A thermodynamic analysis of monovalent cation permeation through a K(+)-selective ion channel.
Ionic selectivity characteristics of the K+ channel from the sarcoplasmic reticulum were studied as a function of temperature in order to decompose the profile of Gibbs free energy along the conduction pore into its enthalpic and entropic components. For Li+, Na+, K+, and Rb+, the enthalpy of binding to the channel is close to zero. Activation enthalpies for transferring ions from bulk aqueous solution to the channel's selectivity region are 20-25 kJ/mol for Na+, K+, and Rb+ and substantially higher for Li+ and Cs+. Transfer of Li+ and Na+ to the selectivity region involved large favorable entropies. The results argue that the group IA cations shed about half their waters of hydration in permeating the selectivity region of this channel.


The conformation-specific Hsp90 inhibition interferes with the oncogenic RAF kinase adaptation and triggers premature cellular senescence, hence, acts as a tumor suppressor mechanism.
Cancer emergence is associated with cellular adaptations to altered signal transduction mechanisms arbitrated by mutated kinases. Since conventional kinase inhibitors can exhibit certain limitations to such kinase adaptations, overcoming kinase adaptation for cancer treatment gains importance. The cancer chaperone, Hsp90, is implicated in the conformational maturation and functional stabilization of mutated gene products. However, its role in kinase adaptations is not explored in detail. Therefore, the present study aims to understand the mechanisms of Hsp90-dependent kinase adaptation and develop a novel antitumor strategy. We chose malignant human lung cancer cells to demonstrate Hsp90-dependent RAF oncogene adaptation. We show that RAF oncogene adaptations were predominant over wild type RAF and are facilitated by conformation-specific Hsp90. Consequently, the conformation-specific Hsp90 inhibitor, 17AAG, interfered with oncogenic RAF stability and function and inhibited cell proliferation. The enforced cytostasis further triggered premature cellular senescence and acted as an efficient and irreversible tumor suppressor mechanism. Our results also display that oncogenic RAF interactions with Hsp90 require the middle-charged region of the chaperone. Our mice xenografts revealed that 17AAG pretreated tumor cells lost their ability to proliferate and metastasize in vivo. In summary, we demonstrated Hsp90-dependent kinase adaptation in tumor cells and the effect of Hsp90 inhibition in triggering premature senescence to interfere with the tumor progression. Our findings are of both biological relevance and clinical importance.


Bioinspired Three-Dimensional Magnetoactive Scaffolds for Bone Tissue Engineering.
Bone tissue repair strategies are gaining increasing relevance due to the growing incidence of bone disorders worldwide. Biochemical stimulation is the most commonly used strategy for cell regeneration, while the application of physical cues, including magnetic, mechanical, or electrical fields, is a promising, however, scarcely investigated field. This work reports on novel magnetoactive three-dimensional (3D) porous scaffolds suitable for effective proliferation of osteoblasts in a biomimetic microenvironment. This physically active microenvironment is developed through the bone-mimicking structure of the scaffold combined with the physical stimuli provided by a magnetic custom-made bioreactor on a magnetoresponsive scaffold. Scaffolds are obtained through the development of nanocomposites comprised of a piezoelectric polymer, poly(vinylidene fluoride) (PVDF), and magnetostrictive particles of CoFe2O4, using a solvent casting method guided by the overlapping of nylon template structures with three different fiber diameter sizes (60, 80, and 120 μm), thus generating 3D scaffolds with different pore sizes. The magnetoactive composites show a structure very similar to trabecular bone with pore sizes that range from 5 to 20 μm, owing to the inherent process of crystallization of PVDF with the nanoparticles (NPs), interconnected with bigger pores, formed after removing the nylon templates. It is found that the materials crystallize in the electroactive β-phase of PVDF and promote the proliferation of preosteoblasts through the application of magnetic stimuli. This phenomenon is attributed to both local magnetomechanical and magnetoelectric response of the scaffolds, which induce a proper cellular mechano- and electro-transduction process.


PTP1B and α-glucosidase inhibitors from Selaginella rolandi-principis and their glucose uptake stimulation.
As part of an ongoing search for new protein tyrosine phosphatase 1B inhibitors and glucose uptake stimulators from nature, a new coumarin, selaginolide A (1) and four known isoflavones (2‒5) were isolated from the ethanol extract of a Vietnamese medicinal plant Selaginella rolandi-principis. The chemical structures of the isolates were elucidated by extensive analysis of spectroscopic and physicochemical data. Compounds 3‒5 have been identified from Selaginella genus for the first time. The antidiabetic properties of the isolates (1‒5) were investigated using in vitro assay on 2-NBDG uptake in 3T3-L1 adipocytes and against PTP1B and α-glucosidase enzyme activities as well. Compounds 1 exhibited the most potency with inhibitory IC50 values of 7.40 ± 0.28 and 7.52 ± 0.37 µM against PTP1B and α-glucosidase, respectively. Compounds 3 and 5 possessed potential inhibitions on PTP1B enzyme with IC50 values of 23.02 ± 1.29 and 11.08 ± 0.92 µM and moderate inhibitions on α-glucosidase with IC50 values of 36.47 ± 1.87 and 55.73 ± 2.58 µM, respectively. Compounds 2 and 4 showed weak PTP1B inhibitory activity (IC50 > 30 µM) but displayed remarkable α-glucosidase inhibition with IC50 values of 3.39 ± 0.87 and 9.72 ± 0.62 µM, respectively. Furthermore, ursolic acid as a positive control (IC50 3.42 ± 0.26 µM) and compounds 1 and 5 acted as mixed-competitive inhibitors against PTP1B enzyme with Ki values of 6.46, 10.28, and 15.01 µM, respectively. In addition, compounds 1 and 5 also showed potent stimulatory effects on 2-NBDG uptake at a concentration of 10 µM. The obtained result might suggest the potential of new coumarin (1) as a new type of natural PTP1B and α-glucosidase inhibitor for further research and development of antidiabetic and obese agents.Graphic abstract.


SPARC-mediated long-term retention of nab-paclitaxel in pediatric sarcomas.
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein overexpressed by several cancers. Because SPARC shows high binding affinity to albumin, we reasoned that pediatric sarcoma xenografts expressing SPARC would show enhanced uptake and accumulation of nanoparticle albumin-bound (nab)-paclitaxel, a potent anticancer drug formulation. We first evaluated the expression of SPARC in patient-derived xenografts (PDXs) of Ewing sarcoma, rhabdomyosarcoma and osteosarcoma, finding variable SPARC gene expression that correlated well with SPARC protein measured by immunoblotting. We revealed that the activity of the fusion gene chimera EWSR1-FLI1, the genetic driver of Ewing sarcoma, leads to lower expression of the gene SPARC in these tumors, likely due to enriched acetylation marks of the histone H3 lysine 27 at regions including the SPARC promoter and potential enhancers. Then, we used SPARC-edited Ewing sarcoma cells (A673 line) to demonstrate that SPARC knocked down (KD) cells accumulated significantly less amount of nab-paclitaxel in vitro than SPARC wild type (WT) cells. In vivo, SPARC KD and SPARC WT subcutaneous xenografts in mice achieved similar maximum intratumoral concentrations of nab-paclitaxel, though drug clearance from SPARC WT tumors was significantly slower. We confirmed such SPARC-mediated long-term intratumoral accumulation of nab-paclitaxel in Ewing sarcoma PDX with high expression of SPARC, which accumulated significantly more nab-paclitaxel than SPARC-low PDX. SPARC-high PDX responded better to nab-paclitaxel than SPARC-low tumors, although these results should be taken cautiously, given that the PDXs were established from different patients that could have specific determinants predisposing response to paclitaxel. In addition, SPARC KD Ewing sarcoma xenografts responded better to soluble docetaxel and paclitaxel than to nab-paclitaxel, while SPARC WT ones showed similar response to soluble and albumin-carried drugs. Overall, our results show that pediatric sarcomas expressing SPARC accumulate nab-paclitaxel for longer periods of time, which could have clinical implications for chemotherapy efficacy.


