Mimicry of Cellular A Kinase-Anchoring Proteins Is a Conserved and Critical Function of E1A across Various Human Adenovirus Species.
The E1A proteins of the various human adenovirus (HAdV) species perform the critical task of converting an infected cell into a setting primed for virus replication. While E1A proteins differ in both sequence and mechanism, the evolutionary pressure on viruses with limited coding capacity ensures that these proteins often have significant overlap in critical functions. HAdV-5 E1A is known to use mimicry to rewire cyclic AMP (cAMP) signaling by decoupling protein kinase A (PKA) from cellular A kinase-anchoring proteins (AKAPs) and utilizing PKA to its own advantage. We show here that E1As from other species of HAdV also possess this viral AKAP (vAKAP) function and examine how they manipulate PKA. E1A from most species of HAdV examined contain a small AKAP-like motif in their N terminus which targets the docking-dimerization domain of PKA as the binding interface for a conserved protein-protein interaction. This motif is also responsible for an E1A-mediated relocalization of PKA regulatory subunits from the cytoplasm into the nucleus, with species-specific E1A proteins having preference for one particular isoform of PKA subunit over another. Importantly, we showed that these newly characterized vAKAPs can integrate into cAMP-responsive transcription as well as contribute to viral genome replication and infectious progeny production for several distinct HAdV species.IMPORTANCE These data enhance the mechanistic knowledge on how HAdV E1A manipulates cellular PKA to benefit infection. The work establishes that mimicry of AKAPs and subversion of PKA-mediated cAMP signaling are conserved features for numerous human adenoviruses. This study also highlights the molecular determinants conferring selective protein-protein interactions between distinct PKA regulatory subunits and the different E1A proteins of these viruses. Additionally, it further emphasizes the utility of using viral proteins like E1A as tools for studying the molecular biology of cellular regulatory pathways.


A novel de novo frameshift mutation of RPGR ORF15 is associated with X-linked retinitis pigmentosa in a Chinese family.
To identify the genetic basis of disease in a Chinese family with retinitis pigmentosa (RP). Linkage analysis was performed for 15 family members in the RP family using microsatellite markers flanking candidate genetic loci for known autosomal dominant RP (adRP) and markers covering the entire X chromosome by every 10 cM. To screen for a mutation causing RP, PCR and DNA sequence analyses of the complete coding region (including ORF15) and exon-intron boundaries of the retinitis pigmentosa GTPase regulator (RPGR) gene associated with X-linked RP (xlRP) were carried out for the proband in the RP family. After the mutation was identified, direct DNA sequence analysis was preformed for all 15 family members and 101 controls to determine whether the mutation co-segregated with RP in the family and whether it was present or absent in the controls. Linkage analysis excluded all known adRP loci. However, positive linkage was identified with two markers on the X chromosome, DXS993 and DXS1068, where the RPGR gene is located. Direct DNA sequence analysis revealed a hemizygous mutation, g.ORF15+1166delA (c.2919delA), in affected males. The deletion results in a frameshift leading to early termination of RPGR. The g.ORF15+1166delA mutation arose de novo and co-segregated with all male patients, but was not present in normal family members and 101 controls. The clinical features of the mutation carriers showed intrafamilial variability. The novel g.ORF15+1166delA mutation of RPGR causes X-linked RP in a four generation Chinese family. The deletion arose de novo. An interesting feature of mutation g.ORF15+1166delA is that it was associated with RP in all hemizygous males and four of five heterozygous female carriers in the Chinese family. These results revealed the broader xlRP genotypic and phenotypic spectrum of RPGR mutations.


Preparation of two-dimensional magnetic molecularly imprinted polymers based on boron nitride and a deep eutectic solvent for the selective recognition of flavonoids.
New types of two-dimensional (2D) boron nitride (BN) were developed as a 2D scaffold material. After modification with ternary deep eutectic solvents (DES, ChCl-caffeic acid-ethylene glycol), the processed BN was applied to the preparation of magnetic molecularly imprinted polymers (MMIPs). In the polymerization of MMIPs, DESs and hydrophobic Fe3O4 magnetite were applied as the functional monomer and magnetically susceptible component, respectively. A 2D ellipsoid material was formed successfully by polymerization on the surface of the processed BN. The proposed 2D-MMIPs were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and nitrogen sorption analysis techniques. The surface area of the 2D-MMIPs was increased using eco-friendly chemicals. The proposed 2D-MMIPs had a 2D oblate structure and a large surface area. The 2D-MMIPs were used for the preconcentration of flavonoids from Ginkgo biloba leaf extracts. High performance liquid chromatography-ultraviolet analysis revealed that the 2D-MMIPs have higher recoveries for the flavonoids (quercetin 96.8%, isorhamnetin 93.6% and kaempferol 94.8%) in Ginkgo biloba leaves than common MMIPs.


Enhancing the Performance of Perovskite Solar Cells by Hybridizing SnS Quantum Dots with CH3 NH3 PbI3.
The combination of perovskite solar cells and quantum dot solar cells has significant potential due to the complementary nature of the two constituent materials. In this study, solar cells (SCs) with a hybrid CH3 NH3 PbI3 /SnS quantum dots (QDs) absorber layer are fabricated by a facile and universal in situ crystallization method, enabling easy embedding of the QDs in perovskite layer. Compared with SCs based on CH3 NH3 PbI3 , SCs using CH3 NH3 PbI3 /SnS QDs hybrid films as absorber achieves a 25% enhancement in efficiency, giving rise to an efficiency of 16.8%. The performance improvement can be attributed to the improved crystallinity of the absorber, enhanced photo-induced carriers' separation and transport within the absorber layer, and improved incident light utilization. The generality of the methods used in this work paves a universal pathway for preparing other perovskite/QDs hybrid materials and the synthesis of entire nontoxic perovskite/QDs hybrid structure.


Temporary axillary-carotid shunting for unusual instances of carotid stenosis.
A method has been developed which entails the introduction of the larger end of a Javid shunt tube in the axillary artery and the other in the internal carotid with only momentary interruption of blood flow. The method of closing the incision after the thromboendarterectomy almost entirely eliminates a second period of carotid occlusion. This procedure may be useful in unusual instances in which it is believed advantageous to avoid even the relatively short occlusion periods usually necessary when using the standard intraluminal shunt technique.


Screening Eating Disorders Among Female High School Students in Makkah City: A Cross-Sectional Survey.
Eating disorders (EDs) are defined as disturbances in health and psychosocial functioning. They are more predominant in young and adult women and can start at an early age and continue into adulthood. These types of mental illnesses can be prevented with proper training. However, there is a significant lack of understanding of EDs among teachers. Therefore, this study aimed to estimate the prevalence rates of EDs among female high school students in Makkah city. We surveyed 384 female students from high schools in Makkah city in this cross-sectional study using a validated questionnaire adapted from a previously published study after translating it into Arabic. Most of the students had suffered an ED (n=211, 54.4%), while 45.6% had not. There was an insignificant relation between the frequency of EDs and participants' age, nationality, family history of ED, and awareness of EDs (P-value, 0.158, 0.486, 0.671, and 0.718, respectively). Further studies are needed to evaluate the understanding of EDs among the general population as well as assess the prevalence rates of EDs among larger female populations.


The classification of acute leukaemia in childhood.
In 1976 a French, American and British (FAB) cooperative group proposed a morphological classification of acute leukaemia which they hoped would prove more reproducible than previous classification. We present our preliminary experience with this classification, based on a 2-year study of 39 patients. Cytochemical and cell surface marker characteristics of the leukaemic cells were also studied. We found this classification to be satisfactory but some problems were noted in regard to its reproducibility, especially in acute lymphoblastic leukaemia (ALL). Cell surface markers were absent in the majority of cases of ALL ("null cell" type), while the remainder had T-cell characteristics. No B-cell types were seen. Cytochemical staining patterns clearly distinguished ALL from acute myeloid leukaemia (AML) and also helped to categorize AML into its subtypes. The implications of our finding are discussed.


Different Phenotypes at Onset in Neuromyelitis Optica Spectrum Disorder Patients with Aquaporin-4 Autoimmunity.
Although rare, brain abnormalities without optic neuritis (ON) or transverse myelitis (TM) diagnosed with neuromyelitis optica spectrum disorder (NMOSD) have been reported in patients positive for the aquaporin-4 (AQP4) antibody. To analyze demographic and clinical differences among NMOSD patients without ON or TM, those with either ON or TM, and patients with simultaneous ON and TM at disease onset. In this retrospective study, patients who were positive for the AQP4 antibody, as detected using a cell-based assay, at the Second Affiliated Hospital of Guangzhou Medical University in China were recruited. Demographic and clinical data were obtained from each patient's medical record. A total of 292 patients were included in this study and were divided into four subgroups based on their initial manifestations: (i) NMOSD without ON or TM (NMOSD-ON-TM-, n = 70); (ii) NMOSD with ON (NMOSD-ON+, n = 95); (iii) NMOSD with TM (NMOSD-TM+, n = 116); and (iv) simultaneous ON and TM [neuromyelitis optica (NMO), n = 11]. We found that age at onset was lower in the NMOSD-ON-TM- group than that in the other groups. The interval from the first episode to relapse was shorter in the NMOSD-ON-TM- group than that in NMOSD-TM+ group. Cerebral spinal fluid white cell counts and protein levels were significantly higher in the NMOSD-ON-TM- group than those in the other groups. Lower Expanded Disability Status Scale scores were observed in the NMOSD-ON-TM- group. Brain abnormalities, including in area postrema and hemisphere lesions, were more frequent in the NMOSD-ON-TM- group. Kaplan-Meier analysis showed that patients in the NMOSD-ON-TM- group experienced earlier relapse than those in other groups. Conversion to NMO in the NMOSD-ON+ group was greater than that in the other groups. Only 14 patients (4.8%, 14/292) had pure brain abnormalities, of which 12 had disease duration of several more years and 8 (57.1%) experienced relapses. NMOSD patients with different initial manifestations present with significant differences in clinical features during follow-up. Patients with long-term AQP4 autoimmunity in the brain in the absence of ON or TM are not common.


