin, thereby enhancing our understanding of bacterial mycophagy. P. busanensis is a promising source of antifungal volatiles and putative novel secondary metabolites.


Successful treatment of refractory immune thrombocytopenia with rituximab in a 10-week-old infant.
Immune thrombocytopenic purpura (ITP) that is unresponsive to conventional treatment is uncommon. In this situation, additional therapeutic options are limited and management is challenging. We describe the case of a 10-week-old infant that developed life-threatening ITP that was unresponsive to immunoglobulin and corticosteroids that was successfully managed with the monoclonal antibody rituximab. The literature on the use of rituximab in nonresponsive ITP is reviewed.


Bimodal Seasonality and Alternating Predominance of Norovirus GII.4 and Non-GII.4, Hong Kong, China, 2014-20171.
We report emerging subtropical bimodal seasonality and alternating predominance of norovirus GII.4 and non-GII.4 genotypes in Hong Kong. GII.4 predominated in summer and autumn months and affected young children, whereas emergent non-GII.4 genotypes predominated in winter months and affected all age groups. This highly dynamic epidemiology should inform vaccination strategies.


[Molecular cytogenetic monitoring of chimerism and minimal residual disease in patient with chronic myeloid leukemia after allogenic and syngenic bone marrow transplantation].
To study trends in restoration of normal and tumor hemopoiesis after transplantation of allogenic and syngenic hemopoietic cells. The examination of bone marrow before transplantation and 1, 2, 3, 6, 9 months, 1, 2 and 3 years after bone marrow transplantation (BMT) was made in 25 patients with chronic myeloid leukemia (CML) after allogenic transplantation of the bone marrow (TBM) and 4 patients after syngenic TBM. The method of G-differential staining of chromosomes and fluorescent hybridization in situ (FISH) with DNA probe to centromeric sites X/Y of chromosomes and genes BCR/ABL was used. 56% of CML patients after allogenic BMT were in cytogenetic and clinicohematological remission, 16% developed early cytogenetic recurrence. Single metaphase with t(9;22) were identified in 28%; 14.3% developed late cytogenetic and hematological recurrence. In patients in posttransplantation remission there were from 0.1 to 5.8% cells of the host. The number of cells of the host and the number of BCR/ABL-positive cells correlated significantly. The results of 8-year monitoring of chimerism and minimal residual disease validate application of molecular-cytogenetic methods for assessing transplant condition.


Structural and thermodynamic correlates of T cell signaling.
The first crystal structures of intact T cell receptors (TCRs) bound to class I peptide-MHC (pMHCs) antigens were determined in 1996. Since then, further structures of class I TCR/pMHC complexes have explored the degree of structural variability in the TCR-pMHC system and the structural basis for positive and negative selection. The recent determination of class II and allogeneic class I TCR/pMHC structures, as well as those of accessory molecules (e.g., CD3), has pushed our knowledge of TCR/pMHC interactions into new realms, shedding light on clinical pathologies, such as graft rejection and graft-versus-host disease. Furthermore, the determination of coreceptor structures lays the foundation for a more comprehensive structural description of the supramolecular TCR signaling events and those assemblies that arise in the immunological synapse. While these telling photodocumentaries of the TCR/pMHC interaction are composed mainly from static crystal structures, a full description of the biological snapshots in T cell signaling requires additional analytical methods that record the dynamics of the process. To this end, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and ultracentrifugation (UC) have furnished both affinities and kinetics of the TCR/pMHC association. In the past year, structural, biochemical, and molecular biological data describing TCR/pMHC interactions have sublimely coalesced into a burgeoning well of understanding that promises to deliver further insights into T cell recognition. The coming years will, through a more intimate union of structural and kinetic data, allow many pressing questions to be addressed, such as how TCR/pMHC ligation is affected by coreceptor binding and what is the mechanism of TCR signaling in both early and late stages of T cell engagement with antigen-presenting cells.


A practical update on the epidemiology and risk factors for the emergence and mortality of bloodstream infections from real-world data of 3014 hematological malignancy patients receiving chemotherapy.
Background: Bloodstream infection (BSI) is a common and serious complication after patients with hematologic malignancies (HM) receiving chemotherapy. This study examined real-world data seeking to characterize HM BSI and identify risk factors for BSI emergence and mortality. Methods: We retrospectively analyzed the pathogenic epidemiology, antibiotic resistance, and BSI risk factors in a single-center cohort including 3014 consecutive patients with HM receiving chemotherapy between 2013 and 2016. Results of the pathogenic epidemiology were validated via comparison to available reported data. Results: We found that 725 patients (24.1%) had BSIs. Gram-negative (G-) bacteria represented 64.7% of the 744 isolated pathogenic strains, while Gram-positive (G+) bacteria and fungi accounted for 27.7% and 7.7% of the BSIs, respectively. The most common isolates were Klebsiella pneumoniae (19.2%), and 95.1% of the multidrug-resistant strains (MDR) were extended-spectrum beta-lactamase producing strains. G- bacteria were the main microflora responsible for BSI in our cohort of Chinese HM patients compared to studies in developed countries or in neutropenic children with HM or solid tumors. Multivariate analysis revealed that male sex, age ≥ 45 and < 65 yr, hospital length of stay ≥ 9d, neutropenia ≥ 7d before cultures, ≥ 2 antibiotics, and infections (gastrointestinal, perirectal, or urinary tract) independently predicted BSI emergence. Furthermore, age ≥ 65 yr, neutropenia ≥ 7d before blood cultures, no HM remission, lower white blood cell count, ≥ 3 antibiotics, respiratory infections, and Acinetobacter baumannii and Stenotrophomonas maltophilia BSI were independent predictors of 30-day mortality. Conclusions: G- bacteria were the predominant microflora during the study period and antibiotic resistance levels of the pathogens detected were high, especially for MDR strains. The mortality of BSI patients was high in this large cohort. Close attention should be paid to the risk factors identified here to facilitate timely and effective clinical management of such patients.


Influence of image reconstruction kernel on computed tomography-based finite element analysis in the clinical opportunistic screening of osteoporosis-A preliminary result.
This study aimed to evaluate the difference in vertebral mechanical properties estimated by finite element analysis (FEA) with different computed tomography (CT) reconstruction kernels and evaluate their accuracy in the screening and classification of osteoporosis. There were 31 patients enrolled retrospectively from the quantitative CT database of our hospital, uniformly covering the range from osteoporosis to normal. All subjects' CT raw data were reconstructed both with a smooth standard convolution kernel (B40f) and a sharpening bone convolution kernel (B70f), and FEA was performed on L1 of each subject based on two reconstructed images to obtain vertebral estimated strength and stiffness. The trabecular volumetric bone mineral density (vBMD) of the same vertebral body was also measured. FEA measurements between two kernels and their accuracy for osteoporosis screening were compared. The vertebral stiffness and strength measured in FEA-B40f were significantly lower compared with those of FEA-B70f (12.0%, p = 0.000 and 10.7%, p = 0.000, respectively). The correlation coefficient between FEA-B70F and vBMD was slightly higher than that of FEA-B40F in both vertebral strength and stiffness (strength: r 2-B40f = 0.21, p = 0.009 vs. r 2-B70f = 0.27, p = 0.003; stiffness: r 2-B40f = 0.37, p = 0.002 vs. r 2-B70f = 0.45, p=0.000). The receiver operator characteristic curve showed little difference in the classification of osteoporosis between FEA-B40f and FEA-B70f. Two kernels both seemed to be applicable to the opportunistic screening of osteoporosis by CT-FEA despite variance in FE-estimated bone strength and bone stiffness. A protocol for CT acquisition and FEA is still required to guarantee the reproducibility of clinical use.


