Initial stages of cell-matrix adhesion can be mediated and modulated by cell-surface hyaluronan.
A conceptual temporal and spatial gap exists between the first encounter of a cell with an adhesive substrate and the advanced stages of focal adhesion formation. Although ample information is available on focal adhesions structure and function, the mechanism of the first interaction events and the nature of the molecules mediating them are largely unknown. In this paper we identify cell-surface-associated hyaluronan as a mediator and modulator of the first steps of adhesion of A6 and other cells to conventional tissue culture substrates as well as to the surfaces of calcium-(R,R)-tartrate tetrahydrate crystals. Treatment of A6 cells with hyaluronidase suppresses their rapid interactions with these adhesive substrates, and incubation of either the hyaluronidase-treated cells or the substrate with hyaluronan restores cell adhesion. In contrast, excess hyaluronan on both the cells and the substrate strongly inhibits adhesion. We thus propose that cell-surface-associated hyaluronan can mediate and modulate cell-matrix adhesion at the very first encounter with the substrate. It may promote it through the establishment of exquisitely stereospecific chemical interactions or inhibit it by virtue of steric exclusion and/or electrostatic repulsion.


Detection of viral antibodies in camel sera using magnetic particle spectroscopy.
Pandemics like SARS-Cov-2 very frequently have their origin in different animals and in particular herds of camels could be a source of zoonotic diseases. This study took advantage on a highly sensitive and adaptable method for the fast and reliable detection of viral antibodies in camels using low-cost equipment. Magnetic nanoparticles (MNP) have high variability in their functionalization with different peptides and proteins. We confirm that 3-aminopropyl triethoxysilane (APTES)-coated MNP could be functionalized with viral proteins. The protein loading could be confirmed by simple loading controls using FACS-analysis (p < 0.05). Complementary combination of antigen and antibody yields in a significant signal increase could be proven by both FACS and COMPASS. However, COMPASS needs only a few seconds for the measurement. In COMPASS, the phase φn on selected critical point of the fifth higher harmonic (n = 5th). Here, positive sera display highly significant signal increase over the control or negative sera. Furthermore, a clear distinction could be made in antibody detection as an immune response to closely related viruses (SARS-CoV2 and MERS). Using modified MNPs along with COMPASS offers a fast and reliable method that is less cost intensive than current technologies and offers the possibility to be quickly adapted in case of new occurring viral infections. KEY POINTS: • COMPASS (critical offset magnetic particle spectroscopy) allows the fast detection of antibodies. • Magnetic nanoparticles can be adapted by exchange of the linked bait molecule. • Antibodies could be detected in camel sera without washing steps within seconds.


Monitoring groundwater contamination and delineating source zones at industrial sites: uncertainty analyses using integral pumping tests.
Field-scale characterisations of contaminant plumes in groundwater, as well as source zone delineations, are associated with uncertainties that can be considerable. A major source of uncertainty in environmental datasets is due to variability of sampling results, as a direct consequence of the heterogeneity of environmental matrices. We develop a methodology for quantifying uncertainties in field-scale mass flow and average concentration estimations, using integral pumping tests (IPTs), where the contaminant concentration is measured as a function of time in a pumping well. This procedure increases the sampling volume and reduces the effect of small-scale variability that may bias point-scale measurements. In particular, using IPTs, the interpolation uncertainty of conventional point-scale measurements is transformed to a quantifiable uncertainty related to the (unknown) plume position relative to the pumping well. We show that this plume position uncertainty generally influenced the predicted mass flows and average concentrations (of acenapthene, benzene and CHCs) to a greater extent than a boundary condition uncertainty related to the local water balance, considering 19 control planes at a highly heterogeneous industrial site in southwest Germany. Furthermore, large (order of magnitude) uncertainties only occurred if the conditions were strongly heterogeneous in the nearest vicinity of the well. We also develop a consistent methodology for an assessment of the combined effect of uncertainty in hydraulic conditions and uncertainty in reactive transport parameters for delimiting of both contaminant source zones and zones absent of source, based on (downgradient) IPTs.


(18)F-FDG PET and conventional imaging for assessment of Hodgkin's disease and non Hodgkin's lymphoma. An analysis of 193 patient studies.
The AIM of this study was to assess the diagnostic value of FDG-PET and conventional imaging (CI) in a large series of patient with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) at three time points during their course of disease. 169 consecutive lymphoma patients (69 HD; 100 NHL) were included. 193 FDG-PET studies were performed for staging at baseline in 42 cases, for post-therapeutic monitoring in 103, and for diagnosis of recurrence in 48 cases. Performance indices of sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and accuracy of metabolic FDG-PET and morphological CI were calculated. Differences in staging and diagnosis of residual or recurrent lymphoma were compared. FDG-PET changed staging in 36% of cases for staging at baseline, in 52% of cases for monitoring response to treatment, and in 29% for diagnosis of recurrence. FDG-PET staging results were confirmed in 80% for staging at baseline, in 74% for monitoring response to treatment, and in 50% for diagnosis of recurrence. FDGPET and CI differed significantly at monitoring response to treatment for sensitivity (0.91 versus 0.69; p < 0.02), specificity (0.90 versus 0.38; p < 0.00001), PPV (0.77 versus 0.42; p < 0.001), and accuracy (0.83 versus 0.55; p < 0.02). FDG-PET should be considered as the diagnostic modality of choice for post-therapeutic assessment of lymphoma patients and may be a reliable alternative to CI for staging at baseline and diagnosis of recurrence.


Saturable rate of cefatrizine absorption after oral administration to humans.
This study examined the absorption kinetics of cefatrizine, an amino-beta-lactam antibiotic, after oral administration of a single 500-mg dose to 12 healthy volunteers. Plasma concentrations were determined by high performance liquid chromatography. The plots of the percentage of drug unabsorbed and the apparent rate of cefatrizine absorption as a function of time showed, first, a delay and, then, an almost constant rate of absorption with a tendency to move toward first-order kinetics at the end of the process. Three compartmental models incorporating a lag time and first-order elimination kinetics, but differing in their input rate, were used for analysis of the time course of cefatrizine plasma concentrations. The model with first-order absorption kinetics was clearly inadequate. The results were improved with the model for which the rate of absorption is constant, but a model incorporating saturable absorption kinetics of the Michaelis-Menten type improved the fit further. This last model was statistically superior to the constant-rate input model in 6 out of 12 subjects, according to the likelihood-ratio method. Because of the innovative feature of the model incorporating the Michaelis-Menten equation, simulations of the effect of altering the model parameters and the dose administered on the concentration-time profile, were performed. Different hypotheses which might explain why cefatrizine absorption kinetics fits the Michaelis-Menten equation were examined. The observation of saturable absorption kinetics is consistent with a carrier-mediated transport previously reported to occur in the gastrointestinal tract of rats.


Prostaglandins and the initiation of labor.
A total of 96, dated pregnant, New Zealand white rabbits were studied. In 58 animals the intrauterine pressure (IUP) of the unstimulated and PGF2alpha-stimulated myometrium was recorded, by the extraovular microballoon technique, before, during and after parturition. In the remaining 38 the concentrations of PGE and PGF and progesterone (P) were measured by radioimmunoassays (RIA). The samples were collected individually or sequentially during the perinatal period from uterine tissue and uterine or peripheral vein blood. At the critical time, at around parturition, when the myometrium is converted from a suppressed and refractory muscle into a spontaneously active and reactive organ (quantitated by recording the IUP), the uterine PGE and PGF levels decreased rather than increased (quantitated by RIA). Thus, this critical regulatory and functional change of the myometrium cannot be accounted for by an increase in the intrinsic uterine stimulant: PG, but only by a decrease in the suppressor: P. These findings, 46 years after the discovery of P, demand the further exploration of Corner's legacy.


A possible correlation between the degree of karyotype aberrations and the rate of sister chromatid exchanges in lymphoma lines.
The sister chromatid exchange (SCE) frequencies of six freshly established and two old cell lines derived from patients with lymphatic tumors or leukemia were compared to the SCE rates of lymphoblastoid cell lines of normal controls. All cell lines from malignant tumors displayed significantly higher SCE values than the control lines. In general, the SCE rates seem to be correlated to the number of chromosomal markers and the degree of karyotypic instability of each line.


Recent Advances in Glioma Therapy: Combining Vascular Normalization and Immune Checkpoint Blockade.
Glioblastoma (GBM) accounts for more than 50% of all primary malignancies of the brain. Current standard treatment regimen for GBM includes maximal surgical resection followed by radiation and adjuvant chemotherapy. However, due to the heterogeneity of the tumor cells, tumor recurrence is often inevitable. The prognosis of patients with glioma is, thus, dismal. Glioma is a highly angiogenic tumor yet immunologically cold. As such, evolving studies have focused on designing strategies that specifically target the tyrosine kinase receptors of angiokines and encourage immune infiltration. Recent promising results from immunotherapies on other cancer types have prompted further investigations of this therapy in GBM. In this article, we reviewed the pathological angiogenesis and immune reactivity in glioma, as well as its target for drug development, and we discussed future directions in glioma therapy.


Corneal Epithelium Asymmetry in Children With Atopy: The Effect of Hand Dominance.
To evaluate the effect of eye rubbing on the epithelial thickness profile in tomographically normal corneas by AS-OCT and to compare right and left eyes in right-handed children. Thirty right-handed boys (mean age 11.2 years) with ocular allergy and history of eye rubbing were evaluated using Scheimpflug (Pentacam HR, Oculus Wetzlar, Germany) and anterior segment optical coherence tomography. Epithelial thickness (ET) and full corneal thickness (CT) parameters were compared between right and left eyes with a non-parametric Mann-Whitney test. A p-value lower than 0.05 was considered for statistical significance. No eyes had topometric nor tomographic criteria for keratoconus. The min-max ET was lower in right eyes (-2.8 µm vs -3.5; p = 0.02). The difference between inferior and superior (I-S) octants was lower in right eyes (1.1 µm vs 1.9 µm; p = 0.03) as a result of inferotemporal thinning. The highest ET difference was registered between nasal and temporal octants and was more pronounced in the right eyes (2 µm vs 3.1 µm; p < 0.001). AS-OCT analyses reveal different epithelial thickness patterns between the eyes in young atopic patients, likely eye rubbers. Inferior and temporal epithelial thickness seem to be more affected by thinning in the eye on the side of the dominant hand.


