Desulfoprunum benzoelyticum gen. nov., sp. nov., a Gram-stain-negative, benzoate-degrading, sulfate-reducing bacterium isolated from a wastewater treatment plant.
A strictly anaerobic, mesophilic, sulfate-reducing bacterium, strain KoBa311(T), isolated from the wastewater treatment plant at Konstanz, Germany, was characterized phenotypically and phylogenetically. Cells were Gram-stain-negative, non-motile, oval to short rods, 3-5 µm long and 0.8-1.0 µm wide with rounded ends, dividing by binary fission and occurring singly or in pairs. The strain grew optimally in freshwater medium and the optimum temperature was 30 °C. Strain KoBa311(T) showed optimum growth at pH 7.3-7.6. Organic electron donors were oxidized completely to carbon dioxide concomitant with sulfate reduction to sulfide. At excess substrate supply, substrates were oxidized incompletely and acetate (mainly) and/or propionate accumulated. The strain utilized short-chain fatty acids, alcohols (except methanol) and benzoate. Sulfate and DMSO were used as terminal electron acceptors for growth. The genomic DNA G+C content was 52.3 mol% and the respiratory quinone was menaquinone MK-5 (V-H2). The major fatty acids were C16:0, C16:1ω7c/ω6c and C18:1ω7c. Phylogenetic analysis based on 16S rRNA gene sequences placed strain KoBa311(T) within the family Desulfobulbaceae in the class Deltaproteobacteria. Its closest related bacterial species on the basis of the distance matrix were Desulfobacterium catecholicum DSM 3882(T) (93.0% similarity), Desulfocapsa thiozymogenes (93.1%), Desulforhopalus singaporensis (92.9%), Desulfopila aestuarii (92.4%), Desulfopila inferna JS_SRB250Lac(T) (92.3%) and Desulfofustis glycolicus (92.3%). On the basis of phylogenetic, physiological and chemotaxonomic characteristics, strain KoBa311(T) was distinct from any related type species. Therefore, strain KoBa311(T) is considered to represent a novel species of a new genus, for which the name Desulfoprunum benzoelyticum gen. nov., sp. nov. is proposed. The type strain of Desulfoprunum benzoelyticum is KoBa311(T) ( =DSM 28570(T) =KCTC 15441(T)).


Distinct mechanisms of recognizing endosomal sorting complex required for transport III (ESCRT-III) protein IST1 by different microtubule interacting and trafficking (MIT) domains.
The endosomal sorting complex required for transport (ESCRT) machinery is responsible for membrane remodeling in a number of biological processes including multivesicular body biogenesis, cytokinesis, and enveloped virus budding. In mammalian cells, efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the microtubule interacting and trafficking (MIT) domains of VPS4, LIP5, and Spartin via its C-terminal MIT-interacting motif (MIM). Here, we studied the molecular interactions between IST1 and the three MIT domain-containing proteins to understand the structural basis that governs pairwise MIT-MIM interaction. Crystal structures of the three molecular complexes revealed that IST1 binds to the MIT domains of VPS4, LIP5, and Spartin using two different mechanisms (MIM1 mode versus MIM3 mode). Structural comparison revealed that structural features in both MIT and MIM contribute to determine the specific binding mechanism. Within the IST1 MIM sequence, two phenylalanine residues were shown to be important in discriminating MIM1 versus MIM3 binding. These observations enabled us to deduce a preliminary binding code, which we applied to provide CHMP2A, a protein that normally only binds the MIT domain in the MIM1 mode, the additional ability to bind the MIT domain of Spartin in the MIM3 mode.


Epidemiology and Comorbidities of Excoriation Disorder: A Retrospective Case-Control Study.
Excoriation disorder is a psychocutaneous disorder characterized by repetitive skin-picking and associated with significant morbidity. Currently, epidemiological data in patients with excoriation disorder are lacking so we sought to characterize common patient demographics and comorbidities. We conducted a retrospective case-control study comparing 250 patients with excoriation disorder with 250 age-, race- and sex-matched controls identified between 2007 and 2019 at a single tertiary care center. We found that the majority of excoriation disorder patients were female (76%), Caucasian (82%) and unmarried (62%), with a mean age of 49 years. Compared to the matched controls, patients with excoriation disorder had increased odds of several psychiatric illnesses, including obsessive compulsive disorder (odds ratio (OR) 28.48, 95% confidence interval (CI): 1.68, 481.75), substance use disorder (OR 24.33, 95% CI: 5.81, 101.77), post-traumatic stress disorder (OR 8.23, 95% CI: 2.24, 129.40), depression (OR 8.19, 95% CI: 4.86, 13.80), bipolar disorder (OR 7.55, 95% CI: 2.22, 25.65), attention-deficit/hyperactivity disorder (OR 5.63, 95% CI: 1.62, 19.57), and anxiety (OR 5.01, 95% CI: 2.92, 8.62). Only a minority (42%) of patients were given psychiatry referrals and of those referred, a majority (64%) did not follow-up with psychiatry. The outcomes were also generally unfavorable as only 21% of patients experienced a resolution or improvement in their symptoms. This highlights the need for a multidisciplinary approach to manage patients with excoriation disorder, involving both dermatologists and psychiatrists.


A role for heterologous gap junctions between melanoma and endothelial cells in metastasis.
F10 and BL6 sublines of B16 mouse melanoma cells are metastatic after intravenous injection, but only BL6 cells are metastatic after subcutaneous injection. We found that connexin (Cx) 26 is upregulated in BL6 cells. To examine gap junction formation, we devised a coculture system, in which an opened vein segment was placed at the bottom of a culture dish and then dye-labeled melanoma cells were seeded onto it. Immunohistochemistry indicated that the vein segment preserved the integrity of the endothelial monolayer. In this system, BL6 cells could transfer dye into endothelial cells but F10 cells could not. Transfection with wild-type Cx26 rendered F10 cells competent for coupling with endothelial cells and as spontaneously metastatic as BL6 cells. Conversely, transfection with a dominant-negative form of Cx26 rendered BL6 cells deficient in coupling and less metastatic. In human melanoma lesions, the level of Cx26 expression was low in melanoma cells residing in the basal layer, but significantly upregulated in melanoma cells invading the dermis. The results suggested that Cx26 plays a role in intravasation and extravasation of tumor cells through heterologous gap junction formation with endothelial cells.


Cost Burden of Endothelial Keratoplasty in Fuchs Endothelial Dystrophy: Real-World Analysis of a Commercially Insured US Population (2014-2019).
To assess the incremental burden of corneal transplant surgery for US commercially insured patients with Fuchs endothelial corneal dystrophy (FECD) treated with endothelial keratoplasty (EK) compared to controls. The study design was retrospective cohort using IBM® MarketScan® claims (January 2014-September 2019) and included EK-treated (N=1562) and control patients (N=23,485) having ≥12 months' enrollment before and after diagnosis, who were subsequently matched on select characteristics. The index date was the beginning of the pre-operative period (3 months before EK); synthetic EK index was assigned for controls. All-cause, eye-disease, and complication-related healthcare resource utilization (HCRU) and costs were compared up to 36 months post index. For a small subset of patients, patient data were linked to the Health and Productivity Management supplemental database, which integrates data on productivity loss and disability payments. Matched cohorts included 804 EK-treated and 1453 controls with average age 65.7 years, 1383 (61%) female. Over 12 months of follow-up, all-cause ($41,199 vs $20,222, p<0.001) and eye-disease related costs ($22,951 vs $1389, p<0.001) were higher among EK-treated patients than controls. The cost differential increased additionally by $1000-$2000 per annum by 36 months of follow-up. While balanced at baseline, over follow-up EK-treated patients had higher prevalence of glaucoma, elevated intraocular pressure, cataract, cataract surgery, diagnosis of cornea transplant rejection, retinal edema. By 36 month of follow-up, EK-treated patients had 9 more short-term disability days, resulting in $2992 additional burden of disability payments. This study found a higher cost burden among FECD patients receiving EK treatment versus those who did not. With a shift in management of FECD, cost burden estimates generated in this study could serve as an important benchmark for future studies.


"Signal-on" photoelectrochemical sensing strategy based on target-dependent aptamer conformational conversion for selective detection of lead(II) ion.
A "signal-on" photoelectrochemical sensing strategy for selective determination of Pb(2+) is designed on the basis of the combination of Pb(2+)-induced conformational conversion, the amplified effect of reduced graphene oxide (RGO) and resonance energy transfer between CdS quantum dots (QDs) and gold nanoparticles (AuNPs). The RGO/CdS/aptamer platform is constructed via a stepwise modification method, and characterized by electrochemical impedance spectroscopy. In the absence of Pb(2+), the AuNP-labeled DNA, as a signal quenching element, can be introduced by hybridization with aptamer on the surface of sensing platform, which quenches the photocurrent of QDs via an energy transfer process. Upon addition of Pb(2+), the aptamer is induced into a G-quadruplex structure, which can greatly hinder the hybridization between aptamer and AuNP-labeled DNA due to the competitive occupation of binding sites and steric effect, leading to the recovery of photocurrent. Under optimized conditions, this "signal-on" photoelectrochemical biosensor shows a linear relationship between photocurrent variation and the logarithm of Pb(2+) concentration in the range of 0.1-50 nM with a detection limit of 0.05 nM. Meanwhile, it also exhibits good selectivity for Pb(2+) over other interfering ions, and is successfully applied to the detection of Pb(2+) in environmental water samples. By substituting the aptamers with other sequences, this proposed strategy could be conveniently extended to detect different targets as versatile photoelectrochemical devices.


Expert judgments about transient climate response to alternative future trajectories of radiative forcing.
There is uncertainty about the response of the climate system to future trajectories of radiative forcing. To quantify this uncertainty we conducted face-to-face interviews with 14 leading climate scientists, using formal methods of expert elicitation. We structured the interviews around three scenarios of radiative forcing stabilizing at different levels. All experts ranked "cloud radiative feedbacks" as contributing most to their uncertainty about future global mean temperature change, irrespective of the specified level of radiative forcing. The experts disagreed about the relative contribution of other physical processes to their uncertainty about future temperature change. For a forcing trajectory that stabilized at 7 Wm(-2) in 2200, 13 of the 14 experts judged the probability that the climate system would undergo, or be irrevocably committed to, a "basic state change" as > or =0.5. The width and median values of the probability distributions elicited from the different experts for future global mean temperature change under the specified forcing trajectories vary considerably. Even for a moderate increase in forcing by the year 2050, the medians of the elicited distributions of temperature change relative to 2000 range from 0.8-1.8 degrees C, and some of the interquartile ranges do not overlap. Ten of the 14 experts estimated that the probability that equilibrium climate sensitivity exceeds 4.5 degrees C is > 0.17, our interpretation of the upper limit of the "likely" range given by the Intergovernmental Panel on Climate Change. Finally, most experts anticipated that over the next 20 years research will be able to achieve only modest reductions in their degree of uncertainty.


