A novel methodology for enhanced and consistent heterologous expression of unmodified human cytochrome P450 1B1 (CYP1B1).
Cytochrome P450 1B1 (CYP1B1) is a universal cancer marker and is implicated in many other disorders. Mutations in CYP1B1 are also associated with childhood blindness due to primary congenital glaucoma (PCG). To understand the CYP1B1 mediated etiopathology of PCG and pathomechanism of various cancers, it is important to carry out its functional studies. Heterologous expression of CYP1B1 in prokaryotes is imperative because bacteria yield a higher amount of heterologous proteins in lesser time and so the expressed protein is ideal for functional studies. In such expression system there is no interference by other eukaryotic proteins. But the story is not that simple as expression of heterologous CYP1B1 poses many technical difficulties. Investigators have employed various modifications/deletions of CYP N-terminus to improve CYP1B1 expression. However, the drawback of these studies is that it changes the original protein and, as a result, invalidates functional studies. The present study examines the role of various conditions and reagents in successful and consistent expression of sufficient quantities of unmodified/native human CYP1B1 in E. coli. We aimed at expressing CYP1B1 in various strains of E. coli and in the course developed a protocol that results in high expression of unmodified protein sufficient for functional/biophysical studies. We examined CYP1B1 expression with respect to different expression vectors, bacterial strains, types of culture media, time, Isopropyl β-D-1-thiogalactopyranoside concentrations, temperatures, rotations per minute, conditioning reagents and the efficacy of a newly described technique called double colony selection. We report a protocol that is simple, easy and can be carried out in any laboratory without the requirement of a fermentor. Though employed for CYP1B1 expression, this protocol can ideally be used to express any eukaryotic membrane protein.


The NEXUS criteria: do they stand the test of time?
The National Emergency X-ray Utilisation Study (NEXUS) criteria and the Canadian cervical spine rules are validated clinical decision-making tools used to facilitate selective cervical spine (C-spine) radiography. The NEXUS criteria are frequently used, as the Canadian cervical spine rules have been noted to be difficult to learn, remember and implement. We present a series of significant C-spine injury in three elderly patients who would not have warranted C-spine imaging using the NEXUS criteria. Each patient was mobile and fully orientated after the injury. There was no midline tenderness, neurological deficit, distracting injury or alcohol/drug involvement. Plain film imaging was initially performed as each patient had a reduced range of movement. Significant odontoid peg injury was confirmed on subsequent computed tomography/MRI imaging for all patients. Despite previous validation studies of the NEXUS criteria in the elderly population, we would urge caution in using the NEXUS criteria alone in determining radiography of the C-spine in the elderly.


Detection of HIV seropositivity during an outbreak of Japanese encephalitis in Manipur.
An epidemic outbreak of Japanese encephalitis (JE) occurred during mid 1995. Sixteen serum samples from patients with history of febrile headache, convulsions, mental confusion, neck rigidity etc. were sent to the Department of Virology, School of Tropical Medicine, Calcutta, in August, 1995. Twelve (75%) showed HIV antibody against JEV. Out of these 12 sera showing HIV antibody titre between 1:40 and 1:160, eight (66.6%) showed IgM antibody, giving the presumptive diagnosis of recent JEV infection. Five of these 16 sera showed HIV seropositivity (31.25%). Concomitant JEV and HIV infection could be detected in 3 cases. However, in 2 sera HIV titre were less than 1:20. This is probably the first documentation of concomitant JEV and HIV infection in the eastern India.


Redescription of the male of Ixodes festai Rondelli, 1926 (Ixodida: Ixodidae) on specimens from Sardinia (Italy).
Ixodes festai Rondelli, 1926 is a poorly known bird parasite tick. Its immature forms have not been described yet, while the adult forms only insufficiently, especially the male. In this note the presence of the male of Ixodes festai for the first time in Sardinia (Italy) is reported and a detailed redescription is provided. Morphometric data as well as photographs performed both with optical and electron microscope (ESEM FEI Quanta 200) are also shown.


Steps to Better Cardiovascular Health: How Many Steps Does It Take to Achieve Good Health and How Confident Are We in This Number?
Pedometers and other types of step-counting devices are growing in popularity with both researchers and practitioners. The focus of this article is on describing the most recent pedometer-related advances in terms of cardiovascular health. The emergent body of evidence suggests that pedometer-determined physical activity is related to a number of cardiovascular health outcomes and that intervention participants can realize modest changes in body mass index and blood pressure. Taking into consideration individual baseline values, tailored messages congruent with public health recommendations should promote incremental increases in steps/day on the order of an extra 3,000 to 4,000 (approximately 30 min) of at least moderate intensity and taken in at least 10-minute bouts. Additional health benefits accrue with greater increases. Of course, even more benefits are possible from engaging in vigorous physical activity, but this seems less appealing for most people. Pedometer-based guidelines are not intended to supplant existing public health recommendations, but rather supplement them.


Particle analysis of shape factors according to American Society for Testing and Materials.
Polyethylene wear is one of the major factors influencing the survivorship of joint replacements. Depending on the number, size and morphology of the polyethylene particles, biological responses of the periprosthetic soft tissue in terms of inflammatory processes can occur, leading to loosening of the implant. Various parameters are used to analyze wear particles, which are usually determined by examining scanning electron microscopy (SEM) images with a particle analysis program. In this study, three different software solutions for particle analysis (self-developed Particleanalyzer_HD, Leica QWin and ImageJ) were compared regarding particle number, size and morphology. These solutions were also compared to the American Society for Testing and Materials (ASTM) F1877-16 specifications regarding particle morphology. SEM image analysis revealed no differences for the equivalent circle diameter (p = 0.969). However, a significant difference was found for the aspect ratio between the Particleanalyzer_HD and the other two software solutions (p < 0.001) and between Leica QWin and the other two software solutions regarding the roundness (p < 0.001). Only the Particleanalyzer_HD showed an excellent agreement with the ASTM standard for both morphology parameters (intraclass correlation = 1.000). Only the Particleanalyzer_HD calculated the two morphology parameters according to the ASTM standard. A comparison of the particle morphology between different studies is barely possible, as different algorithms for particle analysis are used. It is strongly recommended that the calculation according to the ASTM standard is used to improve future comparability of findings from wear analysis studies. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:225-233, 2020.


Phytotherapy of High Blood Pressure in Three Phytogeographic Regions of Cameroon.
High blood pressure is a public health challenge worldwide. According to World Health Organization, 30% of men and 50% of women 65 to 75 years old are suffering from high blood pressure. The number of hypertensive patients in the world will attain 1.56 billion of people, with 60% increase in prevalence. The incidence of high blood pressure increases with age, but nowadays, is being noticed an increasing incidence in young people. The socio-cultural medicine may provide new solutions in the management of this pathology. Therefore this study was carried out to record and document plants used against high blood pressure in socio-cultural medicine for future drugs discovery worldwide. An ethno botanical survey was realized between 2002 and 2016 to identify manifold plants used to fight against high blood pressure. This survey was carried out in three phytogeographic regions of Cameroon. Amongst people living in those regions, 1131 randomly screened interviewees distributed in 58 socio-cultural groups were involved in this study. This survey reveals that about 70% of interviewees don't know high blood pressure which is a symptomless disease. A total of 28 species of plants were recorded. These plants belong to 25 genera and 24 families. They were used to prepare 28 herbal remedies for the treatment of high blood pressure. In the morphological point of view about 10/28 (36%) plants are herbs; 9/28 (32%) plants are trees and 9/28 (32%) plants are shrubs. Only 3/28 plants (11%) used including Allium sativum, Aloe barteri and Aloe buttneri) are cultivated. This means that the plants used in this study don't usually have some form of protection through cultivation which is encouraging in terms of their conservation. The uncontrolled use of a hypotensive plants can provoke a fatal hypotension in hypertensive patients. Therefore the use of hypotensive plants needs to be controlled by physician or by a patient verification using a blood pressure monitor. Recorded species which will slow the high blood pressure will be used for the preparation of phytodrugs.


Opiate Analgesia Treatment Reduced Early Inflammatory Response After Severe Chest Injuries.
The frequency of severe chest injuries are increased. Their high morbidity is followed by systemic inflammatory response. The efficacy of pharmacological blockade of the response could prevent complications after chest injures. The aim of the study was to show an inflammatory response level, its prognostic significant and length of hospital stay after chest injures opiate analgesia treatment. Sixty patients from Department of Thoracic Surgery with severe chest injures were included in the prospective study. With respect of non opiate or opiate analgesia treatment, the patients were divided in two groups consisted of 30 patients. As a inflammatory markers, serum values of leukocytes, neutrophils, C-reactive protein (CRP) and fibrinogen in three measurements: at the time of admission, 24hours and 48 hours after admission, were followed. Statistically significant differences were found between the examined groups in mean serum values of neutrophils (p=0.026 and p=0.03) in the second and the third measurement, CRP (p=0.05 and 0.25) in the second and the third measurement and leukocytes in the third measurement (p=0.016). 6 patients in group I and 3 in group II had initial stage of pneumonia, 13 patients in group I and 6 in group II had atelectasis and 7 patients from group I and 4 from group II had pleural effusion. The rate of complications was lower in group of patient who were under opiate analgesia treatment but without significant difference. The length of hospital stay for the patients in group I was 7.3±1.15 days and for the patients in group II it was 6.1±0.87 days with statistically significant difference p=0.017. The opiate analgesia in patients with severe chest injures reduced level of early inflammatory response, rate of intra hospital complications and length of hospital stay.


Infantile hemangioendothelioma of the pericranium presenting as an occipital mass lesion. Case report.
The case of a newborn infant with a large midline mass in the occipital region is presented. Skull x-ray films demonstrated multiple radiolucent defects in the occipital bone. A computerized tomography scan revealed an extracranial mass lesion with marked contrast enhancement. A magnetic resonance image demonstrated that the venous drainage of the lesion passed through the occipital bone into the dural venous sinuses. The anatomy of the hindbrain was normal. The neonate was treated by complete surgical removal of the mass. The histopathological diagnosis was infantile hemangioendothelioma, a tumor commonly found in the liver but rarely in this location. The classification, histopathological characteristics, imaging studies, and treatment of this tumor are discussed.