Enhancement of the immunogenicity of an infectious bronchitis virus DNA vaccine by a bicistronic plasmid encoding nucleocapsid protein and interleukin-2.
A DNA vaccine against infectious bronchitis virus (IBV) can induce specific humoral and cell-mediated immunity. However, compared to conventional vaccines, DNA vaccines usually induce poor antibody responses. To develop a more potent IBV DNA vaccine formulations, a monocistronic vector encoding the nucleocapsid protein of IBV and a bicistronic vector separately encoding the nucleocapsid protein and immune-stimulatory interleukin-2 were constructed. When the DNA vaccines were administered to the quadriceps muscle of chickens, the induced humoral and cellular responses were evaluated. There was a significant difference in ELISA antibody levels elicited by either monocistronic or bicistronic DNA vaccines. The percentage of CD3+, CD3+CD8+ and CD3+CD4+ subgroups of peripheral blood T-lymphocytes in chickens immunized with bicistronic DNA vaccine were higher than those in chickens immunized with monocistronic DNA vaccine. When chickens were challenged with a virulent strain of IBV, the protective efficacy could be enhanced significantly after immunization with bicistronic DNA vaccine. These results demonstrated that bicistronic DNA vaccine is an effective approach to increase IBV DNA vaccine immunogenicity.


Creating an Enabling Environment for a Comprehensive Sexuality Education Intervention in Indonesia: Findings From an Implementation Research Study.
This study examines key factors that facilitated and hindered creating an enabling environment for the implementation of SEmangaT duniA RemajA/Teen's Aspirations (SETARA), a comprehensive sexuality education (CSE) intervention in schools across three sites in Indonesia. Data were collected through interviews with teachers, program implementers, and government officials; a review of program documents and monitoring and evaluation data; and a qualitative evaluation with SETARA students. One of the most important factors for creating an enabling environment for CSE relates to how well the program is introduced to government officials for approval. Findings showed that the relationship between the implementing organization and city government officials was important for obtaining approval, support, and formal agreements on collaboration. Framing the curriculum within local policies and priorities made it easier to communicate to schools, community, and parents. Buy-in from school principals was important for creating a supportive environment. Complexity of the materials, lack of time to prepare and implement sessions, and teacher-level factors such as pedagogical skills and misaligned values remain key challenges despite trainings. The study suggests that it is possible to implement and create political support for CSE in conservative contexts, especially with a good introduction of the program. Potential solutions for implementation and scaling barriers may lie in the digitalization of the intervention and of capacity strengthening and technical support for teacher. More research is needed to investigate which content and exercises can effectively be delivered digitally and which should best be delivered by teachers to maintain the effect of breaching the taboo around sexuality.


Effects of a new β3-adrenoceptor agonist, vibegron, on neurogenic bladder dysfunction and remodeling in mice with spinal cord injury.
To examine vibegron effects on lower urinary tract dysfunction (LUTD) in mice with spinal cord injury (SCI). Female mice underwent Th8-9 spinal cord transection and were orally administered vehicle or vibegron after SCI. We evaluated urodynamic parameters at 4 weeks after SCI with or without vibegron. Fibrosis- and ischemia-related messenger RNA (mRNA) and protein levels of collagen and elastin were measured in bladders of vehicle- and vibegron-treated SCI mice, and spinal intact mice. Non-voiding contractions (NVCs) were significantly fewer (15.3 ± 8.9 vs 29.7 ± 11.4 contractions; P < .05) and the time to the first NVC was significantly longer (1488.0 ± 409.5 vs 782.7 ± 399.7 seconds; P < .01) in vibegron-treated SCI mice vs vehicle-treated SCI mice. mRNAs levels of collagen types 1 and 3, transforming growth factor-β1 (TGF-β1), and hypoxia-inducible factor-1α (HIF-1α) were significantly upregulated in vehicle-treated SCI mice compared with spinal intact and vibegron-treated SCI mice (Col 1: 3.5 vs 1.0 and 2.0-fold; P < .01 and P < .05, Col 3: 2.1 vs 1.0 and 1.2-fold; P < .01 and P < .05, TGF-β1: 1.2 vs 1.0 and 0.9-fold; P < .05 and P < .05, HIF-1α: 1.4 vs 1.0 and 1.0-fold; P < .05 and P < .01). Total collagen and elastin protein levels in vehicle- and vibegron-treated SCI mice did not differ. Vibegron reduced NVCs, delayed the first NVC, and improved collagen types 1 and 3, TGF-β1, and HIF-1α mRNA expression in SCI mice. Vibegron might be effective for SCI-induced LUTD.


Synthesis and SAR study of new thiazole derivatives as vascular adhesion protein-1 (VAP-1) inhibitors for the treatment of diabetic macular edema.
Vascular adhesion protein-1 (VAP-1), an amine oxidase that is also known as a semicarbazide-sensitive amine oxidase (SSAO), is present in particularly high levels in human plasma, and is considered a potential therapeutic target for various inflammatory diseases, including diabetes complications such as macular edema. In our VAP-1 inhibitor program, structural modifications following high-throughput screening (HTS) of our compound library resulted in the discovery that thiazole derivative 10, which includes a guanidine group, shows potent human VAP-1 inhibitory activity (IC(50) of 230 nM; rat IC(50) of 14 nM). Moreover, compound 10 exhibited significant inhibitory effects on ocular permeability in STZ-induced diabetic rats.


Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer.
Complications related to concurrent chemoradiotherapy (CCRT) such as acute radiation-induced esophagitis (ARIE) may cause significant morbidity and unplanned treatment delays in patients with advanced non-small cell lung cancer (NSCLC). We designed a prospective randomized study to assess the impact of glutamine (GLN) supplementation in preventing CCRT-induced toxicities of advanced NSCLC patients. From September 2014 to September 2015, 60 patients diagnosed with NSCLC were included to the study. Thirty patients (50%) received prophylactic powdered GLN orally at a dose of 10 g/8 h. The prescribed radiation dose to the planning target volume was 30 Gy in 2-Gy fractions. The endpoints were radiation-induced esophagitis, mucositis, body weight loss, overall survival and progression-free survival. The 60 patients with NSCLC included 42 men and 18 women with a mean age ± standard deviation of 60.3 years ± 18.2 (range, 44-78 years).At a median follow-up of 26.4 months (range 10.4-32.2), all patients tolerated GLN well. A administration of GLN was associated with a decrease in the incidence of grade 2 or 3 ARIE (6.7% vs 53.4% for Gln+ vs Gln-; P = .004). GLN supplementation appeared to significantly delay ARIE onset for 5.8 days (18.2 days vs 12.4 days; P = .027) and reduced incidence of weight loss (20% vs 73.3%; P = .01). Our study suggests a beneficial effect of oral glutamine supplementation for the prevention from radiation-induced injury and body weight loss in advanced NSCLC patients who receiving CCRT.


Activation of natural Hf and Ta in relation to the production of 177Lu.
The isotope (177)Lu is used in nuclear medicine and biology for in vivo applications as a radioactive label of various targeting agents. To extend the availability of no-carrier added (177)Lu, we investigated the feasibility of its production in a proton accelerator. Tantalum and Hf targets were irradiated and chemically processed to determine the radioisotope yield and cross-sections. The largest cross-sections (approximately 20 mb) were found for the Hf target at 195 MeV; however, the presence of co-produced Lu isotopes may limit the product applications. The results are in good agreement with theoretical data calculated using computer codes MCNPX and ORIGEN2S. Production of relevant medical isotopes such as (167)Tm and (169)Yb from the above targets is discussed as well.


