Valorization of waste chicken skin for conjugated linoleic acid (CLA) production: optimization using response surface methodology.
The valorization of waste chicken skin fat (WCSF) for conjugated linoleic acid (CLA) production was performed by photoisomerization and optimized the process conditions for high CLA production by response surface methodology. The fat extraction yield from waste chicken skin was approximately 52%. The linoleic acid content of the fat obtained from waste chicken skin was increased by the fractionation process approximately 2 times, up to 52%. Optimum iodine amount and processing time for predicted maximum total CLA amount were determined as 0.87% and 116.36 h, respectively. The maximum total CLA amount was predicted and produced experimentally as 32.14% and 29.01%, respectively. Additionally, iodine amount, processing time, and their interaction significantly affected the amount and variety of produced CLA isomers. The results indicated that dominant isomers produced by photoisomerization of WCSF were trans, trans isomers. However, the amount of cis 9, trans 11 and trans 10, cis 12 CLA isomers could be more increased by optimizing the production parameters. The present study indicated that waste chicken skin could be valorized in CLA production by photoisomerization and obtained high value-added product, and also a more economical and faster CLA production could be realized.


Combined Endoscopic and Open Approaches in the Management of Sinonasal and Ventral Skull Base Malignancies.
Combined transcranial and endoscopic endonasal approaches remain useful in the treatment of ventral skull base malignancies. The extended bifrontal transbasal approach provides wide access to the anterior ventral skull base and paranasal sinuses without transfacial incisions. In more extensive lesions, the bifrontal transbasal approach can then be combined with an endoscopic endonasal approach (EEA) from below. This article reviews the indications, surgical technique, and operative nuances of combined transbasal and EEA (cranionasal) approaches for the surgical management of ventral skull base malignancies.


Silencing TTTY15 mitigates hypoxia-induced mitochondrial energy metabolism dysfunction and cardiomyocytes apoptosis via TTTY15/let-7i-5p and TLR3/NF-κB pathways.
Noncoding RNAs are interweaved in pathological processes in myocardial ischemia (MI), such as long noncoding RNA (lncRNA) and microRNAs (miRNAs). The aim of this study was to figure out the role of Testis-specific transcript Y-linked 15 (TTTY15) and let-7i-5p in cell model of MI in cardiomyocytes. Hypoxia-induced cell injury was assessed by Cell counting kit 8 assay, flow cytometry, commercial kits and western blotting. As a result, hypoxia stress induced inhibition on cell proliferation, glucose uptake, and ATP production, and promotion on apoptosis, lactate dehydrogenase (LDH) release, and lactic acid production in human cardiomyocyte AC16 cells. During hypoxia injury, expression of TTTY15 and let-7i-5p was measured by real-time quantitative polymerase chain reaction, and TTTY15 was upregulated, accompanied with let-7i-5p downregulation. Functionally, either silencing TTTY15 or overexpressing let-7i-5p could attenuate hypoxia-induced apoptosis and mitochondrial energy metabolism dysfunction in AC16 cells. Moreover, there was an interaction between TTTY15 and let-7i-5p via target binding, as evidenced by dual-luciferase reporter assay and RNA immunoprecipitation assay. Knockdown of let-7i-5p could counteract the protective role of TTTY15 deletion in hypoxic AC16 cells. Meanwhile, toll-like receptor 3 (TLR3)/nuclear factor-kappa B (NF-κB) signaling was validated by western blotting. Expression of TLR3, tumor necrosis factor receptor-associated factor 6 (TRAF6) and phosphorylated p65 was promoted in hypoxic AC16 cells, which was abrogated by TTTY15 silencing along with let-7i-5p upregulation. Collectively, TTTY15 knockdown protects cardiomyocytes against hypoxia-induced apoptosis and mitochondrial energy metabolism dysfunction in vitro through let-7i-5p/TLR3/NF-κB pathway to suppress.


Secondary structure of ITS2 rRNA provides taxonomic characters for systematic studies--a case in Lycoperdaceae (Basidiomycota).
The secondary structure of the ITS2 rDNA transcript (pre-rRNA) could provide information for identifying homologous nucleotide characters useful for cladistic inference of relationships. Such structure data could become taxonomic characters. This work compares the effect of several modern nucleotide alignment strategies, including those making use of structure data, on phylogenetic inference. From both the phylogenetic analyses and comparative secondary structure, implications for taxonomy and evolution of puffball fungi are discussed. Lycoperdaceae remain insufficiently resolved with present taxon and data sampling. Neither alignment allows statistically robust phylogenetic hypotheses under any current optimality criterion. The secondary structure data at this time are best used as accessory taxonomic characters as their phylogenetic resolving power and confidence in validity is limited compared with underlying nucleotide characters. We introduce a preliminary nomenclature convention to describe secondary structure for defining consensus features. These consensus structures are illustrated for the clades /Calvatia, /Handkea-Echinatum, /Vascellum, /Morganella, and /Plumbea-Paludosa (Bovista).


Measuring professional nursing value development in students participating in international service learning: A quasi-experimental study.
International service learning is becoming widely used in nursing education as a means to provide global learning opportunities as well as part of a clinical learning experiences. Concrete outcomes for these experiences have not been clearly supported in previous research. Professional nursing values are an important learning outcome for nursing students and development of professional nursing values has been found to occur through various learning experiences. Determining if international service learning experiences facilitate the development of professional nursing values can support the use of international service learning as a viable pedagogy. The purpose of the study was to determine if there was a difference in professional nursing values development in students who participate in international service learning as part of their clinical experiences compared to those who do not. The research was a quasi-experimental study with a pre-test, post-test design. Undergraduate students participating in one week international service learning as part of their clinical hours were compared with students who did not participate in international service learning. Comparison of professional nursing values development between the experimental and control group was completed using the Nurses Professional Values Scale. The study showed the use of international service learning as part of clinical was at least equivalent in the development of professional nursing values as traditional clinical. In addition, it supported the development of professional nursing values through clinical learning overall. The use of international service learning is a viable option for clinical experiences as a means to develop professional nursing values.


Vascular complications after orthotopic liver transplantation in Estonia.
The aim of this study was to analyse vascular complications (VC) accompanying the introduction in Estonia of orthotopic liver transplantation (OLT) for treatment of end-stage liver disease. We present the incidence and treatment of VC occurring among our first 23 OLT in 22 patients. The 11 female and 11 male patients were aged 12 to 67 years. Their diagnoses were cholestatic disease (n = 8); hepatitis C virus (HCV) cirrhosis (n = 6); tumor (n = 3); Budd-Chiari syndrome (n = 2); autoimmune hepatitis (n = 1); cystic fibrosis (n = 1); or fulminant hepatic failure (n = 1). Only end-to-end vascular reconstructions were used in OLT. The patients' 1-year post-OLT survival rate was 86%. VC were confirmed using computed tomography (CT) or magnetic resonance imaging (MRI). In cases of VC, we started a 1-week course of subcutaneous anticoagulant therapy with low-molecular weight heparin (LMWH) immediately followed by permanent oral treatment. The incidence of VC was 14% (n = 3). There was no hepatic artery thrombosis. One patient developed hepatic venous thrombosis at 3 weeks after retransplantation. She was treated successfully with immediate LMWH followed by a permanent oral anticoagulation. Two patients experienced portal vein complications: 1 with pre-OLT portal vein thrombosis developed right intrahepatic portal vein thrombosis at 5 weeks after OLT requiring portal thrombectomy. He was treated successfully with immediate LMWH followed by permanent oral anticoagulation. The other subject displayed left intrahepatic portal vein thrombosis at 1 week after OLT. Despite immediate LMWH treatment followed by a permanent oral anticoagulation, he required left lobe necrectomy and Roux-Y choledochojejunostomy for recovery. The survival and recovery of all studied patients with VC allow us to recommend immediate subcutaneous anticoagulant therapy for post-OLT portal or hepatic venous thrombosis.


Children's understanding of ambiguous idioms and conversational perspective-taking.
The aim of this study was to test the hypothesis that conversational perspective-taking is a determinant of unfamiliar ambiguous idiom comprehension. We investigated two types of ambiguous idiom, decomposable and nondecomposable expressions, which differ in the degree to which the literal meanings of the individual words contribute to the overall idiomatic meaning. We designed an experiment to assess the relationship between the acquisition of figurative comprehension and conversational perspective-taking. Our sample of children aged 5-7 years performed three conversational perspective-taking tasks (language acts, shared/unshared information, and conversational maxims). They then listened to decomposable and nondecomposable idiomatic expressions presented in context before performing a multiple-choice task (figurative, literal, and contextual responses). Results indicated that decomposable idiom comprehension was predicted by conversational perspective-taking scores and language skills, whereas nondecomposable idiom comprehension was predicted solely by language skills. We discuss our findings with respect to verbal and pragmatic skills.


Myocardial positron computed tomography with 13N-ammonia at rest and during exercise.
To assess the value of myocardial-perfusion positron computed tomography (PCT) for the evaluation of coronary artery disease (CAD), 13N-ammonia PCT using a whole-body multislice PCT device was performed at rest and during exercise in 6 normal subjects and 19 patients with angiographically documented CAD. The 13N-ammonia distribution in the myocardium was assessed both qualitatively and quantitatively. At rest and during exercise, the tracer distribution was homogeneous in the 6 normal cases. In the 19 patients with CAD, regional hypoperfusion was observed in 14 cases (74%) at rest and in 18 cases (95%) during exercise. Additional perfusion abnormalities were detecting during exercise in 12 cases. Segmental analysis of the myocardial perfusion identified 30 out of 34 stenosed vessels (88%) during exercise, with only one false-positive finding of diseased vessels (specificity, 98%). For the quantitative analysis of myocardial perfusion by PCT, the percentage of change in the tracer concentration in the same region between the rest and stress images was calculated. The concentration was slightly increased in normal myocardial segments (14.4% +/- 5.8%; P less than 0.001), whereas in CAD, it was significantly decreased in segments with stenosed vessels (-18.0% +/- 18.3%; P less than 0.02). We conclude that 13N-ammonia PCT at rest and during exercise provides high-quality images, and is a sensitive and effective technique for detecting CAD and identifying individual stenosed vessels. Furthermore, this technique makes possible quantitative assessment of the coronary reserve function.