Respiratory-related recruitment of the masseter: response to hypercapnia and loading.
To test the hypothesis that a muscle that closes the jaw, the masseter, can be recruited by ventilatory stimuli, we studied the electromyographic activation of the masseter and genioglossus in seven normal awake males who were exposed in random order to progressive hyperoxic hypercapnia, inspiratory threshold loading (-40 cmH2O), and combined hypercapnia and loading. With hypercapnia, the masseter was generally recruited after the genioglossus had been activated. Once recruited, activation of both muscles increased linearly with increasing CO2. Combined hypercapnia and loading produced more activation than either stimulus alone. These data indicate that the masseter is activated by ventilatory stimuli that activate the genioglossus. Earlier recruitment of the genioglossus suggests that activation of the masseter serves to stabilize the mandible and allow the genioglossus to function as a more efficient dilator of the upper airway.


Molecular control and function of endoreplication in development and physiology.
Endoreplication, also called endoreduplication, is a cell cycle variant of multicellular eukaryotes in which mitosis is skipped and cells repeatedly replicate their DNA, resulting in cellular polyploidy. In recent years, research results have shed light on the molecular mechanism of endoreplication control, but the function of this cell-cycle variant has remained elusive. However, new evidence is at last providing insight into the biological relevance of cellular polyploidy, demonstrating that endoreplication is essential for developmental processes, such as cell fate maintenance, and is a prominent response to physiological conditions, such as pathogen attack or DNA damage. Thus, endoreplication is being revealed as an important module in plant growth that contributes to the robustness of plant life.


Phenotype-directed clinically driven low-dose direct oral anticoagulant for atrial fibrillation.
Clinically-driven dose reduction of direct oral anticoagulants in individuals with atrial fibrillation is prevalent worldwide. However, a paucity of evidence to tailor dose selection remained as clinical unmet need. Current doses of anticoagulant were determined largely by landmark clinical trials, in which the enrolled subjects were carefully selected and without major comorbidities. Our study reviewed the relevant real-world studies in specific patient phenotypes, including renal and hepatic diseases, elderly, low body weight, Asians and presence of concomitant drug-drug interactions. Thorough investigations toward the efficacy and safety of direct oral anticoagulants in reduced doses will facilitate substituting current universal approach with individualized prescriptions.


Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation.
DNase II digests the chromosomal DNA in macrophages after apoptotic cells and nuclei from erythroid precursors are engulfed. The DNase II-null mice develop a polyarthritis that resembles rheumatoid arthritis. Here, we showed that when bone marrow cells from the DNase II-deficient mice were transferred to the wild-type mice, they developed arthritis. A deficiency of Rag2 or a lack of lymphocytes accelerated arthritis of the DNase II-null mice, suggesting that the DNase II(-/-) macrophages were responsible for triggering arthritis, and their lymphocytes worked protectively. A high level of TNFα, IL-1β, and IL-6 was found in the affected joints of the DNase II-null mice, suggesting an inflammatory-skewed cytokine storm was established in the joints. A lack of TNFα, IL-1β, or IL-6 gene blocked the expression of the other cytokine genes as well and inhibited the development of arthritis. Neutralization of TNFα, IL-1β, or IL-6 had a therapeutic effect on the developed arthritis of the DNase II-null mice, indicating that the cytokine storm was essential for the maintenance of arthritis in the DNase II-deficient mice. Methotrexate, an antimetabolite that is often used to treat patients with rheumatoid arthritis, had a therapeutic effect with the DNase II-null mice. These properties of arthritis in the DNase II-null mice were similar to those found in human systemic-onset juvenile idiopathic arthritis or Still's disease, indicating that the DNase II-null mice are a good animal model of this type of arthritis.


["Xingnao Kaiqiao" Needling Stimulation Promotes Resuscitation of General Anesthesia Patients Undergoing Anodynia Gastrointestinal Endoscopy].
To observe the effect of "Xingnao Kaiqiao" needling on the recovery of general anesthesia in mid-aged and elderly patients undergoing painless gastrointestinal endoscopy. A total of 140 patients were randomly divided into control and treatment groups, with 70 cases in each group. After termination of the endoscopy, patients of the treatment group received acupuncture stimulation of Neiguan (PC 6), Shuigou (GV 26) and Sanyinjiao (SP 6) with sterilized disposable filiform needles which were manipulated with twirling-reducing method for 3 min in PC 6, with lifting-thrusting reinforcing method in SP 6, and with bird-peck needling in GV 26. The patients of the control group were not given any treatment. Before, the immediate time of termination of the endoscope examination, resuscitation and 10 min after the endoscope examination, the mini-mental state examination (MMSE) scores were obtained to assess the patients' recognition function. The Bi-spectral Index (BIS) values were recorded to assess the patients' depth of sedation and anesthesia, and the Observer's Assessment of Alertness/Sedation Scale (OAA/S) was used to evaluate the resuscitation/sedation level. Compared with the control group, the MMSE score of the treatment group was significantly higher at the 10th min after endoscope examination (P<0.05),suggesting an improvement of the cognitive function after acupuncture intervention. The duration from general anesthetic state (BIS values=40-60 points) to mild sedation (BIS values=80-90 points) was significantly shorter in the treatment group than in the control group (P<0.05). No significant differences were found between the two groups in the OAA/S score at the 10th min after endoscope (P>0.05). "Xingnao Kaiqiao" needling stimulation has a significant effect on the recovery of middle-aged and elderly patients undergoing painless gastroscopy during general anesthesia.


[Team work in nursing: systematic literature review].
The comprehension of the real meaning of team is fundamental, and even necessary for a good and efficient quality in healthcare with, requiring collective involvement of the nursing team. The present article aims to identify and to analyze the national scientific production in Nursing area about team work over the period from 1992 to 2002. It is a literature review proceeded using seven nursing journals. Twenty-four articles concerning the subject were identified and analyzed, with major occurrence in the year of 1997. In the remaining years production is linear and less expressive regarding to publication by year. The issue most emphazised by authors as an estrategic tool and essential in team interaction, was communication.


Nail Unit Blue Nevi: A 11-Case Series and Review of the Literature.
Blue nevus of the nail apparatus is a rare entity and only isolated cases are reported in the literature. The aim of this study was to better characterize blue nevus at the nail unit. Retrospective analysis of all nail unit blue nevi from the Nail Group of the French Society of Dermatology was compared to the literature. Eleven cases were retrieved from 2002 to 2019 with an average age of 45 years. The majority were women (9/11) and acquired (10/11). Hands were more frequently involved (9/11) with a predilection for the thumb and 2 cases were located on the hallux. Nail unit blue nevus mostly presented as a well-delimited blue spot of the lunula (9/11) and histologically was of the common type (10/11). There was no malignancy. Nail unit blue nevus is a rare asymptomatic benign entity, mostly acquired on the thumb or the hallux of women. The most frequent presentation is a painless blue spot on the lunula. Congenital blue nevi seem to only affect the paronychium. Main differential diagnosis is melanoma and histopathological examination is mandatory.


Seroprevalence of hepatitis E virus immunoglobulin G and M antibodies in adults: a hospital-based study.
Sporadic cases of Hepatitis E virus (HEV) infection occur throughout the year in Pakistan. The aim of this study was to determine the prevalence of HEV immunoglobulin (Ig) G and IgM antibodies in 93 hepatitis B and C-negative patients as such patients are not routinely tested further despite having signs and symptoms of hepatitis. Anti-HEV IgG and IgM were detected by the enzyme-linked immunosorbant assay technique. Among them five patients (5.4%) were positive for HEV IgG and IgM, with an average age of 30.95 +/- 15.35 years. Hepatitis E infection was independent of the sex. Liver function tests of hepatitis E-positive IgG and IgM patients showed increased values of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase and bilirubin that indicate damaged hapatocytes and malfunctioning of the liver.


Comparing outcomes in poorly-differentiated versus anaplastic thyroid cancers treated with radiation: a surveillance, epidemiology, and end results analysis.
Poorly differentiated thyroid carcinoma (PDTC) and anaplastic thyroid carcinoma (ATC) are considered the most aggressive cancers of the head and neck. The aim of the study was to evaluate and compare survival outcomes in PDTC and ATC in a large population-based cohort. Patients with PDTC and ATC diagnosed from 1973 to 2008 were obtained from Surveillance, Epidemiology, and End RESULTS database. Kaplan-Meier survival analysis and log-rank analyses were performed to evaluate (1) The effect of histology on cause-specific survival (CSS) and (2) the influence of factors such as treatment, treatment sequence, race, sex, and age on CSS. Multivariate analysis was performed to assess the independent effect of these factors on CSS. A total of 1352 patients with PDTC and ATC were identified. PDTC constituted 52.4% of patients versus 47.6% for ATC. Median CSS was similar in the two histology groups (P = 0.14). Both PDTC and ATC patients receiving radioisotopes showed a significantly better CSS compared to external beam radiation (P < 0.0001). PDTC and ATC Patients receiving radiation prior to surgery demonstrated a significantly lower CSS compared to patients receiving radiation postoperatively (P < 0.0001). Female gender and black/nonwhite race tended to improve CSS in PDTC and ATC patients (P = 0.29 and P = 0.03, for gender and race, respectively). However, multivariate analysis revealed only type of radiation treatment and age to be independently associated with CSS. This is the first large population-based study evaluating PDTC and ATC outcomes in patients who received radiation treatment. Radioisotope use and timing of radiotherapy (postoperative vs. preoperative) were associated with improved CSS in both histologies.


[Over-expression of caveolin-1 inhibits proliferation and invasion of pancreatic carcinoma cells in vitro].
To investigate the effects of caveolin-1 on the biologic behavior of pancreatic carcinoma cell line panc1 cells in vitro. Eukaryotic expression vectors containing human caveolin-1 gene was stably transfected into panc1 cells with Lipofectamine2000. The clones stably overexpressing caveolin-1 were identified by real-time PCR and Western plotting. The cell growth activity was examined by MTT assay. Anchorage-independent growth was detected by colony formation assay in soft agar. Flow cytometry was used to analyze the cell cycle and apoptosis. Cell invasion assay was used for evaluating cell invasion capacity. The relative phosphorylation level of EGFR, c-Raf, Mek, Erk, p38 and SAPK/JNK were detected by Western blotting. Three transfected cell clones overexpressing caveolin-1 were obtained. Comparing with the panc1 cells, the transfected cells exhibited a slower growth rate and formed fewer colonies in soft agar. The results of flow cytometry showed that over-expression of caveolin-1 resulted in the cell cycle arrest at G(0)/G(1) phase and increased the apoptotic cell fraction. Cell invasion assay showed that overexpression of caveolin-1 significantly inhibited the panc1 cell invasion. Western blotting results showed that overexpression of caveolin-1 reduced the phosphorylation of EGFR, c-Raf, Mek and Erk while did not affect the activity of p38 and SAPK/JNK. Over-expression of caveolin-1 inhibits the growth and invasion of pancreatic carcinoma cells in vitro. These phenotypes may be correlated with the inhibition of EGFR-c-Raf-Mek-Erk signaling pathway.


