Effect of early restrictive fluid resuscitation on inflammatory and immune factors in patients with severe pelvic fracture.
To study the effect of early restrictive fluid resuscitation (EFR) on inflammatory and immune factors in patients with severe pelvic fracture (SPF). A total of 174 SPF patients in the Department of Orthopaedics, the First Affiliated Hospital of Chengdu Medical College from July 2015 to June 2018 were involved in this study and divided into EFR group (n = 87) and control group (n = 87) using the random number table method. Conventional fluid resuscitation (CFR) was performed in control group, and EFR was performed in EFR group. The incidences of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS) during rescue, successful rescue rate, blood transfusion volume, fluid input, and resuscitation time were compared between the two groups. The parameters including prothrombin time (PT), hematocrit (HCT), platelet (PLT) and blood lactate (BL) at the 4th hour after fluid resuscitation were recorded. The levels of inflammatory factors (TNF-α, IL-6, CRP) and immune factors (CD3+, CD4+, CD8+, CD4+/CD8+) were compared between the two groups before treatment and 7 days after treatment. The revised acute physiologic and chronic health evaluation system and the sequential organ failure assessment scores were adopted for evaluation before treatment and 7 days after treatment. The incidences of ARDS and MODS during rescue in EFR group were significantly lower than those in control group (p=0.015 and 0.010 respectively), and the successful rescue rate in EFR group was significantly higher than that in control group (p = 0.011). The blood transfusion volume, fluid input, resuscitation time in EFR group were significantly lower than those in control group (p = 0.016, 0.002 and 0.001 respectively). At the 4th hour after fluid resuscitation, PT and BL in EFR group were significantly lower than those in control group (p = 0.021 and 0.003 respectively), while HCT and PLT in EFR group were significantly higher than those in control group (p = 0.016 and 0.021 respectively). On day 7 after treatment, TNF-α, IL-6, CRP and CD8+ in EFR group were significantly lower than those in control group (p = 0.003, 0.004, 0.007 and 0.003 respectively), while CD3+, CD4+ and CD4+/CD8+ in EFR group were significantly higher than those in control group (p = 0.004, 0.000, 0.007 respectively). On day 7 after treatment, the revised acute physiologic and chronic health evaluation (APACHE) system and the sequential organ failure assessment (SOFA) scores in EFR group were significantly lower than those in control group. EFR can effectively eliminate inflammatory factors, improve immune function, maintain the stability of blood components, reduce the incidences of ARDS and MODS, and elevate the successful rescue rate in patients with SPF.


Prostaglandin F2alpha as a mediator of pulmonary changes during platelet aggregation.
Increases in pulmonary arterial pressure, tracheal insufflation pressure, and blood levels of the prostaglandin F2alpha metabolite, 15-keto-13, 14-dihydro F2alpha, were observed after protamine chloride or thrombin-induced platelet aggregation and release reaction in dogs. These effects were largely eliminated after administration of acetylsalicylic acid, an inhibitor of prostaglandin synthesis. The platelet aggregation was not noticeably affected. It is suggested that release of prostaglandin F2alpha from platelets is an important factor for the pulmonary changes during induced platelet aggregation. The necessity of measuring metabolite levels, rather than prostaglandin F2alpha levels, in blood during in vivo conditions is demonstrated.


Cognitive deficits in reading disability and attention deficit disorder.
This paper presents data from three studies (a cross-sectional study of school-referred children, a test-retest study of subtypes of reading disabilities, and a study of a large, random sample of first graders) that focus on specifying the cognitive deficits associated with reading difficulties and separating them from those associated with attentional deficits. The cognitive deficits associated with difficulty in reading were consistent across samples, developmental levels, definitions, and subtypes of reading disabilities. With IQ, age, and sex controlled for, poor readers were significantly impaired on measures of naming and phonological awareness. The effects of attentional deficits were more variable and complex but were clearly separate from the reading disability effects.


Preparation of styrene-co-4-vinylpyridine magnetic polymer beads by microwave irradiation for analysis of trace 24-epibrassinolide in plant samples using high performance liquid chromatography.
In the study, a kind of novel styrene-co-4-vinylpyridine (St-co-4-VP) porous magnetic polymer beads was prepared by microwave irradiation using suspension polymerization. Microwave heating preparation greatly reduced the polymerization time to 1h. Physical characteristic tests suggested that these beads were cross-linking and possessed spherical shape, good magnetic response and porous morphologies with a narrow diameter distribution of 70-180 μm. Therefore, these beads displayed the long-term stability after undergoing 100-time extractions. Then, an analytical method for the determination of trace 24-epiBR in plant samples was developed by magnetic polymer bead extraction coupled with high performance liquid chromatography-fluorescence detection. St-co-4-VP magnetic polymer beads demonstrated the higher extraction selectivity for 24-epiBR than other reference compounds. Linear range was 10.00-100.0 μg/L with a relative standard deviation (RSD) of 6.7%, and the detection limit was 6.5 μg/kg. This analytical method was successfully applied to analyze the trace 24-epiBR in cole and breaking-wall rape pollen samples with recoveries of 77.2-90.0% and 72.3-83.4%, respectively, and RSDs were less than 4.1%. The amount of 24-epiBR in real breaking-wall rape pollen samples was found to be 26.2 μg/kg finally. This work proposed a sensitive, rapid, reliable and convenient analytical method for the determination of trace brassinosteroids in complicated plant samples by the use of St-co-4-VP magnetic polymer bead extraction coupled with chromatographic method.


A Validation Method to Determine Missing Years of Birth in a Cohort Study of Shipyard Workers Using Social Security Number.
The objective of the study is to evaluate the generalizability and feasibility of a prediction method developed by Block et al (1983) to estimate missing age of workers by using their Social Security Numbers (SSNs). Our study used a retrospective occupational cohort of about 15,000 workers from the Long Beach Naval Shipyard (1978 to 1985). Our results showed an 89.2% agreement (P < 0.0001) between the predicted and observed years of birth using Block's method. The correlation increased to 93.1% (P < 0.0001) after our modifications by removing workers with SSNs issued in U.S. territories. The method performed better in shipyard workers who obtained their SSNs after 1950. Although the method is useful in imputing missing age, the accuracy is dependent on the year, age, and location of SSN issuance.


Secretory dynamics of bioactive and immunoreactive prolactin in polycystic ovary syndrome.
To further investigate prolactin (PRL) secretion in polycystic ovary syndrome (PCO), the authors evaluated immunoreactive (immuno) and bioactive (bio) PRL levels in the basal state and in response to provocative testing with intravenous dopamine (DA), metoclopramide (MCP), and gonadotropin-releasing hormone (GnRH), before and after disulfiram. Basal measurements of immuno-PRL, bio-PRL, and the ratio of bio/immuno-PRL were similar in PCO and controls. The immuno-PRL decrement after DA was greater than that of bio-PRL in both groups (P less than 0.05). After MCP, immuno-PRL increased more than bio-PRL in PCO (P less than 0.01), and this immuno-PRL increment was greater than that of controls (P less than 0.05). Bio-PRL and immuno-PRL increased after GnRH in PCO, but not controls, and these responses were inhibited by disulfiram. These data confirm PRL hypersecretion in some women with PCO, which is better expressed by immunoreactivity than bioactivity. Given the assay systems and patients studied, bioactivity


Autologous recovery with protractedly undetectable donor chimerisms can precede stable donor engraftment in a nonmyeloablative cord blood transplant.
Low levels of donor chimerism on day 28 after hematopoietic stem cell transplantation are highly predictive of a subsequent rejection of donor cells A recent report on nonmyeloablative transplants has demonstrated that patients who engrafted after transplantation had at least 10% donor cells detectable at this time point. A patient is described who received a nonmyeloablative umbilical cord blood transplant and experienced subsequent full engraftment of donor cells despite the absence of donor chimerism at 4 weeks posttransplantation.


Image analysis-based recognition and quantification of grain number per panicle in rice.
The number grain per panicle of rice is an important phenotypic trait and a significant index for variety screening and cultivation management. The methods that are currently used to count the number of grains per panicle are manually conducted, making them labor intensive and time consuming. Existing image-based grain counting methods had difficulty in separating overlapped grains. In this study, we aimed to develop an image analysis-based method to quickly quantify the number of rice grains per panicle. We compared the counting accuracy of several methods among different image acquisition devices and multiple panicle shapes on both Indica and Japonica subspecies of rice. The linear regression model developed in this study had a grain counting accuracy greater than 96% and 97% for Japonica and Indica rice, respectively. Moreover, while the deep learning model that we used was more time consuming than the linear regression model, the average counting accuracy was greater than 99%. We developed a rice grain counting method that accurately counts the number of grains on a detached panicle, and believe this method can be a huge asset for guiding the development of high throughput methods for counting the grain number per panicle in other crops.


Rapid transmission of sheep pulmonary adenomatosis (jaagsiekte) in young lambs. Brief report.
Jaagsiekte, a contagious lung tumour of sheep, was induced within 3-6 weeks in day-old lambs by intratracheal inoculation of SPA lung fluids concentrated by centrifugation. Electronmicroscopic examination of the tumour revealed retrovirus particles whose morphogenesis and morphology support biophysical and immunological findings that suggest a relationship with type B and type D retroviruses.


Growth, energy intake, and meal pattern in five-year-old children considered as poor eaters.
To investigate whether 5-year-old children considered poor eaters differ from their peers regarding growth, intake of energy and nutrients, or meal pattern. Study design Parental evaluations of children's (n=494) eating at age 5 years were collected using questionnaires, and energy and nutrient intakes and meal pattern of the children were assessed using 4-day food records. Weight and height were measured at birth and at ages 7 and 13 months, and 2, 3, 4, and 5 years. Of the children 30.2% (149) were poor eaters according to the parents. The rest of the sample (n=345) formed the comparison group. Poor eaters were on average lighter and shorter at birth (P=.026 and P=.020, respectively), and at age 5 years (P<.001 for both weight and height) than the comparison children. At age 5 years the poor eaters on average received less of their daily total energy from warm meals (P=.044) and more from snacks (P=.013) than the comparison group, but the mean daily weight-adjusted intake of energy showed no difference between the groups (P=.153). There appears not to be reason for serious concern about growth and diet of preschool-aged children considered as poor eaters by parents.