Axinopsida serricata shell encrustation: a potential indicator of organic enrichment conditions in sediments in the southern Strait of Georgia, British Columbia, Canada.
We evaluate the potential of the geographic and within-sediment distribution patterns of rust-coloured shell encrustations on an abundant subtidal bivalve, Axinopsida serricata (Carpenter, 1864) as geochemical indicators of organic enrichment from marine municipal outfalls. The progressive development of shell encrustation over the life of the animals is suggested by heavier encrustations on large shells compared to smaller shells regardless of the geochemical conditions of the habitat. Heavy encrustations decline in an exponential manner at sediment acid volatile sulphide (AVS) levels>7 micromol/g. Analyses show that the reddish shell encrustations are from an amorphous iron oxide or hydroxy-oxide likely micro-biologically mediated; the oxides appear to be embedded within the inner matrix of an organic layer, with a chemically distinct outer layer. A schematic model is proposed which shows how enrichment of labile organic carbon around outfalls affects the availability of dissolved iron in sediments and leads to less extensive encrustations on bivalve shells. Predominantly sandy sediments with low organic loading have much less potential for iron oxide deposition than silty sediments due to greater oxygen penetration into the surface sediment. Shell encrustation appears to be relatively persistent and indicative of long-term conditions, regardless of spatial and temporal fluctuations in sediment geochemistry. With more research on development over the life-cycle of the animal, the pattern of A. serricata shell encrustation has the potential to rapidly provide a map of cumulative labile organic loading and oxygen penetration of sediments around municipal outfalls on the west coast of North America where this species is common. However, caution must be used in interpreting results, since background sediment characteristics (substrate type, bottom currents and sediment transport) can affect encrustation patterns.


Interactive format is favoured in case conference.
Follow-up case presentation (FCP), a staple of emergency medicine residency conference curricula nationwide, has traditionally been delivered using PowerPoint(TM) (PP). The sole use of the PP lecture format may limit audience participation. In light of existing literature supporting chalkboard and morning report formats, we changed FCP to an interactive chalkboard format with limited PP slides. We hypothesised that this change will enhance the perceived educational impact of FCP on learners. To examine learners' perceptions regarding the PP-based and 'chalkboard talk' discussion formats, we conducted a time-series investigation with pre- and post-intervention questionnaires using the five-point Likert scale. After obtaining Institutional Review Board exemption, 60 emergency medicine residents (post graduate years 1-4) were recruited through e-mail to complete the pre-intervention questionnaire. The post-intervention questionnaire was administered following a run-in period of nine post-intervention FCPs. The questionnaires were compared using Mantel-Haenszel chi-square tests. The pre- and post-intervention questionnaire completion rates were 83.3 per cent (50/60) and 65 per cent (39/60), respectively. The chalkboard format was perceived by learners to be significantly more effective than PP-based FCPs at educating the learner regarding the topics covered (3.5 versus 4.0, pre- versus post-, respectively, p = 0.003), teaching practical knowledge (3.4 versus 3.8, p = 0.014), stimulating self-knowledge assessment (3.4 versus 3.8, p = 0.023), encouraging the generation of broad differential diagnoses (3.4 versus 3.9, p = 0.008), and promoting an interactive learning environment (3.1 versus 4.1, p < 0.0001). The implementation of chalkboard format with interactive discussion is perceived by learners to be the superior didactic educational medium, compared with the exclusive use of PP slides for FCPs. The chalkboard format was perceived by learners to be significantly more effective.


Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study.
Afatinib, an irreversible ErbB-family blocker, could improve the survival of advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer patients (NSCLCm+). This phase II trial (NCT04201756) aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLCm+. Forty-seven patients received neoadjuvant Afatinib treatment (40 mg daily). The primary endpoint was objective response rate (ORR). Secondary endpoints included pathological complete response (pCR) rate, pathological downstaging rate, margin-free resection (R0) rate, event-free survival, disease-free survival, progression-free survival, overall survival, treatment-related adverse events (TRAEs). The ORR was 70.2% (95% CI: 56.5% to 84.0%), meeting the pre-specified endpoint. The major pathological response (MPR), pCR, pathological downstaging, and R0 rates were 9.1%, 3.0%, 57.6%, and 87.9%, respectively. The median survivals were not reached. The most common TRAEs were diarrhea (78.7%) and rash (78.7%). Only three patients experienced grade 3/4 TRAEs. Biomarker analysis and tumor microenvironment dynamics by bulk RNA sequencing were included as predefined exploratory endpoints. CISH expression was a promising marker for Afatinib response (AUC = 0.918). In responders, compared to baseline samples, increasing T-cell- and B-cell-related features were observed in post-treatment tumor and lymph-node samples, respectively. Neoadjuvant Afatinib is feasible for stage III NSCLC+ patients and leads to dynamic changes in the tumor microenvironment.


Kinetics of intravenous administered L-phenylalanine in patients with cirrohosis of the liver.
The metabolism of intravenously administered L-phenylalanine has been studied in 13 patients with cirrhosis of the liver and in 17 control subjects. The decline in the plasma phenylalanine concentration followed a biexponential curve and the kinetics could be evaluated assuming a two-compartment model. The volume of the central compartment was reduced in the cirrhotic patients, reflecting a diminished liver pool size. The total phenylalanine clearance was lower in the cirrhotic patients, due mainly to a reduction of the liver cell mass or to changes in the intrahepatic membrane permeability and only to a minor extent to a reduced hepatic blood flow. The elimination rate constant from the central compartment was similar in both groups, suggesting that the remaining liver cells, had a normal capacity to hydroxylate phenylalanine to tyrosine. There was considerable overlapping in the kinetic parameters between the two groups, and even in patients with well established cirrhosis an apparently normal phenylalanine metabolism was observed.


The influence of premedication on the occurrence of dysrhythmias during oral surgery.
The incidence of cardiac dysrhythmia during inpatient dental anaesthesia with enflurane was studied following either hyoscine or droperidol as a supplement to papaveretum premedication. None of the subgroup given droperidol exhibited dysrhythmias, compared to 4.4% of those patients given hyoscine. This difference was not significant at the 5% level (0.2 greater than p greater than 0.1).


A diet containing cod backbone proteins attenuated the development of mesangial sclerosis and tubular dysfunction in male obese BTBR ob/ob mice.
The obese black and tan, brachyuric (BTBR) ob/ob mouse spontaneously develops features comparable to human diabetic nephropathy. The primary aim of the present study was to investigate if a diet containing fish proteins would attenuate or delay the development of glomerular hypertrophy (glomerulomegaly), mesangial sclerosis and albuminuria in obese BTBR ob/ob mice. Obese BTBR.CgLepob/WiscJ male mice were fed diets containing 25% of protein from Atlantic cod backbones and 75% of protein from casein (Cod-BB group), or casein as the sole protein source (control group). Kidneys were analysed morphologically, and markers for renal dysfunction were analysed biochemically in urine and serum. The Cod-BB diet attenuated the development of mesangial sclerosis (P 0.040) without affecting the development of glomerular hypertrophy and albuminuria. The urine concentration of cystatin C (relative to creatinine) was lower in mice fed the Cod-BB diet (P 0.0044). A diet containing cod backbone protein powder attenuated the development of mesangial sclerosis and tubular dysfunction in obese BTBR ob/ob mice, but did not prevent the development of glomerular hypertrophy and albuminuria in these mice.


Dissociation and ionization competing processes for H2+ in intense laser field: which one is larger?
Competition between dissociation and ionization of H(2)(+) in intense laser field has been investigated by using an accurate three-dimensional time-dependent wavepacket approach. The disagreement between the experiment and the former one-dimensional theory has been resolved. In a comparison of the calculated results with the available experimental data, a good agreement is reached, not only for the relative probabilities between dissociation and ionization but also for the two-peak structures and the peak energy locations for these two processes.


Asymmetric link between environmental pollution and COVID-19 in the top ten affected states of US: A novel estimations from quantile-on-quantile approach.
This study draws the link between COVID-19 and air pollution (ground ozone O3) from February 29, 2020 to July 10, 2020 in the top 10 affected States of the US. Utilizing quantile-on-quantile (QQ) estimation technique, we examine in what manner the quantiles of COVID-19 affect the quantiles of air pollution and vice versa. The primary findings confirm overall dependence between COVID-19 and air pollution. Empirical results exhibit a strong negative effect of COVID-19 on air pollution in New York, Texas, Illinois, Massachusetts, and Pennsylvania; especially at medium to higher quantiles, while New Jersey, Illinois, Arizona, and Georgia show strong negative effect mainly at lower quantiles. Contrarily, COVID-19 positively affects air pollution in Pennsylvania at extreme lower quantiles. On the other side, air pollution predominantly caused to increase in the intensity of COVID-19 cases across all states except lower quantiles of Massachusetts, and extreme higher quantiles of Arizona and New Jersey, where this effect becomes less pronounced or negative. Concludingly, a rare positive fallout of COVID-19 is reducing environmental pressure, while higher environmental pollution causes to increase the vulnerability of COVID-19 cases. These findings imply that air pollution is at the heart of chronic diseases, therefore the state government should consider these asymmetric channels and introduce appropriate policy measures to reset and control atmospheric emissions.


