[Public health surveillance: historical origin, methods, and assessment].
In the last three decades disease surveillance has grown into a complete discipline, quite distinct from epidemiology. This expansion into a separate scientific area within public health has not been accompanied by parallel growth in the literature about its principles and methods. The development of the fundamental concepts of surveillance systems provides a basis on which to build a better understanding of the subject. In addition, the concepts have practical value as they can be used in designing new systems as well as understanding or evaluating currently operating systems. This article reviews the principles of surveillance, beginning with an historical survey of the roots and evolution of surveillance, and discusses the goals of the public health surveillance. Methods for data collection, data analysis, interpretation, and dissemination are then presented, together with proposed procedures for evaluating and improving a surveillance system. Finally, some points to be considered in establishing a new surveillance system are presented.


Ten-year follow up of previously traumatized immature permanent incisors sustaining second and third traumatic injuries after revascularization treatment: Case reports.
The long-term prognosis of previously traumatized immature permanent teeth treated with guided endodontic repair is well documented, but little is known about how these teeth respond to further traumatic injury after treatment. This case report presents the 10-year clinical and radiographic findings of two patients with traumatized maxillary incisors who underwent guided endodontic repair treatment and sustained two further traumatic injuries. Three crown-fractured maxillary central incisors with pulp necrosis were treated with a protocol that used 2.5% NaOCl irrigation, 3-4 weeks medication with calcium hydroxide or ciprofloxacin-metronidazole paste, induction of apical bleeding, and coronal sealing with mineral trioxide aggregate. One tooth sustained subluxation and a crown fracture after 20 months and 7 years, respectively. Two other teeth had a luxation injury at 9 months and subluxation 6.5 years after the repair treatment. One subluxated and one luxated tooth remained free of symptoms for 10 years with radiographic evidence of progressive root canal calcification, while the other luxated incisor required root canal treatment after 7.5 years. Although teeth treated with the so-called "regenerative" endodontic techniques do not possess true pulp tissue, the reparative tissue may respond to traumatic injuries in a similar manner to teeth with normal pulps.


Acute Changes in Community Violence and Increases in Hospital Visits and Deaths From Stress-responsive Diseases.
Community violence may affect a broad range of health outcomes through physiologic stress responses and changes in health behaviors among residents. However, existing research on the health impacts of community violence suffers from problems with bias. We examined the relations of acute changes in community violence with hospital visits and deaths due to stress-responsive diseases (mental, respiratory, and cardiac conditions) in statewide data from California 2005-2013. The community violence exposure was measured as both binary spikes and continuous acute changes. We applied a combined fixed-effects and time-series design that separates the effects of violence from those of community- and individual-level confounders more effectively than past research. Temporal patterning was removed from community violence rates and disease rates in each place using a Kalman smoother, resulting in residual rates. We used linear regression with place fixed-effects to examine within-place associations of acute changes in community violence with residual rates of each outcome, controlling for local time-varying covariates. We found acute increases in hospital visits and deaths due to anxiety disorders (0.31 per 100,000; 95% confidence interval [CI] = 0.02, 0.59), substance use (0.47 per 100,000; 95% CI = 0.14, 0.80), asthma (0.56 per 100,000; 95% CI = 0.16, 0.95), and fatal acute myocardial infarction (0.09 per 100,000; 95% CI = 0.00, 0.18) co-occurring with violence spikes. The pattern of findings was similar for the exposure of continuous acute violence changes. Although the associations were small, the identified increases in stress-responsive conditions suggest the possibility of health impacts of acute changes in community violence.


Contraceptive Use Before and After Abortion: A Cross-Sectional Study from Nigeria and Côte d'Ivoire.
Post-abortion contraception enables women to effectively manage their fertility to prevent unintended pregnancies. Using data from population-based surveys of women aged 15-49 in Nigeria and Côte d'Ivoire, we examined contraceptive dynamics immediately before and after an abortion and examined factors associated with these changes using multivariable logistic regressions. Covariates included sociodemographic characteristics, abortion source, post-abortion contraceptive communication (wanting to and actually talking to someone about contraception after abortion), and perceived contraceptive autonomy. We observed higher contraceptive use after abortion than before abortion. In Nigeria, wanting to talk to someone about contraception post-abortion was associated with increased adoption and decreased discontinuation, whereas talking to someone about contraception post-abortion was associated with increased adoption. Obtaining care from a clinical abortion source was associated with increased adoption and decreased discontinuation. Both post-abortion contraceptive communication variables were associated with post-abortion contraceptive use in both countries, whereas clinical source was only associated with post-abortion contraceptive use in Nigeria. Our findings suggest that ensuring that women have access to safe abortion as part of the formal health care system and receive comprehensive, high-quality post-abortion care services that include contraceptive counseling enables them to make informed decisions about their fertility that align with their reproductive goals.


Massively Multithreaded Maxflow for Image Segmentation on the Cray XMT-2.
Image segmentation is a very important step in the computerized analysis of digital images. The maxflow mincut approach has been successfully used to obtain minimum energy segmentations of images in many fields. Classical algorithms for maxflow in networks do not directly lend themselves to efficient parallel implementations on contemporary parallel processors. We present the results of an implementation of Goldberg-Tarjan preflow-push algorithm on the Cray XMT-2 massively multithreaded supercomputer. This machine has hardware support for 128 threads in each physical processor, a uniformly accessible shared memory of up to 4 TB and hardware synchronization for each 64 bit word. It is thus well-suited to the parallelization of graph theoretic algorithms, such as preflow-push. We describe the implementation of the preflow-push code on the XMT-2 and present the results of timing experiments on a series of synthetically generated as well as real images. Our results indicate very good performance on large images and pave the way for practical applications of this machine architecture for image analysis in a production setting. The largest images we have run are 320002 pixels in size, which are well beyond the largest previously reported in the literature.


Subacute carbon monoxide poisoning. Another great imitator.
The illnesses of two patients with characteristic symptoms of subacute carbon monoxide poisoning were misdiagnosed initially. This resulted in the needless exposure of one patient and two relatives to a toxic environment. The cherry-red color of the skin commonly cited in the literature was absent in both patients. The carbon monoxide poisoning probably contributed to the myocardial infarction and pulmonary emboli seen in these patients. Vague flu-like illnesses should raise the suspicion of carbon monoxide poisoning.


Effects of MGSA/GRO alpha on melanocyte transformation.
In the work described here we demonstrate that the clonal cell line Mel-a-6, produced by transfection of mouse Melan-a cells with human MGSA, had an increased ability to form large colonies in soft agar and increased ability to form tumors when injected into nude mice as compared to cells transfected with the neomycin resistance gene alone. This effect appeared to be dependent on the levels of MGSA produced since another transfected clone, Mel-a-l, produced only a low level of MGSA transgene mRNA, formed only minimal large colonies in soft agar and had a tumorigenic rate equal to that of neomycin resistant controls. The histology of the Mel-a-6 tumors is compatible with features normally exhibited by melanoma tumors. The cells do not stain for melanin, and they are positive for the neural crest marker protein S-100 as well as the HMB 45 melanoma specific antigen. Immunohistochemical studies revealed expression of the human MGSA in tumor cells from tissues, excised from animals injected with cells from clone Mel-a-6. Whereas DNA ploidy analysis suggests that in vitro the Mel-a parent cell line, control Mel-a-neo, Mel-a-1 and Mel-a-6 cells show no evidence of aneuploidy, the nuclei isolated from the tumors from animals injected with Mel-a-6 do exhibit aneuploidy. These data suggest that over-expression of MGSA in immortalized melanocytes contributes to transformation.


Kinetic analysis of the interaction between poly(amidoamine) dendrimers and model lipid membranes.
We used fluorescence spectroscopy and surface tensiometry to study the interaction between low-generation (G1 and G4) poly(amidoamine) (PAMAM) dendrimers, potential vehicles for intracellular drug delivery, and model lipid bilayers. Membrane association of fluorescently labeled dendrimers, measured by fluorescence anisotropy, increased with increasing size of the dendrimer and with increasing negative charge density in the membrane, indicating the electrostatic nature of the interaction. When the membrane was doped with pyrene-labeled phosphatidyl glycerol (pyrene-PG), pyrene excimer fluorescence demonstrated a dendrimer-induced selective aggregation of negatively charged lipids when the membrane was in the liquid crystalline state. A nonlinear Stern-Volmer quenching of dendrimer fluorescence with cobalt bromide suggested a dendrimer-induced aggregation of lipid vesicles, which increased with the dendrimer's generation number. Surface tensiometry measurements showed that dendrimers penetrated into the lipid monolayer only at subphysiologic surface pressures (<30mN/m). We conclude that the low-generation PAMAM dendrimers associate with lipid membranes predominantly electrostatically, without significantly compromising the bilayer integrity. They bind stronger to membranes with higher fluidity and lower surface pressure, which are characteristic of rapidly dividing cells.


A controllable and efficient method for the fabrication of a single HfC nanowire field-emission point electron source aided by low keV FIB milling.
A single hafnium carbide (HfC) nanowire field-induced electron emitter with a sharp tip apex is fabricated by Pt deposition and focused ion beam (FIB) milling. The structure of the electron emitter is characterized by scanning transmission electron microscopy (STEM) and atom probe tomography (APT). The HfC nanowire is single-crystalline with a thin oxide layer on its tip surface. The field emission properties are determined by using both in situ transmission electron microscopy (TEM) and a field-emission probe in a high-vacuum chamber. A high current of 173 nA was obtained at a low extraction voltage of 631 V with an emission gap of 5 mm. The emission current is stable at 60 nA for 100 min with a fluctuation of 0.7%. The deduced work function was 3.1 eV. It is suggested that the implanted Ga ions and the oxide layer induce more downward dipoles that are beneficial for lowering the work function and creating a stable surface. When the low keV FIB processing is applied, it takes within 30 minutes to finish a HfC nanowire emitter, establishing an efficient procedure for the preparation of nanowire emitters. These results provide a controllable and fast production method for the fabrication of single nanowire field-emission point electron sources.