[Formulation and Efficacy of Liposome-encapsulated Afatinib for Therapy of Non-small Cell Lung Cancer].
Afatinib, a second-generation irreversible epidermal growth factor inhibitor receptor for the development of non-small cell lung cancer and secondary drug resistance, has low bioavailability and adverse reactions due to current oral administration. The aim of this study was to prepare a novel drug delivery system, afatinib liposome, and to establish a method for the determination of encapsulation efficiency. Four different preparation methods were used to prepare afatinib liposomes, and the optimal preparation process was determined by comparing the encapsulation efficiency and particle size. It has been verified that sephadex microcolumn centrifugation can be used to purify afatinib liposomes, and UV spectrophotometry can be employed to determine the entrapment efficiency of liposomes. Among different preparation methods, the encapsulation efficiency of afatinib liposomes prepared by ammonium sulfate gradient method was 90.73% and the average particle size was 108.6 nm. Ammonium sulfate gradient method can be successfully applied to prepare afatinib liposomes that performed higher encapsulation efficiency and smaller particle size. The UV spectrophotometry employed to determine the liposome encapsulation efficiency was easy operation and with high accuracy.


Regulation of Streptococcus pneumoniae distribution by Toll-like receptor 2 in vivo.
The phagocyte pattern recognition receptor Toll-like receptor 2 (TLR2) and the multi-receptor adaptor MyD88 contribute to the reduction of bacterial load in infections with intra- and extra-cellular Gram-positive bacteria. Their mechanism of antibacterial action is mostly unresolved but evident in vivo by an increased pathogen burden in infected TLR2-/- and MyD88-/- compared to C57BL/6 wild type (wt) mice. We had previously observed higher bacterial numbers in brains of TLR2-/- than of wt mice with meningitis. Here we study bacteria-phagocyte interaction by comparing S. pneumoniae distribution and localization in wt and TLR2-/- brain by confocal microscopy using a green fluorescent protein-transformed encapsulated S. pneumoniae (C5017). Colony-forming units were similarly distributed in TLR2-/- and wt mice and exclusively localized in meninges and ventricles. Bacteria were more abundant in ventricles, in and around TLR2-/- than wt GLT1v+ plexus choroideus epithelial cells. S. pneumoniae were also found in and around Gr-1+ granulocytes, but never in F4/80+ macrophages, Iba1+ microglia, GFAP+ astrocytes, Meca-31+ endothelial cells or Neun+ neurons of either mouse strain. The results indicate that TLR2 does not change bacterial distribution, but may contribute to antibacterial defense by modulating S. pneumoniae adherence and uptake in plexus epithelia.


Rectal colonization with multidrug-resistant gram-negative bacteria in patients with hematological malignancies: a prospective study.
To investigate the risk factors for rectal colonization with carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) in hematological malignant patients with febrile neutropenia (FN); rate of rectal colonization and infection/colonization with CRE and ESBL-E; whether empirical treatment can be revised. Adult patients receiving chemotherapy were included. Rectal swab cultures of patients were screened for CRE and ESBL-E using selective chromogenic agars. Fifty-seven FN episodes of 57 patients were studied. Rectal colonization rates were 40.4% (23/57) and 8.8% (5/57) for ESBL-E and CRE, respectively. ESBL-E bacteremia was diagnosed in 2 (8.6%) ESBL-E colonized patients, while CRE bacteremia was detected in 1 (20%) CRE colonized patient. Amikacin (100%) and carbapenem (93%) were the most effective antibiotics against gram-negative enteric bacteria. Beta-lactam usage within the last 3 months was a significant risk factor for ESBL-E colonization. For the treatment of FN patients either colonized with ESBL-E or having significant risk factors for ESBL-E infection, aminoglycoside containing combinations may become an alternative to carbapenems due to their high sensitivity rates. When CRE colonized hematological cancer patients develop FN or if they are hemodynamically unstable, CRE covering empiric antibiotherapy should be preferred due to high mortality rates of CRE bacteremia.


Built Environments and Active Living in Rural and Remote Areas: a Review of the Literature.
Rural children and adults are more likely to have obesity than their urban counterparts even after adjustment for individual-level behaviors, suggesting that rural environments may promote obesity. The rural built environment may be an important area of research that can help us understand rural-urban disparities in obesity. The purpose of this review is to summarize the rural built environment and active living literature, and to address key issues, gaps, and observations in the field. A literature review was conducted in spring 2015 to identify research published from 2000 to 2015. Our review suggests that limited active living built environments in rural communities and unique rural barriers to physical activity may contribute to a higher prevalence of obesity compared to urban populations. More empirical research is needed to build the evidence-base for the association between rural built environments, active living, and obesity. School- and community-based policies that expand active living opportunities in rural areas should also be closely examined.


Crystallization-driven evolution of water occurrence states with implications on dewaterability improvement of waste-activated sludge.
This study proposed to improve the dewaterability of waste-activated sludge (WAS) through crystallization-driven evolution of water occurrence states. Primarily, the feasibility of clathrate hydrate (i.e., CO2 hydrate) formation in WAS was examined. The thermodynamic analysis indicated that the CO2 hydrate formation with the excessive water in WAS followed pseudo-first-order kinetics, and fit of the data yielded a kobs value of 3.905 × 10-5 L∙mol-1∙s-1 for 274.15 K. With the water conversion efficiency of 100%, the crystallization-dissociation process of CO2 hydrate significantly improved the dewaterability of WAS in term of capillary suction time (CST) decreasing from 251.5 s to 57.4 s. Also, the relief of gas pressure can induce the hydrate dissociation, which creates a novel way to recycle CO2 gas and save the consumption of chemicals required by sludge dewatering process. Regarding the mechanism of hydrates-based sludge dewatering, the evolution of water occurrence state was investigated. The in-situ synchrotron X-ray computed microtomography visually analyzed the micro-scale porosity and interstitial water of WAS flocs. The model of three-dimensional pore structure was established and the porosity parameters of solid aggregates were determined. It was found that the volume of connected pores and the total pore volume fraction of solid compositions increased. But the mean volume and mean area of isolated pores simultaneously decreased by 14.6% and 12.4%, respectively, which meant that the steric hindrance caused by isolated pores was weakened due to the reduced solid-water contact area. In addition, the crystallization of water caused the reformation of conformation arrangement of vicinal water and solid molecules, which highly organized the water molecules into the crystal structure. Accordingly, an estimation method for vicinal water layer thickness was developed based on atom force microscope. The thickness of vicinal water layer was found to be reduced by 77.4% and the hydration repulsion among solid compositions was correspondingly weakened, which facilitated the aggregation of solid compositions, and the relatively separated hydrate phase and solid phase could be formed. All the above results open up a novel strategy for enhanced water-solid separation of WAS through the crystallization-driven evolution of water occurrence states. As distinguished from the conventional approaches, the hydrates-based sludge dewatering enhances the water-solid separation only with regulating the spatial arrangement of water-solid molecules, but without altering the chemical compositions. Thus, more chances can be created to increase the environmentally friendly attributes related to WAS dewatering.


Clonal X-chromosome inactivation suggests that splenic cord capillary hemangioma is a true neoplasm and not a subtype of splenic hamartoma.
Splenic hamartoma is a rare tumor-like lesion composed of structurally disorganized red pulp elements. It has been hypothesized that two other splenic lesions, cord capillary hemangioma and myoid angioendothelioma, may fall within the spectrum of splenic hamartoma, simply representing morphological variants. In this study, we compared the vascular and stromal composition of cord capillary hemangioma and myoid angioendothelioma with those of classical hamartoma. In addition, we assessed the clonal vs polyclonal nature of the lesions in nine female cases by performing clonality analysis for X-chromosome inactivation at the human androgen receptor locus (HUMARA) on laser-assisted microdissected samples. In 15 of 17 cases, increased reticulin and/or collagen content was observed. The classical hamartoma cases showed a vasculature predominantly composed of CD8+ CD31+ CD34- splenic sinuses, whereas cases of cord capillary hemangioma and myoid angioendothelioma contained many CD8- CD31+ CD34+ cord capillaries, but very little CD8+ vasculature. All cases lacked expression of D2-40 and Epstein Barr virus-encoded RNA. All cases showed a proliferation index of ≤5% by Ki-67. Cases of classical hamartoma lacked significant perisinusoidal expression of collagen IV and low-affinity nerve growth factor receptor. Both markers were variably expressed in the other lesions. Increased CD163-positive histiocytes were found in four cases (three cord capillary hemangiomas and one myoid angioendothelioma). HUMARA analysis was informative in all nine tested cases, of which three cases showed a non-random X-chromosome inactivation pattern, indicating clonality. All three clonal cases were cord capillary hemangiomas. Our study has shown that in spite of considerable morphologic heterogeneity and overlapping features, classical hamartoma and cord capillary hemangioma and myoid angioendothelioma are different in terms of their vascular and stromal composition. Clonality analysis supports a true neoplastic origin for the cord capillary hemangioma. A larger study using additional immunohistochemical and molecular studies is necessary to further evaluate the biological significance of the current findings.


Synthesis and characterization of 2,7-bis(pentafluorophenylethynyl)hexafluoroheterofluorenes: new materials with high electron affinities.
The synthesis, optical, electrochemical and physical characterization of 2,7-bis(pentafluorophenylethynyl)hexafluoroheterofluorenes is described along with a preliminary evaluation of their performance in photovoltaic applications.


Comparison of adsorption equilibrium and kinetics of four chlorinated organics from water onto GAC.
This study deals with the adsorption of four chlorinated pollutants onto GAC (F-400); two pesticides (lindane and alachlor) and two PCB congeners: 2-PCB (MPCB) and 2,2',5,5'-PCB (TPCB). Equilibrium and kinetic parameters have been obtained for the adsorption of alachlor and each PCB. whereas the kinetic results for lindane presented elsewhere (Proc. First World Water Congr. Int. Water Assoc., Texts of Posters, CD-ROM, AGHTM, Paris, 2000) are reanalyzed in this work. A model assuming a bidisperse structure (macro- and micropores). each region having a different adsorption isotherm, is used to study the adsorption kinetics in a batch system in the period dominated by macropore diffusion. Both the saturation capacity and the rate of internal transport of TPCB are much lower than those of the other solutes. This difference is attributed to a chemisorption mechanism for this compound, which is favored by its very low solubility.