Improving patient satisfaction with waiting time.
Waiting times are a significant component of patient satisfaction. A patient satisfaction survey performed in the author's health center showed that students rated waiting time lowest of the listed categories--A ratings of 58% overall, 63% for scheduled appointments, and 41% for the walk-in clinic. The center used a quality improvement process and instituted schedule and reception area changes. A follow-up survey 3 months later showed A ratings of 73% overall, 81% for scheduled appointments, and 56% for the walk-in clinic. A repeat survey 4 months later showed A satisfaction ratings of 79% overall, 85% for scheduled appointments, and 68% for the walk-in clinic. The author discusses strategies the center used to improve patient satisfaction with waiting time.


Synthesis and activity of Helicobacter pylori urease and catalase at low pH.
Helicobacter pylori produces large amounts of urease presumably to be prepared for the rare event of a sudden acid exposure. The hypothesis that H pylori is acid sensitive and protein production is inhibited by low pH was examined. H pylori or its soluble enzymes were incubated buffered or unbuffered at a pH ranging from 2-7 in the presence of 5 mM urea for 30 minutes. After exposure, urease and catalase activities of whole cells, supernatants, and soluble enzyme preparations were measured at pH 6.8. Newly synthesised enzyme was quantified by immunoprecipitation of [35S]-methionine labelled protein. Exposure to buffer below pH 4 resulted in loss of intracellular urease activity. In soluble enzyme preparations and supernatant, no urease activity was measurable after incubation at pH < 5. In contrast, catalase in whole cells, supernatant, and soluble enzyme preparations remained active after exposure to pH > or = 3. Exposure below pH 5 inhibited synthesis of total protein including nascent urease and catalase. At pH 6 or 7, urease represented 10% of total protein, catalase 1.5%. Exposure of H pylori to unbuffered HCl (pH > 2) resulted in an immediate neutralisation; urease and catalase activities and synthesis were unchanged. Low surrounding pH reduces activity of urease and synthesis of nascent urease, catalase, and presumably of most other proteins. This suggests that H pylori is not acidophilic although it tolerates short-term exposure to low pH.


The Role of Calmodulin vs. Synaptotagmin in Exocytosis.
Exocytosis is a Ca2+-regulated process that requires the participation of Ca2+ sensors. In the 1980s, two classes of Ca2+-binding proteins were proposed as putative Ca2+ sensors: EF-hand protein calmodulin, and the C2 domain protein synaptotagmin. In the next few decades, numerous studies determined that in the final stage of membrane fusion triggered by a micromolar boost in the level of Ca2+, the low affinity Ca2+-binding protein synaptotagmin, especially synaptotagmin 1 and 2, acts as the primary Ca2+ sensor, whereas calmodulin is unlikely to be functional due to its high Ca2+ affinity. However, in the meantime emerging evidence has revealed that calmodulin is involved in the earlier exocytotic steps prior to fusion, such as vesicle trafficking, docking and priming by acting as a high affinity Ca2+ sensor activated at submicromolar level of Ca2+. Calmodulin directly interacts with multiple regulatory proteins involved in the regulation of exocytosis, including VAMP, myosin V, Munc13, synapsin, GAP43 and Rab3, and switches on key kinases, such as type II Ca2+/calmodulin-dependent protein kinase, to phosphorylate a series of exocytosis regulators, including syntaxin, synapsin, RIM and Ca2+ channels. Moreover, calmodulin interacts with synaptotagmin through either direct binding or indirect phosphorylation. In summary, calmodulin and synaptotagmin are Ca2+ sensors that play complementary roles throughout the process of exocytosis. In this review, we discuss the complementary roles that calmodulin and synaptotagmin play as Ca2+ sensors during exocytosis.


Levosulpiride Relieved Persistent Hiccups in a Patient With COVID-19 and Vascular Cognitive Impairment.
The coronavirus disease 2019 (COVID-19) is a systemic illness that implies neurological features and complications. Persistent (>48 hours) hiccups (ie, singultus or hiccoughs) have been recently described as a rare presentation of COVID-19. Even when considered benign, the frequency and duration of hiccup spells can be burdensome and sometimes difficult to treat. We report the case of a 62-year-old man known by the treating physicians for vascular cognitive impairment, who consulted for progressive persistent hiccups that commenced 5 days earlier, about 24 hours after testing positive for the severe acute respiratory syndrome coronavirus 2 by real-time reverse transcription polymerase chain reaction. The patient could barely sleep because the hiccups reached the highest rate of 47 per minute in a spell lasting almost 72 hours. The patient initially received levomepromazine 25 mg by mouth, but sedation and delirium impeded the continuation of treatment, which only reduced the frequency of the hiccup spells by about 25%. Afterward, the patient was offered levosulpiride 25 mg thrice a day by mouth, resulting in a steady reduction in the hiccups rate, as well as the duration and daily frequency of spells, which disappeared after 3 days of levosulpiride treatment. COVID-19 pneumonia was moderate by chest computed tomography scan imaging and biomarkers, meriting continuous oxygen therapy, dexamethasone 6 mg once a day by mouth for 10 days, and enoxaparin 40 mg once a day, subcutaneously, for 7 days (due to elevated D-dimer serum concentration). Oxygen therapy was gradually withdrawn after 12 days. Oral levosulpiride is a suitable option in persistent hiccups that occur in patients with COVID-19 pneumonia. To our knowledge, this is the fourth published case of persistent hiccups as a clinical feature of COVID-19.


Electrochemical characteristics of thin nickel hexacyanoferrate films formed on gold and thiol self-assembled monolayers modified gold electrodes.
Nickel hexacyanoferrate (NiHCF) film was prepared and characterized on gold and thiol self-assembled monolayers (SAMs)-modified gold electrodes. It was found that the film exhibited some different electrochemical characteristics compared with that found on a carbon electrode. In the presence of K+, the film exhibited a redox peak at about 0.5 V. The peak potential shifted linearly with the K+ concentration over the range of about 0.1 mM - 0.1 M with slopes of 54 - 60 mV per log[K+]. However, in solutions containing Na+, Li+ or NH4+ ion the film did not generate well-defined peaks, or even a visible redox peak. Therefore, the film showed a selective potential response to K+. The voltammetric behavior of NiHCF film varied with thiols, the preparation procedure and the solution pH. Under certain conditions, the characteristics of the film could be improved to some extent.


Female physician and pregnancy- effect of the amended German maternity protection act on female doctors' careers.
In Germany, the 2018 amended Maternity Protection Act frequently leads to fundamental restrictions for female physicians, especially surgeons, and now even also for students impeding the progress of their careers. Our goal was to assess the current situation for pregnant female physicians and students, respectively, and their perspective on this amendment regarding their career path. A nationwide survey was conducted in Germany from December 2020 to February 2021. The questionnaire included 790 female physicians and students who were pregnant after the inception of the amended Act. Those women pregnant after the beginning of the corona pandemic were excluded. The survey revealed that two thirds of female physicians worked a maximum of 50% in their previous professional activity as soon as they reported pregnancy. Amongst medical students this amounted up to 72%. 18% of the female physicians and 17% of the female medical students respectively could not follow the sense of these restrictions. 44% of female medical physicians and 33% of female students felt their career impeded. This led up to 43% amongst female medical doctors and 53% amongst female medical students, respectively, who were concerned to announce their pregnancy. As a consequence, pregnancies were reported at 12 weeks in female physicians compared to 19 weeks in medical students. Analyses of the current survey revealed that a relevant number of female physicians and medical students felt impeded in their career path through the application of the amended Maternity Act.


Beta2 adrenergic receptor gene Arg16Gly polymorphism is associated with therapeutic efficacy of benazepril on essential hypertension in Chinese.
There is considerable variability in individual response to antihypertensive agents. The reason for this is not known, but may be related to individual genetic variability. This study examined whether the therapeutic efficacy of benazepril on essential hypertension is modified by beta2 adrenergic receptor gene (ADRB2) Arg16Gly (R16G) polymorphism. We conducted a family-based study of 321 and 610 hypertensive subjects from Yuexi and Huoqiu Counties of Anhui, China, respectively. Both systolic and diastolic blood pressures (SBP and DBP) before and after a 15-day benazepril treatment were measured. ADRB2 R16G genotypes were determined for all subjects. ADRB2 G16 allele frequency was found to be 41.0% and. 47.4% in Huoqiu and Yuexi, respectively. In Yuexi family-based association test (FBAT) revealed that the G16 allele was associated with a greater DBP decrease in response to a 15-day benazepril treatment (Z = 2.12, P = 0.03), and the data were consistent with a dominant inheritance model. A similar trend was observed in Huoqiu Chinese, but the magnitudes of effects were smaller and did not reach statistical significance. The FBAT results were further confirmed by using a generalized estimating equation model. Our family-based study provided the first evidence that ADRB2 R16G polymorphism may play an important role in DBP response to benazepril treatment, although the magnitude of the effect appears to be modified by other risk factors such as plasma lipid and glucose profiles.


Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease.
Th17 is a newly identified T-cell lineage that secretes proinflammatory cytokine IL-17. Th17 cells have been shown to play a critical role in mediating autoimmune diseases such as EAE, colitis, and arthritis, but their role in the pathogenesis of graft-versus-host disease (GVHD) is still unknown. Here we showed that, in an acute GVHD model of C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient, IL-17(-/-) donor T cells manifested an augmented Th1 differentiation and IFN-gamma production and induced exacerbated acute GVHD. Severe tissue damage mediated by IL-17(-/-) donor T cells was associated with increased Th1 infiltration, up-regulation of chemokine receptors by donor T cells, and enhanced tissue expression of inflammatory chemokines. Administration of recombinant IL-17 and neutralizing IFN-gamma in the recipients given IL-17(-/-) donor cells ameliorated the acute GVHD. Furthermore, the regulation of Th1 differentiation by IL-17 or Th17 may be through its influence on host DCs. Our results indicate that donor Th17 cells can down-regulate Th1 differentiation and ameliorate acute GVHD in allogeneic recipients, and that treatments neutralizing proinflammatory cytokine IL-17 may augment acute GVHD as well as other inflammatory autoimmune diseases.