Outcomes of Social Egg Freezing: A Cohort Study and a Comprehensive Literature Review.
The purpose of this study is to evaluate the live birth outcome following oocyte thaw in women who underwent social egg freezing at Guy's Hospital, alongside a detailed published literature review to compare published results with the current study. A retrospective cohort study was conducted between January 2016 and March 2022 for all women who underwent egg freezing during this period. Overall, 167 women had 184 social egg freezing cycles. The mean age at freeze was 37.1 years and an average of 9.5 eggs were frozen per retrieval. In total, 16% of the women returned to use their frozen eggs. The mean egg thaw survival rate post egg thaw was 74%. The mean egg fertilisation rate was 67%. The pregnancy rate achieved per embryo transfer was 48% and the live birth rate per embryo transfer was 35%. We also noted that irrespective of age at freezing, a significantly high live birth rate was achieved when the number of eggs frozen per patient was 15 or more. Despite the rapid increase in social egg freezing cycles, the utilisation rate remains low. Pregnancy and live birth rate post thaw are encouraging if eggs are frozen at a younger age and if 15 eggs or more were frozen per patient.


Short-term memory for the comparative instructions in symbolic comparison.
In the current study, a novel paradigm was used in which participants (N = 24) first compared the sizes of pairs of animals and then were asked, on half of the trials, to make a follow-up identification judgment regarding either the form of the comparative instruction that had just been used for the preceding comparison (i.e., smaller? or larger?) or the size of the stimuli in the comparison pair. To selectively enhance the difficulty associated with processing each of these aspects, on a large number of comparison trials, either the comparative instruction or the stimulus pair, respectively, was presented only very briefly. Results indicate that memory for the comparative instructions was dependent on the relative size of the stimulus pair such that participants were more likely to correctly identify the smaller form of the comparative instruction after comparing pairs of small stimulus items, as well as more likely to correctly identify the larger form of the comparative instruction after comparing pairs of large stimulus items. Such results are consistent with the view that the size of the stimulus pair contextually activates the representation of the congruent form of the comparative instruction.


Comparative analysis of bone marrow micrometastases with sentinel lymph node status in early-stage breast cancer.
Bone marrow micrometastases (BMM) and sentinel lymph node (SLN) status are both prognostic factors in breast cancer (BRCa) patients (pts). A definitive relationship between the two has not yet been proven and the data available is controversial. Thus, a retrospective study was conducted to determine the relationship of BM status and SLN status in pts with early BRCa (T1/T2). All female pts with early BRCa (T1/T2) operated upon by a single surgeon were included in the study. Prior to surgery, all pts underwent bone marrow aspiration from the posterior superior iliac spine bilaterally. Subsequently, pts underwent SLN biopsy and definitive primary breast surgery. BM samples were examined by using a Cytokeratin Detection Kit using CAM 5.2 monoclonal antibody. All pts with BMM underwent repeat BM analysis 6 months after completing all treatments. Data was collected for SLN, BM, estrogen receptor/progesterone receptor (ER/PR), and human epidermal growth factor receptor 2 (Her-2/neu) status and analyzed using chi-square (chi (2)) analysis or Fischer's exact test. A total of 270 consecutive pts with early BRCa were studied. SLN mapping was successful in all pts. SLN metastases (mets) were detected in 28.9% (78/270) pts. Of the 270 pts, 77.0% (208/270) had T1 disease. BMM were detected in 9.6% (26/270) pts, of whom 69.2% (18/26) were found to have BMM unilaterally. BMM were detected in 11.5% (9/78) pts with SLN mets versus 8.9% (17/192) in pts with node-negative disease (p = 0.65). Of the pts with T1 BRCa, BMM were observed in 9.1% (19/208) pts versus 11.3% (7/62) in pts with T2 BRCa (p = 0.6). In pts with ER/PR-negative (-ve) BRCa, BMM were found in 7.7% (2/26) pts versus 9.9% (24/242) in pts with ER/PR-positive (+ve) BRCa (p = 0.27). BMM were detected in 12.3% (9/73) pts with Her-2/neu +ve BRCa and in 8.6% (16/187) pts with Her-2/neu -ve BRCa (p = 0.11). After completion of adjuvant therapy all pts with BMM (n = 26) converted to BM negative status. We conclude that BM status did not correlate with SLN status and occurs independently of lymphatic metastasis possibly through a different mechanism. BMM occur in node-negative pts and may assist in identifying pts at high risk for disease recurrence. Obtaining bone marrow aspirate from two locations resulted in a significant increase in detection of micrometastases.


Genes in the high-density lipoprotein metabolic pathway in age-related macular degeneration and polypoidal choroidal vasculopathy.
To investigate the associations of genetic variants in the high-density lipoprotein (HDL) metabolism pathway with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Cross-sectional, case-control association study. A Chinese case-control group of 200 neovascular AMD patients, 233 PCV patients, and 275 control subjects. Eight single nucleotide polymorphisms (SNPs) from 6 genes of the HDL metabolism pathway and 2 known AMD-associated SNPs, rs800292 (from complement factor H [CFH]) and rs11200638 (from HtrA serine peptidase 1 [HTRA1]), were genotyped in all study subjects using the TaqMan genotyping technology (Applied Biosystems, Foster City, CA). Allele and genotypic frequencies of selected SNPs. The SNP rs3764261 in the cholesteryl ester transfer protein (CETP) gene was associated significantly with neovascular AMD (P = 1.82×10(-4); odds ratio [OR], 1.89) and PCV (P = 4.04×10(-4); OR, 1.80). The associations remained significant after adjusting for the CFH SNP rs800292 and the HTRA1 SNP rs11200638. A significant interaction between the CETP SNP rs3764261 and the CFH SNP rs800292 existed in both neovascular AMD and PCV, the rs800292 G allele conferring a significantly increased risk of the diseases only in individuals carrying the risk allele T of rs3764261. A borderline association was detected between the ATP-binding cassette, subfamily G, member 1 (ABCG1) gene SNP rs57137919 and PCV (P = 0.03). Our results showed that CETP is a susceptibility gene for neovascular AMD and PCV and that ABCG1 a putative gene for PCV. CETP exerts a modifying effect on CFH in the genetic risk. Our data suggest a link of the HDL metabolism pathway with neovascular AMD and PCV.


Metallization of a thiol-terminated organic surface using chemical vapor deposition.
The deposition and the subsequent decomposition of an organometallic precursor, (eta (3)-allyl)(eta (5)-cyclopentadienyl)palladium [Cp(allyl)Pd], on an organic surface exposed by self-assembled monolayers (SAM) was studied using X-ray photoelectron spectroscopy (XPS) and infrared reflection absorption spectroscopy (IRRAS). The interfacial chemical reactions of the vapor-deposited metal precursor with the pendant thiol group of the SAMs made from oligophenyldithiols, which are either prepared directly (terphenyldimethyldithiol, TPDMT) or by a deprotection route from SAMs formed by a monoacylated derivative of biphenyldimethyldithiol (dep. BPDMAc-1) have been studied in detail. When the TPDMT-SAMs were exposed to Cp(allyl)Pd vapor, a Pd (2+)/allyl-terminated SAM surface was obtained (to a lower extent this was also the case for dep. BPDMAc-1 SAMs), which was stable against exposure to H 2 gas. Reduction to Pd (0) by H 2 was only observed when small amounts of Pd (0) were already present, for example, after prolonged exposure to the precursor. The catalytic activity of the small Pd (0) particles also caused a decomposition of the SAMs upon exposure to air.