Arsenic concentrations in rice, vegetables, and fish in Bangladesh: a preliminary study.
Arsenic contaminating groundwater in Bangladesh is one of the largest environmental health hazards in the world. Because of the potential risk to human health through consumption of agricultural produce grown in fields irrigated with arsenic contaminated water, we have determined the level of contamination in 100 samples of crop, vegetables and fresh water fish collected from three different regions in Bangladesh. Arsenic concentrations were determined by hydride generation atomic absorption spectrophotometry. All 11 samples of water and 18 samples of soil exceeded the expected limits of arsenic. No samples of rice grain (Oryza sativa L.) had arsenic concentrations more than the recommended limit of 1.0 mg/kg. However, rice plants, especially the roots had a significantly higher concentration of arsenic (2.4 mg/kg) compared to stem (0.73 mg/kg) and rice grains (0.14 mg/kg). Arsenic contents of vegetables varied; those exceeding the food safety limits included Kachu sak (Colocasia antiquorum) (0.09-3.99 mg/kg, n=9), potatoes (Solanum tuberisum) (0.07-1.36 mg/kg, n=5), and Kalmi sak (Ipomoea reptoms) (0.1-1.53 mg/kg, n=6). Lata fish (Ophicephalus punctatus) did not contain unacceptable levels of arsenic. These results indicate that arsenic contaminates some food items in Bangladesh. Further studies with larger samples are needed to demonstrate the extent of arsenic contamination of food in Bangladesh.


Involvement of increased endoplasmic reticulum stress in the development of cataracts in BALB.NCT-Cpoxnct mice.
The BALB.NCT-Cpoxnct is a mutant mouse model for hereditary cataracts. We previously uncovered that the primary cause of the cataracts of BALB.NCT-Cpoxnct is a mutation in the coproporphyrinogen oxidase (Cpox) gene. Because of the mutation, excessive coproporphyrin is accumulated in the BALB.NCT-Cpoxnct lens. In this study, we analyzed the changes in transcriptome and proteins in the lenses of 4- and 12-week-old BALB.NCT-Cpoxnct to further elucidate the molecular etiology of cataracts in this mouse strain. Transcriptome analysis revealed that endoplasmic reticulum (ER) stress was increased in the BALB.NCT-Cpoxnct lens that induced persistent activation of the PERK signaling pathway of the ER stress response. Also, levels of crystallin transcripts and proteins were reduced in the BALB.NCT-Cpoxnct lens. Analysis of proteins disclosed aggregation of crystallins and keratins prior to the manifestation of cataracts in 4-week-old BALB.NCT-Cpoxnct mice. At 12 weeks of age, insoluble crystallins were accumulated in the cataractous BALB.NCT-Cpoxnct lens. Overall, our data suggest the following sequence of events in the BALB.NCT-Cpoxnct lens: accumulated coproporphyrin induces the aggregation of proteins including crystallins. Aggregated proteins increase ER stress that, in turn, leads to the repression of global translation of proteins including crystallins. The decline in the molecular chaperone crystallin aggravates aggregation and insolubilization of proteins. This vicious cycle would eventually lead to cataracts in BALB.NCT-Cpoxnct.


Microsatellite instability screening in colorectal adenomas to detect Lynch syndrome patients? A systematic review and meta-analysis.
The colorectal cancer spectrum has changed due to population screening programs, with a shift toward adenomas and early cancers. Whether it would be a feasible option to test these adenomas for detection of Lynch syndrome (LS) patients is unclear. Through meta-analysis and systematic review, risk factors for DNA mismatch repair deficiency (dMMR) and microsatellite instability (MSI) in adenomas were identified in LS and unselected patient cohorts. Data were extracted for patient age and MMR variant together with adenoma type, grade, size, and location. A total of 41 studies were included, and contained more than 519 LS patients and 1698 unselected patients with 1142 and 2213 adenomas respectively. dMMR/MSI was present in 69.5% of conventional adenomas in LS patients, compared with 2.8% in unselected patients. In the LS cohort, dMMR/MSI was more frequently present in patients older than 60 years (82% versus 54%). dMMR/MSI was also more common in villous adenomas (84%), adenomas over 1 cm (81%), and adenomas with high grade dysplasia (88%). No significant differences were observed for dMMR/MSI in relation to MMR variants and location of adenomas. In the context of screening, we conclude that detection of dMMR/MSI in conventional adenomas of unselected patients is uncommon and might be considered as indication for LS testing. Within the LS cohort, 69.5% of LS patients could have been detected through dMMR/MSI screening of their conventional adenomas.


Reduced adenosine release from the aged mammalian heart.
Adenosine (ADO) released in the heart results in enhanced coronary blood flow and reduced catecholamine release and myocardial responsiveness to adrenergic stimulation (anti-adrenergic action). ADO release from the adrenergic-stimulated aged heart is less than that from the young adult heart. Because adrenergic signaling in the aged heart is impaired, this study was conducted to determine if reduced ADO release from the aged heart results from this reduced adrenergic responsiveness. Hearts of 3-4 months (young adult) and 21-22 months (aged) Fischer-344 rats were perfused with ADO deamination and re-phosphorylation inhibited. Coronary effluent ADO levels were determined. Cellular-free ADO levels with and without sodium acetate (NaAc)-induced mitochondrial AMP synthesis were assessed using formed S-adenosylhomocysteine (SAH) in L-homocysteine thiolactone (L-HC)-treated hearts. The activities of SAH-hydrolase were determined. Aged heart ADO release was 61% less than from young hearts. NaAc augmented young heart ADO release by 104%, while that of aged hearts remained unchanged. SAH synthesis was 51% and 56% lower in the aged heart in the absence and presence of NaAc, respectively, despite an 89% greater SAH hydrolase activity found in the aged hearts. Since synthesized AMP may be diverted to IMP and ultimately inosine by AMP deaminase, inosine release was determined. Aged heart inosine levels in the absence and presence of NaAc were 74% and 59% less than for the young hearts. It is concluded that a reduced mitochondrial AMP synthesis is in part responsible for the attenuation in ADO release from the adrenergic-stimulated aged heart.


[The safety of telbivudine in preventing mother-to-infant transmission of hepatitis B virus in pregnant women after discontinuation].
To determine the efficacy and safety of telbivudine for blocking intrauterine transmission of hepatitis B virus (HBV) in pregnant women with high-load HBV DNA. Women in general good health and pragnant were enrolled for study between the ages of 20 to 40 year-old, with a diagnosis of HBV infection with high-load HBV DNA level (≥1*10(6) IU/ml). According to each participant's willingness, the women were divided into a telbivudine treatment group (82 women) and an untreated control group (75 women). The telbivudine treatment was initiated at gestation week 26 as oral dosing of 600 mg/d and continued until 1 month after the birth.Women in the control group had not gotten any antiviral drug treatment. All of the women delivered by cesarean section, and all of the neonates were administered the standard passive immunization therapy, which consisted of a hepatitis B immunoglobulin (200 IU) injection given within 12 hours of birth and an injection of hepatitis B vaccine (20 µg) at birth and at postnatal month 1 and 6. None of the mother's performed breastfeeding. The telbivudine-treated women showed a significant decrease in HBV DNA levels prior to delivery, as well as significantly decreased prenatal HBV DNA levels (>2 logl0). Efficiency of the telbivudine treatment was 100%. Immediately prior to delivery, 16 (19.5%) of the women in the telbivudine treatment group showed negative HBV DNA status, as opposed to the untreated control group in which no women showed negative status. The telbivudine treatment group had no case of maternal or fetal adverse reaction or of congenital malformation. Use of telbivudine antiviral therapy during late pregnancy in women with high-load HBV DNA can significantly reduce level of HBV DNA in maternal peripheral blood, block HBV intrauterine transmission, and provide good short-term efficacy, with good tolerability and safety.


Patient-Specific Resection Strategy of Glioblastoma Multiforme: Choice Based on a Preoperative Scoring Scale.
The real association between extent of resection and outcome in patients with glioblastoma multiforme (GBM) remains unclear. The goal of this study was to disclose the effect of gross total resection on survival and establish a scale used for surgical decision making. A retrospective review was undertaken of 416 patients who received operation for GBM from 2008 to 2015 in Beijing Tiantan Hospital. To reduce bias in patient selection, propensity score analysis was conducted and 99 pairs of matched GBMs were generated. Survival between different groups was compared using the Kaplan-Meier method, and independent predictors of survival were identified using the Cox proportional hazards model. Overall, the survival of patients undergoing GTR was significantly longer than those not undergoing GTR (12.0 vs. 9.0 months [p < 0.001] for progression-free survival [PFS], and 20.5 versus 16.0 months [p < 0.001] for overall survival [OS]). In the propensity model, the survival benefit of GTR remained significant, which has been further validated in the multivariate analysis (hazard ratio [HR] 0.613, 95% confidence interval [CI] 0.454-0.827 [p = 0.001] for PFS, and HR 0.475, 95% CI 0.343-0.659 [p < 0.001] for OS). Using a scoring scale based on age, epilepsy, location, tumor size, and Karnofsky performance score, patients were stratified into low-, moderate-, and high-risk cohorts. The survival benefit of GTR could be observed in the low- and moderate-risk cohorts but not the high-risk cohort. GTR was an independent predictor of increased survival for patients with GBM. The risk scoring scale quantified the clinical significance of operation and helped us to project more personalized surgical strategies for individual patients.


Clinical dosimetry of the rectum in cathetron applications for treatment of carcinoma of the uterine cavity.
Rectal dose measurements have been carried out for 60 patients undergoing Cathetron therapy for the treatment of carcinoma of the uterine cervix at the Cancer Hospital, Indore. The measurements show that the maximum rectal dose occurred around 8 cm from the anal verge. In most of the cases (approximately 75%) the maximum rectal dose lies between 50 and 85% of the dose at point A. The combined biologically effective doses from intracavitary and external beam therapy regimes in this centre and the clinical complications have been compared with those of other centres. Although no immediate serious rectal complications have been observed, it is desirable to check the rectal dose using monitoring source pencils, so that the applicators and rectal retractor can be readjusted, if necessary, to minimise the dose.


[Psychic pain, somatic risks and psychological suffering in elderly people].
Physical pain, like psychic pain, is still trivialised by healthcare practitioners working in geriatrics. Physical pains in elderly people are not isolated but often occur in a context of motor and mental incapacities rendering communication of the complaint somewhat erratic. They generate anxiety, which often amplifies their perception. This article represents a reflection about the management of pain in elderly people.


The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1.
Tyrosyl-DNA phosphodiesterase (Tdp1) catalyzes the hydrolysis of a phosphodiester bond between a tyrosine residue and a DNA 3' phosphate. The enzyme appears to be responsible for repairing the unique protein-DNA linkage that occurs when eukaryotic topoisomerase I becomes stalled on the DNA in the cell. The 1.69 A crystal structure reveals that human Tdp1 is a monomer composed of two similar domains that are related by a pseudo-2-fold axis of symmetry. Each domain contributes conserved histidine, lysine, and asparagine residues to form a single active site. The structure of Tdp1 confirms that the protein has many similarities to the members of the phospholipase D (PLD) superfamily and indicates a similar catalytic mechanism. The structure also suggests how the unusual protein-DNA substrate binds and provides insights about the nature of the substrate in vivo.