Change in local environment upon quasicrystallization of Zr-Cu glassy alloys by addition of Pd and Pt.
The effects of Pd and Pt, which are known quasicrystal (QC)-forming elements, on the local atomic structure in Zr(70)Cu(30) glassy alloys are investigated. A QC phase precipitates from a glassy phase above a certain temperature by a cooperative-like motion of icosahedral clusters. Quasicrystallization is accompanied by a significant change in the local environment around the Zr atoms and a slight change around the noble metal. However, the local environment around the Cu atoms remains almost the same during QC formation. It is suggested that two types of icosahedral polyhedra exist in the glassy state: one has a relatively perfect icosahedral structure formed around the Zr atoms. The other is in a distorted state around the Cu atoms. We speculate that the medium-range order (i.e. QC nucleus) has a Zr-centered icosahedral cluster as its core, and the QC grows via aggregation of possible clusters in the initial stage. Pd or Pt atoms stabilize and/or connect individual Zr-centered icosahedral clusters, facilitating the formation of the nucleus and growth of the QC phase.


Genetics, genomics, and cancer risk assessment: State of the Art and Future Directions in the Era of Personalized Medicine.
Scientific and technologic advances are revolutionizing our approach to genetic cancer risk assessment, cancer screening and prevention, and targeted therapy, fulfilling the promise of personalized medicine. In this monograph, we review the evolution of scientific discovery in cancer genetics and genomics, and describe current approaches, benefits, and barriers to the translation of this information to the practice of preventive medicine. Summaries of known hereditary cancer syndromes and highly penetrant genes are provided and contrasted with recently discovered genomic variants associated with modest increases in cancer risk. We describe the scope of knowledge, tools, and expertise required for the translation of complex genetic and genomic test information into clinical practice. The challenges of genomic counseling include the need for genetics and genomics professional education and multidisciplinary team training, the need for evidence-based information regarding the clinical utility of testing for genomic variants, the potential dangers posed by premature marketing of first-generation genomic profiles, and the need for new clinical models to improve access to and responsible communication of complex disease risk information. We conclude that given the experiences and lessons learned in the genetics era, the multidisciplinary model of genetic cancer risk assessment and management will serve as a solid foundation to support the integration of personalized genomic information into the practice of cancer medicine.


When Desire Fades: Women Talk About Their Subjective Experience of Declining Sexual Desire in Loving Long-term Relationships.
Women's sexual desire has been shown to decline over the course of loving long-term relationships. Yet, accounts of partnered women's subjective experience of this occurrence are rather limited. In order to broaden the examination of this topic, the present exploratory qualitative study extended it cross-culturally to explore how women in Israel are impacted by, perceive, and experience this decline in their sexual desire, with the objective of sketching an account of the experiences of women who share this reality. Semi-structured interviews were conducted with 15 women, aged 25 and over, in fulfilling long-term heterosexual relationships. The participants reported a sharp decline in sexual desire in comparison to the early stages of the relationship, experiencing it as quite perplexing given their love and affection for their partner. All also described their intimate connection as based on much more than sex. Additionally, while the reduction in desire did not result from difficulties in the relationship it did create some. These included frustration, conflict, and pressure from partner, which often led to sexual compliance on the women's part. Suggested solutions included open and honest dialogue, thoughtfulness, and mutual respect. A critical discussion of the findings outlines implications for partnered women's and couples' wellbeing.


Soft tissue artifact assessment during treadmill walking in subjects with total knee arthroplasty.
Accurate measurement of knee kinematics during functional activities suffers mainly from soft tissue artifact (STA): the combination of local surface deformations and rigid movement of markers relative to the underlying bone (also called rigid STA movement: RSTAM). This study proposes to assess RSTAM on the thigh, shank, and knee joint and to observe possible features between subjects. Nineteen subjects with knee arthroplasty were asked to walk on a treadmill while a biplane fluoroscopic system (X-rays) and a stereophotogrammetric system (skin markers) recorded their knee movement. The RSTAM was defined as the rigid movement of the cluster of skin markers relative to the prosthesis. The results showed that RSTAM amplitude represents approximately 80-100% of the STA. The vertical axis of the anatomical frame of the femur was influenced the most by RSTAM. Combined with tibial error, internal/external rotation angle and distraction-compression were the knee kinematics parameters most affected by RSTAM during the gait cycle, with average rms values of 3.8° and 11.1 mm. This study highlighted higher RSTAM during the swing phase particularly in the thigh segment and suggests new features for RSTAM such as the particular shape of some RSTAM waveforms and the absence of RSTAM in certain kinematics during the gait phases. The comparison of coefficient of multiple correlations showed some similarities of RSTAM between subjects, while some correlations were found with gait speed and BMI. These new insights could potentially allow the development of new methods of compensation to avoid STA.


Caeoma cassiopae sp. nov., a rust on Cassiope tetragona in the Canadian Rocky Mountains.
Caeoma cassiopae sp. nov. (Uredinales) is described on the arctic-alpine shrub Cassiope tetragona. It was found in three locations in the Rocky Mountains of west-central Alberta, and is the first rust reported on the genus Cassiope. The sori resemble the uredinia of species in the genus Chrysomyxa. The host in the Ericaceae also suggests affinity with that genus. However, the spore morphology, studied by light and scanning electron microscopy, does not resemble known species of Chrysomyxa.


Mitochondria-derived superoxide and voltage-gated sodium channels in baroreceptor neurons from chronic heart-failure rats.
Our previous study has shown that chronic heart failure (CHF) reduces expression and activation of voltage-gated sodium (Na(v)) channels in baroreceptor neurons, which are involved in the blunted baroreceptor neuron excitability and contribute to the impairment of baroreflex in the CHF state. The present study examined the role of mitochondria-derived superoxide in the reduced Na(v) channel function in coronary artery ligation-induced CHF rats. CHF decreased the protein expression and activity of mitochondrial complex enzymes and manganese SOD (MnSOD) and elevated the mitochondria-derived superoxide level in the nodose neurons compared with those in sham nodose neurons. Adenoviral MnSOD (Ad.MnSOD) gene transfection (50 multiplicity of infection) into the nodose neurons normalized the MnSOD expression and reduced the elevation of mitochondrial superoxide in the nodose neurons from CHF rats. Ad.MnSOD also partially reversed the reduced protein expression and current density of the Na(v) channels and the suppressed cell excitability (the number of action potential and the current threshold for inducing action potential) in aortic baroreceptor neurons from CHF rats. Data from the present study indicate that mitochondrial dysfunction, including decreased protein expression and activity of mitochondrial complex enzymes and MnSOD and elevated mitochondria-derived superoxide, contributes to the reduced Na(v) channel activation and cell excitability in the aortic baroreceptor neurons in CHF rats.


Dimethylsulfoxide maintains intercellular communication by preserving the gap junctional protein connexin32 in primary cultured hepatocyte doublets from rats.
Intercellular communication via gap junctions is one of the differentiated functions of cells. Dimethylsulfoxide (DMSO) is known to induce cell differentiation and maintain differentiated cellular functions in primary hepatocyte culture, but the mechanism of action of DMSO is unknown. Therefore, we investigated the effect of DMSO on cell-cell communication via gap junctions of hepatocyte doublets, which are differentiated cells that lose differentiated functions with time in culture. In isolated rat hepatocyte doublets, we assessed the effects of 1, 2 and 3% DMSO in culture medium on morphological changes and dye-coupling activity between pairs of cells by microinjection with fluorescent dye (Lucifer Yellow CH). The distribution of gap junction protein connexin32 (Cx32) was assessed by indirect immunofluorescence analysis and the Cx32 mRNA was detected by the reverse transcription-polymerase chain reaction method. Dimethylsulfoxide delayed the morphological change of hepatocyte doublets from a spherical to a flattened shape. Dye-coupling efficiency significantly decreased with time in culture in the control group, whereas in groups treated with 2 and 3% DMSO, dye-coupling efficiency was retained after 6 and 9 h of inoculation (P < 0.05 and P < 0.01, respectively). Analysis by indirect immunofluorescence showed few fluorescent spots for Cx32 in the control group at 9 h of incubation, whereas many punctate fluorescent spots were seen in the 3% DMSO group at 9 h of incubation. The detection of Cx32 mRNA in the 3% DMSO group was also stronger than in controls. Dimethylsulfoxide significantly maintained intercellular communication via gap junctions in primary cultured rat hepatocytes through the preservation of functional Cx32 protein, thus maintaining cell differentiation.


Anionic water pentamer and hexamer clusters: An extensive study of structures and energetics.
An extensive study of structures and energetics for anionic pentamer and hexamer clusters is performed employing high level ab initio quantum chemical methods, such as the density-fitted orbital-optimized linearized coupled-cluster doubles (DF-OLCCD), coupled-cluster singles and doubles (CCSD), and coupled-cluster singles and doubles with perturbative triples [CCSD(T)] methods. In this study, sixteen anionic pentamer clusters and eighteen anionic hexamer clusters are reported. Relative, binding, and vertical detachment energies (VDE) are presented at the complete basis set limit (CBS), extrapolating energies of aug4-cc-pVTZ and aug4-cc-pVQZ custom basis sets. The largest VDE values obtained at the CCSD(T)/CBS level are 9.9 and 11.2 kcal mol-1 for pentamers and hexamers, respectively, which are in very good agreement with the experimental values of 9.5 and 11.1 kcal mol-1. Our binding energy results, at the CCSD(T)/CBS level, indicate strong bindings in anionic clusters due to hydrogen bond interactions. The average binding energy per water molecules is -5.0 and -5.3 kcal mol-1 for pentamers and hexamers, respectively. Furthermore, our results demonstrate that the DF-OLCCD method approaches to the CCSD(T) quality for anionic clusters. The inexpensive analytic gradients of DF-OLCCD compared to CCSD or CCSD(T) make it very attractive for high-accuracy studies.


