Occupational respiratory allergy in peach crop workers.
Occupational respiratory diseases in workers of peach tree crops have been reported punctually and have been associated with sensitization to proteins present in both pollen and leaf tree. We report the study of 37 workers with respiratory symptoms related to occupational exposure to peach trees. Prick tests and specific IgE determinations were performed with extracts from leaves and branches of peach tree. Immunodetection in leaf extract was realized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis SDS-PAGE-immunoblotting with patient sera and rabbit serum anti-Pru p 3. Immunodetection inhibition was performed with rPru p 3 and pollen profilins. The clinical relevance of sensitization was demonstrated by specific bronchial challenge test (SBCT) with peach leaf extract. Most patients suffered symptoms when peach trees had leaves, specifically during thinning and harvesting fruit (rhinoconjunctivitis: 100% and asthma: 67.5%). Sensitization to leaf extract was demonstrated in 86% of patients. IgE-immunoblotting with peach leaf extract revealed in six patient sera a pair of bands of 10 and 16 kDa, and in nine a 16-kDa band. Those bands could be two isoforms of peach leaf lipid transfer proteins( LTP), so the recognition frequency of some LTP isoform by our patient sera was 42%. 33% of the sera recognized a doubled band of about 14.5 kDa and this recognition was inhibited by nPho d 2. The SBCT with peach leaf extract was positive in the asthmatic sensitized patients tested. Sensitization to peach leaves was the cause of occupational respiratory symptoms in our patients. Some patient sera revealed IgE-binding proteins matching LTP and/or profilin.


Electronically-scanned ophthalmic ultrasound.
A linear-array ultrasonic system has been developed for ophthalmic application. The clinical apparatus gives real-time digital imaging at higher speeds and sensitivity compared to contemporary mechanically-scanned single transducer equipment. The linear-array system is electronically scanned to produce 60 images s-1 with 64 gray-tone levels. The 256 X 580 pixel B-mode image is presented simultaneously with an A-mode display on a television monitor. Fast-frame imaging at high sensitivity has special advantages in ophthalmic differential diagnosis enabling a more comprehensive evaluation of retinal, vitreous and orbital pathology. Imaging of fine blood vessels has improved ultrasonic diagnosis of ocular neoplasms and inflammatory conditions. Clinical advantages of this apparatus and special technical specifications are discussed in this report.


A NAC transcriptional factor BrNAC029 is involved in cytokinin-delayed leaf senescence in postharvest Chinese flowering cabbage.
Both cytokinin and NAC transcription factors were reported to involve in leaf senescence. However, the mechanism of NAC transcription factors how to regulate cytokinin-delayed leaf senescence is still unknown. In this study, application of N-(2-chloro-4-pyridyl)-N'-phenylurea (CPPU), a cytokinin analogue, significantly delayed leaf senescence and maintained cytokinin content of Chinese flowering cabbage during storage. Meanwhile, the expression of an NAC transcriptional activator (BrNAC029) was increased but suppressed by CPPU treatment. Furthermore, BrNAC029 activated the expressions of chlorophyll catabolic genes BrPAO and BrSGR2, cytokinin oxidase gene BrCKX1 and senescence maker gene BrSAG113 by binding to their promoters. Additionally, overexpressions of BrNAC029 in tobacco and Arabidopsis accelerated leaf senescence and up-expressed the related genes. Taken together, it was suggested that BrNAC029 may serve as a transcriptional activator to activate the transcriptions of these related genes to eventually accelerate leaf senescence of Chinese flowering cabbage by promoting chlorophyll degradation and reducing endogenous cytokinin level.


The Contribution of Drug Overdose to Educational Gradients in Life Expectancy in the United States, 1992-2011.
Since the mid-1990s, the United States has witnessed a dramatic rise in drug overdose mortality. Educational gradients in life expectancy widened over the same period, and drug overdose likely plays a role in this widening, particularly for non-Hispanic whites. The contemporary drug epidemic is distinctive in terms of its scope, the nature of the substances involved, and its geographic patterning, which influence how it impacts different education groups. I use vital statistics and National Health Interview Survey data to examine the contribution of drug overdose to educational gradients in life expectancy from 1992-2011. I find that over this period, years of life lost due to drug overdose increased for all education groups and for both males and females. The contribution of drug overdose to educational gradients in life expectancy has increased over time and is greater for non-Hispanic whites than for the population as a whole. Drug overdose accounts for a sizable proportion of the increases in educational gradients in life expectancy, particularly at the prime adult ages (ages 30-60), where it accounts for 25 % to 100 % of the widening in educational gradients between 1992 and 2011. Drug overdose mortality has increased more rapidly for females than for males, leading to a gender convergence. These findings shed light on the processes driving recent changes in educational gradients in life expectancy and suggest that effective measures to address the drug overdose epidemic should take into account its differential burden across education groups.


Calculation of magnetocaloric effect with regard for dependence of heat capacity on magnetic field.
A specific heat of the magnetic solid exhibiting AFM-FM phase transition is computed using the Landau-type theory of phase transitions. The experimentally observed dependence of the specific heat value on the external magnetic field is modelled. It is shown, that this dependence has strong influence on the giant magnetocaloric effect (MCE), which is inherent to the solids exhibiting the phase transitions accompanied by the strong change of magnetization value: the disregard of this dependence leads to the noticeable overestimation of adiabatic temperature change, which is the practically important characteristic of MCE. The temperature change characterizing the giant MCE observed in Fe-Rh alloys is computed. The reasonable agreement between the available experimental data and obtained theoretical results is demonstrated.


Fat embolism to the cardiac conduction system associated with sudden death.
During a brief hospital stay, a patient under treatment with corticosteroids for lymphoma died suddenly and unexpectedly. At autopsy, fat emboli were identified in the lungs, myocardium, liver, and brain. Examination of the cardiac conduction system revealed fat emboli in the vessels of the bundle of His as well as those accompanying the bundle branches, a finding believed to have resulted in the sudden death. This report is the first of fat embolization to the cardiac conduction system and emphasizes the importance of examination of this system in cases of unexplained or sudden death.


A simplified flow cytometry method of CD4 and CD8 cell counting based on thermoresistant reagents: implications for large scale monitoring of HIV-infected patients in resource-limited settings.
To validate a simplified flow cytometry assay for CD4 and CD8 T cell counting based on monoclonal antibodies which are made resistant to high temperatures (simplified thermoresistant assay (STRA)). The STRA employs FITC-conjugated anti-CD4 and anti-CD8 monoclonal antibodies, predispensed into test tubes and chemically treated to be resistant to high temperatures. Five correlation studies were performed in three different laboratories on a total of 560 blood samples from HIV-1 infected patients. Each study correlated the STRA with either double or single platform assays currently available. Accelerated stability tests on the FITC-conjugated monoclonal antibodies were performed to assess the resistance of the STRA to high temperatures. Comparison of STRA with both single platform and double platform assays gave correlation coefficients ranging 0.957-0.987 for CD4+ T cells and 0.946-0.968 for CD8+ T cells. In all correlation studies there was a perfect data overlapping in the low-pathological interval of CD4+ T cells (0-400 cells/ml). The FITC-conjugated CD4 and CD8 monoclonal antibodies maintained intact binding activity and fluorescence brightness after storage for 4 weeks at 45 degrees C and can be stored for up to 8 years in regular conditions (+4 degrees C). The STRA correlates well with both single-platform and double-platform flow-cytometry assays currently used to assess CD4+ T cells. The test procedure is simple, rapid, and easy to perform. The reagents can be stored under unfavorable environmental conditions for long period of time. These features should facilitate access to flow cytometry testing in resource-poor settings.


Impact of HLA eplet mismatch load in immunological outcomes after living donor kidney transplantation.
HLA eplets mismatches (eMM) have been associated with negative kidney outcomes after transplantation, such as the development of de novo donor-specific antibody (dnDSA), antibody-mediated rejection (ABMR), and early graft loss. This study aimed to evaluate the clinical effects of the HLA eMM load on dnDSA development, ABMR, renal function, allograft survival and graft loss. This retrospective study involved 159 living donor kidney transplant patients categorized into groups based on antigen HLA mismatches assessed traditionally and HLA eMM load. Patients had followed for at least one year. The EpViX online program was used to evaluate the HLA eMM load. Cox models were constructed to assess the risk of graft loss. Kaplan-Meier survival curves were carried out. The analyses had performed using the R program and p < 0.05 was considered significant. From all 159 patients, 28 (17.6%) lost their allografts. Rejection episodes occurred in 37.1% of patients, 13.6% of whom were ABMR. Patients with rejection episodes had higher HLA-AB (p = 0.032) and HLA-DR (p = 0.008) HLA eMM load, HLA-AB (p = 0.006) and HLA-DR (p = 0.009) antigens mismatches, and higher proportions of the following eMM in the HLA-DR locus: 70R eMM (p = 0.015), 70RE (p = 0.015), 74E (p = 0.015) and 48Q (p = 0.047). In multiple models, the presence of HLA-DR 70qq eMM (HR 3.75, 95% CI 1.47; 9.55) add an increase in creatinine levels at 1-year (HR 3.87, 95% CI 2.30, 6.53) were associated with the risk of graft loss. The HLA eMM load was related to episodes of rejection and allograft loss. The HLA-DR eMM was most strongly associated with a worse immunologic outcome than eMM mismatches for HLA-AB.


PromPDD, a web-based tool for the prediction, deciphering and design of promiscuous peptides that bind to HLA class I molecules.
Promiscuous peptides that can be presented by multiple human leukocyte antigens (HLAs) have great potential for the development of vaccines with wide population coverage. However, the current available methods for the prediction of peptides that bind to major histocompatibility complex (MHC) are mainly aimed at the rapid or mass screening of potential T cell epitopes from pathogen antigens or proteomics. The current approaches do not allow deciphering the contribution of the residue at each peptide position to the promiscuous binding ability of the peptide or obtaining guidelines for the design of promiscuous peptides. In this study, we re-evaluated and characterized four matrix-based prediction models that have been extensively used for the prediction of HLA-binding peptides and found that the prediction models generated based on the average relative binding (ARB) matrix shared a consistent and conservative threshold for all well-studied HLA class I alleles. Evaluations performed using datasets of HLA supertype-specific peptides with various cross-binding abilities and peptide mutant analogues indicated that the ARB-based binding matrices could be used to decipher and design promiscuous peptides that bind to multiple HLA molecules. A web-based tool called PromPDD was developed using ARB matrix-based models, and this tool enables the prediction, deciphering and design of promiscuous peptides that bind to multiple HLA molecules within or across HLA supertypes in a simpler and more direct manner. Furthermore, we expanded the application of PromPDD to HLA class I alleles with limited experimentally verified data by generating pan-specific matrices using a derived modular method, and 2641 HLA molecules encoded by HLA-A and HLA-B genes are available in PromPDD. PromPDD, which is freely available at http://www.immunoinformatics.net/PromPDD/, is the first tool for the deciphering and design of promiscuous peptides that bind to HLA class I molecules.