Identification of ALG3 as a potential prognostic biomarker in lung adenocarcinoma.
The abnormal expression of Alpha-1,3-mannosyltransferase (ALG3) has been implicated in tumor promotion. However, the clinical significance of ALG3 in Lung Adenocarcinoma (LUAD) remains poorly understood. Therefore, we aimed to assess the prognostic value of ALG3 and its association with immune infiltrates in LUAD. The transcriptional expression profiles of ALG3 were obtained from the Cancer Genome Atlas (TCGA), comparing lung adenocarcinoma tissue with normal tissues. To determine the prognostic significance of AGL3, Kaplan-Meier plotter, and Cox regression analysis were employed. Logistic regression was utilized to analyze the association between ALG3 expression and clinical characteristics. Additionally, a receiver operating characteristic (ROC) curve and a nomogram were constructed. To explore the underlying mechanisms, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene set enrichment analysis (GSEA) was conducted. The relationship between AGL3A mRNA expression and immune infiltrates was investigated using the tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB). Furthermore, an in vitro experiment was performed to assess the impact of ALG3 mRNA on lung cancer stemness abilities and examine key signaling pathway proteins. Our results revealed the ALG3 mRNA and protein expression in patients with LUAD was much higher than that in adjacent normal tissues. High expression of ALG3 was significantly associated with N stage (N0, HR = 1.98, P = 0.002), pathological stage (stage I, HR = 2.09, P = 0.003), and the number of pack years (<40, HR = 2.58, P = 0.001). Kaplan-Meier survival analysis showed that high expression of ALG3 was associated with poor overall survival (P < 0.001), disease-free survival (P < 0.001), and progression-free interval (P = 0.007). Through multivariate analysis, it was determined that elevated ALG3 expression independently impacted overall survival (HR = 1.325, P = 0.04). The Tumor Immune Estimation Resource discovered a link between ALG3 expression and tumor-infiltrating immune cells in LUAD. Additionally, ROC analysis proved that ALG3 is a reliable diagnostic marker for LUAD (AUC:0.923). Functional pathways analysis identified that ALG3 is negatively correlated with FAT4. We performed qRT-PCR to assess that knockdown ALG3 expression significantly upregulated FAT4 expression. Spheroid assay and flow cytometry analysis results showed that downregulated of ALG3 inhibited H1975 cell line stemness. Western blot analysis revealed that decreased ALG3 inhibited the YAP/TAZ signal pathway. High expression of ALG3 is strongly associated with poor prognosis and immune infiltrates in LUAD.


An activatable probe for detecting alcoholic liver injury via multispectral optoacoustic tomography and fluorescence imaging.
A probe has been developed for imaging alcoholic liver injury through detecting the overexpressed cytochrome P450 reductase in hypoxia in the hepatic region. Upon response to the enzyme, the activated probe displays turn-on fluorescence and near-infrared absorption and generates prominent optoacoustic signals.


Understanding plant pathogen interactions using spatial and single-cell technologies.
Plants are in contact with diverse pathogens and microorganisms. Intense investigation over the last 30 years has resulted in the identification of multiple immune receptors in model and crop species as well as signaling overlap in surface-localized and intracellular immune receptors. However, scientists still have a limited understanding of how plants respond to diverse pathogens with spatial and cellular resolution. Recent advancements in single-cell, single-nucleus and spatial technologies can now be applied to plant-pathogen interactions. Here, we outline the current state of these technologies and highlight outstanding biological questions that can be addressed in the future.


Suv39h1 Silencing Recovers Memory Decline in Scopolamine-Induced Amnesic Mouse Model.
Histone post-translational modifications play an important role in the regulation of long-term memory and modulation of expression of neuronal immediate early genes (IEGs). The lysine methyltransferase KMT1A/ Suv39h1 (a mammalian ortholog of the Drosophila melanogaster SU (VAR) 3-9) aids in the methylation of histone H3 at lysine 9. We previously reported that age-related memory decline is associated with an increase in Suv39h1 expression in the hippocampus of male mice. The scopolamine-induced amnesic mouse model is a well-known animal model of memory impairment. In the current study, we have made an attempt to find a link between the changes in the H3K9 trimethylation pattern and memory decline during scopolamine-induced amnesia. It was followed by checking the effect of siRNA-mediated silencing of hippocampal Suv39h1 on memory and expression of neuronal IEGs. Scopolamine treatment significantly increased global levels of H3K9me3 and Suv39h1 in the amnesic hippocampus. Suv39h1 silencing in amnesic mice reduced H3K9me3 levels at the neuronal IEGs (Arc and BDNF) promoter, increased the expression of Arc and BDNF in the hippocampus, and improved recognition memory. Thus, these findings suggest that the silencing of Suv39h1 alone or in combination with other epigenetic drugs might be effective for treating memory decline during amnesia.


[Percutaneous microcompression of the gasserian ganglion. New treatment for trigeminal neuralgia].
The authors discuss on technique and results of percutaneous microcompression of the trigeminal ganglion in patients complaining trigeminal neuralgia.


Basal expression of Fos, Fos-related, Jun, and Krox 24 proteins in rat hippocampus.
The basal expression of the protein products of the inducible immediate early genes (IEGs), Fos, Jun, and Krox 24, was investigated in rat hippocampus using immunocytochemical visualization methods with antisera specific for Fos only, Fos and the Fos-related antigens (FRAs), the Jun family, and Krox 24 (previously described as TIS 8, egr-1, NGF-IA or zif 268). In the normal adult rat brain basal levels of Jun, Krox 24 and Fos-related antigens but not Fos were seen within the hippocampus. More specifically very high basal levels of Jun were seen in the dentate granule cells with high basal Krox 24 levels seen in the CA1-subiculum region of the rat hippocampus. Basal FRAs but not Fos-positive cells were seen at low levels in the dentate granule cells. The implications of these results to the functioning of IEG proteins in hippocampal neurons is discussed.


Oral ketamine and dexmedetomidine in adults' burns wound dressing--A randomized double blind cross over study.
Study was designed to compare analgesic efficacy and side effects of oral dexmedetomidine and ketamine in adults for burn wound dressing. Sixty healthy adults with thermal burns with burn area (20-50%) were randomly assigned into 2 groups. In Group K 5mg/kg ketamine and in Group D 4 mcg/kg dexmedetomidine was given orally. Patients crossed over to the other group the following day. Visual analogue score, sedation score, haemodynamic parameters were recorded from 30min after drug administration to 2h after procedure. Patients' preference was also recorded. Mean VAS score was significantly reduced from baseline in both the groups at all time points (P<0.05). Pain relief in Group K (overall mean VAS 2.6±0.6cm) was significantly better when compared to Group D (overall mean VAS 3.8±0.8cm). Patients in group K were significantly more sedated (median 3) when compared to group D (median 2), P<0.05. Delirium and excessive salivation were significant complications observed with ketamine. More patients preferred ketamine (63.3%) than dexmedetomidine (36.7%), P<0.05. Oral ketamine and dexmedetomidine produced significant pain relief during burns wound dressing. Oral ketamine produced significantly better pain relief than dexmedetomidine but was associated with delirium and excessive salivation.


A fluorescence imaging protocol for correlating intracellular free cationic copper to the total uptaken copper by live cells.
A variety of fluorescence probes have been developed for fluorescence imaging of metals in biological cells. However, accurate quantification of metals with fluorescent approaches is challenging due to the difficulty in establishing a standard calibration curve in living cells. Herein, a fluorescence imaging protocol is developed for imaging intracellular Cu2+ and its correlation with the cellular uptake of copper. The total amount of intracellular Cu is detected by inductively coupled plasma mass spectrometry (ICP-MS) in parallel. Fluorescence imaging of Cu2+ is accomplished with Rhodamine B derivative modified carbon dots (CDs-Rbh) based on fluorescence resonance energy transfer (FRET) from CDs to rhodamine. Intracellular Cu2+ is correlated with fluorescence ratio at λem 500-600 nm (rhodamine) to λem 425-475 nm (CDs) with excitation at λex 405 nm. It is found that Cu2+ is linearly correlated with the total intracellular uptaken copper content, with a linear correlation between the relative fluorescence ratio in fluorescence imaging and intracellular Cu derived from ICP-MS, including both Cu(I) and Cu(II) species. The linear calibration equation is lg(F2/F1) = 0.00148 m[Cu]-0.3622. This approach facilitates further investigation and elucidation of copper transition in live cells and the evaluation of their cytotoxicity.


Involvement of minor salivary glands in the pathogenesis of peritonsillar abscess.
To study the relationship between peritonsillar abscess (PTA) and minor salivary glands surrounding the palatine tonsils. Prospective population-based study. Tertiary care university hospital. Prospective study including 41 patients with PTA and 6 patients with a neck abscess. Amylase levels of the pus and serum were measured and compared between the 2 groups. Clinical data regarding hospitalization length and recurrence rate were also collected. Of the 41 patients with PTA, 7 suffered from recurrent PTA. Average level of amylase in the pus of the PTA group was 3841 U/L versus 7.7 U/L in the neck abscess group (P < .001; median, 62 vs 9.5). Serum amylase was higher in the PTA group (49.3 U/L vs 37.3 U/L; P = .008). There were no recurrences in PTA patients with amylase greater than 65 U/dL in the pus in 0 of 20 (0%) versus 7 of 21 (33%) for amylase lower than 65 U/L (P = .01). High amylase in the pus lends further support for involvement of minor salivary glands. However, high recurrence rates related to low amylase in the pus imply an additional pathogenesis possibly related to tonsillar infection. It is possible that both minor salivary glands as well as tonsillar infection play a role in the pathogenesis of peritonsillar infections.