Bone mass development and bone metabolism in juvenile idiopathic arthritis: treatment with growth hormone for 4 years.
To study the acquisition of bone mass and changes in bone mineral density (BMD) related to age, bone age, pubertal status, and growth hormone (GH) therapy in 11 children with juvenile idiopathic arthritis (JIA) longitudinally over 4 years, in comparison to healthy children. Bone mineral content (BMC), BMD, and vertebral area were measured by dual energy x-ray absorptiometry. Since BMC and BMD increase with size, BMD was converted to volumetric BMD (vBMD) after adjustment for vertebral size. At inclusion all patients (7 female, 4 male, mean age 10.3 +/- 2.1 yrs) had low BMD, with a mean z-score for area BMD (aBMD) of -2.04 +/- 0.8 SD. After adjustment for size, vBMD was 0.198 g/cm3, and after 4 years of GH treatment it increased significantly to 0.232 g/cm3 (p < 0.03), expressed as SD scores that increased from -2.97 +/- 0.81 SD to -2.83 +/- 0.67 SD. In relation to bone age, vBMD SD increased from -2.53 +/- 0.85 to -2.41 +/- 0.79. Compared to pretreatment values, bone formation and resorption markers increased significantly during treatment. Our results reflect an increase in bone turnover under GH therapy in these patients. Despite biochemical changes there was a stabilization of vBMD for age and bone age, with a percentage increase comparable to healthy children. Longterm GH treatment will be necessary to evaluate a potential positive effect of GH on bone density and metabolism in patients with JIA.


Multifactorial drug resistance in an adriamycin-resistant human small cell lung carcinoma cell line.
In a human small cell lung carcinoma cell line, GLC4, Adriamycin (ADR) resistance was induced. In the resistant cell line, GLC4/ADR, a 45% decreased intracellular ADR level was found compared to GLC4, but this could not fully explain the resistance. Evaluation of DNA damage in both cell lines after incubation with ADR by alkaline and neutral elution revealed single-strand breaks, DNA-protein cross-links, and double-strand breaks (DSB). At all incubation concentrations there was a decreased amount of all types of DNA damage in GLC4/ADR. The number of DSB was decreased also when corrected for the decreased intracellular concentration. This can at least partly be explained by the decreased stability of ADR induced DSB. After removal of ADR, 80% of DSB was repaired in 1 h in GLC4/ADR against no repair in GLC4. X-ray induced DSBs were also repaired faster: in GLC4/ADR t1/2 = 10 min and in GLC4 t1/2 = 23 min. Ratios for single strand breaks/DSBs and single strand breaks/DNA-protein cross-links between GLC4 and GLC4/ADR after exposure to ADR differed; these differences were compatible with differences in the distribution of the various types of DNA damage induced in the cell lines due to an altered ADR-topoisomerase II interaction. In this human small cell lung carcinoma cell line the resistance is multifactorial with decreased intracellular ADR levels, increased DNA repair, and altered ADR-topoisomerase interaction.


Agency-offered and officer-utilized suicide prevention and wellness programs: A national study.
Limited research exists in the area of police mental wellness and suicide prevention, especially regarding programs utilized by these agencies. The purpose of this project was to gain a better understanding of the prevalence of use of police officer wellness promotion and suicide prevention programs implemented in the United States and an understanding of the perceptions of program effectiveness (Part A). We also sought to determine whether differences exist in the mental wellness and perspectives of programming of officers from agencies who utilize suicide prevention and wellness programs compared to those agencies who do not (Part B). Data for Part A was collected directly from agencies via a stratified random sample of city police departments and sheriff's offices nationwide. Part B entailed completion of online surveys by individual officers from agencies participating in Part A. The final sample included 55 agencies for Part A and 144 officers for Part B. At the agency level (Part A), Employee Assistance Programs or counseling services were the most common programs offered, and, notably, planning for programming was inconsistent or not well established. At the officer level (Part B), almost 25% of respondents did not know whether their agency had programming; 35% did not feel their agency supports its officers' mental wellness. For officers who did feel their wellness was supported, they reported significantly less stress and higher overall well-being. Of officer respondents, 12.4% indicated it was either "quite" or "very likely" they would attempt suicide someday. Implications and suggestions for law enforcement agencies are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Frequency of Acute Otitis Media in Children Under 24 Months of Age Before and After the Introduction of the 10-valent Pneumococcal Conjugate Vaccine Into the National Immunization Program in Chile.
Streptococcus pneumoniae is the leading cause of acute otitis media (AOM). Ten-valent pneumococcal conjugated vaccine (PCV-10) was introduced to the Chilean National Immunization Program (NIP) in 2011. The aim of this study was to estimate the frequency of AOM in children <24 months of age attending the emergency department (ED) of Hospital Sótero del Río (HSR) 4 years before and 4 years after the introduction of PCV-10 in the Chilean NIP. Register-based nested case-control study. Cases (n = 1907) were all children <24 months of age with a clinical diagnosis discharge of AOM at the ED of HSR, and controls (n = 244,334) were all other children <24 months of age attended at the same ED in the same time period, with any other discharge diagnosis. The data were obtained through HSR Statistical Service. In the study period, there was a mean of 30,695 children <24 months managed each year at the ED of HSR. The percentage with AOM in the prevaccine period was 0.94% and in the postvaccine period was 0.62%, respectively (P = 0.026). Exposure to the PCV-10 was associated with a decreased risk to develop AOM in children <24 months, with an odds ratio of 0.659 (95% confidence interval: 0.60-0.72). Our study showed a significant decrease in the percentage and risk of AOM in children <24 months of age who visited the ED of HSR after implementation of PCV-10 in the NIP in Chile.


Rethinking motor lateralization: specialized but complementary mechanisms for motor control of each arm.
Motor lateralization in humans has primarily been characterized as "handedness", resulting in the view that one arm-hemisphere system is specialized for all aspects of movement while the other is simply a weaker analogue. We have proposed an alternative view that motor lateralization reflects proficiency of each arm for complementary functions that arises from a specialization of each hemisphere for distinct movement control mechanisms. However, before this idea of hemispheric specialization can be accepted, it is necessary to precisely identify these distinct, lateralized mechanisms. Here we show in right-handers that dominant arm movements rely on predictive mechanisms that anticipate and account for the dynamic properties of the arm, while the non-dominant arm optimizes positional stability by specifying impedance around equilibrium positions. In a targeted-reaching paradigm, we covertly and occasionally shifted the hand starting location either orthogonal to or collinear with a particular direction of movement. On trials on which the start positions were shifted orthogonally, we did not notice any strong interlimb differences. However, on trials on which start positions were shifted orthogonally, the dominant arm largely maintained the direction and straightness of its trajectory, while the non-dominant arm deviated towards the previously learned goal position, consistent with the hypothesized control specialization of each arm-hemisphere system. These results bring together two competing theories about mechanisms of movement control, and suggest that they coexist in the brain in different hemispheres. These findings also question the traditional view of handedness, because specialized mechanisms for each arm-hemisphere system were identified within a group of right-handers. It is likely that such hemispheric specialization emerged to accommodate increasing motor complexity during evolution.


[NAD+-kinase from Neurospora crassa: isolation and properties].
The NAD+ kinase (EC 126.96.36.199) of the filamentous fungus N. crassa is localized in cytosol. The activity in the dialyzed cell free extract has a pH optimum 8.3; it utilizes only ATP but not inorganic polyphosphates as a phosphoryl donor. A method for 200-fold purification of NAD+ kinase with a 20% yield has been developed. The procedure includes 105000 g centrifugation, fractionation with (NH4)2SO4, isoelectrofocusing in a Ultrodex layer and preparative electrophoresis in polyacrylamide gel. The molecular heterogeneity of NAD+ kinase was demonstrated by polyacrylamide gradient electrophoresis and by gel filtration through Sephadex G-200. The molecular weights of four individual forms of the enzyme are: 330000-338000, 305000-306000, 215000-229000 and 203000 Da. The Km values for the reaction catalyzed by purified NAD+ kinase for NAD+ and ATP are 3.0 X 10(-4) M and 0.9 X 10(-3) M, respectively.


18F-DCFPyL PET/CT in the Detection of Prostate Cancer at 60 and 120 Minutes: Detection Rate, Image Quality, Activity Kinetics, and Biodistribution.
There is increasing interest in PET/CT with prostate-specific membrane antigen (PSMA) tracers for imaging of prostate cancer because of the higher detection rates of prostate cancer lesions than with PET/CT with choline. For 68Ga-PSMA-11 tracers, late imaging at 180 min after injection instead of imaging at 45-60 min after injection improves the detection of prostate cancer lesions. For 18F-DCFPyL, improved detection rates have recently been reported in a small pilot study. In this study, we report the effects of PET/CT imaging at 120 min after injection of 18F-DCFPyL in comparison to images acquired at 60 min after injection in a larger clinical cohort of 66 consecutive patients with histopathologically proven prostate cancer. Methods: Images were acquired 60 and 120 min after injection of 18F-DCFPyL. We report the positive lesions specified for anatomic locations (prostate, seminal vesicles, local lymph nodes, distant lymph nodes, bone, and others) at both time points by visual analysis, the image quality at both time points, and a semiquantitative analysis of the tracer activity in both prostate cancer lesions as well as normal tissues at both time points. Results: Our data showed a significantly increasing uptake of 18F-DCFPyL between 60 and 120 min after injection in 203 lesions characteristic for prostate cancer (median, 10.78 vs. 12.86, P < 0.001, Wilcoxon signed-rank test). By visual analysis, 38.5% of all patients showed more lesions using images at 120 min after injection than using images at 60 min after injection, and in 9.2% a change in TNM staging was found. All lesions seen on images 60 min after injection were also visible on images 120 min after injection. A significantly better mean signal-to-noise ratio of 11.93 was found for images acquired 120 min after injection (P < 0.001, paired t test; signal-to-noise ratio at 60 min after injection, 11.15). Conclusion:18F-DCFPyL PET/CT images at 120 min after injection yield a higher detection rate of prostate cancer characteristic lesions than images at 60 min after injection. Further studies are needed to elucidate the best imaging time point for 18F-DCFPyL.


Modeling emotional contagion in the COVID-19 pandemic: a complex network approach.
During public health crises, the investigation into the modes of public emotional contagion assumes paramount theoretical importance and has significant implications for refining epidemic strategies. Prior research predominantly emphasized the antecedents and aftermath of emotions, especially those of a negative nature. The interplay between positive and negative emotions, as well as their role in the propagation of emotional contagion, remains largely unexplored. In response to this gap, an emotional contagion model was developed, built upon the foundational model and enriched from a complex network standpoint by integrating a degradation rate index. Stability analyses of this model were subsequently conducted. Drawing inspiration from topological structural features, an enhanced model was introduced, anchored in complex network principles. This enhanced model was then experimentally assessed using Watts-Strogatz's small-world network, Barabási-Albert's scale-free network, and Sina Weibo network frameworks. Results revealed that the rate of infection predominantly dictates the velocity of emotional contagion. The incitement rate and purification rate determine the overarching direction of emotional contagion, whereas the degradation rate modulates the waning pace of emotions during intermediate and later stages. Furthermore, the immunity rate was observed to influence the proportion of each state at equilibrium. It was discerned that a greater number of initial emotional disseminators, combined with a larger initial contagion node degree, can amplify the emotion contagion rate across the social network, thus augmenting both the peak and overall influence of the contagion.