S-adenosylmethionine activates adpA transcription and promotes streptomycin biosynthesis in Streptomyces griseus.
S-adenosylmethionine (SAM), the major methyl donor in diverse biological processes, was previously documented as a regulator for secondary metabolism in Streptomyces. The present study demonstrates that exogenous SAM, in a quantity as low as 10 muM, enhanced streptomycin production and adpA transcription in both Streptomyces griseus wild-type strain and mutant HO1, which displays no ArpA repression on the adpA promoter. SAM also enhanced xylE expression driven by the promoter of adpA or strR in a heterologous host, S. lividans. This report substantiates that exogenous SAM promotes adpA transcription in S. griseus, which is involved in the SAM-mediated promotion of streptomycin, and that the mechanism underlying this event is shared in S. lividans.


Electronic Biosensing with Functionalized rGO FETs.
In the following we give a short summary of examples for biosensor concepts in areas in which reduced graphene oxide-based electronic devices can be developed into new classes of biosensors, which are highly sensitive, label-free, disposable and cheap, with electronic signals that are easy to analyze and interpret, suitable for multiplexed operation and for remote control, compatible with NFC technology, etc., and in many cases a clear and promising alternative to optical sensors. The presented areas concern sensing challenges in medical diagnostics with an example for detecting general antibody-antigen interactions, for the monitoring of toxins and pathogens in food and feed stuff, exemplified by the detection of aflatoxins, and the area of smell sensors, which are certainly the most exciting development as there are very few existing examples in which the typically small and hydrophobic odorant molecules can be detected by other means. The example given here concerns the recording of a honey flavor (and a cancer marker for neuroblastoma), homovanillic acid, by the odorant binding protein OBP 14 from the honey bee, immobilized on the reduced graphene oxide gate of an FET sensor.


Mass extinctions drove increased global faunal cosmopolitanism on the supercontinent Pangaea.
Mass extinctions have profoundly impacted the evolution of life through not only reducing taxonomic diversity but also reshaping ecosystems and biogeographic patterns. In particular, they are considered to have driven increased biogeographic cosmopolitanism, but quantitative tests of this hypothesis are rare and have not explicitly incorporated information on evolutionary relationships. Here we quantify faunal cosmopolitanism using a phylogenetic network approach for 891 terrestrial vertebrate species spanning the late Permian through Early Jurassic. This key interval witnessed the Permian-Triassic and Triassic-Jurassic mass extinctions, the onset of fragmentation of the supercontinent Pangaea, and the origins of dinosaurs and many modern vertebrate groups. Our results recover significant increases in global faunal cosmopolitanism following both mass extinctions, driven mainly by new, widespread taxa, leading to homogenous 'disaster faunas'. Cosmopolitanism subsequently declines in post-recovery communities. These shared patterns in both biotic crises suggest that mass extinctions have predictable influences on animal distribution and may shed light on biodiversity loss in extant ecosystems.Mass extinctions are thought to produce 'disaster faunas', communities dominated by a small number of widespread species. Here, Button et al. develop a phylogenetic network approach to test this hypothesis and find that mass extinctions did increase faunal cosmopolitanism across Pangaea during the late Palaeozoic and early Mesozoic.


Generation of the Antioxidant Hydroxytyrosol from Tyrosol Present in Beer and Red Wine in a Randomized Clinical Trial.
Beer and wine contains the simple phenol tyrosol (TYR) which is endogenously converted into hydroxytyrosol (HT), one of the strongest dietary antioxidants, by CYP2A6 and CYP2D6 polymorphic enzymes. We investigated in humans the rate of this bioconversion after beer and red wine (RW) intake. In a single blind, randomized, crossover, controlled clinical trial (n = 20 healthy subjects), we evaluated TYR absorption and biotransformation into HT following a single dose of (i) RW, (ii) Indian pale ale beer (IPA), (iii) blonde beer, and (iv) non-alcoholic beer (free). Individuals were genotyped for CYP2A6 and CYP2D6, and a polygenic activity score (PAS) was derived. RW triggered the highest increase in total TYR recovered, followed by IPA, blonde, and free beers. Although the HT content in beer was minimal, an increase in HT production was observed in all beers following TYR in a dose-response manner, confirming TYR to HT biotransformation. Sex differences were identified in the rate of the conversion following RW. PAS scores correlated linearly with the recoveries of HT (HT:TYR ratios) after RW intake. In conclusion, after beer and RW consumption, TYR is absorbed and endogenously biotransformed into HT. This mechanism could be modulated by sex, genetics, and matrix components.


Chronic kidney disease: evolving strategies for detection and management of impaired renal function.
Nephrologists have long been concerned about late referral of patients with severe kidney disease, and resultant poor outcomes on dialysis. But there is an increasing realisation that mild to moderate chronic kidney disease is far more common than previously appreciated. Furthermore, the main consequence of chronic kidney disease is not progression to dialysis, but increased risk of cardiovascular disease. Chronic kidney disease is at least as common and important a risk factor for cardiovascular disease as diabetes mellitus. The MDRD formula is a well-validated formula to estimate glomerular filtration rate, which is now being widely implemented by clinical chemistry laboratories, and should increase the recognition of chronic kidney disease. The K/DOQI classification of chronic kidney disease has gained international acceptance and provides the structure to guide referral and management. This classification, and associated guidelines, also focus attention on areas where evidence is lacking, and which urgently require research. These current developments will substantially change and improve how chronic kidney disease is identified and managed.


Design and fabrication of drug-eluting polymeric thin films for applications in ophthalmology.
To study the development, characterisation, and drug release of one- and two-layered thin films based on organic polymers [poly(D,L-lactide-co-glycolide) lactide:glycolide (65:35), poly(D,L-lactide-co-glycolide) lactide:glycolide (75:25), and polycaprolactone] and dexamethasone. To examine their applicability for intraocular lenses (IOLs) and function in intraocular drug delivery systems. Four series of thin films, single and double-layer, were prepared by the spin-coating method on a silicon substrate. The films were studied using atomic force microscopy and spectroscopic ellipsometry. The release rate of dexamethasone was studied for a period of ten weeks. Series A and C demonstrated the formation of large dexamethasone aggregates. The monolayer films of series C and D formed pores, in agreement with previous findings. The spectroscopic ellipsometry study demonstrated that the samples were transparent. The drug release study demonstrated that dexamethasone was released during the first 6 weeks at a desirable rate. The films exhibited properties suitable for use in intraocular drug delivery systems. The single-layer thin films demonstrated a sufficient encapsulation of dexamethasone and appropriate release of the therapeutic substance. Further studies are necessary to investigate the possibility of developing the films directly on the surface of the IOL.


A comparative study of influential factors correlating with early and late hypothyroidism after (131)I therapy for Graves' disease.
(131)I therapy is recognized as the simplest, safest, least expensive, and most effective treatment, and accepted by more and more patients. However its curative effect is influenced by many factors, therefore there are some difficulties for doctors to establish individual treatment strategy. The aims of this study were to determine the incidence of early and late hypothyroidism after (131)I treatment for Graves' disease (GD) and to compare their correlation, to observe and analyze the influential factors and to understand the predictabilities of them. Five hundred GD patients (144 males, 356 females; age (41.2 +/- 12.3) years) received (131)I treatment for the first time. The therapeutic procedure was carried out as the following: undergoing (131)I uptake test to obtain maximum of thyroid uptake value and effective half-life (EHL) time; estimating the thyroid's weight by ultrasonography; determination of thyroid hormones and correlative antibodies; pre-therapy physical examination; thyroid imaging; calculating (131)I therapeutic dosage; per os uptake of the determined (131)I dosage; follow-up appraisal of curative effect. The observing parameters included age, gender, thyroid weight, GD duration, condition of onset, state of disease, course of treatment, EHL time, maximum of thyroid uptake value, (131)I dosage and titer of correlative antibodies. We sorted out the data and used both univariate and multivariate analysis to evaluate them statistically. The incidence rates of early and late hypothyroidism were 33.2% and 6.6% respectively after (131)I treatment and approximately 22.2% cases of late hypothyroidism developed from early hypothyroidism. The influential factors of early hypothyroidism included course of GD, the highest thyroid uptake ratio of (131)I, EHL time and thyroid microsome antibody (TMAb), etc. A multivariate analysis on late hypothyroidism showed that female patients, with recurrence after anti-thyroid drug treatment and higher thyroid weight, had lower possibility of late hypothyroidism after (131)I therapy. The incidence of early hypothyroidism is higher than that of late hypothyroidism. The highest thyroid uptake ratio of (131)I, EHL and TMAb will increase the possibility of early hypothyroidism, while GD course is the protective factor. Higher (131)I dosage, longer EHL and higher TMAb titer will also increase the possibility of late hypothyroidism. The multi-perspective and multi-factor analysis has the benefit to establish individualized treatment strategy.


Cardiac disease in chronic kidney disease: current understandings and opportunities for change.
Cardiovascular disease (CVD) is prevalent in patients with kidney disease: in populations prior to dialysis, on dialysis and after transplantation. Publications over the last decade have focused on this, and more recently, patients with cardiac disease are now recognized as being at increased risk in the presence of even mild kidney dysfunction. The presence of both traditional and non-traditional risk factors contributes to this overwhelming burden of cardiovascular disease in patients with chronic kidney disease (CKD). Recent studies have focused on the impact of anemia and disorders of mineral metabolism on CVD outcomes, in the context of inflammation and evidence of cytokine activation. Cross-sectional and prospective observational studies have led to improved understanding, and generated novel hypotheses. To date, no clinical trial has determined the positive impact of interventions targeted at these novel risk factors. This overview describes the current state of knowledge and emphasizes the interplay between CVD and CKD as two aspects of a set of pathophysiological processes, which impact on patient outcomes.


[Congestive cardiomyopathy and left intraventricular thrombus as a manifestation of Churg-Strauss syndrome].
A case of a 38-year-old female with symptomatic Churg-Strauss syndrome and congestive cardiomyopathy, complicated by cardiac arrest and left ventricular thrombus formation, is presented. Prompt institution of low molecular weight heparin and steroids resulted in rapid thrombus lysis and improvement of systolic left ventricular function.