Graphene oxide-induced conformation changes of glucose oxidase studied by infrared spectroscopy.
The adsorption of proteins on the surface of nanomaterials can induce changes in the structure and biological activity of the proteins. Although there have been a number of studies aimed at developing an understanding of the interactions of proteins with surfaces of nanomaterials, a detailed description of the actual state of the adsorbed proteins or the functional consequences of protein adsorption onto nanomaterials has yet to be reported. In this study, the conformation changes of glucose oxidase (GOx) induced by adsorption on graphene oxide (GO) sheets were investigated by quantitative second-derivative infrared analysis and two-dimensional infrared correlation spectroscopy (2D IR). The adsorption of GOx on GO sheets resulted in the conversion of α-helix to β-sheet structures and therefore led to substantial conformation changes of GOx, even the unfolding of the protein. These alterations in the conformation of GOx caused a significant decrease in the catalytic activity of the enzyme for glucose oxidation. This study demonstrates that nanomaterials can strongly influence the conformation and activity of adsorbed proteins. In addition to the importance of this effect in cases of the direct adsorption of proteins on nanomaterials, the results have implications for proteins adsorbed on materials with nanometer-scale surface roughness.


ATF2-Induced lncRNA GAS8-AS1 Promotes Autophagy of Thyroid Cancer Cells by Targeting the miR-187-3p/ATG5 and miR-1343-3p/ATG7 Axes.
Long non-coding RNAs (lncRNAs) play an essential regulatory role in multiple cancers. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is still unknown. Here, GAS8-AS1, a novel lncRNA that is significantly downregulated in PTC, was selected for further investigation. The roles of GAS8-AS1 in PTC cells were verified by gain- and loss-of-function experiments. The functional mechanism of GAS8-AS1 on the microRNA (miR)-187-3p/ATG5 axis and miR-1343-3p/ATG7 axis in PTC cells was evaluated using bioinformatics analysis, luciferase reporter assay, Cell Counting Kit-8 (CCK-8) assay, immunohistochemistry analysis, transmission electron microscopy, and immunofluorescence. We found that GAS8-AS1 was downregulated in PTC tissues and cell lines. In patients with PTC, low GAS8-AS1 expression was associated with higher tumor-node-metastasis (TNM) stage and lymph node metastasis (LNM). Functionally, GAS8-AS1 significantly promoted autophagy and inhibited PTC cell proliferation in vitro and promoted tumorigenesis in vivo. Mechanistically, GAS8-AS1 acted as a sponge of miR-187-3p and miR-1343-3p and upregulated ATG5 and ATG7 expression, respectively. The transcription factor ATF2 regulated GAS8-AS1 by binding to the GAS8-AS1 promoter. In conclusion, upregulation of ATF2 activated GAS8-AS1-promoted autophagy of PTC cells by sponging oncogenic miR-187-3p and miR-1343-3p and upregulating the expression of ATG5 and ATG7, respectively, making GAS8-AS1 a potential prognostic biomarker and therapeutic target for PTC.


Transient absorption and photovoltage study of' self-assembled bacteriorhodopsin/polycation multilayer films.
A series of organized (PDAC/PM)(n) (poly(diallyldimethylammonium chloride)/purple membrane) multilayer films were prepared by alternate adsorptions of positively charged PDAC polyelectrolyte and negatively charged purple membrane (PM). The kinetics of the photocycle of bacteriorhodopsin (bR) in PM was studied by flash photolysis and transient photovoltage methods. Although the orientation of the adsorbed bR depends on the pH of the PM suspension, the kinetics of the photo-induced reaction cycle in dehydrated films is independent of the deposition pH. In dry (PDAC/PM)(n) films the decay of the M intermediate to the initial bR state is multiexponential and delayed to several minutes for both orientations. A simultaneous two-exponential decay in millisecond time domain was observed at red wavelengths. The source of the red-shifted absorption is suggested to be the C(610) intermediate of the cis photocycle of bR.


Symposium on the immunodiagnosis of rheumatic and related diseases, Part II. Rheumatoid factors.
Human rheumatoid factors are antibodies of IgG, IgA, or IgM class that show reactions with antigenic determinants present on other immunoglobulin molecules. The most commonly measured rheumatoid factor relates to the 19S IgM type, which reacts by agglutination of latex particles coated with 7S IgG and is often measured in the standard latex fixation test. Approximately 65 to 70 per cent of patients with rheumatoid arthritis show positive serologic tests for rheumatoid factor; however, a number of other chronic disease conditions are also associated with positive rheumatoid factor reactions, including infective endocarditis, sarcoidosis, leprosy, and other hyperglobulinemic conditions. Although extensive serologic and immunochemical studies have identified a number of specific antigenic structural sites on immunoglobulin molecules that react with rheumatoid factors, recent studies have shown that a certain proportion of such antibodies may show cross-reactivity with DNA-histone complexes as well. It is still not entirely clear how rheumatoid factors fit into the pathogenesis of rheumatoid arthritis itself.


Is academic rigor in Sudden Infant Death Syndrome (SIDS) research in decline?
To determine how well definitions of SIDS in the literature are being cited and referenced. The "PubMed" database was searched for "sudden infant death syndrome" from 2020 to 2021. Of 421 original papers, 50 were randomly selected and checked to determine whether one of the three internationally accepted definitions of SIDS: Seattle, NICHD and San Diego definitions had been cited/quoted in the text and correctly referenced. Papers that incorrectly cited or did not cite one standard definitions were assigned into: (i) those that used mis-cited, idiosyncratic or other (alternative, non-standard) definitions and, (ii) those where there was no definition. Fifty-six per cent of papers correctly cited standard definitions, a 12% decrease from the 68% in a similar study in 2012. Of those only 22% both correctly cited/referenced one of the standard definitions. Major issues in 78% of papers involved citing one and referencing another standard definition (N = 7, 14%), citing or referencing alternative, non-standard definitions (N = 8, 16%) or not citing or referencing any definition (N = 24, 48%). There is an increasing trend to not follow standard definitions of SIDS. This may hinder data interpretation where cases have not been appropriately defined and negatively impact upon the validity of SIDS research.


Macropinocytosis and Cancer: From Tumor Stress to Signaling Pathways.
Macropinocytosis is an evolutionarily conserved endocytic pathway that mediates the nonselective acquisition of extracellular material via large endocytic vesicles known as macropinosomes. In addition to other functions, this uptake pathway supports cancer cell metabolism through the uptake of nutrients. Cells harboring oncogene or tumor suppressor mutations are known to display heightened macropinocytosis, which confers to the cancer cells the ability to survive and proliferate despite the nutrient-scarce conditions of the tumor microenvironment. Thus, macropinocytosis is associated with cancer malignancy. Macropinocytic uptake can be induced in cancer cells by different stress stimuli, acting as an adaptive mechanism for the cells to resist stresses in the tumor milieu. Here, we review the cellular stresses that are known to promote macropinocytosis, as well as the underlying molecular mechanisms that drive this process.


Social Media Peer Support Groups for Obsessive-Compulsive and Related Disorders: Understanding the Predictors of Negative Experiences.
As social media platforms become commonplace in daily life, online peer support groups have become an increasingly popular resource for people living with physical and mental health issues. Although the benefits of using online peer support groups have been well documented, there can be also be significant risks associated with groups hosted on social media platforms. People living with obsessive-compulsive related disorders may be particularly vulnerable to negative experiences in such groups. Using a mixed-methods approach, the aim of the current study was to identify the predictors of negative experiences among people who used social media peer support groups for obsessive-compulsive and related disorders. Results indicated that barriers to treatment and quality of "offline" interpersonal support predicted users' negative experiences in social media peer support groups for obsessive-compulsive and related disorders. Thematic analysis suggested that the contributing factors towards participants' negative experiences included: (1) confronting content; (2) misinformation; (3) preoccupation with symptoms; (4) social comparison; and (5) hopelessness about recovery prospects. It was concluded that using social media peer support groups for obsessive-compulsive and related disorders, without adequate support structures in place, can pose users at the risk of negative experiences. Further research is necessary to gain a deeper understanding of how to enhance positive experiences and protect against the possible risks for users of unmoderated online peer support groups.


Perioperative and Mid-term Oncological and Functional Outcomes After Partial Nephrectomy for Complex (PADUA Score ≥10) Renal Tumors: A Prospective Multicenter Observational Study (the RECORD2 Project).
Partial nephrectomy (PN) for complex renal masses has a non-negligible risk of perioperative complications. Furthermore, late functional and oncological outcomes of patients submitted to these challenging surgeries still remain to be determined. To report the perioperative and mid-term oncological and functional outcomes of PN for complex masses (Preoperative Aspects and Dimensions Used for an Anatomical [PADUA] score≥10) in a large multicenter prospective observational study. We prospectively evaluated patients treated with PN for complex renal tumors at 26 urological centers (Registry of Conservative and Radical Surgery for Cortical Renal Tumor Disease [RECORD2] project). Multivariate logistic regression analyses explored the predictors of surgical complications. Multivariable Cox regression analyses estimated the hazard of renal function loss and disease recurrence. Kaplan-Meier estimates assessed the probability of survival. In total, 410 patients who underwent PN for complex masses were evaluated. Clinical T1b and T2 tumors accounted for 43.2% and 9.8% of the cases. Overall, 45.9%, 18.8%, and 35.4% of patients underwent open, laparoscopic, and robotic PN, respectively. Intraoperative complications occurred in 15 (3.6%) patients, while postoperative surgical complications were recorded in 76 (18.5%) patients. At multivariable analysis, preoperative hemoglobin (odds ratio [OR]: 0.67; p<0.001) and open (OR: 3.91; p<0.001) versus robotic surgical approach were found to be the only predictors of surgical complications. An estimated glomerular filtration rate drop of >25% from baseline was observed in 30.2% and 17.6% of patients at 1st month and 2 yr after surgery, respectively. Two-year recurrence-free survival was 97.1%; positive surgical margins (hazard ratio [HR]: 3.35; p=0.009), nucleolar grading (HR: 5.61; p<0.001), and tumor stage (HR: 2.62; p=0.05) were associated with recurrence. In a large series, PN for complex renal masses was a safe technique with an acceptable rate of perioperative complications and excellent mid-term oncological and functional results. In this study, we evaluated peri- and postoperative outcomes of patients treated with partial nephrectomy for complex renal masses. Open surgery was associated with higher complications than the robotic approach. Some histological features were found to be associated with disease recurrence.