Schizophrenia and complications of pregnancy and labor: an individual patient data meta-analysis.
Several epidemiological studies have reported an association between complications of pregnancy and delivery and schizophrenia, but none have had sufficient power to examine specific complications that, individually, are of low prevalence. We, therefore, performed an individual patient meta-analysis using the raw data from case control studies that used the Lewis-Murray scale. Data were obtained from 12 studies on 700 schizophrenia subjects and 835 controls. There were significant associations between schizophrenia and premature rupture of membranes, gestational age shorter than 37 weeks, and use of resuscitation or incubator. There were associations of borderline significance between schizophrenia and birthweight lower than 2,500 g and forceps delivery. There was no significant interaction between these complications and sex. We conclude that some abnormalities of pregnancy and delivery may be associated with development of schizophrenia. The pathophysiology may involve hypoxia and so future studies should focus on the accurate measurement of this exposure.


Brefeldin A and mannose 6-phosphate regulation of acrosomic related vesicular trafficking.
Acrosomal biogenesis represents a unique system for the molecular analysis of the various processes involved in vesicular membrane transport. To assess the basic membrane trafficking mechanisms used in spermatids, we have used two fluorescent lipid compounds that label: a) the Golgi and Golgi-derived vesicles (C5-DMB-Cer), and b) endocytic vesicles (FM4-64). Incubation of mouse testicular germ cells at 33 degrees C for 1.5 h with C5-DMB-Cer revealed that C5-DMB-Cer labeling is localized in the Golgi and acrosome of early-maid round spermatid stages, with no labeling of the acrosome in late round spermatid stages. Culturing germ cells with FM4-64 for 1.5 h at 33 degrees C, showed that FM4-64 labeling in spermatids was localized in endocytic vesicles and Golgi of early-mid round spermatid stages, whereas in a small population of late round spermatid stages, FM4-64 was also localized in the apex region of the acrosome. Incubation with brefeldin A (BFA) (5 micrograms/ml) inhibited the distribution of C5-DMB-Cer and FM4-64 to the acrosome, however, it did not affect the localization of acrosin-an acrosome-specific protein-indicating that there was no apparent acrosome disassembly in the presence of BFA. Localization of FM4-64 in late round spermatids in the presence of 2.5 mM mannose 6-phosphate was found in endocytic vesicles and the Golgi, but not the acrosome. These results show that there are at least two sources of vesicular transport to the acrosome derived from the Golgi and plasma membrane.


Frailty among Older Adults Living in Nursing Homes in Indonesia: Prevalence and Associated Factors.
Frailty syndrome is a predictor of all-cause mortality among older adults living in nursing homes. However, data on the prevalence of frailty among individuals living in nursing homes, particularly in middle-income countries, are limited. Thus, this study aimed to determine the prevalence of frailty and identify its associated factors among older adults living in nursing homes in Indonesia. This cross-sectional study of older adults living in six nursing homes in Indonesia was conducted between May and December 2019. Data on demographic characteristics, physical activity (Physical Activity Scale for the Elderly), cognitive status (Abbreviated Mental Test), nutritional status (Mini Nutritional Assessment Short-Form), depression (Geriatric Depression Scale), comorbidity, frailty state (Cardiovascular Health Study criteria), dietary pattern (24-hour food recall), handgrip strength, and gait speed were evaluated. Bivariate and multivariate analyses were performed to identify factors independently associated with frailty. This study recruited a total of 214 participants with a mean age of 73.68±4.30 years. The prevalence rates of frailty and malnutrition were 46.5% and 58%, respectively. The results showed that physical frailty was associated with malnutrition (odds ratio=4.23; 95% confidence interval, 1.730-10.380). Frailty was prevalent and strongly associated with malnutrition among older adults living in nursing homes in Indonesia.


Solution structure of acidocin B, a circular bacteriocin produced by Lactobacillus acidophilus M46.
Acidocin B, a bacteriocin produced by Lactobacillus acidophilus M46, was originally reported to be a linear peptide composed of 59 amino acid residues. However, its high sequence similarity to gassericin A, a circular bacteriocin from Lactobacillus gasseri LA39, suggested that acidocin B might be circular as well. Acidocin B was purified from culture supernatant by a series of hydrophobic interaction chromatographic steps. Its circular nature was ascertained by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and tandem mass spectrometry (MS/MS) sequencing. The peptide sequence was found to consist of 58 amino acids with a molecular mass of 5,621.5 Da. The sequence of the acidocin B biosynthetic gene cluster was also determined and showed high nucleotide sequence similarity to that of gassericin A. The nuclear magnetic resonance (NMR) solution structure of acidocin B in sodium dodecyl sulfate micelles was elucidated, revealing that it is composed of four α-helices of similar length that are folded to form a compact, globular bundle with a central pore. This is a three-dimensional structure for a member of subgroup II circular bacteriocins, which are classified based on their isoelectric points of ∼7 or lower. Comparison of acidocin B with carnocyclin A, a subgroup I circular bacteriocin with four α-helices and a pI of 10, revealed differences in the overall folding. The observed variations could be attributed to inherent diversity in their physical properties, which also required the use of different solvent systems for three-dimensional structural elucidation.


Hydroxyapatite coating improves fixation of pedicle screws. A clinical study.
We investigated the effects of hydroxyapatite (HA) coating on the purchase of pedicle screws. A total of 23 consecutive patients undergoing lumbar fusion was randomly assigned to one of three treatment groups. The first received uncoated stainless-steel screws, the second screws which were partly coated with HA, and the third screws which were fully coated. The insertion torque was recorded. After 11 to 16 months, 21 screws had been extracted. The extraction torque was recorded. Radiographs were taken to assess fusion and to detect loosening of the screws. At removal, the extraction torques exceeded the upper limit of the torque wrench (600 Ncm) for many HA-coated screws. The calculated mean extraction torque was 29 +/- 36 Ncm for the uncoated group, 447 +/- 114 Ncm for the partly-coated group and 574 +/- 52 Ncm for the fully-coated group. There were significant differences between all three groups (p < 0.001). There were more radiolucent zones surrounding the uncoated screws than the HA-coated screws (p < 0.001). HA coating of pedicle screws resulted in improved fixation with reduced risk of loosening of the screws.


Exosome encased spherical nucleic acid gold nanoparticle conjugates as potent microRNA regulation agents.
Exosomes are a class of naturally occurring nanomaterials that play crucial roles in the protection and transport of endogenous macromolecules, such as microRNA and mRNA, over long distances. Intense effort is underway to exploit the use of exosomes to deliver synthetic therapeutics. Herein, transmission electron microscopy is used to show that when spherical nucleic acid (SNA) constructs are endocytosed into PC-3 prostate cancer cells, a small fraction of them (<1%) can be naturally sorted into exosomes. The exosome-encased SNAs are secreted into the extracellular environment from which they can be isolated and selectively re-introduced into the cell type from which they were derived. In the context of anti-miR21 experiments, the exosome-encased SNAs knockdown miR-21 target by approximately 50%. Similar knockdown of miR-21 by free SNAs requires a ≈3000-fold higher concentration.


Haloplanus salinarum sp. nov., an extremely halophilic archaeon isolated from a solar saltern.
An extremely halophilic archaeal strain SP28T was isolated from the Gomso solar saltern, Republic of Korea. Cells of the new strain SP28T were pleomorphic and Gram stain negative, and produced red-pigmented colonies. These grew in medium with 2.5-4.5 M NaCl (optimum 3.1 M) and 0.05-0.5 M MgCl2 (optimum 0.1 M), at 25-50 °C (optimum 37 °C) and at a pH of 6.5-8.5 (optimum pH 8.0). Mg2+ was required for growth. A concentration of at least 2 M NaCl was required to prevent cell lysis. Polar lipids included phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and one glycolipid chromatographically identical to sulfated mannosyl glucosyl diether. 16S rRNA and rpoB' gene sequence analyses showed that strain SP28T is closely related to Haloplanus ruber R35T (97.3 and 94.1 %, 16S rRNA and rpoB' gene sequence similarity, respectively), Haloplanus litoreus GX21T (97.0 and 92.1 %), Haloplanus salinus YGH66T (96.0 and 91.9 %), Haloplanus vescus RO5-8T (95.9 and 90.9 %), Haloplanus aerogenes TBN37T (95.6 and 90.3 %) and Haloplanus natans RE-101T (95.3 and 89.8 %). The DNA G+C content of the novel strain SP28T was 66.2 mol%, which is slightly higher than that of Hpn.litoreus GX21T (65.8 mol%) and Hpn.ruber R35T (66.0 mol%). DNA-DNA hybridization values betweenHpn.ruber R35T and strain SP28T and between Hpn.litoreus GX21T and strain SP28T were about 24.8 and 20.7 %, respectively. We conclude that strain SP28T represents a novel species of the genus Haloplanus and propose the name Haloplanus salinarum sp. nov. The type strain is SP28T (=JCM 31424T=KCCM 43210T).


A model system for investigating the biliary excretion of an anion in the rat.
1. The biliary excretion of phenolphthalein di[35S]sulphate was studied in rats. 2. The conjugate was administered by continuous infusion at rates of 3, 4.5, 6, 9 and 12 mug/min, and kinetic analysis of the rate of biliary excretion was consistent with a two-compartment open-model system. 3. The results obtained after single injections of the ester were also consistent with the model. 4. An essential feature of the model is the presence of a compartment into which the ester may pass as an alternative to direct excretion via the bile. 5. It is suggested that such a compartment may be located within the liver.