[Proposal of a new assessment scale of work load and nursing times (VACTE].
The scale Nine Equivalents of nursing Manpower use Score (NEMS) for the evaluation of the nursing care loads is the most well known and applied worldwide. Nevertheless, we have found a series of limitations: it does not reflect the "proper nursing activity" but only the cares related to the medical intervention. Furthermore, it is directly related to severity while integral attention to the patient implies an infinity of cares, which are not necessarily related to the severity. In addition, we understand that the planned personnel ratios may be unsuitable, with the consequent repercussions for the patient, nurses and the sanitary institution. The primary targets were: elaboration of a representative scale of all the cares and tasks made by the nurses (VACTE) in our unit, to determine if it is more precise and objective than NEMS for the measurement of the service loads and to calculate the operative ratio patient-nurse based on the new proposed scale. We made a descriptive and retrospective study on 91 patients admitted to the Intermediate Care Unit of the Fundación Hospital de Jove during the first three months of 2004. Previously we created scale VACTE, making real measurements of the time inverted in the execution of each one of the cares in 50 patients. Later, a comparison was made between the APACHE II, NEMS and VACTE scales, taking as reference the scores obtained in the same ones during the first 24 hours of the stay. The statistical analysis was made by SPSS 11.0, assuming a confidence level of 95% (p < 0.05): lineal analysis of simple regression to compare the different scales; the force of its correlation with Spearman's coefficient and we compared the independent dichotomize variables with the Mann-Whitney test. The main results determined after the study were the following: regarding the scale to evaluate seriousness applied to the patients, an average APACHE II score of 12.1 +/- 5.9 was obtained. The average value with the NEMS was 19.5 +/- 5.7 and the average one with VACTE was 365 +/- 91.2. Significant differences were found between APACHE II and the NEMS (p = 0.008) and VACTE (p < 0.001) scales. This relationship presented more force with VACTE (r = 0.43; p < 0.001) than with NEMS (r = 0.23; p = 0.002). The operative patient-nurse ratio calculated with VACTE was 2.01. Scale VACTE is representative of nursing activity and seems to be more effective than NEMS to determine service loads. The ratio planned in the unit duplicated the calculated operative ratio.


Electronic spectroscopy of an isolated halocarbocation: the iodomethyl cation CH2I+ and its deuterated isotopomers.
Building upon our recent observation of the gas-phase electronic spectrum of the iodomethyl cation (CH2I+), we report an extensive study of the electronic spectroscopy of CH2I+ and its deuterated isotopomers CHDI+ and CD2I+ using a combination of fluorescence excitation and single vibronic level (SVL) emission spectroscopies. The spectra were measured in the gas phase under jet-cooled conditions using a pulsed discharge source. Fluorescence excitation spectra reveal a dominant progression in nu3 (C-I stretch), the frequency of which is markedly smaller in the upper state. Rotational analysis shows that, while the A constant is similar in the two states, the excited state has significantly smaller B and C constants. These results indicate a lengthening of the C-I bond upon electronic excitation, consistent with calculations which show that this transition is analogous to the well-known pi-pi* transition in the isoelectronic substituted formaldehydes. SVL emission spectra show progressions involving four of the six vibrational modes; only the C-H(D) stretching modes remain unobserved. The vibrational parameters determined from a Dunham expansion fit of the ground state vibrational term energies are in excellent agreement with the predictions of density functional theory (DFT) calculations. A normal-mode analysis was completed to derive a harmonic force field for the ground state, where resonance delocalization of the positive charge leads to partial double bond character, H2C+-I <--> H2C=I+, giving rise to a C-I stretching frequency significantly larger than that of the iodomethyl radical.


Examining group differences in reliability of multiple-component instruments.
A covariance structure modelling method for examining group differences in scale reliability of multi-component measuring instruments is proposed. The procedure is based on a set of appropriate parameter constraints imposed in a multiple-population structural model. Unlike tests of group differences in coefficient alpha that in general do not evaluate the discrepancies in scale reliability coefficients, the described approach permits one to examine differences in the latter quantities of actual interest when concerned with questions pertaining to reliability of composite scores. The method can be used to test whether a given measuring instrument has identical reliabilities in studied populations, and/or whether distinct instruments, or modes of administration of the same instrument, have equal reliabilities across groups. The proposed procedure is illustrated with a pair of examples.


Isolation and structural characterization of the milled wood lignin, dioxane lignin, and cellulolytic lignin preparations from brewer's spent grain.
The structure of the lignin from brewer's spent grain (BSG) has been studied in detail. Three different lignin preparations, the so-called "milled-wood" lignin (MWL), dioxane lignin (DL), and cellulolytic lignin (CEL), were isolated from BSG and then thoroughly characterized by pyrolysis GC/MS, 2D-NMR, and derivatization followed by reductive cleavage (DFRC). The data indicated that BSG lignin presents a predominance of guaiacyl units (syringyl/guaiacyl ratio of 0.4-0.5) with significant amounts of associated p-coumarates and ferulates. The flavone tricin was also present in the lignin from BSG, as also occurred in other grasses. 2D-NMR (HSQC) revealed that the main substructures present are β-O-4' alkyl-aryl ethers (77-79%) followed by β-5' phenylcoumarans (11-13%) and lower amounts of β-β' resinols (5-6%) and 5-5' dibenzodioxocins (3-5%). The results from 2D-NMR (HMBC) and DFRC indicated that p-coumarates are acylating the γ-carbon of lignin side chains and are mostly involved in condensed structures. DFRC analyses also indicated a minor degree of γ-acylation with acetate groups, which takes place preferentially on S lignin (6% of S units are acetylated) over G lignin (only 1% of G units are acetylated).


Computational estimation of decline in sweating in the elderly from measured body temperatures and sweating for passive heat exposure.
Several studies reported the difference in heat tolerance between younger and older adults, which may be attributable to the decline in the sweating rate. One of the studies suggested a hypothesis that the dominant factor causing the decline in sweating was the decline in thermal sensitivity due to a weaker signal from the periphery to the regulatory centres. However, no quantitative investigation of the skin temperature threshold for activating the sweating has been conducted in previous studies. In this study, we developed a computational code to simulate the time evolution of the temperature variation and sweating in realistic human models under heat exposure, in part by comparing the computational results with measured data from younger and older adults. Based on our computational results, the difference in the threshold temperatures for activating the thermophysiological response, especially for sweating, is examined between older and younger adults. The threshold for activating sweating in older individuals was found to be about 1.5 °C higher than that in younger individuals. However, our computation did not suggest that it was possible to evaluate the central alteration with ageing by comparing the computation with the measurements for passive heat exposure, since the sweating rate is marginally affected by core temperature elevation at least for the scenarios considered here. The computational technique developed herein is useful for understanding the thermophysiological response of older individuals from measured data.


Self-reported mental distress under the shifting daylight in the high north.
The validity of the concept of seasonal affective disorder and the causal link to lack of daylight in winter is controversial. There is a need for investigations in large samples of the general population at different latitudes and within general research contexts to avoid selective response bias and sensitization of the population. During a study of health effects of the air pollution from Russia in a small community at 70 degrees north, a self-administered questionnaire was filled in by 3736 inhabitants, 60.8% of the total population between 18 and 69 years. Three questions concerned depression, sleeping problems and other problems related to the two contrasting seasons with regard to daylight. Twenty-seven per cent reported to have some kind of problem in the dark period. Most frequently reported were sleeping problems during winter, in 19.9% of women and 11.2% of men. Self-reported depression in winter was found in 11.1% of women and 4.8%% of men. Sleeping problems increased with age, while depression was most often reported by middle-aged people. The only other reported problem in winter was fatigue. The adjusted relative risk (RR) for winter depression in women compared to men was 2.5 (95% confidence interval: 1.9-3.2). Very few had problems in summer. In the high north, one-third of the women and one-fifth of the men experience problems with sleep, mood or energy related to season. The prevalence of self-reported depression was surprisingly low in winter considering the lack of daylight.


Regeneration of lithium aluminum hydride.
Lithium aluminum hydride (LiAlH(4)) is a promising compound for hydrogen storage, with a high gravimetric and volumetric hydrogen density and a low decomposition temperature. Similar to other metastable hydrides, LiAlH(4) does not form by direct hydrogenation at reasonable hydrogen pressures; therefore, there is considerable interest in developing new routes to regenerate the material from the dehydrogenated products LiH and Al. Here we demonstrate a low-energy route to regenerate LiAlH(4) from LiH and Ti-catalyzed Al. The initial hydrogenation occurs in a tetrahydrofuran slurry and forms the adduct LiAlH(4).4THF. The thermodynamics of this reversible reaction were investigated by measuring pressure-composition isotherms, and the free energy was found to be small and slightly negative (DeltaG = -1.1 kJ/mol H(2)), suggesting an equilibrium hydrogen pressure of just under 1 bar at 300 K. We also demonstrate that the adduct LiAlH(4).4THF can be desolvated at low temperature to yield crystalline LiAlH(4).


Characterization of MOSFET detectors for in vivo dosimetry in interventional radiology and for dose reconstruction in case of overexposure.
As MOSFET (Metal Oxide Semiconductor Field Effect Transistor) detectors allow dose measurements in real time, the interest in these dosimeters is growing. The aim of this study was to investigate the dosimetric properties of commercially available TN-502RD-H MOSFET silicon detectors (Best Medical Canada, Ottawa, Canada) in order to use them for in vivo dosimetry in interventional radiology and for dose reconstruction in case of overexposure. Reproducibility of the measurements, dose rate dependence, and dose response of the MOSFET detectors have been studied with a Co source. Influence of the dose rate, frequency, and pulse duration on MOSFET responses has also been studied in pulsed x-ray fields. Finally, in order to validate the integrated dose given by MOSFET detectors, MOSFETs and TLDs (LiF:Mg,Cu,P) were fixed on an Alderson-Rando phantom in the conditions of an interventional neuroradiology procedure, and their responses have been compared. The results of this study show the suitability of MOSFET detectors for in vivo dosimetry in interventional radiology and for dose reconstruction in case of accident, provided a well-corrected energy dependence, a pulse duration equal to or higher than 10 ms, and an optimized contact between the detector and the skin of the patient are achieved.


Recent research on inherited metabolic diseases in children.
With the improvement in the research level and the diagnosis and treatment technology of inherited metabolic diseases (IMD), the research on pediatric IMD in China has made great progress, but there is still some distance from the international level. Due to the vast territory of China and the uneven distribution of medical resources, the regional characteristics of IMD remain unclear in China, and there are many problems and difficulties in early diagnosis and treatment. Therefore, it is necessary to improve the understanding of pediatric IMD among pediatricians, so as to improve the diagnosis and treatment level, achieve an early identification, diagnosis, and treatment of pediatric IMD, and effectively reduce the fatality and disability rates of children with IMD. This article reviews the research progress of IMD in children in China, and analyzes the features of representative IMDs. Citation:Chinese Journal of Contemporary Pediatrics, 2022, 24(3): 326-331.