[Inoperable brain metastases from bronchogenic cancers. Value of combined chemotherapy with cisplatin and 5 fluorouracil].
We report the results of a combined of chemotherapy with CDDP and 5 FU repeated every 3 weeks in sixteen men (age range 31-73 years) with brain metastases. CT was performed after 2, 4 and 6 cycles to assess efficiency. Response was considered complete when no lesion was found on the CT scan and partial when the lesion shrunk to least half its the total volume. After two cycles, the response rate was 8/16 (50%). Treatment toxicity was mild with only one case of severe but reversible myelotoxicity (grade III). CDDP and 5 FU combined chemotherapy can be a useful treatment for brain metastasis of lung carcinoma.


Developing a Workforce for Health in North Carolina: Planning for the Future.
Among the many trends influencing health and health care delivery over the next decade, three are particularly important: the transition to value-based care and increased focus on population health; the shift of care from acute to community-based settings; and addressing the vulnerability of rural health care systems in North Carolina.


Targeted Integration Through Transformation of Hydroxyurea-Arrested Cells.
Homologous recombination is required to specifically target DNA to a desired genomic locus. Non-homologous end joining is the predominant form of recombination in Yarrowia lipolytica. Transformation of this organism with linear DNA therefore results in random integration of the introduced DNA into the genome. In this protocol, hydroxyurea-mediated cell cycle arrest is applied to significantly increase the rate of homologous recombination during transformation and enhance targeted integration.


Upregulation of endothelial cell-derived exosomal microRNA-125b-5p protects from sepsis-induced acute lung injury by inhibiting topoisomerase II alpha.
Emerging evidence has revealed that exosomal microRNAs (miRNAs) are implicated in human diseases. However, role of exosomal miR-125b-5p in sepsis-induced acute lung injury (ALI) remains further explored. We focused on the effect of exosomal miR-125b-5p on ALI progression via targeting topoisomerase II alpha (TOP2A). The ALI mouse models were established by cecal ligation and perforation, which were then treated with miR-125b-5p agomir or overexpressed TOP2A. Next, the pathological structure of ALI mouse lung tissues were observed, miR-125b-5p, TOP2A and vascular endothelial growth factor (VEGF) expression was determined, and the lung water content, inflammatory response, protein content in bronchoalveolar lavage fluid (BALF) and cell apoptosis in ALI mouse lung tissues were assessed. Exosomes were extracted from endothelial cells (ECs) and identified, which were then injected into the modeled mice to observe their roles in ALI. The targeting relationship between miR-125b-5p and TOP2A was confirmed. MiR-125b-5p was downregulated while TOP2A was upregulated in ALI mice. MiR-125b-5p elevation or ECs-derived exosomes promoted VEGF expression, improved pathological changes and restrained lung water content, inflammatory response, protein content in BALF and cell apoptosis in lung tissues ALI mice. TOP2A overexpression reversed the repressive role of miR-125b-5p upregulation in ALI, while downregulated miR-125b-5p abrogated the effect of ECs-derived exosomes on ALI. TOP2A was confirmed as a direct target gene of miR-125b-5p. Our study indicates that ECs-derived exosomes overexpressed miR-125b-5p to protect from sepsis-induced ALI by inhibiting TOP2A, which may contribute to ALI therapeutic strategies.


COVID-19 and the research scholarship ecosystem: help!
Data sharing practices remain elusive in biomedicine. The COVID-19 pandemic has highlighted the problems associated with the lack of data sharing. The objective of this article is to draw attention to the problem and possible ways to address it. This article examines some of the current open access and data sharing practices at biomedical journals and funders. In the context of COVID-19 the consequences of these practices is also examined. Despite the best of intentions on the part of funders and journals, COVID-19 biomedical research is not open. Academic institutions need to incentivize and reward data sharing practices as part of researcher assessment. Journals and funders need to implement strong polices to ensure that data sharing becomes a reality. Patients support sharing of their data. Biomedical journals, funders and academic institutions should act to require stronger adherence to data sharing policies.


Pediatric critical care.
Care of the ill and injured child requires knowledge of unique pediatric anatomic and physiologic differences. Subtleties in presentation and pathophysiologic differences impact management. This article discusses pediatric resuscitation, the presentation and management of common childhood illness, pediatric trauma, and common procedures required in the critically ill child.


Fretting-corrosion of CoCr-alloys against TiAl6V4: The importance of molybdenum in oxidative biological environments.
Periprosthetic fluids often contain reactive oxygen species, including H2O2, that are generated during inflammatory processes. Here, we investigated the fretting-corrosion behavior of CoCrX-alloys (X = Mo, Fe) in a complex protein-containing lubricant, with and without the addition of H2O2. Given the known protective role of molybdenum as an alloying element in metal degradation, we considered its effects by designing a two-way factorial experiment. The aim of the study was to investigate tribocorrosive mechanisms in modular joints of knee and hip prostheses. A previously described test-rig was used to run fretting corrosion tests of CoCrX-alloys with (X=Mo) and without (X=Fe) molybdenum against TiAl6V4 in bovine calf serum (BCS) with and without a physiological relevant H2O2 level (3 mM) in gross slip mode (4 Hz, ±50 μm, pmax=0.18 GPa, 37 °C, 50,000 cycles). Two CoCr-pins were pressed against a cylindrical TiAl6V4-rod, forming a line contact. Normal and frictional forces, the displacement, and the open circuit potential (OCP) were measured and recorded continuously. The dissipated frictional work was independent of alloy composition. The addition of H2O2 lowered the dissipated frictional work and increased wear, and this was significant in the absence of Mo. The mean OCP value was lower with Mo-containing than with Mo-free alloy in both pure BCS (p = .042), and BCS ± H2O2 (p < .0005). The wear scar was deeper for the Mo-free alloy, and this was significant (p = .013) in the presence of H2O2. These findings suggest a marked weakening of the passive film in the presence of H2O2, which is mitigated by the availability of Mo.


Calpain and caspase inhibitors protect vestibular sensory cells from gentamicin ototoxicity.
Apoptosis may play an important role in the mechanism of aminoglycoside ototoxicity. Caspases and calpains are regarded to be important factors in the regulation of cell death in the inner ear. We hypothesized that caspase or calpain inhibitors would protect hair cells from aminoglycoside ototoxicity. In order to test this hypothesis we carried out a pilot study to determine if gentamicin (GM) would induce caspase and calpain immunolabeling in guinea pig hair cells Having confirmed this we carried out the main experiment using guinea pig vestibular organ culture to determine if caspase and calpain would protect the hair cells from GM ototoxicity. Immunoreactivity for caspase-3 and m-calpain was detected in the vestibular sensory cells and ganglia after GM treatment. Both caspase and calpain inhibitors protected hair cells against gentamicin ototoxicity. It is suggested that inhibition of apoptosis is essential in order to block aminoglycoside ototoxicity.


Non-biological factors associated with tooth retention in Irish adults.
To identify non-biological factors associated with retention of natural teeth and sound untreated natural teeth among adults in Ireland. Data were collected in the 2000/'02 epidemiological survey of the oral health of Irish adults. Participants underwent a clinical oral examination in health board dental clinics and a detailed interview pertaining to oral and general health. The analysis is based on a random sample of adults aged 16-24 years (n = 1,196), 35-44 years (n = 978), and 65 years and older (n = 714). Dependent variables were number of natural teeth present (NT), number of sound untreated natural teeth (SUNT), likelihood of being dentate, having 21 or more NT (21+NT), 28 or more NT (28+NT), and 18 or more SUNT (18+SUNT). Socioeconomic status (SES) was based on being disadvantaged, occupation status and educational attainment. Behavioural factors included smoking, snacking, brushing frequency and dental visiting patterns. Bivariate and multivariate regression analyses were performed. Tooth retention decreased with increasing age group. Level of education, disadvantage status, being in employment, frequent brushing and visiting the dentist for a check-up (instead of when in need or pain) were associated with tooth retention. Attending for a check-up moderated the impact of disadvantage on tooth retention among 35-44 year-olds. The results of this study indicate that several non-biological determinants are important for dental health in this adult population.


Brefeldin A does not inhibit the movement of phosphatidylethanolamine from its sites for synthesis to the cell surface.
Brefeldin A, a fungal metabolite which interrupts trafficking of proteins via the Golgi by causing disassembly of the Golgi stacks, has been used to investigate the mechanism of movement of phosphatidylethanolamine (PtdEtn) from its sites of synthesis to the cell surface. PtdEtn is made in hepatocytes by two major pathways, (a) from CDP-ethanolamine on the endoplasmic reticulum and (b) by decarboxylation of phosphatidylserine in mitochondria. Monolayer cultures of rat hepatocytes were incubated with radiolabeled precursors of PtdEtn ([3H]ethanolamine or [3H]serine) in the presence or absence of brefeldin A. The movement of newly made PtdEtn to the plasma membrane was studied by treatment of intact cells with trinitrobenzene sulfonate which reacted only with PtdEtn on the outside surface of the cells to produce N-trinitrophenyl-PtdEtn; PtdEtn in intracellular membranes remained underivatized by this reagent. Using this method, the incorporation of radioactivity into cell surface and intracellular PtdEtn could be differentiated. The studies showed that PtdEtn made by the two different biosynthetic routes was rapidly transported to the outside leaflet of the plasma membrane. However, the kinetics and the extent of labeling of the cell surface PtdEtn, relative to that of the intracellular PtdEtn pool, were different from each labeled precursor. The incorporation of [3H]ethanolamine into PtdEtn on the cell surface gradually increased to a constant level of 1.8% of the label of intracellular PtdEtn after 3 h. In contrast, after 0.5-1 h, cell surface PtdEtn labeled from [3H]serine comprised 4% of the intracellular PtdEtn pool; the extent of labeling gradually declined to a constant level of approximately 2.4% by 3 h. Brefeldin A did not interrupt the movement of PtdEtn, derived from either biosynthetic origin, to the cell surface even though protein secretion was greatly reduced. Thus, apparently PtdEtn and proteins are independently transported to the cell surface of hepatocytes.