[Effect of sigetin on anovulation in rats].
The effect of sygethin on anovulatory cycle was studied in mature female rats. Anovulation was experimentally induced in rats on the one hand by stress effect (keeping rats in crowded conditions), and on the other hand by removing one ovary (hemicastration). Sygethin therapy (10 mg/kg for 4-5 days) proved to restore normal ovulation. When higher sygethin doses were used, and when it was administered for longer periods (for 2 to 3 weeks) no such effect proved to ensue. The results of these experiments suggest that small doses of sygethin stimulated luteinizing hormone secretion.


Effects of N-acetylcysteine and 2,3-dimercaptosuccinic acid on lead induced oxidative stress in rat lenses.
Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to biochemical and physiological dysfunction. The present study investigated the effects of exposure on the redox status of the lenses of Fisher 344 rats and examined whether antioxidant or chelator administration reversed these changes. Animals were given 5 weeks of 2000 ppm Pb exposure followed by 1 week of either antioxidant, chelator or distilled water administration. Glutathione (GSH) and cysteine (CYS) levels decreased in the Pb-exposed group. N-acetylcysteine or 2,3-dimercaptopsuccinic acid (Succimer) supplementation following Pb intoxication resulted in increases in the GSH and CYS levels. Protein bound glutathione (PSSG) and cysteine (PSSC) increased following Pb exposure. In the Succimer-treated animals, the PSSG decreased significantly. The glutathione disulfide (GSSG) levels remained unchanged. Malondialdehyde (MDA) levels, a major lipid peroxidation byproduct, increased following Pb exposure and decreased following Succimer treatment. Our results suggest that antioxidant supplementation, as well as chelation, following Pb exposure may enhance the reductive status of lenses.


Crystallization of a ribonuclease-resistant fragment of Escherichia coli 5 S ribosomal RNA and its complex with protein L25.
A ribonuclease-resistant fragment of Escherichia coli 5 S ribosomal RNA has been crystallized. The space group is P6(1)22 or P6(5)22, with a = 59.5 A and C = 268 A. The crystals contain one molecule per asymmetric unit, and show diffraction to 4.0 A resolution. Also, a complex of this fragment with L25 ribosomal protein has been crystallized in the same space group, but with a = 119 A, c = 250 A and four molecules per asymmetric unit.


Author Correction: ZFP36L1 and ZFP36L2 inhibit cell proliferation in a cyclin D-dependent and p53-independent manner.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Further verification of some postulates of the combined toxicity theory: New animal experimental data on separate and joint adverse effects of lead and cadmium.
Outbred male rats were repeatedly injected intraperitoneally two-level sub-lethal doses of lead acetate and/or cadmium chloride solutions 3 times a week during 6 weeks. The animals developed explicit, even if moderate, subchronic intoxication characterized by a large number of indices, both common to both metals (including increased DNA fragmentation coefficient) and lead-specific. Special attention was paid to hemodynamic and electrocardiographic effects. The combined action of lead and cadmium was modeled with the help of the Response Surface Methodology to obtain additional support for the previously substantiated postulates of combined toxicity's typological ambiguity. This is dependent on which particular effect comes under consideration, on its level, and on the acting dose ratio. For one and the same toxic combination, the type of combined toxic action can vary from synergistic to contra-directional. In particular, the actions of lead and cadmium on blood pressure were found to be opposite in direction. Furthermore, it is shown once again that the systemic toxic effects of a metal combination, its in vivo genotoxicity included, can be more or less attenuated by background administration of a theoretically justified composition of biologically active agents.


[Catheter ablation of cardiac arrhythmias : Forms of energy and biophysical principles].
Catheter ablation of cardiac arrhythmias has evolved over the years and has become a cornerstone in the modern treatment of various supraventricular and ventricular arrhythmias. The goal of ablation is to permanently damage myocardium that is critically involved in the individual arrhythmia mechanism. Different catheters and forms of energy are available. Radiofrequency (RF) ablation is most common. Application of an alternating current at the catheter tip induces heating of tissue and, thus, leads to ablation of a targeted arrhythmogenic substrate. High temperatures (>70 °C at the catheter tip and >95 °C within the tissue) bear the risk of coagulum formation and steam pops and should be avoided, which limits power application. The evolution of irrigated RF ablation catheters enables the transfer of more power to the tissue and thereby increases the dimensions of the lesions. Cryoablation represents a valuable alternative. Cooling of tissue to -80 °C causes the intra- and extracellular formation of ice crystals, finally resulting in a dense circumscribed scar. The cryomapping procedure grants improved surveillance of the safety of ablation. Cryoenergy is very popular for pulmonary vein isolation (PVI) using the cryoballoon. In addition to the laser balloon that is established for PVI, ultrasound, microwaves, and stereotactic irradiation complete the arsenal.


An investigation in to the impact of acquisition location on error type and rate when undertaking panoramic radiography.
Panoramic radiography is a common radiographic examination carried out in the UK. This study was carried out to determine if acquisition site has an impact on image quality. An image quality audit was carried out in South Wales across a number of dental and general radiology settings. The image quality was assessed retrospectively against national standards. A total of 174 radiographs were assessed from general radiology departments and 141 from dental radiology units. Chi-squared analysis was used to investigate whether there were differences in the grading between dental radiology units and general radiology departments. Differences between the two settings in terms of the number of errors in the radiographs was analysed using the Mann-Whitney test. Chi-squared analysis was used to see if there were differences between the types of errors in the two clinical settings. There was a significant association (p = 0.021) between the quality of the radiograph grading and type of radiology department. However when excellent and diagnostically acceptable radiographs were grouped together there was no significant difference between the two clinical settings. Although the vast majority of radiographs were diagnostic (89% for general radiology and 92% for dental radiology units), neither reached the required standards. The most common errors were patient positioning errors (54.6% radiographs affected) and preparation/instructional errors (47.9% radiographs affected). Errors in panoramic radiography are relatively high and further instruction to staff undertaking these procedures is required to ensure the targets are reached.


Technical differences between sequencing and microarray platforms impact transcriptomic subtyping of colorectal cancer.
Gene expression profiling has increasing relevance in the molecular screening of patients with colorectal cancer (CRC). We investigated potential platform-specific effects on transcriptomic subtyping according to established frameworks by comparisons of expression profiles from RNA sequencing and exon-resolution microarrays in 126 primary microsatellite stable CRCs. There was a strong platform correspondence in global gene expression levels, albeit with systematic technical bias likely attributed to few sequencing reads covering short (<2000 nucleotides) and/or lowly expressed genes (<1 FPKM), as well as over-saturation of highly expressed genes on microarrays. Classification concordances according to both the consensus molecular subtypes and CRC intrinsic subtypes (CRIS) were also strong, but with disproportionate subtype distributions between platforms caused by frequent disagreements in adherence to sample classification thresholds. Subtypes defined largely by genes expressed at low levels, including the CRIS-D subtype and the estimated level of tumor-infiltrating cytotoxic lymphocytes, had a weaker correspondence in classification metrics between platforms. In conclusion, even subtle differences between platforms suggest that clinical translation of transcriptomic CRC subtyping frameworks is dependent on assay standardization, and systematic technical biases reinforce the need for careful selection of classifier genes.


Excessive risk and poor outcome of hospital-acquired peritoneal dialysis-related peritonitis.
Peritoneal dialysis (PD) is a home-based renal replacement therapy. Since hospital staff are not often familiar with PD and its complications, PD patients may have an excess risk of developing PD-related peritonitis during hospital admission for unrelated reasons, and the outcome may be affected. We reviewed 371 episodes of hospital-acquired PD peritonitis in our center from 2000 to 2019. Their clinical characteristics and outcomes were compared with 825 episodes that required hospital admission and 1964 episodes that were treated as outpatient. Hospitalized PD patients had a significantly higher risk of developing peritonitis than outpatients [incident rate ratio 4.41 (95% confidence interval 3.95-4.91]. Hospital-acquired peritonitis episodes were more commonly culture negative. Bacterial isolates from the hospital-acquired episodes were more likely resistant to ceftazidime (P < .0001) than the other groups. The primary response rate, complete cure rate and overall mortality of the hospital-acquired episodes were 66.6%, 62.0%, and 23.2%, respectively, all worse than episodes that developed outside the hospital (P < .0001 for all). PD patients admitted to the hospital had a 4-fold increase in the risk of developing peritonitis. Hospital-acquired peritonitis episodes were more likely culture negative and resistant to antibiotics. They also had a lower primary response rate, a lower complete cure rate and higher mortality than episodes that developed outside the hospital.


Familial occurrence of dermatomyositis and progressive scleroderma after injection of a local anaesthetic for dental treatment.
In an 11-year-old boy severe dermatomyositis occurred a few days after injection in the jaw of a local anaesthetic of the amide type for tooth extraction. The patient's grandmother was affected by progressive scleroderma at the age of 34 years, also after injection of a local anaesthetic for dental treatment. Both cases are discussed with special reference to the immuno-genetic aspects of the origin of dermatomyositis.


Evaluation and treatment of stage 0 Charcot's neuroarthropathy of the foot and ankle.
Charcot's neuroarthropathy is a relatively common disease in patients with diabetic neuropathy. If unrecognized or left untreated, Charcot's neuroarthropathy can result in a severely misshapen and unstable foot and ankle. Ulceration, soft-tissue infection, and osteomyelitis frequently ensue, and partial or complete amputation of the foot is not uncommon. A high index of suspicion and proper interpretation of clinical and diagnostic findings are essential to establish a timely and accurate diagnosis and to institute appropriate treatment. The pathogenesis of neuroarthropathy is reviewed and diagnosis and treatment of the stage 0 diabetic Charcot foot are presented.


Biomass and lipid production from Nannochloropsis oculata growth in raceway ponds operated in sequential batch mode under greenhouse conditions.
The effect of sequential batch cultures of the marine microalgae Nannochloropsis oculata on lipid and biomass production was studied in 200-L raceway ponds for 167 days (nine harvesting cycles) during winter and spring seasons under greenhouse conditions. The highest biomass concentration and productivity were 1.2 g/L and 49.8 mg/L/day on days 73 (5th cycle) and 167 (9th cycle), respectively. The overall interval of lipid production was between 131 and 530 mg/L. Despite the daily and seasonal variations of light irradiance (0-1099 μmol photon/m2 s), greenhouse temperature (2.1-50.7 °C), and culture temperature (12.5-31.4 °C), ANOVA analysis showed no statistical difference (p value > 0.01) on the fatty acid methyl ester (FAMES) composition over the nine harvesting cycles evaluated. The most abundant FAMES were palmitic (C16:0), stearic (C18:0) and palmitoleic (C16:1∆9) acids with 37.1, 28.6, and 8.4 %, respectively. The sequential batch cultures of N. oculata in raceway ponds showed an increasing biomass production in each new cycle while keeping the quality of the fatty acid mixture under daily and seasonal variations of light irradiance and temperature.