BushenHuoxue decoction suppresses M1 macrophage polarization and prevents LPS induced inflammatory bone loss by activating AMPK pathway.
Abnormal bone metabolism and subsequence osteoporotic fractures are common complications of chronic inflammatory diseases. No effective treatment for these bone-related complications is available at present. The chronic inflammatory state in these diseases has been considered as a key factor of bone loss. Therefore, the combination of inflammation inhibition and bone loss suppression may be an important strategy for reducing bone damage associated with inflammatory diseases. Bushen Huoxue Decoction (BSHXD) is a traditional Chinese herbal compound that has demonstrated the ability to improve bone quality and increase bone density. However, the efficacy of BSHXD on inflammatory bone loss and its underlying mechanisms remain unclear. This study aimed to investigate whether BSHXD inhibits inflammatory bone loss in mice and its potential molecular mechanisms. In the present study, the effect of BSHXD on lipopolysaccharide (LPS)-induced M1 polarization of RAW264.7 macrophage and on local inflammatory bone loss model of mouse skull was determined. The results showed that after treating RAW264.7 cells with LPS for 24 h, the expression levels of IL-1β (39.42 ± 3.076 ng/L, p < 0.05), IL-6 (49.24 ± 1.766 mg/L, p < 0.05) and TNF-α (286.3 ± 27.12 ng/L, p < 0.05) were significantly increased. The addition of BSHXD decreased the expression levels of IL-1β, IL-6, and TNF-α to 31.55 ± 1.296 ng/L, 37.94 ± 0.8869 mg/L, and 196.4 ± 25.25 ng/L, respectively (p < 0.05). The results of immunofluorescence staining, Western blotting (WB) and flow cytometry indicated that the proportion of M1 macrophages in RAW264.7 cells treated with BSHXD for 24 h was significantly lower than that in the LPS group (13.36% ± 0.9829% VS 24.80% ± 4.619%, p < 0.05). The evidence from in-vitro experiments showed that the immunomodulatory ability of BSHXD may be associated with the activation of AMP-dependent protein kinase (AMPK) pathway in LPS-treated macrophages. In addition, the results of micro-CT, H&E staining, immunohistochemical staining and immunofluorescence staining of mouse skull further demonstrated that BSHXD treatment significantly alleviated LPS-induced local bone loss and inflammatory damage in mouse skull model. All results indicated that BSHXD significantly inhibited inflammatory factors release and M1 polarization of macrophage through AMPK signaling pathway. Therefore, BSHXD may be a promising drug for the treatment of inflammatory bone loss.


Material reaction to suture anchor.
The authors present a case of material reaction to suture anchor, which is rarely reported. Leukocyte rate, leukocyte differential, multiple cultures, and gram stain test could not prove infection. A second surgery for exploration of the shoulder joint was performed to reconstruct the rotator cuff without using anchors, and the rotator cuff tear healed after the second surgery. During the second surgery, the bone surrounding the anchors was found to be eroded and substituted with necrotic tissue. The anchors protruded outside the bone. The pathological examination of the necrotic tissue showed multinucleated giant cells of foreign body type, some of which had engulfed minute splinters of particulate foreign material. Either metal- or suture-induced bioreaction is suspected in this case.


Biochar-enriched soil mitigated N2O and NO emissions similarly as fresh biochar for wheat production.
Biochar amendment has been recommended as a potential strategy to mitigate nitrous oxide (N2O) and nitric oxide (NO) emissions for wheat production, but its mechanism and effective duration are not well understood. The 1-octyne and 2-pheny l-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO) in combination with potassium chlorate were used to evaluate the relative contribution of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to potential ammonia oxidation (PAO) and N2O and NO production as affected by biochar. Acidic and alkaline soils were collected during wheat-growing season, and four treatments were installed in each soil type: CK, urea alone; BE, biochar-enriched soil for 2-6 years; FB, fresh biochar added to CK; and AB, aged biochar added to CK. The results showed that octyne and PTIO efficiently assessed AOB and AOA activities in soil incubation. The AOB-driven PAO in acidic soil was largely enhanced by increased soil pH in BE and FB treatments, whereas AOA-driven PAO was not. And the contribution of AOB to PAO exceeded 80% in alkaline soil. The N2O and NO production were positively correlated with PAO in both soils. BE treatment decreased the direct N2O and NO production in alkaline soil, while both BE and FB treatments decreased the N2O and NO yields in acidic soil, indicating that biochar mitigated soil N2O and NO emissions for wheat production. The lack of differences between AB and CK treatments indicated that aged biochar lost its initial effects on PAO, while the biochar-enriched soil amended with biochar years earlier still functioned similarly as fresh biochar.


Ependyma: normal and pathological. A review of the literature.
A review of the available literature reveals that proliferation of ependyma occurs during embryological and early postnatal periods of development. Turnover, however, declines significantly during postnatal life and only low levels of residual activity persist into adulthood under normal conditions. In some regions of the ventricle, however, morphological and histochemical differentiation of ependyma is not attained for some considerable time postnatally. Recent immunocytochemical studies using GFAP indicate that only tanycytes may acquire antigenicity during development and that they may share a common phylogeny and/or function with astrocytes. Under pathological conditions, the bulk of available evidence suggests that inherent differences may exist in the proliferative capacity of ependyma in different regions of the neuraxis. Although the response of ependyma to various pathological conditions is equivocal, proliferation has been often observed in response to spinal cord injury. Indeed, ependyma is believed to play a significant role in the initiation and maintenance of the regenerative processes in the spinal cord of inframammalian vertebrates. In hydrocephalus there appears to be a remarkable similarity in cytopathological changes regardless of the mode of induction. The sequence, severity and extensiveness of damage appear to correlate with the degree of ventricular dilatation. The most commonly observed changes are (1) stretching and flattening of ependyma, most pronounced over white matter, (2) characteristic ependymal cell surface changes associated with ventricular distension, (3) increased extracellular space and periventricular edema and (4) demyelination and subependymal gliosis. Although ependymal cell proliferation has been reported as part of the overall tissue response to chronic hydrocephalus and to the pathology of ventricular shunt occlusion, the evidence is not entirely convincing and there is clearly a need for further research on the subject.


Synthesis of betulinic acid derivatives with activity against human melanoma.
Betulinic acid has been modified at C-3, C-20, and C-28 positions and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. This preliminary investigation demonstrates that simple modifications of the parent structure of betulinic acid can produce potentially important derivatives, which may be developed as antitumor drugs.


Three-dimensional macroporous wood-based selective separation membranes decorated with well-designed Nd(III)-imprinted domains: A high-efficiency recovery system for rare earth element.
Three-dimensional (3D) basswood materials, for the first time, were successfully used for the construction of rare-earth Nd(III)-imprinted nanocomposite membranes. Herein, polydopamine (PDA)-modified layers could be initially synthesized on basswood surfaces. After the double-bonded modification procedure, the 3D wood-based ionic imprinted membranes (3DW-IIMs) system was finally accomplished by developing a re-modified two-step-temperature free radical polymerization process. The as-design PDA@basswood surface structure was first proposed and applied as imprinting-initiated factors for the preparation of Nd(III)-imprinted sites. Importantly, excellent rebinding capacity (120.87 mg g-1), adsorption kinetics and permselectivity coefficients (more than 10) were achieved successfully. Furthermore, an important research result had also been found that the PDA-modified layers caused significant promotions to the rebinding capacities of the as-prepared 3DW-IIMs, that is to say, more and more Nd(III)-imprinted sites could be synthesized because of the PDA-modified surfaces. The as-obtained selective rebinding and separation results together with the green natural wood-based materials strongly demonstrated that our synthesis methodology of 3DW-IIMs had great potential for applications in various fields of rare earth separation, chemical industry, and environment protection.


The correlation between 13-hydroxyoctadecadienoate dehydrogenase (13-HODE dehydrogenase) and intestinal cell differentiation.
The enzyme 13-hydroxyoctadecadienoate dehydrogenase (13-HODE dehydrogenase) catalyzes the NAD(+)-dependent oxidation of 13-hydroxyoctadecadienoic acid to 13-oxooctadecadienoic acid. In that the oxygenation of linoleic acid is increasingly being shown to be involved in the regulation of cellular function, this enzyme is poised to play a key role in the expression of the biological activity of these compounds. We have measured the activity of 13-HODE dehydrogenase in rat intestinal cells at various stages of differentiation. The specific activity of 13-HODE dehydrogenase shows a strong positive correlation with the degree of differentiation of intestinal mucosal cells from both the small and large intestines. In the small intestine the gradient of activity parallels that of alkaline phosphatase, while in the colon the incorporation of 3H-deoxythymidine and 13-HODE dehydrogenase are inversely related. Since the expression of 13-HODE dehydrogenase is most likely not associated with the nutritive function of the intestinal tract, these data raise the possibility the enzyme plays a role in the process of cellular differentiation.


Effect of trichloroacetic acid on iron oxidation: Implications on the control of DBPs and deposits in drinking water.
In drinking water distribution system (DWDS), disinfection byproducts (DBPs) have a large possibility of participating in iron oxidation by dissolved oxygen (DO), which may induce particle structure transformations and increase unknown risks. In this work, the influence of trichloroacetic acid (TCAA, one of the most typical DBPs) on iron oxidation processes was studied, and the potential effects of the resulting α-FeOOH particles were evaluated through two aspects: (i) influence on the bacterial community and (ii) toxicity to human cells. TCAA promoted iron oxidation process through an Fe-O-C linkage, which led to a sharper surface of the particles (TCAA-mediated Fe oxide particles, TFOP) than that without TCAA (Fe oxide particles, FOP). Interestingly, the influence of particles on the richness of bacterial community of drinking water was different under anaerobic and aerobic conditions: under anaerobic conditions, the richness of bacterial community increased with the addition of particles, while under aerobic conditions, the richness of bacterial community decreased. The higher affinity of TFOP for electron-accepting DO than FOP indicated the role of DO on TFOP under aerobic conditions. TFOP exhibited the strongest cytotoxicity among FOP and the actual deposits. DFT calculations confirmed that TCAA in iron particles promoted the adsorption and dissociation of H2O2 to generate more •OH with an obvious decrease in the energy barrier from 1.51 to 0.80 eV. This study indicates the high potential of adverse effects of DBPs on loose deposits in DWDS and gives implications for the control of DBPs and deposits in drinking water.