Formation of the unusual semivolatile diterpene rhizathalene by the Arabidopsis class I terpene synthase TPS08 in the root stele is involved in defense against belowground herbivory.
Secondary metabolites are major constituents of plant defense against herbivore attack. Relatively little is known about the cell type-specific formation and antiherbivore activities of secondary compounds in roots despite the substantial impact of root herbivory on plant performance and fitness. Here, we describe the constitutive formation of semivolatile diterpenes called rhizathalenes by the class I terpene synthase (TPS) 08 in roots of Arabidopsis thaliana. The primary enzymatic product of TPS08, rhizathalene A, which is produced from the substrate all-trans geranylgeranyl diphosphate, represents a so far unidentified class of tricyclic diterpene carbon skeletons with an unusual tricyclic spiro-hydrindane structure. Protein targeting and administration of stable isotope precursors indicate that rhizathalenes are biosynthesized in root leucoplasts. TPS08 expression is largely localized to the root stele, suggesting a centric and gradual release of its diterpene products into the peripheral root cell layers. We demonstrate that roots of Arabidopsis tps08 mutant plants, grown aeroponically and in potting substrate, are more susceptible to herbivory by the opportunistic root herbivore fungus gnat (Bradysia spp) and suffer substantial removal of peripheral tissue at larval feeding sites. Our work provides evidence for the in vivo role of semivolatile diterpene metabolites as local antifeedants in belowground direct defense against root-feeding insects.


A new optical intra-tissue fiber irradiation ALA-PDT in the treatment of acne vulgaris in rabbit model: improved safety and tolerability.
Photodynamic therapy with topical aminolevulinic acid (ALA-PDT) has been suggested to be effective in treatment of acne vulgaris. However, adverse events occur during and after treatment. To compare the efficacy and tolerability of optical intra-tissue fiber irradiation (OFI) ALA-PDT versus traditional ALA-PDT in treatment of acne vulgaris in rabbit models. Twenty-five rabbits of clean grade were used. Twenty rabbits were randomly selected to establish acne model and the other five were used as control. Rabbits in model group (40 ears) were further divided into four groups (10 ears/group): I, OFI-ALA-PDT with the head of optical fiber inserted into the target lesion (intra-tissue); II, traditional ALA-PDT group; III, OFI group; IV, blank control group without any treatment. Uncomfortable symptoms, adverse events, and effectiveness rates were recorded on post-treatment day 14, 30, and 45. On post-treatment day 14, the effectiveness rate in OFI-ALA-PDT group was obviously higher than that of the other three groups (P<0.05). However, no improved effects were observed in OFI-ALA-PDT group on day 30 and 45. During the period of treatment, the frequencies of uncomfortable symptoms in ALA-PDT group were obviously higher than those in the other three groups (P<0.05). The adverse event rate in OFI-ALA-PDT group was obviously lower than that of the ALA-PDT group (P<0.05). The unblindness of the study and temporary animal models of acne induced may hamper the assessment and monitoring of the results, and future studies are still needed to clarify it further. The OFI-ALA-PDT group (intra-tissue irradiation) showed no improved efficacy on treating rabbit ear acne but had higher safety and better tolerability.


Frischella japonica sp. nov., an anaerobic member of the Orbales in the Gammaproteobacteria, isolated from the gut of the eastern honey bee, Apis cerana japonica Fabricius.
The gut of honey bees is characterized by a stable and relatively simple community of bacteria, consisting of seven to ten phylotypes. Two closely related honey bees, Apis mellifera (western honey bee) and Apis cerana (eastern honey bee), show a largely comparable occurrence of those phylotypes, but a distinct set of bacterial species and strains within each bee species. Here, we describe the isolation and characterization of Ac13T, a new species within the rare proteobacterial genus Frischella from A. cerana japonica Fabricius. Description of Ac13T as a new species is supported by low identity of the 16S rRNA gene sequence (97.2 %), of the average nucleotide identity based on orthologous genes (77.5 %) and digital DNA-DNA hybridization relatedness (24.7 %) to the next but far related type strain Frischella perrara PEB0191T, isolated from A. mellifera. Cells of Ac13T are mesophilic and have a mean length of 2-4 µm and a width of 0.5 µm. Optimal growth was achieved in anoxic conditions, whereas growth was not observed in oxic conditions and strongly reduced in microaerophilic environment. Strain Ac13T shares several features with other members of the Orbaceae, such as the major fatty acid profile, the respiratory quinone type and relatively low DNA G+C content, in accordance with its evolutionary relationship. Unlike F. perrara, strain Ac13T is susceptible to a broad range of antibiotics, which could be indicative for an antibiotic-free A. cerana bee keeping. In conclusion, we propose strain Ac13T as a novel species for which we propose the name Frischella japonica sp. nov. with the type strain Ac13T (=NCIMB 15259=JCM 34075).


Isolation and characterization of bacteriophages infecting nocardioforms in wastewater treatment plant.
Activated sludge plants (ASP) are associated with the stable foaming problem worldwide. Apart from the physical and chemical treatment methods, biological treatment method has been least explored and may prove to be a novel and ecofriendly approach to tackle the problem of stable foam formation. In ASP Nocardia species are commonly found and are one of the major causes for forming sticky and stable foam. This study describes the isolation and characterization of three Nocardia bacteriophages NOC1, NOC2, and NOC3 for the control of Nocardia species. The bacteriophages isolated in this study have shown promising results in controlling foam producing bacterial growth under laboratory conditions, suggesting that it may prove useful in the field as an alternative biocontrol agent to reduce the foaming problem. To the best of our knowledge to date no work has been published from India related to biological approach for the control of foaming.


An iron-induced nitric oxide burst precedes ubiquitin-dependent protein degradation for Arabidopsis AtFer1 ferritin gene expression.
Ferritins play an essential role in iron homeostasis by sequestering iron in a bioavailable and non-toxic form. In plants, ferritin mRNAs are highly and quickly accumulated in response to iron overload. Such accumulation leads to a subsequent ferritin protein synthesis and iron storage, thus avoiding oxidative stress to take place. By combining pharmacological and imaging approaches in an Arabidopsis cell culture system, we have identified several elements in the signal transduction pathway leading to the increase of AtFer1 transcript level after iron treatment. Nitric oxide quickly accumulates in the plastids after iron treatment. This compound acts downstream of iron and upstream of a PP2A-type phosphatase to promote an increase of AtFer1 mRNA level. The AtFer1 gene transcription has been previously shown to be repressed under low iron conditions with the involvement of the cis-acting element iron-dependent regulatory sequence identified within the AtFer1 promoter sequence. We show here that the repressor is unlikely a transcription factor directly bound to the iron-dependent regulatory sequence; such a repressor is ubiquitinated upon iron treatment and subsequently degraded through a 26 S proteasome-dependent pathway.


The production effect over the long term: Modeling distinctiveness using serial positions.
The production effect is a well-established finding: If some words within a list are read aloud, that is, produced, they are better remembered than their silently read neighbors. The effect has been extensively studied with long-term memory tasks. Recently, using immediate serial recall and short-term order reconstruction, Saint-Aubin et al. (2021) reported informative interactions between the production effect and serial positions. Here, we asked whether these interactions would also be observed with the long-term memory tasks used in the field. In Experiment 1, pure and mixed lists of eight words were presented in both order reconstruction and free recall tasks, with a 30-s filled retention interval. In Experiment 2, the list length was extended to 24 words; in Experiment 3, 10-word lists were used with a 2-min retention interval. Results from all experiments aligned well with those observed in short-term memory. With mixed lists, where produced and silently read words alternated, produced items were better recalled, leading to sawtooth serial position curves. With pure lists, produced items were better recalled when studied in the last serial positions, but they were less well recalled for the primacy positions. Results were readily accounted for by the revised feature model, originally developed to explain short-term memory performance. The findings and model suggest that produced items are encoded with more item-specific, modality-related features and that this generates a relative distinctiveness advantage in short- and long-term memory. However, the richer encoding comes at a cost: It appears to disrupt rehearsal. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Influence of inulin on plasma isoflavone concentrations in healthy postmenopausal women.
Bacterial intestinal glucosidases exert an important role in isoflavone absorption. Insoluble dietary fibers such as inulin may stimulate the growth of these bacteria in the colon and, hence, stimulate the absorption of these substances in subjects who may need isoflavone supplementation. The objective was to assess the influence of inulin on plasma isoflavone concentrations after intake of soybean isoflavones in healthy postmenopausal women. Twelve healthy postmenopausal women participated in a randomized, double-blind, crossover study. They consumed 40 mg of a conjugated form of soybean isoflavones (6 mg daidzein and 18 mg genistein as free form) with or without 3.66 g inulin twice daily in two 21-d experimental phases. Blood samples were collected 0, 1, 2, 3, 4, 6, 10, 12, and 24 h after intake of isoflavones with breakfast and dinner at the end of each 21-d experimental phase. Plasma concentrations of isoflavones were assessed by HPLC with an electrochemical detector. Plasma 24-h areas under the curve indicated that the intake of soybean isoflavones with inulin for 21 d was followed by higher plasma concentrations of daidzein and genistein (38% and 91%, respectively) compared with the formulation without inulin. Furthermore, the time for the maximum concentration of daidzein and genistein appeared to be lower after the 21-d intake of soybean isoflavones, with or without inulin. However, the time for the maximum concentration of daidzein and genistein after supplementation with the inulin-containing formulation on day 21 was not significantly different from that after supplementation with the formulation without inulin. Inulin may increase the apparent plasma concentrations of the soybean isoflavones daidzein and genistein in postmenopausal women. The higher plasma concentrations of the 2 isoflavones suggests that the absorption of each was facilitated by the presence of inulin.


Should I stay or should I go? The influence of individual and organizational factors on pharmacists' future work plans.
To examine the association between individual (demographic) and organizational (work environment and workload) factors and pharmacists' future work plans and explore reasons for either leaving or staying with current employers (culture/climate factors). Cross-sectional study. United States in 2004. 1,263 pharmacists. Seven-page mail survey. Future work plans, time spent in practice activities, staffing levels, and actual and perceived workload and demographic variables. Overall, 15% of respondents reported that they planned to leave their current employer within the year subsequent to this survey. More than 50% reported that their workload had significantly increased in the previous year. Multivariate analyses showed that nonwhites were 2.1 times more likely to be planning to leave their current employer, compared with whites, and unmarried respondents were 1.7 times more likely to leave than were married individuals. More negative perceptions regarding the impact of workload on various personal, work, and patient care outcomes predicted leaving. A main factor that prompted their inclinations was described by 72% of leavers (insufficient and/or unqualified staff) and 49% of stayers (flexible scheduling). The most common reasons for staying were good salary and relationships with coworkers, while the most common reasons for leaving were a desire for change and stress/workload issues. Future work plans of pharmacists are influenced by a variety of individual, organizational, and culture/climate factors. While employers have little latitude for influencing demographic characteristics of employees, many organizational and culture/climate factors (scheduling, opportunities for interpersonal interactions, salary/benefits, staffing, and workload) can be addressed with the intent of reducing pharmacist turnover.