Elucidation of non-parallel EIA curves.
Quantitative determinations by EIA can be only obtained by reverse regression when linear portions of sample and standard curves are parallel. However, analysis of complex biological fluids often yields sigmoid curves displaying lower slopes, thus invalidating any quantitative interpretation. We hypothesized that this phenomenon was due to a competition effect between the target (for example an antigen) and related molecules for the binding sites (for example a capture antibody) immobilized onto the solid phase. This has been confirmed experimentally using various target-to-competitor ratios and formulated as a mathematical model. The slope decrease in target detection was related to the proportion of competitor, not in a linear, but in an exponential manner. This mathematical model has been computerized and can be used to correct aberrant sample curves provided the relevant parameters have been previously determined in the same systems.


The Enigmatic Universe of the Herbivore Gut.
The herbivore gut is a fascinating ecosystem exquisitely adapted to plant biomass degradation. Within this ecosystem, anaerobic fungi invade biomass and secrete hydrolytic enzymes. In a recent study, Solomon et al. characterized three anaerobic fungi by transcriptomics, proteomics, and functional analyses to identify novel components essential for plant biomass deconstruction.


Lincolnshire nurses trial phone assessment service.
A nurse-led telephone service is helping patients to have investigative tests on their bowels up to two weeks faster than usual.


Cell-based therapy for neural disorders--anticipating challenges.
Neurological syndromes, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, Huntington's disease, amyotrophic lateral sclerosis, and lysosomal storage disorders, such as Battens disease, are devastating because they result in increasing loss of cognitive and physical function. Sadly, no drugs are currently available to halt their progression. The relative paucity of curative approaches for these and other conditions of the nervous system have led to a widespread evaluation of alternative treatment modalities including cell-based interventions. Several cell types have been tested successfully in animal models where safety and efficacy have been demonstrated. Early clinical trials have also been initiated in humans, and some have shown a degree of success albeit on a more limited scale than in animal experiments. Recent demonstrations that pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, can differentiate into a variety of specific neural phenotypes has stimulated worldwide enthusiasm for developing cell-based intervention of neurological disease. Indeed, several groups are preparing investigational new drug applications to treat disorders as diverse as macular degeneration, lysosomal storage diseases, and Parkinson's disease. It is noteworthy that cell replacement therapies for neurological conditions face key challenges, some of which are unique, because of the development and organization of the nervous system, its metabolism, and connectivity. Choice of the cell (or cells), the process of manufacturing them, defining the delivery pathway, developing and testing in an appropriate preclinical model, selecting a patient population, and visualizing and following or monitoring patients all pose specific issues as related to the central and peripheral nervous systems. In this review, we address a myriad of challenges that are solvable, but require careful planning and attention to the special demands of the human nervous system.


Comparing Asthma Control Questionnaire (ACQ) and National Asthma Education and Prevention Program (NAEPP) asthma control criteria.
Adequate assessment of control is critical to asthma management. The Asthma Control Questionnaire (ACQ) and the National Asthma Education and Prevention Program (NAEPP) criteria are commonly used measures of asthma control. To examine the associations between the ACQ and NAEPP criteria and compare the validity in association with lung function, asthma exacerbation, and quality of life. The ACQ and the NAEPP criteria were administered to 373 adolescents with asthma aged 12 to 20 years. The 2 measures correlated with forced expiratory volume in 1 second (FEV1), asthma exacerbation (oral corticosteroid use, hospitalization, and emergency department [ED] use) in the past 12 months, and quality of life. Agreement between the ACQ and NAEPP criteria was moderate (κ = 0.40-0.61). Neither of the 2 measures was a reliable predictor of FEV1 less than 80% because of the high rate of false-positive results for the ACQ (68%) and low sensitivity for the NAEPP (49%). The NAEPP identified more cases of uncontrolled asthma (84.6%) than the ACQ (64.6%). The ACQ was a significant predictor of recent oral corticosteroid use, hospitalization, and ED visits (area under the curve = 0.66, 0.66, and 0.64, respectively; P < .001), as was NAEPP (area under the curve = 0.63, 0.66, and 0.61, respectively; P < .001). Both measures were significantly associated with quality of life, and the associations were particularly strong for the ACQ (r = -0.87 for symptom subscale, r = -0.76 for activity subscale, and r = -0.78 for emotional function subscale). Neither the ACQ nor the NAEPP appears to reliably predict lung function, whereas both measures reasonably associate with acute asthma exacerbation. The ACQ may be the superior measure in gauging the psychosocial effect of asthma control given its particularly strong associations with quality of life. ClinicalTrials.gov Identifier: NCT02293499.


Validity of the Hewlett-Packard actograph in detecting fetal movements.
To detect fetal movements during non-stressed cardiotocography to evaluate the validity of the Hewlett-Packard Doppler ultrasound actograph in detecting fetal movements. This was a prospective, observational study. Thirty healthy pregnant women were divided into two gestational age groups (Group I, 31 + 0 to 34 + 0 weeks, n = 15; Group II, 37 + 0 to 40 + 0 weeks, n = 15). A Hewlett-Packard M-1350-A actocardiograph was used to make recordings of 45 min for each woman. Fetal movements were also detected sonographically by an observer and they were recorded independently by the pregnant woman. Ninety consecutive 30-s periods were analyzed to study agreement between the three techniques. The mean total agreement for fetal activity plus quiescence between ultrasound and the actograph was 63.7% for Group I, and 72.2% for Group II. In cases of fetal activity only, these values were 45.8% and 47.6%, respectively. Total agreements between ultrasound and the pregnant woman were 74.0% and 79.0%, respectively, for Groups I and II. Cohen's kappa values for total agreement between ultrasound and actograph were 0.31 (95% CI, 0.27-0.36), indicating 'fair' agreement in Group I, and 0.43 (95% CI, 0.38-0.47), indicating 'moderate' agreement in Group II. Use of the Hewlett-Packard actograph may offer some additional information during routine cardiotocography. However, our results were disappointing; the technique appears not to be suitable for detailed recordings of fetal behavior, and may even be misleading when difficult cardiotocographic patterns have to be interpreted.


The worsening of skeletal muscle atrophy induced by immobilization at the early stage of remobilization correlates with BNIP3-dependent mitophagy.
Recent studies have shown that immobilization enhances reactive oxygen species (ROS) production and mitophagy activity in atrophic skeletal muscle. However, there are relatively few studies examining the biological changes and underlying mechanisms of skeletal muscle during remobilization. In this study, we aimed to investigate the effects of remobilization on skeletal muscle and explore the role of BNIP3-dependent mitophagy in this process. Thirty rats were randomly divided into six groups based on immobilization and remobilization time: control (C), immobilization for two weeks (I-2w), and remobilization for one day (R-1d), three days (R-3d), seven days (R-7d), and two weeks (R-2w). At the end of the experimental period, the rectus femoris muscles were removed and weighed, and the measurements were expressed as the ratio of muscle wet weight to body weight (MWW/BW). Sirius Red staining was performed to calculate the values of cross-sectional area (CSA) of rectus femoris. Oxidative fluorescent dihydroethidium was used to evaluate the production of ROS, and the levels of superoxide dismutase (SOD) were also detected. The morphological changes of mitochondria and the formation of mitophagosomes in rectus femoris were examined and evaluated by transmission electron microscope. Immunofluorescence was employed to detect the co-localization of BNIP3 and LC3B, while Western blot analysis was performed to quantify the levels of proteins associated with mitophagy and mitochondrial biogenesis. The total ATP content of the rectus femoris was determined to assess mitochondrial function. Within the first three days of remobilization, the rats demonstrated decreased MWW/BW, CSA, and ATP concentration, along with increased ROS production and HIF-1α protein levels in the rectus femoris. Results also indicated that remobilization triggered BNIP3-dependent mitophagy, supported by the accumulation of mitophagosomes, the degradation of mitochondrial proteins (including HSP60 and COX IV), the elevation of BNIP3-dependent mitophagy protein markers (including BNIP3, LC3B-II/LC3B-I, and Beclin-1), and the accumulation of puncta representing co-localization of BNIP3 with LC3B. Additionally, PGC-1α, which is involved in the regulation of mitochondrial biogenesis, was upregulated within the first seven days of remobilization to counteract this adverse effect. Our findings suggested that BNIP3-denpendent mitophagy was sustained activated at the early stages of remobilization, and it might contribute to the worsening of skeletal muscle atrophy.