Dorsally recumbent urinary endoscopic surgery.
Laparoscopic cystotomy is the method of choice for treatment of a cystic calculus in the horse. The main advantage of this procedure over others is the excellent ability to view and gain operative access to the urinary bladder. This article describes the procedure, including techniques, instrumentation, preoperative and postoperative care, and complications.


Prevalence of preeclampsia and the associated risk factors among pregnant women in Bangladesh.
Preeclampsia is a multi-organ system disorder of pregnancy and is responsible for a significant rate of maternal morbidity and mortality worldwide. In Bangladesh, a large number of obstetric deaths occur every year but the exact reasons are not well investigated. The data regarding preeclampsia and its associated risk factors are scarce or limited in pregnant women in Bangladesh. Therefore, we aimed to conduct a cross-sectional study to estimate the prevalence of preeclampsia and identify the possible risk factors in a pregnant women cohort in Bangladesh. In this cross-sectional study, a total of 111 participants were enrolled and asked to include their anthropometric, socio-demographic, and other related lifestyle information in a standard questionnaire form. Blood samples were also collected from each participant to analyze serum levels of lipid profile, liver enzymes, uric acid, and creatinine by using standard methods. Logistic regression analysis was performed to identify the factors associated with preeclampsia. The overall prevalence of preeclampsia was 14.4%. About 10% of the pregnancies were found to have preeclampsia after 20 weeks of gestation without a previous history of hypertension. On the other hand, the prevalence of preeclampsia that superimposed on chronic hypertension was found to be 5.4%. Serum levels of TC, LDL-C, ALT and uric acid were significantly higher and HDL-C was significantly lower in preeclamptic pregnancies than the non-preeclamptic pregnancies. Respondents who required to take antihypertensive medications (AOR 5.45, 95% CI [1.09, 27.31]) and who never took antenatal care (AOR 6.83, 95% CI [1.00, 46.48]) were more likely to be preeclamptic. In conclusion, the present study showed a comparatively high prevalence of preeclampsia among pregnant women in Bangladesh. Some programmatic interventions such as medication for hypertension, antenatal visits to doctors, delivery and postnatal care services should be considered to reduce and prevent the hypertensive pregnancy disorders in Bangladesh.


Accuracy and predictability of the compensatory function of Orbscan II in intraocular pressure measurements after laser in situ keratomileusis.
To evaluate the usefulness of the compensatory function of Orbscan II (Orbtek, Bausch & Lomb) for measuring postoperative intraoperative pressure (IOP) in laser in situ keratomileusis (LASIK) patients. Department of Ophthalmology, Ilsan Paik Hospital, Inje University, Ilsan, Korea. Two hundred ten patients had LASIK using the Hansatome microkeratome (Bausch & Lomb) and the MEL 70 G-scan laser (Aesclepion-Meditec) and were examined retrospectively. The patients included in the study were divided into 2 groups: Group 1, 123 eyes with less than -6.0 diopters (D) of myopia; Group 2, 60 eyes with more than -6.0 D of myopia. The IOP was measured preoperatively and 2 and 4 weeks after LASIK using a noncontact tonometer (NCT CT-60, Topcon). The results were corrected with the Orbscan II program. The mean IOPs in Group 1 were 16.35 mm Hg +/- 2.90 (SD) preoperatively, 10.80 +/- 2.21 mm Hg at 2 weeks, and 10.63 +/- 2.28 mm Hg at 4 weeks. After compensation with Orbscan II, the 2-week and 4-week values were 16.81 +/- 3.14 mm Hg and 16.68 +/- 3.22 mm Hg, respectively. The mean IOPs in Group 2 were 17.63 +/- 2.93 mm Hg, 10.07 +/-1.55 mm Hg, and 10.43 +/- 1.84 mm Hg, respectively; after compensation, they were 18.40 +/- 4.09 mm Hg and 18.05 +/- 4.09 mm Hg, respectively. After compensation with Orbscan II, there were no statistically significant differences between the preoperative and postoperative IOPs. Orbscan II may help predict actual IOP values after LASIK and avoid the misinterpretation of high IOPs as normal IOPs.


Lymphocyte detection for cancer analysis using a novel fusion block based channel boosted CNN.
Tumor-infiltrating lymphocytes, specialized immune cells, are considered an important biomarker in cancer analysis. Automated lymphocyte detection is challenging due to its heterogeneous morphology, variable distribution, and presence of artifacts. In this work, we propose a novel Boosted Channels Fusion-based CNN "BCF-Lym-Detector" for lymphocyte detection in multiple cancer histology images. The proposed network initially selects candidate lymphocytic regions at the tissue level and then detects lymphocytes at the cellular level. The proposed "BCF-Lym-Detector" generates diverse boosted channels by utilizing the feature learning capability of different CNN architectures. In this connection, a new adaptive fusion block is developed to combine and select the most relevant lymphocyte-specific features from the generated enriched feature space. Multi-level feature learning is used to retain lymphocytic spatial information and detect lymphocytes with variable appearances. The assessment of the proposed "BCF-Lym-Detector" show substantial improvement in terms of F-score (0.93 and 0.84 on LYSTO and NuClick, respectively), which suggests that the diverse feature extraction and dynamic feature selection enhanced the feature learning capacity of the proposed network. Moreover, the proposed technique's generalization on unseen test sets with a good recall (0.75) and F-score (0.73) shows its potential use for pathologists' assistance.


[Patho-physiology of anemia in kala-azar (author's transl)].
In kala-azar, anemia is caused by an hemolysis induced by an activation of the complement by antigen-antibodies complexes in which the antigen is wether the parasite itself or a messenger from it.


Using Two- and Three-Dimensional Human iPSC Culture Systems to Model Psychiatric Disorders.
Psychiatric disorders are among the most challenging human diseases to understand at a mechanistic level due to the heterogeneity of symptoms within established diagnostic categories, the general absence of focal pathology, and the genetic complexity inherent in these mostly polygenic disorders. Each of these features presents unique challenges to disease modeling for biological discovery, drug development, or improved diagnostics. In addition, live human neural tissue has been largely inaccessible to experimentation, leaving gaps in our knowledge derived from animal models that cannot fully recapitulate the features of the disease, indirect measures of brain function in human patients, and from analyses of postmortem tissue that can be confounded by comorbid conditions and medication history.


Considerations in the quantitative analysis of autoradiograms from 2-dimensional gels.
Two-dimensional (2-D) gel electrophoresis has been used in conjunction with autoradiography and computerized optical densitometry for quantitating specific protein synthesis. However, accurate quantitation of 2-D autoradiograms requires the prior assessment of such parameters as linearity, reciprocity, and reproducibility. The present study was performed to determine the contribution of each of these to the dissimilation of beta-emission and autoradiographic density, and of density and protein synthesis. Various aliquot volumes of a single complex protein specimen labeled with 35S-amino acids were subjected to 2-D gel electrophoresis, and these gels were serially exposed at graded intervals. The peak densities and volumes of the 111 visualized spots were used to examine the above parameters. In our computerized scanning system, the peak density is a more accurate and reproducible parameter of optical density than is spot volume. Approximately 30% of the dynamic range of peak density is non-linear; quantitation of spots above or below the linear range leads to inaccuracies in quantitation. In addition, the phenomenon of reciprocity, which states that density is directly proportional to exposure (beta-emission of 35S x time), is shown to fail as aliquot volume, or mass of 35S increases. The implications of reciprocity failure to accurate quantitation are discussed. Finally, the sources of variance in autoradiographic analysis were examined, by assessing the intra-scan, intra-gel run, and inter-gel run coefficients of variation. The results of this study show that autoradiographic densitometry is an effective method for quantitation of 2-D gels, but linearity, reciprocity, and reproducibility must be assessed prior to its experimental use. Restrictions of such use are suggested.


MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products.
In search of antiinflammatory drugs with a new mechanism of action, U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with an IC50 of 0.07 microM for MEK 1 and 0.06 microM for MEK 2. U0126 can undergo isomerization and cyclization reactions to form a variety of products, both chemically and in vivo, all of which exhibit less affinity for MEK and lower inhibition of AP-1 activity than parent, U0126.


Effects of diclofenac, sulfamethoxazole, and wastewater from constructed wetlands on Eisenia fetida: impacts on mortality, fertility, and oxidative stress.
Soil contamination with micropollutants is an important global problem and the impact of these pollutants on living organisms cannot be underestimated. The effects of diclofenac (DCF) and sulfamethoxazole (SMX), their mixture (MIX), and wastewater containing these drugs on the mortality and reproduction of Eisenia fetida were investigated. The impact on the activities of antioxidant enzymes in earthworm cells was also assessed. Furthermore, the influence of the following parameters of the vertical flow constructed wetlands on wastewater toxicity was investigated: the dosing system, the presence of pharmaceuticals and the plants Miscanthus giganteus. The compounds and their mixture significantly affected the reproduction and mortality of earthworms. The calculated values of LC50,28 days values were 3.4 ± 0.3 mg kg-1 for DCF, 1.6 ± 0.3 mg kg-1 for SMX, and 0.9 ± 0.1 mg kg-1 for MIX. The EC50 (reproduction assay) for DCF was 1.2 ± 0.2 mg kg-1, whereas for SMX, it was 0.4 ± 0.1 mg kg-1, and for MIX, it was 0.3 ± 0.1 mg kg-1, respectively. The mixture toxicity index (MTI) was calculated to determine drug interactions. For both E. fetida mortality (MTI = 3.29) and reproduction (MTI = 3.41), the index was greater than 1, suggesting a synergistic effect of the mixture. We also observed a negative effect of wastewater (raw and treated) on mortality (32% for raw and 8% for treated wastewater) and fertility (66% and 39%, respectively) of E. fetida. It is extremely important to analyze the harmfulness of microcontaminants to organisms inhabiting natural environments, especially in the case of wastewater for irrigation of agricultural fields.


