Phylogeny, expression and enzyme activity of zebrafish cyp19 (P450 aromatase) genes.
The cyp19 encodes P450 aromatase, the enzyme catalyzing the conversion of estrogens from androgens. Estrogens affect the dimorphic, anatomical, functional and behavioral aspects of development of both males and females. In zebrafish, two cyp19 genes, cyp19a and cyp19b were found. They are expressed in ovary and brain, respectively. Expression of cyp19b can be detected by 11 days post-fertilization (dpf) by in situ hybridization in the olfactory bulbs, ventral telencephalic region and the hypothalamus of the brain in both male and female, where it is generally known to be affecting the reproductive function and sexual behavior. COS-1 clones permanently expressing the enzymes have been isolated. Both aromatase enzymes encoded by these two genes are functional in COS-1 cells and they can use androstenedione and testosterone equally efficiently. The presence of two functional cyp19 in zebrafish has its evolutionary and physiological importance.


Pharmacokinetic-pharmacodynamic (PK/PD) modeling to study the hepatoprotective effect of Perilla Folium on the acute hepatic injury rats.
Perilla Folium (PF), is a traditional medicinal material with the homology of medicine and food in China and has been widely used due to its rich nutritional content and medicinal value. The hepatoprotective effects of PF extract include their protection against acute hepatic injury, tert-butylhydroperoxide (t-BHP) induced oxidative damage, and Lipopolysaccharide (LPS) and D-galactosamine (D-GalN) induced hepatic injury have been well studied. However, there are few reports on the pharmacokinetics studies of PF extract in acute hepatic injury model rats, and the anti-hepatic injury activity of PF is still unclear. The differences in the plasma pharmacokinetic of 21 active compounds between the normal and model groups were compared, and established pharmacokinetics/pharmacodynamics (PK/PD) modeling was to analyze the hepatoprotective effects of PF. The acute hepatic injury model was induced with an intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-GalN), and the plasma pharmacokinetics of 21 active compounds of PF were analyzed in the normal and model groups using ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). The correlation between plasma components and hepatoprotective effects indicators (the alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactic dehydrogenase (LDH)) in the model group was also investigated and established a Pharmacokinetic/pharmacodynamic (PK/PD) correlation analysis of the hepatoprotective effects of PF. The results revealed that organic acid compounds possessed the characteristics of faster absorption, shorter peak time and slower metabolism, while the flavonoid compounds had slower absorption and longer peak time, and the pharmacokinetics of various components were significantly affected after modeling. The results of PK/PD modeling analysis demonstrated that the plasma drug concentration of each component existed a good correlation with the three AST, ALT, and LDH, and the lag time of the efficacy of each component is relatively long. The plasma drug concentration of each component existed a good correlation with the three AST, ALT, and LDH, and the lag time of the efficacy of each component is relatively long in vivo.


Evaluation of the application potential of bentonites in phenanthrene bioremediation by characterizing the biofilm community.
Application of clay minerals in bioremediation has emerged as a new and promising research field. In this study, the application of calcinated bentonite (CB) and calcinated organobentonite (COB) in phenanthrene (Phe) bioremediation showed high Phe removal efficiency. Clone libraries based on 16S rRNA gene and scanning electronic microscopy showed that diverse taxa of bacteria formed biofilms on both COB and CB particles. The family Sphingomonadaceae was the major group and made up 18% and 23% of the COB and CB biofilm composition, respectively. All and 80% of dioxygenase genes from COB and CB biofilms were closely related to that of Sphingomonas sp., and others matched to that of Comamonas and Mycobacterium. The selective effect of COB on bacterial community was also evident. This study characterized for the first time the bacterial diversity of biofilm community and functional Phe degrading groups on bentonites particles, and provided useful information for future applications.


Radiofrequency treatment.
This article discusses radiofrequency energy as a treatment of musculoskeletal tumors,focusing on osteoid osteomas. The technique has also been applied to a number of different primary musculoskeletal tumors and is increasingly being used as a palliative method in the management of painful skeletal metastases. Radiofrequency treatment of musculoskeletal tumors can be of great clinical value. When the low-power, highly limited methods are applied to small tumors such as osteoid osteomas, the technique is effective and exceptionally safe. Creation of larger thermal lesions, however, can be accompanied by significant risks, and the risk-to-benefit ratio should be carefully considered before undertaking such a treatment.


Meta-analysis of the association of maternal smoking and passive smoking during pregnancy with neural tube defects.
It is unclear whether the incidence of neural tube defects (NTDs) is greater with maternal smoking or with passive smoking during pregnancy. To compare the effects of smoking and passive smoking during pregnancy on the risk of NTDs. English and Chinese databases were searched for relevant papers published before March 2017, using search terms including "smoking" and "NTD." Case-control and cohort studies on the aforementioned association were included. Two authors independently extracted the original data. Meta-analyses were performed to assess the risks associated with smoking and passive smoking, followed by a comparison of the two pooled effect estimates. The I2 statistic was used to examine between-study heterogeneity. The final analysis included 23 articles representing 33 studies. The pooled odds ratio (OR) and 95% confidence interval (CI) for the risk of NTDs was 1.052 (0.907-1.220) with smoking and 1.898 (1.557-2.313) with passive smoking. Comparison of these ORs indicated that the risk of NTDs was higher with passive smoking than with smoking (OR 1.804, 95% CI 1.409-2.309). Compared with smoking, exposure to passive smoking during pregnancy carries a higher risk of having infants with NTDs.


From NAFLD to HCC: Advances in noninvasive diagnosis.
Non-alcoholic fatty liver disease (NAFLD) has gradually become one of the major liver health problems in the world. The dynamic course of the disease goes through steatosis, inflammation, fibrosis, and carcinoma. Before progressing to carcinoma, timely and effective intervention will make the condition better, which highlights the importance of early diagnosis. With the further study of the biological mechanism in the pathogenesis and progression of NAFLD, some potential biomarkers have been discovered, and the possibility of their clinical application is gradually being discussed. At the same time, the progress of imaging technology and the emergence of new materials and methods also provide more possibilities for the diagnosis of NAFLD. This article reviews the diagnostic markers and advanced diagnostic methods of NAFLD in recent years.


Serum high-mobility group box 1 as a predictive marker for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and interstitial lung disease.
High-mobility group box 1 (HMGB1) is a pro-inflammatory protein, that is associated with tumorigenesis, interstitial lung disease (ILD), and acute lung injury. Chemotherapy-induced lung injury is a common and serious adverse event in patients with lung cancer and ILD, but its pathogenesis and predictive biomarkers are not known. This study aimed to investigate the predictive potential of serum HMGB1 levels for cytotoxic chemotherapy-induced lung injury in these patients. From 743 patients with advanced lung cancer, we enrolled 83 consecutive patients with ILD and background-matched 83 patients without ILD. Additionally, 83 healthy subjects were included. After measuring baseline levels of serum HMGB1 in three groups, we evaluated the predictive values of baseline HMGB1 levels for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and ILD. Higher levels of serum HMGB1 were independently associated with higher tumor burden, as assessed by total tumor size, and the presence of ILD. Twenty-five (30.1%) of patients with lung cancer and ILD experienced cytotoxic chemotherapy-induced lung injury within one year. Univariate Cox proportional hazards model showed that higher levels of HMGB1 and higher tumor burden were associated with disease onset. Moreover, multivariate analysis revealed that only HMGB1 was independently associated with this severe complication in patients with lung cancer and ILD. HMGB1 is a potential predictive blood biomarker for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and ILD. This study also suggests a potential pathogenesis of this serious adverse event that tumor- and ILD-derived HMGB1 accelerates lung injury.


[Endoscopic retrograde cholangiopancreatography in the differential diagnosis of chronic pancreatitis and pancreatic cancer (author's transl)].
The endoscopic retrograde cholangiopancreatography (ERCP) findings in 30 patients with chronic pancreatitis and 25 cases of pancreatic cancer are presented in this report. The diagnosis was confirmed in every case by surgery or at autopsy. ERCP was found to be a reliable means of differentiating between pancreatic cancer and chronic pancreatitis in most cases. Multiple lesions are typical of chronic pancreatitis. In solitary lesions a diagnosis can be reached only by consideration of the pancreatographic findings in conjunction with the clinical picture.


An alternative lower tract approach to ectopic duplex system ureteroceles feasible in young children.
The best surgical approach to ectopic ureters and ureteroceles is yet to be determined. The objective of this study is to provide an alternative lower tract surgical approach to ectopic ureters and duplex system ureteroceles that can be safely performed in young children. The "in-and-out" bladder approach was performed via an open intravesical incision. The upper and lower pole ureters were mobilized and brought into the bladder. The dilated ureter/ureterocele was cut open, and the distal part was deuroepithelialized. Subsequently, common sheath reimplantation was performed. The ureterocele wall was not involved during the whole procedure. We retrospectively reviewed all patients who underwent surgery for ureteroceles and ectopic ureters between January 1, 2004, and December 31, 2019. Patients with intravesical ureteroceles were excluded. Outcome parameters included the presence of hydronephrosis or reflux, split renal function on DMSA scan, incidence of urinary tract infection, and urinary incontinence. A total of 32 patients with ectopic duplex system ureterocele who underwent the "in-and-out" bladder approach between 2004 and 2019 were included in the retrospective study. The median age at operation was 7.8 months (range: 1.5 months-3.0 years). The median length of follow-up was 6.1 years (range: 1.0 years-14.3 years). Sixteen patients (55%) had ipsilateral vesicoureteral reflux. Five patients postoperatively developed a urinary tract infection within 1-3 years. No patients required further endoscopic treatment or surgeries. During long-term follow-up, two patients (6.3%) had intermittent day wetting at the ages of 4 and 5 years and were managed conservatively. The symptoms of intermittent day wetting subsided during follow-up. The "in-and-out bladder" approach can be performed in complex duplex system ureteroceles and enables early intervention; it is a single and simple operation with a satisfactory long-term continence rate.