Ecophysiological studies of Sonoran Desert plants : IV. Seasonal photosynthetic capacities of Acacia greggii and Cercidium microphyllum.
The gas exchange and water relations of two Sonoran Desert plants were measured throughout a 12 month period. Seasonal photosynthesis patterns of both species followed the seasonal variation in soil and plant water potential. Acacia greggii, a winter deciduous shrub, appears to be fall active since the day-long mean photosynthesis rate was maximum, i.e., 16 mg CO2 dm-2 h-1, at this time. Cercidium microphyllum, a drought deciduous and chlorophyllous-stemmed tree, also appears to be mainly fall active. For this species the day-long mean photosynthesis rate was not in excess of 14 mg CO2 dm-2 h-1. Both species initiate leaf production in the spring and neither experiences severe plant water stress. Seasonal minima of dawn plant water potential were-44 and-32 bars for the shrub and tree species, respectively. The two species differ slightly in their tolerance of heat and water stress, since foliated plants of Acacia greggii maintain summer gross photosynthesis.All of the aboveground organs for plants of C. microphyllum are capable of exogenous 14CO2 assimilation. This species appears to be unique in the magnitude of the photosynthetic production contributed by stems. Seasonal production by stems, leaves and flowers/fruits averaged 72, 24 and 4% of the total carbon gain per tree, respectively. Aboveground gross primary production was over 4.5-fold greater than aboveground net primary production. This difference between these two production estimates is likely due to the very small foliar biomass maintained throughout the year and the energy expenditure required to maintain the metabolically active cells of the chlorophyllous stems.


The intestinal microflora and its colon cancer connection.
Epidemiologic studies suggest that the incidence of colon cancer is influenced by environmental factors, especially diet. The high beef-high fat-low fiber diet of Western societies is associated with a high risk of colon cancer. The intestinal microflora may play a role in colon cancer by metabolic activation of procarcinogens in the lumen of the large bowel. The link between diet and colon cancer can be explained, in part, by the alterations in fecal bacterial enzyme activity induced by a Western-style diet. For example, fecal bacterial beta-glucuronidase, nitroreductase, azoreductase and steroid 7-alpha-dehydroxylase activities are increased in animals or humans consuming a high beef diet. These enzyme activities can be reduced by eating a grain diet, by the addition of Lactobacillus acidophilus to the diet, or by administration of low dose antibiotics. In experimental animals these three measures to reduce the activity of the microflora also produce few colon tumors in animals given the chemical carcinogen dimethylhydrazine. Further studies are needed to establish whether alterations in the metabolism of the colonic microflora can reduce the risk of large bowel cancer in humans.


Hypoxia inducible factor (HIF)-2α accelerates disease progression in mouse models of leukemia and lymphoma but is not a poor prognosis factor in human AML.
Hypoxia-inducible factor (HIF)-1α accumulation promotes hematopoietic stem cells' quiescence and is necessary to maintain their self-renewal. However, the role of HIF-2α in hematopoietic cells is less clear. We investigated the role of HIF-2α in leukemia and lymphoma cells. HIF-2α expression was high in subsets of human and mouse leukemia and lymphoma cells, whereas it was low in normal bone marrow leukocytes. To investigate the role of HIF-2α, we transduced human HIF-2α cDNA in mouse syngeneic models of myeloid preleukemia and a transgenic model of B lymphoma. Ectopic expression of HIF-2α accelerated leukemia cell proliferation in vitro. Mice transplanted with cells transduced with HIF-2α died significantly faster of leukemia or B lymphoma than control mice transplanted with empty vector-transduced cells. Conversely, HIF-2α knockdown in human myeloid leukemia HL60 cells decreased proliferation in vitro and significantly prolonged animal survival following transplantation. In human acute myeloid leukemia (AML), HIF-2α mRNA was significantly elevated in several subsets such as the t(15;17), inv(16), complex karyotype and favorable cytogenetic groups. However, patients with high HIF-2α expression had a trend to higher disease-free survival in univariate analysis. The different effects of HIF-2α overexpression in mouse models of leukemia and human AML illustrates the complexity of this mutliclonal disease.


Effects of epinephrine, glucagon and insulin on glucose metabolism of planaria.
Epinephrine and insulin increased glucose uptake in Planaria, but epinephrine did so to a much grater extent. Glucagon proved to be without effect. The experiments support earlier results according to which in unicellular and invertebrate organisms membrane patterns can be found, which are similar to those of higher organisms and behave like receptors.


Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-ST-segment elevation myocardial infarction: results of the SELECT-ACS trial.
The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction. P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties. Patients (N = 544) with non-ST-segment elevation myocardial infarction scheduled for coronary angiography and possible ad hoc PCI were randomized to receive 1 pre-procedural infusion of inclacumab 5 or 20 mg/kg or placebo. The primary endpoint, evaluated in patients who underwent PCI, received study medication, and had available efficacy data (n = 322), was the change in troponin I from baseline at 16 and 24 h after PCI. There was no effect of inclacumab 5 mg/kg. Placebo-adjusted geometric mean percent changes in troponin I with inclacumab 20 mg/kg were -24.4% at 24 h (p = 0.05) and -22.4% at 16 h (p = 0.07). Peak troponin I was reduced by 23.8% (p = 0.05) and area under the curve over 24 h by 33.9% (p = 0.08). Creatine kinase-myocardial band yielded similar results, with changes of -17.4% at 24 h (p = 0.06) and -16.3% at 16 h (p = 0.09). The incidence of creatine kinase-myocardial band increases >3 times the upper limit of normal within 24 h was 18.3% and 8.9% in the placebo and inclacumab 20-mg/kg groups, respectively (p = 0.05). Placebo-adjusted changes in soluble P-selectin level were -9.5% (p = 0.25) and -22.0% (p < 0.01) with inclacumab 5 and 20 mg/kg. There was no significant difference in adverse events between groups. Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction [Non-STEMI] Undergoing Percutaneous Coronary Intervention; NCT01327183).


Effect of SINC Feeding Protocol on Weight Gain, Transition to Oral Feeding, and the Length of Hospitalization in Preterm Infants: A Randomized Controlled Trial.
The present study aims to test the effect of the Safe Individualized Nipple-Feeding Competence (SINC) protocol on the preterm infants' weight gain, transition to oral feeding, and duration of hospitalization. The procedure was designed as a single-blind, parallel-group randomized controlled trial. The trial was conducted in a neonatal intensive care unit (NICU) in Konya, Turkey. Data were collected from 80 preterm infants between February 2018 and March 2019. Infants (gestational weeks 28-33) were randomly assigned to the intervention (n = 39) and control groups (n = 41). The intervention group received the SINC feeding protocol, whereas the control group received the standard feeding. Data were collected using the Family Information Form, the Preterm Infant Follow-Up Form, and the SINC Protocol Evaluation Checklist. Infants were followed from hospitalization to discharge. The outcomes were weight gain, transition to oral feeding, and the length of hospitalization from birth to discharge. Pearson χ2 test, Fisher exact test, independent t-test, Mann-Whitney U test, and general linear model test were used in analyzing the data. The main effects of groups on weight measurements were found to be statistically significant (P < .001). There were no significant differences in terms of the transition from gavage to full oral feeding and the length of hospitalization (P > .05). SINC protocol positively influences weight gain in preterm infants. It is important to evaluate different evidence-based feeding methods both as they apply to the NICU stay and how they may affect long-term outcomes of preterm infant.