Negative Pressure Wound Treatment of Infections Caused By Extensively Drug-Resistant Gram-Negative Bacteria After Liver Transplantation: Two Case Reports.
Although survival after liver transplantation (LT) has progressively improved over the last years, an increased prevalence of clinically relevant infections in LT patients is well documented. In particular, the spread of infections sustained by extensively drug-resistant bacteria (XDR) produced an increase in the incidence of wound infections. Implementation of treatments for these life-threatening events is mandatory. This study describes 2 LT patients in whom XDR wound infection was effectively treated using negative pressure wound treatment (NPWT) combined with targeted local and systemic antibiotic therapy. Over the last 3 years, 2 of 8 patients with XDR infection admitted to our unit developed wound infection caused by XDR Klebsiella pneumoniae (KP-XDR). Positive results of the abdominal fluid culture and of the wound swab for KP-XDR were followed by sepsis. In both cases wound debridement was required and deep fascial layer dehiscence was detected. Combination antibiotic therapy was administered for sepsis treatment and, after failure of conventional NPWT, a NPWT with local instillation (NPWTi; V.A.C.-Ulta/VeraFlo-Instillation Therapy-KCI USA, Inc., San Antonio, TX, USA) of colistin-rifampicin was applied. After NPWTi application a reduction in bacterial load and exudate was observed with reduction in inflammatory markers. A complete healing of wound was achieved and both patients are currently alive. Instillation and NPWT are widely discussed in the literature. Results of the present study indicate beneficial effects of NPWT combined with targeted local and systemic antibiotic therapy; in both cases a life-threatening complication was cured. We consider local instillation of selected antibiotics applied to NPWTi a valuable tool for deep wound infection sustained by XDR bacteria.


[Bacillus Calmette-Guérin (BCG) and alternatives : Drug treatment of high-risk non-muscle invasive bladder cancer].
Intravesical instillation of bacillus Calmette-Guérin (BCG) is an accepted strategy to reduce the risk of recurrence and possibly progression of high-risk non-muscle invasive bladder cancer (NMIBC). However, side effects are not uncommon. In addition, the tumors may be BCG refractory or unresponsive. These tumors have a very high risk of recurrence and progression, so cystectomy must be weighed against conservative treatment options. We describe the current recommendations regarding treatment of NMIBC with BCG and alternatives for BCG failure. Literature search on current treatment options and their alternatives with the help of mainly primary literature and guideline recommendations. For high-risk NMIBC, instillation therapy with BCG remains standard-of-care, applied according to a standard regimen in terms of dose and dosing intervals (induction: weekly instillation for 6 weeks, maintenance: weekly instillation for 3 weeks, 3, 6 and 12 months after initiation of BCG therapy plus, for high-risk NMIBC, 18, 24, 30 and 36 months after initiation of BCG therapy). Potential future treatment options for BCG failure are systemic (i.v.) pembrolizumab (FDA approved) and, possibly, intravesical nadofaragene firadenovec. Ongoing randomized clinical trials are furthermore evaluating the role of PD-(L)1 immune checkpoint inhibitors in combination with BCG.


Determinants of Human Papillomavirus Vaccine Uptake by Adult Women Attending Cervical Cancer Screening in 9 European Countries.
Human papillomavirus-vaccinated cohorts, irrespective of age, will likely reduce their subsequent screening requirements, thus opening opportunities for global cost reduction and program sustainability. The determinants of uptake and completion of a 3-dose human papillomavirus vaccination program by adult women in a European context were estimated. This was an intervention study. Study participants were women aged 25-45 years, attending opportunistic or population-based cervical cancer screening in Belgium, Denmark, Finland, France, Germany, Slovenia, Spain, Sweden, and the United Kingdom between April 2016 and May 2018. Study participants completed a questionnaire on awareness and attitudes on adult female human papillomavirus vaccination and were invited to receive free human papillomavirus vaccination. Main outcome measures were acceptance, uptake, and completion of vaccination schedule. Determinants of vaccine uptake were explored using multilevel logistic models in 2019. Among 3,646 participants, 2,748 (range by country=50%-96%) accepted vaccination, and 2,151 (range=30%-93%) received the full vaccination course. The factors associated with higher vaccine acceptance were previous awareness of adult female (OR=1.22, 95% CI=1.00, 1.48) and male (OR=1.59, 95% CI=1.28, 1.97) vaccination. Women in stable relationships (OR=0.56, 95% CI=0.45, 0.69) or with higher educational level (OR=0.76, 95% CI=0.63, 0.93) were more likely to refuse vaccination. Recruitment by postal invitation versus personal invitation from a healthcare professional resulted in lower vaccine acceptance (OR=0.13, 95% CI=0.02, 0.76). Vaccination coverage of >70% of adolescent girls in national public programs was of borderline significance in predicting human papillomavirus vaccine uptake (OR=3.23, 95% CI=0.95, 10.97). The main reasons for vaccine refusal were vaccine safety concerns (range=30%-59%) and the need for more information on human papillomavirus vaccines (range=1%-72%). No safety issues were experienced by vaccinated women. Acceptance and schedule completion were largely dependent on recruitment method, achieved coverage of national vaccination programs, and personal relationship status. Knowledge of benefits and safety reassurance may be critical to expanding vaccination target ages. Study results suggest that there are no major opinion barriers in adult women to human papillomavirus vaccination, especially when vaccination is offered face to face in healthcare settings. EudraCT Number 2014-003177-42.


Assessment of bacterial acyltransferases for an efficient lipid production in metabolically engineered strains of E. coli.
Microbially produced lipids like triacylglycerols or fatty acid ethyl esters are currently of great interest as fuel replacements or other industrially relevant compounds. They can even be produced by non-oleaginous microbes, like Escherichia coli, upon metabolic engineering. However, there is still much room for improvement regarding the yield for a competitive microbial production of lipids or biofuels. We genetically engineered E. coli by expressing fadD, fadR, pgpB, plsB and 'tesA in combination with atfA from Acinetobacter baylyi. A total fatty acid contents of up to 16% (w/w) was obtained on complex media, corresponding to approximately 9% (w/w) triacylglycerols and representing the highest titers of fatty acids and triacylglycerols obtained in E. coli under comparable cultivation conditions, so far. To evaluate further possibilities for an optimization of lipid production, ten promising bacterial wax ester synthase/acyl-Coenzyme A:diacylglycerol acyltransferases were tested and compared. While highest triacylglycerol storage was achieved with AtfA, the mutated variant AtfA-G355I turned out to be most suitable for fatty acid ethyl ester biosynthesis and enabled an accumulation of approx. 500 mg/L without external ethanol supplementation.


Shape of magnifiers affects controllability in children with visual impairment.
This study aimed to examine the controllability of cylinder-shaped and dome-shaped magnifiers in young children with visual impairment. This study investigates goal-directed arm movements in low-vision aid use (stand and dome magnifier-like object) in a group of young children with visual impairment (n = 56) compared to a group of children with normal sight (n = 66). Children with visual impairment and children with normal sight aged 4-8 years executed two types of movements (cyclic and discrete) in two orientations (vertical or horizontal) over two distances (10 cm and 20 cm) with two objects resembling the size and shape of regularly prescribed stand and dome magnifiers. The visually impaired children performed slower movements than the normally sighted children. In both groups, the accuracy and speed of the reciprocal aiming movements improved significantly with age. Surprisingly, in both groups, the performance with the dome-shaped object was significantly faster (in the 10 cm condition and 20 cm condition with discrete movements) and more accurate (in the 20 cm condition) than with the stand-shaped object. From a controllability perspective, this study suggests that it is better to prescribe dome-shaped than cylinder-shaped magnifiers to young children with visual impairment.


Experimental transmission of West Nile virus (Flaviviridae: Flavivirus) by Carios capensis ticks from North America.
Seabird soft ticks, Carios capensis (Ixodida: Argasidae), originally collected from coastal Georgia, USA, were allowed to ingest a blood meal from pekin ducklings (Anas domesticus) infected with WNV. After 35 days of extrinsic incubation, the ticks transmitted virus to naive ducklings. WNV was detected via plaque assay and RTPCR in ticks and in tissues and serum of ducklings 7 days post infestation.


Nitrogenase model complexes [Cp*Fe(mu-SR(1))2(mu-eta(2)-R(2)N=NH)FeCp*] (R(1) = Me, Et; R(2) = Me, Ph; Cp* = eta(5)-C5Me5): synthesis, structure, and catalytic N-N bond cleavage of hydrazines on diiron centers.
The reactions of [Cp*Fe(mu-SR1)3FeCp*] (Cp* = eta5-C5Me5; R1 = Et, Me) with 1.5 equiv R2NHNH2 (R2 = Ph, Me) give the mu-eta2-diazene diiron thiolate-bridged complexes [Cp*Fe(mu-SR1)2(mu-eta2-R2N NH)FeCp*], along with the formation of PhNH2 and NH3. These mu-eta2-diazene diiron thiolate-bridged complexes exhibit excellent catalytic N-N bond cleavage of hydrazines under ambient conditions.


A cross-sectional analysis of facial palsy-related quality of life in 125 patients: Comparing linear, quadratic and cubic regression analyses.
Facial function correlates with quality of life in facial palsy. Previous studies have examined a linear relationship; based on clinical experience, we hypothesize a curved regression (i.e. quadratic or cubic) will be more fitting to show the correlation between quality of life and facial function. We compared the fit of a linear regression model between Sunnybrook scores (facial function) and FaCE and FDI scores (quality of life) to a quadratic and cubic regression model in 125 patients cross-sectionally. A total of 125 patients were included, 53.6% female with a mean (standard deviation) age of 56.6 (16.7) and a median (interquartile range) duration of palsy of 6.6 (1.5; 18.3) years. The quadratic regression proved a significant improvement over a linear regression analysis in the model using the FaCE total score (linear R2 =.346, quadratic R2 = .378, p = .033) and the FDI physical score (linear R2 = .245, quadratic R2 =.276, p = .034). The cubic regression analysis was no significant improvement over a quadratic regression. The relationship between facial function and quality of life in facial palsy is not linear meaning that there is a lot of variation in QoL in cases with severe and moderate facial impairment. This is most applicable to patients suffering from post-paralysis synkinesis, proving the highly individually experienced burden of synkinesis. As the relationship is not linear it should not be included as such in future research studies.


Verrucous Psoriasis: Rare Variant and Novel Treatment.
Xenopoulou D, Pochat C, Greco E. Verrucous psoriasis: rare variant and novel treatment. J Drugs Dermatol. 2023;22(8):826-827. doi:10.36849/JDD.C6874R1.