Degraded carrageenan-induced colitis in CF1 mice. A clinical, histopathological and kinetic analysis.
Delivery of 10% carrageen (degraded carrageenan, Glaxo, France) for 10 days in the drinking water to CF1 mice induced bloody diarrhea, pericryptal inflammation, and marked dilatation of the cecum and ascending colon. Histologically, the mucosa was characterized by distorted crypt architecture, inflammatory infiltration of the lamina propria, and ulceration, conditions which were more pronounced in the proximal colon but were also present in the distal colon. Treatment with hydrocortisone and levamisole reduced the severity of all phases of the reaction. Alterations in colonic epithelial cell proliferation corresponded with the clinical and histopathological findings. Labeling indices (LI) significantly increased over control values in both proximal (12.9 +/- 4.9 vs. 7.6 +/- 2.9) and distal colon (13.9 +/- 5.2 vs. 7.2 +/- 2.4), effectively doubling the number of proliferating cells per crypt column in both areas. However, DNA-synthesizing cells extended further upward along the cryptal wall of the proximal colon reflecting greater mucosal damage. Only in the proximal colon did the proliferative compartment (PC) extend to the upper third of the glands, normally not a proliferative zone. Hydrocortisone and levamisole administered concurrently with 10% carrageen were less effective in protecting the proximal colon since LI and numbers of labeled cells per crypt column were consistently lower in the distal colon. Moreover, hydrocortisone alone significantly depressed DNA synthesis only in the distal colon. All distal colonic crypts were not equally protected by administration of hydrocortisone since some continued to express large numbers of proliferating cells and an extended PC, well characterized preneoplastic defects in regulatory control of colonic epithelial cell proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)


Distal esophageal spasm.
Distal esophageal spasm (DES) is an uncommon esophageal motility disorder associated with dysphagia and/or chest pain. Its pathophysiology implies an impairment of esophageal inhibitory neural function. Using conventional manometry, DES was defined by the presence of simultaneous esophageal contractions. With the introduction of high-resolution manometry and esophageal pressure topography (EPT) in clinical practice, rapidly propagated contractions are nonspecific of esophageal spasm. Hence, a more physiological and clinically relevant definition was proposed. Distal latency (DL) measures the period of inhibition that precedes contraction in the distal esophagus immediately proximal to the esophagogastric junction (EGJ). Premature contractions, defined as reduced DL, appeared to be much more specific for DES in EPT. Premature contractions with normal EGJ relaxation constitute DES, while premature contractions with impaired EGJ relaxation are diagnostic of spastic achalasia. Because of the interaction between DES and gastroesophageal reflux disease, 24-h esophageal pH monitoring should also be considered in patient evaluation. Medical treatment of DES aims to compensate for the deficient inhibitory neural function. Sildenafil, which blocks nitric oxide degradation and thus prolongs esophageal muscle relaxation, is a promising treatment. Endoscopic injection of botulinum toxin in the esophageal muscle is also an interesting therapeutic option. Finally, extended surgical myotomy might be discussed in extreme cases after failure of other therapeutic options.


[Adsorption mechanism of chromium cation by floc-type biosorbent ZL 5-2].
Biosorption of Cr(VI) by the novel biosorbent ZL5-2 produced by Agrobacterium sp. was studied and infrared spectra of native, absorbing and desorbing ZL 5-2 were compared. The initial pH was important for biosorption. The optimum effect on Cr(VI) biosorption was acquired within initial pH 0.5 to approximately 1.5, then with the pH increasing, the effect on Cr6+ biosorption was reduced. The biosorption for Cr(VI) was a quick process,only within 10 min 65.4% Cr(VI) is biosorbed, and the biosorption rate was over 90% after 60 min, then all the Cr(VI) was biosorbed after 80 min. The biosorption were fitted with Langmuir and Freundlich isotherm adsorption equations. The absorbed Cr(VI) could be recovered by desorption and the desorption rate reached 13.696% to approximately 67.9%. Progress of biosorption was reversible adsorption and irreversible adsorption simultaneously through infrared spectra analysis, however the reversible adsorption was more important in the biosorption and the adsorption belongs to physics adsorption.


Red blood cell alloimmunization complicating plasma transfusion.
Well-known adverse effects of plasma transfusion include viral transmission, allergic complications, and rare anaphylactic reactions. In making clinical decisions to transfuse plasma, a seldom-considered complication is that of red blood cell (RBC) alloimmunization. The authors report a patient in whom strong IgM and IgG anti-E and weak IgG anti-JKa RBC antibodies developed 15 days after infusion of two units of fresh-frozen plasma for volume expansion. These antibodies are potentially hemolytic. This case underscores the importance of considering risks of plasma infusion. Plasma should not be used casually, especially for indications for which alternate therapies, such as crystalloid and colloid solutions, are available.


Definition and dynamic control of a continuous chromatography process independent of cell culture titer and impurities.
Advances in cell culture technology have enabled the production of antibody titers upwards of 30g/L. These highly productive cell culture systems can potentially lead to productivity bottlenecks in downstream purification due to lower column loadings, especially in the primary capture chromatography step. Alternative chromatography solutions to help remedy this bottleneck include the utilization of continuous processing systems such as periodic counter-current chromatography (PCC). Recent studies have provided methods to optimize and improve the design of PCC for cell culture titers up to about 3g/L. This paper defines a continuous loading strategy for PCC that is independent of cell culture background and encompasses cell culture titers up to about 31g/L. Initial experimentation showed a challenge with determining a difference in change in UV280nm signal (ie. ΔUV) between cell culture feed and monoclonal antibody (mAb) concentration. Further investigation revealed UV280nm absorbance of the cell culture feedstock without antibody was outside of the linear range of detection for a given cell pathlength. Additional experimentation showed the difference in ΔUV for various cell culture feeds can be either theoretically predicted by Beer's Law given a known absorbance of the media background and impurities or experimentally determined using various UV280nm cell pathlengths. Based on these results, a 0.35mm pathlength at UV280nm was chosen for dynamic control to overcome the background signal. The pore diffusion model showed good agreement with the experimental frontal analysis data, which resulted in definition of a ΔUV setpoint range between 20 and 70% for 3C-PCC experiments. Product quality of the elution pools was acceptable between various cell culture feeds and titers up to about 41g/L. Results indicated the following ΔUV setpoints to achieve robust dynamic control and maintain 3C-PCC yield: ∼20-45% for titers greater than 10g/L depending on UV absorbance of the HCCF and ∼45-70% for titers of up to 10g/L independent of UV absorbance of the HCCF. The strategy and results presented in this paper show column loading in a continuous chromatography step can be dynamically controlled independent of the cell culture feedstock and titer, and allow for enhanced process control built into the downstream continuous operations.


The Modified Overt Aggression Scale: how valid in this environment?
The Modified Overt Aggression Scale (MOAS) has been validated for use in the study of aggression in the developed world; unlike in the undeveloped world. The aim of this study therefore is to ascertain the discriminant validity of the MOAS for use in this part of the world using psychiatric in-patients at the Jos University Teaching Hospital. Forty aggressive psychiatric patients and 40 non-aggressive healthy subjects were randomly selected for this study. The psychiatric patients were enlisted after fulfilling the ICD-10 (World Health Organization, 1993) criteria for a specific clinical diagnosis. The 40 non-aggressive subjects were mainly medical students and hospital staff. The MOAS was subsequently used to assess aggression in the entire cohort. The males had higher mean global weighted score than the females in both the aggressive and nonaggressive categories. The mean global weighted scores of the aggressive and non-aggressive categories were 13.70 +/- 7.25 and 0.65 +/- 1.01 respectively. The difference in means is statistically significant; hence the MOAS has discriminant validity. Therefore, the modified overt aggression scale is a valid instrument in this environment for the study of aggression.


Is the detection of optical activity in extraterrestrial samples a safe indicator for life?
Since Pasteur's times it has been accepted that optical activity and life are intimately correlated with each other, i.e. the one could not exist without the other. This argument logically allows the following speculation related to interplanetary exploration: detection of optical activity in an extraterrestrial sample would be the most straightforward proof of the existence of living matter outside the earth. On the other hand it has been shown that spontaneous production of optical activity can be achieved without the help of living matter, so that the close association of optical activity with life is not necessarily true. The paper discusses the possibilities which allow a proof of some sort of life on other planets by polarimetric methods.


Management of chyle leak in right side neck dissection: a rare case and review of literature (a case report).
Chyle leak is a well-recognized iatrogenic thoracic duct injury but a rare and serious complication of head and neck surgery affecting 1-2.5% of head and neck surgery dissections. It is potentially a life-threatening condition and management may be problematic and prolonged. Here we presented a rare case report of right sided chyle leak with its surgical management and review of literature. A 56-year-old patient with a complain of non-healing ulcer in the right buccal vestibule in the last 1-2 months reported to the outpatient department (OPD). After complete preoperative profile and counseling patient's consent was taken and wide local excision of lesion was done with bite composite resection with right hemimandibulectomy and maxillary alveolectomy till pterygoid plates, with right side selective neck dissection, level I-III followed by reconstruction with right side pectoralis major myofascial flap. Then the patient was on 5 days octreotide therapy. Regular post-operative follow-up was taken and no leak was noted further. In case of a chyle leak early diagnosis and aggressive treatment is essential to avoid local and systemic complications that prolong hospitalization.


Fear and avoidance of healthcare workers: An important, under-recognized form of stigmatization during the COVID-19 pandemic.
During past disease outbreaks, healthcare workers (HCWs) have been stigmatized (e.g., shunned, ostracized) by members in their community, for fear that HCWs are sources of infection. There has been no systematic evaluation of HCW stigmatization during the COVID-19 pandemic. Non-HCW adults from the United States and Canada (N = 3551) completed an online survey, including measures of HCW stigmatization, COVID Stress Syndrome, and avoidance. Over a quarter of respondents believed that HCWs should have severe restrictions placed on their freedoms, such as being kept in isolation from their communities and their families. Over a third of respondents avoided HCWs for fear of infection. Participation in altruistic support of HCWs (i.e., evening clapping and cheering) was unrelated to stigmatizing attitudes. Demographic variables had small or trivial correlations with HCW stigmatization. People who stigmatized HCWs also tended to avoid other people, avoid drug stores and supermarkets, and avoid leaving their homes. Factor analysis suggested that HCW stigmatization is linked to the COVID Stress Syndrome. Fear and avoidance of HCWs is a widespread, under-recognized problem during the COVID-19 pandemic. It is associated with the COVID Stress Syndrome and might be reduced by interventions targeting this syndrome.