Activity of ceftaroline versus ceftobiprole against staphylococci and pneumococci in the UK and Ireland: analysis of BSAC surveillance data.
Ceftaroline and ceftobiprole inhibit most MRSA and MDR pneumococci. Few direct comparisons of their activity have been published, but in several years (2008, 2013, 2017 and 2018) both were tested in parallel in the BSAC Resistance Surveillance Programme, giving paired results. These are reviewed. Isolates included were bloodstream Staphylococcus aureus [n = 1884 (MRSA, n = 234)], bloodstream CoNS (n = 813; 574 methicillin resistant), and bloodstream (n = 852) and respiratory (n = 670) Streptococcus pneumoniae. MICs were determined by BSAC agar dilution and reviewed against EUCAST breakpoints; S. aureus breakpoints were assumed for CoNS. Ceftaroline MICs were mostly 2-fold lower than those of ceftobiprole, but, for all groups, MICs of both agents were strongly inter-related. Methicillin-susceptible staphylococci were universally susceptible to both agents; all MRSA were susceptible to ceftobiprole, whereas 10/234 had intermediate/high-dose susceptibility to ceftaroline. Among methicillin-resistant CoNS, 88% were susceptible to both agents, but reduced ceftaroline susceptibility and ceftobiprole resistance were frequent (65%) among methicillin-resistant Staphylococcus haemolyticus. One S. pneumoniae was resistant to both ceftaroline (MIC 0.5 mg/L) and ceftobiprole (MIC 1 mg/L) and seven others were only resistant to ceftobiprole (MIC 1 mg/L); seven of these eight pneumococci belonged to serotype 19A or 19F. No time trend in susceptibility was seen for either cephalosporin. Ceftaroline and ceftobiprole have similarly good activity against staphylococci and pneumococci. Therapeutic choices between these agents should be predicated on other differentiating factors, including licensed indications, clinical experience and need for Gram-negative coverage.


A simple method for the removal of epithelium grown beneath the hinge after LASIK.
The purpose of this study is to demonstrate a method of how to remove epithelium grown beneath the hinge area after laser in situ keratomileusis (LASIK) without affecting the refractive part of the lenticule. In three cases, an incision was made at the base of the hinge by RK diamond knife to free the lenticule from the stroma. The lenticule was lifted from the nasal edge. The epithelium grown along the interface beneath the hinge area was removed with a Bard-Parker No. 15 knife. The lenticular flap was repositioned with interrupted sutures using 10-0 nylon. No further epithelial ingrowth was observed. The central cornea remained clear leaving a peripheral ring-shaped opacity without affecting the preoperative naked visual acuity. In conclusion, epithelial ingrowth along the interface after LASIK can be removed safely without affecting the refractive part by the incision of the hinge area with a RK diamond knife, removal of the epithelium, and suturing of the lenticule to the stromal bed.


Increased YKL-40 levels in patients with isolated coronary artery ectasia: an observational study.
YKL-40, a new biomarker of localized inflammation, is secreted by macrophages within the atherosclerotic plaques. Coronary artery ectasia (CAE) is a clinical entity with unclear etiopathogenesis. Some studies have revealed that CAE may be a form of atherosclerosis that has more localized and intense inflammatory properties than atherosclerosis. The goal of this study was to investigate YKL-40 and C-reactive protein (CRP) levels in patients with isolated CAE compared to patients with normal coronary arteries (NCA) and coronary artery disease (CAD). Our study has an observational and cross-sectional design. Forty-nine patients with isolated CAE (mean age: 60±10 years), 30 age-and gender-matched control participants with NCA (30 patients, mean age: 58±12 years) and 30 patients with CAD (mean age: 61±10 years), were included in the study. The relationship between YKL-40, CRP levels and the presence of CAE was investigated. Univariate and multiple logistic regression analysis were used for analysis of independent variables to predict CAE. Serum YKL-40 levels were significantly different among study groups (NCA: 110±53 μg/L, CAE: 144±68 and CAD: 180±117, p=0.005). CAD group and CAE group had significantly higher YKL-40 levels than NCA group (p=0.004 and p=0.015, respectively). CRP was not significantly different between three groups. In addition, there were no any statistically significant differences, with respect to age, gender, the presence of hypertension or diabetes mellitus, and the smoking status (p>0.05). Logistic regression analysis revealed only YKL-40 level as the determinant of CAE (OR: 1.010, 95% CI: 1.001-1.019, p=0.027). YKL-40 levels in patients with isolated CAE compared to patients with NCA were found significantly high and only YKL-40 level was established as the determinant of CAE. We believe that further studies are needed to clarify the possible causative roles of YKL-40 in patients with isolated CAE.


Recruitment of clathrin to intracellular membranes is sufficient for vesicle formation.
The formation of a clathrin-coated vesicle (CCV) is a major membrane remodeling process that is crucial for membrane traffic in cells. Besides clathrin, these vesicles contain at least 100 different proteins although it is unclear how many are essential for the formation of the vesicle. Here, we show that intracellular clathrin-coated formation can be induced in living cells using minimal machinery and that it can be achieved on various membranes, including the mitochondrial outer membrane. Chemical heterodimerization was used to inducibly attach a clathrin-binding fragment 'hook' to an 'anchor' protein targeted to a specific membrane. Endogenous clathrin assembled to form coated pits on the mitochondria, termed MitoPits, within seconds of induction. MitoPits are double-membraned invaginations that form preferentially on high curvature regions of the mitochondrion. Upon induction, all stages of CCV formation - initiation, invagination, and even fission - were faithfully reconstituted. We found no evidence for the functional involvement of accessory proteins in this process. In addition, fission of MitoPit-derived vesicles was independent of known scission factors including dynamins and dynamin-related protein 1 (Drp1), suggesting that the clathrin cage generates sufficient force to bud intracellular vesicles. Our results suggest that, following its recruitment, clathrin is sufficient for intracellular CCV formation.


Recent progress in transition metal phosphides with enhanced electrocatalysis for hydrogen evolution.
Increasing demand for hydrogen energy has boosted the exploration of inexpensive and effective catalysts. Transition metal phosphides (TMPs) have been proven as excellent catalysts for the hydrogen evolution reaction (HER). Very recently, the search for TMP-based catalysts has being mainly directed at enhanced electrocatalytic performance. Hence, a concluded guideline for enhancing HER activity is highly desired. In this mini review, we briefly summarize the most recent and instructive developments in the design of TMP-based catalysts with enhanced electrocatalysis for hydrogen evolution from composition and structure engineering strategies. These strategies and perspectives are also meaningful for designing other inexpensive and high-performance catalysts.


Systems analysis reveals down-regulation of a network of pro-survival miRNAs drives the apoptotic response in dilated cardiomyopathy.
Apoptosis is a hallmark of multiple etiologies of heart failure, including dilated cardiomyopathy. Since microRNAs are master regulators of cardiac development and key effectors of intracellular signaling, they represent novel candidates for understanding the mechanisms driving the increased dysfunction and loss of cardiomyocytes during cardiovascular disease progression. To determine the role of cardiac miRNAs in the apoptotic response, we used microarray technology to monitor miRNA levels in a validated murine phospholambam mutant model of dilated cardiomyopathy. 24 miRNAs were found to be differentially expressed, most of which have not been previously linked to dilated cardiomyopathy. We showed that individual silencing of 7 out of 8 significantly down-regulated miRNAs (mir-1, -29c, -30c, -30d, -149, -486, -499) led to a strong apoptotic phenotype in cell culture, suggesting they repress pro-apoptotic factors. To identify putative miRNA targets most likely relevant to cell death, we computationally integrated transcriptomic, proteomic and functional annotation data. We showed the dependency of prioritized target abundance on miRNA expression using RNA interference and quantitative mass spectrometry. We concluded that down regulation of key pro-survival miRNAs causes up-regulation of apoptotic signaling effectors that contribute to cardiac cell loss, potentially leading to system decompensation and heart failure.


BNP Consensus Panel 2004: A clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases.
Among the most exciting developments in the field of heart failure in recent times has been the rediscovery of the natriuretic peptide system and its pleuripotent effects on cardiac structure and function. This is particularly true of its natriuretic and hemodynamic effects. There has been an explosion of the knowledge base seeking to understand the wide range of homeostatic, regulatory, and counter-regulatory functions in which the natriuretic peptide system participates. Additional interest has been stimulated by advances in technology such as point-of-care and core laboratory BNP assays and the use of the recombinant B-type natriuretic peptide nesiritide as a treatment option. Despite this recent interest, the available literature lacks a comprehensive expert review of the current science and roles of natriuretic peptides for diagnostic, prognostic, screening, treatment monitoring, and therapeutic purposes. More importantly, a summary updating and guiding the clinician on most of these advances was lacking. An expert Consensus Panel with basic, methodological, and clinical expertise was convened to summarize current knowledge in these areas and the findings and consensus statements are contained herein.


Colour detection thresholds in faces and colour patches.
Human facial skin colour reflects individuals' underlying health (Stephen et al 2011 Evolution & Human Behavior 32 216-227); and enhanced facial skin CIELab b* (yellowness), a* (redness), and L* (lightness) are perceived as healthy (also Stephen et al 2009a International Journal of Primatology 30 845-857). Here, we examine Malaysian Chinese participants' detection thresholds for CIELab L* (lightness), a* (redness), and b* (yellowness) colour changes in Asian, African, and Caucasian faces and skin coloured patches. Twelve face photos and three skin coloured patches were transformed to produce four pairs of images of each individual face and colour patch with different amounts of red, yellow, or lightness, from very subtle (deltaE = 1.2) to quite large differences (deltaE = 9.6). Participants were asked to decide which of sequentially displayed, paired same-face images or colour patches were lighter, redder, or yellower. Changes in facial redness, followed by changes in yellowness, were more easily discriminated than changes in luminance. However, visual sensitivity was not greater for redness and yellowness in nonface stimuli, suggesting red facial skin colour special salience. Participants were also significantly better at recognizing colour differences in own-race (Asian) and Caucasian faces than in African faces, suggesting the existence of cross-race effect in discriminating facial colours. Humans' colour vision may have been selected for skin colour signalling (Changizi et al 2006 Biology Letters 2 217-221), enabling individuals to perceive subtle changes in skin colour, reflecting health and emotional status.