Engineered RebH Halogenase Variants Demonstrating a Specificity Switch from Tryptophan towards Novel Indole Compounds.
Activating industrially important aromatic hydrocarbons by installing halogen atoms is extremely important in organic synthesis and often improves the pharmacological properties of drug molecules. To this end, tryptophan halogenase enzymes are potentially valuable tools for regioselective halogenation of arenes, including various industrially important indole derivatives and similar scaffolds. Although endogenous enzymes show reasonable substrate scope towards indole compounds, their efficacy can often be improved by engineering. Using a structure-guided semi-rational mutagenesis approach, we have developed two RebH variants with expanded biocatalytic repertoires that can efficiently halogenate several novel indole substrates and produce important pharmaceutical intermediates. Interestingly, the engineered enzymes are completely inactive towards their natural substrate tryptophan in spite of their high tolerance to various functional groups in the indole ring. Computational modelling and molecular dynamics simulations provide mechanistic insights into the role of gatekeeper residues in the substrate binding site and the dramatic switch in substrate specificity when these are mutated.


[Update on current care guidelines: melanoma].
This updated guideline focuses on the diagnosis and treatment of cutaneous melanoma. Diagnosis is based on the excision and histopathological analysis of a suspected skin lesion. Definitive surgery should be performed by an experienced surgical unit. Sentinel node biopsy is standard care in the case of clinically nodal-negative patients with intermediate-thickness or thick melanomas. Complete lymph node dissection is performed selectively in the case of sentinel-positive patients. Adjuvant therapy with interferon-alpha can be considered in high-risk patients. The follow-up schedule of an asymptomatic patient can be based on histopathological and clinical prognostic factors.


The acute effects of ionizing radiation on DNA synthesis and the development of antibody-producing cells.
Ionizing radiation inhibited the development of specific haemolysin-producing cells (PFC) and depressed the incorporation of (3H) thymidine by rabbit spleen explants responding to SRC in the culture medium. In contrast to these effects, the rates of incorporation of precursors for protein and RNA synthesis were much less affected. The depression of (3H) thymidine incorporation was found to result from a quantitative reduction of new DNA synthesis, without any change in the proportion of labelled cells, at any time after irradiation. The DNA synthesis occurring in these cells preparing to develop antibody-producing capacity was thus radio-sensitive, but the exact nature of the defect resulting from exposure to radiation requires further study.


Developing a Knowledge Graph for Pharmacokinetic Natural Product-Drug Interactions.
Pharmacokinetic natural product-drug interactions (NPDIs) occur when botanical or other natural products are co-consumed with pharmaceutical drugs. With the growing use of natural products, the risk for potential NPDIs and consequent adverse events has increased. Understanding mechanisms of NPDIs is key to preventing or minimizing adverse events. Although biomedical knowledge graphs (KGs) have been widely used for drug-drug interaction applications, computational investigation of NPDIs is novel. We constructed NP-KG as a first step toward computational discovery of plausible mechanistic explanations for pharmacokinetic NPDIs that can be used to guide scientific research. We developed a large-scale, heterogeneous KG with biomedical ontologies, linked data, and full texts of the scientific literature. To construct the KG, biomedical ontologies and drug databases were integrated with the Phenotype Knowledge Translator framework. The semantic relation extraction systems, SemRep and Integrated Network and Dynamic Reasoning Assembler, were used to extract semantic predications (subject-relation-object triples) from full texts of the scientific literature related to the exemplar natural products green tea and kratom. A literature-based graph constructed from the predications was integrated into the ontology-grounded KG to create NP-KG. NP-KG was evaluated with case studies of pharmacokinetic green tea- and kratom-drug interactions through KG path searches and meta-path discovery to determine congruent and contradictory information in NP-KG compared to ground truth data. We also conducted an error analysis to identify knowledge gaps and incorrect predications in the KG. The fully integrated NP-KG consisted of 745,512 nodes and 7,249,576 edges. Evaluation of NP-KG resulted in congruent (38.98% for green tea, 50% for kratom), contradictory (15.25% for green tea, 21.43% for kratom), and both congruent and contradictory (15.25% for green tea, 21.43% for kratom) information compared to ground truth data. Potential pharmacokinetic mechanisms for several purported NPDIs, including the green tea-raloxifene, green tea-nadolol, kratom-midazolam, kratom-quetiapine, and kratom-venlafaxine interactions were congruent with the published literature. NP-KG is the first KG to integrate biomedical ontologies with full texts of the scientific literature focused on natural products. We demonstrate the application of NP-KG to identify known pharmacokinetic interactions between natural products and pharmaceutical drugs mediated by drug metabolizing enzymes and transporters. Future work will incorporate context, contradiction analysis, and embedding-based methods to enrich NP-KG. NP-KG is publicly available at https://doi.org/10.5281/zenodo.6814507. The code for relation extraction, KG construction, and hypothesis generation is available at https://github.com/sanyabt/np-kg.


Multi-walled carbon nanotubes under focused electron beam: metal passivation effect and nanoscaled curvature effect.
The elongation and length contraction in multi-walled carbon nanotubes without/with metal (Au) nanoparticles under focused electron beam irradiation is in situ studied experimentally at room temperature with transmission electron microscopy. It is observed that the plastic flow and direct evaporation of carbon atoms strongly rely on the nanoscaled negative curvature and surface energy of the nanotubes. The multi-walled carbon nanotubes without metal nanoparticles shrink and elongate by the diffusion and plastic flow of carbon atoms along the shells in the tube axis direction by self contraction of shells. In contrast, multi-walled carbon nanotubes with metal nanoparticles shrink and reduce their lengths by direct evaporation (sputtering) of carbon atoms into the free space under passivation by the metal nanoparticles. Thus, experimental demonstration is provided that the non-uniform structural evolution process in multi-walled carbon nanotubes induced fleetly by the nanoscaled negative curvature effect under athermal activation effect of electron beam passivates by metal nanoparticles.


[Study of electromechanical coupling in smooth muscle cells of the ureter using phenothiazines].
Chlorpromazine (ClP) and trifluoperazine (TFP) depress electrical and mechanical activity of ureter smooth muscle cells. Contraction was depressed by less doses of the substances applied as compared with the processes responsible for generation of spike activity. ClP causes the displacement of the dose-effect curve for Ca2+ towards larger concentrations of the latter. Trifluoperazine displaces the dose-effect curve for contraction to the right and downwards. It is concluded that inhibition of contraction and depression of ClP and TFP spikes is due to the calmodulin blocking on which kinase activity of myosin light chains depends. It is supposed that processes responsible for activation of the membrane systems of Ca2+ transport in the process of spike generation are also calmodulin-dependent.


Expression of the histidine-rich protein PfHRP1 by knob-positive Plasmodium falciparum is not sufficient for cytoadherence of infected erythrocytes.
Six culture-adapted knob-positive Plasmodium falciparum parasites, four of which were nonbinding in an in vitro cytoadherence assay, were tested for the presence of the knob-associated histidine-rich protein PfHRP1. Two knob-positive, strongly cytoadherence-positive P. falciparum strains from Aotus monkeys were also examined. All parasites expressed PfHRP1, suggesting that it plays a structural or functional role related to knobs but is not by itself sufficient for cytoadherence of P. falciparum-infected erythrocytes.


[Quality of life and vegetative status of patients with ulcer disease].
To analyse features of vegetative status of patients with ulcer disease (UD) with reference to quality of life (QL), course of UD, clinical and secretory-motor characteristics. A total of 200 UD patients were examined. UD was at the stage of exacerbation, new-onset, with a favourable or unfavourable course. The vegetative status was studied by parameters of Kerdo index, variation pulsometry, vegetative crises, insomnia. Quality of life (QL) was assessed by a medicosocial questionnaire. The patients were divided into two groups: with satisfactory and unsatisfactory QL. 120 patients had 24-h pH-metry. Among patients with normal QL normotonics and vagotonics prevailed. Low QL was seen in sympathicotonics. Sleep disorders and vegetative crises were in patients with vegetative imbalance, especially in combination with unsatisfactory QL. The worst QL was associated with sympathicotony. Vegetative balance was observed in a favourable UD course, moderate in time duodenogastric reflux (DGR). Sympathicotony runs with marked DGR, vasotony--minimal DGR, scare symptoms. Vegetative dysfunction in UD is due to permanent or paroxysmal vegetative disorders. Sympathicotony is accompanied with dyskinetic pain syndrome and longer duodenogastric reflux which is tolerated bad. Vegetative dystonia is more often in unfavorable course of UD.


Breast cancer and lifestyle risks among Chinese women in the Klang Valley in 2001.
Breast cancer is one of the commonest cancers among women in Malaysia. The relation between lifestyle practices and the risk of breast cancer in Chinese women aged 21-55 years were assessed using data collected from June to October 2001, via a face-to face interview in a case control study in the Breast Clinics of Kuala Lumpur Hospital and University Malaya Medical Centre. A total of 89 cases with breast cancer were compared with 85 controls without the disease. Our study showed that breastfeeding had an odds ratio of 4.43 after adjustment for confounders. The results add to the evidence of a protective association between breast feeding practices and breast cancer particularly among Chinese women receiving treatment at two government hospitals in the Klang Valley.


Tachycardia caused by A2A adenosine receptor agonists is mediated by direct sympathoexcitation in awake rats.
Adenosine-induced tachycardia is suggested to be mediated via A(2A) receptors; however, the exact mechanism for this effect remains to be understood. The present study was carried out using regadenoson, a selective A(2A) adenosine receptor agonist, to determine the role of the A(2A) receptor subtype in adenosine-induced tachycardia. Regadenoson (0.3-50 microg/kg) given as a rapid i.v. bolus to awake rats caused a dose-dependent increase in heart rate (HR). Mean arterial pressure (MAP) increased at lower doses, whereas at higher doses, there was a decrease in MAP. The increase in HR was evident at the lowest dose (0.3 microg/kg) of regadenoson at which there was no appreciable decrease in MAP. Pretreatment with 30 microg/kg ZM 241385 [4-(2-[7-amino-2-(2-furyl)-[1,2,4]-triazolo-[2,3-a]-[1,3,5]-triazin-5-ylamino]ethyl)phenol], an A(2A) receptor antagonist, attenuated the decrease in MAP and the increase in HR caused by regadenoson. Pretreatment with metoprolol (1 mg/kg), a beta-blocker, attenuated the increase in HR but had no effect on the hypotension caused by regadenoson. In the presence of hexamethonium (10 mg/kg), a ganglionic blocker, the tachycardia was completely prevented even though MAP was further reduced. Regadenoson treatment (10 microg/kg) significantly (p < 0.05) increased plasma norepinephrine levels almost 2-fold above baseline. The dissociation of HR and MAP effects by dose, time, and pharmacological interventions provides evidence that tachycardia caused by regadenoson is independent of the decrease in MAP and may not entirely be baroreflex-mediated, suggesting that regadenoson may cause a direct stimulation of the sympathetic nervous system via activation of A(2A) adenosine receptors.