High risk and low prevalence diseases: Acute limb ischemia.
Acute limb ischemia is a rare but serious condition that carries with it a high rate of morbidity and mortality. This review highlights the pearls and pitfalls of acute limb ischemia, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. Acute limb ischemia is defined as a sudden decrease in limb perfusion resulting in cessation of blood flow and nutrient and oxygen delivery to the tissues. This leads to cellular injury and necrosis, ultimately resulting in limb loss and potentially systemic symptoms with significant morbidity and mortality. There are several etiologies including native arterial thrombosis, arterial thrombosis after an intervention, arterial embolus, and arterial injury. Patients with acute limb ischemia most commonly present with severe pain and sensory changes in the initial stages, with prolonged ischemia resulting in weakness, sensory loss, and color changes to the affected limb. The emergency clinician should consult the vascular specialist as soon as ischemia is suspected, as the diagnosis should be based on the history and examination. Computed tomography angiography is the first line imaging modality, as it provides valuable information concerning the vasculature and surrounding tissues. Doppler ultrasound of the distal pulses may also be obtained to evaluate for arterial and venous flow. Once identified, management includes intravenous unfractionated heparin and vascular specialist consultation for revascularization. An understanding of acute limb ischemia can assist emergency clinicians in diagnosing and managing this potentially deadly disease.


Factors that may effect the reduction of hunger and body weight following d-fenfluramine administration.
Three studies have been undertaken to investigate why there are individual differences in the response to d-fenfluramine with respect to food intake and hunger in the short term and on body weight loss in the long term. Fenfluramine and norfenfluramine plasma levels have been used as probes to help detect and normalize these variances. In a single dose ranging volunteer study (0, 30, 40, and 60 mg), d-fenfluramine levels were significantly related to caloric intake and hunger rating scales when compared individually, and the slopes of the regression lines showed intersubject variation. These slopes, an index of each subject's response to fenfluramine, appear to be related to both the percentage underweight and more weakly to the percentage overweight. Those subjects at the extremes of weight showed a greater response to a given drug level. In two placebo-controlled 3 month studies (30 mg/day), the variances in weight loss were not explained by steady state drug levels, the percentage overweight, initial weight, duration of obesity, or caloric intake even when weight loss was normalized for differences in drug levels. Age, however, was significantly related to weight loss, with each additional 10 years increasing weight loss by approximately 1 kg. If confirmed, the sensitivity of fenfluramine anorexia may be an objective acute test of the central control of food intake. However, in long term clinical studies, drug levels were only weakly related to weight loss and other undefined factors seem to determine which patients responded better to fenfluramine treatment.


Palladium-Catalyzed Decarboxylative ortho-Amidation of Indole-3-carboxylic Acids with Isothiocyanates Using Carboxyl as a Deciduous Directing Group.
Palladium-catalyzed ortho-amidation of indole-3-carboxylic acids with isothiocyanates by using the deciduous directing group nature of carboxyl functionality to afford indole-2-amides is demonstrated. Both C-H functionalization and decarboxylation took place in one pot, and hence, this carboxyl group served as a unique, deciduous (or traceless) directing group. This reaction offers a broad substrate scope as demonstrated for several other heterocyclic carboxylic acids like chromene-3-carboxylic acid, imidazo[1,2- a]pyridine-2-carboxylic acid, benzofuran-2-carboxylic acid, pyrrole-2-carboxylic acid, and thiophene-2-carboxylic acid. In the reaction using 2-naphthoic acid, of the two possible isomers, only one isomer of the amide was exclusively formed. The indole-2-amide product underwent palladium-catalyzed C-H functionalization to afford the diindole-fused 2-pyridones by combining two molecules of the indole moiety, with the elimination of an amide group from one of them, attached at the C3-position for the C-C/C-N bond formation. The structures of key products are confirmed by X-ray crystallography.


[Ophthalmological imaging with ultrahigh field magnetic resonance tomography: technical innovations and frontier applications].
This review documents technical progress in ophthalmic magnetic resonance imaging (MRI) at ultrahigh fields (UHF, B(0) ≥ 7.0 T). The review surveys frontier applications of UHF-MRI tailored for high spatial resolution in vivo imaging of the eye, orbit and optic nerve. Early examples of clinical ophthalmic UHF-MRI including the assessment of melanoma of the choroid membrane and the characterisation of intraocular masses are demonstrated. A concluding section ventures a glance beyond the horizon and explores research promises along with future directions of ophthalmic UHF-MRI.


Lip dimensions of an adult Nigerian population with normal occlusion.
The soft tissue paradigm is placing greater emphasis on the importance of the soft tissue profile to orthodontic treatment planning. The purpose of this study was to determine the lip dimensions of a Nigerian adult population; compare the male and female values and to compare the values obtained for Nigerians with those reported for other population. Lateral cephalometric radiographs of 100 students (44 males and 56 females) of the College of Medicine, University of Lagos, aged 18 to 25 years were taken. Selected subjects were of Nigerian ancestry with normal occlusion and a harmonious facial appearance. The radiographs were manually traced and the upper and lower lip length and thickness of each subject was measured. Statistical analysis was carried out using SPSS, while the male and female values were compared using student's t-tests. Mean values for the lip dimensions were computed for the entire sample. Marked sexual dimorphism was observed with the males having thicker and longer upper and lower lips than the females. The Nigerian sample also had a longer upper lip and a thicker and shorter lower lip than that reported for Caucasians. However, both population had a similar upper lip thickness. Cephalometric norms were developed for the lip dimensions of a Nigerian population. Marked sexual dimorphism was observed in the Nigerian population studied with the males having longer and thicker lips than the females. The lip dimensions of the Nigerian population studied differed from that reported for Caucasians and other racial groups.


Body mass index and nutritional status of adults in two rural villages in northern malaysia.
There has been a change in the lifestyles of populations, including reduced physical activity and consumption of foods high in calories. Overweight and obesity are now replacing the more traditional public health concerns such as under-nutrition and infectious diseases as some of the most significant contributors to ill health. Determination of the body mass index (BMI) profile and nutritional status of adults of two rural coastal villages in Northern Malaysia was part of a community diagnosis in a community survey. Height and weight were measured and BMI calculated. Blood pressure was measured using a manual sphygmomanometer according to WHO guidelines. A standardised questionnaire was used to interview the villagers concerning their health. Out of the total population, 504 were above 20 years of age. Data was available for 441 persons for analysis. There were 210 (47.6%) males and 231 (52.4%) females. The prevalence of underweight was 9.8% (n=43), overweight 25.9% (n=114) and obesity 17% (n=75). The problem of over-nutrition was significantly higher among females, especially housewives. (p< 0.05). Those in ages 41-70 years were the majority with problems of over-nutrition (p=<0.05). More than half (52.9%; n=39) of those who were obese had hypertension (p=<0.05). Results show that a higher number of women especially housewives were obese and more than half of those obese subjects had hypertension. A more thorough nutritional profile using waist, hip and body fat measurement as well as an assessment of the dietary intake and activity regime of these villagers is needed. Interventions need to be carried out before more serious complications of obesity become rooted in this community.