Survey of organosilicone compounds, including cyclic and linear siloxanes, in personal-care and household products.
The determination of organosiloxanes in consumer products is important for the evaluation and characterization of sources of human and environmental exposures. In this study, we determined concentrations of cyclic siloxanes [octamethylcyclotetrasiloxane (D(4)), decamethylcyclopentasiloxane (D(5)), dodecamethylcyclohexasiloxane (D(6))], tetradecamethylcycloheptasiloxane (D(7))] and linear siloxanes (L(4) to L(14)) in a variety of consumer products (n = 76), including hair-care products, skin lotions, body washes, cosmetics, nursing nipples (i.e., pacifiers), cookware, and household sanitation products such as cleansers and furniture polishes, using gas chromatography-mass spectrometry with selected ion monitoring. Prior to the analysis of samples, a method was developed to reduce the contamination arising from organosiloxanes present in certain gas chromatograph (GC) parts, such as the inlet septum; use of a Restek BTO septum at an inlet temperature of 200 degrees C gave the lowest background level (D(4): 0.8 pg; D(5): 0.3 pg; D(6): 0.2 pg). Concentrations of cyclic siloxanes in consumer products analyzed ranged from <0.35 to 9380 microg/g, from <0.39 to 81,800 microg/g, from <0.33 to 43,100 microg/g, and from <0.42 to 846 microg/g for D(4), D(5), D(6), and D(7), respectively. Concentrations of linear siloxanes varied from <0.059 to 73,000 microg/g. More than 50% of the samples analyzed contained D(4), D(5), or D(6). Cyclic siloxanes were predominant in most of the sample categories; D(5) was predominant in hair-care products, skin lotions, and cosmetics; D(6) or D(7) was predominant in rubber products, including nipples, cookware, and sealants. Potential daily exposure to total organosiloxanes (sum of cyclic and linear siloxanes) from the use of personal-care products by adult women in the United States has been estimated to be 307 mg. Significant positive correlations (p < 0.01) existed in our study between D(4) and D(7), D(4) and linear siloxanes, D(5) and D(6), and D(5) and linear siloxanes. The correlations can be related to the composition of organosiloxanes used in consumer products. The results of our study suggest that a wide variety of consumer products that are used on a daily basis contain cyclic and linear siloxanes and these products can contribute considerably to human exposures.


Racial/Ethnic Disparities in Female Sexual Health from Adolescence to Young Adulthood: How Adolescent Characteristics Matter?
To describe sexual initiation patterns in female adolescents and examine their association with adolescent characteristics and racial disparities in adverse sexual health across adolescence into early adulthood. A prospective, longitudinal, observational study from adolescence to adulthood. Nationally representative, the National Longitudinal Study of Adolescent to Adult Health data, in the range of 24-32 years old at final assessment. Data from 43,577 US women from 1994 to 2008. Adolescent sex-related characteristics at the individual-, family-, and school peer-level were assessed, and multiple sex partners, sexually transmitted infections (STIs)/HIV, and intimate partner violence (IPV) were longitudinally tracked. The sexual initiation pattern and its longitudinal association with sexual health were analyzed using latent class analysis and mixed effects Poisson regression models. Of the 43,577 subjects, the sexual initiation patterns were determined as normative (n = 28,712, 65.9%), late (n = 10,799, 24.8%), and early but unempowered (n = 4,066, 9.3%). The highest rate of the early-unempowered group was shown in Hispanic individuals (1,054/7,307 = 14.4%); they were more likely to be depressed, unsatisfied with their bodies, receiving welfare, and have less educated/permissive parents to their sexual initiation than others. The late group had a higher body mass index and greater satisfaction with their bodies. The highest number of STIs/HIV and IPV victimization was shown in non-Hispanic Black (NHB) and Hispanic individuals, respectively. However, NHB females' higher number of STIs/HIV was shown in the late/normative groups, not in the early-unempowered group. Among Hispanic females, adolescent sexual initiation patterns were not directly associated with their frequent IPV victimization. NHB females' higher STI/HIV in late/normative groups and Hispanic females' frequent IPV victimization regardless of their sexual initiation patterns might indicate that racial/ethnic disparities in female sexual health was not directly determined by adolescent risk behaviors.


Percutaneous cholecystostomy: a nonsurgical therapeutic option for acute cholecystitis in high-risk and critically ill patients.
Percutaneous cholecystostomy offers a potentially important type of therapy for critically ill patients with acute cholecystitis who present high risk when undergoing laparotomy or laparoscopy under general anesthesia. It offers a distinct advantage for these kinds of patients by avoiding the risks of the surgical intervention. Percutaneous cholecystostomy is a safe and effective minimally invasive procedure with a high success rate and low procedure-related complications. It should be considered not only in temporary management of calculous cholecystitis, but also in definitive treatment in cases of acalculous cholecystitis.


Antihelminthic effect of thymoquinone against biliary amphistome, Gigantocotyleexplanatum.
Recent research on the emergence of parasitic resistance to commonly prescribed anthelmintics has sparked a greater interest in finding novel therapeutic molecules, including those derived from plants. The use of medicinal plants and their derivatives has been viewed as an alternative source of anti-parasitic compounds and as being safe in comparison to synthetic medications due to the absence of adverse effects, ease of accessibility, and little to no expense. Consequently, in the current study, thymoquinone (TQ), an active component of Nigella sativa (Black cumin), has been tested to see their effect on the activity of some important parameters of Gigantocotyle explanatum worms, including Gamma-glutamyl Transpeptidase (GGT), glutathione (GSH), Glutathione-S-Transferase (GST), Superoxide dismutase (NO). Additionally, various other survival indicators are also used, such as assays for motility, tegument damage, and DNA fragmentation. G. explanatum adult flukes were in vitro treated to thymoquinone at various concentrations for 3 h at 37 °C. Even though all of the worms were still alive after 3 h of exposure, there was a substantial (p < 0.05) reduction in worm motility at a concentration of 90 M. There were pronounced tegumental disturbances, a loss of surface annulations, and erosion in the papillae posterior region and around the acetabulum. A significant (p < 0.05) decrease in glutathione-S-transferase and superoxide dismutase activity and reduced glutathione (GSH) level was observed. A significant inhibition of Gamma-glutamyl Transpeptidase (GGT) in thymoquinone treated worms was also evident. Thymoquinone and GGT also displayed a high interaction during in silico molecular docking, suggesting that this combination may be more effective at inhibiting the antioxidant enzymes of G. explanatum. The present findings suggest that thymoquinone would reduce the worm capacity for detoxification, while GGT inhibition would have a major impact on their ability to transport amino acids across the tegument. Thymoquinone thus seemed to be a promising anthelmintic compound for future investigations.


Recognizing off-target drug effects in the gut and brain: revisiting isotretinoin and depression.
Clinicians often face complex decisions regarding off-target drug effects, both in diagnosis and treatment. A key component in the formulation of the correct diagnosis is the temporal relationship between drug introduction and adverse effect. The sentinel injury may target the gut and brain. The description of the complaint may vary among providers. Modeling Information visualization for clinicians in real time will require the integration of time-stamped data with organ-specific complaints.


Enhanced murine CD4+ T cell responses induced by the CD2 ligand CD48.
The physiological functions of murine CD2 and its ligand CD48 are uncertain. We have examined the role of the CD2-CD48 interaction in murine T cell activation using a series of Chinese hamster ovary (CHO) cell transfectants. CHO cells expressing I-Ad together with CD48 induced more potent activation of OVA-specific, I-Ad-restricted DO11.10-transgenic T cells than CHO cells expressing I-Ad alone. CD48 augmented proliferation and IL-2 production in response to antigen. The enhancing effect of CD48 was of the same magnitude as that seen for CD80 (B7-1). Conjugate assays revealed the ability of CD48 to increase adhesion between T cells and CHO transfectants. The enhancing effects of CD48 on T cell-antigen-presenting cell adhesion and T cell activation were inhibited by anti-CD2 monoclonal antibody. This report provides the first evidence that the CD2 ligand CD48 contributes to the interactions of murine CD4+ T cells with antigen-presenting cells.


The introduction of RNA-DNA differences underlies interindividual variation in the human IL12RB1 mRNA repertoire.
Human interleukin 12 and interleukin 23 (IL12/23) influence susceptibility or resistance to multiple diseases. However, the reasons underlying individual differences in IL12/23 sensitivity remain poorly understood. Here we report that in human peripheral blood mononuclear cells (PBMCs) and inflamed lungs, the majority of interleukin-12 receptor β1 (IL12RB1) mRNAs contain a number of RNA-DNA differences (RDDs) that concentrate in sequences essential to IL12Rβ1's binding of IL12p40, the protein subunit common to both IL-12 and IL-23. IL12RB1 RDDs comprise multiple RDD types and are detectable by next-generation sequencing and classic Sanger sequencing. As a consequence of these RDDs, the resulting IL12Rβ1 proteins have an altered amino acid sequence that could not be predicted on the basis of genomic DNA sequencing alone. Importantly, the introduction of RDDs into IL12RB1 mRNAs negatively regulates IL12Rβ1's binding of IL12p40 and is sensitive to activation. Collectively, these results suggest that the introduction of RDDs into an individual's IL12RB1 mRNA repertoire is a novel determinant of IL12/23 sensitivity.


[Optimize ethanol-extraction procedure of Shenlian granules by orthogonal design with pharmacodynamics index].
To optimize the ethanol extraction process for Shenlian formula. On the basis of the pharmacodynamics index for different extraction process routes, the contents of salvianolic acid B, tanshinone ⅡA and berberine, as well as the extraction ratio in different experimental schemes were used as the ethanol extraction examining indexes, and multi-criterion synthesizing grading method was used for data analysis to optimize and verify the ethanol-extraction process conditions in orthogonal experiment. The optimum ethanol extraction process was as follows: adding 60% ethanol, 10 times amount, extracting for 2.0 h each time for a total of 2 times. This extraction process showed good stability and availability.


Motor sequence learning in children with recovered and persistent developmental stuttering: preliminary findings.
Previous studies have associated developmental stuttering with difficulty learning new motor skills. We investigated non-speech motor sequence learning in children with persistent developmental stuttering (CWS), children who have recovered from developmental stuttering (CRS) and typically developing controls (CON). Over the course of two days, participants completed the Multi-Finger Sequencing Task, consisting of repeated trials of a10-element sequence, interspersed with trials of random sequences of the same length. We evaluated motor sequence learning using accuracy and response synchrony, a timing measure for evaluation of sequencing timing. We examined error types as well as recognition and recall of the repeated sequences. CWS demonstrated lower performance accuracy than CON and CRS on the first day of the finger tapping experiment but improved to the performance level of CON and CRS on the second day. Response synchrony showed no overall difference among CWS, CRS and CON. Learning scores of repeated sequences did not differ from learning scores of random sequences in CWS, CRS and CON. CON and CRS demonstrated an adaptive strategy to response errors, whereas CWS maintained a high percentage of corrected errors for both days. Our study examined non-speech sequence learning across CWS, CRS and CON. Our preliminary findings support the idea that developmental stuttering is not associated with sequence learning per se but rather with general fine motor performance difficulties.