Effect of advance directives on the management of elderly critically ill patients.
To evaluate the effects of advance directives on the management of elderly, critically ill patients. Retrospective chart review. Teaching hospital medical/surgical, noncardiac intensive care unit (ICU). The medical records of 401 patients, > or =65 yrs of age, admitted to the ICU between 1992 and 1995 were reviewed. None. Advance directive statements included refusal of cardiopulmonary resuscitation (CPR), nutrition, intravenous medications, antibiotics, mechanical ventilation, and blood products. Nineteen (5%) patients had advance directives (study group). These patients were compared with 28 case-matched (age, Acute Physiology and Chronic Health Evaluation II score, and diagnosis) critically ill patients without advance directives (control group). We compared the following data: cost per day; number of surgical procedures; number of radiographic studies; number of central venous and pulmonary artery catheter insertions; number of complete blood counts, electrolytes, and cultures sent for laboratory testing; number of days in the ICU/hospital; and mortality rates. Statistical analysis was performed using the Student's t-test for independent means and the chi-square equation. For all observed parameters, quantitative and dichotomous differences between study and control groups were not statistically significant. Two patients received CPR, despite advance directive statements refusing this treatment. Few critically ill seniors have advance directives. As assessed by objectively documented information, the level of care delivered to elderly ICU patients is not affected by the presence or absence of advance directive statements. Medical personnel need to be aware of whether or not patients have advance directive statements, as unauthorized CPR was administered to 11% of the patients who died with advance directives.


Multifunctional Screen-Printed TiO2 Nanoparticles Tuned by Laser Irradiation for a Flexible and Scalable UV Detector and Room-Temperature Ethanol Sensor.
Recently, multifunctional devices printed on flexible substrates, with multisensing capability, have found new demand in practical fields of application, such as wearable electronics, soft robotics, interactive interfaces, and electronic skin design, revealing the vital importance of precise control of the fundamental properties of metal oxide nanomaterials. In this paper, a novel low-cost and scalable processing strategy is proposed to fabricate all-printed multisensing devices with UV- and gas-sensing capabilities. This undertaken approach is based on the hierarchical combination of the screen-printing process and laser irradiation post-treatment. The screen-printing is used for the patterning of silver interdigitated electrodes and the active layer based on anatase TiO2 nanoparticles, whereas the laser processing is utilized to fine-tune the UV and ethanol-sensing properties of the active layer. Different characterization techniques demonstrate that the laser fluence can be adjusted to optimize the morphology of the TiO2 film by increasing the contribution from volume porosity, to improve its electrical properties and enhance its UV photoresponse and ethanol-sensing characteristics at room temperature. Furthermore, results of the UV and ethanol-sensing investigation show that the optimized UV and ethanol sensors have good repeatability, relatively fast response/recovery times, and excellent mechanical flexibility.


Electrospray ionization LC-MS/MS validated method to quantify griseofulvin in human plasma and its application to bioequivalence study.
A simple, sensitive and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and validated to quantify griseofulvin in human plasma using propranolol hydrochloride as internal standard (IS). Samples were prepared using solid phase extraction and analysed without drying and reconstitution. The analytes were chromatographed on Hypersil, hypurity C18 reverse phase column under isocratic conditions using 0.05% formic acid in water:acetonitrile (30:70, v/v) as the mobile phase. Total chromatographic run time was 3.0 min. Quantitation was done on a triple quadrupole mass analyzer API-3000, equipped with turbo ion spray interface and operating in multiple reaction monitoring (MRM) mode to detect parent-->product ion transition for analyte and IS. The method was validated for sensitivity, matrix effect, accuracy and precision, linearity, recovery and stability studies. Linearity in plasma was observed over the concentration range 20-3000 ng/mL for griseofulvin. Lower limit of quantification (LLOQ) achieved was 20 ng/mL with precision (CV) less than 10% using 5 microL injection volume. The absolute recovery of analyte (87.36%) and IS (98.91%) from spiked plasma samples was consistent and reproducible. Inter-batch and intra-batch coefficients of variation across four validation runs (LLOQ, LQC, MQC and HQC) was less than 7.5%. The accuracy determined at these levels was within +/-4.2% in terms of relative error. The method was applied to a pilot bioequivalence study of 500 mg griseofulvin tablet in six healthy human subjects under fed condition.


Rehabilitation and Return to Play Following Meniscus Repair.
Injuries to the meniscus, particularly tears, can have significant negative impacts on pain, function, and quality of life. Preservation of the meniscus is favorable, especially in the athletic and active populations. While first line treatment is often nonoperative in nature, recalcitrant, and more complex tears, typically require surgery. Meniscus repair rates have increased significantly during the last 2 decades as surgical techniques and postoperative outcomes have improved. Longer postoperative timeframes are to be expected when compared with menisectomy, however, accelerated programs have demonstrated favorable outcomes. Rehabilitation and return to play guidelines should reflect the intricacies of the tear type and repair procedure. Close communication with the surgeon is a vital component to optimize patient outcomes. Further, the patient's goals and expected level of return to function, or sport, must be taken into account for a rehabilitation program to be fully successful.


Detection efficiency of auditory steady state evoked by modulated noise.
This study aimed to investigate the efficiency of Magnitude Squared Coherence (MSC) and Spectral F test (SFT) for the detection of auditory steady state responses (ASSR) obtained by amplitude-modulated noises. Twenty individuals (12 women) without any history of neurological or audiological diseases, aged from 18 to 59 years (mean ± standard deviation = 26.45 ± 3.9 years), who provided written informed consent, participated in the study. The Audiostim system was used for stimulating and ASSR recording. The tested stimuli were amplitude-modulated Wide-band noise (WBN), Low-band noise (LBN), High-band noise (HBN), Two-band noise (TBN) between 77 and 110 Hz, applied in intensity levels of 55, 45, and 25 dB sound pressure level (SPL). MSC and SFT, two statistical-based detection techniques, were applied with a significance level of 5%. Detection times and rates were compared using the Friedman test and Tukey-Kramer as post hoc analysis. Also based on the stimulation parameters (stimuli types and intensity levels) and detection techniques (MSC or SFT), 16 different pass/fail protocols, for which the true negatives (TN) were calculated. The median detection times ranged from 68 to 157s for 55 dB SPL, 68-99s for 45 dB SPL, and 84-118s for 25 dB SPL. No statistical difference was found between MSC and STF considering the median detection times (p > 0.05). The detection rates ranged from 100% to 55.6% in 55 dB SPL, 97.2%-38.9% in 45 dB SPL and 66.7%-8.3% in 25 dB SPL. Also for detection rates, no statistical difference was observed between MSC and STF (p > 0.05). True negatives (TN) above 90% were found for Protocols that employed WBN or HBN, at 55 dB SPL or that used WBN or HBN, at 45 dB SPL. For Protocols employing TBN, at 55 dB SPL or 45 dB SPL TN below 60% were found due to the low detection rates of stimuli that included low-band frequencies. The stimuli that include high-frequency content showed higher detection rates (>90%) and lower detection times (<3 min). The noise composed by two bands applied separately (TBN) is not feasible for clinical applications since it requires prolonging the exam duration, and also led to a reduced percentage of true negatives. On the other hand, WBN and HBN achieved high detection performance and high TN and should be investigated to implement pass/fail protocol for hearing screening with clinical population. Finally, both WBN and HBN seemed to be indifferent to the employed technique (SFT or MSC), which can be seen as another advantage of ASSR employment.


Microbiome, holobiont and the net of life.
Holistic emerging approaches allow us to understand that every organism is the result of integration mechanisms observed at every level of nature: integration of DNA from virus and bacteria in metazoans, endosymbiotic relationships and holobionts. Horizontal gene transfer events in Bacteria, Archaea and Eukaryotes have resulted in the chimeric nature of genomes. As a continuity of this genomic landscape, the human body contains more bacterial than human cells. Human microbiome has co-evolved with the human being as a unity called holobiont. The loss of part of our microbiome along evolution can explain the continuous increasing incidence of immune and inflammatory-related diseases. Life is a continuous process in which the organism experiences its environment and this interaction impacts in the epigenetic system and the genomic structure. The emerging perspectives restitute the great importance of Lamarck's theoretical contributions (the milieu) and Darwin's pangenesis theory.


Neural mechanisms of goal-contingent task disengagement: Response-irrelevant stimuli activate the default mode network.
As we experience the world, we must decide not only when and how to act based on input from the environment, but also when to avoid responding in situations where acting could lead to a detrimental outcome. The ability to regulate behavior in this way requires flexible cognitive control, as the same stimulus may call for a response in one context but not in another. In this sense, explicit non-responding can be characterized as an active, goal-directed cognitive process. Little is known about the mechanisms by which a currently active goal state modulates information processing to support the avoidance of undesired responding. In the present study, participants executed or withheld responses to a color target based whether its color matched that of a cue at the beginning of each trial. Behavioral and neural responses to task-irrelevant stimuli appearing as distractors were examined as a function of their relationship to the currently response-relevant color indicated by the cue. We observed a robust pattern in which stimuli possessing the currently response-irrelevant feature activate the default mode network (DMN), which was associated with a behavioral cost on trials in which this stimulus competed with a response-relevant target. Our findings reveal a role for the DMN in goal-directed cognitive control, facilitating active disengagement based on contextually-specific task demands.