Computational Investigation of the Aminolysis of RAFT Macromolecules.
This work presents a detailed computational study and kinetic analysis of the aminolysis of dithioates, dithiobenzoates, trithiocarbonates, xanthates, and thiocarbamates, which are frequently used as chain-transfer agents for reversible addition-fragmentation chain-transfer (RAFT) polymerization. Rate coefficients were obtained from ab initio calculations, taking into account a diffusional contribution according to the encounter pair model. A kinetic model was constructed and reveals a reaction mechanism of four elementary steps: (i) formation of a zwitterionic intermediate, (ii) formation of a complex intermediate in which an assisting amine molecule takes over the proton from the zwitterionic intermediate, (iii) breakdown of the complex into a neutral tetrahedral intermediate with release of the assisting amine molecule, and (iv) amine-assisted breakdown of the neutral intermediate to the products. Furthermore, a comparative analysis indicates that the alkanedithioates and dithiobenzoates react the fastest, followed, respectively, by xanthates and trithiocarbonates, which react almost equally fast, and dithiocarbamates, which are not reactive at typical experimentally used conditions.


Assessment of community psycho-behavioral responses during the outbreak of novel coronavirus (2019-nCoV): a cross-sectional study.
The novel coronavirus 2019 (2019-nCoV) is a public health emergency of international concern resulting in adverse psychological impacts during the epidemic. From 1 to 10 April 2020, we conducted an online survey. The online survey collected information on demographic data, precautionary measures against (2019-nCoV), self-health evaluation, knowledge, and concerns about (2019-nCoV), and appraisal of crisis management. The psychological impact was assessed by the General Anxiety Disorder 7-item (GAD-7) scale. The designed questionnaire was answered by participants, and collected data were statistically analyzed. This study included 1200 respondents. In total, 80% of respondents rated the psychological impact; 18% reported minimal anxiety; 34% reported mild anxiety, and 48% with moderate anxiety symptoms. A large proportion (74%) believed that they were very or somewhat likely to contract (2019-nCoV) while only (35%) believed they were unlikely to survive if they contracted the disease. (58%) of the respondents, practiced the precautionary measures directed against person-to-person droplet spread. Respondents with a moderate level of anxiety were most likely to take comprehensive precautionary measures against the infection. Also, older, female, more educated people as well as those who are more likely to contract the infection. During the outbreak, more than half of the respondents rated the psychological impact as moderate anxiety. Thus, the psychological needs during the outbreak should be addressed appropriately. Our results highlight the need to promote protective personal health practices to interrupt the transmission of the (2019-nCoV) in the community. Therefore, educational public programs about preventive measures should be targeted at the identified groups with low current uptake of precautions.


Efficacy of therapeutic ultrasound in the treatment of spasticity: a randomized controlled study.
The purpose of this study was to investigate the effect of ultrasound (US) on the spasticity occurring in the ankle plantar flexor muscles after a cerebrovascular event. According to the modified Ashworth scale (MAS), the hemiplegic patients with stage 2-3 spasticity on the ankle plantar flexor muscles were enrolled in the study and divided into two groups. Passive stretching exercise was applied to both groups. Additionally, 10-minute US was applied to one of the groups, using the mode of continuous wave of 1.5w/cm<formula>^{2}</formula> to the calf muscles before stretching. In order to monitor the efficacy of the treatment in the patients, MAS, Hmax/Mmax ratio, the ankle range of motion (ROM), Functional Independence Measure and Brunnstrom Motor Recovery Stage were evaluated. While a significant recovery was monitored in the MAS and ankle ROM measurements after treatment in both groups, no change was obtained in the other parameters. No significant difference was detected in any of the measurements between the groups. In this study, US treatment applied in combination with the ankle plantar flexor muscles passive stretching exercise was determined to have no effect on the stretching treatment in minimizing the spasticity.


Rice Ribosomal Protein Large Subunit Genes and Their Spatio-temporal and Stress Regulation.
Ribosomal proteins (RPs) are well-known for their role in mediating protein synthesis and maintaining the stability of the ribosomal complex, which includes small and large subunits. In the present investigation, in a genome-wide survey, we predicted that the large subunit of rice ribosomes is encoded by at least 123 genes including individual gene copies, distributed throughout the 12 chromosomes. We selected 34 candidate genes, each having 2-3 identical copies, for a detailed characterization of their gene structures, protein properties, cis-regulatory elements and comprehensive expression analysis. RPL proteins appear to be involved in interactions with other RP and non-RP proteins and their encoded RNAs have a higher content of alpha-helices in their predicted secondary structures. The majority of RPs have binding sites for metal and non-metal ligands. Native expression profiling of 34 ribosomal protein large (RPL) subunit genes in tissues covering the major stages of rice growth shows that they are predominantly expressed in vegetative tissues and seedlings followed by meiotically active tissues like flowers. The putative promoter regions of these genes also carry cis-elements that respond specifically to stress and signaling molecules. All the 34 genes responded differentially to the abiotic stress treatments. Phytohormone and cold treatments induced significant up-regulation of several RPL genes, while heat and H2O2 treatments down-regulated a majority of them. Furthermore, infection with a bacterial pathogen, Xanthomonas oryzae, which causes leaf blight also induced the expression of 80% of the RPL genes in leaves. Although the expression of RPL genes was detected in all the tissues studied, they are highly responsive to stress and signaling molecules indicating that their encoded proteins appear to have roles in stress amelioration besides house-keeping. This shows that the RPL gene family is a valuable resource for manipulation of stress tolerance in rice and other crops, which may be achieved by overexpressing and raising independent transgenic plants carrying the genes that became up-regulated significantly and instantaneously.


[A longitudinal study on deterioration of physical function in people aged over 55 in Beijing].
The objective of this study is to explore the index of physical performance test in detecting physical functional status among elderly people. Physical performance test, recommended by Yale University in EPESE was used in the study. A total number of 1,986 people aged 55 and over in urban and rural area of Beijing was studied in a three-year longitutinal observation. Among 1,986 cases studied in 1992, 168 died between 1992-1994. The mortality rate increased along with the degree of functional disablement, lowest in non-disabled (3.4%), followed by mild ones (5.2%), moderate (10.5%) and highest in severely disabled (18.4%). It is shown that performance test can be used as a tool in observing and detecting risk groups in the progress of functional disability It's an important index describing the decline of health status.


High Spatial Resolution Simulation of Sunshine Duration over the Complex Terrain of Ghana.
In this paper, we propose a remote sensing model based on a 1 × 1 km spatial resolution to estimate the spatio-temporal distribution of sunshine percentage (SSP) and sunshine duration (SD), taking into account terrain features and atmospheric factors. To account for the influence of topography and atmospheric conditions in the model, a digital elevation model (DEM) and cloud products from the moderate-resolution imaging spectroradiometer (MODIS) for 2010 were incorporated into the model and subsequently validated against in situ observation data. The annual and monthly average daily total SSP and SD have been estimated based on the proposed model. The error analysis results indicate that the proposed modelled SD is in good agreement with ground-based observations. The model performance is evaluated against two classical interpolation techniques (kriging and inverse distance weighting (IDW)) based on the mean absolute error (MAE), the mean relative error (MRE) and the root-mean-square error (RMSE). The results reveal that the SD obtained from the proposed model performs better than those obtained from the two classical interpolators. This results indicate that the proposed model can reliably reflect the contribution of terrain and cloud cover in SD estimation in Ghana, and the model performance is expected to perform well in similar environmental conditions.


Subacute thyroiditis associated with COVID-19.
We report a case of a hospitalised patient with COVID-19 who developed subacute thyroiditis in association with SARS-COV-2 infection. The patient presented with tachycardia, anterior neck pain and thyroid function tests revealing hyperthyroidism together with consistent ultrasonographic evidence suggesting subacute thyroiditis. Treatment with corticosteroids resulted in rapid clinical resolution. This case illustrates that subacute thyroiditis associated with viruses such as SARS-CoV-2 should be recognised as a complication of COVID-19 and considered as a differential diagnosis when infected patients present with tachycardia without evidence of progression of COVID-19 illness.


Regulator of G Protein Signaling Protein 12 (Rgs12) Controls Mouse Osteoblast Differentiation via Calcium Channel/Oscillation and Gαi-ERK Signaling.
Bone homeostasis intimately relies on the balance between osteoblasts (OBs) and osteoclasts (OCs). Our previous studies have revealed that regulator of G protein signaling protein 12 (Rgs12), the largest protein in the Rgs super family, is essential for osteoclastogenesis from hematopoietic cells and OC precursors. However, how Rgs12 regulates OB differentiation and function is still unknown. To understand that, we generated an OB-targeted Rgs12 conditional knockout (CKO) mice model by crossing Rgs12fl/fl mice with Osterix (Osx)-Cre transgenic mice. We found that Rgs12 was highly expressed in both OB precursor cells (OPCs) and OBs of wild-type (WT) mice, and gradually increased during OB differentiation, whereas Rgs12-CKO mice (OsxCre/+ ; Rgs12fl/fl ) exhibited a dramatic decrease in both trabecular and cortical bone mass, with reduced numbers of OBs and increased apoptotic cell population. Loss of Rgs12 in OPCs in vitro significantly inhibited OB differentiation and the expression of OB marker genes, resulting in suppression of OB maturation and mineralization. Further mechanism study showed that deletion of Rgs12 in OPCs significantly inhibited guanosine triphosphatase (GTPase) activity and cyclic adenosine monophosphate (cAMP) level, and impaired Calcium (Ca2+ ) oscillations via restraints of major Ca2+ entry sources (extracellular Ca2+ influx and intracellular Ca2+ release from endoplasmic reticulum), partially contributed by the blockage of L-type Ca2+ channel mediated Ca2+ influx. Downstream mediator extracellular signal-related protein kinase (ERK) was found inactive in OBs of OsxCre/+ ; Rgs12fl/fl mice and in OPCs after Rgs12 deletion, whereas application of pertussis toxin (PTX) or overexpression of Rgs12 could rescue the defective OB differentiation via restoration of ERK phosphorylation. Our findings reveal that Rgs12 is an important regulator during osteogenesis and highlight Rgs12 as a potential therapeutic target for bone disorders. © 2018 American Society for Bone and Mineral Research.