Intermittent Cyclic Mechanical Tension-Induced Calcification and downregulation of ankh gene expression of end plate chondrocytes.
Intermittent Cyclic Mechanical Tension (ICMT) was applied to end plate chondrocytes by using an FX-4000T Flexercell Tension Plus unit (Flexcell International Corporation, Hillsborough, NC). Changes of end plate chondrocytes were observed after ICMT stimulation. To investigate the relationship between mechanical stimulation and calcification of end plate chondrocytes. Previous study showed that end plate calcification was related to mechanical stress, but there was no clear evidence to indicate whether or not mechanical stimulation could induce calcification of end plate chondrocytes in vitro. Rat end plate chondrocytes were cultured and ICMT (strain at 0.5 Hz sinusoidal curve at 10% elongation) was applied for 25 days, 4 hours a day and continued to culture for 5 days. End plate chondrocytes were incubated for 12 hours in the presence or absence of 10 ng/mL of transforming growth factor-β1 (TGF-β1) (prepared from a stock solution at 10 μg/mL in 2 mM citric acid containing 2 mg/mL bovine serum albumin) in MEM/F-12 containing a final concentration of 1% FCS. End plate chondrocytes calcification was stained by alizarin red S (AR-S). End plate chondrocytes viability was examined by LIVE/DEAD viability/cytotoxicity kit (Invitrogen, Carlsbad, CA). Related gene expression was examined by reverse transcription-polymerase chain reaction and Western blot. LIVE/DEAD assay verified that the nonloading (NC) group and the ICMT group end plate chondrocytes remained adherent, with no change in viability after the application of ICMT. Alizarin red staining showed that ICMT induced the calcification of end plate chondrocytes. Real-time reverse transcription-polymerase chain reaction showed that mRNA expression of endogenous TGF-β1 decreased and mRNA expression of type I, type X, osteocalcin and osteopontin increased after ICMT. The ankh gene expression of both mRNA and protein levels decreased in the ICMT stimulation. The ankh gene expression of both mRNA and protein levels increased in TGF-β1 stimulation. Compared with NC group, the alkaline phosphatase activities significantly increased in ICMT group. Our results directly showed that ICMT induced the calcification and downregulation of ankh gene expression of end plate chondrocytes, which may be caused by the endogenous TGF-β1.


Responses of V1 neurons to two-dimensional hermite functions.
Neurons in primary visual cortex are widely considered to be oriented filters or energy detectors that perform one-dimensional feature analysis. The main deviations from this picture are generally thought to include gain controls and modulatory influences. Here we investigate receptive field (RF) properties of single neurons with localized two-dimensional stimuli, the two-dimensional Hermite functions (TDHs). TDHs can be grouped into distinct complete orthonormal bases that are matched in contrast energy, spatial extent, and spatial frequency content but differ in two-dimensional form, and thus can be used to probe spatially specific nonlinearities. Here we use two such bases: Cartesian TDHs, which resemble vignetted gratings and checkerboards, and polar TDHs, which resemble vignetted annuli and dartboards. Of 63 isolated units, 51 responded to TDH stimuli. In 37/51 units, we found significant differences in overall response size (21/51) or apparent RF shape (28/51) that depended on which basis set was used. Because of the properties of the TDH stimuli, these findings are inconsistent with simple feedforward nonlinearities and with many variants of energy models. Rather, they imply the presence of nonlinearities that are not local in either space or spatial frequency. Units showing these differences were present to a similar degree in cat and monkey, in simple and complex cells, and in supragranular, infragranular, and granular layers. We thus find a widely distributed neurophysiological substrate for two-dimensional spatial analysis at the earliest stages of cortical processing. Moreover, the population pattern of tuning to TDH functions suggests that V1 neurons sample not only orientations, but a larger space of two-dimensional form, in an even-handed manner.


IgD (kappa) "nonsecretory" multiple myeloma: report of a case.
A case of IgD "nonsecretory" multiple myeloma in a 46-yr-old woman is reported. Despite the presence of disseminated osteolytic lesions, both serum protein electrophoresis and serum and urine immunoelectrophoresis were normal. In addition, bone scintigraphic study was normal. Bone marrow biopsy and aspirate obtained from the left femur lytic lesion showed only myelomatous proplasmocytes; when examined by immunofluorescence with monospecifc antisera, the cytoplasm showed only the presence of delta and kappa chains, suggesting that the neoplastic plasma cells might belong to a single clone. Lymphocyte studies indicated the presence of a normal amount of both B and T cells.


A new crossed molecular beam apparatus using time-sliced ion velocity imaging technique.
A new crossed molecular beam apparatus has been constructed for investigating polyatomic chemical reactions using the time-sliced ion velocity map imaging technique. A unique design is adopted for one of the two beam sources and allows us to set up the molecular beam source either horizontally or vertically. This can be conveniently used to produce versatile atomic or radical beams from photodissociation and as well as electric discharge. Intensive H-atom beam source with high speed ratio was produced by photodissociation of the HI molecule and was reacted with the CD(4) molecule. Vibrational-state resolved HD product distribution was measured by detecting the CD(3) product. Preliminary results were also reported on the F+SiH(4) reaction using the discharged F atom beam. These results demonstrate that this new instrument is a powerful tool for investigating chemical dynamics of polyatomic reactions.


Economic Operation of the Regional Integrated Energy System Based on Particle Swarm Optimization.
Aiming at the problems of single planning technology and relatively few resource types in the process of regional comprehensive energy system planning at the current stage, this paper proposes a method based on the construction of regional comprehensive energy system planning and the operation model. Through the integration of the particle swarm optimization algorithm, this method can better realize the optimization and economic operation of the regional comprehensive energy system and build a system optimization mode based on two stages of planning and operation to pursue the optimal configuration of system equipment. Through the simulation algorithm, it is found that the solution time of the traditional basic particle swarm optimization algorithm is 10.49s, while the average solution time of the particle swarm optimization system proposed in this study is 7.93s; the efficiency is increased by 24.4%, and the system operation efficiency is significantly improved, providing theoretical and technical guidance for the economic operation of the regional comprehensive energy system.


Antioxidant markers in human senile and diabetic cataractous lenses.
To determine the role of free radicals and antioxidant enzymes in patients suffering from cataract due to aging and diabetes. Experimental study. Department of Biochemistry, University of Karachi from December 2004 to May 2005. The study was conducted on 80 cataract patients. Lens and plasma samples from senile and diabetic subjects suffering from cataract were analyzed and activity of Cu, Zn-superoxide dismutase (Cu, Zn-SOD) was measured using xanthine oxidase system. Catalase (CAT) activity was estimated. Levels of malondialdehyde (MDA) was measured by thiobarbituric acid reaction. Student's t- test was employed for analysis of results. Significant difference (p<0.001) was found in activity of Cu, Zn-SOD in cataract lenses from diabetic patients as compared to senile subjects, CAT activities was also lower (p<0.001) in lenses from diabetic cataract patients when compared to lenses from senile cataractous subjects. Lens MDA levels were significantly higher (p<0.001) in cataract lenses from diabetic patients than in senile subjects. Plasma MDA levels were lowest (p<0.001) in controls as compared to senile and diabetic cataractous patients. Results of present study suggest that increased production of high levels of free oxygen species is linked to glucose oxidation and non-enzymatic glycation of proteins. Furthermore, elevated glucose levels might be involved in the insufficiency of antioxidant enzymatic activity and in the progression of lipid peroxidation.