Maternal nicotine intoxication before pregnancy induces depressive- and anxiety-like behaviors as well as cognitive deficits in male offspring and correlates with neurobiological changes.
Maternal nicotine use has been suggested to affect the behavior of children and is linked to changes in neurological systems; however, the specific mechanism is yet to be understood. Mice were used to establish a maternal nicotine intoxication model. At postnatal day 60 (adolescent stage), male offspring were tested for behavioral tasks including sucrose preference, open field, elevated plus maze, light/dark box, object recognition, Morris water maze (MWM), and forced swimming. Enzyme-linked immunoassays were used to measure plasma concentrations of neurotransmitters including norepinephrine, dopamine, serotonin, and corticosterone. Serotonin transporter (Sert), brain-derived neurotrophic factor (Bdnf), cAMP response element binding protein (Creb), and phosphorylated (p)Creb mRNA levels were measured using quantitative real-time polymerase chain reaction. Male offspring of nicotine-intoxicated dams had significantly reduced sucrose preference, mobility time in the forced swimming test, and locomotor and exploratory activities. Offspring in the maternal nicotine intoxication group showed increased signs of depressive- and anxiety-like behavior. Recognition memory in the MWM was compromised in these animals. The hippocampal and prefrontal cortical regions showed significant changes in Bdnf, pCreb, and Sert gene expression, whereas CREB mRNA levels were unaffected. Moreover, compared to the controls, neurogenesis and neuronal viability were also reduced in these animals. Prenatal nicotine exposure might affect the hypothalamic-pituitary-adrenal axis and reduce neurogenesis, potentially leading to depressive-like behaviors and cognitive deficiencies in male offspring.


Review of state-of-the-art beta-blocker therapy.
Beta-adrenoceptor blocking drugs have been used in the treatment of hypertension for more than 2 decades. During this time they have reached the position of first-line therapy for hypertension and are recommended as such by the Joint National Committee (U.S.A.) in 1988 and by the World Health Organization/International Society of Hypertension in 1983 and 1989. This is because of the favorable relationship between the antihypertensive efficacy of these drugs and the rate and severity of their adverse effects. Of particular interest is the possibility that beta blockers may protect against coronary artery disease (CAD). With regard to secondary prevention against CAD, statistically highly significant and clinically relevant reductions of mortality and the risk of reinfarction have been shown in prospective, double-blind, placebo-controlled trials. A primary preventive effect against CAD, on the other hand, has only been shown in open trials without placebo control. However, in spite of the lack of clear proof, this effect still appears to be a logical possibility. Some new findings with beta blockers appear to be of particular interest: beta blockade may reduce myocardial necrosis in patients with marked elevations of plasma catecholamines due to traumatic head injury; a similar protective effect in other situations of severe stress, e.g., acute myocardial infarction, would be of great clinical value. Experimental studies also suggest that beta blockers may have antiatherosclerotic effect in animals fed an atherogenic diet and subjected to stress. Again, clinical confirmation of such results would be of great significance.


Elaborate ligand-based modeling reveal new migration inhibitory factor inhibitors.
Recent research suggested the involvement of migration inhibitor factor (MIF) in cancer and inflammatory diseases, which prompted several attempts to develop new MIF inhibitors. Accordingly, we investigated the pharmacophoric space of 79 MIF inhibitors using seven diverse subsets of inhibitors to identify plausible binding hypotheses (pharmacophores). Subsequently, we implemented genetic algorithm and multiple linear regression analysis to select optimal combination of pharmacophores and physicochemical descriptors capable of explaining bioactivity variation within the training compounds (QSAR model, r63=0.62, F=42.8, rLOO(2)=0.721,rPRESS(2) against 16 external test inhibitors=0.58). Two orthogonal pharmacophores appeared in the optimal QSAR model suggestive of at least two binding modes available to ligands inside MIF binding pocket. Subsequent validation using receiver operating characteristic (ROC) curves analysis established the validity of these two pharmacophores. We employed these pharmacophoric models and associated QSAR equation to screen the National Cancer Institute (NCI) list of compounds. Eight compounds gave >50% inhibition at 100μM. Two molecules illustrated >75% inhibition at 10μM.


Disease phenotype prediction in multiple sclerosis.
Progressive multiple sclerosis (PMS) is currently diagnosed retrospectively. Here, we work toward a set of biomarkers that could assist in early diagnosis of PMS. A selection of cerebrospinal fluid metabolites (n = 15) was shown to differentiate between PMS and its preceding phenotype in an independent cohort (AUC = 0.93). Complementing the classifier with conformal prediction showed that highly confident predictions could be made, and that three out of eight patients developing PMS within three years of sample collection were predicted as PMS at that time point. Finally, this methodology was applied to PMS patients as part of a clinical trial for intrathecal treatment with rituximab. The methodology showed that 68% of the patients decreased their similarity to the PMS phenotype one year after treatment. In conclusion, the inclusion of confidence predictors contributes with more information compared to traditional machine learning, and this information is relevant for disease monitoring.


Secretion of recombinant ribonuclease T1 into the periplasmic space of Escherichia coli with the aid of the signal peptide of alkaline phosphatase.
The ribonuclease T1 (RNase T1) gene was ligated to a synthetic gene for the signal peptide of Escherichia coli alkaline phosphatase. When this fusion gene was expressed in E. coli under the control of the trp promoter, active RNase T1 having the correct N-terminal sequence was secreted into the periplasmic space, indicating that the heterologous signal peptide had been cleaved off correctly. The enzyme could be readily purified from the periplasmic fraction with a yield of 1.8 mg from 1 liter culture. Adopting the same strategy, it was possible to produce a labile mutant of RNase T1 (Glu-58----Ala mutant) in E. coli, the yield of the purified mutant enzyme being 2.0 mg from 1 liter culture.


The diagnostic accuracy of pocket-size cardiac ultrasound performed by unselected residents with minimal training.
Pocket-size imaging devices may represent a tool for fast initial cardiac screening in the emergency setting. Pocket-size cardiac ultrasound (PCU) examinations performed by experienced echocardiographers yield acceptable diagnostic accuracy compared to standard echocardiogram (SE). However, the success of this method when used by unselected non-cardiologists remains unexplored. The current study studies the diagnostic accuracy of PCU when used by unselected internal medicine residents with minimal training. All residents were given a 2-hour introductory course in PCU (Vscan) and reported PCU results for up to 15 predefined cardiac landmarks. These were arbitrarily divided into 3 priority groups, such that left ventricle (LV) and pericardium were of first priority. Diagnostic accuracy [sensitivity/specificity and negative/positive predictive values (PPV/NPV)] and agreement were evaluated using a subsequent SE as reference. During a 9.2 months period a total of 303 patients were included in the study, the majority on the basis of presenting with chest pain or suspected heart failure. In the pooled LV and pericardial (1st priority) data, sensitivity/specificity/PPV/NPV were 61/92/70/89% respectively. Similar specificities and NPVs were observed for the 11 remaining indices, as were lower sensitivities and PPVs. The best PCU sensitivity (76%) was attained for the assessment of LV wall motion abnormalities. Overall agreement was k = 0.50. PCU examination performed by internal medicine residents with minimal training could provide a suitable means of ruling out cardiac pathology, as reflected in the high specificities and NPVs. It is not, however, a satisfactory tool for identifying patients with various cardiac disorders.


Population estimates of Thiobacillus thioparus in composting biofilters by PCR analysis.
A direct most-probable-number polymerase chain reaction method (MPN-PCR) was used to monitor populations of Thiobacillus thioparus in compost biofilters used to treat air contaminated with dymethyl disulphide and ammonia. The PCR method quantified this bacterium at numbers ranging from log 2 to log 8 cells per gram of biofilter media.