Prediction of Orthokeratology Lens Decentration with Corneal Elevation.
Lens decentration is common and unavoidable to some extent during ortho-k treatment. By using a simplified method, we are able to predict the magnitude and direction of ortho-k lens decentration, which provides useful insights in screening for ideal ortho-k candidates and to make a quick decision when decentration happens. The aim of this study was to investigate the influence of corneal elevation asymmetry on ortho-k lens decentration. Thirty-six eyes of 36 subjects were fitted with four-curve reverse geometry ortho-k contact lenses. Corneal topography was collected before and 1 month after ortho-k lens wear. The difference in corneal elevation at the 8-mm chord of the respective two principal meridians of corneal astigmatism was calculated. Vector analyses were performed on these differences to calculate the magnitude and direction of a vector (corneal asymmetry vector). The relationship between the angle and magnitude of corneal asymmetry vector and lens decentration was analyzed. Baseline refractive sphere and cylinder for the 36 tested eyes were -2.84 ± 1.04 diopters (D) (range, -4.75 to -1.00 D) and -0.21 ± 0.28 D (range, -1.00 to 0 D), respectively. The mean magnitude of lens decentration was 0.72 ± 0.26 mm (0 to 1.34 mm). For overall displacement, inferotemporal decentration was the most common as observed in 24 eyes (67%). The mean angle of the corneal asymmetry vector (202 ± 39 degrees) was significantly correlated to the mean angle of lens decentration (200 ± 39 degrees) (r = 0.76, P < .001). The magnitude of corneal asymmetry vector significantly contributed to the magnitude of lens decentration (standardized β = 0.448, P = .002) whereas the other tested variables did not affect lens decentration (all P > .05). Lens decentration is a common phenomenon in ortho-k that mostly happens toward the inferotemporal quadrant of the cornea. The magnitude and direction of lens decentration are predetermined by paracentral corneal asymmetry.


I can hear my shunt-audible noises associated with CSF shunts in hydrocephalic patients.
Cerebrospinal fluid (CSF) shunts are life-long implants, and patients have reported anecdotally on noises associated with their shunts. There is, however, a marked lack of information regarding acoustic phenomena related to CSF shunts. We identified all patients who had been treated or followed in our neurosurgical department within a 15-year period from January 2000 up to the end of 2014. After approval of the local ethics committee all patients who were cognitively intact were explored by a questionnaire and by personal interview about acoustic phenomena related to their shunts. Three hundred forty-seven patients were eligible for the survey, and 260 patients completed the questionnaire. Twenty-nine patients (11.2%) reported on noises raised by their shunts. All of them experienced short-lasting noises while changing body posture, mainly from a horizontal to an upright position, or while reclining the head. Most of the patients reported on soft sounds, but loud and even very loud noises occurred in some patients. Seventy-six percent of the patients were not bothered by these noises as they considered it as a normal part of the therapy or as proof that the shunt device was functioning. Modern valves with gravitational units are prone to produce noises in young adults, but nearly all valve types can evoke noises. Noises caused by a shunt do occur in a considerable number of patients with shunts. One should be aware of this phenomenon, and these patients must be taken seriously.


Pharmacological advances in the treatment of insomnia.
Insomnia is a highly prevalent condition, and due to ongoing demand from patients suffering with this condition, new pharmacological treatments are actively being sought. As our neurophysiological understanding of insomnia grows, so too do the available treatment options. A significant advance in the treatment of insomnia came with the development of the nonbenzodiazepine hypnotic medications, zolpidem, zaleplon and eszopiclone. These medications have shorter durations of action than many traditional benzodiazepines and may be associated with less risk of tolerance and abuse. They have also been demonstrated to be helpful in cases in which insomnia is comorbid with depression or anxiety, leading to beneficial effects not only with sleep but also with mood and anxiety symptoms. Melatonin, a naturally-occurring substance intimately involved in the regulation of the circadian rhythm, has also been explored as a hypnotic. Little data to date support its use; however, there is evidence that ramelteon, a melatonin agonist, may be helpful for sleep initiation difficulties. Tri-cyclic antidepressants have long been used for insomnia, but use has been limited by unwanted anticholinergic side effects. Low-dose doxepin, at doses of 3 and 6mg, has been demonstrated to have the unique property among its class of being free of anticholinergic effects at those doses. In addition, it seems to have particular efficacy for sleep maintenance insomnia, exhibiting the most robust effects in the latter third of the night. The hypocretin/orexin system has been identified as a possible target. Almorexant, a hypocretin/orexin antagonist displayed evidence of efficacy during Phase III clinical trials but these trials were recently discontinued due to its side effect profile. Another hypocretin/orexin antagonist with a different mechanism of action, MK-4035, is presently in clinical trials. Serotonin antagonists and inverse agonists have been investigated; however, a recent trial with APD125 was discontinued due to lack of efficacy. Sodium oxybate has been used off-label for insomnia by some providers, although data supporting its use are limited. While the sleep-promoting effects of GABA(A) (nonbenzodiazepines and benzodiazepines) enhancement is well-established, newer research examining other mechanisms of action suggest that agents which modulate the histaminergic, serotonergic, melontonergic, and hypocretin/orexin and perhaps GABA-B systems show promise.


Banked fibula and the locking anterior cervical plate in anterior cervical fusions following cervical discectomy.
Eighty-eight consecutive patients underwent anterior cervical discectomy (ACD) with banked fibula fusion and internal fixation using the locking cervical plate. Pathology included cervical spondylotic radiculopathy in 48, cervical spondylotic radiculomyelopathy in 30, cervical facet dislocations with associated disc herniations in six, and autologous iliac crest graft collapse pseudoarthrosis with recurrent symptoms in four patients. Operations were single-level banked fibula fusion with plating in 37, multilevel banked fibula fusion with plating in 45, and combined single-level ACD banked fibula fusion with plating and posterior fusion in six patients. The only perioperative complication was transient hoarseness. There were no transfusions, infections, neurological injuries, or deaths. The mean time in the hospital for the nontraumatic cases was 1.8 days. The mean follow up was 22 months (range 12-30 months). There has been no motion at the fused level on flexion/extension films, no kyphosis, no screw plate backout, and no banked fibula has suffered graft collapse. Following a high-speed motor vehicle accident 6 months after a multilevel fusion, one alcoholic man suffered a fractured plate with transient worsening of neck pain, and the plate has remained in place for an additional 11 months of follow-up care. Compared to 100 consecutive autologous iliac crest fusions performed by the same surgeon, there were significantly fewer graft-related complications (p < 0.001). There was a significantly greater chance of autologous iliac crest collapsing with the passage of time as compared to banked fibula. Time until return to work was shorter by 5 weeks for the plate/banked fibula group (p < 0.05). When fusion is considered following ACD, the combination of banked fibula and locking cervical plates is significantly superior to autologous iliac crest grafts.


Early experience with laparoscopic surgery in children in Ile-Ife, Nigeria.
Laparoscopy is not yet routinely employed in many Paediatric Surgical Units in Nigeria despite the advantages it offers. This study describes the preliminary experience with laparoscopic procedures in a single centre. A retrospective analysis of all children who had laparoscopic surgery between January 2009 and December 2013 at the Paediatric Surgical Unit of Obafemi Awolowo University Teaching Hospitals Complex Ile-Ife was carried out. Their sociodemographic, preoperative and intraoperative data along with postoperative records were subjected to descriptive analysis. Eleven (44%) diagnostic and 14 (56%) therapeutic procedures were performed on 25 children whose age ranged from 5 months to 15 years (Median: 84 months, Mean: 103 ± 64.1 months), including eight (32%) females and 17 (68%) males. Indications included acute appendicitis in 12 (48%), intra-abdominal masses in six (24%), three (12%) disorders of sexual differentiation, two (8%) ventriculoperitoneal shunt malfunctions and impalpable undescended testes in two (8%) children. The procedures lasted 15-90 minutes (Mean = 54 (±21.6) minutes). Conversion rate was 17% for two patients who had ruptured retrocaecal appendices. No intra operative complications were recorded while three (12%) patients had superficial port site infections post-operatively. All diagnostic (11) and two therapeutic procedures were done as day case surgery. The mean duration of hospital stay was 3.1 (±3.3) days for those who had appendectomies. Laparoscopic surgery in children is safe and feasible in our hospital. We advocate increased use of laparoscopy in paediatric surgical practice in Nigeria and similar developing settings.


Risk Factors for contrast-related acute kidney injury according to risk, injury, failure, loss, and end-stage criteria in patients with coronary interventions.
Although a series of risk factors for contrast-induced nephropathy are known, data on significance of some of the risk factors such as age, sex, hypercholesterolemia, hyperuricemia, and dose of contrast medium are inconsistent. Our aim was to identify risk factors for contrast-related acute kidney injury (AKI). In this prospective study, 290 consecutive patients with a serum creatinine level lower than 3 mg/dL undergoing percutaneous angiography were analyzed. Contrast-related AKI was evaluated using the risk, injury, failure, loss, and end-stage (RIFLE) criteria, and its correlation with clinical and laboratory data of the patients was analyzed. Contrast-related AKI was found in 15.5% of the patients, with a maximum RIFLE category (risk in 13.8%, injury in 1.4%, and failure in 0.3%). Serum creatinine level, contrast volume, safe contrast volume factor, diabetes mellitus, and dehydration were significantly associated with contrast-related AKI. Age, sex, and serum uric acid level did not differ significantly between those with and without contrast-related AKI. Multiple logistic regression analysis disclosed diabetes mellitus to be the strongest predictor for being at risk of contrast-related AKI (odds ratio, 5.1; 95% confidence interval, 1.9 to 11.0; P = .001), followed by hypercholesterolemia (odds ratio, 4.6; 95% confidence interval, 1.1 to 8.3; P = .03), and an estimated glomerular filtration rate lower than 90 mL/min/1.73 m2 (odds ratio, 3.0; 95% confidence interval, 1.8 to 5.7; P = .003). Our results indicate that diabetes mellitus, hypercholesterolemia, and underlying chronic kidney disease are the major factors of contrast-related AKI.


Effects of guanotrophication and warming on the abundance of green algae, cyanobacteria and microcystins in Lake Lesser Prespa, Greece.
Lake Lesser Prespa in Greece is a vital breeding habitat for the Dalmatian and Great White Pelican and a shelter for numerous rare and endemic species. However, eutrophication processes are distressing the lake system and the outbreaks of cyanobacterial blooms during the warm months may pose a threat to aquatic organisms due to the presence of microcystins (MCs). In this study we hypothesize that nutrients (eutrophication), nutrient-rich pelican droppings (guanotrophication) and warming (climate change) can affect the algal growth and MCs production in the water layer of Lake Lesser Prespa. Seston collected from three lake sites was incubated at ambient (20°C) and high (30°C) temperature with or without the addition of nutrients (nitrogen (N), phosphorus (P)), or pelican droppings. Results showed increased chlorophyll-a at higher temperature (30°C). N addition yielded higher chlorophyll-a levels than the non-treated water or when only P was added. The addition of both N and P as well as the addition of pelican dropping resulted in the highest chlorophyll-a at both temperatures. Notably, in the dropping-treatments, cyanobacteria and MCs were promoted while changes were evoked in the relative contribution of toxic MC-variants. Guanotrophication may thus influence the cyanobacterial dynamics and most likely their toxicity profile at Lesser Prespa.