New insights into the roles of the N-terminal region of the ABCC6 transporter.
ABCC6 is a human ATP binding cassette (ABC) transporter of the plasma membrane associated with Pseudoxanthoma elasticum (PXE), an autosomal recessive disease characterized by ectopic calcification of elastic fibers in dermal, ocular and vascular tissues. Similar to other ABC transporters, ABCC6 encloses the core structure of four domains: two transmembrane domains (TMDs) and two nucleotide binding domains (NBDs) but also an additional N-terminal extension, including a transmembrane domain (TMD0) and a cytosolic loop (L0), which is only found in some members of ABCC subfamily, and for which the function remains to be established. To investigate the functional roles of this N-terminal region, we generated several domain deletion constructs of ABCC6, expressed in HEK293 and polarized LLC-PK1 cells. ABCC6 lacking TMD0 displayed full transport activity as the wild type protein. Unlike the wild type protein, ABCC6 without L0 was not targeted to the basolateral membrane. Moreover, homology modeling of L0 suggests that it forms an ATPase regulatory domain. Furthermore, we show that the expression of ABCC6 is linked to a cellular influx of Ca(2+). The results suggest that TMD0 is not required for transport function and that L0 maintains ABCC6 in a targeting-competent state for the basolateral membrane and might be involved in regulating the NBDs. These findings shed new light on a possible physiological function of ABCC6 and may explain some of the hallmarks of the clinical features associated with PXE that could contribute to the identification of novel pharmacological targets.


Characteristics of slag, fly ash and deposited particles during melting of dewatered sewage sludge in a pilot plant.
This study examines slag, fly ash, and deposited particles during melting of dewatered sewage sludge in a pilot plant. In addition, the chemical composition of particles in flue gas was simulated using a thermodynamics program, namely FACTSage 5.2. The results showed that the main components of slag were Al, Fe, Ca, P and Si; the minor components were Na, K, Mg, Cu, and Zn. The main chemical compound of slag was Ca4(Mg,Fe)5(PO4)6. For fly ash particles, heavy metals with the highest concentrations were in the order of Zn and As, Pb, Cu, and Cd, respectively. For non-heavy metals, Al, Fe and P were also found in significant amounts. The majority of deposited particles were composed of elements of Zn, P, S, Na, Fe, Al, Si, and Ca and such chemical compounds as Zn3(PO4)2, AlPO4, FePO4 and Fe(OH)3 while the minority consisted of elements of As, Cu, and Pb. Moreover, the compositions of deposited particles in each chamber differed due to different flue gas temperatures inside. In the secondary chamber at 760 degrees C, the amounts of Fe and Al were higher than Zn, whereas, in the other chambers (600-400 degrees C), the amount of Zn was higher. In other words, at the lower temperature the deposition of Zn was higher than the deposition of Fe and Al. In the water cooling section, volatile elements (i.e. Zn, As, Cu, Pb) were found in the highest concentrations due to a big difference in temperature between the wall surface and flue gas. From the simulation results, most of the elements in the gas phase were found to be chloride compounds, whereas those in the solid phase were in the form of oxide, sulfate, and phosphate compounds.


Recombinant expression, characterization and expressional analysis of clam Meretrix meretrix cathepsin B, an enzyme involved in nutrient digestion.
Cathepsin B is one of the most important proteolytic enzymes involved in the nutrient metabolism of clam Meretrix meretrix. The recombinant fusion protein GST-MmeCB (rGST-MmeCB) was obtained at a high level from Escherichia coli and identified using LC-ESI-MS/MS. The GST tag was cleaved from rGST-MmeCB, and the resulting recombinant MmeCB (rMmeCB) was able to degrade the selective substrate carbobenzoxy-L-arginyl-L-arginyl-7-amino-4-trifluoromethylcoumarin (Z-Arg-Arg-AFC) in vitro. The kinetic parameters of the rMmeCB were calculated as follows: K (m), V(max) and k (cat) are 6.11 μM, 0.0174 μM min(-1) and 277.57 s(-1), respectively. Rabbit anti-rGST-MmeCB polyclonal antibodies was prepared and used to analyze the tissue distribution of MmeCB protein in M. meretrix. The results showed that the highest level of cathepsin B was found in the digestive gland and moderate levels were found in gill and mantle. Similar expression patterns were found at the mRNA level as detected by real time PCR. Further analysis showed that starvation caused a slight increase in MmeCB protein synthesis in the digestive gland, while refeeding after starvation caused an apparent increase in MmeCB synthesis in digestive gland, gill and mantle. Real time PCR analysis showed that MmeCB mRNA in digestive gland was significantly up-regulated by starvation and returned to normal level after the starved clams were refed. Together, these results indicated that cathepsin B is probably involved in the nutrient digestion of M. meretrix.


Rehabilitation outcomes of cardiac and non-cardiac anoxic brain injury: a single institution experience.
To compare the functional outcomes of patients with anoxic brain injury (ABI) due to cardiac and non-cardiac aetiologies. Retrospective chart review over 4 years. Freestanding rehabilitation hospital. Thirteen patients with cardiac ABI and 13 patients with non-cardiac ABI. Comprehensive, multi-disciplinary inpatient rehabilitation services. Rehabilitation hospital length of stay (LOS) and cost; Functional Independence Measure (FIM) scores and its various sub-sets on admission and discharge; FIM efficiency and change; and discharge disposition. Patients with cardiac ABI were similar in gender and ethnicity when compared to patients with non-cardiac ABI but were older (average age 52 vs 42) with a higher percentage of cardiac patients married (77% vs 39%). No statistically significant differences were found between the two groups on all sub-sets of the FIM on admission and discharge as well as the different FIM efficiencies. However, there was a trend for the cardiac ABI patients to have a greater efficiency in improving mobility during rehabilitation when compared to non-cardiac ABI patients. The rehabilitation hospital LOS was approximately 28 days less for patients with cardiac ABI (41.49 vs 69.84 days), but this difference was not statistically significant (p=0.26). The mean rehabilitation cost for patients with cardiac ABI was approximately $14,000 less than that for those with non-cardiac ABI ($44,181 vs $58,187). This difference was not statistically significant (p=0.15). Cardiac ABI patients were more likely to be discharged directly to home from rehabilitation when compared to non-cardiac ABI patients (p=0.06). This pilot study demonstrates some differences in the recovery patterns of patients with ABI who had a cardiac aetiology and those who had non-cardiac aetiologies. While both groups experienced similar progress during rehabilitation, those with cardiac ABI made gains with a shorter LOS and less rehabilitation costs when compared to non-cardiac ABI patients. These data suggest a trend towards greater cost and length of stay for patients with ABI who had non-cardiac aetiologies.


Benign cecal villous adenoma presenting as a bladder mass.
Involvement of contiguous organs by a neoplasm is ordinarily evidence of aggressive malignant behavior. A patient presented with a bladder mass found to be arising in the cecum and diagnosed as a benign villous adenoma. Growth down a diseased appendix is proposed to explain the apparent extension of a relatively nonaggressive lesion into an adjacent organ.


Parallel investigation of exocytosis kinetics and membrane fluidity changes in human platelets with the fluorescent probe, trimethylammonio-diphenylhexatriene.
A simple, flexible and sensitive fluorescence method is described, which, from the same experiment, provides coupled quantitative informations on membrane fluidity changes and exocytosis, and reliable kinetic analyses of these effects, in intact cell suspensions. The method is based on the features peculiar to trimethylammonio-diphenylhexatriene (TMA-DPH), a fluorescent hydrophobic probe, which, in intact cells, is incorporated specifically into the plasma membranes, according to an instantaneous partition equilibrium. The method was tested on human platelets upon stimulation with various agents, such as human alpha-thrombin, adenosine diphosphate (ADP), adrenaline and ionomycin, which act through different types of mechanism. The experimental conditions were chosen to allow platelet shape change and exocytosis, but no aggregation. The kinetics and the dose-dependence of the changes in TMA-DPH fluorescence intensity and anisotropy were compared to the simultaneous physiological responses of platelets to the same stimuli, under the same conditions. Quantitative correlations were established between serotonin secretion and the increase in fluorescence intensity, whereas fluorescence anisotropy, which monitors membrane fluidity changes was associated with platelet shape change. The specificity of the effects was confirmed with appropriate antagonistic or modulating agents.


Current progress for the use of miRNAs in glioblastoma treatment.
Glioblastoma (GBM) is a highly aggressive brain cancer with the worst prognosis of any central nervous system disease despite intensive multimodal therapy. Inevitably, glioblastoma is fatal, with recurrence of treatment-resistant tumour growth at distal sites leading to an extremely low median survival rate of 12-15 months from the time of initial diagnosis. With the advent of microarray and gene profiling technology, researchers have investigated trends in genetic alterations and, in this regard, the role of dysregulated microRNAs (highly conserved endogenous small RNA molecules) in glioblastoma has been studied with a view to identifying novel mechanisms of acquired drug resistance and allow for development of microRNA (miRNA)-based therapeutics for GBM patients. Considering the development of miRNA research from initial association to GBM to commercial development of miR-based therapeutics in less than a decade, it is not beyond reasonable doubt to anticipate significant advancements in this field of study, hopefully with the ultimate conclusion of improved patient outcome. This review discusses the recent advancements in miRNA-based therapeutic development for use in glioblastoma treatment and the challenges faced with respect to in vivo and clinical application.


FBXW7β isoform drives transcriptional activation of the proinflammatory TNF cluster in human pro-B cells.
Noncanonical exon usage plays many important roles in cellular phenotypes, but its contribution to human B-cell development remains sketchily understood. To fill this gap, we collected various B-cell fractions from bone marrow (BM) and tonsil donors, performed RNA sequencing, and examined transcript variants. We identified 150 genes that harbor local splicing variations in all pairwise comparisons. One of them encodes FBXW7, an E3 ubiquitin ligase implicated as a driver in several blood cancers. Surprisingly, we discovered that in normal human pro-B cells, the predominant transcript used an alternative first exon to produce the poorly characterized FBXW7β isoform, previously thought to be restricted to neural tissues. The FBXW7β transcript was also abundant in cell lines and primary samples of pediatric B-cell acute lymphoblastic leukemia (B-ALL), which originates in the BM. When overexpressed in a heterologous cell system, this transcript yielded the expected protein product, as judged by anti-FLAG immunoblotting and mass spectrometry. Furthermore, in REH B-ALL cells, FBXW7β mRNA was the only FBXW7 isoform enriched in the polyribosome fraction. To shed light on possible functions of FBXW7β, we used gain- and loss-of-function approaches and identified an FBXW7-dependent inflammatory gene signature, apparent in a subset of B-ALL with high FBXW7β expression. This signature contained several members of the tumor necrosis factor superfamily, including those comprising the HLA Class III cluster (LTB, LST1, NCR3, LTA, and NFKBIL1). Our findings suggest that FBXW7β expression drives proinflammatory responses, which could contribute to normal B-cell development, leukemogenesis, and responses to anticancer therapies.