Improving Readiness and Reducing Costs: An Analysis of Factors That Influence Site Selection for Army Outpatient Surgical Services.
The variable costs of providing surgical procedures for military beneficiaries are greater when care is rendered in the civilian purchased care network than when provided at a direct care military treatment facility (MTF). To reduce healthcare-related costs, retaining surgical services is a priority at MTFs across the U.S. Army Medical Command. This study is the first to identify factors significantly associated with outpatient surgical service site selection in the military health system (MHS). We analyzed 1,000,305 patient encounters in fiscal year 2014, of which 970,367 were direct care encounters and 29,938 were purchased care encounters. We used multiple binomial logistic regression to assess and compare the odds of site selection at a purchased care facility and an MTF. We found that an increase in provider administrative time (OR = 1.024, p < .001) and an increase in case complexity (OR = 1.334, p < .001) were associated with increased odds that an outpatient surgical service was provided in a purchased care setting. The increased odds that highly complex cases were seen in purchased care has the potential to affect the medical readiness of military providers and the efficacy of graduate medical education programs. Healthcare administrators can use the results of this study to develop and implement MTF level policies to enhance outpatient surgical service practices in the Army medical system. These efforts may reduce costs and increase military provider medical readiness.


Nuclear Translocation of SGPP-1 and Decrease of SGPL-1 Activity Contribute to Sphingolipid Rheostat Regulation of Inflammatory Dendritic Cells.
A balanced sphingolipid rheostat is indispensable for dendritic cell function and survival and thus initiation of an immune response. Sphingolipid levels are dynamically maintained by the action of sphingolipid enzymes of which sphingosine kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate. TLR-dependent activation caused SGPL-1 protein downregulation with subsequent decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive dendritic cells and was translocated into the cytoplasmatic compartment upon inflammatory stimulation resulting in dephosphorylation of S1P. Mass spectrometric determination showed that a part of the resulting sphingosine was released from the cell, increasing extracellular levels. Another route of diminishing intracellular S1P was possibly taken by its export via ATP-binding cassette transporter C1 which was upregulated in array analysis, while the S1P transporter, spinster homolog 2, was not relevant in dendritic cells. These investigations newly describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation.


Adding value to antiretroviral proficiency testing.
Clinical trial specimens tested for antiretroviral (ARV) concentrations often require compliance with Clinical Laboratory Improvement Act and/or the Food and Drug Administration bioanalytical guidance. The Clinical Pharmacology Quality Assurance Program (CPQA) designed 8 proficiency testing (PT) rounds over 4 years to assess precision, specificity and stability. Ten laboratories provided blinded proficiency data to support continued acceptable precision of ARV methods. Specificity samples identified little bias for individual methods; hemolyzed (87%) and lipemic (86%) results were ≤ 10% of their control results. Stability was established for ARVs in plasma at -70°C for 2.5-3.6 years. PT provided by the CPQA assured continued acceptability of individual laboratory assay performances for precision and specificity, and obtained ARV stability during long term storage.


Evidence for a glycosaminoglycan on the nudel protein important for dorsoventral patterning of the drosophila embryo.
Dorsoventral patterning of the Drosophila embryo requires Nudel, a large mosaic protein with a protease domain. Previous studies have implicated Nudel's protease domain as the trigger of a proteolytic cascade that activates the Toll signaling pathway to establish dorsoventral polarity in the embryo. However, the function of other regions of Nudel has been unclear. By using two-dimensional gel electrophoresis and site-directed mutagenesis, we have obtained evidence that the N-terminal region of Nudel contains a site for glycosaminoglycan (GAG) attachment that is required for dorsoventral patterning. Disruption of this site blocks a disulfide-based association between N- and C-terminal Nudel polypeptides and proteolytic activation of Nudel's protease domain. We discuss how a GAG chain on Nudel might be required for Nudel protease activation.


Relationship of Serum Total Insulin-Like Growth Factor Binding Protein-3 with Insulin-Like Growth Factor-I and Glucose Tolerance in Korean Children and Adolescents.
Insulin is important in glucose metabolism. However, insulin-like growth factor binding protein (IGFBP) also plays an important role in glucose homeostasis, although the IGF-independent role of IGFBP-3 in the glucose intolerance state is poorly understood. We investigated the relationship of serum IGF-I with total IGFBP-3 levels and glucose tolerance in Korean children and adolescents who underwent the oral glucose tolerance test (OGTT). A total of 187 children without known diabetes underwent OGTT, and data related to their clinical and laboratory parameters were collected. Serum IGF-I and total IGFBP-3 levels, fasting plasma glucose levels, lipid profiles, insulin levels, C-peptide levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, and glycated hemoglobin (HbA1c) levels were measured. Serum IGF-I and total IGFBP-3 levels were significantly higher in individuals with impaired glucose tolerance and type 2 diabetes (DM) than in those with normal glucose tolerance (NGT) (P < 0.05). Serum IGF-I and IGFBP-3 levels were correlated with age, HbA1c, C-peptide, insulin, and HOMA-IR in the NGT group. However, these relationships were altered in patients with glucose intolerance, especially in those with DM. In the DM group, serum IGF-I and total IGFBP-3 levels were positively correlated with fasting plasma glucose and HbA1c levels. In addition, total IGFBP-3 levels were positively correlated with total cholesterol and low-density lipoprotein cholesterol and IGF-I levels but not with age or body mass index. The IGF-I-IGFBP-3 axis, especially IGFBP-3, may be involved in the pathogenesis and metabolic control of glucose intolerance, specifically in diabetes patients. Moreover, IGFBP-3 might be a therapeutic marker.


Variation in the apolipoprotein B gene and development of type 2 diabetes mellitus.
Several studies have demonstrated an association between variation in the apolipoprotein (apo) B gene, principally as detected by the XbaI and EcoRI restriction fragment length polymorphisms (RFLPs), and lipoprotein levels or cardiovascular disease. We have examined the frequency of the EcoRI and XbaI RFLPs of the apoB gene in 95 white Type 2 diabetic patients aged between 45 and 80 years in order to ascertain whether variation in this gene may be influencing the development of Type 2 diabetes and associated atherosclerosis through obesity. Neither of the two RFLPs had a significant association with clinically defined cardiovascular disease or with body mass index in our sample. However, while XbaI displayed no association with circulating levels of lipids, lipoproteins or apolipoproteins, the presence of the rare (R2) alele of EcoRI (absence of cutting site) was associated with significantly higher levels of circulating triglycerides. Furthermore, the EcoRI R2 allele was over-represented in the diabetic sample when compared to a healthy control group. Our findings support previous studies which have shown an effect of variation at the apoB gene on circulating lipid levels; additionally, variation in this gene may contribute to the development of Type 2 diabetes mellitus.


Platinum-palladium-on-reduced graphene oxide as bifunctional electrocatalysts for highly active and stable hydrogen evolution and methanol oxidation reaction.
In the context of the gradual depletion of global fossil fuel resources, it is increasingly necessary to explore new alternative energy. Hydrogen energy has attracted great interest from researchers because of its green and pollution-free characteristics. Moreover, the methanol oxidation reaction (MOR) can combine the hydrogen evolution reaction (HER), replacing the anode reaction (oxygen evolution reaction-OER) in overall water splitting and efficiently producing hydrogen. In this study, platinum-palladium nanoparticles on reduced graphene oxide (PtPd/rGO) were successfully synthesized as HER and MOR bifunctional electrocatalysts under alkaline conditions by the stepwise loading of Pt and Pd bimetallic nanoparticles on rGO using a simple liquid-phase reduction method. PtPd/rGO-2 with 0.99 wt% Pt and 2.86 wt% Pd in the HER has the lowest overpotential (87.16 mV at 100 mA cm-2), with the smallest Tafel slope (18.9 mV dec-1). The exceptional mass activity of PtPd/rGO-2 in the MOR reaches 10.75 A mg-1PtPd, which is 18.22 and 53.75 times greater than that of commercial Pt/C (Pt/C) and commercial Pd/C (Pd/C), respectively. PtPd/rGO-2 is 0.935 V lower in the coupling reaction of HER and MOR (MOR ∥ HER) compared to the overall water splitting (OER ∥ HER) without methanol (10 mA cm-2). This is probably because appropriate Pt and Pd loading exposes many more catalytic sites, and the synergistic interaction between Pt, Pd, and Pt-Pd enhances the catalytic performance. This strategy can be used for the synthesis of novel bifunctional electrocatalysts.