Ultrasound-assisted percutaneous trigger finger release: is it safe?
Trigger fingers can be treated by open or percutaneous division of the A1 pulley. The open approach allows for visualization of the pulley, the tendon, and the adjacent neurovascular bundles. The percutaneous trigger finger release (PTFR) lacks an incision and is thought to lead to a quicker recovery, but the safety and efficacy of this blind procedure are often questioned. Ultrasound imaging has recently been introduced as an adjunct for guiding the needle during percutaneous trigger finger release. This study was designed to evaluate the safety and efficacy of needle trigger finger release with added ultrasound imaging. Eighteen fresh cadaver A1 pulleys were divided percutaneously and then evaluated by converting to an open technique and examining the pulleys, the tendons, and the neurovascular bundles. This study's ultrasound images demonstrated repeated puncture of the tendon sheath and of the neurovascular bundle during PTFR. The subsequent dissection revealed three out of 18 tendons with visible lacerations and 15 out of 18 A1 pulleys with incomplete division. We concluded that ultrasound-guided PTFR can be complicated by flexor tendon lacerations, potential injury to neurovascular bundles, and incomplete division of the A1 pulleys. While the clinical significance of these findings is unclear to us, it does raise questions regarding the safety and efficacy of percutaneous trigger finger release, even when adding ultrasound guidance.


[Local approval procedures act as a brake on RCTs].
Large multicentre randomised controlled trials (RCTs) in the Netherlands are increasingly being impeded by major differences between local approval procedures. However, no national agenda exists as yet to improve this situation. The existence of major local differences in processing time and documentation required has been reported previously but little is known about the costs incurred and whether or not specific certifications and research contracts are mandatory. The current study evaluated these aspects of local procedures for obtaining approval of two oncological multicentre RCTs. Retrospective, descriptive. All local procedures for obtaining approval of two randomised clinical trials were evaluated: the CAIRO5 and CHARISMA trials initiated by the Dutch Colorectal Cancer Group (DCCG). We objectified time between approval by the Medical Ethics Review Committee (METC) and final approval by the Board of Directors (RvB), the type and number of documents needed, and costs charged. The median time interval between the approval by the Medical Ethics Review Committee and the approval by the Board of Directors was 90 days (range 4-312). The number of documents required per centre ranged from 6-20. The costs charged ranged from € 0-€ 1750, and amounted to € 8575 for all procedures combined. No costs were charged by the majority of the centres. The approval procedures for multicentre clinical trials in the Netherlands demonstrate major differences. Processing times, documentation required and costs are unpredictable; greater uniformity is highly desirable in this context.


Isolation and Characterization of Mouse Monoclonal Antibodies That Neutralize SARS-CoV-2 and Its Variants of Concern Alpha, Beta, Gamma and Delta by Binding Conformational Epitopes of Glycosylated RBD With High Potency.
Antibodies targeting Receptor Binding Domain (RBD) of SARS-CoV-2 have been suggested to account for the majority of neutralizing activity in COVID-19 convalescent sera and several neutralizing antibodies (nAbs) have been isolated, characterized and proposed as emergency therapeutics in the form of monoclonal antibodies (mAbs). However, SARS-CoV-2 variants are rapidly spreading worldwide from the sites of initial identification. The variants of concern (VOC) B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.167.2 (Delta) showed mutations in the SARS-CoV-2 spike protein potentially able to cause escape from nAb responses with a consequent reduction of efficacy of vaccines and mAbs-based therapy. We produced the recombinant RBD (rRBD) of SARS-CoV-2 spike glycoprotein from the Wuhan-Hu 1 reference sequence in a mammalian system, for mice immunization to isolate new mAbs with neutralizing activity. Here we describe four mAbs that were able to bind the rRBD in Enzyme-Linked Immunosorbent Assay and the transmembrane full-length spike protein expressed in HEK293T cells by flow cytometry assay. Moreover, the mAbs recognized the RBD in supernatants of SARS-CoV-2 infected VERO E6 cells by Western Blot under non-reducing condition or in supernatants of cells infected with lentivirus pseudotyped for spike protein, by immunoprecipitation assay. Three out of four mAbs lost their binding efficiency to completely N-deglycosylated rRBD and none was able to bind the same recombinant protein expressed in Escherichia coli, suggesting that the epitopes recognized by three mAbs are generated by the conformational structure of the glycosylated native protein. Of particular relevance, three mAbs were able to inhibit Wuhan SARS-CoV-2 infection of VERO E6 cells in a plaque-reduction neutralization test and the Wuhan SARS-CoV-2 as well as the Alpha, Beta, Gamma and Delta VOC in a pseudoviruses-based neutralization test. These mAbs represent important additional tools for diagnosis and therapy of COVID-19 and may contribute to the understanding of the functional structure of SARS-CoV-2 RBD.


A comparison of the cost-effectiveness of two pedometer-based telephone coaching programs for people with cardiac disease.
Following a cardiac event it is recommended that cardiac patients participate in cardiac rehabilitation (CR) programs. However, little is known about the relative cost-effectiveness of lifestyle-related interventions for cardiac patients. This study aimed to compare the cost-effectiveness of a telephone-delivered Healthy Weight intervention to a telephone-delivered Physical Activity intervention for patients referred to CR in urban and rural Australia. A cost-utility analysis was conducted alongside a randomised controlled trial of the two interventions. Outcomes were measured as Quality Adjusted Life Years (QALYs) gained. The estimated cost of delivering the interventions was $201.48 per Healthy Weight participant and $138.00 per Physical Activity participant. The average total cost (cost of health care utilisation plus patient costs) was $1,260 per Healthy Weight participant and $2,112 per Physical Activity participant, a difference of $852 in favour of the Healthy Weight intervention. Healthy Weight participants gained an average of 0.007 additional QALYs than did Physical Activity participants. Thus, overall the Healthy Weight intervention dominated the Physical Activity intervention (Healthy Weight intervention was less costly and more effective than the Physical Activity intervention). Subgroup analyses showed the Healthy Weight intervention also dominated the Physical Activity intervention for rural participants and for participants who did not attend CR. The low-contact pedometer-based telephone coaching Healthy Weight intervention is overall both less costly and more effective compared to the Physical Activity intervention, including for rural cardiac patients and patients that do not attend CR.


Efficacy of commercial enzymes in diets containing various concentrations and sources of dried distillers grains with solubles for nursery pigs.
In 2 experiments, 530 pigs were used to evaluate the effects of adding commercial enzymes to diets containing dried distillers grains with solubles (DDGS) on pig growth performance. In the first experiment, 180 pigs (9.0 kg initial BW) were fed a corn-soybean meal-based control diet, a diet containing 30% corn DDGS, or the 30% DDGS diet with 0.05% of enzyme A, B, or C. There were 6 pigs per pen and 6 pens per treatment. Overall (d 0 to 27), neither DDGS nor enzyme addition increased ADG and G:F. Pigs fed enzyme B had decreased (P < 0.05) ADG as a result of a tendency (P <or= 0.10) for decreased ADFI compared with control pigs or pigs fed DDGS without added enzyme. In Exp. 2, 350 pigs (11.0 kg initial BW) were fed 1 of 10 dietary treatments. Pigs were fed a control corn-soybean meal-based diet or the control diet containing 15 or 30% DDGS from 3 sources (corn, sorghum 1, or sorghum 2). Diets containing 30% DDGS were fed with or without the same enzyme (enzyme A) as Exp. 1. There were 5 pigs per pen and 7 pens per treatment. Overall (d 7 to 28), there were no (P > 0.10) enzyme x DDGS source interactions observed. Corn DDGS did not influence (P > 0.10) ADG, ADFI, or G:F. Sorghum DDGS reduced (P = 0.003) G:F, with no difference (P > 0.10) between sorghum DDGS sources. Adding the commercial enzyme to the 30% DDGS diets did not improve performance. In summary, feeding diets with sorghum DDGS resulted in poorer G:F with no change in ADG compared with feeding the control diet or diets containing corn DDGS. Adding the enzymes used in this study to corn-soybean meal-based diets containing 30% DDGS did not improve growth performance.


Clostridium difficile colitis in lung transplantation.
Clostridium difficile colitis (CDC) is the most common nosocomial infection of the gastrointestinal tract in patients with recent antibiotic use or hospitalization. Lung transplant recipients receive aggressive antimicrobial therapy postoperatively for treatment and prophylaxis of respiratory infections. This report describes the epidemiology of CDC in lung recipients from a single center and explores possible associations with bronchiolitis obliterans syndrome (BOS), a surrogate marker of chronic rejection. Patients were divided into those with confirmed disease (CDC+) and those without disease (CDC-) based on positive C. difficile toxin assay. Because of a bimodal distribution in the time to develop CDC, the early postoperative CDC+ group was analyzed separately from the late postoperative CDC+ cohort with respect to BOS development. Between 1990 and 2005, 202 consecutive patients underwent 208 lung transplantation procedures. Of these, 15 lung recipients developed 23 episodes of CDC with a median follow-up period of 2.7 years (range, 0-13.6). All patients with confirmed disease had at least 1 of the following 3 risk factors: recent antibiotic use, recent hospitalization, or augmentation of steroid dosage. Of the early CDC+ patients, 100% developed BOS, but only 52% of the late CDC+ patients developed BOS, either preceding or following infection. CDC developed in 7.4% of lung transplant patients with identified risk factors, yielding a cumulative incidence of 14.7%. The statistical association of BOS development in early CDC+ patients suggests a relationship between early infections and future chronic lung rejection.


Prevention of postmenopausal bone loss and treatment of osteoporosis.
Osteoporosis is now recognized as an increasingly prevalent disorder throughout the world. Fragility fractures and their subsequent short- and long-term complications are the adverse outcomes of this disease that is essentially silent until fractures occur. Given that the presence of one fragility fracture is an important predictor of the risk of subsequent fractures, prevention of the first fracture is critical whenever possible. Two key elements in fracture prevention that are discussed in this article are the attainment of optimal peak bone mass and the prevention of bone loss at menopause, with the major focus on the prevention of postmenopausal bone loss.