Cost of human papillomavirus vaccine delivery in a single-age cohort, routine-based vaccination program in Senegal.
In 2018, Senegal introduced human papillomavirus (HPV) vaccine into its routine immunization program for all nine-year-old girls nationwide. We evaluated the costs of Senegal's introduction of HPV vaccine via this delivery approach. We conducted a retrospective, incremental, ingredients-based cost evaluation from the provider perspective. The study timeframe included Senegal's first planning meeting in 2018 through data collection in early 2020. We collected costs from all involved units at the national and regional levels. A multi-stage cluster sampling approach was used to obtain a nationally representative sample of districts and health facilities. Weights were applied to costs from sampled units to estimate costs across all units. The cost evaluation was based on four dimensions: program activity, resource input, payer, and administrative level. Total costs were divided by the number of HPV doses administered to determine cost per dose and per dimension. Excluding vaccine program activity costs, the total financial and economic delivery costs of Senegal's HPV vaccination program were US$ 1,152,351 and US$ 2,838,466, respectively (US$ 3.07 and US$ 7.56 per dose, respectively). A total of 375,608 HPV vaccine doses were administered during the cost evaluation. Training and per diem represented the largest shares of financial costs. Service delivery and personnel time accounted for the largest shares of economic costs. By administrative level, district and health facility levels had the largest shares of financial and economic costs, respectively. Senegal's Ministry of Health accounted for the largest share of financial and economic costs. Including vaccine program activity costs (US$ 4.68/per dose), the total financial cost was US$ 2,911,343 (US$ 7.75 per dose). This cost evaluation can support Senegal's future vaccine introductions and inform other countries planning to introduce HPV vaccine nationwide. These findings support previous costing studies which anticipated potential economies of scale during the transition from HPV vaccine pilot demonstration projects to national introduction.


[Functional magnetic resonance imaging of the kidneys].
Interest in functional renal magnetic resonance imaging (MRI) has significantly increased in recent years. This review article provides an overview of the most important functional imaging techniques and their potential clinical applications for assessment of native and transplanted kidneys, with special emphasis on the clarification of renal tumors.


Behavior of morphometric indices in pancreatic elastase-induced emphysema in rats.
Two morphometric indices, the destructive index (DI), a measure of alveolar wall destruction, and the proportion of destroyed alveolar attachments to the airways (AA), have been proposed as measures of early lung destruction in human smokers. The aim of this study was to compare DI and AA to the usual measure of airspace enlargement--the mean linear intercept (Lm)--in experimental emphysema. Porcine pancreatic elastase was administered intratracheally to 2 groups of Brown Norway rats (high-dose, n = 8, 1 IU/g body weight; low-dose, n = 4, 0.7 IU/g; control, n = 7). Total lung capacity (TLC), functional residual capacity (FRC) and pressure-volume curves were measured 3 weeks after administration of elastase. Lung elasticity was assessed by chord compliance (Cst). Administration of high-dose, but not low-dose, elastase led to significant increases in FRC and TLC. Cst significantly increased after high-dose elastase compared to controls (p less than 0.01). Lm increased after both low-dose and high-dose elastase compared to controls (p less than 0.01); DI and AA were increased only after high-dose elastase. Significant correlations were found between each morphometric index and Cst; the highest correlation was with AA. Behavior of the morphometric indices in this model differed from that reported in human smokers: Lm was a more sensitive measure of destruction than DI, reflecting a process marked by predominance of airspace enlargement over alveolar septal breaks. These differences from human smokers may result from a differing underlying pathogenesis of lung destruction.


Strangers in sync: Achieving embodied rapport through shared movements.
This paper examines the emergence of behavioral synchrony among strangers in the context of self-disclosure, and their path in predicting interaction quality. Specifically, we hypothesize that behavioral synchrony mediates the direct effect of self-disclosure on the development of embodied rapport. Same-sex stranger pairs (n=94) were randomly assigned to a videorecorded self-disclosure or control condition, and afterward each member rated their social interaction. Following the procedure used by Bernieri, Reznick, & Rosenthal (1988), two trained judges independently watched each video record and rated each pair interaction on behavioral synchrony. Bootstrapping analyses provide support for the hypothesized mediating effect of behavioral synchrony, which emerged as independent of the effects of self-other overlap and positive affect. The authors discuss implications of behavioral synchrony for relationship formation processes and the inevitable entwinement of behavior and judgments in light of embodied cognition.


A cone-triggered c-wave in the chicken ERG time integration characteristics.
The c-waves recorded from the cone-dominant retina of the chicken proved to be cone-triggered. The time course and time integration properties of this retinal potential were compared with those of the rod-triggered c-wave recorded in the frog under scotopic conditions. The results clearly demonstrate that there is no evidence for time integration in cone-triggered c-waves but that rod-triggered c-waves follow the Bunsen-Roscoe law over more than 2 log units. We propose that these time-related differences may be used in other species as a differentiation criterion between cone-triggered and rod-triggered c-waves.


Gastritis, intestinal metaplasia and dysplasia versus benign ulcer in stomach and duodenum and gastric carcinoma -- a histotopographical study.
In histological examination of gastrectomy specimens from patients with duodenal ulcer, gastric ulcer, and early and advanced cancer, both chronic atrophic gastritis and intestinal metaplasia were identified in 54% of the cases with duodenal ulcer. At 90 to 100%, respectively, these mucosal changes were approximately twice as frequent with gastric ulcer and early and advanced gastric cancer. Mild dysplasia occurred in 54% of the cases with duodenal ulcer; occurred somewhat more frequently with gastric ulcer, in 75% of the cases; and in almost all cases with early and advanced gastric cancer, at 90% and 100%, respectively. Whereas 27% of the cases with duodenal ulcer, 62% with gastric ulcer, and 90% and 95% of the respective cases with early and advanced gastric cancer showed moderate dysplasia, only severe dysplasia in early gastric cancer (40%) and advanced gastric (81%) was clearly more frequent in comparison to duodenal ulcer (9%) and gastric ulcer (12%). In the cases with duodenal ulcer chronic atrophic gastritis and intestinal metaplasia were limited mostly to the antrum; with gastric ulcer and cancerous stomach disorders, they also occurred in other stomach sections. Mild and moderate dysplasia conformed to the same distribution pattern. Severe dysplasia, which was only detected in two ulcer cases, was not only substantially more frequent in cases with early and advanced gastric cancer, but also showed a clear topographic relationship to cancer localization in the stomach.


Cellular dissection of zebrafish hematopoiesis.
Zebrafish as a model system have been instrumental in understanding early vertebrate development, especially of the hematopoietic system. The external development of zebrafish and their genetic amenability have allowed in-depth studies of multiple blood cell types and their respective genetic regulation. This chapter highlights some new data in zebrafish hematopoiesis regarding primitive and definitive hematopoiesis in the embryonic and adult fish, allowing the isolation of prospective progenitor subsets. It also highlights assays developed to examine the function of these progenitors in vivo and in vitro, allowing an evolutionary understanding of the hematopoietic system and how zebrafish can be better utilized as a model system for a multitude of hematopoietic disorders.


Strain improvement of Aspergillus sojae for increased l-leucine aminopeptidase and protease production.
Conventional random mutagenesis was implemented to improve l-leucine aminopeptidase (LAP) and protease production in Aspergillus sojae. Through successive mutagenesis by ethyl methanesulfonate (EMS), UV, and 1-methyl-2-nitro-1-nitrosoguanidine (NTG), EMS25, EU36, and EUN13 mutants from each mutagenesis process were screened using a newly developed quick and easy screening method. The mutant EUN13 exhibited a 9.6-fold increase in LAP [50.61 ± 4.36 U/g-initial dried substrate (IDS)] and a 3.8-fold increase in protease production (13.36 ± 0.31 U/g-IDS) on solid-state fermentation. This mutant showed more frequent branching and higher lap1 mRNA expression as compared to the parent strain SMF 131, which at least in part contributed to the increased LAP and protease production. The mutant EUN13 can be used as a starter organism for diverse industrial soybean fermentation processes for the production of conventional products such as meju, doenjang, and ganjang as well as for the production of new fermented soybean-based sauces.


Application of Harvey-Garabedian model for describing bacterial removal in Sand Abstraction Systems associated with ephemeral rivers.
There have been concerted efforts to find alternative sources of water for small rural communities in the Southern Africa region, and one such initiative is Sand Abstraction Systems (SAS) or infiltration galleries. The sand formation of the riverbed of an ephemeral river is utilised as a natural filter giving potable water of high quality, but is prone to pathogenic contamination. The main objective of our study was to test the suitability of Harvey and Garabedian model for describing bacterial removal in SAS. The Harvey and Garabedian model with some modifications was adopted due to the few parameters required in applying the model. The coefficients and media properties were established from laboratory experiments and field studies. The implicit finite difference method was applied to solve the numerical model equation and to simulate the aquifer response to Escherichia coli for Nkayi SAS. The results of the bacterial simulation from the model fitted well with measured field data and with a small margin of error between the field results and the model (+/-5 coliform count/100 ml).