Defects in Protein Folding and/or Quality Control Cause Protein Aggregation in the Endoplasmic Reticulum.
Protein aggregation is now a common hallmark of numerous human diseases, most of which involve cytosolic aggregates including Aβ (AD) and ⍺-synuclein (PD) in Alzheimer's disease and Parkinson's disease. However, it is also evident that protein aggregation can also occur in the lumen of the endoplasmic reticulum (ER) that leads to specific diseases due to loss of protein function or detrimental effects on the host cell, the former is inherited in a recessive manner where the latter are dominantly inherited. However, the mechanisms of protein aggregation, disaggregation and degradation in the ER are not well understood. Here we provide an overview of factors that cause protein aggregation in the ER and how the ER handles aggregated proteins. Protein aggregation in the ER can result from intrinsic properties of the protein (hydrophobic residues in the ER), oxidative stress or nutrient depletion. The ER has quality control mechanisms [chaperone functions, ER-associated protein degradation (ERAD) and autophagy] to ensure only correctly folded proteins exit the ER and enter the cis-Golgi compartment. Perturbation of protein folding in the ER activates the unfolded protein response (UPR) that evolved to increase ER protein folding capacity and efficiency and degrade misfolded proteins. Accumulation of misfolded proteins in the ER to a level that exceeds the ER-chaperone folding capacity is a major factor that exacerbates protein aggregation. The most significant ER resident protein that prevents protein aggregation in the ER is the heat shock protein 70 (HSP70) homologue, BiP/GRP78, which is a peptide-dependent ATPase that binds unfolded/misfolded proteins and releases them upon ATP binding. Since exogenous factors can also reduce protein misfolding and aggregation in the ER, such as chemical chaperones and antioxidants, these treatments have potential therapeutic benefit for ER protein aggregation-associated diseases.


A simple radiological screening method for assessment of osteoporosis.
A simple radiological grading of osteoporosis of the hand using a postero-anterior radiograph is presented as a screening technique. Five gradings are discussed, and the relationship of osteoporosis between the hand and axial portions of the skeleton is underlined.


Effects of the calcium ionophore A23187 on airway responsiveness to histamine and substance P in guinea pigs.
We evaluated the mechanism of the airway hyperresponsiveness (AHR) induced by a calcium ionophore in guinea pigs. Airway responsiveness to intravenous histamine (HS) and substance P (SP) was measured 24 h after a 1-h exposure to aerosolized A23187 (0.03 or 0.1 mg/ml) or its vehicle (10% DMSO). Changes were assessed by calculating -logPC350HS and logPC350SP. Neutral endopeptidase (NEP) activity in the airway tissues, as well as the nitrite (NO2) levels and the cell population in bronchoalveolar lavage fluid (BALF) was determined after measurement of pulmonary function. Changes in SP-induced vascular permeability 24 h after exposure to A23187 were measured by the Evans Blue dye extravasation technique. Exposure to A23187 caused a significant AHR to SP, along with a significant increase in the number of neutrophils and epithelial cells in the BALF. While there was no significant change in NEP activity in the airway tissues, the levels of nitrite in the BALF were significantly decreased in A23187-exposed animals. Significant correlations were found between the number of epithelial cells in the BALF and logPC350SP (r = 0.477, p < 0.05) and between nitrite levels in the BALF and -logPC350SP (r = 0.491, p < 0.05) A23187 exposure did not significantly change the SP-induced airway microvascular leakage. These data suggest that A23187 exposure induced AHR to SP possibly by reducing NO levels in the airway tissues. This may be due to damaged airway epithelium and/or NO breakdown by activated inflammatory cells in the airways of these guinea pigs.


Isolation of IgG3 from normal human sera and from a patient with multiple myeloma by using protein A-sepharose 4B.
Affinity chromatography of IgG on protein A-Sepharose was used to isolate the human subclass IgG3 from normal serum and from a patient with multiple myeloma. The isolated material was purified by chromatography on Sephadex G-150 and characterized immunochemically. Ultracentrifugation studies gave so20,w values of about 6.80 for both normal and myeloma IgG3. Approximately 54 half-cystine residues per molecule of IgG3 were obtained as judged from amino acid analysis after performic acid oxidation of the proteins. Polyacrylamide gel electrophoresis in 0.1% sodium dodecyl sulfate of the isolated and reduced material resulted in two bands corresponding to molecular weights of approximately 23,000 and 56,000, respectively. The yield of normal human IgG3 represented 1%-2% of the total IgG.


Canonical Wnt signaling enhances pro-inflammatory response to titanium by macrophages.
Biomaterial characteristics like surface roughness and wettability can determine the phenotype of macrophages following implantation. We have demonstrated that inhibiting Wnt ligand secretion abolishes macrophage polarization in vitro and in vivo; however, the role of canonical Wnt signaling in macrophage activation in response to physical and chemical biomaterial cues is unknown. The aim of this study was to understand whether canonical Wnt signaling affects the response of macrophages to titanium (Ti) surface roughness or wettability in vitro and in vivo. Activating canonical Wnt signaling increased expression of toll-like receptors and interleukin receptors and secreted pro-inflammatory cytokines and reduced anti-inflammatory cytokines on Ti, regardless of surface properties. Inhibiting canonical Wnt signaling reduced pro-inflammatory cytokines on all Ti surfaces and increased anti-inflammatory cytokines on rough or rough-hydrophilic Ti. In vivo, activating canonical Wnt signaling increased total macrophages, pro-inflammatory macrophages, and T cells and decreased anti-inflammatory macrophages on both smooth and rough-hydrophilic implants. Functionally, canonical Wnt activation increases pro-inflammatory macrophage response to cell and cell-extracellular matrix lysates. These results demonstrate that activating canonical Wnt signaling primes macrophages to a pro-inflammatory phenotype that affects their response to Ti implants in vitro and in vivo.


Expression of emotion and quality of life after facial nerve paralysis.
To investigate the facial expression of emotion and quality of life in patients after long-term facial nerve paralysis. Cross-sectional. Facial nerve paralysis clinic. Twenty-four patients with facial nerve paralysis and 24 significant others (partner, relative, friend). Patients were assessed using Sunnybrook, Sydney, and House-Brackmann grading scales and SF-36, Glasgow Benefit Inventory, and Facial Disability Index quality-of-life measures. When patients identified themselves as either effective or not effective at facially communicating each of Ekman's primary emotions (happiness, disgust, surprise, anger, sadness, and fear), 50% classified themselves as not effective at expressing one or more of the six emotions. Significant others of the not effective patients rated the emotions as more difficult for their partner-patients to communicate facially than did the significant others of effective patients. The SF-36 quality-of-life survey revealed lower social functioning relative to physical functioning for not effective patients. From the Sunnybrook Facial Grading System, more synkinesis was found for those patients not effective at expressing happiness, less brow and eye movement for patients not effective at expressing sadness, and less voluntary movement for those not effective with surprise. Movement deficits associated with expressing specific emotions and an association with quality-of-life measures were identified in patients with long-term facial nerve paralysis who saw themselves as not effective at facial expression of emotions. To improve management of emotional expression in patients with facial nerve paralysis, a broader approach is recommended, linking the practitioner's treatment goals with patient-driven outcome goals.


Considerations on the clinical application of the human papillomavirus vaccine in Spain.
The circumstances that in the opinion of the authors influence the lower than expected uptake of the vaccine against human papillomavirus in Spain are analyzed. Among others, aspects related to doubts about efficacy and safety, the attitude of the Spanish health authorities or the role of media and the antivaccine groups, as well as the vaccination "culture" of the gynecologist, are discussed. The authors conclude that only with the coordinated effort of all involved bodies in the vaccination process (health authorities, scientific societies, social agents, media...) wide coverage of HPV vaccine will be achieved.


Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chloride and sucrose intake in rats.
GABA(A) and GABA(B) receptors are present in the lateral parabrachial nucleus (LPBN), a pontine area involved with inhibitory mechanisms related to the control of sodium appetite. Activation of GABA(A) receptors in the LPBN induces strong ingestion of 0.3 M sodium chloride (NaCl) in normonatremic and euhydrated rats. In the present study, we investigated the effects of the GABA(B) receptor agonist baclofen, injected alone or combined with GABA(A) or GABA(B) receptor antagonists into the LPBN on 0.3 M NaCl, water, 0.06 M sucrose and food intake in normonatremic and euhydrated rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. In normonatremic and euhydrated rats, bilateral injections of baclofen (0.5 nmol/0.2 μl) into the LPBN induced 0.3 M NaCl (24.0±3.1 vs. saline: 2.0±0.8 ml/240 min) and water intake (10.6±1.4 vs. saline: 3.5±0.7 ml/240 min) in a two-bottle test. Injections of GABA(B) receptor antagonists CGP 35348 (50 nmol/0.2 μl) or 2-hydroxysaclofen (5 nmol/0.2 μl) or GABA(A) receptor antagonist bicuculline (1.6 nmol/0.2 μl) into the LPBN reduced 0.3 M NaCl (14.1±4.7 ml/240 min; 9.97±2.5 ml/210 min; 8.8±5.9 ml/240 min, respectively) and water intake induced by baclofen injected into the LPBN. Baclofen (0.5 nmol/0.2 μl) injected into the LPBN also induced 0.06 M sucrose intake (21.8±5.9 vs. saline: 5.0±2.6 ml/180 min). Urinary volume and sodium excretion had a tendency to decrease after baclofen injection into the LPBN, whereas arterial pressure and food intake were not affected. The results show that baclofen injected into the LPBN, in normonatremic and euhydrated rats, produces a natriorexigenic effect dependent on GABA(A) and GABA(B) receptor activation. The natriorexigenic effect is not secondary to alterations in blood pressure or sodium urinary excretion. In addition, baclofen injected into the LPBN also induces 0.06 M sucrose intake.


Comparative Genomic Analysis of Pseudoxanthomonas sp. X-1, a Bromoxynil Octanoate-Degrading Bacterium, and Its Related Type Strains.
Most Pseudoxanthomonas species described have been derived from water, plants, or contaminated soils. Here, a strain Pseudoxanthomonas sp. X-1 isolated from bromoxynil octanoate (BO)-contaminated soil is presented. Strain X-1 could degrade BO and produce bromoxynil. The optimal conditions for degradation of BO by strain X-1 were an initial BO concentration of 0.1 mM, 30 °C, pH 7, and Mn2+ concentration of 1.0 mM. The bacterial morphological, physiological, and biochemical characteristics of strain X-1 were described, which showed differences comparing with other related type strains. The genome of strain X-1 was sequenced, and a comparative genomic analysis of X-1 and other Pseudoxanthomonas species was conducted to explore the mechanisms underlying the differences among these strains. The genome of strain X-1 encodes 4160 genes, 4078 of which are protein-coding genes and 68 are RNA coding genes. Specifically, strain X-1 encodes enzymes belonging to 778 Enzyme Commission (EC) numbers, much more than those of other related strains, and 62 of them are unique. Eight genes coding esterase are detected in strain X-1 which leads to the ability of BO degradation. This study provides strain, enzyme, and genome resources for the microbial remediation of environments polluted by herbicide BO.