MRI lesions can often precede trigeminal neuralgia symptoms by years in multiple sclerosis.
Understanding when multiple sclerosis (MS) lesions become clinically symptomatic may provide insight into disease pathophysiology. Our objective was to temporally associate lesion formation and trigeminal neuralgia (TN) symptom onset in MS. This is a retrospective case series of patients with MS, analysing time difference between TN symptom onset and oldest MRI showing a correlative lesion. For the 26 patients with MS, a correlative lesion was noted on MRI on average 5±4 years prior to TN symptom onset; 57% had primary or secondary progressive MS. TN lesions can be present years prior to symptom onset, suggestive of alternative explanations than typical relapses. This phenomenon may hint at alternative pathophysiology of progressive MS in comparison to relapsing-remitting MS.


Expanded click conjugation of recombinant proteins with ubiquitin-like modifiers reveals altered substrate preference of SUMO2-modified Ubc9.
Wrestling with SUMO: the chemical conjugation of proteins with small ubiquitin-like modifiers (SUMO) can be achieved by a copper(I)-catalyzed cycloaddition and unnatural amino acid mutagenesis. This approach overcomes previous restrictions related to the primary sequence of proteins and coupling conditions. Moreover, biochemical data suggests that this triazole linkage presents the modifier in a proper distance and orientation relative to the target protein.


Analysis of bi-atrial function using CMR feature tracking and long-axis shortening approaches in patients with diastolic dysfunction and atrial fibrillation.
Atrial function can be assessed using advancing cardiovascular magnetic resonance (CMR) post-processing methods: atrial feature tracking (FT) strain analysis or a long-axis shortening (LAS) technique. This study aimed to first compare the two FT and LAS techniques in healthy individuals and cardiovascular patients and then investigated how left (LA) and right atrial (RA) measurements are related to the severity of diastolic dysfunction or atrial fibrillation. Sixty healthy controls and 90 cardiovascular disease patients with coronary artery disease, heart failure, or atrial fibrillation, underwent CMR. LA and RA were analyzed for standard volumetry as well as for myocardial deformation using FT and LAS for the different functional phases (reservoir, conduit, booster). Additionally, ventricular shortening and valve excursion measurements were assessed with the LAS module. The measurements for each of the LA and RA phases were correlated (p < 0.05) between the two approaches, with the highest correlation coefficients occurring in the reservoir phase (LA: r = 0.83, p < 0.01, RA: r = 0.66, p < 0.01). Both methods demonstrated reduced LA (FT: 26 ± 13% vs 48 ± 12%, LAS: 25 ± 11% vs 42 ± 8%, p < 0.01) and RA reservoir function (FT: 28 ± 15% vs 42 ± 15%, LAS: 27 ± 12% vs 42 ± 10%, p < 0.01) in patients compared to controls. Atrial LAS and FT decreased with diastolic dysfunction and atrial fibrillation. This mirrored ventricular dysfunction measurements. Similar results were generated for bi-atrial function measurements between two CMR post-processing approaches of FT and LAS. Moreover, these methods allowed for the assessment of incremental deterioration of LA and RA function with increasing left ventricular diastolic dysfunction and atrial fibrillation. A CMR-based analysis of bi-atrial strain or shortening discriminates patients with early-stage diastolic dysfunction prior to the presence of compromised atrial and ventricular ejection fractions that occur with late-stage diastolic dysfunction and atrial fibrillation. • Assessing right and left atrial function with CMR feature tracking or long-axis shortening techniques yields similar measurements and could potentially be used interchangeably based on the software capabilities of individual sites. • Atrial deformation and/or long-axis shortening allow for early detection of subtle atrial myopathy in diastolic dysfunction, even when atrial enlargement is not yet apparent. • Using a CMR-based analysis to understand the individual atrial-ventricular interaction in addition to tissue characteristics allows for a comprehensive interrogation of all four heart chambers. In patients, this could add clinically meaningful information and potentially allow for optimal therapies to be chosen to better target the dysfunction.


Complications and Healthcare Consumption of Pregnant Women with a Migrant Background: Could There be an Association with Psychological Distress?
Previous studies reported less prenatal healthcare consumption and more perinatal complications in women with a migrant background. Hence, we investigated in a country with free healthcare access whether women with a migrant background differed with respect to pregnancy complications, healthcare consumption and in terms of associations with psychological distress in comparison to native Dutch. We included 324 native Dutch and 303 women with a migrant background, who visited two hospitals in Amsterdam for antenatal care between 2014 and 2015. Participants completed the Edinburgh Postnatal Depression Scale, the Hospital Depression and Anxiety Scale, and sociodemographic questions. Complications and healthcare consumption during pregnancy were extracted from medical records. Regression analyses were used with adjustment for covariates. Except for gestational diabetes [adjusted OR = 3.09; 95% CI = (1.51, 6.32)], no differences were found between groups in perinatal complications [OR = 1.15; 95% CI = (0.80, 1.64)], nor in healthcare consumption [OR = 0.87; 95% CI = (0.63, 1.19)]. Women with a migrant background reported more depressive symptoms [Cohen's d = 0.25; 95% CI = (0.10, 0.41)], even after adjustment for socio-economic factors. Psychological distress was associated with more hospital admissions during pregnancy. When experiencing depressive symptoms, women with a migrant background had an increased risk to be admitted [OR = 1.11; 95% CI = (1.01, 1.21)]. This cohort study found no differences in pregnancy-related complications, except for diabetes, nor different healthcare consumption, in women with a migrant background versus native Dutch, in a country with free health care access. However, women with a migrant background experienced more depressive symptoms, and when depressed their risk for hospital admission increased. Additional research is warranted to improve healthcare for this population.


Value of prenatal magnetic resonance imaging in the prediction of postnatal outcome in fetuses with diaphragmatic hernia.
To investigate the potential value of antenatally determined total fetal lung volume (TFLV) by magnetic resonance imaging (MRI) in the prediction of the postnatal survival in congenital diaphragmatic hernia (CDH). We examined fetuses with isolated CDH, in which MRI was used at 22-38 weeks of gestation to measure TFLV and assess intrathoracic herniation of abdominal viscera, that were liveborn after 30 weeks of gestation and had postnatal follow-up until death or discharge from hospital. Regression analysis was used to investigate the effect on survival of gestational age at diagnosis, observed to expected (o/e) TFLV, intrathoracic herniation of the liver, side of CDH, gestational age at MRI, institution, year and gestational age at delivery. In 76 fetuses measurements of o/e TFLV and the lung area to head circumference ratio (LHR) were performed within 2 weeks of each other; in these cases o/e TFLV and o/e LHR were compared for their prediction of postnatal survival. In the 148 cases that fulfilled the entry criteria, multiple regression analysis demonstrated that significant predictors of survival were the presence or absence of intrathoracic herniation of the liver and o/e TFLV. The area under the receiver-operating characteristics curves for prediction of postnatal survival from o/e TFLV was 0.786 (standard error, 0.059; P < 0.001) and that from o/e LHR was 0.743 (standard error, 0.069; P = 0.001). In the assessment of fetuses with CDH, MRI-based o/e TFLV is useful in the prediction of postnatal survival.


Color-deficient cone mosaics associated with Xq28 opsin mutations: a stop codon versus gene deletions.
Our understanding of the etiology of red-green color vision defects is evolving. While missense mutations within the long- (L-) and middle-wavelength sensitive (M-) photopigments and gross rearrangements within the L/M-opsin gene array are commonly associated with red-green defects, recent work using adaptive optics retinal imaging has shown that different genotypes can have distinct consequences for the cone mosaic. Here we examined the cone mosaic in red-green color deficient individuals with multiple X-chromosome opsin genes that encode L opsin, as well as individuals with a single X-chromosome opsin gene that encodes L opsin and a single patient with a novel premature termination codon in his M-opsin gene and a normal L-opsin gene. We observed no difference in cone density between normal trichomats and multiple or single-gene deutans. In addition, we demonstrate different phenotypic effects of a nonsense mutation versus the previously described deleterious polymorphism, (LIAVA), both of which differ from multiple and single-gene deutans. Our results help refine the relationship between opsin genotype and cone photoreceptor mosaic phenotype.


GSK-3beta inhibitors reduce protein degradation in muscles from septic rats and in dexamethasone-treated myotubes.
Sepsis is associated with muscle wasting, mainly reflecting increased muscle proteolysis. Recent studies suggest that inhibition of GSK-3beta activity may counteract catabolic stimuli in skeletal muscle. We tested the hypothesis that treatment of muscles from septic rats with the GSK-3beta inhibitors LiCl and TDZD-8 would reduce sepsis-induced muscle proteolysis. Because muscle wasting during sepsis is, at least in part, mediated by glucocorticoids, we also tested the effects of GSK-3beta inhibitors on protein degradation in dexamethasone-treated cultured myotubes. Treatment of incubated extensor digitorum longus muscles with LiCl or TDZD-8 reduced basal and sepsis-induced protein breakdown rates. When cultured myotubes were treated with LiCl or one of the GSK-3beta inhibitors SB216763 or SB415286, protein degradation was reduced. Treatment of incubated muscles or cultured myotubes with LiCl, but not the other GSK-3beta inhibitors, resulted in increased phosphorylation of GSK-3beta at Ser9, consistent with inactivation of the kinase and suggesting that the other inhibitors used in the present experiments inhibit GSK-3beta by phosphorylation-independent mechanisms. The present results suggest that GSK-3beta inhibitors may be used to prevent or treat sepsis-induced, glucocorticoid-regulated muscle proteolysis.


Effects of thermal stimulation on neurons and astrocytes cultured from the rat median preoptic nucleus.
Warming or cooling of the median preoptic nucleus (MnPO) in-vivo evokes appropriate thermoregulatory responses. In the present study, we aimed to investigate whether single neurons (and astrocytes) of primary rat MnPO cell cultures maintain properties, which are consistent with their putative role within the central thermoregulatory structures. Using the fura-2 ratio imaging technique, we therefore measured changes of intracellular Ca concentrations ([Ca]i) in neurons of rat MnPO primary cultures stimulated by rapid cooling from 37 to 25°C, or warming from 37 to 45°C, or glutamate, the transmitter which transfers thermal information to MnPO neurons. In the first experiment, we tested the responses to external cooling in a group of 212 neurons. Overall, 165 of these neurons were responsive to stimulation with glutamate; just four of them responded to the cold-stimulus with an increase of [Ca]i, and only one of these neurons was responsive to stimulation with menthol. In the second experiment, 24 of 327 neurons and 23 of 241 astrocytes responded to external warming with quick and pronounced Ca signals. Another 33 (10%) neurons showed a moderate and slowly developing increase of [Ca]i during the warming, which reflected the temperature changes in the chamber. These data correspond to properties of MnPO neurons upon thermal stimulation obtained by other experimental approaches. Primary cultures derived from the rat MnPO can thus be used to investigate neuronal thermosensitive properties and their possible modulation by other stimuli.