Common Drug Review recommendations: an evidence base for expectations?
The Common Drug Review (CDR) was created to provide a single process to review the comparative clinical efficacy and cost effectiveness of new drugs, and then to make formulary listing recommendations to Canadian publicly funded drug benefit plans. The objective was to conduct an in-depth analysis of Canadian Expert Drug Advisory Committee (CEDAC) recommendations to date, to explore predictors and possible explanatory factors associated with negative recommendations. Final recommendations were identified from inception (September 2003) to 31 December 2009. Using only publicly available information, recommendations were analysed under the following categories: submission specifics, drug characteristics, clinical factors and economic factors. Descriptive analyses were conducted, followed by statistical analyses, to determine which factors independently predicted a 'do not list' (DNL) recommendation. The database consisted of 138 unique final recommendations. The overall DNL rate was 48%. Significant differences in DNL rates were observed between therapeutic areas, ranging from 0% for HIV antivirals up to 88% for analgesic drugs. In the univariate analysis, several factors were significantly associated with a DNL recommendation, including first-in-class drugs and use of clinical scales as an outcome. In the multivariate regression, four factors were significantly predictive of a DNL recommendation: clinical uncertainty (odds ratio [OR] 14), price higher than comparators (OR 9), request for reconsideration (OR 10) and price as the only economic evidence used (OR 18). Incremental cost-effectiveness thresholds were not predictive of recommendations. The hypothesis that economic factors did not impact recommendations when clinical factors were included first was supported by the analysis. This analysis documented an evidence-driven process that simultaneously weighted multiple factors. Clinical uncertainty and price considerations, but not economic results, had a strong impact on the recommendations. Insufficiency of clinical evidence may have resulted from the gap in evidence available at the time of product launch and the absence of demonstrated benefits to support innovative drugs.


Evaluation of the protein quality of an isolated soy protein in young men: relative nitrogen requirements and effect of methionine supplementation.
The protein nutritional value of an isolated soy protein (Supro-620) was evaluated in a series of nitrogen balance studies in healthy young male MIT students. Experiment 1 involved giving eight subjects graded intakes of the isolated soy protein while seven additional subjects received egg protein. Mean nitrogen intake required for N balance for the isolated soy protein and the egg protein were not significantly different (p greater than 0.1). In experiment 2, nine subjects received soy and the effects on N balance at various levels of L-methionine supplementation were studied. In experiment 3 eight subjects each were studied at two nitrogen intake levels of isolated soy protein/kg/day with methionine supplementation, and an unsupplemented egg protein period included. Results from experiment 2 and 3 at an 82 mg N/kg/day test level showed that N balance for 1.6% supplementation was significantly below that of unsupplemented egg while 1.1% and unsupplemented soy were indistinguishable from egg. No beneficial effects of methionine supplementation were observed when the test nitrogen intake level was 128 mg N/kg/day. These results indicate that for healthy adults, the isolated soy protein is of high nutritional quality, comparable to that of animal protein sources, and that the methionine content is not limiting for adult protein maintenance.


Acute myocardial infarction in early postpartum.
We present a case of acute anterior myocardial infarction in a breastfeeding woman, 10 days after delivery. The presumed cause was proximal left anterior artery vasospasm, induced by a combination of smoking a first cigarette in the early morning and salbutamol inhalation, in the particular context of peripartum. We discuss briefly the epidemiology, pathophysiology, risk factors, diagnosis, treatment and prognosis of myocardial infarction related to pregnancy and the postpartum period.


Hidden species diversity in Sylvirana nigrovittata (Amphibia: Ranidae) highlights the importance of taxonomic revisions in biodiversity conservation.
Accurately delimiting species and their geographic ranges is imperative for conservation, especially in areas experiencing rapid habitat loss. Southeast Asia currently has one of the highest rates of deforestation in the world, is home to multiple biodiversity hotspots, and the majority of its countries have developing economies with limited resources for biodiversity conservation. Thus, accurately delimiting species and their ranges is particularly important in this region. We examined genetic and morphological variation in the widespread frog species Sylvirana nigrovittata (and its long-treated junior synonym S. mortenseni) with the goal of clarifying its taxonomic content and geographic range boundaries for conservation. We present evidence that the current concept of S. nigrovittata contains at least eight species, two of which are each known from only two localities, but that S. mortenseni is more geographically widespread than currently realized. Five of these species are described as new to science.


Is it possible to predict the development of an incisional surgical site infection and its severity after biliary tract surgery for benign disease?
Wound infection; that is, incisional surgical site infection (ISSI), is a common complication after biliary tract surgery. The aim of the present study was to identify the various risk factors for wound infection and to establish a formula to predict the development and severity of wound infections. We analyzed the clinical data on 207 consecutive patients who underwent biliary surgery for benign diseases at our hospital. We identified the factors with the greatest influence on wound infection after biliary tract surgery, based on a statistical procedure. An original scoring system (ISSI predictive score) was proposed based on these risk factors. The incidence of postoperative wound infection was 9.7% (20/207). The patient's performance status; bile culture; perioperative fasting period (days); and intraoperative bile spillage were the most influential risk factors for wound infection. The incidences of wound infection in patients with ISSI predictive scores of >2.7 points and those with scores of 0-2.7 points were 75.0% (12/16) and 4.2% (8/191), respectively. Our score also correlated significantly with the severity of wound infection (r = 0.488, P < 0.001) and the length of the postoperative hospital stay (R = 0.508, P < 0.001). Our original scoring system makes it possible to predict not only the development of a wound infection and its severity after biliary tract surgery, but also the length of the postoperative hospital stay.


Additive-free size-controlled synthesis of gold square nanoplates using photochemical reaction in dynamic phase-separating media.
Ultrafast phase separation of water and 2-butoxyethanol mixture was induced by nanosecond IR laser pulse irradiation. After a certain delay time, a UV laser pulse was introduced to induce photoreduction of aurate ions, which led to the formation of gold nanoparticles in dynamic phase-separating media. The structure and size of the nanoparticles varied depending on the delay time between the IR and UV pulses. For a delay time of 5 and 6 μs, gold square plates having edge lengths of 150 and 100 nm were selectively obtained, respectively. With a delay time of 3 μs, on the other hand, the size of the square plates varied widely from 100 nm to a few micrometers. The size of the gold square plates was also varied by varying the total irradiation time of the IR and UV pulses. The size distribution of the square plates obtained under different conditions suggests that the growth process of the square plates was affected by the size of the nanophases during phase separation. Electron diffraction patterns of the synthesized square plates showed that the square plates were highly crystalline with a Au(100) surface. These results showed that the nanophases formed during laser-induced phase separation can provide detergent-free reaction fields for size-controlled nanomaterial synthesis.


Spreading depression determines acute cellular damage in the hippocampal slice during oxygen/glucose deprivation.
During ischaemia neurons depolarize and release the neurotransmitter L-glutamate, which accumulates extracellularly and binds to postsynaptic receptors. This initiates a sequence of events thought to culminate in immediate and delayed neuronal death. However, there is growing evidence that during ischaemia the development of spreading depression (SD) can be an important determinant of the degree and extent of ischaemic damage. In contrast, SD without metabolic compromise (as occurs in migraine aura) causes no discernible damage to brain tissue. SD is a profound depolarization of neurons and glia that propagates like a wave across brain tissue. Brain cell swelling, an early event of both the excitotoxic process and of SD, can be assessed by imaging associated intrinsic optical signals (IOSs). We demonstrate here that IOS imaging clearly demarcates the ignition site and migration of SD across the submerged hippocampal slice of the rat. If SD is induced by elevating [K+]O, the tissue fully recovers, but in slices that are metabolically compromised at 37.5 degrees C by oxygen/glucose deprivation (OGD) or by ouabain exposure, cellular damage develops only where SD has propagated. Specifically, the evoked CA1 field potential is permanently lost, the cell bodies of involved neurons swell and their dendritic regions increase in opacity. In contrast to OGD, bath application of L-glutamate (6-10 mM) at 37.5 degrees C evokes a non-propagating LT increase in CA1 that reverses without obvious cellular damage. Moreover, application of 2-20 mM glutamate or various glutamate agonists fail to evoke SD in the submerged hippocampal slice. We propose that SD and OGD together (but not alone) constitute a 'one-two punch', causing acute neuronal death in the slice that is not replicated by elevated glutamate. These findings support the proposal that SD generation during stroke promotes and extends acute ischaemic damage.


Data Sharing Platform for MIMIC-IV and MIMIC-ED Data Marts: Designing a Data Retrieving System Based on the Intra-Hospital Patient Transfer Pathway.
Accessibility to high-quality historical data for patients in hospitals may facilitate related predictive model development and data analysis experiments. This study provides a design for a data-sharing platform based on all possible criteria for Medical Information Mart for Intensive Care (MIMIC) IV and Emergency MIMIC-ED. Tables containing columns of medical attributions and outcomes were studied by a team of 5 experts in Medical Informatics. They completely agreed about the columns connection using subject-id, HDM-id, and stay-id as foreign keys. The tables of two marts were considered in the intra-hospital patient transfer path with various outcomes. Using the constraints, queries were generated and applied to the backend of the platform. The suggested user interface was drawn to retrieve records based on various entry criteria and present the output in the frame of a dashboard or a graph. This design is a step toward platform development that is useful for studies aimed at patient trajectory analysis, medical outcome prediction, or studies that require heterogeneous data entries.


Listeners' identification of human-imitated animal sounds.
To determine whether listeners can accurately identify human-imitated animal sounds, 20 speakers (10 females and 10 males) recorded their imitations of cows, cats, dogs, pigs, and sheep. These recordings were randomly arranged on a master tape and presented to 30 judges for identification. Analysis indicates that listeners can accurately identify various human-imitated animal sounds. Implications and suggestions for future research are discussed.