Knockdown of peroxisome proliferator-activated receptor-beta induces less differentiation and enhances cell-fibronectin adhesion of colon cancer cells.
The role of peroxisome proliferator-activated receptor-beta/delta (PPAR-beta/delta) in the pathogenesis of colon cancer remains highly controversial. This study specifically silenced the PPAR-beta expression in three colon cancer cell lines with different metastatic potentials. Although PPAR-beta knockdown resulted in more malignant morphological changes, bigger colony sizes and lower carcinoembryonic antigen (CEA) secretion, and enhanced the cell-fibronectin adhesion, cell invasion and migration were unaffected. These effects were stronger in poorly metastatic cell lines compared with highly metastatic ones. Simultaneously, PPAR-beta knockdown decreased the mRNAs encoding adipocyte differentiation-related protein and liver fatty acid binding protein, and increased the mRNA of ILK, whereas the mRNAs encoding integrin-beta1 and angiopoietin-like 4 were unchanged. Using immunohistochemistry, we determined that the intensity of PPAR-beta expression was stronger in rectal cancers with better differentiation than in those with poor differentiation, and was stronger in early-stage tumors than in advanced ones. Together, these findings consistently indicate that PPAR-beta may facilitate differentiation and inhibit the cell-fibronectin adhesion of colon cancer, having a role as an inhibitor in the carcinogenesis and progression of colorectal cancer. Interestingly, PPAR-beta seems to have a more important role in poorly metastatic cells than in highly metastatic ones.


Recent developments and applications of liquid phase microextraction in fruits and vegetables analysis.
The sample preparation step has been identified as the bottleneck of analytical methodology in chemical analysis. Therefore, there is need for the development of cost-effective, easy to operate, and environmentally friendly miniaturized sample preparation technique. The microextraction techniques combine extraction, isolation, concentration, and introduction of analytes into analytical instrument, to a single and uninterrupted step, and improve sample throughput. The use of liquid-phase microextraction techniques for the analysis of pesticide residues in fruits and vegetables are discussed with the focus on the methodologies employed by different researchers and their analytical performances. Analytes are extracted using water-immiscible solvents and are desorbed into gas chromatography, liquid chromatography, or capillary electrophoresis for identification and quantitation.


Visualization of diffuse centromeres with centromere-specific histone H3 in the holocentric plant Luzula nivea.
Although holocentric species are scattered throughout the plant and animal kingdoms, only holocentric chromosomes of the nematode worm Caenorhabditis elegans have been analyzed with centromeric protein markers. In an effort to determine the holocentric structure in plants, we investigated the snowy woodrush Luzula nivea. From the young roots, a cDNA encoding a putative centromere-specific histone H3 (LnCENH3) was successfully isolated based on sequence similarity among plant CENH3s. The deduced amino acid sequence was then used to raise an anti-LnCENH3 antibody. Immunostaining clearly revealed the diffuse centromere-like structure that appears in the linear shape at prophase to telophase. Furthermore, it was shown that the amount of LnCENH3 decreased significantly at interphase. The polar side positioning on each chromatid at metaphase to anaphase also confirmed that LnCENH3 represents one of the centromere-specific proteins in L. nivea. These data from L. nivea are compared with those from C. elegans, and common features of holocentric chromosomes are discussed.


Change in serum ferritin concentration in experimentally induced anemia of chronic inflammation in dogs.
In veterinary medicine, hyperferritinemia is often observed in dogs with various diseases (e.g., histiocytic sarcoma and immune-mediated hemolytic anemia) without evidence of iron overload. The mechanism underlying hyperferritinemia development is not well understood. Anemia caused by inflammation is termed as anemia of chronic disease (ACD), and experimentally induced ACD is known to cause slight hyperferritinemia. However, almost all these studies were based on short-term acute inflammation. Hepcidin, a protein mainly produced by hepatocytes, is thought to be a key regulator in iron release from reticuloendothelial cells (RECs), and its expression is related to ACD. We hypothesized that in the case of long-term ACD, iron deposition in RECs increases through hepcidin, causing a diachronic increase in serum ferritin levels. In the present study, we used a canine model with repeated subcutaneous administration of turpentine oil every 3 days over a period of 42 days (15 injections) and induced long-term inflammatory conditions; furthermore, we evaluated the change in serum ferritin concentration. Hypoproliferative anemia, bone marrow iron deposition and hypoferremia, which are characteristic of ACD, were observed on administering the turpentine injections. Hepatic iron content, hepatic hepcidin mRNA expression and serum ferritin concentration increased during the early period after turpentine injection, but returned to normal levels later. These results show that experimentally induced long-term ACD caused hypoproliferative anemia without sustained increase in hepcidin expression and did not cause systemic iron overload. Thus, chronic inflammation may not contribute greatly to increase in hyperferritinemia.


Predicting serum gentamicin levels in adult trauma patients.
A one-compartment, open-linear, pharmacokinetic model for gentamicin dosing has been developed at the Maryland Institute for Emergency Medical Service Systems (MIEMSS). The model was used to predict both the gentamicin dose required to achieve desired peak and trough serum concentrations and the peak and trough serum concentrations that would result from administering empirically chosen doses. This model was tested in 31 patients, aged 15 to 82 years (mean 39.3 +/- 17.7 years), whose creatinine clearance (CCI) ranged from 12 ml/min to 197 ml/min (mean 106.9 +/- 53.1 ml/min). The predictions of the dosage model were compared with the measured peak and trough serum concentrations in these patients. The predicted peak serum levels correlated highly with the measured peak serum levels (r 0.97). The mean difference (+/- SD) between the predicted and measured peak levels was 0.28 +/- 0.22 mu g/ml. The predicted trough serum levels correlated well with the measured trough serum levels (r 0.91). The mean difference between the predicted and measured trough levels was -0.03 +/- 0.18 mu g/ml. This approach makes it possible for bactericidal levels of gentamicin to be maintained in patients with wide variations in stable renal function. Frequent serum gentamicin determinations are unnecessary. Requiring only an inexpensive calculator, the method has proved to be economical as well as clinically useful.


Nitrate-regulated auxin transport by NRT1.1 defines a mechanism for nutrient sensing in plants.
Nitrate is both a nitrogen source for higher plants and a signal molecule regulating their development. In Arabidopsis, the NRT1.1 nitrate transporter is crucial for nitrate signaling governing root growth, and has been proposed to act as a nitrate sensor. However, the sensing mechanism is unknown. Herein we show that NRT1.1 not only transports nitrate but also facilitates uptake of the phytohormone auxin. Moreover, nitrate inhibits NRT1.1-dependent auxin uptake, suggesting that transduction of nitrate signal by NRT1.1 is associated with a modification of auxin transport. Among other effects, auxin stimulates lateral root development. Mutation of NRT1.1 enhances both auxin accumulation in lateral roots and growth of these roots at low, but not high, nitrate concentration. Thus, we propose that NRT1.1 represses lateral root growth at low nitrate availability by promoting basipetal auxin transport out of these roots. This defines a mechanism connecting nutrient and hormone signaling during organ development.


Pneumatosis intestinalis associated with Henoch-Schönlein purpura.
Henoch-Schönlein purpura (HSP) is the most common vasculitis in children. It is a disorder of the inflammatory cascade leading to immunoglobulin A deposition and leukocytoclastic vasculitis of small vessels of skin, kidneys, joints, and gastrointestinal (GI) tract. A wide variety of GI manifestations are seen in ∼50% to 75% of patients with HSP. Diffuse colicky abdominal pain is the most common GI symptom. The small bowel is the most frequently involved GI site. Intussusception is rare but is the most common surgical complication. We report the case of a 2-year-old girl with a 5-day history of abdominal pain followed by a palpable purpuric rash. Her urinalysis, complete blood cell count, and tests of renal function were normal. An acute abdominal series was unremarkable initially, and abdominal ultrasound imaging showed ascites and thickened small bowel loops. She was diagnosed with HSP. The abdominal pain worsened, and an abdominal computed tomography scan demonstrated distal small bowel wall thickening and pneumatosis intestinalis in the descending colon. She was started on total parenteral nutrition and antibiotics and placed on bowel rest. She was given 2 mg/kg of intravenous immunoglobulin. Her abdominal pain gradually improved over the next week, and a repeat computed tomography scan showed significant improvement of the small bowel wall thickening and pneumatosis. The purpuric rash improved, and her abdominal pain resolved. We report a case of HSP and pneumatosis intestinalis, an association that has not been reported previously.


[Preparation of smears of isolated hepatocytes and the glycogen preservation in them after cryopreservation of the liver tissue].
A method is proposed for preparation of smears of isolated hepatocytes from liver samples frozen in liquid nitrogen or dry ice. The thawing of liver samples and the preparation of smears of isolated hepatocytes were produced by a successive maintenance of the samples in a mixture of 0.067 M phosphate buffer and 5% sucrose (pH 8.0) at 20 degrees C, followed by placing in 0.067 M phosphate buffer (pH 7.4) at the same temperature. Then hepatocytes were fixed by methanol. The cytofluorometric analysis has shown that isolation of cells from the frozen and thawing liver tissue using the proposed method does not influence the level of glycogen preservation in the hepatocytes. The proposed method may be used in the clinical practice.


The relationship between nursing instructors' clinical teaching behaviors and nursing students' learning in Tabriz University of Medical Sciences in 2016.
Clinical teaching is at the core of the nursing profession. However, clinical teaching may not empower students to gain clinical competency and skills. In this context, the performance of instructors is one of the main determinants of effective clinical teaching. Therefore, the present study aimed to determine the relationship between nursing instructors' clinical teaching behaviors and students' learning. This descriptive, correlational study was conducted with 267 nursing students selected through convenience sampling. The data were collected using the Nursing Clinical Teacher Effectiveness Inventory, developed by Knox and Morgan. The questionnaire included two parts: the extent to which nursing instructors used teaching behaviors and the effectiveness of these behaviors on students' learning. The data were entered into the SPSS statistical software, version 19, and were analyzed using descriptive and inferential statistics and the Pearson's correlation coefficient. The results showed a significant positive relationship between the extent to which nursing instructors used teaching behaviors and the effectiveness of these behaviors on students' learning (P = 0.001). In terms of the utilization of teaching behaviors, the highest average rates were related to the dimensions of interpersonal relations and teaching abilities, while the lowest average rates were found for the evaluation dimension. With regard to the effectiveness of these teaching behaviors on learning, the dimensions of teaching ability and evaluation gained the highest and lowest average rates, respectively. Instructors' capabilities have to be improved regarding the effective utilization of some behaviors related to evaluation, personal characteristics, and nursing competency. In this respect, the use of comprehensive teaching programs can be quite beneficial.