Role of serum VEGF-A biomarker for early diagnosis of ovarian cancer instead of CA-125.
To assess the significance of serum vascular endothelial growth factor-A (VEGF-A) as a potential biomarker for the diagnosis of ovarian cancer instead of cancer antigen-125 (CA-125). The case-control study was conducted at the obstetrics departments of Sir Ganga Ram Hospital and Jinnah Hospital, Lahore, Pakistan, from April to September 2018, and comprised cases of epithelial ovarian tumour and healthy female controls. Serum VEGF-A and CA-125 levels were evaluated using Luminex multi-analyte profiling technology and enzyme immunoassays technique. Age, stage, grading, metastasis and ascites of ovarian cancer patients were investigated and compared with serum VEGF-A and CA-125 levels. Data was analysed using SPSS 20. Of the 89 subjects, 44(49.4%) were cases and 45(49.6%) were controls. Among the cases, 13(29.5%) were benign and 31(70.5%) were malignant. The mean serum VEGF-A values were inversely proportional to the stages of ovarian cancer i.e. stage I, II, III and IV showed 762.2pg/ml, 267.3pg/ml, 233.1pg/ml and 125.5pg/ml VEGF-A levels respectively. A steady increase in the mean serum CA-125 values with the progression of the disease was observed i.e. in stage I, II, III and IV the levels of CA-125 were 146.2U/ml, 268.5U/ml and 477.2U/ml and 844.4U/ml respectively. The detection of high concentrations of serum VEGF-A level supported its use as one of the diagnostic parameters in the timely investigation of ovarian cancer.


Processing stored stallion semen doses by Single Layer Centrifugation.
The purpose of this study was to determine if the quality of stored stallion semen doses could be enhanced by the scaled-up version of Single Layer Centrifugation using Androcoll-E-Large. Three semen doses from each of fifteen stallions were transported overnight to the Swedish University of Agricultural Sciences (SLU) for processing 24 h after semen collection. Sperm quality in the resulting SLC-selected samples was significantly improved compared to the uncentrifuged samples: mean progressive motility was increased by 8% on the day of processing (P < 0.001) and by 13% after 24 h cold storage (P < 0.001), normal morphology was increased by 4% (P < 0.01), whereas mean %DFI was decreased by 2% (P < 0.001). When these SLC-selected samples were compared retrospectively to fresh samples processed by SLC with Androcoll-E Small, sperm quality was found to be similar, although it was not maintained for as long in the sperm samples stored before SLC. These results suggest an additional option for improving sperm quality in stallion semen doses for artificial insemination.


Clomazone improves the interactions between soil microbes and affects C and N cycling functions.
Clomazone, a widely used herbicide, is mainly used in soybean fields. We previously found that clomazone alters Proteobacteria and Nitrospirae abundances and also alters urease activity, which result in changes in NH4+ and NO3- contents in soil nitrogen cycling. It remains unknown, however, how the co-occurrence patterns of species and functions of soil ecosystems change in response to clomazone applications in soil. We designed a 3-month greenhouse experiment to investigate soil microorganism dynamics in response to clomazone. Clomazone was applied at three doses (e.g., T1, T10, T100), which significantly increased bacterial abundance at days 15 and 60. Fungal abundance was stimulated at day 30 in T10-treated soils, whereas fungal abundances decreased in T100-treated soils at day 15. Clomazone altered bacterial and fungal community structures. Network analyses showed more complex and highly connected microbial communities in clomazone-treated soils. Moreover, an Acidobacteria-dominated cluster was identified within each network of clomazone-treated soils. Clomazone applied at the recommended rate decreased the functional groups that were associated with denitrification and hydrogen oxidation at days 15 and 60, and enhanced photoheterotrophy from days 30 to 60. High clomazone inputs increased trophic types (e.g., chemoheterotrophy, phototrophy, photoautotrophy and cyanobacteria) and C cycling functional groups (e.g., fermentation and cellulolysis). The half-life of clomazone ranged from 40.1 to 93.5 days in three cases. Our results provide important information for use of this herbicide.


Growth of enterotoxigenic Staphylococcus aureus in povi masima, a traditional Pacific island food.
To obtain preliminary data on the microbiology and hurdles to pathogen growth in the traditional Pacific Island food, povi masima, which is essentially beef brisket cured in brine. Six containers of povi masima were prepared and two were inoculated with five enterotoxigenic strains of Staphyloccocus aureus. The povi masima were divided into two lots each containing two uninoculated control and an inoculated container. Lot 1 was incubated at room temperature (20 degrees C) and lot 2 under refrigeration (4-5 degrees C) for up to 98 days. During storage, samples were removed and tested for aerobic plate count, coagulase-producing Staphylococci, Clostridium perfringens, staphylococcal enterotoxin and various chemical parameters of the food. Coagulase-producing Staphylococci and aerobic plate counts grew to high levels in both the inoculated and uninoculated lots stored at room temperature, but enterotoxin was only detected at one time point in these lots and this may represent a false positive result. The concentration of NaCl in the meat increased with time as concentrations equilibrated, and nitrite was rapidly lost in those lots stored at room temperature. Storage at 4-5 degrees C prevented proliferation of coagulase-producing Staphylococci. For safe curing and storage, this food should be kept under refrigeration as this prevented growth of staphylococci. Optimum storage would also be achieved with improved attempts to ensure equal distribution of NaCl prior to storage. Under conditions traditionally used to cure and store this food, enterotoxigenic staphylococci can grow to numbers where toxigenesis might occur, especially during the early stages of curing where the salt has not diffused from the brine into the meat.


Quantitative Characterization of Local Thermal Properties in Thermoelectric Ceramics Using "Jumping-Mode" Scanning Thermal Microscopy.
Thermoelectric conversion may take a significant share in future energy technologies. Oxide-based thermoelectric composite ceramics attract attention for promising routes for control of electrical and thermal conductivity for enhanced thermoelectric performance. However, the variability of the composite properties responsible for the thermoelectric performance, despite nominally identical preparation routes, is significant, and this cannot be explained without detailed studies of thermal transport at the local scale. Scanning thermal microscopy (SThM) is a scanning probe microscopy method providing access to local thermal properties of materials down to length scales below 100 nm. To date, realistic quantitative SThM is shown mostly for topographically very smooth materials. Here, methods for SThM imaging of bulk ceramic samples with relatively rough surfaces are demonstrated. "Jumping mode" SThM (JM-SThM), which serves to preserve the probe integrity while imaging rough surfaces, is developed and applied. Experiments with real thermoelectric ceramics show that the JM-SThM can be used for meaningful quantitative imaging. Quantitative imaging is performed with the help of calibrated finite-elements model of the SThM probe. The modeling reveals non-negligible effects associated with the distributed nature of the resistive SThM probes used; corrections need to be made depending on probe-sample contact thermal resistance and probe current frequency.


Implicit self-esteem and social anxiety: differential self-favouring effects in high and low anxious individuals.
This study was designed to investigate the role of negative self-image in social phobia. Participants were 19 high and 19 low socially anxious women. Because self-report measures of self-esteem are sensitive to self-presentation and impression management strategies, an implicit association test (IAT) was used to assess participants' self-esteem as well as their general evaluation of others ('other-esteem'). Socially anxious women displayed relatively low levels of self-esteem on self-report measures. However, at the implicit level, low and high anxious women were characterised by a similar, highly positive self-image. Both groups displayed a relatively low 'other-esteem'. Yet, this self-favouring effect was considerably weaker in high than in low anxious participants. The results provide no unequivocal support for the idea that low self-esteem plays an important role in social anxiety. Yet, rather than by low self-esteem per se, socially anxious people are characterised by a small discrepancy between esteem of self and others, and it may be this reduced tendency to self-favouring that is pivotal to social anxiety.


Genetic variability of the invasive cyanobacteria Cylindrospermopsis raciborskii from Bir M'cherga reservoir (Tunisia).
Cylindrospermopsis raciborskii is an invasive freshwater cyanobacteria of tropical origin, also found in temperate regions. Due to its known ability to produce potent toxins, such as cylindrospermopsin and the paralytic shellfish poisoning, this species is of major concern from a water quality perspective. This study presents a genetic characterization of four C. raciborskii strains isolated from the Bir M'cherga Tunisian reservoir. The toxicity assessment was investigated via molecular biology tools, which suggested that all the isolated strains were not producing cylindrospermopsin, saxitoxin, or microcystin. This result was further confirmed by HPLC and MALDI-TOF analyses. However, we report for the first time in C. raciborskii the presence of mcyA and mcyE, two segments of the microcystin synthetase mcy cluster. All the strains were identified taxonomically based on the 16S rRNA sequences, and their phylogenetic relationships were assessed using the rpoC1 region. Tunisian strains formed a distinct clade separated from the other African strains.


Validation of the Ramsay scale for invasive procedures under deep sedation in pediatrics.
The Ramsay scale is the most widely used scale during pediatric procedures although it has not been formally validated. To validate the Ramsay scale during invasive procedures under sedation in pediatrics. A prospective analytic study was conducted in two hospitals. All patients ≥6 months that were undergoing invasive procedures under sedation were enrolled. All were recorded, and these videos were edited and randomized. 150 videos were scored by four observers (a pediatrician, a pediatric intensive care unit nurse, an anesthetist, and an operating room nurse). All videos were scored with the Ramsay scale and University of Michigan Sedation Scale. Observers were blinded to drug administration. Construct validity was measured through Wilcoxon test paired samples after administration of sedatives. Criterion validity, intra-observer reliability, and interobserver correlation were evaluated by comparing the scores of the scales using Spearman's correlation coefficient. Interobserver agreement was measured using the intraclass correlation coefficient. To assess test-retest reliability, 50 videos were randomly selected and reevaluated. Sixty-five patients were included. Construct validity was demonstrated through changes in the Ramsay scale scoring after administration of sedatives (p < .0001). Regarding criterion validity, the Ramsay scale had a high correlation with the UMSS (ρ = 0.621). Intra-observer agreement was ρ = 0.884. The Ramsay scale showed interobserver reliability with an intraclass correlation coefficient = 0.94 when comparing it with the University of Michigan Sedation Scale. Internal consistency was α = 0.91. Regarding applicability, in our study, it was applied in two hospitals in different areas by four professionals from distinct categories. The Ramsay scale is valid, reliable, and applicable to monitoring sedation for invasive procedures under deep sedation in pediatrics.