The risk of intracranial hemorrhage in glioma patients receiving anticoagulant treatment for venous thromboembolism: a bayesian network meta-analysis.
We aimed to perform a Bayesian network meta-analysis to assess the risk of intracranial hemorrhage (ICH) in patients with glioma receiving anticoagulant treatment for venous thromboembolism. The PubMed, Embase and Web of Science databases were searched for relevant publications until September 2022. All studies evaluating the risk of ICH in patients with glioma receiving anticoagulant treatment were included. Bayesian network meta-analysis and pairwise meta-analysis were performed to compare the ICH risk between the anticoagulant treatments. The Cochrane's Risk of Bias Tool and the Newcastle-Ottawa Scale (NOS) were used to evaluate the quality of studies. A total of 11 studies with 1301 patients were included. Pairwise comparisons showed no significant differences excepted with LMWH vs. DOACs (OR: 7.28, 95% CI: 2.11-25.17) and LMWH vs. Placebo (OR: 3.66, 95% CI: 2.15-6.24). For network meta-analysis, significant difference was found between patients treated with LMWH vs. Placebo (OR: 4.16, 95% CI: 2.00-10.14) and LMWH vs. DOACs (OR: 10.13, 95% CI: 2.70-70.19). It seems that LMWH has the highest risk of ICH in glioma patients, while no evidence indicates that DOACs increase the risk of ICH. The use of DOACs may perhaps be a better choice. Further larger studies focusing on the benefit-to-risk ratio are warranted.


Bibliometric analysis of scientific literature on intestinal parasites in Argentina during the period 1985-2014.
The study of scientific production is a good indicator of the progress in research and knowledge generation. Bibliometrics is a scientific discipline that uses a set of indicators to quantitatively express the bibliographic characteristics of scientific publications. The scientific literature on the epidemiology of intestinal parasites in Argentina is scattered in numerous sources, hindering access and visibility to the scientific community. Our purpose was to perform a quantitative, bibliometric study of the scientific literature on intestinal parasites in humans in Argentina published in the period 1985-2014. This bibliometric analysis showed an increase in the number of articles on intestinal parasites in humans in Argentina published over the past 30 years. Those articles showed a collaboration index similar to that of the literature, with a high index of institutionality for national institutions and a very low one for international collaboration. The original articles were published in scientific journals in the American Continent, Europe and Asia. The use of bibliometric indicators can provide a solid tool for the diagnosis and survey of the research on epidemiology of intestinal parasites and contributes to the dissemination and visibility of information on the scientific production developed in Argentina.


Tocilizumab, a Potent Interleukin-6 Receptor Inhibitor, Decreases Bone Resorption and Increases the Rate of Bacterial Infection After Tooth Extraction in Rats.
Our objective was to evaluate the influence of pretreatment with tocilizumab (TCZ) in bone healing after tooth extraction in rats. Wistar male rats were equally divided into sham (ie, nonoperated), saline (both treated with 0.1 ml/kg saline), and six TCZ groups treated with 1, 2, 4, 8, 16, and 32 mg/kg TCZ (TCZ1 to TCZ32, respectively). Twenty-four hours after administration of vehicle or TCZ, exodontia of the first lower left molar was performed, and the animals were euthanized three days later for hematological analysis and organ (liver, spleen, and kidney mass indexes, and histological evaluation), gingiva (myeloperoxidase [MPO] assay), and mandible (radiographic, histomorphometric analysis, and IL-6 immunostaining) evaluation. Analysis of variance/Bonferroni test (statistical significance, P < .05) was performed using GraphPad Prism version 5.0 (GraphPad Inc, San Diego, CA, USA). There was no difference in radiographic results; however, leukopenia (P = .039) and neutropenia (P < .001) were statistically significant in the TCZ16 and TCZ32 groups. Weight loss (P < .001) and reduced liver index (P = .001) were significantly dose-dependent; however, no histological alterations were observed in the other organs. Osteoclast counts were reduced in groups TCZ4 to TCZ32 (P < .001), and IL-6 immunostaining increased in the TCZ8 to TCZ32 groups (P < .001). Alveolar infection rates increased in groups TCZ4 to TCZ32 (P < .001), and MPO had a biphasic response, exhibiting a reduction in groups TCZ2 and TCZ4, and an increase in group TCZ32 (P = .004). TCZ-induced immunosuppression led to a reduction in osteoclast function, an increase in alveolar infection, and compensatory neutrophil infiltration.


New approaches to smoldering myeloma.
Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by the presence of one or both features of serum M-protein ≥ 30 g/L and bone marrow plasma cell infiltration ≥ 10 %. However, myeloma-related symptomatology is absent from this condition. The risk of progression to active MM is not uniform, and several markers are useful for identifying SMM patients at high risk of progression to active MM. These include the size of the M-protein and the infiltration in the bone marrow, the serum-free light-chain ratio, the presence of immunoparesis and percentage of plasma cell with aberrant phenotype by flow cytometry, or the presence of focal lesions in magnetic resonance imaging. Overall, the presence of these factors identifies patients who have a 50 % probability of progression at 2 years, and the forthcoming challenge will be to identify ultra-high-risk patients who have an 80 % risk of progression at 2 years. The current standard of care is not to treat until progression to symptomatic disease occurs. Several trials of melphalan, thalidomide and bisphosphonates have been conducted in the overall SMM patient population to examine the delay in time to progression (TTP) to symptomatic disease, but these have shown no significant benefit. However, a randomized trial that focused on high-risk SMM patients allocated to receive early treatment with lenalidomide plus dexamethasone versus observation did report a significant benefit with respect to TTP and overall survival. In summary, high-risk SMM patients should be targetted for early treatment, and more so efforts should be made to identify the ultra-high-risk subgroup within the high-risk SMM patient population which may be considered as early MM and thereby candidates for receiving therapy before they develop myeloma-related symptomatology.


Influence of Sensory Stimulation on Exhaled Volatile Organic Compounds.
The real-time exhaled volatile organic compounds (VOCs) have been suggested as a new biomarker to detect and monitor physiological processes in the respiratory system. The VOCs profile in exhaled breath reflects the biochemical alterations related to metabolic changes, organ failure, and neuronal activity, which are, at least in part, transmitted via the lungs to the alveolar exhaled breath. Breath analysis has been applied to investigate cancer, lung failure, and neurodegenerative diseases. There are by far no studies on the real-time monitoring of VOCs in sensory stimulation in healthy subjects. Therefore, in this study we investigated the breath parameters and exhaled VOCs in humans during sensory stimulation: smell, hearing, sight, and touch. Responses sensory stimulations were recorded in 12 volunteers using an iAQ-2000 sensor. We found significant effects of sensory stimulation. In particular, olfactory stimulation was the most effective stimulus that elicited the greatest VOCs variations in the exhaled breath. Since the olfactory pathway is distinctly driven by the hypothalamic and limbic circuitry, while other senses project first to the thalamic area and then re-project to other brain areas, the findings suggest the importance of olfaction and chemoreception in the regulation lung gas exchange. VOCs variations during sensory activation may become putative indicators of neural activity.


Bile 5'-nucleotidase in the serum of jaundiced rats.
Rat serum 5'-nucleotidase, L-leucyl-beta-naphthylamidase and beta-glycerophosphatase activities are increased whilst alkaline p-nitrophenylphosphatase and alkaline phosphodiesterase activities are unchanged or decreased three days after bile duct ligation. Affinity chromatography on an immobilised antiserum raised against highly purified liver plasma membranes showed that although 5'-nucleotidase in normal serum is unrelated to the 5'-nucleotidase of liver plasma membrane, the 5'-nucleotidase of bile and much of the 5'-nucleotidase in the jaundiced serum are closely related to the plasma membrane enzyme. Since bile is rich in 5'-nucleotidase, the changes in level of this enzyme after bile duct ligation are most simply explained by leakage of bile into the blood; changes in the patterns of the other enzymes are shown to be consistent with this explanation. The jaundiced serum was examined by gel exclusion chromatography and flotation in sucrose gradients for the presence of small fragments of plasma membrane as reported in human jaundiced sera, but no such fragments could be detected three days after bile-duct ligation.


Acid-base balance during social interactions in rainbow trout (Oncorhynchus mykiss).
Socially subordinate rainbow trout (Oncorhynchus mykiss) experience chronic stress that impacts upon a variety of physiological functions, including Na(+) regulation. Owing to the tight coupling between Na(+) and Cl(-) uptake and, respectively, H(+) and HCO(3)(-) loss at the gill, ionoregulatory changes associated with social status may affect acid-base regulation. The present study assessed the responses of dominant, subordinate and control trout to hypercapnia (1% CO(2)) to test this hypothesis. Social status appeared to impact net acid excretion (J(net)H(+)) as subordinate individuals failed to increase net acid flux in response to hypercapnia. However, blood acid-base status was found to be unaffected by social status before or during hypercapnic exposure, indicating that subordinate fish were as effective as dominant or control trout in achieving compensation for the acid-base disturbance induced by hypercapnic exposure. Compensation in all groups involved decreasing Cl(-) uptake in response to hypercapnia. The branchial activities of both Na(+),K(+)-ATPase (NKA) and V-type H(+)-ATPase were affected by social interactions and/or exposure to hypercapnia. Branchial NKA activity was higher but V-ATPase activity was lower in control fish than in dominant or subordinate trout. In addition, control and subordinate but not dominant trout exposed to 24h of hypercapnia exhibited significantly higher branchial V-ATPase activity than fish maintained in normocapnia. Collectively, the data suggest that subordinate trout are able to regulate blood pH during a respiratory acidosis.


Assessment of angiogenic markers and female sex hormone receptors in pregnancy tumor of the gingiva.
Oral pregnancy tumors (OPTs) arise on the inflamed gingiva of women after the first trimester of pregnancy. The expression of angiogenic markers and female hormone receptors was assessed. Immunohistochemistry was used to analyze the expression of estrogen and progesterone receptors and the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) and its receptor, fibroblast growth factor (FGF), and hypoxia inducible factors 1α and 3α (HIF1α and HIF3α). Experimental groups included 9 OPTs, 10 oral pyogenic granulomas from nonpregnant women of the same age, and 9 oral pyogenic granulomas from postmenopausal women. VEGF expression in stromal histiocytes and endothelial cells of small vessels was positively correlated in the OPT group (P < .05 by χ(2) test). VEGF receptor also was overexpressed in stromal histiocytes and endothelial cells of OPTs compared with oral pyogenic granulomas from nonpregnant and postmenopausal women (P < .005 by χ(2) test). No correlation was detected among estrogen and progesterone receptors, FGF and HIF1α and HIF3α (ER and PgR respectively) in the 3 experimental groups. VEGF-associated angiogenesis is most likely involved in the pathogenesis of the lesion. These results imply that local inhibition of VEGF activity could be an adjuvant therapeutic approach for OPTs to control hemorrhage, which can be massive at the surgical excision of such lesions during pregnancy.