Chlorpropamide hepatotoxicity: report of a case and review of the literature.
Chlorpropamide, a sulfonylurea compound used in the treatment of diabetes mellitus, type II, has been implicated as the cause of untoward reactions involving the hematopoietic, cutaneous, and gastrointestinal systems. The hepatotoxic reactions induced by this drug generally present as hepatocanalicular cholestatic reactions, in contrast to the hepatocellular reactions induced by the older sulfonylurea compounds. An unusual presentation of chlorpropamide toxicity, presenting as a mixed hepatocanalicular reaction, is reported, along with a review of the literature.


An AFM/rotaxane molecular reading head for sequence-dependent DNA structures.
DNA secondary structure may prove to be a significant obstacle both for enzymes that process DNA through an orifice and for the passage of DNA through nanopores proposed for some novel sequencing schemes. A nanomechanical molecular "tape reader" is assembled by threading a nanopore over DNA and pulling it using an atomic force microscope. Its formation is confirmed by studying the force required to open hairpins under that geometry. Unfolding induced by this 0.7-nm-diameter aperture requires 40 times more force than that reported for pulling on the ends of the DNA. Kinetic analysis shows that much less strain is required to destabilize the double helix in this geometry. Consequently, much more force is required to provide the free energy needed for opening.


Isolation and characterization of an acyl-CoA thioesterase from dark-grown Euglena gracilis.
An acyl-CoA hydrolase from dark-grown Euglena gracilis Z was purified 700-fold by subjecting the 105,000g supernatant of the cell-free extract to (NH4)2SO4 precipitation, acid precipitation, calcium phosphate gel treatment, gel filtration on Sephadex G-100, and chromatography on QAE-Sephadex, hydroxylapatite, and CM-Sephadex. Polyacrylamide disc gel electrophoresis of the purified enzyme showed a major protein band (greater than 80%) which contained thioesterase activity and a minor protein band with no thioesterase activity. Molecular weight estimated by gel filtration was 37,000 and sodium dodecyl sulfate-electrophoresis showed one major band (greater than 80%) corresponding to a molecular weight of 37,000 and a minor band of molecular weight 32,000, suggesting that the enzyme was monomeric. The pH optimum of the purified enzyme progressively increased with the chain length of the substrate, with hexanoyl-CoA showing a pH optimum at 4.5 and stearoyl-CoA at 7.0. The rate of hydrolysis of acyl-CoA showed a nonlinear dependence on protein concentration, and bovine serum albumin overcame this effect as well as stimulated the rate. The extent of stimulation by albumin increased with chain length of the substrate up to lauroyl-CoA and then decreased as chain length increased; albumin inhibited the hydrolysis of stearoyl-CoA. This enzyme hydrolyzed CoA esters of C6 to C18 fatty acids with a maximal rate of 17 mumol min-1 mg protein-1 for C14. Typical substrate saturation patterns were obtained with all substrates except that high concentrations were inhibitory. Studies on the effect of pH on the apparent Km and Vmax values for octanoyl-CoA, lauroyl-CoA, and palmitoyl-CoA showed that in all cases Vmax was greatest and Km was lowest at the respective pH optima. Active-serine-directed reagents severely inhibited the thioesterase activity, suggesting the participation of an active serine residue in catalysis; thiol-directed reagents were not effective inhibitors. Diethylpyrocarbonate also inhibited the enzyme and hydroxylamine reversed this inhibition, suggesting the involvement of a histidine residue in catalysis as expected for enzymes containing active serine. This thioesterase did not affect the chain length distribution of the products generated by the Euglena fatty acid synthase I.


Spontaneous peritonitis in critically ill cirrhotic patients: a diagnostic algorithm for clinicians and future perspectives.
Spontaneous peritonitis (SP) is the most common infection among decompensated end-stage liver disease patients. SP is the infection of ascitic fluid (neutrophil ascitic count ≥250/mL) without an alternative focus of abdominal infection. According to the causative agent, clinicians can make the diagnosis of spontaneous bacterial peritonitis or spontaneous fungal peritonitis. The mortality rate is very high, ranging from one-fifth of the patients with spontaneous bacterial peritonitis to four-fifths of the patients with spontaneous fungal peritonitis. An immediate and accurate diagnosis can improve the outcome in end-stage liver disease patients. The aim of this work is to provide physicians with a practical diagnostic guidance for SP diagnosis according to current evidence, in order to improve the management of cirrhotic patients with infected ascitic fluid.


A Retrospective Cohort Study of Lung Cancer Incidences and Epidemiological Analysis in Saudi Arabian Population from 2006-2016.
Lung cancer is one of the leading causes of cancer-related deaths worldwide, including in Saudi Arabia. In the past few decades, the incidence and mortality has increased considerably among the Saudi population. The incidence of lung cancer has increased more than 3% in less than two decades. The current study focuses on analyzing the frequency of diagnosed lung cancer cases, age-standardized incidence rate (ASIR), and crude incidence rate (CIR) classified by year of diagnosis, age group, and different administrative regions of Saudi Arabia, based on the Saudi cancer registry (SCR) for the period of 10 years from 2006-2016. The present study is a cohort study that focuses on the epidemiological analysis of lung cancer cases. The statistical analysis was performed by t-test, sex ratio, Kruskal-Wallis, and descriptive statistics through SPSS version 20.0. A total of 4530 lung cancer cases were reported from January 2006 to December 2016. Among males, the ASIR range was reported as 1.2 to 12.3 per 100,000 cases in different regions of Saudi Arabia. Moreover, among females, the ASIR range was reported from 0.2 to 3.1 per 100,000 cases in different regions of Saudi Arabia. Additionally, the overall age-standardized incidence sex ratio was 3.2 per 100,000 cases. The incidence of lung cancer increased with age as 23% was reported in the age group of more than 75 years. The study concludes a rise in crude incidence rates and ASIR for lung cancer among Saudi population. Among males, the Eastern region had the highest overall ASIR followed by Tabuk region, and, among females, the highest overall ASIR was reported in the Eastern region followed by Riyadh and the Northern region.


Residents as role models: the effect of the obstetrics and gynecology clerkship on medical students' career interest.
Medical students' choice of residency specialty is based in part on their clerkship experience. Postclerkship interest in a particular specialty is associated with the students' choice to pursue a career in that field. But, many medical students have a poor perception of their obstetrics and gynecology clerkships. To determine whether fourth-year medical students' perceptions of teaching quality and quantity and amount of experiential learning during the obstetrics-gynecology clerkship helped determine their interest in obstetrics-gynecology as a career choice. We distributed an anonymous, self-administered survey to all third-year medical students rotating through their required obstetrics and gynecology clerkship from November 2006 to May 2007. We performed bivariate analysis and used χ(2) analysis to explore factors associated with general interest in obstetrics and gynecology and interest in pursuing obstetrics and gynecology as a career. Eighty-one students (N = 91, 89% response rate) participated. Postclerkship career interest in obstetrics and gynecology was associated with perceptions that the residents behaved professionally (P < .0001) and that the students were treated as part of a team (P = .008). Having clear expectations on labor and delivery procedures (P = .014) was associated with postclerkship career interest. Specific hands-on experiences were not statistically associated with postclerkship career interest. However, performing more speculum examinations in the operating room trended toward having some influence (P = .068). Although more women than men were interested in obstetrics and gynecology as a career both before (P = .027) and after (P = .014) the clerkship, men were more likely to increase their level of career interest during the clerkship (P = .024). Clerkship factors associated with greater postclerkship interest include higher satisfaction with resident professional behavior and students' sense of inclusion in the clinical team. Obstetrics and gynecology programs need to emphasize to residents their role as educators and professional role models for medical students.


High- and Low-contrast Letter Acuity during Image Motion in Normal Observers and Observers with Infantile Nystagmus Syndrome.
High-contrast acuity in individuals with infantile nystagmus syndrome (INS) is poorer than expected from their ongoing retinal image motion, indicating a sensory loss. Conversely, acuity for larger low-contrast letters in these observers may be limited by image motion alone. The aim of this study was to assess visual acuity for letters of different contrast in normal observers and individuals with idiopathic INS under conditions of comparable retinal image motion. Visual acuity was measured using projected Landolt C charts in 3 normal observers and 11 observers with presumed idiopathic INS. Normal observers viewed each chart after reflection from a front-surface mirror that underwent continuous 4-Hz ramp motion with amplitudes ranging from 4 to 9.6° and simulated foveation durations of 20 to 80 milliseconds. Observers with INS viewed the charts directly. By reciprocally varying the luminance of the projected charts and a superimposed veiling source, Landolt C's were presented on a background luminance of 43 cd/m2 with Weber contrasts between -12 and -89%. Whereas normal observers' high-contrast acuity during imposed image motion depends only on the duration of the simulated foveation periods, acuity for low-contrast optotypes also worsens systematically as motion intensity (frequency × amplitude) increases. For comparable parameters of retinal image motion, high-contrast acuity in all but one of the observers with INS was poorer than in normal observers. On the other hand, low-contrast acuity in the two groups of observers was similar when the retinal image motion was comparable. Reduced high-contrast acuity in observers with INS appears to be attributable primarily to a sensory deficit. On the other hand, the reduction of low-contrast acuity in observers with INS may be accounted for on the basis of retinal image motion.


Control of the stoichiometry in host-guest complexation by redox chemistry of guests: inclusion of methylviologen in cucurbit[8]uril.
The binding stoichiometry of a host-guest complex can be effectively controlled by the redox chemistry of the guest: a 1:1 inclusion complex of methylviologen dication (MV2+) in cucurbit[8]uril (CB[8]) converts completely and reversibly to a 2:1 inclusion complex of cation radical (MV+.) in CB[8] upon the reduction of the guest.


Facile depositing strategy to fabricate a hetero-affinity hybrid film for improving gas-sensing performance.
A novel co-spray method was proposed to fabricate a reduced graphene oxide (rGO)-poly (3-hexylthiophene) (P3HT) hybrid sensing device utilizing immiscible solution for ammonia detection at room temperature. The spectrum and Scanning Electron Microscopy (SEM) results revealed uniformly crimped morphology and favorable π-π interaction for the hybrid film. The hybrid film-based sensor showed obviously enhanced ammonia sensing performance, such as increased response, reduced response time, and reinforced sensitivity, in comparison to bare rGO, P3HT, and traditional rGO/P3HT layered film-based sensors, which could be attributed to an adsorption energy barrier and the p-n heterojunction effect. The synergetic strengthened sensing mechanism is discussed. Meanwhile, recovery ratio was introduced to evaluate the abnormal baseline drift induced high-response behavior. The excellent sensing properties of the hybrid sensor indicate that the co-spray method could be an alternative process for the preparation of hetero-affinity hybrid films or functional devices.