[Homeopathic treatment of adenoid vegetations. Results of a prospective, randomized double-blind study].
In a monocenter prospective randomized double-blind clinical trial the efficacy of homeopathic treatment was investigated on children with adenoid vegetations justifying an operation. Patients were treated with either homeopathic remedies such as Nux vomica D200, Okoubaka D3, Tuberculinum D200, Barium jodatum D4 and Barium jodatum D6 or with placebo. The duration of the study for each patient was 3 months. Examination of the ears using a microscope, rhinoscopy, stomatoscopy and pharyngoscopy, as well as tympanometry and audiometry were performed after 4, 8 and 12 weeks. Out of a total of 97 children studied between the ages of 4 to 10 years 82 could be analyzed. At the end of the study no operation was required in 70.7% of the placebo-treated children and in 78.1% of the children treated with homeopathic preparations. These results show no statistical significance.


Media and human capital development: Can video game playing make you smarter?
According to the literature, video game playing can improve such cognitive skills as problem solving, abstract reasoning, and spatial logic. I test this hypothesis using The Child Development Supplement to the Panel Study of Income Dynamics. The endogeneity of video game playing is addressed by using panel data methods and controlling for an extensive list of child and family characteristics. To address the measurement error in video game playing, I instrument children's weekday time use with their weekend time use. After taking into account the endogeneity and measurement error, video game playing is found to positively affect children's problem solving ability. The effect of video game playing on problem solving ability is comparable to the effect of educational activities.


Protein-silver nanoparticle interactions to colloidal stability in acidic environments.
We report a kinetic study of Ag nanoparticles (AgNPs) under acidic environments (i.e., pH 2.3 to pH ≈7) and systematically investigate the impact of protein interactions [i.e., bovine serum albumin (BSA) as representative] to the colloidal stability of AgNPs. Electrospray-differential mobility analysis (ES-DMA) was used to characterize the particle size distributions and the number concentrations of AgNPs. Transmission electron microscopy was employed orthogonally to provide visualization of AgNPs. For unconjugated AgNPs, the extent of aggregation, or the average particle size, was shown to be increased significantly with an increase of acidity, where a partial coalescence was found between the primary particles of unconjugated AgNP clusters. Aggregation rate constant, kD, was also shown to be proportional to acidity, following a correlation of log(kD) = -1.627(pH)-9.3715. Using ES-DMA, we observe BSA had a strong binding affinity (equilibrium binding constant, ≈ 1.1 × 10(6) L/mol) to the surface of AgNPs, with an estimated maximum molecular surface density of ≈0.012 nm(-2). BSA-functionalized AgNPs exhibited highly-improved colloidal stability compared to the unconjugated AgNPs under acidic environments, where both the acid-induced interfacial dissolution and the particle aggregation became negligible. Results confirm a complex mechanism of colloidal stability of AgNPs: the aggregation process was shown to be dominant, and the formation of BSA corona on AgNPs suppressed both particle aggregation and interfacial dissolution of AgNP samples under acidic environments.


When this means that: the role of working memory and inhibitory control in children's understanding of representations.
We investigated cognitive skills that contribute to 4-year-olds' understanding of representations. In our main task, children used representations on a perspective line drawing to find stickers hidden in a model room. To compare the contributions made by various cognitive skills with children's understanding of different types of representations, we manipulated the resemblance between the representations and their referents. Our results indicate that when representations are iconic (i.e., look like their referents), children have very little difficulty with the task. Controlling for performance on this baseline version of the task, we found that specific cognitive skills are differentially predictive of performance when using arbitrary and conflicting representations (i.e., symbols). When the representation was arbitrarily linked to the sticker, performance was related to phonological and visuospatial working memory. When the representation matched the color of an alternate sticker (thereby conflicting with the desired sticker), performance was related to phonological working memory and inhibitory control. We discuss the role that different cognitive skills play in representational understanding as a function of the nature of the representation-referent relation.


Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats.
One cause of cigarette smoking is oxidative stress that may alter the cellular antioxidant defense system, induce apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. It has been shown that Chinese green tea (CGT) (Lung Chen Tea) has higher antioxidant property than black tea. In this paper, we will explore the preventive effect of CGT on cigarette smoke-induced oxidative damage, apoptosis and tissues inflammation in albino rat model. Albino rats were randomly divided into four groups, i.e. sham air (SA), cigarette smoke (CS), CGT 2% plus SA or plus CS. The exposure to smoking was carried out as a single daily dose (1 cigarette/rat) for a period of 90 days using an electronically controlled smoking machine. Sham control albino rats were exposed to air instead of cigarette smoke. Tissues were collected 24 hr after last CS exposure for histology and all enzyme assays. Apoptosis was evidenced by the fragmentation of DNA using TUNEL assay. Long-term administration of cigarette smoke altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. All these pathophysiological and biochemical events were significantly improved when the cigarette smoke-exposed albino rats were given CGT infusion as a drink instead of water. Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT.


Quality and methodology of clinical practice guidelines on antiviral pharmacotherapy for COVID‑19 during the early phase of the pandemic.
Despite availability of reliable guidelines development methods, the risk of producing less reliable documents may be higher when the guidelines are developed rapidly. The aim of this study was to assess quality of guidelines on coronavirus disease 2019 (COVID-19), developed in the early stages of COVID-19 pandemic and assess if recommendations for pharmacotherapy were supported by evidence. We performed the search for documents, that considered antiviral therapies and contained a recommendations for clinicians. The quality of the guidelines was assessed using the AGREE II-Global Rating Scale Instrument and series of additional criteria. The analysis included 40 publications. The median of quality of documents assessed with the AGREE II-GRS tool was 2.0 (interquartile range 1.5-2.5). Most documents did not fulfill the rigour of guideline development quality criteria. The AGREE II-GRS scores did not differ significantly across the type of the document, issuing institution and the mode of publication. 75% of documents provided recommendations for the use of antiviral medications despite apparent lack of sufficient evidence supporting such treatments. Of the included documents, 75% were not updated within the 2 months after the publication of the first randomized controlled trial on COVID-19 antiviral therapy. Most guidelines or guidance documents published during the early phase of the COVID-19 pandemic were of poor quality, contained recommendations for the use of antiviral therapy for SARS-CoV-2 infection despite only very low quality of evidence available, and were not updated on a regular basis.


Prediction of short- and long-term outcome in patients with autoimmune hepatitis.
Autoimmune hepatitis (AIH) is a chronic inflammatory disease characterized by a loss of tolerance toward the hepatocellular epithelium. Liver transplantation (LT) represents the ultimate therapeutic option for a fulminant course or end-stage liver disease. The aim of this study was to elucidate the clinical, serological, and genetic features of remission, relapse, and overall and LT-free survival. Between 2000 and 2014, 354 AIH patients from Hannover Medical School were included. Clinical, laboratory, and histological reports were analyzed. DRB1 allele analyses were performed in 264 AIH and 399 non-AIH patients. Cox's regression analysis was performed to identify factors significantly associated with survival. Patients diagnosed in childhood were at higher risk for relapses (P=0.003), requirement for LTs (P=0.014, log rank), and had a reduced life expectancy (P<0.001, log rank). Detection of soluble liver antigen/liver pancreas antigen (SLA/LP) antibodies was significantly associated with reduced overall and LT-free survival (P=0.037; P=0.021). Cirrhosis, which was evident in 25% at first diagnosis, was found to be a predictor of poor survival and requirement for LT (P=0.003; P=0.009). DRB1*04:01-positive phenotype was associated with a higher rate of complete remissions and with a lower frequency of cirrhosis and LTs. There were no significant differences for subsequent relapses or survival in patients achieving either partial or complete remission. Diagnosis<18 years, histological cirrhosis at first diagnosis and SLA/LP antibodies are major risk factors for a poor short- and long-term outcome. These patients are in need of high surveillance. Separating patients with positive SLA/LP antibodies into a third group may be reconsidered. DRB1*04:01 positivity has been identified in association with a favorable clinical outcome.


Complete nucleotide sequence of Pelargonium zonate spot virus and its relationship with the family Bromoviridae.
The complete sequence of the Pelargonium zonate spot virus (PZSV) genome was determined. It comprises 8477 nt, distributed in three positive-strand RNA species encoding four proteins. RNA-1 is 3383 nt long, with an ORF that encodes a polypeptide with a molecular mass of 108 419 Da (denoted protein 1a). This protein contains the conserved sequence motifs I-III of type I methyltransferases and the seven consensus motifs of the helicases of superfamily 1. RNA-2 is 2435 nt long and encodes a major polypeptide with a molecular mass of 78 944 Da (denoted protein 2a), which shows identity to the RNA-dependent RNA polymerases of positive-strand RNA viruses. RNA-3 is 2659 nt long and contains two major ORFs. The first ORF is located in the 5' portion of the genome and sequence comparison of the putative translation product revealed similarities with the 30K superfamily of virus movement proteins. The second ORF is located in the 3' half and encodes the viral coat protein, which is expressed via a subgenomic RNA, RNA-4. The transcription initiation site of RNA-4 maps to the intergenic region of RNA-3. The organization of the PZSV genome, including the primary structure of terminal non-coding regions, strongly suggests that this virus belongs to the family Bromoviridae. The overall biological and genomic characteristics of PZSV indicate affinities in diverging directions with one or other of the virus species in this family, thus enabling it to be considered as a possible representative of a new genus within the family Bromoviridae.


Downregulation of Nrp1 transcription promotes blood-brain barrier disruption following experimental cerebral ischemia-reperfusion.
Disruption of the blood-brain barrier (BBB) following cerebral ischemia-reperfusion injury (CIRI) is a major factor in the pathophysiology of stroke. Endothelial cell-cell communication is essential for maintaining BBB integrity. By analyzing GSE227651 data, we found that a decrease in endothelial cell-cell communication mediated by Sema3/Nrp1 may be due to the downregulation of Nrp1 transcription, which could contribute to BBB breakdown after CIRI. We confirmed this hypothesis by using western blot analysis to show a reduction in Nrp1 protein levels in penumbra endothelial cells after CIRI in mice. We then overexpressed Nrp1 specifically in brain endothelial cells using adeno-associated virus in mice. Furthermore, Nrp1 overexpression had a protective effect on BBB integrity, as evidenced by a decrease in IgG and albumin leakage caused by CIRI in mice. Finally, we found that Nrp1 overexpression also reduced brain cell death and neurological deficits induced by cerebral ischemia-reperfusion in mice. Our findings suggest that Nrp1 downregulation may be a key factor in the breakdown of endothelial cell-cell communication and subsequent BBB disruption following CIRI. Targeting Nrp1-mediated pathways may be a promising approach for mitigating BBB damage and alleviating neurological consequences in stroke patients.