Adapting to the Era of Virtual Recruitment: Radiology Departmental Website Response to COVID-19 and Portrayal of the Resident Experience.
The COVID-19 pandemic has transformed radiology recruitment into a virtual affair and placed an even stronger emphasis on the importance of departmental websites. In this study, we evaluate residency websites in detailing the response to COVID-19 as well as initiatives which help describe the resident experience. Program websites for diagnostic radiology residencies listed in the 2022 Electronic Residency Application Service (ERAS) program list were evaluated for 31 criteria related to departmental response to COVID-19, online outreach, and resident wellness. Of 184 programs, 182 had functioning websites for review. One program was excluded from analysis as the website was almost entirely video-based. In response to COVID-19, ≤1% described resident redeployment, vaccination information, departmental response to ABR Core Exam changes, or regular administration updates. Six (3.3%) described revised read-out protocols, four (2.2%) mentioned supplementary non-clinical education, and 14 (7.7%) indicated changes to educational conferences. The majority of websites (122, 67.4%) offered an informational or tour video, while 44 (24.3%) described expectations for virtual interviewing, and 20 (11.0%) had virtual "open-houses." Departmental social media, primarily Twitter, was linked for 60 (33.1%) programs. A total of 134 (74.0%) websites described community highlights. More than a quarter mentioned meal stipends (72, 39.8%), paid sick time (54, 29.8%) and healthcare resources (57, 31.5%). Although social activities were described by 44 (24.3%) programs, some specifically indicating changes to COVID-19, formal resident mentoring (25, 13.8%) and wellness committees (28, 15.5%) were less common. These criteria were found more commonly at the largest third of residency programs (chi square, p < 0.00625). Programs rarely described work flow changes to COVID-19, and websites could improve in virtual outreach. Compared with prior literature, departmental websites have improved in describing wellness initiatives and related measures.


Preparation and characterization of a thermostable enzyme (Mn-SOD) immobilized on supermagnetic nanoparticles.
Superoxide dismutase (SOD) has been widely applied in medical treatments, cosmetic, food, agriculture, and chemical industries. In industry, the immobilization of enzymes can offer better stability, feasible continuous operations, easy separation and reusing, and significant decrease of the operation costs. However, little attention has focused on the immobilization of the SOD, as well as the immobilization of thermostable enzymes. In this study, the recombinant thermostable manganese superoxide dismutase (Mn-SOD) of Thermus thermophilus wl was purified and covalently immobilized onto supermagnetic 3-APTES-modified Fe(3)O(4)@SiO(2) nanoparticles using glutaraldehyde method to prepare the Mn-SOD bound magnetic nanoparticles. The Mn-SOD nanoparticles were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, X-ray diffraction, transmission electron microscopy, and vibrating sample magnetometer analysis. The results indicated that the diameter of Mn-SOD nanoparticles was 40 (± 5) nm, and its saturation magnetization value was 27.9 emu/g without remanence or coercivity. By comparison with the free Mn-SOD, it was found that the immobilized Mn-SOD on nanoparticles exhibited better resistance to temperature, pH, metal ions, enzyme inhibitors, and detergents. The results showed that the immobilized Mn-SOD on nanoparticles could be reused ten times without significant decrease of enzymatic activity. Therefore, our study presented a novel strategy for the immobilization of thermostable Mn-SOD and for the application of thermostable enzymes.


pH-dependent effect of heat-induced antigen retrieval of epoxy section for electron microscopy.
The aim was to examine how the pH in the antigen retrieval medium (citrate) affects the yield of immunogold labeling of epoxy sections. Renal swine tissue with glomerular immune complex deposits with reactivity against IgG was embedded in epoxy resin. Prior to immunogold labeling with anti-IgG, ultrathin sections from these blocks were exposed to antigen retrieval by heating in citrate solution (pH 6, 9 or 12) at 95 degrees C in a PCR-machine or at 121 or 135 degrees C min in an autoclave. The level of immunogold labeling was significantly higher for pH 12 than for pH 6 when heated at 95 degrees C (50% more intense), but at the cost of the ultrastructural preservation of the tissue. At pH 12 and temperature 135 degrees C the epoxy sections were completely destroyed. The sections which had been heated at 135 degrees C, pH 6 appeared significantly better both with respect to intensity of immunogold labeling (85% more intense) and to ultrastructural preservation than those which were heated at 95 degrees C, pH 12. Therefore, our results indicate that relatively low pH (pH 6) and high temperature is the method of choice, but low temperature and high pH can be used when an autoclave is not available.


The effects of a geographic continuing education program on physician referral behavior: an unobtrusive study.
This study reports on an unobtrusive study of changes in physician referral behavior after a need-oriented continuing medical education program.


The neuropeptide bradykinin stimulates phosphoinositide turnover in HSDM1C1 cells: B2-antagonist-sensitive responses and receptor binding studies.
Bradykinin (BK) and its analogs (1 nM-100 microM) stimulated phosphoinositide (PI) turnover in murine fibrosarcoma (HSDM1C1) cells in a concentration-dependent manner. The relative potencies (EC50) were: BK = 48 +/- 4 nM; Lys-BK = 39 +/- 3 nM; Met-Lys-BK = 158 +/- 33 nM, Des-Arg9-BK = 2617 +/- 598 nM (means +/- SEM, n = 3-14). All these analogs were full agonists and they produced up to 5.4 +/- 0.4-fold stimulation of PI turnover at the highest concentration (10-100 microM) of the peptides. In contrast, the analogs [D-Arg0-HYP3-Thienyl5,8-D-Phe7]-BK (HYP3-antagonist), [D-Arg0-HYP3-Thienyl,5,8-D-Phe7]-BK (Thienyl antagonist) and Des-Arg9-Leu8-BK were inactive, as agonists, at 0.1 nM-1 microM in this system. These data suggested that BK-induced PI turnover in these cells was mediated via B2-type of BK receptors. This was confirmed further by the fact that both the B2-selective Hyp3- and Thienyl-antagonists inhibited BK-induced PI turnover with KBS of 369 +/- 51 nM and 368 +/- 118 nM respectively while the B1-selective antagonist, Des-Arg9-Leu8-BK, was inactive at 1 microM. [3H]BK receptor binding studies revealed two binding sites, one with high affinity (Kd = 0.24 +/- 0.06 nM; Bmax = 1.4 +/- 0.4 pmol/g tissue) and the other with low affinity (Kd = 18.5 +/- 0.95 nM; Bmax = 25.1 +/- 0.52 pmol/g tissue), on HSDM1C1 cell homogenates. The rank order of affinity of BK analogs at inhibiting specific [3H]BK binding was similar to that found for PI turnover.(ABSTRACT TRUNCATED AT 250 WORDS)


Treatment with aztreonam or tobramycin in critical care patients with nosocomial gram-negative pneumonia.
During the course of one year, 47 critical care patients with gram-negative bacillary pneumonia at Millard Fillmore Hospital were randomly assigned to aztreonam or tobramycin therapy (two to one). Of these, 40 were fully evaluable for microbiologic and clinical response. All evaluable patients had gram-negative organisms in tracheal aspirate culture specimens and confirmed susceptibility of the organism to both study drugs. There was no difference between the two groups with respect to the percentage of patients who received concurrent antibiotics for gram-positive organisms. More than 60 percent of the patients received mechanical ventilation. Essentially, all had new lung infiltrates as shown by chest radiography, leukocytosis, recent onset of fever, and increased volume of purulent secretions. Half had multilobar pulmonary infiltrates. Their mean age was 73 years, with none under age 50. Most had chronic obstructive pulmonary disease, congestive heart failure, or both. By the prognostic nutritional index criteria, over 70 percent were nutritionally deficient at entry. The majority of infections were caused by Pseudomonas, Enterobacter, Klebsiella, and Escherichia coli. Aztreonam eradicated 92 percent of the causative gram-negative organisms, compared with 57 percent for tobramycin (p less than 0.05). Aztreonam produced a favorable clinical response (cure or improvement) in 93 percent of patients, compared with 50 percent for tobramycin (p less than 0.05). There were no differences in the minor adverse effects observed in the two treatment groups. Overall, aztreonam was superior to tobramycin for treatment of pneumonia due to susceptible gram-negative bacteria in these critical care patients.


Intensification of high cell-density cultivations of rE. coli for production of S. pneumoniae antigenic surface protein, PspA3, using model-based adaptive control.
This work proposes an innovative methodology to control high density fed-batch cultures of E. coli, based on measurements of the concentration of dissolved oxygen and on estimations of the cellular specific growth rate (µ), of the yield of biomass/limiting substrate (Y (xs)) and of the maintenance coefficient (m). The underlying idea is to allow cells to grow according to their metabolic capacity, without the constraints inherent to pre-set growth rates. Cellular concentration was assessed on-line through a capacitance probe. Three configurations of the control system were compared: (1) pre-set value for the three control parameters; (2) continuously updating µ; (3) updating µ, Y (xs) and m. Implementation of an efficient noise filter for the signal of the capacitance probe was essential for a good performance of the control system. The third control strategy, within the framework of an adaptive model-based control, led to the best results, with biomass productivity reaching 9.2 g(DCW)/L/h.


Additional Evidence Supports Association of Common Variants in COL11A1 with Increased Risk of Hip Osteoarthritis Susceptibility.
In a recent study single nucleotide polymorphisms (SNPs) in the COL11A1 gene were found to be associated with hip osteoarthritis (OA) among European populations. In this study, our aim was to identify common genetic variants in COL11A1 predisposing to primary hip OA in Han Chinese individuals. We designed a case-control study that included 313 hip OA patients and 911 unrelated healthy controls. Fourteen tagging single-nucleotide polymorphisms (SNPs) were genotyped, and single SNP and haplotypic association analyses were performed. Two SNPs (rs1241164 and rs4907986) were found to be significantly associated with hip OA risk (adjusted p = 0.000731 and 0.000477). An increased risk of OA was associated with possession of the C allele of rs1241164 (adjusted odds ratio [OR] = 1.73, 95% confidence interval [CI] = 1.27-2.36) and the T allele of rs4907986 (adjusted OR = 1.72, 95% CI = 1.24-2.35). Similar results were confirmed via genotypic association analyses. Moreover, two different haplotype blocks, including rs1241164 and rs4907986, respectively, were found to be strongly associated with hip OA risk as well. Variants in the COL11A1 gene modify individual susceptibility to hip OA in the Han Chinese population.