MICA and NKG2D: Is There an Impact on Kidney Transplant Outcome?
This paper aims to present an overview of MICA and natural killer group 2 member D (NKG2D) genetic and functional interactions and their impact on kidney transplant outcome. Organ transplantation has gone from what can accurately be called a "clinical experiment" to a routine and reliable practice, which has proven to be clinically relevant, life-saving and cost-effective when compared with non-transplantation management strategies of both chronic and acute end-stage organ failures. The kidney is the most frequently transplanted organ in the world (transplant-observatory). The two treatment options for end-stage renal disease (ESRD) are dialysis and/or transplantation. Compared with dialysis, transplantation is associated with significant improvements in quality of life and overall longevity. A strong relationship exists between allograft loss and human leukocyte antigens (HLA) antibodies (Abs). HLA Abs are not the only factor involved in graft loss, as multiple studies have shown that non-HLA antigens are also involved, even when a patient has a good HLA matche and receives standard immunosuppressive therapy. A deeper understanding of other biomarkers is therefore important, as it is likely to lead to better monitoring (and consequent success) of organ transplants. The objective is to fill the void left by extensive reviews that do not often dive this deep into the importance of MICA and NKG2D in allograft acceptance and their partnership in the immune response. There are few papers that explore the relationship between these two protagonists when it comes to kidney transplantation. This is especially true for the role of NKG2D in kidney transplantation. These reasons give a special importance to this review, which aims to be a helpful tool in the hands of researchers in this field.


Mixed Spices at Culinary Doses Have Prebiotic Effects in Healthy Adults: A Pilot Study.
Spices were used as food preservatives prior to the advent of refrigeration, suggesting the possibility of effects on microbiota. Previous studies have shown prebiotic activities in animals and in vitro, but there has not been a demonstration of prebiotic or postbiotic effects at culinary doses in humans. In this randomized placebo-controlled study, we determined in twenty-nine healthy adults the effects on the gut microbiota of the consumption daily of capsules containing 5 g of mixed spices at culinary doses by comparison to a matched control group consuming a maltodextrin placebo capsule. The 16S ribosomal RNA sequencing data were used for microbial characterization. Spice consumption resulted in a significant reduction in Firmicutes abundance (p < 0.033) and a trend of enrichment in Bacteroidetes (p < 0.097) compared to placebo group. Twenty-six operational taxonomic units (OTUs) were different between the spice and placebo groups after intervention. Furthermore, there was a significant negative correlation between fecal short-chain fatty acid propionate concentration and Firmicutes abundance in spice intervention group (p < 0.04). The production of individual fecal short-chain fatty acid was not significantly changed by spice consumption in this study. Mixed spices consumption significantly modified gut microbiota, suggesting a prebiotic effect of spice consumption at culinary doses.


[Effects of D1 and D2 dopamine receptor agonists and antagonists on cerebral ischemia/reperfusion injury].
Gerbil forebrain ischemia/reperfusion(I/R) injury model was used to study the effects of D(1) and D(2) receptor agonists and antagonists on neuronal apoptosis of hippocampal CA1 area. All animals were tested for habituation deficits in an open field test on the 1st, 3rd and 7th days after reperfusion. The animals were then killed, and brains underwent paraffin embedding for hematoxylin-eosin staining, in situ terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) staining and immunohistochemistry (bax, bcl-2). The result of open field test showed that the I/R group was significantly impaired (higher activity scores) when compared with the control group. Pretreatment with pergolide significantly reduced this habituation impairment. Forebrain ischemia for 5 min resulted in extensive CA1 apoptosis on the 3rd and 7th days after I/R injury. About 95% neurons in hippocampal CA1 area entered apoptosis and only 2%-7% pyramidal neurons stayed alive due to an inhibition of bcl-2 expression and an increase in bax expression. Pretreatment of pergolide attenuated neuronal damage caused by transient ischemia. Infusion of pergolide could induce the expression of bcl-2 and reduce the expression of bax. Pretreatment with SKF38393, SCH23390 and spiperone had no effects on these changes in this transient I/R injury model. All these results indicate that pergolide plays an important role in the protection of hippocampal neurons from apotosis through upregulating the expression of bcl-2 protein and reducing the expression of bax protein.


Age-dependent survival analyzed with Bayesian models of mark-recapture data.
We describe a Bayesian random effects model of mark-recapture data that accounts for age-dependence in survival and individual heterogeneity in capture probabilities and survival. The model is applied to data on the Glanville fritillary butterfly (Melitaea cinxia) collected from a population enclosed in a large cage in the field. The cage population consisted of a mixture of butterflies originating from newly established and old populations in a large metapopulation in the Aland Islands in Finland. The explanatory variables in the model included the effects of temperature, sex, and population type (new vs. old) on capture probabilities, and the effects of age, sex, population type, and day vs. night on survival. We found that mortality rate increased with age, that mortality rate was much higher during the day than during the night, and that the life span of females originating from newly established populations was shorter than the life span of females from old populations. Capture probability decreased with increasing temperature and decreased with increasing mobility of individuals.


Organic synthesis in soft wall-free microreactors: real-time monitoring of fluorogenic reactions.
A new approach of "laboratory on a chip" (LOC) devoted to organic synthesis based on electrically operated ionic liquid microdroplets used as air-stable "soft" microreactors was recently introduced. A number of challenging issues have yet to be addressed to allow standard macroscale organic chemistry to be directly transposed in these nonclassical microreactors. In particular, since standard (i.e., magnetical or mechanical) stirring methods are prohibited in such wall-free microreactors, effective alternatives have to be developed to circumvent mass-transfer limitations. With this aim in mind, a fluorogenic version of a click chemistry reaction was developed to evaluate the efficiency of alternative mixing methods on the reaction kinetics. We demonstrate that the combination of chaotic advection created by surface acoustic waves combined with a temperature increase (Marangoni effect) leads to the same kinetics regime as in standard macroscale conditions. This opens the route for application of the new generation of LOC to efficient organic synthesis in microscale.


4,4'-Oxybis{N-[(E)-quinolin-2-yl-methyl-idene]aniline}.
The title Schiff base compound, C(32)H(22)N(4)O, was prepared by a reaction of 4,4'-diamino-diphenyl ether and 2-quinoline-carboxaldehyde. The mol-ecule consists of two 4-{N-[(E)-quinolin-2-yl-methyl-idene]amino}-phenyl units linked by an oxygen bridge. The dihedral angles between two benzene rings and between the two quinoline ring systems are 53.81 (7) and 42.56 (4)°, respectively. Inter-molecular C-H⋯N hydrogen bonding is present in the crystal structure.