Investigations of nontumoral hydrocephalus in children.
An analysis was made of 175 cases of pediatric nontumoral hydrocephalus. CT scan by itself permits a precise diagnosis in only one-third of the cases. However, when the clinical context suggests that hydrocephalus is secondary to certain conditions such as infection, bleeding, or trauma, CT scan may suffice, unless more advanced investigation permits more efficient treatment. When hydrocephalus is associated with brain malformations, however, more complete investigation is needed for a better understanding of the condition. Conventional contrast studies are quite safe, especially ventriculography which is easy to perform in this type of patient, who is usually investigated during the first 12 months of life.


Use of Palliative Care Services in a Tertiary Cancer Center.
Despite increasing prevalence of palliative care (PC) services in cancer centers, most referrals to the service occur exceedingly late in the illness trajectory. Over the years, we have made several attempts to promote earlier patient access to our PC program, such as changing the name of our service from PC to supportive care (SC). This study was conducted to determine the use of PC/SC service over the past 8 years. We reviewed billing data for all PC/SC encounters. We examined five metrics for use: inpatient consultations as a percentage of hospital admissions, ratio of inpatient consultations to average number of operational beds, time from hospital registration to outpatient consultation, time from advanced cancer diagnosis to consultation, and time from first outpatient consultation to death/last follow-up. Over the years, we found a consistent increase in patient referrals to the PC/SC program. In the inpatient setting, we found approximate doubling of the inpatient consultations as a percentage of hospital admissions and the ratio of inpatient consultations to hospital beds (from 10% to 19% and from 2.4 to 4.9, respectively; p < .001). In the outpatient setting, we observed variations in referral pattern between oncology services, but, overall, the time from consultation to death/last follow-up increased from 4.8 months to 7.9 months (p = .001), which was accompanied by a significant decrease in the interval to consultation from hospital registration and advanced cancer diagnosis (p < .001). We have observed a consistent annual increase in new patient referrals as well as earlier access for outpatient referrals to our SC service, supporting increased use of palliative care at our cancer center. In response to accumulating evidence on the benefits of palliative care (PC) referral to oncology patients, efforts are being made to increase PC use. This study, conducted at MD Anderson Cancer Center, demonstrates consistent annual growth in PC referrals, which was accompanied by a significant increase in the outpatient referral of patients with nonadvanced cancer and earlier referral of those with advanced cancer. However, significant variations in the referral patterns between oncology services were observed. These results have implications for other cancer centers looking to enhance use of PC services by having a business model that allows for appropriate space and staff expansion.


Enhancing robustness of interdependent network under recovery based on a two-layer-protection strategy.
The robustness of coupled networks has attracted great attention recently, because the spread of failures from one network to its coupled network makes the coupled networks more vulnerable. Most existing achievements mainly focused on the integrity properties of coupled networks. However, failures also exist when networks are being reconstructed. Moreover, existing node-protection methods which aim to enhance the robustness of coupled networks only protect the influential nodes in one layer. In this paper, firstly, a two-layer-protection strategy is proposed to enhance the robustness of coupled networks under their reconstruction. Secondly, we adopt five strategies based on different centralities to select influential nodes, and propose a two-layer vision for each of them. Lastly, experiments on three different coupled networks show that by applying the two-layer-protection strategy, the robustness of coupled networks can be enhanced more efficiently compared with other methods which only protect nodes in one layer.


Coverage and Prior Authorization Policies for Medications for Opioid Use Disorder in Medicaid Managed Care.
Medicaid is a key policy lever to improve opioid use disorder treatment, covering approximately 40% of Americans with opioid use disorder. Although approximately 70% of Medicaid beneficiaries are enrolled in comprehensive managed care organization (MCO) plans, little is known about coverage and prior authorization (PA) policies for medications for opioid use disorder (MOUD) in these plans. To compare coverage and PA policies for buprenorphine, methadone, and injectable naltrexone across Medicaid MCO plans and fee-for-service (FFS) programs and across states. This cross-sectional study analyzed MOUD data from 266 Medicaid MCO plans and FFS programs in 38 states and the District of Columbia in 2018. For each medication, the percentages of MCO plans and FFS programs that covered the medication without PA, covered the medication with PA, and did not cover the medication were calculated, as were the percentages of MCO, FFS, and all (MCO and FFS) beneficiaries who were covered with no PA, covered with PA, and not covered. In addition, MCO plan coverage and PA policies were mapped by state. Analyses were conducted from January 1 through May 31, 2022. Coverage and PA policies were compared for MOUD in 266 MCO plans and 39 FFS programs, representing approximately 70 million Medicaid beneficiaries. Overall, FFS programs had more generous MOUD coverage than MCO plans. However, a higher percentage of FFS programs imposed PA for the 3 medications (47.0%) than did MCOs (35.9%). Furthermore, although most Medicaid beneficiaries were enrolled in a plan that covered MOUD, 53.2% of all MCO- and FFS-enrolled beneficiaries were subject to PA. Results also showed wide state variation in MCO plan coverage and PA policies for MOUD and the percentage of Medicaid beneficiaries subject to PA. This cross-sectional study found variation in MOUD coverage and PA policies across Medicaid MCO plans and FFS programs and across states. Thus, Medicaid beneficiaries' access to MOUD may be heavily influenced by their state of residency and the Medicaid plan in which they are enrolled. Left unaddressed, PA policies are likely to remain a barrier to MOUD access in the nation's Medicaid programs.


Covid-19 vaccination during pregnancy: A mixed-methods study of attitudes in a sample of Italian women and the role of health professionals' communication.
We examined Italian pregnant women's attitudes about the diphtheria, tetanus, and pertussis (DTP) vaccine, seasonal influenza, and Covid-19 vaccines, healthcare professionals' (HP) communication, reasons and potential predictors for non-adherence. From August 2021 to January 2022, we carried out a cross-sectional study in Italy using an online self-administered questionnaire addressed to women of age and pregnant, designed using LimeSurvey and disseminated through social media. Questions explored vaccination attitude/perceptions, satisfaction, and trust in HPs' information. Thematic analysis of free-text responses was performed using MaxQDA 2022. Statistical analyses were performed using STATA. 1594 responses were obtained. 52% of women hesitated to be vaccinated against Covid-19 while pregnant. Information received by HPs was deemed incomplete by 56% of participants, unclear by 52%, and untrustworthy by 46%; 49% felt unsupported in their decision-making process. This variable was one predictor of vaccine hesitancy together with concern about vaccine safety in the multivariate model. The analysis of open-ended questions revealed a pervasive feeling of dissatisfaction. The perceived lack of adequate communication and support by HPs affected pregnant women's decision-making process on Covid-19 vaccination. HPs need to understand and communicate the importance of vaccination during pregnancy, learning to better tailor their messages.


Monolithically integrated dual-channel coherent receiver with widely tunable local oscillator for 100 Gbps dual-polarization quadrature phase shift keying applications.
We report implementation of a monolithically integrated 100 Gbps dual-polarization quadrature phase shift keying (DP-QPSK) wavelength tunable coherent receiver on a 1 mm×3 mm die that consists of a tunable C-Band local oscillator with a 40 nm range, eight 30 GHz photodetectors, and two parallel 90° optical hybrids. A BER of 10(-3) with an OSNR of 7.5 dB operating at 50 Gbps NRZ-QPSK data per channel is reported.


Denervation in the primary olfactory pathway of mice. IV. Biochemical and morphological evidence for neuronal replacement following nerve section.
Unilateral olfactory nerve section was performed in the mouse. Three biochemical markers of the olfactory chemoreceptor neurons: carnosine, carnosine synthetase activity and the olfactory marker protein, were measured in the olfactory bulb and epithelium. Parallel observations were made by light microscopy as well as at the ultrastructural level. The specific biochemical markers decrease rapidly in both bulb and epithelium and reach a minimum by the end of the first week after surgery. They then slowly return to 80% of control values by one month. Carnosinase activity in epithelium was essentially unaffected. These biochemical observations coincide temporally with the onset of degenerative changes seen morphologically, in both the bulb and epithelium. The degenerative changes persist for up to two weeks in the bulb and for about one week in the epithelium. At this time basal cell division and differentiation begins in the epithelium with subsequent regrowth of olfactory axons into the glomerular layer of the olfactory bulb with ther reappearance of olfactory axon terminals. The temporal coincidence of these biochemical and morphological observations suggests they are manifestations of the same process, and is consistent with the idea that the olfactory chemoreceptor neurons are perhaps unique in being able to be replaced from undifferentiated stem cells.


What is the most needed competence for newly graduated generation z nurses? Focus groups study.
Research conducted so far in the area of identifying competence needed for newly graduated nurses has allowed for the identification of both strengths and weaknesses of nurses beginning work. However, the analyses conducted so far requires supplements in terms of difficulties and the strengths in respect to competence of graduates from the currently entering Generation Z. To explore Generation Z newly graduated nurses' competence that increase their work efficiency and support them during periods of professional adaptation. A qualitative exploratory-descriptive design. Twenty-nine participants attended the interviews conducted in 4 focus groups: nursing students, newly graduated nurses, nurse managers and clinical nurses with at least 10 years of working experience. Qualitative research utilized focus groups that were conducted based on the same semi-structured interview, which ensured similar key topics were discussed by each group. The COREQ criteria were used in the reporting of this study. We determined the characteristics and difficulties of the adaptation period for newly graduated Generation Z nurses and identified six of the most needed competence: knowledge and the ability to use it in practice, communication skills, teamwork, openness to development, decision-making, coping with stress and empathy. The topics of self-confidence, assertiveness and empathy were also discussed in each group. Analysis based on focus groups identified good preparation in knowledge, openness to development and empathy; however, deficiencies were found in the other competence. Competence indicated as the most important in Generation Z nurses' practice were interrelated. Deficits in some of them can cause difficulties in using others.


The Double Jones Birefringence in Magneto-electric Medium.
In this paper, the Maxwell's equations for a tensorial magneto-electric (ME) medium are solved, which is an extension to the work on the uniaxial anisotropic nonmagnetic medium. The coefficients of the dielectric permittivity, magnetic permeability, and of the magneto-electric effect are considered as tensors. The polarization is shown lying in the plane of two perpendicular independent vectors, and the relationship for the transverse polarization is given. The propagation of an electromagnetic wave through a ME medium gives rise to double Jones birefringence. Besides, the condition for an independent phenomenon of D'yakonov surface wave in a magneto-isotropic but with magneto-electric medium is given, which is measurable experimentally when the incident angle is π/4. Lastly, it is shown that the parameter for the magneto-electric effect plays a role in the damping of the wave.