Synthesis and acrosin inhibitory activity of substituted 4-amino-N-(diaminomethylene) benzenesulfonamide derivatives.
A series of new substituted 4-amino-N-(diaminomethylene) benzenesulfonamides were synthesized and their in vitro acrosin inhibitory activities were evaluated. Most of the compounds showed potent acrosin inhibitory activities with compounds 4o and 4p being significantly more potent than the control compound N-alpha-tosyl-L-lysyl-chloromethyl-ketone (TLCK). The compounds provide a new scaffold for the development of acrosin inhibitory agents.


Endogenously decreasing tissue n-6/n-3 fatty acid ratio reduces atherosclerotic lesions in apolipoprotein E-deficient mice by inhibiting systemic and vascular inflammation.
To use the fat-1 transgenic mouse model to determine the role of tissue n-6/n-3 fatty acid ratio in atherosclerotic plaque formation. Although it has been suggested that a low ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) is more desirable in reducing the risk of atherosclerotic cardiovascular disease, the role of tissue n-6/n-3 fatty acid ratio in atherosclerosis has not been sufficiently tested in a well-controlled experimental system. The fat-1 transgenic mouse model, expressing an n-3 fatty acid desaturase, is capable of producing n-3 PUFAs from n-6 PUFAs and thereby has a ratio of n-6/n-3 fatty acids close to 1:1 in tissues and organs. To generate apolipoprotein E-deficient plus fat-1 transgenic mice (apoE(-/-)/fat-1), we crossed heterozygous fat-1 mice with apoE(-/-) mice. After 14 weeks of a Western-type diet rich in n-6 PUFAs, the apoE(-/-)/fat-1 mice showed a lower ratio of n-6/n-3 fatty acids than the apoE(-/-) mice in all organs and tissues tested. The aortic lesion area in apoE(-/-)/fat-1 mice was significantly reduced when compared with that of apoE(-/-) littermates (7.14±0.54% versus 13.49±1.61%). There were no differences in plasma cholesterol or high- and low-density lipoprotein levels between the 2 groups, except for a higher triglyceride level in the apoE(-/-)/fat-1 mice. A significant reduction of interleukin 6 and prostaglandin E(2) in both plasma and aorta culture medium was observed in apoE(-/-)/fat-1 mice. RT-PCR analysis also indicated that the expression of intercellular adhesion molecule-1, monocyte chemoattractant protein-1, interleukin 6, and cyclooxygenase-2 was lower in the aortas and the circulating monocytes from apoE(-/-)/fat-1 mice. In addition, the expression of nuclear factor κB/p65 in the aorta and the recruitment of macrophages into atherosclerotic plaques were reduced in apoE(-/-)/fat-1 mice, compared with apoE(-/-) mice. To our knowledge, this is the first study to provide direct evidence for the role of tissue n-6/n-3 ratio in atherosclerosis using the fat-1 transgenic mouse model. Our findings demonstrate that a decreased n-6/n-3 fatty acid ratio reduces atherosclerotic lesions in apoE(-/-) mice. This protective effect may be attributed to the antiinflammatory properties of n-3 fatty acids, rather than their lipid-lowering effect.


Mini-max feedback control as a computational theory of sensorimotor control in the presence of structural uncertainty.
We propose a mini-max feedback control (MMFC) model as a robust approach to human motor control under conditions of uncertain dynamics, such as structural uncertainty. The MMFC model is an expansion of the optimal feedback control (OFC) model. According to this scheme, motor commands are generated to minimize the maximal cost, based on an assumption of worst-case uncertainty, characterized by familiarity with novel dynamics. We simulated linear dynamic systems with different types of force fields-stable and unstable dynamics-and compared the performance of MMFC to that of OFC. MMFC delivered better performance than OFC in terms of stability and the achievement of tasks. Moreover, the gain in positional feedback with the MMFC model in the unstable dynamics was tuned to the direction of instability. It is assumed that the shape modulations of the gain in positional feedback in unstable dynamics played the same role as that played by end-point stiffness observed in human studies. Accordingly, we suggest that MMFC is a plausible model that predicts motor behavior under conditions of uncertain dynamics.


Reconstruction of the ZnAl Mixed Oxides Into the Layered Double Hydroxide Catalysts Active in the Aldol Condensation of Furfural: The Role of ZnO Particles.
A memory effect is the ability to restore the original, lamellar layered double hydroxide structure. Herein, we have described 1) the changes in the structural and basic properties of ZnAl mixed oxides during their transformation into ZnAl-reconstructed LDHs (RE-LDHs); 2) the extraordinary properties of ZnAl RE-LDHs compared to the original ZnAl LDHs; and 3) the changes of basic properties during the interaction of ZnAl RE-LDHs with atmospheric CO2. Aldol condensation was selected as probe reaction to prove the catalytic potential of ZnAl RE-LDHs. We have described a target method for preparing ZnAl RE-LDHs with a large number of basic sites. ZnAl RE-LDHs possess significantly higher furfural conversion in the aldol condensation of furfural than MOs. The structural, textural, and basic properties of the studied materials were described by temperature-programmed analysis, X-ray diffraction, N2 adsorption, temperature-programmed desorption of CO2, and in-situ diffuse reflectance spectroscopy.


Role of medical and molecular imaging in COPD.
Chronic obstructive pulmonary disease (COPD) is expected to climb on the podium of the leading causes of mortality worldwide in the upcoming decade. Clinical diagnosis of COPD has classically relied upon detecting irreversible airflow obstruction on pulmonary function testing as a global assessment of pulmonary physiology. However, the outcome is still not favorable to decrease mortality due to COPD. Progress made in both medical and molecular imaging fields are beginning to offer additional tools to address this clinical problem. This review aims to describe medical and molecular imaging modalities used to diagnose COPD and to select patients for appropriate treatments and to monitor response to therapy.


Combinational Effects of Polymer Viscoelasticity and Immobilized Peptides on Cell Adhesion to Cell-selective Scaffolds.
Immobilization of functional peptides on polymer material is necessary to produce cell-selective scaffolds. However, the expected effects of peptide immobilization differ considerably according to the properties of selected polymers. To understand such combinational effects of peptides and polymers, varieties of scaffolds including a combination of six types of poly(ε-caprolactone-co-D,L-lactide) and four types of cell-selective adhesion peptides were fabricated and compared. On each scaffold, the scaffold properties (i.e. mechanical) and their biological functions (i.e. fibroblast-/endothelial cell-/smooth muscle cell-selective adhesion) were measured and compared. The results showed that the cell adhesion performances of the peptides were considerably enhanced or inhibited by the combination of peptide and polymer properties. In the present study, we illustrated the combinational property effects of peptides and polymers using multi-parametric analyses. We provided an example of determining the best scaffold performance for tissue-engineered medical devices based on quantitative data-driven analyses.


Monoclonal gammopathies in the dog: a retrospective study of 18 cases (1986-1999) and literature review.
Eighteen dogs with monoclonal gammopathies were evaluated retrospectively. Most of the cases were associated with lymphoproliferative tumors (i.e., nine multiple myelomas, one Waldenström's macroglobulinemia, one lymphoma, one chronic lymphocytic leukemia, and one mucocutaneous plasmacytoma). The prevalence of nonmyelomatous monoclonal gammopathies (28%) was also significant (three leishmaniasis and two ehrlichiosis). Presenting complaints and clinical signs often were nonspecific or related to bleeding diathesis. Significant laboratory findings included proteinuria, hypoalbuminemia, and anemia. Some unusual features were also observed: a multiple myeloma with immunoglobulin M secretion, another myeloma with two narrow spikes on the electrophoretic pattern, and a mucocutaneous plasmacytoma secreting an immunoglobulin G paraprotein.


The association of perinatal and clinical factors with outcomes in infants with gastroschisis-a retrospective multicenter study in Finland.
The aim of the present study was to assess the prognostic factors for the outcome of gastroschisis in Finland. A retrospective multicenter study of gastroschisis patients born between 1993 and 2015 in four Finnish university hospitals was undertaken, collecting perinatal, surgical, and clinical data of neonates for uni- and multifactorial modeling analysis. The aim of the present study was to identify risk factors for mortality and the composite adverse outcome (death and/or short bowel syndrome or hospital stay > 60 days). Of the 154 infants with gastroschisis, the overall survival rate was 90.9%. In Cox regression analysis, independent risk factors for mortality included liver herniation, pulmonary hypoplasia, relaparotomy for perforation or necrosis, abdominal compartment syndrome, and central line sepsis. Furthermore, a logistic regression analysis identified central line sepsis, abdominal compartment syndrome, complex gastroschisis, and a younger gestational age as independent predictors of the composite adverse outcome.Conclusion: The risk of death is increased in newborns with gastroschisis who have liver herniation, pulmonary hypoplasia, abdominal compartment syndrome, relaparotomy for perforation or necrosis, or central line-associated sepsis. Special care should be taken to minimize the risk of central line sepsis in the clinical setting. What is known: • Gastroschisis is a relatively rare congenital anomaly of the abdominal wall and its incidence is increasing. • Complex gastroschisis has been reported to increase risk of mortality and complications. What is new: • Central line sepsis was found to be independently associated with mortality in gastroschisis patients. • Liver herniation was also significantly associated with mortality.