Li-Fraumeni Syndrome, A Rarity Among Rarities: A Case Report and Review of Literature.
Li-Fraumeni syndrome (LFS) is a rare inherited cancer susceptibility disorder with a wide tumour spectrum, particularly in children and young adults. Patients with LFS have life-long cancer risk, and the most commonly encountered tumours include soft tissue sarcoma, breast cancer, brain tumours, osteosarcoma, leukaemia and adrenocortical carcinoma. LFS is associated with mutations in the tumour suppressor gene TP53, andnearly two-thirds of families with LFS have this germline mutation. However, the diagnosis of LFS is currently based on recognised strict clinical criteria regardless of the genetic mutation status, as a few families with the clinical characteristics and cancer predisposition of LFS do not have TP53 mutations. Breast cancer is particularly significant among the common malignancies associated with LFS as it is the most common cancer in women worldwide. We present a case of a 27-year-old woman with unilateral breast cancer, in whom further history revealed a brain tumour at the age of 14 years. Due to the early onset of breast cancer and history of childhood malignancy, we suspected LFS. Genetic testing revealed a TP53 mutation, further suggesting the diagnosis of LFS. This has important implications in managing this patient's breast cancer, as the need for risk-reducing mastectomy and arranging a special surveillance programme. It also has great implications for the patient's family members, especially in terms of psychological impact, particularly when the mutation has been detected in children. Also, there is a need for periodic surveillance, which can help in early diagnosis and timely treatment with a more favourable outcome.


[Coverage rates of influenza vaccine in Italy during the 2002/3 and 2003/04 seasons: a cross-sectional study].
The objective of this survey was to assess the level of influenza vaccination coverage in the season 2002/ 2003 compared with the season 2003/2004 in Italy, to understand the drivers and barriers to vaccination and to determine the intention for vaccination for the following winter. We conducted a random-sampling, telephone-based household survey among non-institutionalised individuals representative of the population aged 14 years and above. The surveys for 2002/2003 and 2003/2004 used the same questionnaire and were subsequently pooled. Four target groups were determined for analysis: (1) persons aged 65 years and above; (2) people working in the medical field; (3) persons suffering from a chronic illness and (4) all other groups. The overall sample consisted of 4010 people. The influenza vaccination coverage rate in Italy increased from 19.6% in season 2002/2003 to 22.2% in season 2003/2004. The most frequent reasons mentioned by vaccinees to get vaccinated were advice received from the family doctor or nurse (48.9%), influenza being considered a serious illness which people did not want to contract (38.5%) and not wanting to pass the influenza bug to family and friends (29.2%). Reasons mentioned by never vaccinated people for not getting vaccinated were the fact that people did not consider it before (34.9%), the opinion that one was not very likely to catch influenza (32.2%) and influenza not being a serious illness (23.4%). Options encouraging an influenza vaccination are a recommendation by the family doctor or nurse (58.4%), more available information on the vaccine regarding efficacy and tolerance (34.4%) and more available information on the disease (24.3%). We therefore suggest that family doctors be better informed on influenza vaccine and the disease itself in order to enable them to actively inform their patients on these topics accordingly.


Red Blood Cell Transfusion Need for Elective Primary Posterior Lumbar Fusion in A High-Volume Center for Spine Surgery.
(1) Background: This study evaluated the perioperative red blood cell (RBC) transfusion need and determined predictors for transfusion in patients undergoing elective primary lumbar posterior spine fusion in a high-volume center for spine surgery. (2) Methods: Data from all patients undergoing spine surgery between 1 January 2014 and 31 December 2016 were reviewed. Patients' demographics and comorbidities, perioperative laboratory results, and operative time were analyzed in relation to RBC transfusion. Multivariate logistic regression analysis was performed to identify the predictors of transfusion. (3) Results: A total of 874 elective surgeries for primary spine fusion were performed over the three years. Only 54 cases (6%) required RBC transfusion. Compared to the non-transfused patients, transfused patients were mainly female (p = 0.0008), significantly older, with a higher ASA grade (p = 0.0002), and with lower pre-surgery hemoglobin (HB) level and hematocrit (p < 0.0001). In the multivariate logistic regression, a lower pre-surgery HB (OR (95% CI) 2.84 (2.11-3.82)), a higher ASA class (1.77 (1.03-3.05)) and a longer operative time (1.02 (1.01-1.02)) were independently associated with RBC transfusion. (4) Conclusions: In the instance of elective surgery for primary posterior lumbar fusion in a high-volume center for spine surgery, the need for RBC transfusion is low. Factors anticipating transfusion should be taken into consideration in the patient's pre-surgery preparation.


Treatment Preferences for Active Surveillance versus Active Treatment among Men with Low-Risk Prostate Cancer.
Due to the concerns about the overtreatment of low-risk prostate cancer, active surveillance (AS) is now a recommended alternative to the active treatments (AT) of surgery and radiotherapy. However, AS is not widely utilized, partially due to psychological and decision-making factors associated with treatment preferences. In a longitudinal cohort study, we conducted pretreatment telephone interviews (N = 1,140, 69.3% participation) with newly diagnosed, low-risk prostate cancer patients (PSA ≤ 10, Gleason ≤ 6) from Kaiser Permanente Northern California. We assessed psychological and decision-making variables, and treatment preference [AS, AT, and No Preference (NP)]. Men were 61.5 (SD, 7.3) years old, 24 days (median) after diagnosis, and 81.1% white. Treatment preferences were: 39.3% AS, 30.9% AT, and 29.7% NP. Multinomial logistic regression revealed that men preferring AS (vs. AT) were older (OR, 1.64; CI, 1.07-2.51), more educated (OR, 2.05; CI, 1.12-3.74), had greater prostate cancer knowledge (OR, 1.77; CI, 1.43-2.18) and greater awareness of having low-risk cancer (OR, 3.97; CI, 1.96-8.06), but also were less certain about their treatment preference (OR, 0.57; CI, 0.41-0.8), had greater prostate cancer anxiety (OR, 1.22; CI, 1.003-1.48), and preferred a shared treatment decision (OR, 2.34; CI, 1.37-3.99). Similarly, men preferring NP (vs. AT) were less certain about treatment preference, preferred a shared decision, and had greater knowledge. Although a substantial proportion of men preferred AS, this was associated with anxiety and uncertainty, suggesting that this may be a difficult choice. Increasing the appropriate use of AS for low-risk prostate cancer will require additional reassurance and information, and reaching men almost immediately after diagnosis while the decision-making is ongoing. Cancer Epidemiol Biomarkers Prev; 25(8); 1240-50. ©2016 AACR.


Association between caregiver depression and child after-school program participation.
Depressive symptoms in parents and caregivers to children are associated with adverse biopsychosocial outcomes for caregivers themselves and the children in their custody. Higher overall and parenting-related stress, including stress over children's unsupervised after-school time, is associated with increased caregiver depression risk. Child after-school program participation is a form of social support that may mitigate parenting-related stress and reduce caregiver depression risk. This study tested for the association between child after-school program participation and caregiver depression in a sample of 486 caregivers in Richmond, Virginia. Child after-school program participation was associated with a significant reduction in the likelihood of a past caregiver depression diagnosis (OR = 0.58, 95% CI = 0.39 - 0.86, p = 0.007). This relationship remained significant after adjusting for the influence of caregiver anxiety, stress, financial hardship, and sociodemographic characteristics (OR = 0.49, 95% CI = 0.27 - 0.86, p = 0.015). Child after-school program participation may function as a protective factor that reduces caregiver depression risk. More research is needed to determine whether the observed association is causal in nature and dosage dependent. Findings from this and future studies may be used to inform evaluation of the impact of after-school programs at the family-level.


Some simple epidemic models.
The SARS epidemic of 2002-3 led to the study of epidemic models including management measures and other generalizations of the original 1927 epidemic model of Kermack and McKendrick. We consider some natural extensions of the Kermack-McKendrick model and show that they share the main properties of the original model.


Relevance of chemistry to conservation of isolated populations: the case of volatile leaf components of Dicerandra mints.
Chemical analysis of the essential oils of four congeneric species of mint plant (Dicerandra spp.) endemic to Florida revealed a pattern of chemical similarity and dissimilarity that would not have been predicted on morphological or geographic criteria. Dicerandra christmanii differs fundamentally from its congeners in that it produces fewer compounds and lacks the acyclic components. Yet D. christmanii is more closely similar to Dicerandra frutescens than to other Dicerandra species in morphological characters and geographic range. We conclude that the potential chemical value of a species should not be prejudged on the basis of nonchemical characters and that designation of surplus plant populations by conservationists should be resisted unless such populations have also been chemically studied.


Ultrathin β-Ni(OH)2 nanoplates vertically grown on nickel-coated carbon nanotubes as high-performance pseudocapacitor electrode materials.
Various metal hydroxides/oxides grown on conductive substrates such as nickel foam have been reported and studied as supercapacitor electrode materials. However, the capacitances of these electrodes are extremely limited because of the low content of active materials grown on the limited surface of nickel foam. To achieve high capacitance, we use nickel-coated carbon nanotubes (Ni-CNTs) as the conductive substrate for the growth of β-Ni(OH)2. By a facile chemical method, ultrathin β-Ni(OH)2 nanoplates are vertically grown on the surface of Ni-CNTs. The density, thickness, and content of β-Ni(OH)2 can be easily controlled by modulating the ratio of NiCl2·6H2O to Ni-CNTs. This hierarchical nanostructure can provide remarkable synergistic effects: facilitate electron and ion transport and accelerate the reversible redox reactions. As-prepared Ni-CNTs@β-Ni(OH)2 composites exhibit high specific capacitances (∼1807 F g(-1) at 2 A g(-1), based on the mass of β-Ni(OH)2; ∼1283 F g(-1) at 2 A g(-1), based on the mass of composite), good rate capabilities, and excellent cycling stabilities. This strategy has potential for large-scale production and can be applied to the preparation of other hierarchical nanostructured metal hydroxide/oxide composites.


Radioiodinated human pituitary and amniotic fluid prolactins with preserved molecular integrity;.
Human pituitary prolactin (hPRL) contains a single major component. Upon iodination by a lactoperoxidase procedure approximately 50% of this component remains ulaltered in molecular size and net charge by the criteria of quantitative polyacrylamide gel electrophoresis (PAGE). Aminiotic fluid hPRL contains two components which remained ulaltered after iodination by the lactoperoxidase procedure used. Unaltered iodinated products can also be obtained from both sources by a stoichiometric chloramine T procedure, but in vastly diminished yield.