Effect of intravenous flecainide on atrial vulnerability in man.
Sixteen patients were investigated by means of programmed atrial stimulation at two different driving rates: 100 and 120/min. All patients had an increased atrial vulnerability at both driving rates. After intravenous flecainide application (1 mg/kg body weight as a bolus followed by the same amount given by infusion over a period of 20 min) the increased vulnerability was abolished in 11 and 9 patients respectively. In the remaining patients the rate of induced atrial tachyarrhythmia decreased. These findings correlate with a significant prolongation of the effective refractory period of the right atrium and a significant shortening of the relative refractory period of the right atrium. It is concluded that flecainide may be effective in the treatment of atrial arrhythmias in man.


Safer injection facility use and syringe sharing in injection drug users.
Safer injection facilities provide medical supervision for illicit drug injections. We aimed to examine factors associated with syringe sharing in a community-recruited cohort of illicit injection drug users in a setting where such a facility had recently opened. Between Dec 1, 2003, and June 1, 2004, of 431 active injection drug users 49 (11.4%, 95% CI 8.5-14.3) reported syringe sharing in the past 6 months. In logistic regression analyses, use of the facility was independently associated with reduced syringe sharing (adjusted odds ratio 0.30, 0.11-0.82, p=0.02) after adjustment for relevant sociodemographic and drug-use characteristics. These findings could help inform discussions about the merits of such facilities.


Strain differentiation of barley yellow dwarf virus isolates using specific monoclonal antibodies in immunosorbent electron microscopy.
Three strain-specific monoclonal antibodies, MAC. 91, MAC. 92 and MAb. MAFF2, were compared with two polyclonal antisera for the diagnosis of barley yellow dwarf virus (BYDV) strains in immunosorbent electron microscopy (ISEM). Used at 1 micrograms ml-1, the three monoclonal antibodies specifically trapped the Rothamsted PAV, RPV and MAV-like type isolates respectively, unlike the polyclonal antisera, which showed considerable heterologous reaction. The efficiency of the monoclonal and polyclonal antibodies in trapping and detecting these isolates of BYDV were compared quantitatively using ISEM and enzyme-linked immunosorbent assay (ELISA) techniques. The test provides a simple and sensitive diagnostic method for BYDV, suitable for small numbers of samples and is useful in confirming doubtful ELISA results.


Patients with Positive Lymph Nodes after Radical Prostatectomy and Pelvic Lymphadenectomy-Do We Know the Proper Way of Management?
Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it significantly affects both survival rates and recurrence, proper management remains a controversial and unsolved issue. The thorough evaluation of risk factors associated with nodal involvement, such as lymph node density or extracapsular extension, is crucial to establish the potential expansion of the disease and to substratify patients clinically. There are multiple strategies that may be employed for patients with positive lymph nodes. Nowadays, therapeutic methods are generally based on observation, radiotherapy, and androgen deprivation therapy. However, the current guidelines are incoherent in terms of the most effective management approach. Future management strategies are expected to make use of novel diagnostic tools and therapies, such as photodynamic therapy or diagnostic imaging with prostate-specific membrane antigen. Nevertheless, this heterogeneous group of men remains a great therapeutic concern, and both the clarification of the guidelines and the optimal substratification of patients are required.


Insertion sequence IS256 in canine pyoderma isolates of Staphylococcus pseudintermedius associated with antibiotic resistance.
Staphylococcus pseudintermedius is the most frequent staphylococcal species isolated from canine pyoderma. The control of S. pseudintermedius infection is often difficult due to the expanded antimicrobial resistance phenotypes. Antibiotic resistance in staphylococcal pathogens is often associated to mobile genetic elements such as the insertion sequence IS256 that was first described as a part of the transposon Tn4001, which confers aminoglycoside resistance in Staphylococcus aureus and in Staphylococcus epidermidis. In this study a collection of 70 S. pseudintermedius isolates from canine pyoderma was used to investigate antimicrobial susceptibility to 15 antibiotics and the presence of IS256, not revealed in S. pseudintermedius yet. Antibiotic resistance profiling demonstrated that all S. pseudintermedius isolates had a multi-drug resistance phenotype, exhibiting simultaneous resistance to at least five antibiotics; indeed methicillin resistant S. pseudintermedius isolates were simultaneously resistant to at least nine antibiotics and all were also gentamicin resistant. PCR analyses revealed the presence of IS256 in 43/70 S. pseudintemedius isolates. The association between the presence of IS256 and the resistance was particularly significant for certain antibiotics: cefovecin, amikacin, gentamicin and oxacillin (χ(2)p-value<0.05). However, there was a striking result in frequency of strains resistant to gentamicin and oxacillin, suggesting a specific association between the presence of the IS256 element and the determinants for the resistance to these antibiotics. To the best of our knowledge, this is the first report showing the detection of IS256 in S. pseudintermedius isolates and its association with antibiotic resistance. Our findings suggest that S. pseudintermedius may acquire antibiotic resistance genes through mobile genetic elements which may play a predominant role in the dissemination of multi-drug resistance.


Effect of PCO2-adjusted pH on the neonatal heart during hypothermic perfusion and ischemia.
The effect of pH regulation on the function of the isolated neonatal heart during continuous hypothermic perfusion and arrest was tested in 3- to 6-day-old piglet hearts. Three groups of hearts were perfused from an adult support pig, with pH varied by a carbon dioxide/oxygen gas exchanger and temperature controlled by a heat exchanger. After control function studies were obtained at normothermia with a pH of 7.4, the hearts were cooled over 15 minutes to 10 degrees C. Hypothermic perfusion was maintained for 1 hour, followed by rewarming to 37 degrees C. In group 1 (n = 5), the alpha stat (neutral) model, the blood perfusate was maintained at a pH of 7.4 (calculated at 37 degrees C). In group 2, the alkaline model, the pH was maintained at 7.9, and in group 3, the pH-stat (acid) model, the pH was maintained at 7.0. In addition, the effect of 1 hour of hypothermic ischemia after hypothermic perfusion at a pH of 7.0 was evaluated in five hearts (group 4). After rewarming no significant difference was noted in functional recovery (group 1 = 93% +/- 5%, group 2 = 92% +/- 6%, group 3 = 96% +/- 5%, and group 4 = 95% +/- 2%), oxygen consumption, coronary resistance, lactate extraction, and myocardial extravascular water content. We conclude that neonatal heart function is resistant within the range of this study to changes in pH caused by changes in carbon dioxide tension during hypothermic perfusion and ischemia.


A survey of the on-farm treatment of sole ulcer and white line disease in dairy cattle.
A telephone survey of UK dairy farmers was conducted to investigate current on-farm practice in the treatment of mild sole ulcer (SU)/sole bruising (SB), and white line disease (WLD), and the potential barriers associated with therapy. A total of 84 dairy farmers were questioned about the process of detecting and treating lame cows on their farm as well as about the specific treatments they applied. Farmers were also canvassed for their views on the efficacy of different potential treatments for mild SU/SB and WLD. In general, respondents discussed treatments for SU and WLD rather than specifically for mild SU/SB and WLD. Furthermore, when describing treatment methods, farmers rarely differentiated between SU and WLD. Trimming the affected claw with or without the additional use of orthopaedic blocks was the most commonly reported treatment method considered effective and practical by the majority of farmers. Antibiotics and/or analgesics were used by a small number of farmers, and some housed their most severely lame cows in straw pens. Lack of time, inadequate equipment and poor farm layout were identified by many survey respondents as barriers to the prompt and/or effective treatment of their lame animals.


Does lack of tocopherols and tocotrienols put women at increased risk of breast cancer?
Breast cancer is the leading site of new cancers in women and the second leading cause (after lung cancer) of cancer mortality in women. Observational studies that have collected data for dietary exposure to alpha-tocopherol with or without the other related tocopherols and tocotrienols have suggested that vitamin E from dietary sources may provide women with modest protection from breast cancer. However, there is no evidence that vitamin E supplements confer any protection whatever against breast cancer. Observational studies that have assessed exposure to vitamin E by plasma or adipose tissue concentrations of alpha-tocopherol have failed to provide consistent support for the idea that alpha-tocopherol provides any protection against breast cancer. In addition, evidence from studies in experimental animals suggest that alpha-tocopherol supplementation alone has little effect on mammary tumors. In contrast, studies in breast cancer cells indicate that alpha- gamma-, and delta-tocotrienol, and to a lesser extent delta-tocopherol, have potent antiproliferative and proapoptotic effects that would be expected to reduce risk of breast cancer. Many vegetable sources of alpha-tocopherol also contain other tocopherols or tocotrienols. Thus, it seems plausible that the modest protection from breast cancer associated with dietary vitamin E may be due to the effects of the other tocopherols and the tocotrienols in the diet. Additional studies will be required to determine whether this may be the case, and to identify the most active tocopherol/tocotrienol.


Sensitivity of glomalin-related soil protein to wildfires: Immediate and medium-term changes.
Forest fires are part of many ecosystems, especially in the Mediterranean Basin. Depending on the fire severity, they can be a great disturbance, so it is of special importance to know their impact on the ecosystem elements. In this study, we measured the sensitivity of glomalin related soil protein (GRSP), a glycoprotein produced by arbuscular mycorrhizal fungi (AMF), to fire perturbation. Two wildfire-affected areas in the SE Spain (Gata and Gorga) were studied. Soil organic carbon (SOC) was also measured. Effects on GRSP immediately after fire were analyzed in both areas, while in Gorga a monitoring of GRSP stocks over a year period after the fire was also carried out. Soil samplings were carried out every 4months. Plots (1×2m2) were installed beneath pines and shrubs in burned and an adjacent control area. Results of GRSP content immediately after a fire only showed significant differences for shrub plots (burned vs control) (p<0.01) in the Gorga site. However, a year of monitoring showed significant fire effect on GRSP content in both plot types (pines and shrubs). Control plots varied considerably over time, while in burned plots GRSP content remained constant during the whole studied period. This research provides evidence of the sensitivity of GRSP to a wildfire perturbation.


The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of Rhizoma Coptidis, has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta-analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM. Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2-hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), along with inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine. Forty-six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c (MD = -0.73; 95% CI (-0.97, -0.51)), FPG (MD = -0.86, 95% CI (-1.10, -0.62)), and 2hPG (MD = -1.26, 95% CI (-1.64, -0.89)). Improved insulin resistance was assessed by lowering FINS (MD = -2.05, 95% CI (-2.62, -1.48)), HOMA-IR (MD = -0.71, 95% CI (-1.03, -0.39)), and BMI (MD = -1.07, 95% CI (-1.76, -0.37)). Lipid metabolisms were also ameliorated via the reduction of TG (MD = -0.5, 95% CI (-0.61, -0.39)), TC (MD = 0.64, 95% CI (-0.78, -0.49)), and LDL (MD = 0.86, 95% CI (-1.06, -0.65)) and the upregulation of HDL (MD = 0.17, 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.