[Features of hybridization of domestic hen and guinea fowl and structuro-functional organization of hybrid chromosomes in comparison with original species].
Hybridization of the domestic hen and the guinea fowl is accompanied by low fertility of eggs, high embryonic mortality of hybrid embryos and feti at various development stages and absolute sterility of the hybrid progeny. Cytological analysis of the hybrids obtained reveals heteromorphity of the 6th pair of their chromosomes although the character of the DNA synthesis in this pair is unchanged and is inherited from the initial species. A program of the DNA synthesis in the sexual chromosomes of hybrids differs from that in parents and seems to be one of the main causes of their sterility.


An easy, fast, and efficient assay for the quantification of peptide Hepcidin-25 in serum and plasma with LC-MS/MS.
The peptide hormone hepcidin-25 plays an important role in iron metabolism. Low or high levels of hepcidin-25 are associated with various iron disorders; therefore, hepcidin-25 is an important biomarker. This study describes an easy and fast analytical assay for the quantification of hepcidin-25 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample preparation was performed by protein precipitation with trichloroacetic acid, and injection onto a LC-MS/MS was directly conducted from a LoBind 96-well plate. The concentration range covered by the quality control samples, ranged from 0.25 nmol/L (12.3% CV) to 11.9 nmol/L (CV < 9%). Matrix effect was limited (mean recovery of 99.9% with a CV of 6.4%). The assay was validated for serum, EDTA and heparin plasma. An international secondary reference material was used for calibration. The reference interval (90% CL) was estimated for hepcidin-25 by analysing serum and plasma samples from 156 healthy subjects with a lower limit: 0.12 (0.07-0.19) and upper limit: 11.2 nmol/L (9.5-13.0). We present a fast and easy assay for the quantification of hepcidin-25 in serum and plasma samples. The assay was successfully used for the detection of various forms of hereditary haemolytic anaemias, to characterize the interplay between erythropoiesis and iron levels.


The molecules recognized by anti-MT2 alloantisera and anti-MT2-like (DRw52) monoclonal antibodies are different.
The human class II alloantigens include the HLA-DR, DQ, and MT determinants. Previous reports in the literature suggest that while the DQ determinants appear to be on a molecule separate from DR, the MT determinants are variably present on DR or DQ molecules. We have previously reported, using the homozygous DR5 cell line Swei, that the MT4 determinant defined by the allosera, MGH88B, was only on the DQw3 molecule, while MT2, defined by the functionally monospecific anti-MT2 alloantiserum MGH87B, was present on both the DR5 and DQw3 molecules. We now report using the monoclonal antibody ILR2 directed against an MT2-like determinant DRw52, that DRw52 is present on the DR molecules only. The MT2 determinant(s) recognized by the functionally monospecific alloantisera MGH87B appear to include the DRw52 determinant(s) recognized by the monoclonal antibody ILR2.


Antidepressants in short-term treatment of binge eating disorder: systematic review and meta-analysis.
To evaluate the effects of antidepressant interventions for patients with Binge Eating Disorder (BED). A systematic review and meta-analysis of available randomized controlled trials including a quality appraisal was conducted. Six databases: PUBMED, EMBASE, PSYINFO, LILACS, The Cochrane Collaboration Controlled Trials Register and The Cochrane Depression, Anxiety and Neurosis Group Database of Trials were searched using an electronic search strategy. Articles published during the period from January 1994 to December 2005 were included. From the 3357 articles initially identified, 19 full manuscripts were selected and analyzed and 7 studies fulfilled the inclusion criteria and were included in the final analysis. Data from the meta-analysis revealed that binge-eating remission rates were higher in patients receiving antidepressants when compared with placebo. No difference in body weight has been found as measured by short-term change in body mass index. Most studies were short-term trials (median duration: 8 weeks). The only 16-week duration study did not show superiority of antidepressants over placebo. Available data are not sufficient to formally recommend antidepressants as a single first line therapy for both short-term remission of binge-eating episodes and weight reduction in patients with BED. BED is a chronic condition and very short-term studies (8 weeks) may be of limited value.


Establishing priorities for evaluation and evaluation research: a nursing perspective.
After a brief definition of evaluation research, research priorities set by the American Nurses' Association and other nursing organizations are reviewed and a framework for establishing nursing research priorities is suggested.


Dissociation of the PAF-receptor from NADPH oxidase and adenylate cyclase in human neutrophils results in accelerated influx and delayed clearance of cytosolic calcium.
The magnitude and duration of the abruptly occurring increases in cytosolic Ca2+ in human neutrophils following activation with PAF (20 and 200 nM) and FMLP (1 microM), have been compared and related to alterations in NADPH oxidase activity, membrane potential and intracellular cyclic AMP. Cytosolic Ca2+ and membrane potential were measured by spectrofluorimetry, transmembrane fluxes of Ca2+ by radiometric procedures, and NADPH oxidase activity and cyclic AMP by chemiluminescence and radioimmunoassay respectively. Activation of neutrophils with both PAF (200 nM) and FMLP (1 microM) was accompanied by an abrupt increase in cytosolic Ca2+, which was of similar magnitude for each activator (393+/-9 and 378+/-17 nM respectively). Unlike FMLP-activated cells in which Ca2+ was rapidly removed from the cytosol, peak levels of cytosolic Ca2+ were sustained for longer (0.14+/-0.02 vs 1.16+/-0.04 min, P<or=0.0001) and declined at a slower rate in PAF-treated neutrophils. The prolonged elevation of cytosolic Ca2+ in PAF-treated cells was due to accelerated store-operated influx of extracellular cation and was attenuated by dibutyryl cyclic AMP (4 mM), the Ca2+-chelator, EGTA (5 mM), and SKF 96365 (10 microM). In contrast to FMLP, basal levels of superoxide production and cyclic AMP were unaltered in PAF-activated neutrophils, while only moderate membrane depolarization was detected. These observations demonstrate that mechanisms which restore Ca2+ homeostasis to FMLP-activated neutrophils, viz. activation of NADPH oxidase and adenylate cyclase, are not operative in PAF-treated cells, presenting the potential hazard of Ca2+ overload and hyperactivity.


Theranostic nanocarriers combining high drug loading and magnetic particle imaging.
We report preparation of theranostic nanocarriers loaded with up to 50 wt% of the anticancer drug doxorubicin that contain magnetic nanoparticles which enable Magnetic Particle Imaging (MPI), an emerging technology for quantitative and unambiguous imaging of the nanocarriers. The nanocarriers, coated with poly(ethylene glycol)-block-poly(lactic acid) (PEG4.9kD-b-PLA6kD) block copolymer for colloidal stability, are composed of a hydrophobic core of precipitated hydrolysable doxorubicin prodrug (proDox) and magnetic nanoparticles. Transmission electron microscopy (TEM) shows evidence of precipitated proDox for nanocarriers with high drug loading of up to 50 wt%. MPI measurements show that the nanocarriers can be quantitatively imaged. The nanocarriers are internalized by MDA-MB-231 cells and their IC50 value via metabolic assay is 1.1 µM, compared to 0.21 µM for free doxorubicin. The release rate from the nanocarriers was dependent on environmental pH. These nanocarriers with high drug loading and quantitative imaging are promising candidates for future applications.


Impacts of the psychological stress response on nonsuicidal self-injury behavior in students during the COVID-19 epidemic in China: the mediating role of sleep disorders.
The sudden outbreak of COVID-19 had a great impact on the physical and mental health of people all over the world, especially for students whose physical and mental development was not yet mature. In order to understand the physical and mental conditions of students during the epidemic period and provide a theoretical basis for coping with psychological problems in public health emergencies, this study explored the mediating role of sleep disorders in the effect of the psychological stress response (PSR) on non-suicidal self-injury (NSSI), along with the moderating role of emotional management ability (EMA). The SRQ-20, Pittsburgh Sleep Quality Index, NSSI Behavior Questionnaire, and Emotional Management Questionnaire were used to investigate the mental health of Chinese students in April 10-20 (Time point 1, T1) and May 20-30 (Time point 2, T2), 2020. A total of 1,955 students (Mage = 19.64 years, 51.4% male) were examined at T1 and 342 students (Mage = 20.06 years, 48.2% male) were reassessed at T2. Overall, the detection rate of PSR and NSSI were 17.60% (n = 344) and 24.90% (n = 486) respectively in the T1 sample, and were 16.37% (n = 56) and 25.44% (n = 87), in the T2 sample. We also found that sleep disorders played a mediating role in the effect of PSR on NSSI in the T1 and T2 samples. In addition, EMA was shown to regulate the effect of PSR on sleep disorders and the effect of sleep disorders on NSSI in the T1 samples. We found that PSR resulting from public health emergency might lead to NSSI behaviors in individuals. PSR may also cause sleep disorders, which can bring about NSSI. However, these effects were also moderated by the EMA. This research expands our understanding of PSR and NSSI in students during the pandemic.


Unlocking the potential of Mesenchymal stem cells in liver Fibrosis: Insights into the impact of autophagy and aging.
Liver fibrosis is a chronic liver disease characterized by extracellular matrix protein accumulation, potentially leading to cirrhosis or hepatocellular carcinoma. Liver cell damage, inflammatory responses, and apoptosis due to various reasons induce liver fibrosis. Although several treatments, such as antiviral drugs and immunosuppressive therapies, are available for liver fibrosis, they only provide limited efficacy. Mesenchymal stem cells (MSCs) have become a promising therapeutic option for liver fibrosis, because they can modulate the immune response, promote liver regeneration, and inhibit the activation of hepatic stellate cells that contribute to disease development. Recent studies have suggested that the mechanisms through which MSCs gain their antifibrotic properties involve autophagy and senescence. Autophagy, a vital cellular self-degradation process, is critical for maintaining homeostasis and protecting against nutritional, metabolic, and infection-mediated stress. The therapeutic effects of MSCs depend on appropriate autophagy levels, which can improve the fibrotic process. Nonetheless, aging-related autophagic damage is associated with a decline in MSC number and function, which play a crucial role in liver fibrosis development. This review summarizes the recent advancements in the understanding of autophagy and senescence in MSC-based liver fibrosis treatment, presenting the key findings from relevant studies.