Katdetectr: an R/bioconductor package utilizing unsupervised changepoint analysis for robust kataegis detection.
Kataegis refers to the occurrence of regional genomic hypermutation in cancer and is a phenomenon that has been observed in a wide range of malignancies. A kataegis locus constitutes a genomic region with a high mutation rate (i.e., a higher frequency of closely interspersed somatic variants than the overall mutational background). It has been shown that kataegis is of biological significance and possibly clinically relevant. Therefore, an accurate and robust workflow for kataegis detection is paramount. Here we present Katdetectr, an open-source R/Bioconductor-based package for the robust yet flexible and fast detection of kataegis loci in genomic data. In addition, Katdetectr houses functionalities to characterize and visualize kataegis and provides results in a standardized format useful for subsequent analysis. In brief, Katdetectr imports industry-standard formats (MAF, VCF, and VRanges), determines the intermutation distance of the genomic variants, and performs unsupervised changepoint analysis utilizing the Pruned Exact Linear Time search algorithm followed by kataegis calling according to user-defined parameters.We used synthetic data and an a priori labeled pan-cancer dataset of whole-genome sequenced malignancies for the performance evaluation of Katdetectr and 5 publicly available kataegis detection packages. Our performance evaluation shows that Katdetectr is robust regarding tumor mutational burden and shows the fastest mean computation time. Additionally, Katdetectr reveals the highest accuracy (0.99, 0.99) and normalized Matthews correlation coefficient (0.98, 0.92) of all evaluated tools for both datasets. Katdetectr is a robust workflow for the detection, characterization, and visualization of kataegis and is available on Bioconductor: https://doi.org/doi:10.18129/B9.bioc.katdetectr.


Cultivation of Spirulina platensis using pig wastewater in a semi-continuous process.
The effluent from anaerobic digestion contains organic nitrogen and phosphorus, which are both required for growth of Spirulina platensis. Effluent (20%) from the upflow anaerobic sludge blanket (UASB) from a pig farm, supplemented with 4.5 g/l sodium bicarbonate (NaHCO(3)) and 0.2 g/l urea fertilizer (46:0:0, N:P:K), was found to be not only a suitable medium for the growth of Spirulina platensis but also a low-cost alternative. Cost calculation showed that this medium is 4.4 times cheaper than modifized Zarrouk's medium. The average productivities of a semi-continuous culture grown under outdoor conditions in a 6-l scale and a 100-l pilot scale were 19.9 g/m2/d and 12 g/m(2)/d, respectively. In addition, the biomass of organisms grown in UASB effluent contained approximately 57.9% protein, 1.12% gamma-linolenic acid, and 19.5% phycocyanin. The average rates of bicarbonate, total nitrogen, and phosphorus removal were 380 mg/l/d, 34 mg/l/d, and 4 mg/l/d, respectively.


Psy-feld: An Innovative Didactic Using the TV Show Seinfeld to Teach Delusional Disorder Subtypes.
The primary purpose of this article is to introduce Psy-feld, an innovative didactic used to review mental disorders through discussion of the interpersonal relationships of the fictional characters created in Larry David's situational comedy, Seinfeld. To introduce this novel didactic, several peripheral Seinfeld characters were selected, who while not afflicted with a psychotic disorder, demonstrate traits that serve to facilitate discussion to review the different subtypes of Delusional Disorder. Psy-feld is a 30-min faculty-facilitated didactic where a selected episode of the sitcom allows for review of multidisciplinary content areas considered germane to the practice of psychiatry. At Rutgers-Robert Wood Johnson Medical School, 104 third-year medical students rotated on the Consultation-Liaison Service from July 2011-March 2014 and participated in Psy-feld. Of the 104 students who participated in Psy-feld, 99 completed surveys on the didactic. Students found the didactic to be of high quality, believed it enhanced their learning, and thought that it prepared them for their final SHELF exam. Students also found it enjoyable and preferred the didactic to more traditional forms of teaching such as large group lectures. Psy-feld is an example of an innovative teaching method that medical students found informative in reviewing teaching points of Delusional Disorder.


Fast growth synthesis of GaAs nanowires with exceptional length.
We report the first synthesis of GaAs nanowires (NWs) by Au-assisted vapor-liquid-solid (VLS) growth in the novel hydride vapor phase epitaxy (HVPE) environment. Forty micrometer long rodlike <111> monocrystalline GaAs nanowires exhibiting a cubic zinc blende structure were grown in 15 min with a mean density of 10(6) cm(-2). The synthesis of such long figures in such a short duration could be explained by the growth physics of near-equilibrium HVPE. VLS-HVPE is mainly based on solidification after direct and continuous feeding of the arsenious and GaCl growth precursors through the Au-Ga liquid catalyst. Fast solidification (170 microm/h) is then assisted by the high decomposition frequency of GaCl. This predominant feeding through the liquid-solid interface with no mass and kinetic hindrance favors axial rather than radial growth, leading to twin-free nanowires with a constant cylinder shape over unusual length. The achievement of GaAs NWs several tens of micrometers long showing a high surface to volume ratio may open the field of III-V wires, as already addressed with ultralong Si nanowires.


Association of baseline steroid use with long-term rates of infection and sepsis in the REGARDS cohort.
Prior studies associate steroid use with infection risk but were limited to select populations and short follow-up periods. The association of steroid use with long-term risk of community-acquired infections is unknown. We sought to determine the association of steroid risk with long-term risks of community- acquired infections and sepsis. We used data on 30,239 adults aged ≥ 45 years old from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was oral or injectable steroid use, determined from medication inventory obtained at baseline in-home visit. The primary outcome was time to first infection event during 2003-2012, determined through adjudicated review of hospital records. We determined associations between baseline steroid use and first infection hospitalization events using Cox proportional hazards models, adjusting for demographics, health behaviors, chronic medical conditions, and medication adherence. Among the first infection hospitalization events, we also determined the association between baseline steroid use and sepsis. Steroid use was reported in 2.24% (n = 677) of the study population. There were 2593 incident infection events during the 10-year follow-up period. Infection incidence rates were higher for steroid than non-steroid users (37.99 vs. 13.79 per 1000 person-years). Steroid use was independently associated with increased risk of infection (adjusted HR 2.10, 95% CI: 1.73-2.56). Among first-infection events, steroid use was associated with increased odds of sepsis (adjusted OR 2.11, 95% CI: 1.33-3.36). The associations persisted in propensity matched analyses as well as models stratified by propensity score and medication adherence. In this population-based cohort study, baseline steroid use was associated with increased long-term risks of community-acquired infections and sepsis.


Expression and regulation of tissue inhibitors of metalloproteinases (TIMP1 and TIMP3) in goat oviduct.
Tissue inhibitors of metalloproteinases (TIMPs) are associated with several reproductive processes, such as mammalian follicular growth, ovulation, CL formation, and embryonic development. However, the expression and function of TIMPs in goat oviducts remain unclear. This work aimed to identify TIMP1 and TIMP3 expression in the goat oviduct during the estrous cycle via immunohistochemistry, real-time polymerase chain reaction (PCR), and functional studies in cultured goat oviductal epithelial cells. Real-time PCR results demonstrated that TIMP1 and TIMP3 messenger RNAs were expressed in all goat oviductal regions at all stages of the estrous cycle. TIMP1 and TIMP3 proteins were also highly expressed in oviductal epithelial cells with very limited expression in other cell types. Oviductal epithelial cells were treated in vitro with various estradiol concentrations (1-100 nM) for 24 hours. The findings showed that TIMP1 expression increased up to 20 nM but then gradually decreased, whereas no significant effects existed among TIMP3 messenger RNA levels. Time-course studies indicated that estradiol significantly increased TIMP1 expression in a time-dependent manner from 8 hours to 24 hours. By contrast, TIMP3 expression was transiently induced in oviductal epithelial cells at 2 and 4 hours after estradiol treatment. Furthermore, treatment with TIMP1 functionally increased the viability of cultured oviductal epithelial cells. Overall, the results suggested that the differential regulation and function between TIMP1 and TIMP3 might be associated with their unique roles in fertilization and early embryonic development.


Application of in silico and in vitro methods in the development of adverse outcome pathway constructs in wildlife.
There is a long history of using both in silico and in vitro methods to predict adverse effects in humans and environmental species where toxicity data are lacking. Currently, there is a great deal of interest in applying these methods to the development of so-called 'adverse outcome pathway' (AOP) constructs. The AOP approach provides a framework for organizing information at the chemical and biological level, allowing evidence from both in silico and in vitro studies to be rationally combined to fill gaps in knowledge concerning toxicological events. Fundamental to this new paradigm is a greater understanding of the mechanisms of toxicity and, in particular, where these mechanisms may be conserved across taxa, such as between model animals and related wild species. This presents an opportunity to make predictions across diverse species, where empirical data are unlikely to become available as is the case for most species of wildlife.


The cell surface-exposed glycopeptidolipids confer a selective advantage to the smooth variants of Mycobacterium smegmatis in vitro.
The cell surface of mycobacteria is quite rich in lipids. Glycopeptidolipids, surface-exposed lipids that typify some mycobacterial species, have been associated with a phenotypic switch between rough and smooth colony morphotypes. This conversion in Mycobacterium smegmatis is correlated with the absence/presence of glycopeptidolipids on the cell surface and is due to insertion sequence mobility. Here, we show that the occurrence of a high amount of glycopeptidolipids in the smooth variant leads to lower invasion abilities and lower internalization by macrophages. We further show that the high production of glycopeptidolipids on the cell surface can confer a selective advantage to the smooth variant when grown in vitro. This higher fitness under the laboratory condition might explain the selection of smooth variants in several independent laboratories. The implications of these findings are discussed.


Exciton photophysics of carbon nanotubes.
The goal of this chapter is to review the importance of excitons to single-wall carbon nanotube (SWNT) optics. We have developed the presentation for both researchers in the SWNT field who want to learn more about the unusual aspects of SWNT exciton photophysics and researchers more knowledgeable about the physics of excitons, but not about SWNT physics. Excitons in SWNTs are special because graphite has two energy bands at the Fermi energy related to time-reversal symmetry and because SWNTs are actually one dimensional. This review discusses both theoretical and experimental points of view, thus aiming to provide a summary of the most important work in the field, as well as to identify open questions.


[Ionizing and non-ionizing radiation (comparative risk estimations)].
The population has widely used mobile communication for already more than 15 years. It is important to note that the use of mobile communication has sharply changed the conditions of daily exposure of the population to EME We expose our brain daily for the first time in the entire civilization. The mobile phone is an open and uncontrollable source of electromagnetic radiation. The comparative risk estimation for the population of ionizing and non-ionizing radiation was carried out taking into account the real conditions of influence. Comparison of risks for the population of ionizing and non-ionizing radiation leads us to a conclusion that EMF RF exposure in conditions of wide use of mobile communication is potentially more harmful than ionizing radiation influence.