Targeting caspase-2 interactions with tau in Alzheimer's disease and related dementias.
Targeting amyloid-β plaques and tau tangles has failed to provide effective treatments for Alzheimer's disease and related dementias (ADRD). A more fruitful pathway to ADRD therapeutics may be the development of therapies that target common signaling pathways that disrupt synaptic connections and impede communication between neurons. In this review, we present our characterization of a signaling pathway common to several neurological diseases featuring dementia including Alzheimer's disease, frontotemporal dementia, Lewy body dementia, and Huntington's disease. This signaling pathway features the cleavage of tau by caspase-2 (Casp2) yielding Δtau314 (Casp2/tau/Δtau314). Through a not yet fully delineated mechanism, Δtau314 catalyzes the mislocalization and accumulation of tau to dendritic spines leading to the internalization of AMPA receptors and the concomitant weakening of synaptic transmission. Here, we review the accumulated evidence supporting Casp2 as a druggable target and its importance in ADRD. Additionally, we provide a brief overview of our initial medicinal chemistry explorations aimed at the preparation of novel, brain penetrant Casp2 inhibitors. We anticipate that this review will spark broader interest in Casp2 as a target for restoring synaptic dysfunction in ADRD.


Effect of Topical Tranexamic Acid on Seroma Formation in a Rat Mastectomy Model.
Seroma is the most common complication after mastectomy and reconstruction surgery. Therefore, this study aimed to determine whether the topical application of tranexamic acid would be useful to reduce seromas in a rat mastectomy model. Forty-eight Sprague-Dawley rats were divided into four groups. After mastectomy and axillary lymph node dissection, 0.4 mL of normal saline was administered to group A in the dead space. In group B, 0.4 mL of a triamcinolone mixed solution was administered. In group C, 0.4 mL of a tranexamic acid (10 mg/kg) mixed solution was administered. In group D, 0.4 mL of a tranexamic acid (50 mg/kg) mixed solution was administered. Gross examination, assessment with micro-computed tomography (CT), quantitative analysis via aspiration, and histopathologic assessment were implemented 7 and 14 days postoperatively. No other complications such as wound infection and skin necrosis were observed. At postoperative week 1, groups B and C showed significantly lower seroma volume values on micro-CT (P < 0.001 and P < 0.05, respectively) and seroma volume values at aspiration (P < 0.01 and P < 0.001, respectively) than group A. According to histopathologic analysis, inflammation was observed more frequently in groups A and D than in the other groups, and angiogenesis was more active in groups B and C than in the other groups. Topical application of tranexamic acid was as effective as topical application of triamcinolone to prevent seroma formation. The stability of tranexamic acid was confirmed when the high dose of tranexamic acid was used. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Liver resection of hepatocellular carcinoma within and beyond the Barcelona Clinic Liver Cancer guideline recommendations: Results from a high-volume liver surgery center in East Asia.
The Barcelona Clinic Liver Cancer (BCLC) guidelines were updated in 2012, and a single large hepatocellular carcinoma (HCC) more than 5 cm was regarded as BCLC stage A rather than B in the updated version. In this study, we sought to re-evaluate the outcomes of patients with HCC who underwent liver resection (LR) within (stage 0 and A) and beyond (stage B and C) the BCLC guideline recommendations of the updated BCLC staging system. This retrospective study enrolled 774 consecutive patients with naïve HCC who underwent LR from 2011 to 2018 at our institution. The overall survival (OS) and recurrence-free survival (RFS) of these patients were examined. Of the patients, 606 had BCLC stage 0 or A HCC, and 168 had BCLC stage B or C HCC. The 5-year OS and RFS among the patients within the BCLC criteria for LR were 75.2% and 56.1%, respectively, vs 54.9% and 34.0%, respectively, among the patients beyond the BCLC criteria (P < .001). Alpha-fetoprotein more than 400 ng/mL (hazard ratio = 2.06, 95% confidence interval, 1.31-3.26, P = .002) was the only independent variable associated with recurrence among the patients beyond the BCLC criteria. LR provided acceptable outcomes among selected patients with BCLC stage B and C HCC.


Infectious mimics of rheumatoid arthritis.
Rheumatoid arthritis (RA) can have various infectious mimics. As immunosuppressive agents used in treatment can aggravate the underlying infections, correct diagnosis of RA and ruling out infections is important. Numerous viral infections (Parvovirus B19, Hepatitis B, Hepatitis C, Chikungunya and other alphaviruses, human immunodeficiency virus (HIV) and various other viruses), mycobacterial infections (Poncet's disease, tubercular septic arthritis, and leprosy), bacterial arthritis, brucellosis and Lyme disease are among common infections that mimic RA. Widespread travel and tourism, especially to exotic areas, high risk sexual behavior and widespread use of immunosuppressive and chemotherapeutic agents has led to numerous outbreaks of infections in areas where these infections were never reported before. Hence, rheumatologists all over the world should be familiar with musculoskeletal manifestations of infections. History of travel, comorbid fever, skin rash, genital ulcers, urethral discharge, the consumption of unpasteurized milk, lymphadenopathy, tenosynovitis, low platelet count, and positive Mantoux test can offer potential diagnostic clues. Serological testing, cultures, specific radiological signs and deoxyribonucleic Acid (DNA) amplification techniques often aid in diagnosis. Treatment mainly consists of antimicrobial agents, analgesics, and nonsteroidal anti-inflammatory drugs (NSAIDs). However, immunosuppressive agents including steroids and disease modifying anti-rheumatic drugs (DMARDs) are needed occasionally in different refractory and prolonged illnesses. Most of the times, episodes of arthritis are self-limiting and respond to treatment of underlying cause. However, few infections like Chikungunya and Lyme's disease can lead to chronic arthritis as well.


Osteoarthritis. Emerging evidence for cell interactions in the breakdown and remodeling of cartilage.
Interactions among the cells of joint components appear to contribute to the dynamic events associated with breakdown of the cartilage matrix and remodeling of the articular surface in osteoarthritis. The mediator interleukin-1 may be one of the stimuli that induce release of hydrolytic factors from synovial membrane cells and chondrocytes, which contribute to the degradation of collagen and proteoglycans in the cartilage matrix. The remodeling process is associated with chondrocyte proliferation and vascular and cellular ingrowth from subchondral bone with osteophyte formation. It is postulated that growth factors isolated from cartilage and bone may contribute to repair and remodeling of the articular end of the joint.


Registration of two-dimensional cardiac images to preprocedural three-dimensional images for interventional applications.
To evaluate the accuracy and efficiency of rigid-body registration of two-dimensional fast cine and real-time cardiac images to high-resolution and SNR three-dimensional preprocedural reference volumes for application during MRI-guided interventional procedures. Mutual information (MI) and correlation ratio (CR) similarity measures were evaluated. The dependence of registration accuracy and efficiency on different resolution and SNR parameters, and also on cardiac-phase differences was evaluated in a porcine model. Two-dimensional images were initially misoriented at distances (d) of 2-10 mm, and rotations of +/-5 degrees about all axes. Registration error and computation time were evaluated, and performance was also assessed visually. The maximum registration error using MI (<2.7 mm and <3.6 degrees ) occurred for d = 10 mm, misrotation of +/-5 degrees , and relative SNR = 1. The computation time was 15 seconds for MI and 10 seconds for CR. Registration accuracy was not highly dependent on the relative timing, within the cycle, between the two-dimensional and three-dimensional images. Registration using CR was faster than that using MI, although accuracy was marginally higher with MI. J.


Machine learning prediction of exposure to acrylamide based on modelling of association between dietary exposure and internal biomarkers.
The ubiquitous occurrence of acrylamide in various thermal processing food products poses a potential health risk for the public. An accurate exposure assessment is crucial to the risk evaluation of acrylamide. Machine learning emerging as a powerful computational tool for prediction was employed to establish the association between internal exposure and dietary exposure to acrylamide among a Chinese cohort of middle-aged and elderly population (n = 1,272). Five machine learning regression models were constructed and compared to predict the daily dietary acrylamide exposure based on urinary biomarkers including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA), and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Other important covariates such as age, gender, physical activities, and total energy intake were also considered as predictors in the models. Average dietary intake of acrylamide among Chinese elderly participants was 8.9 μg/day, while average urinary contents of AAMA, AAMA-sul, GAMA, and iso-GAMA were 52.2, 19.1, 4.4, and 1.7 nmol/g Ucr (urine creatinine), respectively. Support vector regression (SVR) model showed the best prediction performance with a R of 0.415, followed by light gradient boosting machine (LightGBM) model (R = 0.396), adjusted multiple linear regression (MLR) model (R = 0.378), neural networks (NN) model (R = 0.365), MLR model (R = 0.363), and extreme gradient boosting (XGBoost) model (R = 0.337). The present study firstly correlated dietary exposure with internal exposure to acrylamide among Chinese elderly population, providing an innovative perspective for the exposure assessment of acrylamide.


Combining multiple quantitative and qualitative goals when assessing biomanufacturing strategies under uncertainty.
This paper reports how financial and operational results from bioprocess simulations can be combined with other criteria pertinent to decision-making predictions to provide a more holistic approach to the evaluation of biomanufacturing alternatives. The classical additive weighting method, which is a multiattribute decision-making technique that can account for both the quantitative and qualitative parameters that ultimately need to be considered, is used. Its application is demonstrated through a case study that addresses whether start-up companies should invest in a stainless steel pilot plant or use disposable equipment for the production of early phase clinical trial material. The technique is extended to allow for uncertainty in parameters. An illustration of its use to compare alternatives based on cumulative frequency curves of the aggregate scores is provided. For cases where it is difficult to discriminate between the options, plots of risk versus reward are shown to be useful for identifying the best alternative based on the risk preference of the company's management.