Amino acid sequence of an inducible cysteine proteinase inhibitor (cystatin) from submandibular glands of isoproterenol-treated rats.
We have previously reported the purification of an inducible cysteine proteinase inhibitor from submandibular glands of isoproterenol-treated rats by sequential gel filtration and ion-exchange chromatography [G. S. Bedi (1989) Arch. Biochem. Biophys. 270, 335-343]. This inhibitor is not detected in normal rat tissues but is induced in submandibular glands following beta-adrenergic stimulation of rats. In this study the complete amino acid sequence and the position of disulfide bridges of the purified protein were determined by automated Edman degradation of the protein and its tryptic, chymotryptic, and Staphylococcus aureus V8 protease peptides and were as follows: (sequence; see text) Computer analysis revealed the presence of 40-50% sequence identity between inducible cysteine proteinase inhibitor and cystatins from human saliva, human cystatin C, bovine cystatins, and chicken cystatins, all members of Family 2 cystatins. The inhibitor has little sequence similarity with rat liver and epidermal cysteine proteinase inhibitors, which belong to Family 1 cystatins.


Structural analysis of the N-glycans of the major cysteine proteinase of Trypanosoma cruzi. Identification of sulfated high-mannose type oligosaccharides.
Trypanosoma cruzi, the parasitic protozoan that causes Chagas disease, contains a major cysteine proteinase, cruzipain. This lysosomal enzyme bears an unusual C-terminal extension that contains a number of post-translational modifications, and most antibodies in natural and experimental infections are directed against it. In this report we took advantage of UV-MALDI-TOF mass spectrometry in conjunction with peptide N-glycosidase F deglycosylation and high performance anion exchange chromatography analysis to address the structure of the N-linked oligosaccharides present in this domain. The UV-MALDI-TOF MS analysis in the negative-ion mode, using nor-harmane as matrix, allowed us to determine a new striking feature in cruzipain: sulfated high-mannose type oligosaccharides. Sulfated GlcNAc2Man3 to GlcNAc2Man9 species were identified. In accordance, after chemical or enzymatic desulfation, the corresponding signals disappeared. In addition, by UV-MALDI-TOF MS analysis (a) a main population of high-mannose type oligosaccharides was shown in the positive-ion mode, (b) lactosaminic glycans were also identified, among them, structures corresponding to monosialylated species were detected, and (c) as an interesting fact a fucosylated oligosaccharide was also detected. The presence of the deoxy sugar was further confirmed by high performance anion exchange chromatography. In conclusion, the total number of oligosaccharides occurring in cruzipain was shown to be much higher than previous estimates. This constitutes the first report on the presence of sulfated glycoproteins in Trypanosomatids.


Human-caused increases in reactive nitrogen burial in sediment of global lakes.
Human activities have increased reactive nitrogen (Nr) input to terrestrial ecosystems compared with the pre-industrial era. However, the fate of such Nr input remains uncertain, leading to missing sink of the global nitrogen budget. By synthesizing records of Nr burial in sediments from 303 lakes worldwide, here we show that 9.6 ± 1.1 Tg N year-1 (Tg = 1012 g) accumulated in inland water sediments from 2000 to 2010, accounting for 3%-5% of global Nr input to the land from combined natural and anthropogenic pathways. The recent Nr burial flux doubles pre-industrial estimates, and Nr burial rate significantly increases with global increases in human population and air temperature. Sediment ratios of C:N decrease after 1950 while N:P ratios increase over time due to increasingly elevated Nr burial and other related processes in lakes. These findings imply that Nr burial in lakes is overlooked as an important global sink of Nr input to terrestrial ecosystems.


Invertebrate predator-prey body size relationships: an explanation for upper triangular food webs and patterns in food web structure?
It has been suggested by Cohen and Newman (1985) that many of the patterns in published food webs can be derived from a stochastic model in which the species are arranged in a trophic hierarchy (the 'cascade model'). We suggest that, if predators are larger than their prey, a trophic hierarchy can be generated on the basis of body size Empirical evidence from the literature shows that there is a positive relationship between predator and prey size for a range of invertebrates and that predators are usually larger than their prey. Using experimental data on an aquatic food web we show that body size can lead to the type of trophic hierarchy used in the cascade model, suggesting that many food web patterns may be a product of body size. This conclusion is discussed with respect to the limitations of the food web data and the relationship between 'static' and 'dynamic' models of web structure.


Auraptene induces oligodendrocyte lineage precursor cells in a cuprizone-induced animal model of demyelination.
We investigated the effects of auraptene on mouse oligodendroglial cell lineage in an animal model of demyelination induced by cuprizone. Auraptene, a citrus coumarin, was intraperitoneally administered to mice fed the demyelinating agent cuprizone. Immunohistochemical analysis of the corpus callosum and/or Western blotting analysis of brain extracts revealed that cuprizone reduced immunoreactivity for myelin-basic protein, a marker of myelin, whereas it increased immunoreactivity to platelet derived-growth factor receptor-α, a marker of oligodendrocyte precursor cells. Administration of auraptene enhanced the immunoreactivity to oligodendrocyte transcription factor 2, a marker of oligodendrocyte precursor cells and oligodendrocyte lineage precursor cells, but had no effect on immunoreactivity to myelin-basic protein or platelet-derived growth factor receptor-α. These findings suggest that auraptene promotes the production of oligodendrocyte lineage precursor cells in an animal model of demyelination and may be useful for individuals with demyelinating diseases.


Aggregation and adsorption behavior of low concentration aqueous solutions of hexadecyltrimethylammonium ortho, meta, and parafluorobenzoate.
The aggregation properties of 2-, 3-, and 4-fluorobenzoic acids (2FBA, 3FBA, and 4FBA, respectively) and their salts with hexadecyltrimethylammonium cations (HTA2FB, HTA3FB, and HTA4FB) in water were studied with a battery of techniques. Their activity at the air/solution interface has been also studied. The position of the fluorine atom in the acid affected the solubility, adsorption, and aggregation in the pure acids solutions. The 4FBA is less water soluble, more hydrophobic, and has the lower critical aggregation concentration of the three isomers. The behavior of the HTA2FB compound in aqueous solution is different from that of HTA3FB and HTA4FB. The critical micelle concentration, critical concentration for sphere-to-rod-like micelle transition, and Krafft point of HTA3FB and HTA4FB are lower than those of the other surfactant but their surface activities are higher. The differences between the HTA2FB and the other two surfactants have been explained on the basis of the regular solution theory of mixed micelles and in light of the analysis of the hydration shell of the acids through molecular dynamic simulations. The results of the present work suggest that the different behaviors are due to a combination of different dehydration tendencies and the steric possibility of inclusion of the counterions in the micelle palisade layer. The formation of rod-like micelles by HTA2FB, while the tetradecyltrimethylammonium 2-fluorobenzoate only forms spherical aggregates, is explained on the basis of the packing parameter. The mentioned factors are complementary to others presented in literature. These conditions may be used in the rational design of micelles by means of molecular dynamics simulations, reducing the trial-and-error approach used to date.


Drinking saccharin increases food intake and preference--III. Sensory and associative factors.
Rats that drink saccharin solution increase their short-term food intake and develop a preference for flavored food eaten when saccharin is ingested. Here we describe experiments that examined whether these changes in feeding behavior were due to learning and/or the reinforcing sensory properties of saccharin solution. It was found that learning was unnecessary for the feeding response, as rats that drank saccharin increased food intake whether or not their food contained saccharin-contingent flavor cues. However, learning helped support and maintain the response, as rats repeatedly given flavored food together with saccharin to drink later increased intake when given the flavored food without saccharin (i.e. in extinction). The rewarding or hedonic effects of the immediate orosensory properties of saccharin were not responsible for its effects on feeding, as drinking saccharin before but not after eating flavored food increased food intake and food preference. Furthermore, hungry rats developed an aversion to flavored food paired with saccharin ingestion when the quantity of food was limited. This implies that the flavored food preference produced by drinking saccharin involves an association between sensory aspects of the food and the metabolic consequences of food ingestion, which interact with a postingestive action of drinking saccharin that is related to the rat's metabolic state.


The Purkinje network plays a major role in low-energy ventricular defibrillation.
During ventricular fibrillation (VF), targeting the excitable gap (EG) of reentry throughout the myocardium with low-energy surface stimulation shows promise for painless defibrillation. However, the Purkinje network may provide alternative pathways for reentry to evade termination. This study investigates the role of the Purkinje network in painless defibrillation. In a computational human biventricular model featuring a Purkinje network, VF was initiated with 4 Hz epicardial pacing. Defibrillation was attempted by stimulating myocardial surface EG with a low-energy 2 ms duration pulse at 2x stimulus capture, which was administered at coupling intervals incremented by 0.25 s between 0.25 and 5 s after VF initiation. Defibrillation was accomplished if reentry ceased ≤ 1 s after the defibrillation pulse. The protocol was repeated with the Purkinje network and myocardial surface EG stimulated simultaneously, and again after uncoupling the Purkinje network from the myocardium. VF with the Purkinje network coupled and uncoupled had comparable dominant frequency in the left (3.81 ± 0.44 versus 3.77 ± 0.53 Hz) and right (3.80 ± 0.37 versus 3.76 ± 0.48 Hz) ventricles. When uncoupling the Purkinje network, myocardial surface EG stimulation terminated VF for all defibrillation pulses. When coupled, myocardial EG surface stimulation terminated VF for only 55% of the defibrillation pulses, but improved to 100% when stimulated simultaneously with Purkinje network EG. Defibrillation failures were attributed to EG evading stimulation in the Purkinje network. Defibrillation that exclusively targets myocardium can fail due to accessory pathways in the Purkinje network that allow for reentrant activity to evade termination and maintain VF. Painless defibrillation strategies should be adapted to include the Purkinje network.


Murine embryonic stem cell-derived hepatocytes correct metabolic liver disease after serial liver repopulation.
Although embryonic stem (ES) cell-derived hepatocytes have the capacity for liver engraftment and repopulation, their in vivo hepatic function has not been analyzed yet. We aimed to determine the metabolic function and therapeutic action of ES cell-derived hepatocytes after serial liver repopulations in fumaryl acetoacetate hydrolase knockout (Fah(-/-)) mice. Albumin expressing (Alb(+)) cells were obtained by hepatic differentiation of ES cells using two frequently reported methods. After transplantation, variable levels of liver repopulation were found in Fah(-/-) mice recipients. FAH expressing (FAH(+)) hepatocytes were found either as single cells or as nodules with multiple hepatocytes. After serial transplantation, the proportion of the liver that was repopulated by the re-transplanted FAH(+) hepatocytes increased significantly. ES cell-derived FAH(+) hepatocytes were found in homogenous nodules and corrected the liver metabolic disorder of Fah(-/-) recipients and rescued them from death. ES cell-derived hepatocytes had normal karyotype, hepatocytic morphology and metabolic function both in vitro and in vivo. In conclusion, ES cell-derived hepatocytes were capable of liver repopulation and correction of metabolic defects after serial transplantation. Our results are an important piece of evidence to support future clinical applications of ES cell-derived hepatocytes in treating liver diseases.