Gonorrhea and chlamydia infection among women visiting family planning clinics: racial variation in prevalence and predictors.
Black women are disproportionately infected with gonorrhea and chlamydia. Because of the potential impact of these infections on women's reproductive health, it is important to determine whether different factors are predictive of infection in women of different races. Data from 31,762 women aged 15-24 who were tested for gonorrhea and chlamydia at Missouri family planning clinics in 2001 were used to calculate the prevalence of each infection by selected variables. Logistic regression analysis was used to assess factors associated with the risk of infection. Overall, 0.7% of women had gonorrhea, and 4% had chlamydia. The gonorrhea rate was 4% for blacks and 0.4% for whites; the chlamydia rate, 9% and 4%, respectively. Independent predictors of gonorrhea in both races were symptoms, recent sexual contact with a partner who had STD symptoms, and chlamydia infection. Predictors specific to whites were visiting the clinic for STD care and having a new partner or multiple partners in the past year. Being aged 15-21 was associated with an elevated risk of gonorrhea for blacks only. In both racial groups, chlamydia infection was associated with younger age, contact with a symptomatic partner, cervicitis, cervical friability and gonorrhea positivity. Additional predictors among whites were having a new partner, having multiple partners and having pelvic inflammatory disease; no other factors were significant for blacks. The prevalence and predictors of gonorrhea and chlamydia infection differ significantly between blacks and whites. Until these disparities are better understood, it will be difficult to establish screening criteria for gonorrhea.


Fungal Biofilms and Polymicrobial Diseases.
Biofilm formation is an important virulence factor for pathogenic fungi. Both yeasts and filamentous fungi can adhere to biotic and abiotic surfaces, developing into highly organized communities that are resistant to antimicrobials and environmental conditions. In recent years, new genera of fungi have been correlated with biofilm formation. However, Candida biofilms remain the most widely studied from the morphological and molecular perspectives. Biofilms formed by yeast and filamentous fungi present differences, and studies of polymicrobial communities have become increasingly important. A key feature of resistance is the extracellular matrix, which covers and protects biofilm cells from the surrounding environment. Furthermore, to achieve cell-cell communication, microorganisms secrete quorum-sensing molecules that control their biological activities and behaviors and play a role in fungal resistance and pathogenicity. Several in vitro techniques have been developed to study fungal biofilms, from colorimetric methods to omics approaches that aim to identify new therapeutic strategies by developing new compounds to combat these microbial communities as well as new diagnostic tools to identify these complex formations in vivo. In this review, recent advances related to pathogenic fungal biofilms are addressed.


Sulfotransferase 2B1b in human breast: differences in subcellular localization in African American and Caucasian women.
Breast cancer (BC) is the most commonly diagnosed cancer among American women; however, the development of post-menopausal BC is significantly lower in African Americans as compared to Caucasians. Hormonal stimulation is important in BC development and differences in the conversion of dehydroepiandrosterone (DHEA) into estrogens may be involved in the lower incidence of post-menopausal BC in African American women. DHEA sulfation by sulfotransferase 2B1b (SULT2B1b) is important in regulating the conversion of DHEA into estrogens in tissues. SULT2B1b is localized in both cytosol and nuclei of some tissues including cancerous and associated-normal breast tissue. Immunohistochemical staining was used to evaluate the total expression and subcellular localization of SULT2B1b in African American and Caucasian breast tissues. Cell fractionation, immunoblot analysis and sulfation assays were used to characterize the subcellular expression and activity of SULT2B1b in BC tissues and T-47D breast adenocarcinoma cells. Immunohistochemical analysis of SULT2B1b showed that African Americans had a significantly greater amount of SULT2B1b in epithelial cells of associated-normal breast tissue as compared to Caucasians. Also, more SULT2B1b in African American associated-normal breast epithelial cells was localized in the nuclei than in Caucasians. Equivalent levels of SULT2B1b were detected in breast adenocarcinoma tissues from both African American and Caucasian women. Nuclei isolation and immunoblot analysis of both BC tissue and human T-47D breast adenocarcinoma cells demonstrated that SULT2B1b is present in nuclei and cytoplasm.


Complement in asthma: sensitivity to activation and generation of C3a and C5a via the different complement pathways.
Studies in rodent models suggested that complement may play a critical role in susceptibility to airway hyperresponsiveness (AHR) and as a mediator of bronchial obstruction and inflammation in asthma. Complement may participate in susceptibility to asthma because of an intrinsic abnormality in complement activation and generation of C3a, C5a, or other products that affect cellular responses, resulting in T(H)2 predominance and asthma susceptibility. Alternatively, an intrinsic abnormality in the cellular response to complement activation products could determine susceptibility to asthma. In this study, the authors investigated whether complement in patients with atopic asthma versus nonatopic controls possesses an increased propensity to become activated. Despite reports that total complement plasma levels in unchallenged asthmatics are normal, an abnormal sensitivity of complement to activation may exist if an isoform or a polymorphic variant of a complement protein was present and resulted in gain or loss of function without associated changes in total complement levels. Therefore, complement activation was induced in vitro in plasma of asthmatics and controls using activators of the classical, alternative, and lectin pathways and measured C3a, other C3 fragments, and C5a. For each pathway, similar amounts of generated fragments, as well as C3a/C3 and C5a/C5 ratios, were found in asthmatics and controls. Also, similar basal plasma levels of C3a and C5a were found in both groups; however, mannan-binding lectin (MBL) levels were moderately elevated in asthmatics. In conclusion, the results suggest that, in asthmatic patients, complement activation does not exhibit an abnormal sensitivity to activation by any of the known activation pathways.


[The diagnosis of pleural diseases with a fiberbronchoscope under open pneumothorax].
Thoracoscopy, using a fiberbronchoscope under open pneumothorax, was performed in 27 cases suffering from pleural diseases undiagnosed. The overall diagnostic rate was 92.3%. The items observed included pulse rate, respiration rate, blood pressure, blood gas analysis, electrocardiography and thoracic pressure measure. It was found that this method has little influence on cardiopneumatic function, no harm fiberbronchoscope, and is simple and safe.


Exogenous peritonitis.
A syndrome of abdominal pain, intestinal obstruction, weight loss, and fever can be caused by adhesions from granulomatous peritonitis. Contamination of the abdominal cavity at operation by cotton lint from disposable surgical drapes and laparotomy pads appears to be the etiological factor. Exogenous granulomatous peritonitis has been virtually ignored as a cause of postoperative intestinal obstruction, but we recognized three cases in the same community hospital during a 6-month period. Special stains and characteristic morphology identified the offending agent. Some patients may require corticosteroids or nonsteroidal anti-inflammatory drugs, such as indomethacin, to prevent recurrence of the syndrome.


Semantic and phonological priming in schizophrenia.
This study of 70 schizophrenic patients used a lexical decision task involving the recognition of words that were preceded (primed) either by meaningfully or phonologically associated or by nonassociated words to study the intrusion of contextually inappropriate associations in thought disorder (TD). The patients were split into subgroups of TD and non-TD patients, and the data from these two groups were compared with data from 44 normal control participants. TD schizophrenic patients exhibited more semantic priming than non-TD patients and controls, and differences in phonological priming dependent on stimulus onset asynchrony (SOA) were obtained. Results support the hypotheses of an increase in activation or a decrease in inhibition in the spreading of semantic and phonological associations in TD schizophrenic patients.


Radiographic temporomandibular joint abnormalities in patients with juvenile chronic arthritis during a controlled study of sodium aurothiomalate and D-penicillamine.
Sixty-two patients with juvenile chronic arthritis (JCA) were randomized to 50-week treatment with either sodium aurothiomalate (G) or D-penicillamine (PEN) and followed with regard to radiographic changes of the temporomandibular joints (TMJ). The radiographic methods comprised panoramic radiography and oblique lateral transcranial radiography, occasionally supplemented with other methods. The radiographs were read by a single assessor who did not know the type of drug treatment. Radiographic progression was seen in one G-treated and six PEN-treated patients with polyarticular JCA, and in one G-treated patient with pauci-articular JCA. A relation between changes in radiographic TMJ findings and disease activity was demonstrated. Radiographic examination of the TMJ seems to be of value in therapeutic trials in patients with JCA.


Genome Sequences of the First WHO Repository of Platelet Transfusion-Relevant Bacterial Reference Strains.
To develop novel techniques for improving blood safety, dedicated bacterial strains, which are able to persist and to proliferate in blood platelet concentrates, are needed. Here, we present draft genome sequences of the four bacterial strains approved for the first WHO repository of platelet transfusion-relevant bacterial reference strains.


Conversion of lignocellulosic agave residues into liquid biofuels using an AFEX™-based biorefinery.
Agave-based alcoholic beverage companies generate thousands of tons of solid residues per year in Mexico. These agave residues might be used for biofuel production due to their abundance and favorable sustainability characteristics. In this work, agave leaf and bagasse residues from species Agave tequilana and Agave salmiana were subjected to pretreatment using the ammonia fiber expansion (AFEX) process. The pretreatment conditions were optimized using a response surface design methodology. We also identified commercial enzyme mixtures that maximize sugar yields for AFEX-pretreated agave bagasse and leaf matter, at ~ 6% glucan (w/w) loading enzymatic hydrolysis. Finally, the pretreated agave hydrolysates (at a total solids loading of ~ 20%) were used for ethanol fermentation using the glucose- and xylose-consuming strain Saccharomyces cerevisiae 424A (LNH-ST), to determine ethanol yields at industrially relevant conditions. Low-severity AFEX pretreatment conditions are required (100-120 °C) to enable efficient enzymatic deconstruction of the agave cell wall. These studies showed that AFEX-pretreated A. tequilana bagasse, A. tequilana leaf fiber, and A. salmiana bagasse gave ~ 85% sugar conversion during enzyme hydrolysis and over 90% metabolic yields of ethanol during fermentation without any washing step or nutrient supplementation. On the other hand, although lignocellulosic A. salmiana leaf gave high sugar conversions, the hydrolysate could not be fermented at high solids loadings, apparently due to the presence of natural inhibitory compounds. These results show that AFEX-pretreated agave residues can be effectively hydrolyzed at high solids loading using an optimized commercial enzyme cocktail (at 25 mg protein/g glucan) producing > 85% sugar conversions and over 40 g/L bioethanol titers. These results show that AFEX technology has considerable potential to convert lignocellulosic agave residues to bio-based fuels and chemicals in a biorefinery.