Quantitative levels of noise exposure and 20-year hearing decline: findings from a prospective cohort study (the HUNT Study).
We aimed to assess the association between occupational noise exposure and long-term hearing decline. This prospective cohort study used linear regression to investigate the association between occupational noise exposure and 20-year hearing decline, adjusted for important confounders. The Norwegian cohort (N = 4,448) participated in two population-based health studies with pure-tone audiometry; HUNT2 1996-1998 and HUNT4 2017-2019. Exposure assessments included a quantitative job exposure matrix (JEM) and questionnaires. The participants (40.2% men, 20-39 years at baseline) had a mean 20-year decline (3-6 kHz) of 11.3 ± 9.8 decibels (dB). There was a positive association between 20-year logarithmic average noise level (JEM-based, LEX,20y) and 20-year hearing decline among men. Compared with no exposure ≥80 dB during follow-up, minimum 5 years of exposure ≥85 dB (JEM-based) predicted 2.6 dB (95% CI: 0.2-5.0) larger 20-year decline for workers aged 30-39 years at baseline, and -0.2 dB (95% CI: -2.2 to 1.7) for workers aged 20-29 years. Combining JEM information with self-reported noise exposure data resulted in stronger associations. This large longitudinal study shows an association between JEM-based noise exposure level and increased 20-year hearing decline among men. Contrary to expectations, the associations were weaker among younger workers, which might reflect a latency period.


Development and psychometric assessment of a psychological well-being instrument for adults with mild intellectual disability or borderline intellectual functioning.
Measuring eudaimonic well-being is important to gain a complete picture of the well-being of individuals with mild intellectual disabilities or borderline intellectual functioning (MID-BIF), but there is no measurement instrument available for this population coding for multiple dimensions of eudaimonic well-being. The current study developed and piloted a new instrument coding for eudaimonic well-being in individuals with MID-BIF. The instrument (SPWB-ID) was adapted from Ryff's scales of psychological well-being, including subscales addressing purpose in life, environmental mastery, positive relationships, self-acceptance, personal growth, and autonomy. Adaptations were based on the literature and interviews with people with MID-BIF and experts in the field. The SPWB-ID was piloted among 103 adults with MID-BIF. The trimmed version of the SPWB-ID showed sufficient to good internal consistency and test-retest reliability. Hypothesis testing for construct validity suggested the subscales of the SPWB-ID measured well-being, showing moderate to high correlations with quality of life, and differences in eudaimonic well-being between participants with and without clinically relevant depression scores. The SPWB-ID reliably measures eudaimonic well-being in individuals with MID-BIF. This enables support providers to collect information on eudaimonic well-being, providing input for person-centred care and support for individuals with MID-BIF.


Reactive transport modeling of processes controlling the distribution and natural attenuation of phenolic compounds in a deep sandstone aquifer.
Reactive solute transport modeling was utilized to evaluate the potential for natural attenuation of a contaminant plume containing phenolic compounds at a chemical producer in the West Midlands, UK. The reactive transport simulations consider microbially mediated biodegradation of the phenolic compounds (phenols, cresols, and xylenols) by multiple electron acceptors. Inorganic reactions including hydrolysis, aqueous complexation, dissolution of primary minerals, formation of secondary mineral phases, and ion exchange are considered. One-dimensional (1D) and three-dimensional (3D) simulations were conducted. Mass balance calculations indicate that biodegradation in the saturated zone has degraded approximately 1-5% of the organic contaminant plume over a time period of 47 years. Simulations indicate that denitrification is the most significant degradation process, accounting for approximately 50% of the organic contaminant removal, followed by sulfate reduction and fermentation reactions, each contributing 15-20%. Aerobic respiration accounts for less than 10% of the observed contaminant removal in the saturated zone. Although concentrations of Fe(III) and Mn(IV) mineral phases are high in the aquifer sediment, reductive dissolution is limited, producing only 5% of the observed mass loss. Mass balance calculations suggest that no more than 20-25% of the observed total inorganic carbon (TIC) was generated from biodegradation reactions in the saturated zone. Simulations indicate that aerobic biodegradation in the unsaturated zone, before the contaminant entered the aquifer, may have produced the majority of the TIC observed in the plume. Because long-term degradation is limited to processes within the saturated zone, use of observed TIC concentrations to predict the future natural attenuation may overestimate contaminant degradation by a factor of 4-5.


Altered hyaluronan biosynthesis in cancer progression.
Microenvironmental stimuli can influence the malignant phenotype of cancer cells. Notably, the altered biosynthesis of hyaluronan, a constituent of the extracellular microenvironment, has been implicated in the progress and metastasis of carcinomas. The discovery of hyaluronan synthase (HAS) genes, which encode the key enzymes in hyaluronan biosynthesis, has enabled great strides in understanding the mechanism underlying altered hyaluronan production in cancer and the involvement of this polysaccharide in tumor progression. Recent studies using HAS transgenic mice have provided evidence that overproduction of hyaluronan in mammary tumors accelerates tumor growth through the recruitment of stromal cells and vasculature, revealing further insight into how increased hyaluronan influences the malignant behaviors of cancer cells.


Treatment techniques and site considerations regarding dysphagia-related quality of life in cancer of the oropharynx and nasopharynx.
To assess the relationship for oropharyngeal (OP) cancer and nasopharyngeal (NP) cancer between the dose received by the swallowing structures and the dysphagia related quality of life (QoL). Between 2000 and 2005, 85 OP and 47 NP cancer patients were treated by radiation therapy. After 46 Gy, OP cancer is boosted by intensity-modulated radiation therapy (IMRT), brachytherapy (BT), or frameless stereotactic radiation/cyberknife (CBK). After 46 Gy, the NP cancer was boosted with parallel-opposed fields or IMRT to a total dose of 70 Gy; subsequently, a second boost was given by either BT (11 Gy) or stereotactic radiation (SRT)/CBK (11.2 Gy). Sixty OP and 21 NP cancer patients responded to functional and QoL questionnaires (i.e., the Performance Status Scales, European Organization for Research and Treatment of Cancer H&N35, and M.D. Anderson Dysphagia Inventory). The swallowing muscles were delineated and the mean dose calculated using the original three-dimensional computed tomography-based treatment plans. Univariate analyses were performed using logistic regression analysis. Most dysphagia problems were observed in the base of tongue tumors. For OP cancer, boosting with IMRT resulted in more dysphagia as opposed to BT or SRT/CBK. For NPC patients, in contrast to the first booster dose (46-70 Gy), no additional increase of dysphagia by the second boost was observed. The lowest mean doses of radiation to the swallowing muscles were achieved when using BT as opposed to SRT/CBK or IMRT. For the 81 patients alive with no evidence of disease for at least 1 year, a dose-effect relationship was observed between the dose in the superior constrictor muscle and the "normalcy of diet" (Performance Status Scales) or "swallowing scale" (H&N35) scores (p < 0.01).


The role of radiology in the diagnosis and treatment of biliary complications after liver transplantation.
Hepatic transplantation is now an accepted therapeutic option for selected patients with terminal liver disease. Biliary complications are, however, relatively common after transplantation. We reviewed our experience with diagnostic and therapeutic biliary radiologic procedures in 151 hepatic recipients. Biliary complications were seen in 25% of patients. Interventional radiologic procedures were an integral part of the diagnostic and therapeutic management of these patients; reoperation was, nonetheless, occasionally required.


Exosome-mediated crosstalk between tumor cells and innate immune cells: implications for cancer progression and therapeutic strategies.
The increasing number of cancer-associated deaths despite the substantial improvement in diagnosis and treatment has sparked discussions on the need for novel biomarkers and therapeutic strategies for cancer. Exosomes have become crucial players in tumor development and progression, largely due to the diverse nature of their cargo content released to recipient cells. Importantly, exosome-mediated crosstalk between tumor and stromal cells is essential in reprogramming the tumor microenvironment to facilitate tumor progression. As a result, exosomes have gradually become a marker for the early diagnosis of many diseases and an important tool in drug delivery systems. However, the precise mechanisms by which exosomes participate in tumor progression remain elusive, multifaceted, and a double-edged sword, thus requiring further clarification. The available evidence suggests that exosomes can facilitate communication between innate immune cells and tumor cells to either support or inhibit tumor progression. Herein, this review focused on exosome-mediated intercellular communication between tumor cells and macrophages, neutrophils, mast cells, monocytes, dendritic cells, and natural killer cells. Specifically, how such intercellular communication affects tumor progression has been described. It has also been discussed that, depending on their cargo, exosomes can suppress or promote tumor cell progression. In addition, the potential application of exosomes and strategies to target exosomes in cancer treatment has been comprehensively discussed.


Defective monocyte and polymorphonuclear leukocyte chemotaxis in atopic disease.
Monocyte (MN) and polymorphonuclear (PMN) leukocyte chemotaxis was studied in 17 atopic children with hyperimmunoglobulinemia E (IgE), 9 age- and diagnosis-matched children with normal IgE levels, 10 pediatric controls, and 45 adult controls. Twenty-one of the 26 atopic patients had eczema, while 5 had only respiratory allergies. All patients were free of infection and receiving no systemic corticosteroids. Depressed PMN chemotaxis was found in only one patient. Defects of MN chemotaxis were detected in 8 of 17 atopic children with IgE and 2 of 9 with normal IgE values. Seven of 21 patients with atopic eczema and 3 of 5 with respiratory allergies had depressed MN chemoatxis. No evidence was found for a cell-directed chemotactic inhibitor in the plasma of patients with abnormal MN chemotaxis. These data demonstrate that: (1) MN chemotaxis is frequently depressed in uninfected atopic patients; (2) this abnormality occurs in patients with respiratory allergies as well as in those with eczema and is more prevalent in atopics with IgE; and (3) PMN chemotactic defects are uncommon in allergic patients. Whether abnormal MN chemotaxis is a primary or a secondary event in atopy requires further investigation.


Prostaglandin F2 alpha-1-isopropylester lowers intraocular pressure without decreasing aqueous humor flow.
Using fluorophotometry, we performed a randomized, dose-response study of the effects of a prostaglandin derivative on aqueous humor flow. Prostaglandin F2 alpha 1-isopropylester, 0.224 micrograms, 0.448 micrograms, and 1.120 micrograms, in saline with polysorbate 80 was instilled into one eye of 20 subjects in three separate dose studies. Polysorbate 80 in saline was instilled in the fellow eye as a control. The drug had no measurable effect on aqueous humor flow or corneal endothelial permeability. Intraocular pressure measured eight hours after administration of the highest dose, 1.120 micrograms, was 20% lower in the treated eye as compared to the fellow eye (P less than .001).