The influence of implantation site on the biocompatibility and survival of alginate encapsulated pig islets in rats.
This work investigated the impact of implantation sites on the biocompatibility of alginate encapsulated pig islets. Non-diabetic rats were implanted with adult pig islets encapsulated in alginate either intraperitoneally (IP; n=25), subcutaneously (SC; n=37) or under the kidney capsule (KC; n=34). Capsule biocompatibility (retrieval rate, capsule diameter, degree of capsule broken and cellular overgrowth, CD68/CD3 staining) as well as islets viability and functionality were assessed until 30 days after transplantation. Implantation site did not significantly influence the biocompatibility of empty alginate capsules after transplantation (n=48). Most of the empty capsules (>90%) were retrieved after harvesting and were free of cellular overgrowth until day 30 post-transplantation. Three days after implantation, no significant difference for encapsulated pig islets was observed in terms of capsule biocompatibility and islet functionality in peritoneum, KC or subcutaneously. However, between days 5 and 30 after transplantation, explanted capsules from IP demonstrated a higher degree of broken capsules (>13%) and capsules with severe cellular overgrowth (>50%, CD68+ infiltration) than capsules removed from SC and KC (p<0.05). This was associated with a significant reduction of islet viability, insulin content and insulin secretion. In rats, the peritoneum site seems not appropriate for promoting the engraftment of encapsulated pig islets. Kidney subcapsular and subcutaneous spaces represent an interesting alternative.


Correlation of Day 8 Steroid Response with Bone Marrow Status Measured on Days 14 and 35, in Patients with Acute Lymphoblastic Leukemia Being Treated with BFM Protocol.
Berlin-Frankfurt-Munster (BFM) protocol is commonly used in India for treatment of acute lymphoblastic leukemia (ALL). The present study was conducted to correlate day 8 steroid response with bone marrow status (by morphology and flow cytometry) at day 14 and day 35 of treatment. It was a prospective study which included all newly diagnosed ALL patients who visited hospital between March 2013 and February 2015 i.e. 2 years. On 8th day, the number of lymphoblasts was counted in the peripheral blood. Based on the number of blasts patients were classified as good steroid responders and poor steroid responders. Following pre-induction steroids patients were given induction therapy. During this phase on day 14 and day 35 bone marrow (BM) aspiration study was done. Later day 8 steroid response, Day 14 BM status and day 35 BM status were correlated. Results showed that there was a statistically significant correlation between day 8 steroid response and day 14 BM status (both by morphology and flow cytometry). There was no statistically significant correlation between day 8 steroid response and day 35 BM status (both by morphology and flow cytometry). There was no statistically significant correlation between day 14 and day 35 BM status (both by morphology and flow cytometry). Sensitivity and specificity of morphological evaluation of BM was much lower compared to minimal residual disease assessment by flow cytometry. There is a need to incorporate flow cytometry in risk stratification of patients who are being treated with BFM 2002 protocol.


Effects of repeated callbacks on response rate and nonresponse bias: results from a 17-state pharmacy survey.
Although surveys are the most common method of data collection in research in the social & behavioral pharmaceutical sciences, little evidence exists on pharmacists' and pharmacies' patterns of telephone survey participation and the impact of repeated callbacks on minimizing nonresponse bias. To (1) describe final disposition of the survey sample, (2) describe the effect of repeated callbacks on response rate, and (3) examine whether hard-to-contact cases differ from those that are relatively easier to contact in terms of general pharmacy characteristics and characteristics specific to survey topics. This study used a cross-sectional descriptive survey design that gathered information from key informants of 2558 community pharmacies in 17 states. Telephone interviews were conducted using a Computer Assisted Telephone Interview system. Final disposition of the sample units and the final response rate were reported. General pharmacy characteristics and characteristics specific to immunization delivery (ID) and emergency preparedness and response (EPR) activities were compared across different ease-of-contact levels. A total of 1707 pharmacies (66.7%) completed the interview; 757 (29.6%) were eligible cases that were not interviewed; 8 (0.3%) and 86 (3.4%) were cases of unknown eligibility and ineligibility, respectively. The final response rate was 69.1%. The number of calls to pharmacies was most productive on the first 9 calls and leveled off after the 14th call. When comparing characteristics among different ease-of-contact levels, 2 out of 3 characteristics related to ID activities were different. No differences were found in general pharmacy characteristics and characteristics specific to EPR activities, however. The greater number of callbacks resulted in higher response rates due to greater number of completed interviews. The increase in response rate did not rule out nonresponse bias, however. Hard-to-contact cases differed from relatively easier to contact cases in terms of characteristics related to the survey topic, but not general characteristics.


Effects of Race and Poverty on Sleep Duration: Analysis of Patterns in the 2014 Native Hawaiian and Pacific Islander National Health Interview Survey and General National Health Interview Survey Data.
There are health concerns associated with unhealthy sleep duration. A growing body of evidence indicates that there are disparities in sleep duration based upon race/ethnicity and socioeconomic status. Prior studies have suffered from inadequate measures of poverty and have not included Native Hawaiians and Pacific Islanders (NHPI). Using the 2014 National Health Interview Survey (NHIS) and the 2014 NHPI-NHIS, the effect of race/ethnicity and poverty was examined for associations with sleep duration. Significant differences among race/ethnicity groups and sleep duration were found in adjusted associations. Compared with Whites, NHPIs and Blacks were twice as likely to experience very short sleep; NHPI, Hispanic, and Blacks were more likely to experience short sleep; Blacks were also more likely to experience long sleep. Asians were less likely to experience unhealthy sleep (very short, short, or long sleep). Persons living in poverty were significantly more likely to experience very short sleep compared with persons not living in poverty. This is the first population-based study that has examined the relationship between sleep duration and poverty with a large sample that included NHPI in relation to other races/ethnicities. The difference in sleep duration between NHPI and Asians provides a strong rationale for not aggregating Asian and NHPI data in population-based studies.


Decreased extracellular pH inhibits osteogenesis through proton-sensing GPR4-mediated suppression of yes-associated protein.
The pH of extracellular fluids is a basic property of the tissue microenvironment and is normally maintained at 7.40 ± 0.05 in humans. Many pathological circumstances, such as ischemia, inflammation, and tumorigenesis, result in the reduction of extracellular pH in the affected tissues. In this study, we reported that the osteogenic differentiation of BMSCs was significantly inhibited by decreases in the extracellular pH. Moreover, we demonstrated that proton-sensing GPR4 signaling mediated the proton-induced inhibitory effects on the osteogenesis of BMSCs. Additionally, we found that YAP was the downstream effector of GPR4 signaling. Our findings revealed that the extracellular pH modulates the osteogenic responses of BMSCs by regulating the proton-sensing GPR4-YAP pathway.


Brain metastasis in children with sarcoma, neuroblastoma, and Wilms' tumor.
To determine the incidence and prognosis of children who develop brain metastasis. The medical and tumor registry records of 611 children treated at the University of Iowa Hospitals and Clinics between 1965 and 2000 for a sarcoma, neuroblastoma, or Wilms' tumor were reviewed. Thirty children (4.9%) were found to have brain metastasis. Brain metastasis occurred in 9 of 113 (8%) neuroblastoma, 7 of 104 (6.7%) rhabdomyosarcoma, 6 of 105 (5.7%) Ewing's sarcoma, 5 of 106 (4.7%) osteosarcoma, 2 of 83 (2.4%) nonrhabdomyosarcoma soft-tissue sarcoma, and 1 of 100 (1%) Wilms' tumor patients. There were 22 male and 8 female patients, with a median age of 14 years at the time of diagnosis of brain metastasis (range 8 months-20 years). Four patients were diagnosed at autopsy, whereas five had brain metastasis at initial diagnosis. For the 25 children who did not have brain metastasis at initial presentation, the median interval from initial diagnosis to development of brain metastasis was 5 months (range 1-43 months). Twenty-nine (97%) had concurrent or prior history of distant metastasis. Eighteen (60%) had solitary brain metastasis. Treatment for the 26 non-autopsy-diagnosed children included surgery (S), followed by postoperative radiotherapy (RT) and chemotherapy (CT) in 2, S and postoperative RT in 1, RT and CT in 16, S alone in 2, CT alone in 2, RT alone in 1, and no treatment in 2. Median survival was 4 months after diagnosis of brain metastasis, with a 1-year survival rate of 11.5%. On multivariate analysis, only the use of RT was found to positively influence freedom from neurologic progression (p = 0.005). Brain metastasis is uncommon in children with a diagnosis of sarcoma, neuroblastoma, or Wilms' tumor and is often accompanied by concurrent distant disease. Children treated with RT for brain metastasis had a better freedom from neurologic progression rate than those who did not receive radiotherapy.


An exploratory study of young women adjusting to developmental dysplasia of the hip and deciding on treatment choices.
To explore the experiences of young women adjusting to living with developmental dysplasia of the hip (DDH) and deciding on treatment choices. Exploratory study of a set of online postings from one message board aimed at women with DDH. Postings of five, purposively selected users were explored from first posting to the time of their peri-acetabular osteotomy surgery. Data analysis was performed through the approach of interpretive phenomenological analysis. Two major concepts were prominent across participants' accounts; first, 'challenging the life course and identity as a young woman' and second, 'saving my joints'. Central was the women's description of how the diagnosis of DDH challenged the way they viewed themselves as young women. Once the women began to understand the long-term implications of having DDH they all began a quest to save their 'native joint', delaying the need for an artificial joint for as long as possible. The findings demonstrate the personal nature and diversity of the journeys the women followed. DDH potentially provides a critical case for exploration of the process of adjustment, as its treatment pathway and rehabilitation are lengthy and both physically and emotionally demanding.