PI3K Signaling in Tissue Hyper-Proliferation: From Overgrowth Syndromes to Kidney Cysts.
The members of the PhosphoInositide-3 Kinase (PI3K) protein family are well-known regulators of proliferative signals. By the generation of lipid second messengers, they mediate the activation of AKT/PKB (AKT) and mammalian Target Of Rapamycin (mTOR) pathways. Although mutations in the PI3K/AKT/mTOR pathway are highly characterized in cancer, recent evidence indicates that alterations in the proliferative signals are major drivers of other diseases such as overgrowth disorders and polycystic kidney disease. In this review, we briefly summarize the role of the PI3K/AKT/mTOR pathway in cell proliferation by comparing the effect of alterations in PI3K enzymes in different tissues. In particular, we discuss the most recent findings on how the same pathway may lead to different biological effects, due to the convergence and cooperation of different signaling cascades.


Xylitol concentrations in artificial saliva after application of different xylitol dental varnishes.
The present study analyzed xylitol concentrations in artificial saliva over time after application of varnishes containing 10% and 20% xylitol. Fifteen bovine enamel specimens (8x4 mm) were randomly allocated to 3 groups (n=5/group), according to the type of varnish used: 10% xylitol, 20% xylitol and no xylitol (control). After varnish application (4 mg), specimens were immersed in vials containing 500 µL of artificial saliva. Saliva samples were collected in different times (1, 8, 12, 16, 24, 48 and 72 h) and xylitol concentrations were analyzed. Data were assessed by two-way repeated-measures ANOVA (p<0.05). Colorimetric analysis was not able to detect xylitol in saliva samples of the control group. Salivary xylitol concentrations were significantly higher up to 8 h after application of the 20% xylitol varnish. Thereafter, the 10% xylitol varnish released larger amounts of that polyol in artificial saliva. Despite the results in short-term, sustained xylitol releases could be obtained when the 10% xylitol varnish was used. These varnishes seem to be viable alternatives to increase salivary xylitol levels, and therefore, should be clinically tested to confirm their effectiveness.


Exploring the behavioral determinants of COVID-19 vaccine acceptance among an urban population in Bangladesh: Implications for behavior change interventions.
While vaccines ensure individual protection against COVID-19 infection, delay in receipt or refusal of vaccines will have both individual and community impacts. The behavioral factors of vaccine hesitancy or refusal are a crucial dimension that need to be understood in order to design appropriate interventions. The aim of this study was to explore the behavioral determinants of COVID-19 vaccine acceptance and to provide recommendations to increase the acceptance and uptake of COVID-19 vaccines in Bangladesh. We employed a Barrier Analysis (BA) approach to examine twelve potential behavioral determinants (drawn from the Health Belief Model [HBM] and Theory of Reasoned Action [TRA]) of intended vaccine acceptance. We conducted 45 interviews with those who intended to take the vaccine (Acceptors) and another 45 interviews with those who did not have that intention (Non-acceptors). We performed data analysis to find statistically significant differences and to identify which beliefs were most highly associated with acceptance and non-acceptance with COVID-19 vaccines. The behavioral determinants associated with COVID-19 vaccine acceptance in Dhaka included perceived social norms, perceived safety of COVID-19 vaccines and trust in them, perceived risk/susceptibility, perceived self-efficacy, perceived positive and negative consequences, perceived action efficacy, perceived severity of COVID-19, access, and perceived divine will. In line with the HBM, beliefs about the disease itself were highly predictive of vaccine acceptance, and some of the strongest statistically-significant (p<0.001) predictors of vaccine acceptance in this population are beliefs around both injunctive and descriptive social norms. Specifically, Acceptors were 3.2 times more likely to say they would be very likely to get a COVID-19 vaccine if a doctor or nurse recommended it, twice as likely to say that most people they know will get a vaccine, and 1.3 times more likely to say that most close family and friends will get a vaccine. The perceived safety of vaccines was found to be important since Non-acceptors were 1.8 times more likely to say that COVID-19 vaccines are "not safe at all". Beliefs about one's risk of getting COVID-19 disease and the severity of it were predictive of being a vaccine acceptor: Acceptors were 1.4 times more likely to say that it was very likely that someone in their household would get COVID-19, 1.3 times more likely to say that they were very concerned about getting COVID-19, and 1.3 times more likely to say that it would be very serious if someone in their household contracted COVID-19. Other responses of Acceptors on what makes immunization easier may be helpful in programming to boost acceptance, such as providing vaccination through government health facilities, schools, and kiosks, and having vaccinators maintain proper COVID-19 health and safety protocols. An effective behavior change strategy for COVID-19 vaccines uptake will need to address multiple beliefs and behavioral determinants, reducing barriers and leveraging enablers identified in this study. National plans for promoting COVID-19 vaccination should address the barriers, enablers, and behavioral determinants found in this study in order to maximize the impact on COVID-19 vaccination acceptance.


De novo assembly and characterization of the transcriptome of the parasitic weed dodder identifies genes associated with plant parasitism.
Parasitic flowering plants are one of the most destructive agricultural pests and have major impact on crop yields throughout the world. Being dependent on finding a host plant for growth, parasitic plants penetrate their host using specialized organs called haustoria. Haustoria establish vascular connections with the host, which enable the parasite to steal nutrients and water. The underlying molecular and developmental basis of parasitism by plants is largely unknown. In order to investigate the process of parasitism, RNAs from different stages (i.e. seed, seedling, vegetative strand, prehaustoria, haustoria, and flower) were used to de novo assemble and annotate the transcriptome of the obligate plant stem parasite dodder (Cuscuta pentagona). The assembled transcriptome was used to dissect transcriptional dynamics during dodder development and parasitism and identified key gene categories involved in the process of plant parasitism. Host plant infection is accompanied by increased expression of parasite genes underlying transport and transporter categories, response to stress and stimuli, as well as genes encoding enzymes involved in cell wall modifications. By contrast, expression of photosynthetic genes is decreased in the dodder infective stages compared with normal stem. In addition, genes relating to biosynthesis, transport, and response of phytohormones, such as auxin, gibberellins, and strigolactone, were differentially expressed in the dodder infective stages compared with stems and seedlings. This analysis sheds light on the transcriptional changes that accompany plant parasitism and will aid in identifying potential gene targets for use in controlling the infestation of crops by parasitic weeds.


[On the centenary of József Török's death (1813-1894) a physician and scientist].
The author investigates the career of József Török (1813-1894), who was a physician, surgeon, and a lecturer in chemistry and sciences at the College of the Reformed Church at Debrecen. Török's reputation was established, nevertheless, by his famous work, the First class medical waters and spas of the two Hungarian homelands. On their natural, chemical and therapeutical power, which he finished in 1847. Török, born in a family of a reformed clergyman, was educated in Debrecen, studied medicine at the university of Pest and spent two years at the universities of Paris, Berlin and Vienna. At Paris he attended the courses of Eluard Chassaignac, at Berlin those of Schönlein and Dieffenbach and at Vienna Rokitansky, Skoda and Hebre were his professors. Though returning to Hungary he practiced as a private doctor and later lectured in dietetics, he was unable--probably owing to his Calvinist faith--to receive a full time post at the university and in 1847 accepted the invitation of the College of Debrecen to lecture in chemistry, botany and mineralogy. He took part as a head physician in legal forensic medicine, and public health. The author emphasizes that Török not only introduced chemistry into secondary school education of human anthropology but created a new curriculum of science for secondary schools as well. His enterprise was a very important innovation in Hungarian public school education. His other main contribution was his famous book on the mineral waters of Hungary, which was awarded by the Hungarian Academy of Sciences in 1847. This balneological work detailed the spas of 19th century Hungary, and--in its second edition in 1859--gave an elaborated bibliography for such books published between 1631-1856. The work was a real breakthrough in Hungarian balneology. The author also investigates the interests of Török in the flora and fauna of the surrounding area of Debrecen, and his geological publications as well.