[Methicillin-reistant Staphylococcus aureus: risk factors for infection-colonization and clonal heterogeneity in intensive care units].
The aim of this study was to determine the risk factors associated with colonisation/infection by methicillin-resistant Staphylococcus aureus (MRSA) and to demonstrate the chain of infections by genotyping of all MRSA isolates. A total of 6143 microbiological samples from 1753 patients was obtained at a surgical ICU of Frankfurt University hospital during 1995. MRSA was detected in 1.6% of patients and three members of staff (3.3%). Typing of these 31 MRSA-strains (first isolates) by macrorestriction analysis of chromosomal DNA revealed nine different genotypes. More than 60% of all isolates belonged to one type that was confirmed to be closely related to the "South Germany" epidemic strain. A strong correlation between severity of underlying disease and length of hospitalisation on the one hand and detection of MRSA on the other could be demonstrated. Detection of MRSA was significantly more common in patients with adult respiratory distress syndrome (ARDS), sepsis, kidney failure, prolong respiratory treatment and in patients with prolonged phases of haemodynamic instability. It appeared that the mortality rate of MRSA-infected patients was higher (28.6%) than the mortality rate of all patients (6.5%). Following of a strict hygiene regime is important to prevent clonal spread of MRSA and especially to protect immunocompromised patients from complicating infections.


Electro-fenton and photoelectro-fenton degradation of sulfanilic acid using a boron-doped diamond anode and an air diffusion cathode.
The mineralization of sulfanilic acid has been studied by electro-Fenton (EF) and photoelectro-Fenton (PEF) reaction with UVA light using an undivided electrochemical cell with a boron-doped diamond (BDD) anode and an air diffusion cathode able to generate H(2)O(2). Organics were then oxidized by hydroxyl radicals formed at the anode surface from water oxidation and in the bulk from Fenton's reaction between generated H(2)O(2) and added Fe(2+). The UVA irradiation in PEF enhanced the production of hydroxyl radicals in the bulk, accelerating the removal of organics and photodecomposed intermediates like Fe(III)-carboxylate complexes. Partial decontamination of 1.39 mM sulfanilic acid solutions was achieved by EF until 100 mA cm(-2) at optimum conditions of 0.4 mM Fe(2+) and pH 3.0. The increase in current density and substrate content led to an almost total mineralization. In contrast, the PEF process was more powerful, yielding almost complete mineralization in less electrolysis time under comparable conditions. The kinetics for sulfanilic acid decay always followed a pseudo-first-order reaction. Hydroquinone and p-benzoquinone were detected as aromatic intermediates, whereas acetic, maleic, formic, oxalic, and oxamic acids were identified as generated carboxylic acids. NH(4)(+) ion was preferentially released in both treatments, along with NO(3)(-) ion in smaller proportion.


Ionic interaction of sulfatide with choline lipids.
Aqueous systems of sphingomyelin-sulfatide and lecithin-sulfatide were compared with aqueous systems of the individual lipids. The acid capacity of the mixed lipids increased, a result of the formation of an ionic bond between the sulfate of one molecule and the positive nitrogen of the other, making the phosphate available for direct titration. Cholesterol reduces this ionic interaction, probably because of the increased spacing of the ionized groups.


fMRI connectivity as a biomarker of antipsychotic treatment response: A systematic review.
Antipsychotic drugs are the first-choice therapy for psychotic episodes, but antipsychotic treatment response (AP-R) is unpredictable and only becomes clear after weeks of therapy. A biomarker for AP-R is currently unavailable. We reviewed the evidence for the hypothesis that functional magnetic resonance imaging functional connectivity (fMRI-FC) is a predictor of AP-R or could serve as a biomarker for AP-R in psychosis. A systematic review of longitudinal fMRI studies examining the predictive performance and relationship between FC and AP-R was performed following PRISMA guidelines. Technical and clinical aspects were critically assessed for the retrieved studies. We addressed three questions: Q1) is baseline fMRI-FC related to subsequent AP-R; Q2) is AP-R related to a change in fMRI-FC; and Q3) can baseline fMRI-FC predict subsequent AP-R? In total, 28 articles were included. Most studies were of good quality. fMRI-FC analysis pipelines included seed-based-, independent component- / canonical correlation analysis, network-based statistics, and graph-theoretical approaches. We found high heterogeneity in methodological approaches and results. For Q1 (N = 17) and Q2 (N = 18), the most consistent evidence was found for FC between the striatum and ventral attention network as a potential biomarker of AP-R. For Q3 (N = 9) accuracy's varied form 50 till 93%, and prediction models were based on FC between various brain regions. The current fMRI-FC literature on AP-R is hampered by heterogeneity of methodological approaches. Methodological uniformity and further improvement of the reliability and validity of fMRI connectivity analysis is needed before fMRI-FC analysis can have a place in clinical applications of antipsychotic treatment.


Sequence diversity and antigenic variation at the rag locus of Porphyromonas gingivalis.
The rag locus of Porphyromonas gingivalis W50 encodes RagA, a predicted tonB-dependent receptor protein, and RagB, a lipoprotein that constitutes an immunodominant outer membrane antigen. The low G+C content of the locus, an association with mobility elements, and an apparent restricted distribution in the species suggested that the locus had arisen by horizontal gene transfer. In the present study, we have demonstrated that there are four divergent alleles of the rag locus. The original rag allele found in W50 was renamed rag-1, while three novel alleles, rag-2 to rag-4, were found in isolates lacking rag-1. The three novel alleles encoded variants of RagA with 63 to 71% amino acid identity to RagA1 and each other and variants of RagB with 43 to 56% amino acid identity. The RagA/B proteins have homology to numerous Bacteroides proteins, including SusC/D, implicated in polysaccharide uptake. Monoclonal and polyclonal antibodies raised against RagB1 of P. gingivalis W50 did not cross-react with proteins from isolates carrying different alleles. In a laboratory collection of 168 isolates, 26% carried rag-1, 36% carried rag-2, 25% carried rag-3, and 14% carried rag-4 (including the type strain, ATCC 33277). Restriction profiles of the locus in different isolates demonstrated polymorphism within each allele, some of which is accounted for by the presence or absence of insertion sequence elements. By reference to a previously published study on virulence in a mouse model (M. L. Laine and A. J. van Winkelhoff, Oral Microbiol. Immunol. 13:322-325, 1998), isolates that caused serious disease in mice were significantly more likely to carry rag-1 than other rag alleles.


Sharp Versus Electric Suction Curettage in Gynecologic Patients Undergoing Evaluation for Abnormal Uterine Bleeding.
Suction curettage is preferred over sharp curettage in obstetric settings. We compare the quality of operative tissue sampling between sharp curettage and suction curettage using electric vacuum aspiration for nonobstetric abnormal uterine bleeding in reproductive-aged women. A retrospective cohort study. Community hospital in Long Island, New York. Women ages 21 to 45 years (n = 257) who underwent operative curettage procedure for nonobstetric abnormal uterine bleeding. Independent ratings of specimens from suction curettage using electric vacuum aspiration and sharp curettage by 2 pathologists blinded to method of tissue collection. The primary outcome was percentage of organized tissue, indicative of a higher-quality pathology specimen. Specimens obtained by electric suction curettage (p <.001) had a significantly higher percentage of organized tissue (M = 66.28, SD = 20.33) than sharp curettage (M = 55.51, SD = 24.17). There were no differences between the curettage groups for operative time, blood loss, intraoperative complications, or pathology diagnosis. Specimens obtained with suction curettage contained more organized tissue with similar pathologist satisfaction and confidence scores than sharp curettage. We suggest clinicians consider electric suction curettage in the diagnostic workup of abnormal uterine bleeding in reproductive-aged women. In addition, patient-centered benefits include no increase in operative time, blood loss, or complication rate compared with sharp curettage.


Evaluation of the therapeutic effects of conditioned media from mesenchymal stem cells in a rat bisphosphonate-related osteonecrosis of the jaw-like model.
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is defined as an exposed necrotic bone in the oral cavity that does not heal after appropriate intervention for >8weeks with present or previous bisphosphonate treatment in the absence of radiotherapy. Until now, although several risk factors, including invasive dental procedures, infection, mechanical trauma to the jawbone, and concomitant use of immunosuppressive and chemotherapy drugs have been implicated in the etiology of BRONJ, its underlying mechanisms and treatments remain largely unknown. A study recently showed that intravenous administration of mesenchymal stem cells (MSCs) improved BRONJ, and it was hypothesized that paracrine effects by secretomes from MSCs are the main constituent. Here we used rat BRONJ models to examine the therapeutic effects with serum-free conditioned media from human MSCs (MSC-CM), including various secretomes. We showed that MSC-CM has protected rat MSCs and rat osteoclasts. MSC-CM enhanced the expression of osteogenic-related genes and neovascularization-related genes by real-time reverse-transcriptase polymerase chain reaction analysis in in vitro study. In in vivo study, 5-week-old Wistar/ST male rats received zoledronate (35μg/kg/week) and dexamethasone (1mg/kg/day) subcutaneously for 2weeks. Unilateral maxillary molars were then extracted. Two weeks later, rats were divided into non-treatment, serum-free Dulbecco's modified Eagle's medium, and MSC-CM groups. In the MSC-CM group, the open alveolar sockets in 63% of the rats with BRONJ healed with complete soft tissue coverage and socket bones, whereas the exposed necrotic bone with inflamed soft tissue remained in the other groups. Histological analysis showed new bone formation and the appearance of osteoclasts in the MSC-CM group. Osteoclasts were significantly reduced in the non-treatment group. Thus, we concluded that the antiapoptotic and antiinflammatory effects of MSC-CM dramatically regulated the turnover of local bone and indicated therapeutic effects on BRONJ.