In vivo imaging of cartilage degeneration using microCT-arthrography.
In vivo imaging of cartilage degeneration in small animal models is nowadays practically impossible. In the present study, we investigated the use of micro-computed tomography (microCT) in combination with a negatively charged ionic iodine dimer (ioxaglate) for in vivo assessment of cartilage degeneration in a small animal model. Cartilage degeneration was induced in the right knee of rats by injection of mono-iodoacetate (MIA). We imaged the rat knees with ioxaglate enhanced microCT-arthrography at 4, 16 and 44 days after MIA injection. Subsequently, microCT-arthrographic findings were evaluated and compared with quantitative histology of the patellar cartilage. In vivo microCT-arthrography clearly detected cartilage degeneration in the rat knee-joints, in which the ioxaglate diffused into the degenerated cartilage layer. Higher microCT-attenuation values and smaller total volumes of the cartilage layer were detected at longer time periods after MIA injection, which is quantitatively confirmed by histology. In vivo microCT-arthrography is a valuable tool for detection of minor cartilage alterations and distinguishes different stages of cartilage degeneration in a small animal model. Since microCT, at the same time, also visualizes osteophyte formation and changes in the underlying subchondral bone structures, the technique will be very useful for longitudinal overall assessment of the development of (osteo)arthritis and to study interventions in small animal models.


1,4-Naphthoquinone accumulates reactive oxygen species in Staphylococcus aureus: a promising approach towards effective management of biofilm threat.
Staphylococcus aureus, a Gram-positive opportunistic microorganism, promotes pathogenicity in the human host through biofilm formation. Microorganisms associated with biofilm often exhibit drug-resistance property that poses a major threat to public healthcare. Thus, the exploration of new therapeutic approaches is the need of the hour to manage biofilm-borne infections. In the present study, efforts are put together to test the antimicrobial as well as antibiofilm activity of 1,4-naphthoquinone against Staphylococcus aureus. The result showed that the minimum bactericidal concentration (MBC) of this compound was found to be 100 µg/mL against Staphylococcus aureus. In this regard, an array of experiments (crystal violet, biofilm protein measurement, and microscopic analysis) related to biofilm assay were conducted with the sub-MBC concentrations (1/20 and 1/10 MBC) of 1,4-naphthoquinone. All the results of biofilm assay demonstrated that these tested concentrations (1/20 and 1/10 MBC) of the compound (1,4-naphthoquinone) showed a significant reduction in biofilm development by Staphylococcus aureus. Moreover, the tested concentrations (1/20 and 1/10 MBC) of the compound (1,4-naphthoquinone) were able to reduce the microbial motility of Staphylococcus aureus that might affect the development of biofilm. Further studies revealed that the treatment of 1,4-naphthoquinone to the organism was found to increase the cellular accumulation of reactive oxygen species (ROS) that resulted in the inhibition of biofilm formation by Staphylococcus aureus. Hence, it can be concluded that 1,4-naphthoquinone might be considered as a promising compound towards biofilm inhibition caused by Staphylococcus aureus.


Boronic acid disk tests for identification of extended-spectrum beta-lactamase production in clinical isolates of Enterobacteriaceae producing chromosomal AmpC beta-lactamases.
A study using boronic acid (BA) was designed to detect the extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae producing chromosomal AmpC beta-lactamases. A total of 197 clinical isolates of Enterobacter spp. (n=100), Serratia marcescens (n=62) and Citrobacter freundii (n=35) were analysed. Genes encoding ESBLs were detected by polymerase chain reaction (PCR) amplification followed by direct sequencing of PCR products. The Clinical and Laboratory Standards Institute confirmatory test detected only 72.1% of the ESBL-producing isolates. When a > or =5mm increase in the zone diameter of either the cefotaxime/clavulanic acid and/or the ceftazidime/clavulanic acid disks tested in combination with BA versus cefotaxime and/or ceftazidime containing BA was considered to be a positive for ESBL, the method detected 60 (98.4%) of the 61 isolates that harboured ESBLs and showed no false-positive results for ESBL-non-producing isolates. In conclusion, the BA disk test is a highly sensitive and specific method for the detection of ESBLs in Enterobacteriaceae producing chromosomal AmpC beta-lactamases.


Clinical outcomes among unresectable, locally advanced, and metastatic cutaneous squamous cell carcinoma patients treated with systemic therapy.
Prior studies of conventional chemotherapy or epidermal growth factor receptor inhibitors for advanced (ie, locally advanced cutaneous squamous cell carcinoma [laCSCC] or metastatic [mCSCC]) cutaneous squamous cell cancer enrolled ≤ 40 patients. This retrospective, observational study assessed real-world treatment patterns and clinical outcomes in patients with unresectable laCSCC or mCSCC using electronic health records of patients who initiated first-line (1L) systemic treatment from 1 January 2008 to 31 December 2015, with follow-up to 30 September 2017. The median duration of follow-up from 1L treatment was 10.1 months (range 0.03-67.6 months). Duration of therapy (DOT) and overall survival (OS) were assessed using Kaplan-Meier analysis. Response rate was calculated as the proportion of patients who achieved physician-assessed-response. Eighty-two patients were identified (17 laCSCC and 65 mCSCC). Median age at 1L treatment initiation was 75 years; 85% were male, 88% had an Eastern Cooperative Oncology Group performance status of 1, and 84% had received radiotherapy. The most common 1L regimens were carboplatin + paclitaxel (27%) and cetuximab monotherapy (24%). The median 1L DOT was 4.1 months for laCSCC and 2.3 months for mCSCC. The physician-assessed response rate for 1L therapy was 17.6% for laCSCC, and 18.5% for mCSCC. The median OS from 1L treatment initiation was 16.2 months for laCSCC, and 15.3 months for mCSCC. Only 24 patients (29%) received second-line therapy. This is the largest retrospective data set regarding patients with advanced CSCC treated with anticancer systemic therapy prior to approval of the anti-programmed cell death-1 antibody, cemiplimab. Efficacy was low in both laCSCC and mCSCC. These data provide historic benchmarks for outcomes in patients with advanced CSCC prior to Food and Drug Administration approval of cemiplimab-rwlc.


Adult periodontal comparison after treatment of palatally impacted canines aligned by conventional or accelerated minimally-invasive corticotomy-assisted orthodontic traction: A randomized controlled trial.
To compare the post-treatment periodontal status of the palatally impacted canines and their adjacent teeth treated by an accelerated minimally-invasive corticotomy-assisted method versus the conventional traction method. A parallel-group two-arm randomized controlled trial was conducted on patients with palatally or mid-alveolar unilateral impacted canines. Participants were randomly selected and allocated to receive the conventional treatment (CT) with a closed surgical approach, or accelerated treatment (CAT). The evaluated periodontal variables were periodontal pocket depth (PPD), keratinized tissue width (KTW), gingival recession level (GRL), papillary bleeding index (PBI) and Gingival Index (GI). All post-treatment periodontal measurements were performed two weeks after removing the fixed orthodontic appliance. In total, 46 patients were included (CT group: n=23; mean age: 20.26±2.17 years), or accelerated treatment (CAT group: n=23; mean age: 20.39±2.27 years). The differences between the two study groups were non-significant for all periodontal outcomes at all measurement points (P>.05). The mean total values of PPD around the aligned canine did not exceed 2mm (XPPD=1.99±0.25mm; 1.91±0.26mm, in the CT and CAT group, respectively, P=0.677). The results of total values of PPD on the adjacent teeth were nearly similar in the two study groups (mean difference: 0.12mm; 0.02mm, for the lateral incisor and the first premolar, respectively). Very low GRL values were detected in the two study groups. The use of corticotomy-assisted method did not impair the periodontal health in the short follow-up term. Both treatment modalities are considered acceptable in terms of post-treatment periodontal outcomes, as the gingival indices levels were at low values.


Pharmacokinetic aspects of digoxin-specific Fab therapy in the management of digitalis toxicity.
Digoxin intoxication occurs frequently and may require treatment with digoxin-specific Fab therapy. Little is known, however, regarding the biological fate of this compound. Pharmacokinetic studies have not been performed in healthy volunteers, but there are limited kinetic data from patients who have received therapy for the treatment of digoxin toxicity. Digoxin-specific Fab is eliminated via renal and nonrenal routes, having a volume of distribution slightly exceeding extracellular volume (0.40 L/kg) and an elimination half-life of 16 to 20 hours. Patients with renal impairment and end-stage renal disease have elimination half-life values that are prolonged up to 10-fold in magnitude, while volume of distribution is unaffected. Systemic clearance of digoxin-specific Fab is approximately 0.32 ml/min/kg in digoxin-toxic patients with preserved renal function. Renal failure also decreases Fab clearance by up to 75%. Therefore, Fab may reside in the serum of anephric patients for 2 to 3 weeks after administration. More important is the effect of Fab on the disposition of digoxin. Because digoxin-specific Fab has a stronger digoxin-binding affinity than do biological membranes, it can sequester tissue-bound and intracellular digoxin into the extracellular spaces. This results in a rapid increase in digoxin serum concentrations in the central compartment. Since the majority of digoxin is bound by Fab, it cannot interact with its biological receptor and thus reverses digoxin toxicity. The pharmacokinetic fate of total digoxin after administration of digoxin-specific Fab follows that of Fab. However, it appears that the elimination half-life of Fab is slightly shorter than that of total digoxin in patients with end-stage renal disease, suggesting that the clearance of Fab is slightly faster than that of total digoxin. Free digoxin concentrations fall rapidly after Fab administration and then rebound upwards within 12 to 24 hours. This rebound in free digoxin concentrations, however, is delayed by 12 to 130 hours in patients with renal dysfunction and end-stage renal disease. Rebound in free digoxin concentrations occurs during the initial phase of the biexponential decline of the serum concentration-time profile for digoxin-specific Fab, suggesting that distribution from the vascular spaces is the likely cause. Following the increase, free digoxin concentrations decline in a manner that is dependent on renal and nonrenal routes of elimination. During this time period it is evident that Fab retains it capability of binding digoxin while it resides in plasma. There is no evidence to support a dissociation between the Fab-digoxin complex over extended periods of time.(ABSTRACT TRUNCATED AT 250 WORDS)


Association between MGMT Promoter Methylation and Risk of Breast and Gynecologic Cancers: A Systematic Review and Meta-Analysis.
The role of the promoter methylation of O 6-methylguanine-DNA methyltransferase (MGMT) remains controversial for breast and gynecologic cancers. We conducted a meta-analysis to assess the association between hypermethylation of MGMT promoter and the risk of breast and gynecologic cancers. A comprehensive search was conducted in PubMed and Embase electronic databases up to 19th August 2017 for studies about the association between MGMT promoter hypermethylation and breast and gynecologic cancers. A total of 28 articles including 2,171 tumor tissues and 1,191 controls were involved in the meta-analysis. The pooled results showed that MGMT promoter methylation status was significantly associated with an increased risk of breast and gynecologic cancers (OR = 4.37, 95% CI: 2.68-7.13, P < 0.05). The associations were robust in subgroup analysis based on ethnicity, cancer type, methylation detection method, and control source. This meta-analysis indicated that MGMT hypermethylation was significantly associated with the risk of breast and gynecological cancers, and it may be utilized as a valuable biomarker in early diagnostics and prognostication of these cancers. Further efforts are needed to identify and validate this finding in prospective studies, especially in situation with new methylation testing methods and samples from plasma circulating DNA.