The effect of the enhanced recovery programme on long-term survival following liver resection for colorectal liver metastases.
Enhanced recovery programmes are associated with improved short-term outcomes following liver surgery. The impact of enhanced recovery programmes on medium- and long-term outcomes is incompletely understood. This study aimed to assess the impact of an enhanced recovery programme on long-term survival in patients undergoing surgery for colorectal liver metastases. At a tertiary hepatobiliary centre, we analysed short-, medium- and long-term outcomes in consecutive patients undergoing liver resection for colorectal liver metastases. A five-year retrospective review was carried out comparing the enhanced recovery programme to standard care. A total of 172 patients were included in the analysis: 87 on standard care and 85 on an enhanced recovery programme. Open surgery was performed in 122 patients: 74 (85.1%) and 48 (56.5%) patients in the standard care and enhanced recovery programme, respectively (p < 0.001). There was a significant reduction in the median (IQR) length of hospital stay in the enhanced recovery programme compared with standard care (7 (5) days vs. 8 (3) days, p = 0.0009). There was no significant difference in survival between standard care and the Enhanced Recovery Programme at one (p = 0.818), three (p = 0.203), and five years (p = 0.247). An enhanced recovery programme was associated with a reduced length of hospital stay. There was no effect on the one-, three- and five-year survival.


Stress-induced dopamine release in humans at risk of psychosis: a [11C]raclopride PET study.
Drugs that increase dopamine levels in the brain can cause psychotic symptoms in healthy individuals and worsen them in schizophrenic patients. Psychological stress also increases dopamine release and is thought to play a role in susceptibility to psychotic illness. We hypothesized that healthy individuals at elevated risk of developing psychosis would show greater striatal dopamine release than controls in response to stress. Using positron emission tomography and [(11)C]raclopride, we measured changes in synaptic dopamine concentrations in 10 controls and 16 psychometric schizotypes; 9 with perceptual aberrations (PerAb, ie positive schizotypy) and 7 with physical anhedonia (PhysAn, ie negative schizotypy). [(11)C]Raclopride binding potential was measured during a psychological stress task and a sensory-motor control. All three groups showed significant increases in self-reported stress and cortisol levels between the stress and control conditions. However, only the PhysAn group showed significant stress-induced dopamine release. Dopamine release in the entire sample was significantly negatively correlated with smooth pursuit gain, an endophenotype linked to frontal lobe function. Our findings suggest the presence of abnormalities in the dopamine response to stress in negative symptom schizotypy, and provide indirect evidence of a link to frontal function.


Minimization of human relaxin-3 leading to high-affinity analogues with increased selectivity for relaxin-family peptide 3 receptor (RXFP3) over RXFP1.
Relaxin-3 is a neuropeptide that is implicated in the regulation of stress responses and memory. The elucidation of its precise physiological role(s) has, however, been hampered by cross-activation of the relaxin-2 receptor, RXFP1, in the brain. The current study undertook to develop analogues of human relaxin-3 (H3 relaxin) that can selectively bind and activate its receptor, RXFP3. We developed a high-affinity selective agonist (analogue 2) by removal of the intra-A chain disulfide bond and deletion of 10 residues from the N terminus of the A chain. Further truncation of this analogue from the C terminus of the B chain to Cys(B22) and addition of an Arg(B23) led to a high-affinity, RXFP3-selective, competitive antagonist (analogue 3). Central administration of analogue 2 in rats increased food intake, which was blocked by prior coadministration of analogue 3. These novel RXFP3-selective peptides represent valuable pharmacological tools to study the physiological roles of H3 relaxin/RXFP3 systems in the brain and important leads for the development of novel compounds for the treatment of affective and cognitive disorders.


Bio-cake layer based ultrafiltration in treating iron-and manganese-containing groundwater: Fast ripening and shock loading.
Groundwater was a desired alternative for decentralized water supply. However, the presence of iron, manganese and ammonia significantly limited its extensive adoptions. In this study, an innovative gravity-driven membrane (GDM) process has been developed to address such problems. The results indicated that GDM process can efficiently diminish the concentrations of iron, manganese and ammonia, with average removal efficiencies of 97%, 95% and 70%, respectively, since the bio-cake layer on the membrane surface can serve as a dynamic barrier for the foulants rejection. In GDM filtration, the manganese removal was mainly attributed to the synergistic effects between the chemically auto-catalytic oxidation by manganese oxides (MnOx) and biological activity by manganese-oxidizing bacteria (MnOB). Pre-addition of MnOx particles into GDM system could significantly enhance the manganese removal and shorten its ripening time by approximately 50%. During long-term filtration, the fluxes of GDM remained stabilized (4-5 L m-2 h-1), and MnOx particles pre-additions could improve the stable fluxes by 23%-37%. The flux stabilization of GDM process was mainly determined by the heterogeneous structures of bio-cake layer, and the generated iron and manganese oxides would improve its heterogeneities. Furthermore, MnOx assisted GDM process conferred robust capacities in resisting the shock loading of manganese and ammonia in the feed water, and the highest concentrations of manganese and ammonia were suggested to be less than 2.96 mg/L and 0.9 mg/L, respectively. Therefore, these findings are full of relevance to develop new strategies to treat the iron- and manganese-containing groundwater and promote the extensive application of UF technology for decentralized water supply.


Highly variable iron content modulates iceberg-ocean fertilisation and potential carbon export.
Marine phytoplankton growth at high latitudes is extensively limited by iron availability. Icebergs are a vector transporting the bioessential micronutrient iron into polar oceans. Therefore, increasing iceberg fluxes due to global warming have the potential to increase marine productivity and carbon export, creating a negative climate feedback. However, the magnitude of the iceberg iron flux, the subsequent fertilization effect and the resultant carbon export have not been quantified. Using a global analysis of iceberg samples, we reveal that iceberg iron concentrations vary over 6 orders of magnitude. Our results demonstrate that, whilst icebergs are the largest source of iron to the polar oceans, the heterogeneous iron distribution within ice moderates iron delivery to offshore waters and likely also affects the subsequent ocean iron enrichment. Future marine productivity may therefore be not only sensitive to increasing total iceberg fluxes, but also to changing iceberg properties, internal sediment distribution and melt dynamics.


The Akt/protein kinase B-dependent anti-apoptotic pathway and the mitogen-activated protein kinase cascade are alternatively activated in human glioblastoma multiforme.
We investigated the activation of two important signal transduction pathways in human glioblastoma cells and found a constitutive phosphorylation of either Akt or mitogen-activated protein kinase (MAPK) under serum free conditions. In all but one cell line Wortmannin-sensitive activation of Akt could be attributed to the loss of functional PTEN protein. All cell lines with Akt activation exhibited only weak phosphorylation of the MAPK signal pathway, whereas those without constitutive Akt activation demonstrated high levels of phosphorylated MAPK under serum free conditions. Our data might indicate the presence of two functional subtypes of glioblastoma multiforme, since Akt and MAPK are involved in cellular survival and proliferation signalling, respectively.


Efficacy of Online Multi-Player Versus Single-Player Exergames on Adherence Behaviors Among Children: A Nonrandomized Control Trial.
Exergames have the potential to significantly increase physical activity in children. Studies to date have shown mixed results and often rely on self-reported data. Multi-player gaming may augment participation. The purpose of the study was to examine children's adherence behaviors in multi-player online exergames compared to a single-player condition within a home environment. Seventy-two children, aged 9-12 years, who were not meeting physical activity guidelines at baseline, were allocated to the multi-player or single-player condition. Six-week cycle-based exergaming trials took place 5 day/week in the early evening with online game supervision. Bike use was objectively recorded via game logs. Adherence was high throughout the trial. Play session duration was M = 37.65 (SD = 15.39) min/day, and overall play duration was M = 133.45 (SD = 81.27) min in Week 1 and M = 77.23 (SD = 84.09) min in Week 6. Total physical activity was significantly higher at 6 weeks compared to baseline (p = .01, ηp2 = .13). There was no significant difference in play duration between conditions (p = .57, ηp2 = .01). This trial objectively demonstrated that exergames can promote high adherence levels. Multi-player capabilities did not augment adherence levels. Introducing new games throughout the trial may have motivated participants to keep playing, regardless of whether play was against real or artificial opponents. Weekly play duration decreased due to a significant drop in play frequency. For children who enjoy exergames, innovative solutions to promote more frequent exergame play are needed. NCT02032667.


Selective isolation of Pseudomonas stutzeri from vertebrate faeces on Rambach agar.
Faecal samples collected from 308 wild birds of 25 species and 19 rodents of 3 species in South Moravia (Czechland) were pre-incubated in Müller-Kauffmann tetrathionate broth at 42 degrees C for 24 h and then streaked onto Rambach agar plates which were incubated at 37 degrees C for 48 h. Seventeen out of 22 isolates forming orange-red colonies on Rambach agar were identified as Pseudomonas stutzeri, the rest as Pseudomonas sp. and Alcaligenes sp. The colonies of P. stutzeri were either dry, wrinkled and adherent to the agar (resembling Bacillus) or smooth, less adherent (mimicking Salmonella). P. stutzeri was recovered from five species of vertebrates caught in farmland habitats: the house sparrow (Passer domesticus), the tree sparrow (P. montanus), the great warbler (Acrocephalus arundinaceus), the wood mouse (Apodemus sylvaticus) and the common vole (Microtus arvalis). The overall isolation rate was 4.5% in birds (12.6% in house sparrows) and 15.8% in rodents. The procedure can be useful for the isolation of P. stutzeri in clinical and environmental studies.


Epigenetic m6A RNA Modification Reader YTHDF1 in Merkel Cell Carcinoma.
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine cutaneous malignancy that commonly affects older individuals with a high mortality rate [...].


Relationship between haemophilia and social status.
The impact of haemophilia and its treatment on social status has not been well studied, although research into the quality of life of patients with haemophilia has shed some light on aspects of social and role functioning. Studies conducted before the advent of safe and effective coagulation factor replacement therapy suggest that the haemophilia population was predominantly of low socioeconomic status with many social disadvantages, including high rates of disability and unemployment and low rates of marriage. Since the availability of purified factor VIII concentrates that could be used in a home-care setting and as prophylaxis, most research suggests that social status and well-being amongst children, adolescents, and adults with haemophilia is not compromised, and is comparable to that of the general population. Children and adolescents with haemophilia do not generally feel disadvantaged, although haemophilia-related issues at school and amongst peer groups do arise. Recent studies in adults show higher than average rates of marriage and cohabitation and the attainment of a generally good educational status, but, as in the past, employment rates remain comparatively lower. Social status amongst the elderly with haemophilia who may have developed severe disability as a result of their condition is poorly defined and has never been formally studied. Additional research is recommended.