TGF-β1 inhibition of ACE2 mediated by miRNA uncovers novel mechanism of SARS-CoV-2 pathogenesis.
SARS-CoV-2 utilizes receptor binding domain (RBD) of spike glycoprotein to interact with angiotensin-converting enzyme 2 (ACE2). Decreased cell surface density of ACE2 contributes to mortality during COVID-19. Studies published early during the pandemic reported that people with cystic fibrosis (PwCF) treated with the high efficiency CFTR modulators ETI (elexacaftor-tezacaftor-ivacaftor) had higher ACE2 levels and milder COVID-19 symptoms, compared to people without CF. Subsequent studies did not confirm these findings. TGF-β1 gene polymorphisms associated with higher TGF-β1 levels, present in approximately 40% of CF patients, lead to more severe CF lung disease. To understand whether TGF-β1 modulates COVID-19 severity by affecting ACE2 levels in the airway, we performed small RNAseq and microRNA profiling and identified pathways uniquely affected by TGF-β1, including those associated with SARS-CoV-2 invasion. TGF-β1 inhibited ACE2 expression by miR-136-3p and miR-369-5p. ACE2 levels were higher in CF bronchial epithelial cell models. ETI did not prevent TGF-β1 inhibition of ACE2. Finally, TGF-β1 reduced the interaction between ACE2 and RBD by lowering ACE2 levels and its binding to RBD. Our data demonstrate novel mechanism whereby TGF-β1 inhibition of ACE2 in CF and non-CF bronchial epithelia may modulate SARS-CoV-2 pathogenicity and COVID-19 severity. By reducing ACE2 levels, TGF-β1 may decrease entry of SARS-CoV-2 into host cells while hindering recovery from COVID-19 due to loss of anti-inflammatory effects of ACE2.


JPEG quality transcoding using neural networks trained with a perceptual error measure.
A JPEG Quality Transcoder (JQT) converts a JPEG image file that was encoded with low image quality to a larger JPEG image file with reduced visual artifacts, without access to the original uncompressed image. In this article, we describe technology for JQT design that takes a pattern recognition approach to the problem, using a database of images to train statistical models of the artifacts introduced through JPEG compression. In the training procedure for these models, we use a model of human visual perception as an error measure. Our current prototype system removes 32.2% of the artifacts introduced by moderate compression, as measured on an independent test database of linearly coded images using a perceptual error metric. This improvement results in an average PSNR reduction of 0.634 dB.


New lesions after MDT in PB and MB leprosy: a report of 28 cases.
Appearance of new skin and/or nerve lesions during or after fixed duration of multi drug therapy (MDT), both in multibacillary (MB) and paucibacillary (PB) leprosy, is not uncommon. It could be a lesion due to reaction (type 1 or type 2), relapse due to multiplication of persisting or drug resistant bacilli or reinfection due to re-entry of lepra bacilli from outside. It is relatively easier to recognize the lesions due to classical reaction, both clinically and histopathologically. However, the differentiation could be difficult in other situations, especially when many of the relapse cases may present with features of reaction at the onset. Similarly, sometimes in late reversal reaction in addition to development of classical acute inflammation of old lesions, many of the patients developed multiple fresh new lesions without any sign of inflammation. We report a study of group of 28 relapsed leprosy cases, who developed new skin and/or nerve lesions at greatly varying time intervals (3 months to 22 years) after stopping MDT. Of these 28 patients, 11 were MB (1 LL,6 BL and 4 BB) and 17 were PB (12 BT, 4 TT and 1 Neuritic) at their first treatment. They reported to the Urban Leprosy Center (ULC) of Dr R M L Hospital during the period of 5 years (2002-2007). All patients came through self referral, 13 of them (46.4%) had received MDT outside our hospital (regular in 11 cases and irregular in 2 cases, as per the patient's statement), while the rest 15 had received full MDT regularly from our center (irregular in 1 case). All previously 11 MB cases developed new skin lesions of MB type (1 LL to LL, 3 BL to LL, 3 BL to BL, 1 BB to BL and 3 BB to BB). Of the 17 cases PB at their first treatment, 16 developed new lesions of PB type. Out of 4 TT cases, 1 had new lesions of TT, 1 BT and 2 LRR type lesions. Of the 12 BT cases at first presentation, 9 had BT, 1 secondary neuritic and 1 presented as LRR, while 1 BT case had new lesions of BL type. The one pure neuritic leprosy case presented as neuritic case only, after an interval of over 20 years. The post-MDT intervals of appearance of new lesions were 3-6 months in 5 cases (Group A), 8-30 months in 13 cases (Group B), from 3-10 years in 4 cases (Group C) and 15-22 years in 6 cases (Group D). All patients were successfully treated with a second course of MDT, as per the spectrum of the disease according to the number of fresh lesions. The likely cause of new lesions in group A (<6 months interval) could be either (1) mild type 1 reaction or (2) early relapse due to inadequate MDT. Similarly, the new lesions appearing in group B (0.5-3 years) could also represent mild type 1 reaction following improvement of CMI or a true early relapse. The possible causes of early relapse may be because of original misclassification or inadequate chemotherapy/irregular treatment or insufficient duration of therapy. In group C (3-10 years), the cause would most probably be late relapse, the possible causes of late relapse is either due to drug resistance and M. leprae persisters. When the time interval goes beyond 10 years (Group D), as in 6 of our cases, the possibility of reinfection can not be excluded besides causes of late relapse, since this period is usually considered equivalent to the maximum incubation period of lepra bacilli. In lepromatous leprosy, where the specific CMI against M. leprae is highly compromised, there is always a possibility of reinfection as long as the source of infection persists in the community and in such cases immunotherapy would be highly beneficial for prevention of reinfection. The post MDT time interval, lepromin test or drug resistance study both in vitro and in vivo may provide some clue to the mechanism responsible. All doubtful cases of new lesions with clinical presentation of type 1 reaction were diagnosed as relapse, through the therapeutic trial with oral prednisolone for 4-6 weeks and other cases. All cases with new lesions were treated with a second course of MDT (MB or PB) as per classification of new lesions.


Outpatient antibiotic use and prevalence of antibiotic-resistant pneumococci in France and Germany: a sociocultural perspective.
The prevalence of penicillin-nonsusceptible pneumococci is sharply divided between France (43%) and Germany (7%). These differences may be explained on different levels: antibiotic-prescribing practices for respiratory tract infections; patient-demand factors and health-belief differences; social determinants, including differing child-care practices; and differences in regulatory practices. Understanding these determinants is crucial for the success of possible interventions. Finally, we emphasize the overarching importance of a sociocultural approach to preventing antibiotic resistance in the community.


Metal-Free Multicomponent Strategy for Amidine Synthesis.
Amidines are a ubiquitous class of bioactive compounds found in a wide variety of natural products; thus, efficient strategies for their preparation are in great demand. Specifically, their common structural core decorated with three substituents sets amidines as perfect candidates for multicomponent synthesis. Herein, we present a highly modular metal-free multicomponent strategy for the synthesis of sulfonyl amidines. This work was focused on selecting readily accessible reagents to facilitate the in situ formation of enamines by the addition of amines to ketones. These components were coupled with azides to provide a broad reaction scope with respect to all three coupling partners. Aromatic and aliphatic amines and ketones were tolerated under our reaction conditions. Likewise, the presence of a methyl group on the ketone was critical to reactivity, which was leveraged for the design of a highly regioselective reaction with aliphatic ketones. A biologically active compound was successfully synthesized in one step, demonstrating the practical utility of our methodology. Finally, the postulated mechanism was investigated and supported both experimentally and by means of a multivariate statistical model.


Correlation between Skip N2 Metastases and SUVmax, Long Diameter of Tumor, and Ki67 Expression in Patients with Non-Small-Cell Lung Cancer.
We aim at investigating the correlation between skip N2 metastases (SN2) and SUVmax, long diameter of tumor mass after 18F-FDG PET/CT, and pathological Ki67 expression in patients with non-small-cell lung cancer (NSCLC). We retrospectively analyzed the factors that might affect the pathogenesis of SN2 in these patients. The clinical SN2 symptoms in patients with squamous carcinoma or adenocarcinoma were investigated. The work curve was utilized to analyze the optimal cutoff value for the SUVmax and long diameter of tumor. Multivariate analysis revealed that high expression of Ki67 was a risk factor for mediastinal SN2 (OR = 1.042, 95% CI: 1.009-1.076). Subgroup analysis indicated that the SUVmax of the non-SN2 group was significantly higher than that of the SN2 group in patients with squamous carcinoma (16.3 ± 6.0 vs. 10.7 ± 5.6, P = 0.026). In the patients with adenocarcinoma, the long diameter of tumor in the SN2 group was significantly longer than that of the non-SN2 group (43.8 ± 16.3 mm vs. 30.1 ± 13.8 mm, P = 0.032). The Ki67 expression in the SN2 group was significantly higher than that of the non-SN2 group (51.7 ± 24.0 vs. 30.0 ± 19.2, P = 0.028). The differences of clinical features of the patients in the SN2 group and non-SN2 group in the NSCLC patients were associated with the pathological subtypes, which were featured by lower SUVmax in the SN2 of the squamous carcinoma, and longer diameter of SN2 in the adenocarcinoma patients.


Dietary fructose causes tubulointerstitial injury in the normal rat kidney.
Recent studies suggest that the metabolic syndrome is associated with renal disease. We previously reported that a high-fructose diet, but not a high-glucose diet, can induce metabolic syndrome and accelerate chronic renal disease in rats. We now examined the effects of a high-fructose diet on normal rat kidneys. Three groups of Sprague-Dawley rats were pair fed a special diet containing 60% fructose, 60% glucose, or control standard rat chow for 6 wk, and then histological studies were performed. The effect of fructose to induce cell proliferation in cultured proximal tubular cells was also performed. Fructose diet, but not glucose diet, significantly increased kidney weight by 6 wk. The primary finding was tubular hyperplasia and proliferation involving all segments of the proximal tubules while glomerular changes were not observed. This is the same site where the fructose transporters (GLUT2 and -5) as well as the key enzyme in fructose metabolism (ketohexokinase) were expressed. Consistently, fructose also induced proliferation of rat proximal tubular cells in culture. In vivo, tubular proliferation was also associated with focal tubular injury, with type III collagen deposition in the interstitium, an increase in alpha-smooth muscle actin positive myofibroblasts, and an increase in macrophage infiltration. In conclusion, a high-fructose diet induces cell proliferation and hyperplasia in proximal tubules, perhaps via a direct metabolic effect. The effect is independent of total energy intake and is associated with focal tubulointerstitial injury. These studies may provide a mechanism by which metabolic syndrome causes renal disease.