Increased Parasympathetic Activity as a Fall Risk Factor Beyond Conventional Factors in Institutionalized Older Adults with Mild Cognitive Impairment.
This study aimed to investigate autonomic nervous function during the orthostatic challenge and its relationship with depression and fall, and to elucidate fall-associated factors, including autonomic function, executive function, and depression among institutionalized older adults with mild cognitive impairment (MCI). This study employed a descriptive cross-sectional design. Fall experiences in the current institutions were researched. Heart rate variability (HRV) during the orthostatic challenge was measured. Executive function was evaluated using the semantic verbal fluency test and clock drawing test. Depression was assessed using the Geriatric Depression Scale. Of the 115 older adults, 17 (14.8%) experienced falls in the current institution. None of the HRV indices during the orthostatic challenge showed any significant changes except for the standard deviation of normal RR intervals (p = .037) in the institutionalized older adults with MCI. None of the HRV indices was significantly related to the depressive symptoms. Multivariate logistic regression analysis showed that normalized high frequency on lying was independently associated with falls (OR = 1.027, p = .049) after adjusting for other conventional fall risk factors although executive function and depressive symptoms were not significant factors for falls. Institutionalized older adults with MCI were vulnerable to autonomic nervous modulation, especially to sympathetic modulation, during the orthostatic challenge, which was not associated with depressive symptoms. As increased resting parasympathetic activity seemed to play a key role in association with falls, autonomic nervous function assessment should be considered for fall risk evaluation.


Dietary nickel chloride restrains the development of small intestine in broilers.
The aim of this study was to determine the effects of dietary NiCl2 on the development of the small intestine in broilers by the methods of light microscopy, histochemistry and enzyme-linked immunosorbent assay. A total of 240 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet or the same basal diet supplemented with 300, 600 and 900 mg/kg of nickel chloride (NiCl2) for 42 days. Results showed that the small intestinal villus height, crypt depth and villus/crypt ratio were significantly decreased, and also the small intestinal goblet cells numbers and insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF) contents were significantly decreased in the 300-, 600- and 900-mg/kg groups when compared with those of the control group. In conclusion, dietary NiCl2 in excess of 300 mg/kg reduced the villus height, crypt depth, the goblet cells population and the IGF-1 and EGF contents in the small intestine, indicating that the normal development and function of the small intestine were finally impaired in broilers. This study firstly provided the new experimental information for future studies on the effects of NiCl2 on the intestinal function in humans and other animals.


Hydrogenation of nitroarenes into aromatic amines over Ag@BCN colloidal catalysts.
The present work reports that two-dimension layered ternary boron carbon nitrogen nanosheets can serve as good carriers to support and disperse noble metal nanoparticles. The Ag@BCN colloids have thus been prepared by attaching Ag nanoparticles on the surfaces of BCN nanosheets. The detailed structures of the Ag@BCN samples were investigated by X-ray diffraction, transmission electron microscopy, atomic force microscope, infrared, and X-ray photoelectron spectroscopy. It is found that the surface NH groups of BCN nanosheets are beneficial for the attachment of Ag nanopaprticles. Compared with the conventional organic capping compounds, the two dimensional planar BCN nanosheets endow the attached nanoparticle with the high active surfaces. Moreover, the hydrogenation of nitroarenes into the corresponding aromatic amines can be highly achieved over Ag@BCN colloids by NaBH4. In particular, the apparent activation energy of the conversion reaction of p-nitroaniline to p-phenylenediamine was found to be 76.0kJ/mol over the Ag@BCN colloids with 3wt% Ag content. Our results may provide a new approach for the design noble metal based composites and find the practical application for the hydrogenation of nitroarenes.


Staphylolytic enzyme from Pseudomonas aeruginosa: characterization and immunocytochemical localization.
Staphylolytic enzyme, a specific peptidase produced by Pseudomonas aeruginosa, has been characterized by using immunochemical procedures. Lytic activity was detected in the extracellular medium of Pseudomonas cultures at the beginning of the stationary growth phase. No activity was detected in bacterial cells. However, lytic protein antigen was present in periplasmic and cytoplasmic fractions, suggesting that staphylolytic enzyme is synthesized as an inactive precursor which becomes active during translocation to the extracellular broth. Results obtained in immunolocalization experiments indicate the presence of the precursor in the outer part of cells. The export pathway of staphylolytic enzyme through the periplasmic space is proposed.


Prospective comparative study of quantitative X-ray (QXR) versus dual energy X-ray absorptiometry to determine the performance of QXR as a predictor of bone health for adult patients in secondary care.
To evaluate a method of quantitative X-ray (QXR) for obtaining bone health information from standard radiographs aimed at identifying early signs of osteoporosis to enable improved referral and treatment. This QXR measurement is performed by postexposure analysis of standard radiographs, meaning bone health data can be acquired opportunistically, alongside routine imaging. The relationship between QXR and dual energy X-ray absorptiometry (DEXA) was demonstrated with a phantom study. A prospective clinical study was conducted to establish areal bone mineral density (aBMD) prediction model and a risk prediction model of a non-normal DEXA outcome. This was then extrapolated to a larger patient group with DEXA referral data. Secondary care National Health Service Hospital. 126 consenting adult patients from a DEXA clinic. All participants underwent a DEXA scan to determine BMD at the lumbar spine (L2-L4) and both hips. An additional Antero-Posterior pelvis X-ray on a Siemens Ysio, fixed digital radiograph system was performed for the study. Performance of QXR as a risk predictor for non-normal (osteoporotic) BMD. Interim clinical study data from 78 patients confirmed a receiver operator curve (area under the ROC curve) of 0.893 (95% CI 0.843 to 0.942) for a risk prediction model of non-normal DEXA outcome. Extrapolation of these results to a larger patient group of 11 029 patients indicated a positive predictive value of 0.98 (sensitivity of 0.8) for a population of patients referred to DEXA under current clinical referral criteria. This study confirms that the novel QXR method provides accurate prediction of a DEXA outcome. ISRCTN98160454; Pre-results.


Infrared spectroscopic laser scanning confocal microscopy for whole-slide chemical imaging.
Chemical imaging, especially mid-infrared spectroscopic microscopy, enables label-free biomedical analyses while achieving expansive molecular sensitivity. However, its slow speed and poor image quality impede widespread adoption. We present a microscope that provides high-throughput recording, low noise, and high spatial resolution where the bottom-up design of its optical train facilitates dual-axis galvo laser scanning of a diffraction-limited focal point over large areas using custom, compound, infinity-corrected refractive objectives. We demonstrate whole-slide, speckle-free imaging in ~3 min per discrete wavelength at 10× magnification (2 μm/pixel) and high-resolution capability with its 20× counterpart (1 μm/pixel), both offering spatial quality at theoretical limits while maintaining high signal-to-noise ratios (>100:1). The data quality enables applications of modern machine learning and capabilities not previously feasible - 3D reconstructions using serial sections, comprehensive assessments of whole model organisms, and histological assessments of disease in time comparable to clinical workflows. Distinct from conventional approaches that focus on morphological investigations or immunostaining techniques, this development makes label-free imaging of minimally processed tissue practical.


Selenium bioaccessibility in stomach, small intestine and colon: Comparison between pure Se compounds, Se-enriched food crops and food supplements.
Selenium (Se) is an essential nutrient for humans as it plays an important role in glutathione peroxidase (GPx) activity. Moreover, it may reduce cancer risks. The objective of this work was to examine in vitro the bioaccessibility of Se in three different Se-enriched food supplements and two different Se-enriched food crops, with reference to two pure Se standards, and changes in its speciation during intestinal digestion. Selenate was found to be stable throughout the entire digestion, whereas incubation of selenomethionine resulted in the chemical and microbial production of minor metabolites. The bioaccessibility of Se in Se-enriched food supplements and food crops was found to be highest in the small intestine. Compared to SelenoPrecise and Se-ACE tablets, a yoghurt-based supplement exhibited a much lower Se bioaccessibility, possibly due to the presence of nano- or microparticles of elemental Se. Colon microbiota were found to primarily affect Se bioaccessibility in the colon environment, with the presence of inactivated microbiota resulting in a higher bioaccessibility. A higher potential of Se to reach the colon and become accessible in this phase may result in beneficial effects on the colon health.


A test of statistical techniques for detecting density dependence in sequential censuses of animal populations.
Principal and reduced major axes, and Bulmer's (1975) tests have been suggested as methods for detecting the presence of density dependence in a series of population censuses that are unsuitable for analysis by alternative means e.g. by k-factor analysis. These alternative methods are tested using census data, some of which are previously unpublished, from natural populations known from independent evidence to be subject to density dependent processes. All the methods fail to detect density dependence reliably, irrespective of sample size and the dynamics of the population. We conclude that none of the methods tested is sufficiently reliable to be useful as a test of density dependence in sequential censues of animal populations.


HLA-C*07:465, a novel HLA-C*07 variant, detected in a Singaporean Chinese individual.
One nucleotide replacement in codon 50 of HLA-C*07:02:01:01 results in a novel allele, HLA-C*07:465.


Breast Cancer Cryoablation in the Multidisciplinary Setting: Practical Guidelines for Patients and Physicians.
Breast cancer cryoablation has emerged as a minimally invasive alternative to lumpectomy for treating early-stage breast cancer. However, no consensus exists on what should be considered the standard of care for the multidisciplinary management of patients treated with breast cancer cryoablation. In lieu of national guidelines, this review of the literature provides a multidisciplinary framework and an evidence-based discussion of the integration of "standard of care practices" in the comprehensive management of breast cancer cryoablation patients.