GLYX-13 pretreatment ameliorates long-term isoflurane exposure-induced cognitive impairment in mice.
Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment. GLYX-13 (rapastinel) acts on the glycine site of N-methyl-D-aspartate receptors (NMDARs) and has been shown to enhance hippocampus-dependent learning and memory function. However, the mechanisms by which GLYX-13 affects learning and memory function are still unclear. In this study, we investigated these mechanisms in a mouse model of long-term anesthesia exposure. Mice were intravenously administered 1 mg/kg GLYX-13 at 2 hours before isoflurane exposure (1.5% for 6 hours). Cognitive function was assessed using the contextual fear conditioning test and the novel object recognition test. The mRNA expression and phosphorylated protein levels of NMDAR pathway components, N-methyl-D-aspartate receptor subunit 2B(NR2B)-Ca2+/calmodulin dependent protein kinase II (CaMKII)-cyclic adenosine monophosphate response element binding protein (CREB), in the hippocampus were evaluated by quantitative RT-PCR and western blot assay. Pretreatment with GLYX-13 ameliorated isoflurane exposure-induced cognitive impairment and restored NR2B, CaMKII and CREB mRNA and phosphorylated protein levels. Intracerebroventricular injection of KN93, a selective CaMKII inhibitor, significantly diminished the effect of GLYX-13 on cognitive function and NR2B, CaMKII and CREB levels in the hippocampus. Taken together, our findings suggest that GLYX-13 pretreatment alleviates isoflurane-induced cognitive dysfunction by protecting against perturbation of the NR2B/CaMKII/CREB signaling pathway in the hippocampus. Therefore, GLYX-13 may have therapeutic potential for the treatment of anesthesia-induced cognitive dysfunction. This study was approved by the Experimental Animal Ethics Committee of Drum Tower Hospital affiliated to the Medical College of Nanjing University, China (approval No. 20171102) on November 20, 2017.


The effect of alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory drug, on leucocyte migration in rat carrageenan pleurisy.
KME-4,alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-buty rolactone was found to reduce the accumulation of leucocytes and exudate volume in the rat carrageenan pleurisy model. When administered orally 1 h before carrageenan, KME-4 (3-10 mg kg-1) induced a degree of inhibition of leucocyte migration almost equal to that of indomethacin (3-10 mg kg-1) in both 5 h and 24 h pleurisies. Furthermore, KME-4, when administered orally 5 h after the carrageenan, inhibited both monocyte numbers and exudate volume in a 24 h pleurisy and was more effective than indomethacin and BW755c which inhibited only monocyte migration. These results suggest that KME-4 has a differential anti-inflammatory activity. Dexamethasone (0.25 mg kg-1) showed strong inhibition of total cell numbers and exudate volume.


The Structure of Processing Speed in Children and its Impact on Reading.
The present study had two aims. First, we set out to evaluate the structure of processing speed in children by comparing five alternative models: two conceptual models (a unitary model, a complexity model) and three methodological models (a stimulus material model, an output response model, and a timing modality model). Second, we then used the resulting models to predict multiple types of reading, a highly important developmental outcome, using other well-known predictors as covariates. Participants were 844 children enrolled in third through fifth grade in urban public elementary schools who received 16 measures of processing speed that varied in the above dimensions. A two-factor complexity model that differentiated between simple and complex processing speed was the preferred model and fit the data well. Both types of PS predicted reading fluency, and complex (but not simple) PS predicted single word reading and comprehension. Results offer insight to the structure of processing speed, its relation to closely related concepts (such as executive function), and provide nuance to the understanding of the way processing speed influences reading.


T cell-B cell interaction: autoreactive T cells recognize B cells through a terminal mannose-containing superantigen-like glycoprotein.
Rat autoreactive T cells (ATs) recognize a membrane component(s) on syngeneic B cells in association with class II MHC antigens resulting in proliferation of ATs as well activation and differentiation of B cells. Results presented herein indicate that ATs recognize a stimulating antigen(s) SA, in association with class II MHC antigens, on the B cell surface. Our studies using inhibitors of carbohydrate and protein synthesis suggest that SA is a glycoprotein(s) with a high turnover rate but is not an immunoglobulin. Treatment of B cells with mannosidase abrogates their ability to stimulate AT proliferation. Furthermore, pretreatment of B cells with GNA (a lectin from Galanthus nivalis that reacts with free terminal-mannose residues on glycoconjugates) also inhibits their ability to stimulate ATs. However, these treatments do not affect the competence of B cells to stimulate an allogeneic MLR or present a conventional antigen to T cells. The frequency of CD4+ T cells proliferating in response to syngeneic B cells is very high (0.2-0.5%) and is in line with frequencies seen in "superantigen"-type responses. Moreover, T cell receptors expressed on ATs use mainly V beta 6, V beta 11, and V beta 8 regions. Based on these data, SA appears to be a fast turnover, terminal mannose-containing, superantigen-like glycoprotein on the B cell surface.


A novel method for removing residual acetone from gelatin microspheres.
To develop a method for removing residual acetone from gelatin microspheres. Free-flowing gelatin microspheres were either heated under vacuum or subjected to a stream of humidified air in a specially designed apparatus for removal of the residual acetone. To understand the removal mechanism, hygroscopic and thermal properties of the microspheres were examined. Heating the gelatin microspheres under vacuum did not reduce the acetone level below 2%, but the use of humidified air under fluidizing condition reduced the residual acetone in gelatin microspheres by an additional two orders of magnitude. The rate of acetone removal was a strong function of the relative humidity (RH) of the air stream; higher RH accelerated acetone removal. Other variables influencing the acetone removal rate are the mean particle diameter and the linear velocity of the humidified air. Under high relative humidities, significant amounts of moisture were absorbed into gelatin microspheres, reducing their glass transition temperature below 25 degrees C. The residual acetone in gelatin microspheres can be efficiently removed when exposed to air of high RH. Mechanisms of water-dependent acetone removal are proposed.


Evaluating maturation and genetic modification of human dendritic cells in a new polyolefin cell culture bag system.
Dendritic cells (DCs) are applied worldwide in several clinical studies of immune therapy of malignancies, autoimmune diseases, and transplantations. Most legislative bodies are demanding high standards for cultivation and transduction of cells. Closed-cell cultivating systems like cell culture bags would simplify and greatly improve the ability to reach these cultivation standards. We investigated if a new polyolefin cell culture bag enables maturation and adenoviral modification of human DCs in a closed system and compare the results with standard polystyrene flasks. Mononuclear cells were isolated from HLA-A*0201-positive blood donors by leukapheresis. A commercially available separation system (CliniMACS, Miltenyi Biotec) was used to isolate monocytes by positive selection using CD14-specific immunomagnetic beads. The essentially homogenous starting cell population was cultivated in the presence of granulocyte-macrophage-colony-stimulating factor and interleukin-4 in a closed-bag system in parallel to the standard flask cultivation system. Genetic modification was performed on Day 4. After induction of maturation on Day 5, mature DCs could be harvested and cryopreserved on Day 7. During the cultivation period comparative quality control was performed using flow cytometry, gene expression profiling, and functional assays. Both flasks and bags generated mature genetically modified DCs in similar yields. Surface membrane markers, expression profiles, and functional testing results were comparable. The use of a closed-bag system facilitated clinical applicability of genetically modified DCs. The polyolefin bag-based culture system yields DCs qualitatively and quantitatively comparable to the standard flask preparation. All steps including cryopreservation can be performed in a closed system facilitating standardized, safe, and reproducible preparation of therapeutic cells.


Isolation and characterization of a Pseudomonas aeruginosa genomic DNA sequence, encoding a putative DNA helicase belonging to superfamily I.
The isolation and characterization of a 2,122 bp DNA fragment from a Pseudomonas aeruginosa genomic library containing a 1,495 bp open reading frame (ORF) encoding a putative DNA helicase is described. The deduced amino acid (498 residues) sequence derived from this ORF, exhibited a high degree of homology to the rep and uvrD helicases of Escherichia coli (55 and 38% identities, respectively), and to those of Staphylococcus aureus and Haemophilus influenzae (43 and 39% identities, respectively), all of them belonging to superfamily I.


Altered Biological Properties in Dp71 Over-Expressing HBE Cells.
In order to further characterize the biological traits of Dp71, HBE over expressing two most abundantly expressed Dp71 spliced isoforms, Dp71d and Dp71f, were established and their biological traits were explored. The proliferation, migration and invasion capabilities of HBE-Dp71d and HBE-Dp71f cells were evaluated by MTT, colony formation, transwell and scratch assay. Cell cycle and apoptosis induced by H2O2 were measured by flow cytometer. Co-IP was performed to prove the interaction between lamin B1, FAK and Dp71. Western blot was performed to detect lamin B1, FAK, ERK and Cyclin D expression in HBE-Dp71d and HBE-Dp71f cells. HBE-Dp71d and HBE-Dp71f cells proliferated faster than their mock and blank controls; shortened their G0/G1 phase; enhanced their invasion and migration capabilities; reduced their apoptosis induced by H2O2. Co-IP proved Dp71 directly interacting with focal adhesion kinase (FAK) and lamin B1 in HBE cells. Increased lamin B1, FAK mRNA and protein expression, over activation of integrin/focal adhesion kinase/extracellular signal-regulated kinase (ERK)/cyclin D pathway were observed in HBE-Dp71d and HBE-Dp71f cells. Via increasing FAK in the cytoplasmic FAK-Dp71 , lamin B1 of nucleus laminB1-Dp71 complex, HBE-Dp71d and HBE-Dp71f cells alter their proliferation, migration, invasion, cell cycle and apoptosis rate induced by H2O2.


Clinical Efficacy and Safety of Bevacizumab, Apatinib, and Recombinant Human Endothelial Inhibitor in the Treatment of Advanced Gastric Cancer.
To investigate the clinical efficacy and safety of bevacizumab, apatinib, and recombinant human endothelial inhibitor in the treatment of advanced gastric cancer. The medical data of 204 patients with a medium to advanced gastric cancer assessed for eligibility treated in our hospital from February 2019 to April 2020 were retrospectively analyzed. The eligible patients were assigned at a ratio of 1 : 1:1 : 1 to either the control group (chemotherapy), study group I (bevacizumab combined with chemotherapy), study group II (apatinib combined with chemotherapy), or study group III (recombinant human endothelial inhibitor combined with chemotherapy) according to different treatment methods. The treatment efficacy, drug toxicity, quality of life, and serum tumor marker levels before and after treatment were compared among the four groups. Regarding the treatment effects, the effective rate of study group II (68.63%) was significantly higher than that of the control group (33.33%), study group I (58.82%), and study group III (49.02%) (P < 0.05). The four groups showed similar safety and tolerability profiles (P > 0.05). The treatment in study group II led to a significantly higher physiological function score vs. the other three groups, but the scores of other items were not significantly different. Significant reduction was observed in the serum tumor markers after treatment in the four groups (P < 0.05), but treatment in study group II led to a significantly greater reduction than the other three groups (P < 0.05). The addition of apatinib, bevacizumab, and recombinant human endothelial inhibitor injection to chemotherapy for the treatment of medium to advanced gastric cancer can significantly improve the clinical treatment efficacy, among which the use of apatinib combined with chemotherapy achieves the best results, which is worthy of clinical promotion.