Fatigue assessment and rehabilitation outcomes in patients with brain tumors.
This study seeks to investigate the fatigue severity and the relationship among fatigue and other associated factors in patients with brain tumors, and to evaluate the rehabilitation outcome on fatigue. We assessed 25 patients in whom brain tumors had been resected and transferred to the rehabilitation department of our hospital. Patients were evaluated for fatigue severity using the Piper Fatigue Scale (PFS) and the Brief Fatigue Inventory (BFI), for mood using the Beck Depression Inventory, for motor function using the Motricity Index (MI), for functional status using the Karnofsky Performance Status (KPS) scale and the Modified Barthel Index (MBI), and for quality-of-life using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (EORTC QLQ-C30). We also measured the levels of serum hemoglobin, C-reactive protein, albumin, and creatine kinase; and anthropometric variables before and 4 weeks after rehabilitation. Of the 25 patients, 21 (84.0%) reported fatigue during the previous week. The average PFS score was 4.6 ± 1.8 and the average BFI score 5.2 ± 2.2, indicating the moderate level of fatigue. Patients with recurrent tumors had significantly higher PFS scores than did those with initial tumors. Fatigue correlated significantly with the KPS, MBI, and EORTC QLQ-C30 physical functioning and insomnia scales. In addition, insomnia was a significant predictor of fatigue before rehabilitation, and the baseline fatigue scales, MBI, MI, and EORTC QLQ-C30 physical functioning scale were the important independent predictors of fatigue after rehabilitation. During rehabilitation, the KPS, MBI, and MI scores improved significantly, whereas total PFS and BFI scores did not change. These findings suggest that patients with brain tumors commonly complain of moderate level of fatigue, which may reduce daily functioning and quality of life, with sleep disturbance being a significant predictor of fatigue. During rehabilitation, functional outcomes and motor power showed improvements in those patients, not aggravating fatigue.


Sodium hypochlorite stress in Enterococcus faecalis: influence of antecedent growth conditions and induced proteins.
Compared with exponential growing bacteria, carbohydrate-starved cells of Enterococcus faecalis exhibit a high level of resistance to sodium hypochlorite with maximal resistance observed in cultures entering stationary phase. Chloramphenicol treatment, at various stages of growing phase, does not abolish the hypochlorite resistance of starved cells. However, Enterococcus faecalis conditioned by low sodium hypochlorite concentrations does not develop tolerance towards a lethal dose of the disinfectant. Two-dimensional gel analysis shows that protein synthesis is drastically turned off by hypochlorite treatment, whereas synthesis of a few proteins is enhanced by a low concentration of this chemical agent.


Iliolumbar ligament ossification in undifferentiated seronegative spondyloarthropathy.
The case of a man suffering from undifferentiated seronegative spondyloarthropathy (uSpA) without spine involvement and with iliolumbar ligament ossification is reported. Unlike a similar previously published case showing ossification only of the middle part of the left ligament, our patient had ossification of the whole course of both ligaments.


Biochemical properties and expression profile of human prolyl dipeptidase DPP9.
Dipetidyl peptidase 9 (DPP9) is a prolyl dipeptidase preferentially cleaving the peptide bond after the penultimate proline residue. The biological function of DPP9 is unknown. In this study, we have significantly improved the yield using Strep.Tactin purification system and characterized the biochemical property of DPP9. Moreover, the dimer interaction mode was investigated by introducing a mutation (F842A) at the dimer interface, which abolished the enzymatic activity without disrupting its quaternary structure. Furthermore, DPP9 was found ubiquitously expressed in fibroblasts, epithelial, and blood cells. Surprisingly, contrary to previous report, we found that the expression levels of DPP8 and DPP9 did not change upon the activation of the PBMC or Jurkat cells. These results indicate that the biochemical property of DPP9 is very similar to that of DPP8, its homologous protease. DPP9 and DPP8 are likely redundant proteins carrying out overlapping functions in vivo.


Sex differences in cigarette brand purchases among adult smokers: results from the DePICT national repeated survey of French adults (2016-2017).
The tobacco industry has been reported to employ sex-specific marketing strategies, which include different types of tobacco packaging, publicity, as well as price strategies. We examined whether characteristics associated with the purchase of more expensive cigarette brands varied by sex, in the context of the introduction of plain tobacco packaging and the strengthening of tobacco control policies in France. Our study population consists of 1380 regular smokers of manufactured cigarettes from the DePICT study, a nation-wide two-wave survey of French adults aged 18-64 years. Participants were interviewed by telephone in 2016 and 2017. Factors associated with the use of more vs. less expensive cigarette brands were determined by multivariable logistic regression stratified by sex. Several sex-specific factors were associated with the purchase of more expensive cigarette brands. In women, those factors included higher education, cannabis use, and no use of roll-your-own tobacco. While in men purchase of more expensive cigarette brands was linked to younger age, being born outside of France, living with a non-smoker, and attachment to the cigarette brand. Factors which predict tobacco purchase patterns are different in women and men, highlighting the need for sex-specific tobacco control initiatives to counter the tobacco industry's gendered marketing.


The origin of IgG-containing cells in the bursa of Fabricius.
The bursa of Fabricius of the chicken is known as a primary lymphoid organ for B-cell development. Morphologically, the origin of IgG-containing cells in the bursa has not been clear until now, because abundant maternal IgG (MIgG) is transported to the chick embryo and distributed to the bursal tissue around hatching. Thus, it has been difficult to find out whether these cells themselves biosynthesize IgG or if they acquire MIgG via attachment to their surface. Our present study employing in situ hybridization clarified that IgG-containing cells in the medulla of bursal follicles did not biosynthesize IgG. To study the role of MIgG in the development of those IgG-containing cells, MIgG-free chicks were established from surgically bursectomized hen (SBx-hen). We found that, on the one hand, deprivation of MIgG from chicks completely inhibited the development of IgG-containing cells in the medulla after hatching. On the other hand, administration of MIgG to MIgG-free chicks recovered the emergence of those cells. In addition, we observed that those cells did not bear a B-cell marker and possessed dendrites with aggregated IgG. These results demonstrate that IgG-containing cells in the medulla are reticular cells that capture aggregated MIgG. Moreover, we show that the isolation of the bursa from environmental stimuli by bursal duct ligation (BDL) suppressed the development of IgG-containing cells after hatching. Thus, it is implied that environmental stimulations play a key role in MIgG aggregations and dendritic distributions of aggregated MIgG in the medulla after hatching.


An LCA-based model for assessing prevention versus non-prevention of construction waste in buildings.
Waste generated by the Construction Sector represents an environmental problem in many countries. To achieve increasingly eco-efficient waste management, Life Cycle Assessment (LCA) provides an objective method for the quantification of the potential impact that waste management exerts on the environment. Traditionally, LCA has focused on the evaluation of non-prevention scenarios once the waste is generated, mainly by showing the benefits of recycling vs. disposal. Consequently, the literature has hardly addressed the positive environmental impacts caused by waste prevention, that is, the reduction at source, which constitutes the preferred option of any waste management hierarchy. Therefore, this study proposes a model to simulate the environmental performance of the prevention vs. the non-prevention of construction waste production. The model is applied to an urban system of residential buildings in Spain. The results provide evidence of the environmental benefits achieved with the prevention scenario. The prevention scenario reduces the construction waste generated in the non-prevention scenarios by up to 57%. Furthermore, it allows a potential reduction of up to 4.6 and 171.1 times the impact caused by the disposal scenario; and up to 1.7 and 8.3 times those of the recycling scenario. The model can be implemented in other contexts with other reference buildings, and enables the environmental benefits of reduction strategies to be studied, thereby providing a tool to guide and support decision-making during the building design stage. Moreover, the results obtained can help professionals and policymakers to incorporate effective construction waste prevention measures in waste prevention plans and programs.


Airway remodeling in asthma.
Airway remodeling is a summary term for the pathological changes that occur in airway structure in allergic or suppurative airway diseases. Characteristic changes of airway remodeling in asthma include goblet cell hyperplasia, deposition of collagens in the basement membrane zone, increased size and number of microvessels in the submucosa, hyperplasia and hypertrophy of airway smooth muscle, and hypertrophy of submucosal glands. Some of these changes, such as goblet cell hyperplasia and subepithelial collagen deposition, are present even in mild asthma; other changes such as increases in airway smooth muscle and gland volume appear to be more characteristic of severe asthma. Airway narrowing, airway hyperresponsiveness, and mucus hypersecretion are all functional consequences of airway remodeling leading to clinical manifestations such as dyspnea, wheeze, sputum production, and susceptibility to asthma exacerbations. Noninvasive measures of remodeling are lacking, and monitoring the effects of treatment on remodeling has been difficult. For this reason relatively little is known about the effects of current asthma treatments on airway remodeling. As mechanisms of airway remodeling are developed, it is hoped that novel therapeutic targets will be identified. Treatments specifically targeting mediators of remodeling hold promise as treatments that could modify disease progression in asthma.


Steroid stress hormone changes throughout the menstrual cycle: A rise in evening aldosterone concentration in early luteal phase precedes the symptoms of premenstrual syndrome.
There is still a lack of consistent evidence on dysregulation of steroid stress hormones cortisol and aldosterone in premenstrual syndrome (PMS). We aimed to test the hypothesis that, in healthy women, salivary aldosterone concentrations are higher in those with PMS compared to controls, particularly during the luteal phase of the menstrual cycle. In total, 99 female subjects (49 women with and 50 women without PMS) participated in a prospective non-interventional case-control study. Saliva sampling was performed in the follicular (day 8), early luteal (day 20) and late luteal phase (2 days before expected onset of bleeding) of the menstrual cycle in the morning and the evening. The results confirmed the hypothesis that salivary aldosterone concentrations are higher in women with PMS during the early luteal phase compared to controls (p < .01) in the evening. Early luteal phase aldosterone concentrations positively correlated with the frequency of premenstrual symptoms. Women with PMS exhibited a flatter morning to evening aldosterone slope compared to controls (p < .05). Morning and evening salivary cortisol concentrations were unchanged throughout the menstrual cycle in both groups of women. In conclusion, evening salivary aldosterone, but not cortisol concentrations, are increased in women with PMS during the early luteal phase compared to controls. Cortisol does not appear to be involved in the mechanisms contributing to the course of PMS. High evening salivary aldosterone in the early luteal phase may represent an important risk factor and could be of predictive value for the occurrence of premenstrual symptoms.