Effects of two different anesthesia-analgesia methods on incidence of postoperative delirium in elderly patients undergoing major thoracic and abdominal surgery: study rationale and protocol for a multicenter randomized controlled trial.
Delirium is a common complication in elderly patients after surgery and associated with increased morbidity and mortality. Studies suggest that deep anesthesia and intense pain are important precipitating factors of postoperative delirium. Neuraxial block is frequently used in combination with general anesthesia for patients undergoing major thoracic and abdominal surgery. Compared with general anesthesia alone and postoperative intravenous analgesia, combined epidural-general anesthesia and postoperative epidural analgesia decreases the requirement of general anesthetics during surgery and provided better pain relief after surgery. However, whether combined epidural-general anesthesia plus epidural analgesia is superior to general anesthesia plus intravenous analgesia in decreasing the incidence of postoperative delirium remains unknown. This is a multicenter, open-label, randomized, parallel-controlled clinical trial. One thousand eight hundred elderly patients (age range 60-90 years) who are scheduled to undergo major thoracic or abdominal surgery are randomized to receive either general anesthesia plus postoperative intravenous analgesia or combined epidural-general anesthesia plus postoperative epidural analgesia. The primary outcome is the 7-day incidence of postoperative delirium. Secondary outcomes include the duration of postoperative delirium, the intensity of pain during the first three days after surgery, the 30-day incidences of postoperative non-delirium complications, the length of stay in hospital after surgery and 30-day all-cause mortality. Results of the present study will provide information to guide clinical practice in choosing appropriate anesthesia-analgesia method for elderly patients undergoing major thoracic and abdominal surgery. The study is registered on ClinicalTrials.gov NCT01661907 and Chinese Clinical Trial Registry ChiCTR-TRC-12002371 .


Prediction of drug-target interaction based on protein features using undersampling and feature selection techniques with boosting.
Accurate identification of drug-target interaction (DTI) is a crucial and challenging task in the drug discovery process, having enormous benefit to the patients and pharmaceutical company. The traditional wet-lab experiments of DTI is expensive, time-consuming, and labor-intensive. Therefore, many computational techniques have been established for this purpose; although a huge number of interactions are still undiscovered. Here, we present pdti-EssB, a new computational model for identification of DTI using protein sequence and drug molecular structure. More specifically, each drug molecule is transformed as the molecular substructure fingerprint. For a protein sequence, different descriptors are utilized to represent its evolutionary, sequence, and structural information. Besides, our proposed method uses data balancing techniques to handle the imbalance problem and applies a novel feature eliminator to extract the best optimal features for accurate prediction. In this paper, four classes of DTI benchmark datasets are used to construct a predictive model with XGBoost. Here, the auROC is utilized as an evaluation metric to compare the performance of pdti-EssB method with recent methods, applying five-fold cross-validation. Finally, the experimental results indicate that our proposed method is able to outperform other approaches in predicting DTI, and introduces new drug-target interaction samples based on prediction probability scores. pdti-EssB webserver is available online at http://pdtiessb-uestc.com/.


Knee stability, athletic performance and sport-specific tasks in non-professional soccer players after ACL reconstruction: comparing trans-tibial and antero-medial portal techniques.
a wrong position of bone tunnels, in particular on the femur, is one of the most frequent causes of a failed anterior cruciate ligament (ACL) reconstruction. Several studies demonstrated that drilling the femoral tunnel through the antero-medial portal (AMP) allows a more anatomical placement on the lateral femoral condyle and higher knee stability, compared to trans-tibial (TT) technique. The aim of this study was to retrospectively evaluate two groups of soccer players operated on for ACL reconstruction according to either one of these two techniques. two groups of non-professional soccer players operated on for a single bundle ACL reconstruction with hamstrings autograft using either a TT (20 patients) or an AMP (23 patients) technique were retrospectively evaluated with KT-1000 arthrometer, manual pivot shift test, isokinetic test, the incremental treadmill-running test, athletic and sport specific tasks, and knee scores (IKDC, Lysholm and KOOS). the AMP group showed better results at pivot shift test and KOOS, but lower flexion angles at single leg squat test. There were no differences in all the other considered outcomes. the better rotational stability of the knee achieved in AMP group did not lead to significantly better clinical and functional results in our patients. Case-control study.


In vitro antimalarial drug susceptibility in Thai border areas from 1998-2003.
The Thai-Myanmar and Thai-Cambodia borders have been historically linked with the emergence and spread of Plasmodium falciparum parasites resistant to antimalarial drugs. Indeed, the areas are often described as harbouring multi-drug resistant parasites. These areas of Thailand have experienced significant changes in antimalarial drug exposure patterns over the past decade. This study describes the in vitro antimalarial susceptibility patterns of 95 laboratory-adapted P. falciparum isolates, collected between 1998 and 2003. Ninety five P. falciparum isolates were collected from five sites in Thailand between 1998 and 2003. After laboratory adaptation to in vitro culture, the susceptibility of these parasites to a range of established antimalarial drugs (chloroquine [CQ], mefloquine [MQ], quinine [QN] and dihydroartemisinin [DHA]) was determined by the isotopic microtest. Mefloquine (MQ) sensitivity remained poorest in areas previously described as MQ-resistant areas. Sensitivity to MQ of parasites from this area was significantly lower than those from areas reported to harbour moderate (p = 0.002) of low level MQ resistance (p = 000001). Importantly for all drugs tested, there was a considerable range in absolute parasite sensitivities. There was a weak, but statistically positive correlation between parasite sensitivity to CQ and sensitivity to both QN and MQ and a positive correlation between MQ and QN. In terms of geographical distribution, parasites from the Thai-Cambodia were tended to be less sensitive to all drugs tested compared to the Thai-Myanmar border. Parasite sensitivity to all drugs was stable over the 6-year collection period with the exception of QN. This study highlights the high degree of variability in parasite drug sensitivity in Thailand. There were geographical differences in the pattern of resistance which might reflect differences in drug usage in each area. In contrast to many other studies there were weak, but statistically significant positive, correlations between sensitivity to CQ and sensitivity to MQ and QN. Over the six years of sample collection, parasite sensitivity appears to have stabilized to these drugs in these sites.


Modified vaccinia Ankara vaccine expressing Marburg virus-like particles protects guinea pigs from lethal Marburg virus infection.
We introduce a new vaccine platform against Marburg virus (MARV) combining the advantages of the immunogenicity of a highly attenuated vaccine vector (Modified Vaccinia Ankara, MVA) with the authentic conformation of virus-like particles (VLPs). Our vaccine, MVA-MARV-VLP, expresses the minimal components of MARV VLPs: the envelope glycoprotein GP and the matrix protein VP40. Electron microscopy confirmed self-assembly and budding of VLPs from infected cells. Prime/boost vaccination of guinea pigs with MVA-MARV-VLP-elicited MARV-specific binding and neutralizing antibody responses. Vaccination also induced Fc-mediated innate immune effector functions including activation of NK cells and antibody-dependent phagocytosis by neutrophils and monocytes. Inoculation of vaccinated animals with guinea pig-adapted MARV demonstrated 100% protection against death and disease with no viremia. Therefore, our vaccine platform, expressing two antigens resulting in assembly of VLPs in the native conformation in vaccinated hosts, can be used as a potent vaccine against MARV.


Ocellar system of the insect: comparison of dorsal ocellus and lateral ocellus.
The ocellar receptor and neuropil in the dorsal ocellar system of the cockroach and the lateral ocellar system of the swallowtail butterfly larva have been compared. In the dorsal ocellus of the cockroach more than 10,000 retinular cells each with a rhabdomere are piled up one upon another without a specific pattern in the ocellar capsule. Retinular axons synapse exclusively with branches of four thick second order neurons in the lower region of the capsule. Dark granule-containing neurons, originating in the brain, also synapse with the second order neurons in the ocellar neuropil. The ocellar nerve is comprised of four thick second order processes (ca. 6-16 micron) and 20-40 thin processes (ca. 1-5 micron), which include retinular axons, collaterals of thick processes, possible third order processes and unidentified processes. Synapses occur against these processes in the ocellar nerve and in the extreme proximal region of the ocellar neuropil. Six lateral ocelli occur on both sides of head in the butterfly larva. Each ocellus contains seven retinular cells, which are grouped into three distal cells and four proximal cells, or four distal cells, two peripheral cells and one central cell by the position of their rhabdomeres. Retinular axons extend to the brain, and enter the distal optic neuropil. There are six neuropils, each of which contains the seven axons from one ocellus and a dozen or so second order processes. Of seven retinular axons, four occur peripherally and the remaining three occur centrally in the neuropil. All axons synapse with fine branches of interneurons. Second order processes together with at least three central retinular axons extend to the second optic neuropil, but the peripheral axons could not be followed there. The highly organized receptors and the neuropil in the lateral ocellar system suggest a complexly integrated function. An ocellar nerve and proximal ocellar neuropil appear like an extension of the CNS, and direct connections of retinular axons with interneurons in the CNS appear characteristic of the dorsal ocellus. This difference may be related to the distribution of the two ocellar systems: the dorsal ocelli co-exist with the compound eyes of the adult, whereas the lateral ocelli are the only photoreceptor organs of the larval insect.


Calendrical savants: exceptionality and practice.
The exceptionality of the skills of calendrical savants and the role of practice were investigated. Experiment 1 compared four autistic calendrical savants to Professor Conway, a distinguished mathematician with calendrical skills. Professor Conway answered questions over a greater range of years but some savants knew more calendrical regularities. Experiment 2 studied the development of a calendrical savant's ability to answer date questions for very remote future years. He started by making written calculations and progressed to mental calculation. His variation in response time for remote dates was similar to that for near dates. The findings are consistent with the view that calendrical savants develop their skills through practice.


Implementation and assessment of a novel drug interaction tool (TLC-act) in an entry-to-practice doctor of pharmacy program.
Drug-drug interaction (DDI) assessment is an important role that pharmacists have in practice. Students often struggle with this complex clinical reasoning skill. TLC-Act is a tool that was created to mirror the steps and clinical checkpoints that pharmacists complete when assessing DDIs. Through integration of TLC-Act in the pharmacy curriculum, students will be better prepared for assessing and evaluating DDIs when in practice. For the 2021-2022 academic year, an asynchronous educational activity to teach students how to use TLC-Act was created and implemented. Five videos that encompassed multiple facets of TLC-Act including an introduction to the tool and how to use it, an example application of the tool to a patient case, and the clinical utility of using TLC-Act in the hospital and community settings. Students were instructed to view all five videos and then complete a patient case that focused on the DDI between ciprofloxacin and metformin. A pre- and post-activity survey was disseminated to 640 students across the first three years of the program to gather students' perspectives on the educational activity. Overall, survey response rates were 32% for the pre- and 23% for the post-activity surveys. The TLC-Act educational activity improved students' skills with managing DDIs.