Haematologic parameters on various species of strigiformes and falconiformes.
Normal mean values for packed cell volume, total erythrocyte count, total leukocyte count, total protein and mean corpuscular volume were obtained from 37 species of Strigiformes and Falconiformes representing 207 individuals.


Acute Bronchiolitis: Is There a Role for Lung Ultrasound?
Viral bronchiolitis is a common cause of lower respiratory tract infection in the first year of life, considered a health burden because of its morbidity and costs. Its diagnosis is based on history and physical examination and the role of radiographic examination is limited to atypical cases. Thus far, Lung Ultrasound (LUS) is not considered in the diagnostic algorithm for bronchiolitis. PubMed database was searched for trials reporting on lung ultrasound examination and involving infants with a diagnosis of bronchiolitis. Eight studies were suitable. This review analyzed the current evidence about the potential usefulness of LUS in the clinical management of bronchiolitis. Literature supports a peculiar role of LUS in the evaluation of the affected children, considering it as a reliable imaging test that could benefit the clinical management of bronchiolitis.


Percutaneous management of benign biliary strictures with balloon dilation and self-expanding metallic stents.
Seventy patients with benign biliary strictures were treated by means of percutaneous balloon dilation and stenting. Patients with stenoses relapsing during catheter stenting (18/70) were treated with self-expanding metallic stents. Results were evaluated in 56 patients; in patients without sclerosing cholangitis (n = 47) the patency rate with both modalities of treatment was 96%, while in the patients with secondary sclerosing cholangitis (n = 9), it was 33%, for a total success rate of 86%. The average follow-up was 23 months (range 3-72 months). Major complications included one death for septic shock (1%), three severe hemorrhages (4%), two of which required arterial embolization, two pleural effusions (3%), and one liver abscess following arterial embolization. Moderate fever for 1-2 days was a common finding after percutaneous puncture and balloon dilation. Percutaneous management of benign biliary strictures so far has been attempted only in surgical failures or in complicated cases. In view of our midterm results it may well become the initial treatment in many patients.


Physical activity during school and after school among youth with and without intellectual disability.
Little is known about physical activity (PA) among children with intellectual disability (ID) or their reasons to take part in PA and sport. To investigate PA and PA patterns during school and after school among Icelandic children with mild-to-severe ID. Ninety-one children with ID and a matched group of 93 typically developed individuals (TDI) took part. PA was assessed with accelerometers and a questionnaire was used to collect data on PA behavior. TDI children were more active and less sedentary than children with ID (p<0.001). Both sexes with ID were more active and less sedentary during school than after school (p<0.003) but no difference was found among TDI children. Children with ID (60%) were more likely to name weight loss as a reason to participate in PA than TDI children (34%, p=0.002) but a higher proportion (96%) of TDI children than children with ID (50%) participated in PA to improve skills (p<0.001). Children with ID depend more on schools to accumulate their PA and their reasons for PA participation differ from TDI children. This needs to be considered when designing and implementing PA promotion campaigns for children with ID.


Increased expression of C5a receptor (CD88) mRNA in canine mammary tumors.
Mammary tumors are among the most common neoplastic conditions in dogs, and there is evidence that inflammation plays a role in the development of some tumor types in dogs. The complement system is a major participant in the inflammatory process and the complement activation component, C5a, is a potent inflammatory peptide. This study investigated the mRNA expression of the major receptor for C5a (C5aR; CD88) in histopathological samples of canine mammary tumors by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using canine-specific primers for CD88. A total of seven canine mammary tumors (four malignant carcinomas, two benign mixed mammary tumors, and one myoepithelioma) and eight normal mammary glands were analysed. All the tumor samples expressed low levels of CD88 mRNA, while none of the normal mammary tissues showed any detectable expression. These preliminary results suggest that C5a-CD88 interaction may play a contributory role in the inflammatory response associated with mammary tumor development in dogs. Further studies investigating the mechanisms behind complement activation and C5a receptor expression in canine mammary tumors are warranted.


Sustaining Maternal and Neonatal Tetanus Elimination (MNTE) in countries that have been validated for elimination - progress and challenges.
As of October 2021, 47 (80%) of the 59 countries, identified at highest risk for Maternal and Neonatal Tetanus (MNT), had been validated for elimination. We assessed sustainability of MNT elimination (MNTE) in 28 countries that were validated during 2011‒2020. We assessed the attainment of the following MNTE sustainability indicators: 1) ≥ 90% coverage with three doses of Diphtheria-Tetanus-Pertussis vaccine (DTP3) among infants < 1 year, 2) ≥ 80% coverage with at least two doses of tetanus toxoid-containing vaccine (TTCV2 +) among pregnant women, 3) ≥ 80% protection at birth (PAB), 4) ≥ 70% skilled birth attendance (SBA), and 4) ≥ 80% first (ANC1) and fourth antenatal care (ANC4) visits. We assessed the introduction of TTCV booster doses. Data sources included the 2020 WHO /UNICEF Joint Reporting Forms, and the latest Demographic and Health Survey (DHS) or Multi-Indicator Cluster Surveys (MICS) for each country, if available. We reviewed literature and used DHS/MICS data to identify barriers to sustaining MNTE. Of 28 assessed countries, 7 (25%) reported ≥ 90% DTP3 coverage, 4 of 26 (16%) reported ≥ 80% TTCV2 + coverage, and 23 of 27 (85%) reported ≥ 80% PAB coverage. Based on DHS/MICS in 15 of the 28 countries, 10 (67%) achieved ≥ 70% SBA delivery, 13 (87%) achieved ≥ 80% ANC1 visit coverage, and 3 (20%) ≥ 80% ANC4 visit coverage. We observed sub-optimal coverage in many countries at the subnational level. The first, second and third booster doses of TTCV respectively have been introduced in 6 (21%), 5 (18%), and 1 (4%) of 28 countries. Only three countries conducted post-MNTE validation assessments. Barriers to MNTE sustainability included: competing program priorities, limited resources to introduce TTCV booster doses and implement corrective immunization in high-risk districts and socio-economic factors. Despite good performance of MNTE indicators in several countries, MNTE sustainability appears threatened in some countries. Integration and coordination of MNTE activities with other immunization activities in the context of the Immunization Agenda 2030 lifecourse vaccination strategy such as providing tetanus booster doses in school-based vaccination platforms, during measles second dose and HPV vaccination, and integrating MNTE post-validation assessments with immunization program reviews will ensure MNTE is sustained.


Observation of induction period and oxygenated intermediates in methane oxidation over Pt catalyst.
Selective oxidation of methane is one of the most attractive routes for methane to chemicals. However, mechanistic understanding and avoiding over-oxidation have great challenges because of its very rapid reaction rate. Herein, a capillary micro-reaction system was introduced to monitor the initial stage of methane oxidation over platinum. For the first time, an induction period is observed, during which oxygenated intermediates, such as methanol, acetone, methyl methoxy acetate, etc., are detected. Induction period can be shortened by methane pretreatment at 600°C, which generates highly active species containing unsaturated bonds. Combined these findings and observations of in situ characterizations, the evolution route of methane oxidation over Pt is prosed, i.e., the reaction starts from the formation of initial species containing Pt-C bond, followed by the generation of oxygenated intermediates, and ended with the over-oxidation of the intermediates to CO/CO2.


Impaired language performance in young children with heavy prenatal alcohol exposure.
The aims of this study were to evaluate the language abilities of young children with heavy prenatal alcohol exposure and to determine if these abilities represent a relative strength or weakness for this population. Two matched groups of children (ages 3 to 5) completed the Clinical Evaluation of Language Fundamentals, Preschool version: 25 children with heavy prenatal alcohol exposure (ALC) and 26 non-exposed controls (CON). Consistent with previous research, the CON group had significantly higher full scale IQ (FSIQ) scores than the ALC group. Receptive and expressive language skills of the two groups were compared. The ALC group had significantly poorer language skills than the CON group and both groups had better receptive than expressive abilities. Language performance did not significantly deviate from what would be predicted by FSIQ for either group. These results indicate that receptive and expressive language abilities are impaired in children with heavy prenatal alcohol exposure but not more so than general intellectual functioning. However, these deficits are likely to impact the social interactions and behavioral adjustment of children with prenatal alcohol exposure.


Knee osteoarthritis pain following medial meniscectomy in the nonhuman primate.
A number of promising compounds developed for osteoarthritic pain have failed to demonstrate clinical efficacy. To enhance preclinical translational research for osteoarthritis, a model of knee osteoarthritis pain was developed in Macaca fascicularis and the effects of two distinct pharmacological classes of drugs were tested on pain-related behavior. Behavioral assessments were developed specifically for the macaque. Baseline knee pressure threshold and weight bearing were assessed prior to a unilateral medial meniscectomy (MMx). Fifteen days following MMx, macaques underwent a once daily exercise regimen for 36 days. Sixty-seven days following MMx, macaques were assigned to one of three treatment groups (n = 3/group), either non-steroidal anti-inflammatory drug (NSAID) diclofenac, NK1 receptor antagonist aprepitant or vehicle, and treated for 5 days. Animals were tested 3-4 h after p.o. dosing and testing was performed blinded. Treatment utilized a crossover design-each animal received all treatments-and a 9-day washout period was utilized between treatments. Vehicle-treated macaques consistently demonstrated decreased ipsilateral pressure threshold ("hyperalgesia") and decreased weight bearing. While diclofenac increased weight bearing and pressure threshold, full attenuation of pain was not obtained. No significant improvement of either knee pressure or weight bearing was observed with aprepitant. Unilateral MMx in the macaque evoked pain-related behaviors and knee joint pathology reminiscent of osteoarthritis. The behavioral endpoints were sensitive to NSAID treatment but not sensitive to NK1 receptor block, which parallel clinical findings. The current macaque osteoarthritis model could be used to test potential treatments for osteoarthritis pain.