Accelerated territorial arterial spin labeling based on shared rotating control acquisition: an observer study for validation.
Shared rotating control acquisition can shorten the imaging time of territorial arterial spin labeling (tASL) by 33% compared with the normal control acquisition scheme but potentially results in an inaccurate estimate of vascular territories due to imperfect magnetization transfer compensation. Our purpose was to validate the accuracy of the shared rotating control acquisition method in evaluation of vascular territories. Twenty-four patients underwent tASL at a 3.0-T MRI with the conventional normal control acquisition method. Composite vascular territory maps, in which the blood flows from the right and left internal carotid arteries and the posterior circulation were encoded in red-green-blue, were generated as a normal averaged control-label scheme and as a simulated shared rotating control scheme. Two observers independently reported the most dominant territorial flow in 26 brain regions corresponding to the arterial segments at three post-labeling time points. Inter-reader and inter-method agreements were analyzed using κ statistics. Overall inter-reader agreements were excellent for both the normal control and the shared rotating control methods (κ = 0.98, respectively). Overall inter-method agreement was also excellent (κ = 0.98), although relatively low agreement was noted in the bilateral posterior cerebral artery territories (κ = 0.79 to 0.93). Our results suggested that tASL using shared rotating control acquisition can provide information on the vascular territories comparable to that obtained using the normal control acquisition while substantially shortening the imaging time.


The bird beak configuration has no adverse effect in a magnetic resonance functional analysis of thoracic stent grafts after traumatic aortic transection.
This study used magnetic resonance imaging (MRI) to analyze functional long-term outcome after endovascular repair of blunt aortic injury. This prospective study enrolled 27 of 53 patients who were treated between 1999 and 2008. Patients underwent functional multidimensional contrast-enhanced MRI with flow analysis or compliance measurements of the aorta, or both. Ten patients were treated with the Medtronic Valiant (Medtronic World Medical, Sunrise, Fla), 14 patients received a Gore TAG (W. L. Gore & Associates, Flagstaff, Ariz), and two received a C (conformable)-TAG (W. L. Gore & Associates) stent graft. For several patients, repetitive measurements over time could be done. Median follow-up was 3.92 ± 2.7 years. The MRI parameters were: three-dimensional flow: echo time/repetition time = 3.1/5.3 ms, Δx(pixel density) = 2.5 × 2.5 × 3 mm(3); respiratory navigator, α = 15°, venc(encoding velocity) = 200 cm/s along anterior-posterior, right-left, and foot-head direction, 40 cardiac phases. Cine: echo time/repetition time = 1.7/3.4 ms, Δx(pixel density) = 1.2 × 1.2 × 6 mm(3), breathhold, α = 60°, 40 cardiac phases. The flow analysis showed flow acceleration at the proximal end of the stent graft, with higher values in patients with a nonoptimal alignment of the stent graft. No differences were found between different devices (median acceleration was 75.99 ± 37.98 cm/s for Gore and 71.59 ± 17.22 cm/s for Medtronic). The values were stable during follow-up. In the compliance analysis, the part of the aorta covered with the stent graft showed nearly no expansion, whereas the ascending and descending aorta showed normal expansion. This behavior did not change over the time. At the proximal end of the stent graft, a slight compression could be noted (-0.5 ± 0.14 mm), except in those patients with a C-TAG device from Gore. Functional analysis showed no adverse long-term outcome of the bird beak configuration of stent grafts in the aortic arch after endovascular repair after blunt aortic injury.


Relationship between erythropoiesis and the enhanced intestinal uptake of ferric iron in hypoxia in the mouse.
An in vitro technique was used to determine the unidirectional Fe3+ uptake rates in mouse duodenal fragments. In animals in which erythropoiesis had been stimulated by hypoxia, Fe3+ uptake by the duodenal fragments was enhanced due to an increase in Vappmax, However, when erythropoiesis was increased by injections of erythropoietin, intestinal Fe3+ uptake rates were unaffected. Mice subjected to sub-total nephrectomy showed an increased Vappmax for Fe3+ after exposure to hypoxia, despite the absence of an erythropoietic response. When the bone marrow was obliterated by treatment with 89Sr, a small increase in Vappmax for Fe3+ was found: permeability studies and morphometric analyses demonstrated no apparent irradiation damage to the duodenal mucosa of these animals. Exposure of 89Sr-treated mice to hypoxia caused a further significant increase in Vappmax. These results indicate that the increase in intestinal mucosal iron uptake which follows hypoxia is not mediated by erythropoietin or other factors associated with increased erythropoiesis.


Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs.
The long-term survival of biomaterial implants is often hampered by surgery-induced inflammation that can lead to graft failure. Considering that most corneas receiving grafts are either pathological or inflamed before implantation, the risk of rejection is heightened. Here, we show that bioengineered, fully synthetic, and robust corneal implants can be manufactured from a collagen analog (collagen-like peptide-polyethylene glycol hybrid, CLP-PEG) and inflammation-suppressing polymeric 2-methacryloyloxyethyl phosphorylcholine (MPC) when stabilized with the triazine-based crosslinker 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The resulting CLP-PEG-MPC implants led to reduced corneal swelling, haze, and neovascularization in comparison to CLP-PEG only implants when grafted into a mini-pig cornea alkali burn model of inflammation over 12 months. Implants incorporating MPC allowed for faster nerve regeneration and recovery of corneal sensation. CLP-PEG-MPC implants appear to be at a more advanced stage of regeneration than the CLP-PEG only implants, as evidenced by the presence of higher amounts of cornea-specific type V collagen, and a corresponding decrease in the presence of extracellular vesicles and exosomes in the corneal stroma, in keeping with the amounts present in healthy, unoperated corneas.


Numerical study of the effects of scatterer sizes and distributions on multiple backscattered intensity patterns of polarized light.
We investigate numerically the effects of scatterer sizes on backscattered polarization patterns using the third-order scattering model developed. The calculated results show that both parallel and cross polarization patterns from water suspensions of polystyrene spheres have four-lobe structures of the azimuth dependence of intensities. Particularly, the parallel polarization pattern is sensitive to scatterer sizes, exhibiting good agreement with prior experimental measurements. Furthermore, the polarization patterns from the dysplastic and normal cells with different size distribution widths are calculated and analyzed. The results show that the polarization patterns of dysplastic and normal cells have distinct differences, which might be used for identification of the morphological structure changes of cancer, dysplasia, and regeneration cells.


Child, family and environmental correlates of children's motor skill proficiency.
To identify factors associated with children's motor skills. Cross-sectional. Australian preschool-aged children were recruited in 2009 as part of a larger study. Parent proxy-report of child factors (age, sex, parent perception of child skill, participation in unstructured and structured activity), self-report of parent factors (confidence in their own skills to support child's activity, parent-child physical activity interaction, parent physical activity) and perceived environmental factors (play space visits, equipment at home) were collected. Moderate to vigorous physical activity (MVPA) (ActiGraph GT1M accelerometer) and motor skills (Test of Gross Motor Development-2) were also assessed. After age adjustment, variables were checked for association with raw object control and locomotor scores. Variables with associations of p<0.20 were entered into two multiple regression models with locomotor/object control as respective outcome variables. Motor skills were assessed for 76 children (42 female), mean [SD] age=4.1 [0.68]; 71 completed parent proxy-report and 53 had valid MVPA data. Child age, swimming lessons, and home equipment were positively associated explaining 20% of locomotor skill variance, but only age was significant (β=0.36, p=0.002). Child age and sex, unstructured activity participation, MVPA%, parent confidence, home equipment (all positively associated), and dance participation (inversely associated) explained 32% object control variance. But only age (β=0.67, p<0.0001), MVPA% (β=0.37, p=0.038) and no dance (β=-0.34, p=0.028) were significant. Motor skill correlates differ according to skill category and are context specific with child level correlates appearing more important.


Extensor Mechanism Disruption Remains a Challenging Problem.
Extensor mechanism disruption (EMD) following total knee arthroplasty (TKA) is a devastating problem commonly treated with allograft or synthetic reconstruction. Understanding of reconstruction success rates and patient recorded outcomes is lacking. Patients who have an EMD after TKA undergoing mesh or whole-extensor allograft reconstruction between 2011 and 2019, with minimum 2-year follow-up were reviewed at two tertiary care centers. Functional failure was defined as extensor lag >30 degrees, amputation, or fusion, as well as revision extensor mechanism reconstruction (EMR). Survivorship was assessed using Kaplan-Meier curves, and factors for success were determined with logistic regressions. Of fifty-six EMRs (49 patients), 50.0% (28/56) were functionally successful at 3.2 years of mean follow-up (range, 0.2 to 7.4). In situ survivorship of the reconstructions at 36 months was 75.0% (42 of 58). There were 50.0% (14 of 28) of functionally failed EMRs that retained their reconstruction at last follow-up. Mean extensor lag among successes and failures was 5.4 and 71.0° (P = .01), respectively. Mean Knee Injury and Osteoarthritis Outcome Score, Joint Replacement scores were 67.1 and 48.8 among successes and failures (P = .01). There were 64.0% (16 of 25) of successes and 1 of 19 failures that obtained a Knee Injury and Osteoarthritis Outcome Score, Joint Replacement score above the minimum patient-acceptable symptom state for TKA. Survivorship and success rates were similar between reconstruction methods (P = .86; P = .76). All-cause mortality was 8.2% (4 of 49), each with EMR failure prior to death. All-cause reoperation rate was 42.9% (24 of 56), with a 14.3% (8 of 56) rate of revision EMR and 10.7% (6 of 56) rate of above-knee-amputation or modular fusion. This multicenter investigation of mesh or allograft EMR demonstrated modest functional success at 3.2 years. Complication and reoperation rates were high, regardless of EMR technique. Therefore, EMD after TKA remains problematic.


The effect of ventricular assist devices on long-term post-transplant outcomes: a systematic review of observational studies.
Ventricular assist device (VAD) therapy is widely used as a bridge to cardiac transplant. Studies addressing the effect of VADs on post-transplant outcomes have shown conflicting results. It is imperative to review this evidence to inform clinical decision making and future research. Our aim was to systematically evaluate the effect of VAD therapy on long-term post-transplant outcomes in heart transplant recipients. We searched online databases (Medline, PubMed, Embase, and CINAHL) and references of included articles. Comparative studies evaluating the effect of VADs on post-transplant outcomes in adults were included and study results were meta-analysed using random-effects models. We conducted subgroup analyses to assess the effect estimate of extra- vs. intra-corporeal VADs and to evaluate the impact of transplant era and listing status. Overall, we identified 31 observational studies. One-year post-transplant mortality in recipients bridged with an extra-corporeal VAD was significantly higher than in non-bridged recipients (RR 1.8, 95% CI 1.53-2.13, I(2)= 1%), while patients supported with an intra-corporeal VAD had similar mortality to non-bridged recipients (RR 1.08, 95% CI 0.95-1.22, I(2)= 0%). The risks of rejection within the first post-transplant year and coronary allograft vasculopathy were not significantly different between patients with or without VAD support prior to transplant. Publication bias was low; however, the risk of bias across studies was moderate to high. Intra-corporeal VAD support does not have a deleterious impact on post-transplant outcomes. However, post-transplant survival may be poorer in the subgroup of patients supported with extra-corporeal devices. Studies with greater methodological rigour are warranted.