Sex differences in fatigability following exercise normalised to the power-duration relationship.
Knee-extensors demonstrate greater fatigue resistance in females compared to males during single-limb and whole-body exercise. For single-limb exercise, the intensity-duration relationship is different between sexes, with females sustaining a greater relative intensity of exercise. This study established the power-duration relationship during cycling, then assessed fatigability during critical power-matched exercise within the heavy and severe intensity domains. When critical power and the curvature constant were expressed relative to maximal ramp test power, no sex difference was observed. No sex difference in time to task failure was observed in either trial. During heavy and severe intensity cycling, females experienced lesser muscle de-oxygenation. Following both trials, females experienced lesser reductions in knee-extensor contractile function, and following heavy intensity exercise, females experienced less reduction in voluntary activation. These data demonstrate that whilst the relative power-duration relationship is not different between males and females, the mechanisms of fatigability during critical power-matched exercise are mediated by sex. Due to morphological differences, females demonstrate greater fatigue resistance of locomotor muscle during single-limb and whole-body exercise modalities. Whilst females sustain a greater relative intensity of single-limb, isometric exercise than males, limited investigation has been performed during whole-body exercise. Accordingly, this study established the power-duration relationship during cycling in 18 trained participants (eight females). Subsequently, constant-load exercise was performed at critical power (CP)-matched intensities within the heavy and severe domains, with the mechanisms of fatigability assessed via non-invasive neurostimulation, near-infrared spectroscopy and pulmonary gas exchange during and following exercise. Relative CP (72 ± 5 vs. 74 ± 2% Pmax , P = 0.210) and curvature constant (51 ± 11 vs. 52 ± 10 J Pmax-1 , P = 0.733) of the power-duration relationship were similar between males and females. Subsequent heavy (P = 0.758) and severe intensity (P = 0.645) exercise time to task failures were not different between sexes. However, females experienced lesser reductions in contractile function at task failure (P ≤ 0.020), and greater vastus lateralis oxygenation (P ≤ 0.039) during both trials. Reductions in voluntary activation occurred following both trials (P < 0.001), but were less in females following the heavy trial (P = 0.036). Furthermore, during the heavy intensity trial only, corticospinal excitability was reduced at the cortical (P = 0.020) and spinal (P = 0.036) levels, but these reductions were not sex-dependent. Other than a lower respiratory exchange ratio in the heavy trial for females (P = 0.039), no gas exchange variables differed between sexes (P ≥ 0.052). Collectively, these data demonstrate that whilst the relative power-duration relationship is not different between males and females, the mechanisms of fatigability during CP-matched exercise above and below CP are mediated by sex.


Involvement of the ADAM 12 in thrombin-induced rat's VSMCs proliferation.
Cardiovascular disease is the largest single cause of mortality and its major underlying pathology is atherosclerosis. The proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of the various vascular diseases, including atherosclerosis and hypertension. Thrombin (Thr) is involved in the abnormal proliferation of VSMCs associated with atherosclerosis and hypertension. ADAMs (A Disintegrin And Metalloproteinase) are transmembrane metalloproteinases, belonging to the adamalysins group, that are distinct from matrix metalloproteinases (MMPs) in a way as they have an extracellular disintegrin domain and cytoplasmic domain that can associate with intracellular proteins. There is limited knowledge about the presence of ADAM metalloproteinase activity in Thr-induced VSMCs proliferation. Therefore, this review examines recent findings in signaling mechanisms employed by Thr in modulating the regulation of proliferation of VSMCs with particular emphasis on involvement of ADAM 12 which has been identified as an important mediator of VSMCs hypertrophy and vascular diseases. These findings are critical for understanding the role of Thr in vascular biology and vascular diseases.


Summer osmoregulatory capacity of the world's northernmost living salmonid.
Anadromous Arctic charr (Salvelinus alpinus L.) were caught on their way to and from the sea with the use of a fish trap placed in the Dieset watercourse located on the Spitsbergen Island (79 degrees 10' Northern latitude) within the high-Arctic Svalbard archipelago. When subjected to a seawater challenge test (34 parts/thousand at 4-5 degrees C), charr on their way to the sea showed only minor and temporary changes in blood plasma osmolality and Na+ and Mg2+ concentrations. The seawater tests also revealed good hypoosmoregulatory capacity for Arctic charr returning from the marine environment 4 wk later. A progressive decrease in seawater tolerance was first documented 7-11 days after their return to the freshwater habitat. Thus the Svalbard charr, being the northernmost anadromous salmonid and probably a direct descendant from the first Salvelinus immigrants to freshwater systems, undergoes a preparatory increase of hypoosmoregulatory capacity (smoltification) before entering the oceanic water bodies. Furthermore, the termination of their short annual seawater stay is probably elicited by factors controlling body systems other than osmoregulation.


Mycoremediation with mycotoxin producers: a critical perspective.
Filamentous fungi that produce mycotoxins also demonstrate the ability to degrade a wide variety of naturally occurring and anthropogenically generated hazardous wastes. Hence, these are emerging as excellent candidates for bioremediation. Their mycelia exhibit the robustness of adapting to highly restrictive environmental conditions often experienced in the presence of persistent pollutants, which makes them more useful compared to other microbes. However, it now appears that several regulatory factors that govern mycotoxin synthesis in these toxigenic strains also regulate their bioremediation abilities. To this end, mycoremediation and mycotoxin synthesis have been thoroughly but independently investigated; hence, much less is understood about the overlaps between the two processes. This review aims to shed light on this critical knowledge gap and provide some useful insights into the future research that might overcome the challenges associated with these shared regulatory modules. This will enable the harnessing of the full potential of mycoremediation by minimizing mycotoxin contamination.


Deep brain imaging of three participants across 1 year: The Bergen breakfast scanning club project.
Our understanding of the cognitive functions of the human brain has tremendously benefited from the population functional Magnetic Resonance Imaging (fMRI) studies in the last three decades. The reliability and replicability of the fMRI results, however, have been recently questioned, which has been named the replication crisis. Sufficient statistical power is fundamental to alleviate the crisis, by either "going big," leveraging big datasets, or by "going small," densely scanning several participants. Here we reported a "going small" project implemented in our department, the Bergen breakfast scanning club (BBSC) project, in which three participants were intensively scanned across a year. It is expected this kind of new data collection method can provide novel insights into the variability of brain networks, facilitate research designs and inference, and ultimately lead to the improvement of the reliability of the fMRI results.


In vitro binding of 3,4,5,6-tetrachloro-1,2-benzoquinone by rat liver glutathione S-transferases.
The in vitro interaction of 3,4,5,6-tetrachloro-1,2-benzoquinone (o-chloranil) with rat liver glutathione S-transferases (GST) was studied, using reduced glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB) as substrates. o-Chloranil inhibited the GST activity in crude extracts in a dose dependent manner, while 3,6-dichloro-2,5-dihydroxy-1,4-benzoquinone did not. Each of the GST isoenzymes was inhibited, albeit at different degrees. Kinetic studies never revealed competitive inhibition kinetics, with GSH nor CDNB as the variable substrate. Titration of remaining GSH in appropriate incubation mixtures indicated a minor spontaneous conjugation of o-chloranil with GSH, which was not enzymatically activated. It is concluded that o-chloranil interact with GST by direct binding to these proteins. This binding could have a protective function against o-chloranil.


Malaria knowledge, preventive actions, and treatment-seeking behavior among ethnic minorities in Ratanakiri Province, Cambodia: a community-based cross-sectional survey.
Malaria incidence has been steadily declining in Cambodia, where the government is aiming to eliminate malaria by 2025. Successful malaria elimination requires active engagement and participation of communities to recognize malaria symptoms and the development of prompt treatment-seeking behavior for early diagnosis and appropriate treatment. This study examined malaria knowledge, preventive actions, and treatment-seeking behavior among different groups of ethnic minorities and Khmer in Ratanakiri Province, Cambodia. Face-to-face interviews were conducted in December 2015, targeting 388 mothers with children under 2 years old, who belonged to ten ethnic minority groups or the Khmer group living in 62 rural villages in Ratanakiri. In addition to describing mothers' knowledge and actions for malaria prevention, logistic regression analysis was performed to identify determinants of fever during the most recent pregnancy and among children under two. Overall 388 mothers were identified for enrollment into the study of which 377 (97.2%) were included in analyses. The majority of mothers slept under bed nets at home (95.8%) and wore long-sleeved clothes (83.8%) for malaria prevention. However, knowledge of malaria was limited: 44.6% were aware of malaria symptoms, 40.6% knew the malaria transmission route precisely, and 29.2% knew of mosquito breeding places. Staying overnight at a farm hut was significantly associated with having fever during the most recent pregnancy (adjusted odds ratio [AOR] 2.008, 95% confidence interval [CI]: 1.215-3.321) and a child having fever (AOR 3.681, 95% CI 1.943-6.972). Mothers' partaking in a variety of malaria preventive actions was protective against fever in children (AOR 0.292, 95% CI: 0.136-0.650). Among those who had fever during pregnancy, 39.4% did not seek treatment. Although the majority of mothers took malaria preventive actions, knowledge of malaria epidemiology and vector ecology and treatment-seeking behavior for fever were limited. Staying overnight at farm huts, regardless of the differences in socio-demographic and socio-cultural characteristics, was strongly associated with fever episodes during pregnancy and childhood. This study indicates the necessity of spreading accurate malaria knowledge, raising awareness of health risks related to agricultural practices, and promoting treatment-seeking behavior among ethnic minorities to strengthen their engagement in malaria elimination.


Prostate cancer microvessels: a novel method for three-dimensional reconstruction and analysis.
Studies of prostate cancer microvessels to date have relied on routine two-dimensional images from histologic tissue sections, and there have been no previous reports of three-dimensional (3D) reconstruction and analysis of prostatic microvessels in benign or malignant specimens. Knowledge about the 3D architecture of microvessels would be useful for determining the utility and limitations of two-dimensional (2D) measures, as well as for determining the usefulness of 3D measures to predict pathologic stage and patient outcome in prostate cancer. However, the ability to study microvessels in 3D must first be demonstrated. We developed a novel method to visualize and analyze prostate microvessels in three dimensions from serially-sectioned prostate specimens, including tissue preparation, reconstruction of serial histologic sections into 3D volumes, extraction of vessels from this data set, and calculation of geometric characteristics. Eleven regions of benign and cancer tissue were studied and compared in an effort to validate our methodology. Microvessels and glandular elements from benign and malignant tissue were visualized together in three dimensions. In the 3D visualizations, microvessels associated with cancer were seen to have more arbitrary pathways, increased tortuosity, and a more casual relationship with glandular elements than microvessels associated with benign tissue. A quantitative measure, the volume length density, discriminated between benign tissue and cancer better than simple microvessel density in this exploratory study. Microvessels in prostate cancer have a more homogeneous distribution and greater tortuosity than those in benign tissue. Volume length density of microvessels shows promise as a 3D marker in prostate cancer.