Defective Toll-like receptor 9-mediated cytokine production in B cells from Bruton's tyrosine kinase-deficient mice.
Bruton's tyrosine kinase (Btk), a member of the Tec family of tyrosine kinases, plays an important role in the differentiation and activation of B cells. Mutations affecting Btk cause immunodeficiency in both humans and mice. In this study we set out to investigate the potential role of Btk in Toll-like receptor 9 (TLR9) activation and the production of pro-inflammatory cytokines such as interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and IL-12p40. Our data show that Btk-deficient B cells respond more efficiently to CpG-DNA stimulation, producing significantly higher levels of pro-inflammatory cytokines but lower levels of the inhibitory cytokine IL-10. The quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis presented in this work shows that mRNA production of one of the important new members of the IL-12 family, IL-27, was significantly increased in Btk-deficient B cells after CpG-DNA stimulation. In this study, we demonstrate significant differences in CpG responsiveness between transitional 1 (T1) and T2 B cells for survival and maturation. Furthermore, TLR9 expression, measured both as protein and as mRNA, was increased in Btk-defective cells, especially after TLR9 stimulation. Collectively, these data provide evidence in support of the theory that Btk regulates both TLR9 activation and expression in mouse splenic B cells.


A Smartphone-based Diffusometric Immunoassay for Detecting C-Reactive Protein.
In this study, we developed a portable smartphone-based diffusometry for analyzing the C-reactive protein (CRP) concentration. An optimized fluorescence microscopic add-on system for a smartphone was used to image the 300 nm fluorescent beads. Sequential nanobead images were recorded for a period and the image data were used for fluorescence correlation spectrometric (FCS) analysis. Through the analysis, the nanobeads' diffusion coefficient was obtained. Further, the diffusion coefficients of the anti-CRP-coated nanobeads, which were suspended in the samples with various CRP concentrations, were estimated using smartphone-based diffusometry. After 10 min of reaction, the anti-CRP-coated nanobeads in a higher CRP concentration solution led to a lower diffusion coefficient. Based on the experiments, a linear sensing range of 1~8 µg/mL was found.


Classroom walkthroughs as an effective strategy for preschool improvement during the COVID-19 lockdowns: a Chinese model.
Classroom walkthroughs are a widely used strategy for school improvement, varying over contexts and times. This study aims to explore the Chinese model of classroom walkthroughs in early childhood settings (ECS) during the COVID-19 lockdowns through a triangulated qualitative study. First, a group of ECS leaders (N = 15; Myear of teaching experience = 18.87, SD = 7.74, range = 6-33 years) and a group of teachers (N = 15; Myear of teaching experience = 8.40, SD = 3.96, range = 3-19 years) were interviewed in early 2022, and leaders' observations notes were reviewed. The interview data were transcribed, recoded, and analyzed using an inductive approach, and the walkthrough documents were examined as a triangulation. Four themes and 13 subthemes emerged from the interview data: content, pedagogical skills, tasks, and challenges pertaining to classroom walk-throughs. Two major challenges against efficient classroom walkthroughs during the COVID-19 lockdowns were found: building community and feeding forward. Based on the results, a Chinese model of classroom walkthrough was proposed. Implications for quality improvement were also addressed.


Ionically bridged dexamethasone sodium phosphate-zinc-PLGA nanocomplex in alginate microgel for the local treatment of ulcerative colitis.
Colon-targeted oral drug delivery systems comprising nanoparticles and microparticles have emerged as promising tools for the treatment of ulcerative colitis (UC) because they minimize side effects and maximize the local drug concentration. Dexamethasone sodium phosphate (DSP) is a potent anti-inflammatory glucocorticoid used for the treatment of UC. However, it remains a rather short-term treatment option owing to its side effects. In the present study, we developed the alginate gel encapsulating ionically bridged DSP-zinc-poly(lactic-co-glycolic acid) (PLGA) nanocomplex (DZP-NCs-in-microgel) for the oral local treatment of UC. The successful encapsulation of DSP-zinc-PLGA nanocomplex (DZP-NCs) in alginate microgel was confirmed by SEM imaging. The prepared gel released DZP-NCs in the stimulated intestinal fluid and dampened the release of DSP in the upper gastrointestinal tract. Furthermore, DZP-NCs-in-microgel alleviated colonic inflammation in a mouse model of dextran sodium sulfate-induced colitis by relieving clinical symptoms and histological marks. Our results suggest a novel approach for the oral colon-targeted delivery of dexamethasone sodium phosphate for the treatment of UC.


Linagliptin, the dipeptidyl peptidase-4 enzyme inhibitor, lessens CHOP and GRP78 biomarkers levels in cisplatin-induced neurobehavioral deficits: A possible restorative gateway.
Cisplatin (CP) is a cornerstone chemotherapeutic agent, however, its neurotoxicity is a chief cause of its limited usage. Linagliptin, which is a dipeptidyl peptidase-4 enzyme inhibitor, has exhibited considerable neuroprotective potential. We aimed to evaluate the linagliptin modulatory effects on endoplasmic reticulum (ER) stress, redox status, and apoptosis in CP-induced neurotoxicity. Thirty mice were allocated equally into the control group, Group II: CP group, and Group III: linagliptin treated CP group. All groups were subjected to the measurement of hippocampal messenger RNA gene expression of glucose-regulated protein-78 and C/EBP homologous protein (CHOP). Peroxisome proliferator-activated receptor γ coactivator 1α and cleaved caspase-3 levels were assessed by the enzyme-linked immunosorbent assay technique while malondialdehyde, reduced glutathione levels and superoxide dismutase activity were detected spectrophotometrically. Linagliptin ameliorated ER stress and enhanced antioxidant status with cognitive function improvement. Linagliptin may be considered a promising neuroprotective agent owing to its ability to reduce ER/oxidative stress.


Higher stress and symptom severity are associated with worse depressive symptom profiles in patients receiving chemotherapy.
In a sample of oncology patients, identify subgroups of patients with distinct depressive symptom profiles and evaluate for differences in demographic and clinical characteristics, levels of stress and resilience, and the severity of common co-occurring symptoms. Patients (n = 1327) had a diagnosis of breast, gastrointestinal, gynecological, or lung cancer; had received chemotherapy within the preceding four weeks; and were scheduled to receive at least two additional cycles of chemotherapy. Demographic and clinical characteristics, stress, resilience, and co-occurring symptoms were evaluated at enrollment. Depressive symptoms were evaluated using the Center for Epidemiological Studies-Depression (CES-D) scale a total of six times over two cycles of chemotherapy. Latent profile analysis (LPA) was used to identify subgroups of patients (i.e., latent classes) with distinct depressive symptom profiles using the six CES-D scores. Based on the findings from the LPA, 47.3% of the patients were classified as "None"; 33.6% as "Subsyndromal"; 13.8% as "Moderate"; and 5.3% as "High". Compared to None class, patients in the Subsyndromal, Moderate, and High classes had a lower functional status, a higher comorbidity burden, and a self-reported diagnosis of depression or back pain. Those patients with higher levels of depressive symptoms reported higher levels of stress, lower levels of resilience, and increased severity of co-occurring symptoms. Inter-individual variability in depressive symptoms was associated with demographic and clinical characteristics, multiple types of stress and levels of resilience, as well as with the increased severity of multiple co-occurring symptoms. The risk factors associated with worse depressive symptom profiles can assist clinicians to identify high risk patients and initiate more timely supportive care interventions.


Prevalence of laryngopharyngeal reflux disease in patients with diabetes mellitus.
To study the prevalence of laryngopharyngeal reflux disease (LPRD) in patients with type 2 diabetes mellitus (T2DM) and report the correlation between LPRD and glycemic control, duration of the disease, and presence of neuropathy. This is a cross-sectional study of 100 patients with T2DM and 33 controls matched according to age and gender. The reflux symptom index (RSI) was used to assess the presence of LPRD. A score greater than 10 was considered diagnostic of LPRD. Twenty-two percent of patients with T2DM had RSI above 10 versus 9.1% of controls. The difference was not statistically different (P value of 0.100). The average score of all symptoms of LPRD was higher in the diabetic group compared with the control group. There was a significant increase in the average score of "throat clearing" and "lump sensation in throat," with a borderline significant increase in "annoying cough" in patients with diabetes versus controls (respective P values of 0.03, 0.025, and 0.066). There was no correlation between LPRD and any of the demographic variables except neuropathy. Patients with T2DM are more likely to have LPRD compared with controls. However, the prevalence of LPRD is not significantly higher in diabetic patients compared with controls. When present, LPRD correlates with neuropathy. 2c.


Is proteinuria a rare condition in apparently healthy and sick cats? A feline practice experience (2007-2018).
Proteinuria is assumed to be less frequent in cats than in dogs and is mainly associated with chronic kidney disease (CKD). The current study aimed to evaluate and compare urine protein-to-creatinine (UPC) values retrospectively in cats visited for comprehensive annual health check or for presenting systemic clinical signs related to CKD. UPC ratio was retrospectively evaluated in 112 owned cats, out of which 51 (45.5%) were apparently healthy cats according to their owners who visited for comprehensive annual health checks and 61 (54.5%) sick cats, presenting systemic clinical signs suggesting CKD, such as weight loss or polyuria/polydipsia, among others. Based on UPC, the present study found that 54.5% of all cats included were borderline proteinuric or proteinuric, having increased UPC (UPC ≥ 0.2), with 35.7% included in the sick group and 18.7% in the health-check group. Increased UPC was also statistically associated with azotemia and isosthenuria (urinary-specific gravity between 1,008 and 1,035) in both sick and health-check groups of cats. Independent of the reason for their medical visit, it could be concluded that borderline proteinuria and proteinuria were statistically mainly related to CKD in cats. Furthermore, the measurement of UPC could be very useful in the detection and management of CKD in apparently healthy cats during a medical visit for annual health check irrespective of the age.


A case of acute myocarditis induced by PD-1 inhibitor (sintilimab) in the treatment of large cell neuroendocrine carcinoma.
The combination of Sintilimab with pemetrexed/platinum has become the first-line treatment for non-squamous non-small-cell lung carcinoma (NSCLC). Here, we report a patient with metastatic large cell neuroendocrine carcinoma (LCNEC) treated with Sintilimab for five cycles who developed shortness of breath after activity. The level of creatine kinase (CK), creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) were significantly increased. The cardiac MR suggested that heart function was slightly decreased. Considering that the patient did not take any illicit drugs, without history of autoimmune disease, coronary heart disease, arrhythmia, or chronic heart failure, we diagnosed the patient with Sintilimab-induced myocarditis. The symptoms alleviated after rapid use of glucocorticoids. Myocarditis is a rare immune-related adverse events (irAEs), especially myocarditis induced by programmed cell death receptor-1 (PD-1) inhibitor in the treatment of LCNEC.