Finite-time consensus control for multi-agent systems with full-state constraints and actuator failures.
Aiming at a class of uncertain nonlinear multi-agent systems (MASs) with full-state constraints and actuator failures, a finite-time consensus control method is developed. Full-state constraints and actuator failures are ubiquitous in practical engineering applications. Violation of constraints would drastically affect the performance of MASs, even arise security problems. It is challenging to guarantee the performance of the MASs when undergoing actuator failures. To tackle these problems, an adaptive consensus control method is established by applying the Backstepping technique and Barrier Lyapunov functions (BLFs) to ensure the performance of the MASs with full-state constraints no matter actuator failures occur. Simultaneously, for the uncertain nonlinear MASs, a finite-time neural network (NN) consensus control scheme is established to ensure system's signals are synchronized in finite time. Moreover, an event-triggered control strategy is constructed to relieve the communication pressure of each agent. Finally, numerical and practical examples are employed to verify the effectiveness of the proposed control strategy.


Monocyte chemotaxis in bronchial carcinoma and cigarette smokers.
Chemotaxis of blood monocytes was measured in 31 patients with bronchial carcinoma and 19 cigarette smokers. Thirteen patients with metastatic bronchial carcinoma had significantly less (P less than 0.005) chemotactic response than matched controls. Those with disease confined to the chest, or with recurrent or operable bronchial carcinoma, had no significant depression of monocyte chemotaxis. There was also no significant difference in monocyte chemotaxis between cigarette smokers and matched controls. These results support the concept that in human cancer there is a defect in monocyte chemotaxis, but in bronchial carcinoma significant depression was only apparent in those with advanced disease.


Material symmetry recognition and property prediction accomplished by crystal capsule representation.
Learning the global crystal symmetry and interpreting the equivariant information is crucial for accurately predicting material properties, yet remains to be fully accomplished by existing algorithms based on convolution networks. To overcome this challenge, here we develop a machine learning (ML) model, named symmetry-enhanced equivariance network (SEN), to build material representation with joint structure-chemical patterns, to encode important clusters embedded in the crystal structure, and to learn pattern equivariance in different scales via capsule transformers. Quantitative analyses of the intermediate matrices demonstrate that the intrinsic crystal symmetries and interactions between clusters have been exactly perceived by the SEN model and critically affect the prediction performances by reducing effective feature space. The mean absolute errors (MAEs) of 0.181 eV and 0.0161 eV/atom are obtained for predicting bandgap and formation energy in the MatBench dataset. The general and interpretable SEN model reveals the potential to design ML models by implicitly encoding feature relationship based on physical mechanisms.


The burden associated with generalized pustular psoriasis: A Canadian population-based study of inpatient care, emergency departments, and hospital- or community-based outpatient clinics.
Not much is known about the burden of generalized pustular psoriasis (GPP). To document the burden of GPP in Canada and to compare it with psoriasis vulgaris (PV). National data were used to identify Canadian adult patients with GPP or PV hospitalized or visiting an emergency department (ED) or hospital-/community-based clinic between April 1, 2007, and March 31, 2020. Analyses of 10-year prevalence and 3-year incidence were conducted. Costs were determined when the most responsible diagnosis (MRD) was GPP or PV (MRD costs) and for all reasons (all-cause costs). In the prevalence analysis, 10-year mean (SD) MRD costs were $2393 ($11,410) for patients with GPP and $222 ($1828) for those with PV (P < .01). In the incidence analysis, patients with GPP had higher 3-year mean (SD) MRD costs ($3477 [$14,979] vs $503 [$2267] for PV; P < .01). Higher all-cause costs were also associated with patients with GPP. Inpatient/ED mortality was higher in the GPP group in our 10-year prevalence (9.2% for patients with GPP vs 7.3% for those with PV; P = .01) and 3-year incidence (5.2% for patients with GPP and 2.1% for those with PV; P = .03) analyses. Physician and prescription drug data were not available. Patients with GPP incurred higher costs and mortality than patients with PV.


Daxx functions as a scaffold of a protein assembly constituted by GLUT4, JNK1 and KIF5B.
We have previously reported the physical interaction between Daxx, the adaptor protein that mediates activation of the Jun amino-terminal kinase (JNK), and GLUT4, the insulin-dependent glucose transporter, interaction that involves their C-domains. Co-immunoprecipitation and two-hybrid-based protein-protein interaction studies show now that Daxx and GLUT4 interact with JNK1 through D-sites in their NH(2)-(aa 1-501) and large endofacial loop, respectively. Serum deprivation strongly enhances the association of JNK1 with Daxx and dissociates the kinase from GLUT4. SP600125, a potent JNK1 inhibitor, reduces the JNK1 activity associated with GLUT4 and the phosphorylation of two minor GLUT4 species in serum-starved 3T3-L1 adipocytes. In addition, Daxx interacts with kinesin KIF5B through the 6xTPR domain of the kinesin light chain, a domain engaged in the grab hold of protein cargo by kinesin motors that codistribute with JNK. Depletion of Daxx in 3T3-L1 adipocytes provokes the partial translocation of the GLUT4 retained in the GLUT4 storage compartment to endosomes.


Preventive Strategies for Nonalcoholic Fatty Liver Disease After Liver Transplantation.
Post-transplant nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH) is common and can be recurrent or de novo. The available data suggest that progression of fibrosis is accelerated in these patients compared to NASH in general population. The long-term data suggest more risk of metabolic syndrome and associated metabolic comorbidities and cardiovascular disease in these patients. The current review focuses on prevalence and prevention/treatment of post-transplant NAFLD or NASH.


A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche.
The nutrient-absorbing villi of small intestines are renewed and repaired by intestinal stem cells (ISCs), which reside in a well-organized crypt structure. Genetic studies have shown that Wnt molecules secreted by telocytes, Gli1+ stromal cells, and epithelial cells are required for ISC proliferation and villus homeostasis. Intestinal stromal cells are heterogeneous and single-cell profiling has divided them into telocytes/subepithelial myofibroblasts, myocytes, pericytes, trophocytes, and Pdgfralow stromal cells. Yet, the niche function of these stromal populations remains incompletely understood. We show here that a Twist2 stromal lineage, which constitutes the Pdgfralow stromal cell and trophocyte subpopulations, maintains the crypt structure to provide an inflammation-restricting niche for regenerating ISCs. Ablating Twist2 lineage cells or deletion of one Wntless allele in these cells disturbs the crypt structure and impairs villus homeostasis. Upon radiation, Wntless haplo-deficiency caused decreased production of anti-microbial peptides and increased inflammation, leading to defective ISC proliferation and crypt regeneration, which were partially rescued by eradication of commensal bacteria. In addition, we show that Wnts secreted by Acta2+ subpopulations also play a role in crypt regeneration but not homeostasis. These findings suggest that ISCs may require different niches for villus homeostasis and regeneration and that the Twist2 lineage cells may help to maintain a microbe-restricted environment to allow ISC-mediated crypt regeneration.


Amino acid sequence of alpha-amylase from Bacillus amyloliquefaciens deduced from the nucleotide sequence of the cloned gene.
We have isolated by molecular cloning the gene coding for the alpha-amylase (1,4-alpha-D-glucan glucanohydrolase, EC 184.108.40.206.) from Bacillus amyloliquefaciens and determined its complete nucleotide sequence. The gene cloned in the plasmid pUB110 using Bacillus subtilis as a host, was contained in a 2.3-kilobase insert. Starting from an ATG initiator codon, an open reading frame comprising a total of 514 amino acids (1542 base pairs) was found within the cloned DNA fragment. The gene region encoding the COOH terminus of alpha-amylase was located by direct COOH-terminal analysis of the purified exoenzyme. The NH2-terminal portion of the gene encodes a 31 amino acid-long signal peptide (Palva, L., Pettersson, R. F., Kalkkinen, N., Lehtovaara, P., Sarvas, M., Söderlund, H., Takkinen, K., and Kääriäinen, L. (1981) Gene 15, 43-51). Since the signal peptide is correctly cleaved in the new host, as shown here by direct NH2-terminal sequence analysis, the exoamylase consists of 483 amino acid residues, corresponding to a molecular weight of 54,778. The reading frame used to deduce the amino acid sequence was found to be correct by comparison with partial amino acid sequence data published previously (Detera, S. D., and Friedberg, F. (1979) Int. J. Peptide Protein Res. 14, 364-372; Chung, H., and Friedberg, F. (1980) Biochem. J. 185, 387-395). Several differences between the sequence presented here and the partial ones published previously, however, were found. The nucleotide sequences both 5' and 3' to the alpha-amylase gene revealed palindromic structures including a stretch of six T-residues, suggesting transcription termination signals on both sides of the gene. Thus, it appears that alpha-amylase is translated from a monocistronic mRNA.


The role of internal jugular vein Doppler ultrasonography in predicting hypovolemic shock in polytrauma patients.
The aim of this study was to evaluate the accuracy of internal jugular vein (IJV) Doppler ultrasonography in predicting hypovolemic shock in polytrauma patients. This prospective observational study was conducted on 75 multiple trauma patients (injury severity score >15) with a mean age of 33.00±9.57 years. IJV Doppler ultrasonography was performed in all patients with stable vital signs and a negative extended focused assessment with sonography for trauma. Jugular pulsatility index (JPI) values were calculated using the equation (Vmax-Vmin)/Vmax. Clinical and laboratory indices of hypovolemic shock were recorded at the time of admission. Patients were subsequently divided into those with hemorrhagic shock (n=36) and those without (n=39) based on the occurrence of hemorrhagic shock within 6 hours after admission. The results were compared between these groups. IJV Doppler ultrasound parameters (JPI, Vmin, and Vmax-Vmin) showed significant differences between the two groups. The JPI values of patients with hemorrhagic shock were significantly lower than those in the control group (0.43±0.21 vs. 0.78±0.24, P<0.001). The sensitivity, specificity, and discriminant ability (area under the curve) of JPI with a cutoff of 0.58 in detecting hemorrhagic shock were 86.11%, 82.05%, and 0.853 (P<0.001), respectively. IJV Doppler ultrasonography can reliably predict hemorrhagic shock in polytrauma patients with stable vital signs. Ultrasonography can be used in combination with clinical signs and laboratory findings to diagnose patients at risk of hypovolemic shock.