Preoperative irrigation and vacuum sealing drainage with antibiotic-containing drainage fluid of foot and ankle wounds improves outcome of reconstructive skin flap surgery.
By observing the infection and soft tissue defect on the wound surface of the foot and ankle, this paper attempts to explore the effect of preoperative irrigation and vacuum sealing drainage with antibiotic-containing drainage fluid (abPI-VSD) on the bacterial quantity and the local inflammatory response at the flap, and further to provide a basis for applying this technique before a reconstructive skin flap surgery of foot and ankle wounds. Seventy-five patients were randomly divided into two groups, and all surgeries were done by one physician. The flap reconstructions were done to 31 cases with the abPI-VSD being used (group A); the flap reconstructions were done to the rest 44 cases after wound cleaning using antibiotic irrigation solution without the use of the abPI-VSD (group B). Quantitative bacteriology was made to group A before and after the use of abPI-VSD; quantitative bacteriology was made to group B before and after wound cleaning. Then, the reconstructive skin flap surgery was done. After the surgeries, the time of local inflammatory response at the flap in both groups were recorded. The measured bacterial quantity was evaluated in logarithm and by t test. The bacterial quantity was 3.2 ± 1.9 × 107 cfu/g in group A before the use of abPI-VSD and 2.3 ± 2.0 × 107 in group B (P > 0.05) before debridement. The bacterial quantity was 1.2 ± 2.0 × 104 cfu/g in group A after abPI-VSD and was 2.9 ± 4.0 × 106 in group B after wound cleaning (P < 0.05). The time of postoperative inflammatory response in the flap was 8 ± 2.5 days in group A and 13 ± 3.4 days in group B (P < 0.05). abPI-VSD can distinctly reduce the bacterial quantity on the surface of the wound, provide a good condition of tissue bed for the flap reconstruction, and effectively control the local inflammatory response at the flap and hence improve the survival quality of the flap.


Konjac glucomannan/carboxymethyl chitosan film embedding gliadin/casein nanoparticles for grape preservation.
Constructing biopolymer-based packaging films with fantastic water resistance and mechanical properties for food preservation is highly desirable and challenging. In this work, Gliadin/Casein nanoparticles (GCNPs) were prepared by pH-driven method and embedded into konjac glucomannan/carboxymethyl chitosan (KC) film matrix to improve the water resistance and mechanical properties of KC film. Gliadin and Casein showed good compatibility and co-assembled to form compact GCNPs clusters through hydrogen bonding and hydrophobic interaction verified by FT-IR spectroscopy, and fluorescence spectroscopy. The particle size and zeta potential of GCNPs was 269.7 nm and -7.6 mV, respectively. The effect of GCNPs on the mechanics, water barrier, thermal stability, and UV-shielding of KC-GCNPs film was investigated. SEM images revealed that GCNPs uniformly distributed into KC film matrix and significantly improved the mechanics (tensile strength: 75.6 MPa, elongation at breaking: 36.7 %), water barrier ability (water contact angle: 91.3°, water vapor permeability: 0.994 g mm/m2 day kPa, water solubility: 52.0 %), thermal stability and UV blocking property of KC-GCNPs film. Furthermore, KC-GCNPs film could also be applied to extend the shelf life of grapes. This paper demonstrated the great potential of GCNPs as functional nanofillers in enhancing the physicochemical properties of KC film.


Distinct gating modes determine the biphasic relaxation of NMDA receptor currents.
Following brief stimulation, macroscopic NMDA receptor currents decay with biphasic kinetics that is believed to reflect glutamate dissociation and receptor desensitization. We found that the fast and slow decay components arise from the simultaneous deactivation of receptor populations that gate with short and long openings, respectively. Because individual receptors switched infrequently between gating modes, the relaxation time course was largely determined by the proportion of channels in each gating mode at the time of stimulation.


Immunoregulatory activities of autoreactive T cells: an I-A-specific T cell clone mediates both help and suppression of antibody responses.
We have derived a Ly-1+, 2-3- T cell clone that is specific for autologous I-A on activated but not on resting cells. After activation, this clone produces factors that induce purified (B + adherent) cells to secrete antibody in response to sheep red blood cells and type 2 T-independent antigens. Regulation of plaque-forming cell responses by this clone is dose dependent: low numbers enhance the plaque-forming cell response, whereas high numbers suppress the response. The inhibition observed with high doses is associated with cytolysis of I-A+ cells, and this can be blocked by the addition of anti-I-A antibodies. The physiologic significance of this novel cell type in regulating immune responses is discussed.


Multiple photosynthetic reaction centres using zinc porphyrinic oligopeptide-fulleropyrrolidine supramolecular complexes.
Multiple charge-separation sites have successfully been constructed using supramolecular complexes of multiporphyrinic oligopeptides [P(ZnP)(n), n = 2, 4, 8] with fulleropyrrolidine bearing a pyridine or imidazole coordinating ligand, which are organized by utilizing π-π interaction in addition to the coordination bond.


Recent progress in unraveling the complexities of receptor biology: towards new therapeutics.
This meeting is the main annual event convened by the British Pharmacological Society. The December 2011 meeting featured a joint symposium with the Chinese Pharmacological Society. Held at the Queen Elizabeth II conference centre in London, UK, the meeting was sold out, with more than 800 delegates in attendance. The meeting comprised a diverse selection of symposia, together with award lectures, short oral communications and vibrant poster sessions, in both basic and clinical pharmacology.


Persistent Opioid Use Following Total Knee Arthroplasty: A Signal for Close Surveillance.
Prolonged opioid use following total knee arthroplasty (TKA) has not been extensively studied. A cohort study of primary TKA for osteoarthritis using an integrated healthcare system and Total Joint Replacement Registry (January 2008-December 2011) was conducted. Opioid use during the first year after TKA was the exposure of interest and cumulative daily oral morphine equivalent (OME) amounts were calculated. Total postsurgical OME per 90-day exposure periods were categorized into quartiles. The end point was aseptic revision surgery. Survival analyses were conducted and hazard ratios (HRs) were adjusted for age, gender, prior analgesic use, opioid-related comorbidities, and chronic pain diagnoses. A total of 24,105 patients were studied. After the initial 90-day postoperative period, 41.5% (N = 9914) continued to use opioids. Also, 155 (0.6%) revisions occurred within 1 year and 377 (1.6%) within 5 years. Compared to patients not taking any opioids, patients using medium-low to high OME after the initial 90-day period had a higher adjusted risk of 1-year revision, ranging from HR = 2.4 (95% confidence interval, 1.3-4.5) to HR = 33 (95% confidence interval, 10-110) depending on the OME and time period. Patients who require opioids beyond 90 days after TKA warrant close follow-up.


Impact of environmental factors on the ammonia-oxidizing and denitrifying microbial community and functional genes along soil profiles from different ecologically degraded areas in the Siding mine.
Ammonia oxidizers (ammonia-oxidizing bacteria (AOB amoA) and ammonia-oxidizing archaea (AOA amoA)) and denitrifiers (encoded by nirS, nirK and nosZ) in the soil nitrogen cycle exist in a variety of natural ecosystems. However, little is known about the contribution of these five N-related functional genes to nitrification and denitrification in the soil profile in severely ecologically degraded areas. Therefore, in the present study, the abundance, diversity and community composition of AOA, AOB, nirS, nirK and nosZ were investigated in the soil profiles of different ecologically degraded areas in the Siding mine. The results indicated that, at the phylum level, the dominant archaea were Crenarchaeota and Thaumarchaeota and the dominant bacteria were Proteobacteria. Heavy metal contents had a great impact on AOA amoA, nirS and nirK gene abundances. AOA amoA contributed more during the ammonia oxidation process and was better adapted for survival in heavy metal-contaminated environments. In addition to heavy metals, the soil organic matter (SOM) content and C/N ratio had strong effects on the AOA and AOB community diversity and structure. In addition, variations in the net ammonification and nitrification rates were proportional to AOA amoA abundance along the soil profile. The soil C/N ratio, soil available phosphorus content and soil moisture influenced the denitrification process. Both soil available phosphorus and moisture were more strongly related to nosZ than to nirS and nirK. In addition, nosZ presented a higher correlation with the nosZ/(nirS + nirK) ratio. Moreover, nosZ/(nirS + nirK) was the key functional gene group that drove the major processes for NH4+-N and NO3--N transformation. This study demonstrated the role and importance of soil property impacts on N-related microbes in the soil profile and provided a better understanding of the role and importance of N-related functional genes and their contribution to soil nitrification and denitrification processes in highly degraded areas in the Siding mine.


Encephalitis in primary HIV infection: challenges in diagnosis and treatment.
We report a case of primary HIV encephalitis, which initially presented as acute psychosis. Magnetic resonance imaging of the brain was suggestive of vasculitis and multiple infarctions, whereas a brain biopsy after six weeks of symptoms showed HIV encephalitis with microglial nodules, but no signs of vasculitis. We review previous reported cases and radiological findings in HIV encephalitis and discuss the role of antiretroviral therapy and steroids in its management.


Validation of a rapid, saliva-based, and ultra-sensitive SARS-CoV-2 screening system for pandemic-scale infection surveillance.
Without any realistic prospect of comprehensive global vaccine coverage and lasting immunity, control of pandemics such as COVID-19 will require implementation of large-scale, rapid identification and isolation of infectious individuals to limit further transmission. Here, we describe an automated, high-throughput integrated screening platform, incorporating saliva-based loop-mediated isothermal amplification (LAMP) technology, that is designed for population-scale sensitive detection of infectious carriers of SARS-CoV-2 RNA. Central to this surveillance system is the "Sentinel" testing instrument, which is capable of reporting results within 25 min of saliva sample collection with a throughput of up to 3840 results per hour. It incorporates continuous flow loading of samples at random intervals to cost-effectively adjust for fluctuations in testing demand. Independent validation of our saliva-based RT-LAMP technology on an automated LAMP instrument coined the "Sentinel", found 98.7% sensitivity, 97.6% specificity, and 98% accuracy against a RT-PCR comparator assay, confirming its suitability for surveillance screening. This Sentinel surveillance system offers a feasible and scalable approach to complement vaccination, to curb the spread of COVID-19 variants, and control future pandemics to save lives.