[Lung Adenosquamous Cell Carcinoma in which the Administration of Nivolumab Became Untenable due to Bleeding from Small Intestine Metastasis].
A 59-year-old man who had postoperative recurrence of lung adenosquamous cell carcinoma was administered nivolumab as 3rd-line chemotherapy. Although nivolumab was considered effective, bleeding from a metastatic lesion at the jejunum was recognized by double-balloon enteroscopy, and partial resection was performed. Although the re-administration of nivolumab was planned, the patient died of acute respiratory failure 6 days postoperatively.


Outcome of a single XEN microstent implant for glaucoma patients with different types of glaucoma.
The aim of this retrospective study was to compare the efficacy and safety profile of a single XEN-microstent in different types of primary and secondary open angle glaucoma. A single XEN microstent was implanted in patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), pseudoexfoliation glaucoma (PEX) and secondary glaucoma (Sec.Gl). The intraocular pressure (IOP), the active substances of the applied IOP-lowering drugs, the best corrected visual acuity (BCVA) and the mean deviation (MD) of the perimetry were measured at baseline and at regular follow-ups, scheduled at 2 days and 1, 3, 6 and 12 months after surgery. 153 eyes were included in this analysis. 113 eyes were affected by POAG (74%), 5 eyes by NTG (3%), 22 eyes by PEX (14%) and 13 eyes by Sec. Gl (9%). Mean IOP decreased in all treatment groups during the 12 months of follow-up (complete group: 23.9 ± 7.4 to 15.4 ± 5.1 mmHg (p < 0.01); POAG: 22.8 ± 6.5 to 15.1 ± 4.6 mmHg (p < 0.01); NTG: 16.6 ± 3.4 to 11.6 ± 2.2 mmHg (p < 0.05); PEX: 28.0 ± 7.9 to 17.1 ± 6.6 mmHg (p < 0.01); Sec.Gl: 28.9 ± 13.9 to 15.5 ± 6.9 mmHg (p < 0.05)). In the 153 eyes the average number of IOP-lowering drugs applied decreased from 2.6 ± 1.2 to 0.8 ± 1.3 12 months after surgery (p < 0.01). BCVA and mean deviation of automated standard perimetry remained stable in all groups during follow-up. As in eyes suffering from POAG, IOP and number of IOP-lowering drugs applied can be effectively reduced by XEN implantation in eyes suffering from NTG, PEX and secondary glaucoma while leaving BCVA and visual field unchanged. Trial was registered at DRKS (registration number: DRKS00020800 , Registered 25.February 2020 - Retrospectively registered).


Effects of phytosomal curcumin treatment on modulation of immunomodulatory and pulp regeneration genes in dental pulp mesenchymal stem cells.
Dental pulp stem cells (DPSCs) are a new population of mesenchymal stem cells (MSCs) located in the oral cavity with potential capacities for tissue regeneration and immunomodulation. The purpose from this study was to determine effects of curcumin nanoparticle into phytosomal formulation (PC) on the relative expression of DSPP, VEGF-A, HLA-G5, VCAM1, RelA and STAT3 genes which are among the most important factors influencing processes of immunomodulatory and tissue regenerative by DPSCs. After isolation and culture of DPSCs, these cells were characterized according to predetermined criteria including flow cytometric analysis for detection of the most important cell surface markers and also evaluation of multilineage differentiation potential. Then, the MTT method was employed to check the cell viability in treatment with different concentrations of PC. Following DPSCs' treatment with an optimal-non-toxic dose of this nanoparticle, quantification of expression of target genes was performed using real-time PCR procedure. According to results of immunophenotyping analysis and cell differentiation experiments, the isolated cells were confirmed as MSCs as more than 99% of them expressed specific mesenchymal markers while only about 0.5% of them were positive for hematopoietic marker. The real-time PCR results indicated that PC significantly reduced the expression of RelA, STAT3, VCAM1 and HLA-G5 genes up to many times over while optimally enhanced the expression of DSPP and VEGF-A genes, although this enhance was statistically significant only for VEGF-A (all P < 0.001). The study suggests that PC affects the stemness capabilities of DPSCs and it may facilitate the development of MSCs-based therapeutics in regenerative dentistry.


Profiling, mimicking and masking the flavor of a selected rodenticide.
In Experiment 1, rats drank strychnine solution followed by an injection of LiCl. Generalization of learned strychnine avoidance to 4 non-toxic flavors was then assessed. Additional conditioning and generalization trials followed until 24 flavors had been presented. In Experiment 2, rats were conditioned to avoid individual flavors, or flavor mixtures concocted on the basis of avoidance generalization observed in Experiment 1. Tests followed for generalization of learned avoidance from the simple flavors to the mixtures, from the mixtures to the simple flavors, and from either to strychnine. In Experiment 3, two concentrations of NaCl were mixed with strychnine or one of the flavors (SOA) used in the previous experiments. These stimuli, as well as SOA alone, strychnine alone, and each of the NaCl concentrations, were presented to rats during conditioning. Generalization followed, as in the previous experiments. In Experiment 1, strychnine avoidance generalized to 'bitter' flavors (ps less than 0.01). In Experiment 2, avoidance of flavor mixtures generalized more strongly to strychnine than did learned avoidance of simple flavors (ps less than 0.01). In Experiment 3, NaCl masked or otherwise suppressed the 'bitter' flavor of strychnine or SOA insofar as no groups conditioned with a 'bitter'-salt mixture generalized avoidance to 'bitter' alone (ps less than 0.01). Rats are therefore capable of recognizing the flavor components of strychnine. Moreover, when these components are mixed in proportion to the degree of generalized avoidance, a mimic (either in terms of flavor characteristics or perceived intensity) of strychnine is obtained. Avoidance learning appears useful in the development of rodenticide baits and pre-bait formulations.


Aquaporin-4 in glymphatic system, and its implication for central nervous system disorders.
The clearance function is essential for maintaining brain tissue homeostasis, and the glymphatic system is the main pathway for removing brain interstitial solutes. Aquaporin-4 (AQP4) is the most abundantly expressed aquaporin in the central nervous system (CNS) and is an integral component of the glymphatic system. In recent years, many studies have shown that AQP4 affects the morbidity and recovery process of CNS disorders through the glymphatic system, and AQP4 shows notable variability in CNS disorders and is part of the pathogenesis of these diseases. Therefore, there has been considerable interest in AQP4 as a potential and promising target for regulating and improving neurological impairment. This review aims to summarize the pathophysiological role that AQP4 plays in several CNS disorders by affecting the clearance function of the glymphatic system. The findings can contribute to a better understanding of the self-regulatory functions in CNS disorders that AQP4 were involved in and provide new therapeutic alternatives for incurable debilitating neurodegenerative disorders of CNS in the future.


Assessment of bone remodeling in the temporomandibular joint by serial uptake measurement of technetium 99m-labeled methylene diphosphonate with a cadmium telluride probe.
Regional uptake of technetium 99m-labeled methylene diphosphonate was measured serially over time to follow the healing course of surgically generated lesions, induced unilaterally in the condyles of beagles. A small portable cadmium telluride probe was used for radiation detection, with and without a gold collimator attached. Radioactivity was measured at six periarticular sites on both the operated and the contralateral control sides and expressed as a ratio with respect to a reference site over the sagittal suture. The use of a collimator was crucial to separate the activity associated with bone mineralization in the condylar head from that arising in the adjoining bones. The uptake in the condylar region increased 2 weeks after surgery and remained at a constant level above the presurgery baseline (p less than 0.05) until termination of the study (10 weeks). Postmortem histologic examinations confirmed the high bone turnover level by revealing newly formed bone as well as the presence of osteoclasts. The time course of nuclide uptake in the temporomandibular joint is different from the general pattern of rise and fall of activity displayed in other bones and indicates the persistence of bone remodeling processes during a prolonged period of at least 10 weeks.


OptSSeq explores enzyme expression and function landscapes to maximize isobutanol production rate.
Efficient microbial production of the next-generation biofuel isobutanol (IBA) is limited by metabolic bottlenecks. Overcoming these bottlenecks will be aided by knowing the optimal ratio of enzymes for efficient flux through the IBA biosynthetic pathway. OptSSeq (Optimization by Selection and Sequencing) accomplishes this goal by tracking growth rate-linked selection of optimal expression elements from a combinatorial library. The 5-step pathway to IBA consists of Acetolactate synthase (AlsS), Keto-acid reductoisomerase (KARI), Di-hydroxy acid dehydratase (DHAD), Ketoisovalerate decarboxylase (Kivd) and Alcohol dehydrogenase (Adh). Using OptSSeq, we identified gene expression elements leading to optimal enzyme levels that enabled theoretically maximal productivities per cell biomass in Escherichia coli. We identified KARI as the rate-limiting step, requiring the highest levels of enzymes expression, followed by AlsS and AdhA. DHAD and Kivd required relatively lower levels of expression for optimal IBA production. OptSSeq also enabled the identification of an Adh enzyme variant capable of an improved rate of IBA production. Using models that predict impacts of enzyme synthesis costs on cellular growth rates, we found that optimum levels of pathway enzymes led to maximal IBA production, and that additional limitations lie in the E. coli metabolic network. Our optimized constructs enabled the production of ~3 g IBA per hour per gram dry cell weight and was achieved with 20 % of the total cell protein devoted to IBA-pathway enzymes in the molar ratio 2.5:6.7:2:1:5.2 (AlsS:IlvC:IlvD:Kivd:AdhA). These enzyme levels and ratios optimal for IBA production in E. coli provide a useful starting point for optimizing production of IBA in diverse microbes and fermentation conditions.


Hyperfractionated accelerated radiochemotherapy (HFA-RCT) with mitomycin C for advanced head and neck cancer.
To investigate efficacy and feasibility of hyperfractionated accelerated radiotherapy combined with mitomycin C, patients with locally advanced unresectable squamous cell carcinomas of the head and neck region were administered 64-66 Gy in four weeks and mitomycin C (20 mg/m(2)) on day five. Twenty-one consecutive patients were included between November 1997 and June 1999 (median age: 57 years). All tumours were stage T3-4 and 18/21 were N2-3. Eighteen patients experienced grade 3 and three patients grade 2 mucosal toxicity. With median follow up for surviving patients of 42 months, loco-regional control was 55% at three years, overall survival was 33% at three years. This treatment is at the edge of local tolerability, but there is a good curative chance even for very advanced localised tumours, provided a complete remission is induced at primary treatment.