Dapsone motor neuropathy--an axonal disease.
Dapsone produces a potentially reversible toxic neuropathy, with its primary effect on the soma and axons of motor neurons as opposed to myelin. There is very little evidence to suggest involvement of sensory axons in most cases; if present, it would appear minimal. A "dying back" of motor axons is postulated to produce the clinical features of primarily distal weakness and wasting. Recovery appears to occur via axon regeneration and peripheral sprouting. The sporadic occurrence of this neuropathy may be due to slow acetylation of dapsone in some patients.


Inflammatory and Noninflammatory Itch: Implications in Pathophysiology-Directed Treatments.
Itch is the main chief complaint in patients visiting dermatologic clinics and has the ability to deeply impair life quality. Itch results from activation of cutaneous nerve endings by noxious stimuli such as inflammatory mediators, neurotransmitters and neuropeptides, causing itch signal transduction from peripheral skin, through the spinal cord and thalamus, to the brain cortex. Primarily noninflammatory diseases, such as uremic pruritus, cause itch through certain pruritogens in the skin. In inflammatory skin diseases, atopic dermatitis (AD) is the prototypic disease causing intensive itch by aberrant skin inflammation and epidermal barrier disruption. Recent understanding of disease susceptibility, severity markers, and mechanisms have helped to develop targeted therapy for itch in AD, including monoclonal antibodies against IL-4, IL-13, thymic stromal lymphopoietin (TSLP), IgE and IL-31. Promising effects have been observed in some of them. In this review, we summarized targeted therapies for inflammatory itch in AD and for managing abnormal itch transductions in other common itching skin diseases.


Novel yeast protein kinase (YPK1 gene product) is a 40-kilodalton phosphotyrosyl protein associated with protein-tyrosine kinase activity.
Extracts of bakers' yeast (Saccharomyces cerevisiae) contain protein-tyrosine kinase activity that can be detected with a synthetic Glu-Tyr copolymer as substrate (G. Schieven, J. Thorner, and G.S. Martin, Science 231:390-393, 1986). By using this assay in conjunction with ion-exchange and affinity chromatography, a soluble tyrosine kinase activity was purified over 8,000-fold from yeast extracts. The purified activity did not utilize typical substrates for mammalian protein-tyrosine kinases (enolase, casein, and histones). The level of tyrosine kinase activity at all steps of each preparation correlated with the content of a 40-kDa protein (p40). Upon incubation of the most highly purified fractions with Mn-ATP or Mg-ATP, p40 was the only protein phosphorylated on tyrosine. Immunoblotting of purified p40 or total yeast extracts with antiphosphotyrosine antibodies and phosphoamino acid analysis of 32P-labeled yeast proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the 40-kDa protein is normally phosphorylated at tyrosine in vivo. 32P-labeled p40 immunoprecipitated from extracts of metabolically labeled cells by affinity-purified anti-p40 antibodies contained both phosphoserine and phosphotyrosine. The gene encoding p40 (YPK1) was cloned from a yeast genomic library by using oligonucleotide probes designed on the basis of the sequence of purified peptides. As deduced from the nucleotide sequence of YPK1, p40 is homologous to known protein kinases, with features that resemble known protein-serine kinases more than known protein-tyrosine kinases. Thus, p40 is a protein kinase which is phosphorylated in vivo and in vitro at both tyrosine and serine residues; it may be a novel type of autophosphorylating tyrosine kinase, a bifunctional (serine/tyrosine-specific) protein kinase, or a serine kinase that is a substrate for an associated tyrosine kinase.


Proteic and phenolics compounds contents in Bacupari callus cultured with glutamine and nitrogen sources.
In this study was evaluated the influence of glutamine supplementation on the endogenous content of amino acids, proteins, total phenolics, flavonoids and proanthocyanidins in Bacupari callus. The explants were inoculated in MS medium, MS with half concentration of the nitrogen salts (MS½) and nitrogen-free MS, supplemented with glutamine (5, 10, 30 and 60mM) named as Gln5, Gln10, Gln30 and Gln60. Amino acids and proteins were analyzed after 20, 80 and 140 days and the secondary metabolites on the 140th day. There was no difference in the amino acids on the 20th day. On the 80th day the treatments MS and MS½ presented the lowest levels. On the 140th day MS and MS½ presented the lowest amino acid concentration and Gln10 the highest. Concerning proteins, there was difference only on the 140th day, being the highest concentrations observed in Gln5, and the lowest in MS½ treatment. Total phenolics content was higher in the treatment Gln60 and lowest in MS. Treatments Gln5, Gln10, Gln30 and MS½ were statistically equal. For flavonoids, the highest values occurred in the treatments Gln30, Gln60 and MS½ and the lowest in Gln5, Gln10 and MS. Similarly, for the proanthocyanidins the highest concentrations were observed in treatment Gln60 and the lowest in Gln5 and MS. In conclusion, the treatment with 60mM of glutamine favors the protein accumulation and production of secondary metabolites in Bacupari callus.


Comparison of 30 mCi and 50 mCi I-131 doses for ablation of thyroid remnant in papillary thyroid cancer patients.
To compare efficacy of thyroid remnant ablation using 30 mCi or 50 mCi 131-I in papillary thyroid cancer patients. Five hundred and fifteen consecutive patients with Tumor-Node-Metastasis (TNM) stages T1-T3 N1/N0/NX receiving either 30 mCi or 50 mCi I-131 were analyzed for the effectiveness of remnant ablation using rhTSH-stimulated serum thyroglobulin. One hundred and five consecutive patients receiving 100 mCi I-131 were analyzed for the incidence of radiation thyroiditis and sialadenitis. Doses of 30 mCi and 50 mCi were equally effective for low- and moderate-risk disease but 30 mCi was less effective for T1T2NX disease, and 50 mCi was less effective for T3 compared to T1T2 disease. Low dose radiation hypersensitivity or unknown more extensive disease may have accounted for observed differences. Radiation thyroiditis and sialadenitis were more common in a comparison series of 100 mCi dose compared to 30 mCi, but not more common than in 50 mCi doses.


Reactivity of tumor cells in malignant effusions with a panel of monoclonal and polyclonal antibodies.
A panel of 13 mouse monoclonal antibodies (mAb) and 1 rabbit polyclonal antibody was tested for reactivity with tumor cells in 26 effusions obtained from patients with carcinoma of ovary, breast, or mesothelioma, using an immunoperoxidase staining reaction. Specific staining of tumor cells but not reactive mesothelial cells was demonstrated with some of the mAb in the panel. In 4 of 26 effusions no evidence of malignancy was obtained after routine cytological staining, but this was reversed on the basis of immunoperoxidase staining of tumor cells with the mAb in the panel. Serial effusions were evaluated in 4 patients during the course of chemotherapy, allowing an assessment of effect of therapy on the antigenic characteristics of the tumor cells. In another 4 patients, the results of immunoperoxidase staining of effusions were compared with those obtained by applying the same antibody panel to solid tumor nodules. There was a tendency to develop changes in the pattern of reactivity during therapy, and the pattern of reactivity was more restricted in tumor nodules than in effusions. One of the mAb in our panel (2G3) was consistently shown to produce strong staining of a high proportion of tumor cells in effusions and tumor nodules from patients with ovarian or breast cancer and may be of value in immunocytochemical diagnosis and therapy of epithelial malignancies.