Action Plan and Model to Reduce Potential Opioid Overdose Deaths on K-12 Campuses.
School communities are not immune to the alarming increase in opioid-related deaths occurring in the United States during the past decade. The purpose of this article is to share how a middle school in New York State, beginning in the late fall of 2022, successfully implemented a program to reduce the likelihood of opioid overdose deaths in their building through expansion of the accessibility of and education and training in use of naloxone, an opioid antagonist. The program is applicable for all K-12 campuses and follows the Model of Greater Awareness, Improved Training, and Increased Availability of and Accessibility to Intervention Devices, based on the steps successfully used for out-of-hospital cardiac arrest emergencies. Because opioid addiction does not discriminate, it is confidently projected that these targeted actions will proactively and positively reduce the likelihood of opioid overdose deaths in our school setting, including for students, faculty, staff, administrators, and visitors, when and should they occur.


Long-term observation of periodontal condition following placement of removable partial dentures with rigid retainers and major connector in patients with/without diabetes: A retrospective study.
This retrospective study evaluated the periodontal tissues of the abutment teeth of removable partial dentures (RPDs) with rigid retainers and major connectors in patients with and without type 2 diabetes mellitus (T2D). A total of 313 patients who had been treated with RPDs, including rigid retainers and major connectors, were divided into two groups: T2D and non-T2D. The periodontal parameters and radiographic bone heights of the abutment teeth were evaluated at baseline and at a 5-year examination during supportive periodontal therapy (SPT). For patients with accessible standardized radiographs, bone density was analyzed based on the gray level (GL) using digital subtraction radiography (n = 83). Overall, 739 abutment teeth (86 in the T2D group) of 235 patients (25 in the T2D group) were analyzed, and 95.0% (94.2% in the T2D group, and 95.2% in the non-T2D group) were maintained. The mean probing pocket depth significantly increased in both groups (p < 0.001). There were significant changes in the radiographic bone height (p = 0.038) and GL on the side of the denture base area (p = 0.048) in the T2D group compared to those in the non-T2D group. Regardless of T2D, RPDs with rigid retainers and major connectors could prevent the progression of periodontal disease and successfully maintain most of the abutment teeth during 5-years of SPT. However, T2D may be significantly associated with loss of bone height reduction and density on the side of the denture base area.


Preparation and characterization of a pH-responsive nanogel based on a photo-cross-linked micelle formed from block copolymers with controlled structure.
Poly(ethylene glycol)-b-poly(2-(diethylamino)ethyl methacrylate-co-2-cinnamoyloxyethyl acrylate) (PEG-b-P(DEAEMA/CEA)) was prepared by reversible addition-fragmentation chain transfer (RAFT)-controlled radical polymerization. As solution pH is increased from an acidic pH, the hydrodynamic radius (R(h)) increases abruptly near pH 7, indicative of the micelle formation at pH > 7. The micelle formation at pH > 7 was supported by (1)H NMR and light scattering data. Upon irradiation of light, polymer chains in the core of the polymer micelle are cross-linked as a result of the photodimerization of the cinnamoyl groups, yielding a nanogel. The nanogel was characterized by gel-permeation chromatography (GPC), light scattering, small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), and fluorescence techniques. The nanogel displayed an ability to solubilize N-phenyl-1-naphthylamine (PNA) and 1-pyrenemethanol (hydrophobic guest molecules) into the hydrophobic core at pH > 7. It was confirmed with PNA that the solubilization of a guest molecule occurred at polymer concentrations (C(p)) lower than the critical micelle concentration (cmc) for PEG-b-P(DEAEMA/CEA) because the nanogel retains its micellar structure at C(p) < cmc. 1-Pyrenemethanol is strongly captured by the nanogel at pH 10, whereas it is easily released from the nanogel when pH is reduced to 3. This indicates that the hydrophobicity of the core of the nanogel can be modulated by a change in the degree of protonation of the DEAEMA units in the core, and thus the capture of a guest molecule and its release can be controlled by a change in solution pH.


GenX is not always a better fluorinated organic compound than PFOA: A critical review on aqueous phase treatability by adsorption and its associated cost.
Hexafluoropropylene oxide dimer acid (GenX) has been marketed as a substitute for perfluorooctanoic acid (PFOA) to reduce environmental and health risks. GenX and PFOA have been detected in various natural water sources, and adsorption is recognized as a typical treatment process for PFOA removal. In this paper, comparisons of GenX and PFOA adsorption are evaluated, including adsorption potential, adsorption mechanisms, and associated costs. A detailed literature review suggests that anion-exchange resins are more effective in removing GenX than activated carbon. GenX removal efficiency through activated carbon (30%) is lower than that of PFOA (80-95%), while GenX and PFOA removal efficiencies by anion exchange resins are similar (99%). Unconventional adsorbents, such as ionic fluorogels and covalent organic frameworks can effectively remove GenX from water. The review reveals that GenX adsorption is more challenging, requiring almost 4 times the treatment cost of its predecessor, PFOA. Annual operation and maintenance costs for GenX adsorption (initial concentration of GenX and PFOA = 0.2 µg.L-1) by GAC for treating 10,000 m3 per day is almost US$1,000,000 per year, but only around US$240,000 per year for PFOA. Desorption of GenX in the presence of PFOA highlights GenX's inferior treatability by adsorption. It is believed that GenX is a more environmentally friendly compound than PFOA, but this environmental friendliness comes with the price.


Bee Stressors from an Immunological Perspective and Strategies to Improve Bee Health.
Honeybees are the most prevalent insect pollinator species; they pollinate a wide range of crops. Colony collapse disorder (CCD), which is caused by a variety of biotic and abiotic factors, incurs high economic/ecological loss. Despite extensive research to identify and study the various ecological stressors such as microbial infections, exposure to pesticides, loss of habitat, and improper beekeeping practices that are claimed to cause these declines, the deep understanding of the observed losses of these important insects is still missing. Honeybees have an innate immune system, which includes physical barriers and cellular and humeral responses to defend against pathogens and parasites. Exposure to various stressors may affect this system and the health of individual bees and colonies. This review summarizes and discusses the composition of the honeybee immune system and the consequences of exposure to stressors, individually or in combinations, on honeybee immune competence. In addition, we discuss the relationship between bee nutrition and immunity. Nutrition and phytochemicals were highlighted as the factors with a high impact on honeybee immunity.


Otomastoiditis Caused by Nocardia Farcinica: A Case Report and Literature Review.
Nocardia farcinica usually infects people with impaired immune status and usually manifests in the lungs. Otomastoiditis caused by Nocardia infection is extremely rare, with only 4 cases reported to date. This report describes a case of otomastoid N. farcinica infection in an immunocompetent patient. The case was a 10-month-old immunocompetent infant who presented with an approximately 3-month history of right ear discharge for which treatment with various antibiotics had not resulted in significant improvement. Multiple cultures of secretions and pathologic examination failed to identify the causative organism. The patient then underwent right mastoidectomy. Finally, metagenomic next-generation sequencing identified the pathogen to be N. farcinica. The patient was infection-free at the 6-month follow-up but had developed labyrinthitis ossificans. Otomastoid Nocardia infection has characteristic clinical features, namely, formation of a large amount of granulation tissue and coexistence of bone destruction and new bone formation. Traditionally, Nocardia is challenging to diagnose. Metagenomic next-generation sequencing of lesions is helpful. Complete local debridement and free drainage are key to treatment.


Insertion of internal jugular temporary hemodialysis cannulae by direct ultrasound guidance--a prospective comparison of experienced and inexperienced operators.
Previous studies have shown that inexperienced operators have a lower success rate than experienced operators for insertion of internal jugular cannulae using the anatomical landmark technique. The object of this study was to determine the rate of successful insertion, incidence of immediate complications and incidence of infection for temporary hemodialysis cannulae inserted under ultrasound guidance by experienced and inexperienced operators. The reason for insertion, patient age, reason for failed insertion, immediate complications, duration of cannula survival and reason for removal were recorded prospectively for 107 attempted cannulations by 7 operators in 72 subjects with renal failure. Operators were defined as "experienced" (more than 3 years postgraduate clinical experience and more than 25 previous central vein cannulae inserted) or "inexperienced" (less than 3 years postgraduate clinical experience and less than 3 previous central vein cannulae inserted). Rates of successful cannulation and incidence of complications were compared for experienced and inexperienced operators. Cannula survival without infection was analysed by Kaplan-Meier survival for experienced and inexperienced operators. The overall success rate of cannula insertion at first site was 103/107 (96.3%) with no difference between experienced and inexperienced operators (56/58 vs. 47/49). 103 internal jugular temporary haemodialysis cannulae were inserted into 72 subjects. The only immediate complication was incorrect positioning of the cannula in 6 cases requiring manipulation. The median survival of hemodialysis cannulae was 14 days (range 1-111). 64.1% cannulae functioned for as long as required. Of the remainder, 33/36 were removed because of presumed cannula related infection. There was no difference in the median duration of cannula survival between experienced and inexperienced operators (15 days versus 12 days; Mann-Whitney point estimate = -1.00; 95% confidence interval -6.00, 3.00). p = 0.66) or in the probability of cannula survival without infection by Kaplan Meier analysis. We conclude that ultrasound guided temporary haemodialysis cannulation is a safe procedure with a high rate of success, the success rate for inexperienced operators is much higher than previous studies of cannulation using the anatomical landmark technique and the rate of cannula removal due to infection is not influenced by operator experience.


Glioblastoma.
Glioblastoma (GBM), the most common primary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3 distinct morphologic variants of GBM are currently recognized by the current World Health Organization classification scheme, including GBM, giant cell GBM, and gliosarcoma. Additional variants, some of which have significant morphologic overlap with tumors that have more favorable prognosis and treatment response rates, particularly anaplastic oligodendroglioma, have been described since its publication in 2000 and may be included in the next classification. To summarize the morphologic and molecular genetic diversity of both well-established and novel GBM variants and outline our approach to these heterogeneous neoplasms and their distinction from other diffuse, high-grade gliomas. Published literature and our own experience in an active academic diagnostic surgical neuropathology practice were reviewed. Precise subclassification of GBM is required for accurate prognostication and appropriate treatment planning.