Infrapubic approach for placement of inflatable penile prosthesis: contemporary review of technique and implications.
Inflatable penile prosthesis (IPP) is an effective treatment for erectile dysfunction refractory to nonsurgical management. The infrapubic approach for IPP placement is less frequently employed than the penoscrotal approach, with only about 25% of IPPs placed via this method. Underutilization of the infrapubic method may be due to fear of injuring the penile dorsal neurovascular bundle, perceived difficulties of scrotal pump placement through a distant location, or insufficient distal corporal exposure. However, this approach appears to result in favorable operative times, faster time to device activation, equivalent postoperative satisfaction and quality of life, and similar complication rates. We provide a contemporary review of literature published before May 2019 regarding the infrapubic approach for IPP placement, technical considerations, and postoperative expectations.


Extracorporeal Life Support and Mechanical Circulatory Support in Out-of-Hospital Cardiac Arrest and Refractory Cardiogenic Shock.
The prevalence of extracorporeal cardiopulmonary resuscitation is increasing worldwide as more health care centers develop the necessary infrastructure, protocols, and technical expertise required to provide mobile extracorporeal life support with short notice. Strict adherence to patient selection guidelines in the setting of out-of-hospital cardiac arrest, as well as in-hospital cardiac arrest, allows for improved survival with neurologically favorable outcomes in a larger patient population. This review discusses the preferred approaches, cannulation techniques, and available support devices ideal for the various clinical situations encountered during the treatment of cardiac arrest and refractory cardiogenic shock.


Application of industry 4.0 enablers in supply chain management: Scientometric analysis and critical review.
The supply chain management (SCM) environment is rapidly evolving as a result of the critical role industry 4.0 enablers are playing. Consequently, and to leverage the power of industry 4.0 enablers (I4Es) including; artificial intelligence (AI), machine learning (ML), internet of things (IoT) and big data (BD), researchers and industry practitioners have employed these I4Es to resolve several pain points in supply chain management at all levels, improve operational efficiency, manage demand volatility, tackle cost fluctuations, and make data-driven decisions. Thus, I4Es are working as an evolutionary catalyst for supply chain management in myriads of ways. As such, the application of I4Es in supply chain management (I4Es-in-SCM) research has witnessed tremendous growth over the past years. This study conducted a scientometric analysis and critical review of the I4Es-in-SCM research to monitor trends, visualize the structure of knowledge, identify gaps, and highlight future research avenues. The paper recruited and analysed bibliographic data of 786 papers from Scopus on the application of I4Es-in-SCM research. Analysis showed that the last two decades witnessed a phenomenal growth in research on the application of I4Es-in-SCM, with at least 42 % of all countries making contributions. The analysis showed wider collaboration between countries and noticed a rather significant collaboration among researchers within a given continent. The study also identified the most influential researchers, journals, and countries as well as trending themes and topics in the application of I4Es-in-SCM research. After delineating boundaries of scientific knowledge, the study proffered areas that require further research. The novelty of this study lies in providing a more holistic statistical and visualized analysis of the structure of knowledge, productivity, and scientific collaborations of researchers, journals and countries in the application of I4Es-in-SCM management research. Accordingly, the study outcomes may serve as a useful reference to supply chain academics, early-stage researchers, practitioners, policymakers, and organizations in understanding the structure of knowledge on the application of I4Es-in-SCM research and may constitute a basis for future research.


Effects of a combination of erythromycin sequential therapy and azithromycin on lung function and inflammatory factors in children with severe mycoplasma pneumonia.
This study aimed to investigate the effect of erythromycin sequential therapy plus azithromycin on lung function and inflammatory factors in children with severe mycoplasma pneumonia (MP). Ninety-three severe MP children were selected and randomized into azithromycin group, erythromycin group, and combination group, 31 cases in each. The disappearance time of cough, fever, lung rale and X-ray shadow in the combination group were shorter than those in the azithromycin group and erythromycin group. The clinical treatment efficiency of the combination group was higher than that of the azithromycin group. After treatment, FVC, FEV1/FVC and PEF in combination group were higher than before treatment; IL-8, IL-6, CRP in combination group were lower than erythromycin group and azithromycin group. IL-8, IL-6, CRP are negatively correlated with disappearance time of cough, fever, pulmonary rale, X-ray shadow and clinical treatment efficiency; FEV1/FVC is positively correlated with disappearance time of cough and fever, pulmonary rales and X-ray shadow, and clinical treatment efficiency. Sequential erythromycin therapy combined with azithromycin in the treatment of MP can effectively inhibit high inflammatory reactions, control the disease in a timely manner, improve lung function and produce fewer adverse reactions.


Induction of avidin in the chick oviduct by tissue damage. Effect of promethazine chloride, CaCl2 and hydrocortisone on local induction.
The local effect of the mechanical induction of avidin by ligature was studied in diethylstilbestrol-primed chicks. The highest induction of avidin was always found in the immediate vicinity of the silk ligature of the oviduct. The locality of the induction was highly dependent on the position of the ligature. The nonligated parts of the ligated oviduct also showed a slight avidin induction. These results indicate a strictly local effect of avidin induction by ligature. An antihistamine, promethazine chloride, has a potentiating effect on the avidin induction by ligature when administered after the ligature. On the other hand, membrane stabilization by hydrocortisone or CaCl2 did not influence the ligature-induced avidin synthesis. On the basis of these results it is concluded that the avidin induction is not mediated by histamine activation or membrane damage.


Correction to: Sudden onset of syncope and disseminated intravascular coagulation at 14 weeks of pregnancy: a case report.
An amendment to this paper has been published and can be accessed via the original article.


Effectiveness of Exercise on Fatigue and Sleep Quality in Fibromyalgia: A Systematic Review and Meta-analysis of Randomized Trials.
To determine the effects of exercise on fatigue and sleep quality in fibromyalgia (primary aim) and to identify which type of exercise is the most effective in achieving these outcomes (secondary aim). PubMed and Web of Science were searched from inception until October 18, 2018. Eligible studies contained information on population (fibromyalgia), intervention (exercise), and outcomes (fatigue or sleep). Randomized controlled trials (RCT) testing the effectiveness of exercise compared with usual care and randomized trials (RT) comparing the effectiveness of 2 different exercise interventions were included for the primary and secondary aims of the present review, respectively. Two independent researchers performed the search, screening, and final eligibility of the articles. Of 696 studies identified, 17 RCTs (n=1003) were included for fatigue and 12 RCTs (n=731) for sleep. Furthermore, 21 RTs compared the effectiveness of different exercise interventions (n=1254). Two independent researchers extracted the key information from each eligible study. Separate random-effect meta-analyses were performed to examine the effects from RCTs and from RTs (primary and secondary aims). Standardized mean differences (SMD) effect sizes were calculated using Hedges' adjusted g. Effect sizes of 0.2, 0.4, and 0.8 were considered small, moderate, and large. Compared with usual care, exercise had moderate effects on fatigue and a small effect on sleep quality (SMD, -0.47; 95% confidence interval [CI], -0.67 to -0.27; P<.001 and SMD, -0.17; 95% CI, -0.32 to -0.01; P=.04). RTs in which fatigue was the primary outcome were the most beneficial for lowering fatigue. Additionally, meditative exercise programs were the most effective for improving sleep quality. Exercise is moderately effective for lowering fatigue and has small effects on enhancing sleep quality in fibromyalgia. Meditative exercise programs may be considered for improving sleep quality in fibromyalgia.


The potential of virtual reality in social skills training for people with autistic spectrum disorders.
People with autism experience profound and pervasive difficulties in the social domain. Attempts to teach social behaviours tend to adopt either a behavioural or a 'theory of mind' (ToM) approach. The beneficial aspects and limitations of both paradigms are summarized before an examination of how virtual reality technology may offer a way to combine the strengths from both approaches. This is not an exhaustive review of the literature; rather, the papers are chosen as representative of the current understanding within each broad topic. Web of Science ISI, EMBASE and PsycInfo were searched for relevant articles. Behavioural and ToM approaches to social skills training achieve some success in improving specific skills or understanding. However, the failure to generalize learned behaviours to novel environments, and the unwieldy nature of some behavioural methodologies, means that there is a need for a training package that is easy to administer and successful in promoting learning across contexts. Virtual reality technology may be an ideal tool for allowing participants to practise behaviours in role-play situations, whilst also providing a safe environment for rule learning and repetition of tasks. Role-play within virtual environments could promote the mental simulation of social events, potentially allowing a greater insight into minds. Practice of behaviours, both within and across contexts, could also encourage a more flexible approach to social problem solving. Virtual environments offer a new and exciting perspective on social skills training for people with autistic spectrum disorders.


Correction: Development of an Online Health Care Assessment for Preventive Medicine: A Machine Learning Approach.
[This corrects the article DOI: 10.2196/18585.].


Relationships between cortical, cardiac, and arousal-motor activities in the genesis of rhythmic masticatory muscle activity across sleep cycles in primary sleep bruxism children.
The present study aimed to clarify the physiological relationships between rhythmic masticatory muscle activity (RMMA) and cyclic changes in cortical, autonomic, and arousal-motor activities during sleep in sleep bruxism (SB) children. Polysomnographic recordings were performed on 15 SB children (9 boys, 6 girls, 10.3 ± 2.5 years) and 18 control children (5 boys, 13 girls, 10.7 ± 3.1 years) free from sleep and developmental disorders. Sleep and RMMA were scored by the standard rules. Sleep cycle was divided into NREM and REM sleep segments and the frequency of RMMA, transient arousal and movement, and cortical and cardiac activities were then quantitatively analyzed in relation to sleep cycles. Neither sleep architecture nor sleep stage distribution of RMMA significantly differed between the two groups. In sleep cycles, SB children showed more frequent RMMA in all segments than controls, while cyclic changes in cortical and autonomic activities did not significantly differ between the two groups. In SB children, RMMA was the most frequent in the last NREM segment before REM sleep and was associated with increases in cortical beta activity and arousal; more than 70% of RMMA time-dependently occurred with cortical and motor arousals. This is the first study to suggest that the potentiation of RMMA occurrence was associated with transient arousal under cyclic sleep processes in primary SB children.