Afterglow thermoluminescence band as a possible early indicator of changes in the photosynthetic electron transport in leaves.
The afterglow (AG) band of thermoluminescence (TL) has been investigated in leaves of Arabidopsis thaliana. Excitation of dark-adapted leaves with two saturating single turn-over flashes induced the appearance of a complex TL glow curve that could be well simulated by three components: the two components, B1 and B2, of the usually called B-band, peaking at 18 and 26 degrees C, respectively, and a band with tmax at 41 degrees C, which we attributed to an AG emission. Illumination of dark-adapted leaves with 720 nm monochromatic and FR lights generated the emission of a sharp single band peaking also around at 41 degrees C, that it is usually assigned to an AG emission band. Dark-incubation of whole plants increased the intensity of AG-band in TL curves induced by two flashes and, in parallel, decreased B-bands. Selective illumination of leaves with light mostly absorbed by PS II (650 nm light) completely abolished the AG-band induced by two flashes, B-band being the only TL band observed. The single AG-band induced by 720 nm light was abolished if leaves were also illuminated with 650 nm light. On the other hand, AG-band could be restored if 650 nm illuminated leaves were afterwards illuminated with 720 nm light. The changes in the intensity of B and AG bands induced by selective illuminations seem to be related to alterations in the redox state of QB and plastoquinone pool.


Comparative environmental and socioeconomic assessment on mixed plastic waste management: A Singapore case study.
Proper end-of-life (EOL) management of mixed plastic waste remains a global challenge in both developed and developing countries as disposed plastic circulating within the ecosystem continues to increase at unprecedented rates. Presently, plastic EOL pathways are largely designed based on prevailing geographical conditions and environmental regulations across different regions. Till date, no work has been reported on the environmental and socioeconomic assessment on EOL pathway focusing on mechanical recycling of mixed plastic waste into raw ingredients for construction materials. This paper presents a life cycle assessment to characterize the environmental and socioeconomic impacts of four different plastic EOL pathways using Singapore as a case study. The present study describes how Singapore can redesign its current waste-to-resource taxonomy and reiterates the need to maximize mechanical recycling throughput of mixed plastic waste so to alleviate the reliance on thermal energies for waste valorisation and improve the overall performance of current plastic EOL pathway.


The role and regulation of apoptosis signal-regulated kinase 1 in liver disease.
ASK1, also known as MAP3K5, plays a vital role in the MAPK pathway. The MAPK pathway has a variety of biological functions and plays an important role in regulating cell proliferation, differentiation, and apoptosis. Studies have shown that ASK1 is involved in apoptosis, inflammation, oxidative stress, and other processes and plays an essential role in various liver diseases. Therefore, ASK1 can be a therapeutic target for treating liver disease. Here, we initially summarized the effect of ASK1 on liver disease and described the differential regulation of ASK1, including phosphorylation, ubiquitination and methylation, by which the effects of ASK1 on some liver diseases can be inhibited. Although much has been discovered about the phosphorylation of ASK1, the effects of other post-transcriptional modifications on the activity of ASK1 require further exploration. We hope that by summarizing the existing regulatory mechanism we can shed new light on the research and provide new ideas for finding ASK1-targeting drugs.


Cost-efficient treatment for uninsured or underinsured patients with hypertension, depression, diabetes mellitus, insomnia, and gastroesophageal reflux.
As the number of uninsured and underinsured patients in the United States continues to rise, savvy nurse practitioners (NPs) must balance quality of care with cost of drugs. This article reviews evidence-based treatments in light of prescribing the most cost-efficient medications. Searches of electronic databases including MEDLINE, MEDLINEPlus, EBSCO, PubMed, CINAHL, Clinical Pharmacology, Biomedical Reference Collection--Basic, Health Source--Consumer Edition, Health Source--Nursing/Academic Edition, Ovid, and the Cochrane Library Online. As the role of NP continues to evolve, it is important for NPs to establish themselves as economically conscious healthcare providers, striking a delicate balance between providing quality and cost-efficient care. An NP's familiarity with cost-efficient treatment options for common diagnoses such as hypertension, depression, diabetes mellitus, insomnia, and gastroesophageal reflux disorders can help ease the economic burden uninsured and underinsured patients endure, especially with respect to prescription drugs, and improve compliance with medication regimens. NPs should acquire knowledge on how to best treat uninsured or underinsured patients in the most cost-efficient manner. Knowledge of prescription drug cost is one tool an NP can use to encourage patient compliance, improving the overall health of uninsured or underinsured individuals.


Bipolar plasma enucleation of the prostate vs. open prostatectomy in large benign prostatic hyperplasia: a single centre 3-year comparison.
Aim of our study is to compare the surgery outcomes and safety of button bipolar enucleation of the prostate vs. open prostatectomy in patients with large prostates (> 80 g) in a single-centre cohort study. All patients with lower urinary tract symptoms due to benign prostatic enlargement undergoing button bipolar enucleation of the prostate (B-TUEP) or open prostatectomy (OP) between May 2012 and December 2013 were enroled in our study. Data on clinical history, physical examination, urinary symptoms, erectile function, uroflowmetry and prostate volume were collected at 0, 1, 3, 6, 12, 24 and 36 months. Early and long-term complications were recorded. Overall, 240 patients were enroled. Out of them 111 patients (46%) performed an OP and 129 patients (54%) performed a B-TUEP. In terms of efficacy, both procedures showed durable results at three years with a reintervention rate of 7.5% in the OP group and 5% in the B-TUEP group. In terms of safety, B-TUEP presented less high-grade complications when compared with OP. In our single-centre study, B-TUEP represents a valid alternative to OP with excellent outcomes at three years. Further multicentre studies should confirm our results.


Driving context influences drivers' decision to engage in visual-manual phone tasks: Evidence from a naturalistic driving study.
Visual-manual (VM) phone tasks (i.e., texting, dialing, reading) are associated with an increased crash/near-crash risk. This study investigated how the driving context influences drivers' decisions to engage in VM phone tasks in naturalistic driving. Video-recordings of 1,432 car trips were viewed to identify VM phone tasks and passenger presence. Video, vehicle signals, and map data were used to classify driving context (i.e., curvature, other vehicles) before and during the VM phone tasks (N=374). Vehicle signals (i.e., speed, yaw rate, forward radar) were available for all driving. VM phone tasks were more likely to be initiated while standing still, and less likely while driving at high speeds, or when a passenger was present. Lead vehicle presence did not influence how likely it was that a VM phone task was initiated, but the drivers adjusted their task timing to situations when the lead vehicle was increasing speed, resulting in increasing time headway. The drivers adjusted task timing until after making sharp turns and lane change maneuvers. In contrast to previous driving simulator studies, there was no evidence of drivers reducing speed as a consequence of VM phone task engagement. The results show that experienced drivers use information about current and upcoming driving context to decide when to engage in VM phone tasks. However, drivers may fail to sufficiently increase safety margins to allow time to respond to possible unpredictable events (e.g., lead vehicle braking). Advanced driver assistance systems should facilitate and possibly boost drivers' self-regulating behavior. For instance, they might recognize when appropriate adaptive behavior is missing and advise or alert accordingly. The results from this study could also inspire training programs for novice drivers, or locally classify roads in terms of the risk associated with secondary task engagement while driving.


Cerebrospinal fluid p-tau231 as an early indicator of emerging pathology in Alzheimer's disease.
Phosphorylated tau (p-tau) epitopes in cerebrospinal fluid (CSF) are accurate biomarkers for a pathological and clinical diagnosis of Alzheimer's disease (AD) and are seen to be increased in preclinical stage of the disease. However, it is unknown if these increases transpire earlier, prior to amyloid-beta (Aβ) positivity as determined by position emission tomography (PET), and if an ordinal sequence of p-tau epitopes occurs at this incipient phase METHODS: We measured CSF concentrations of p-tau181, p-tau217 and p-tau231 in 171 participants across the AD continuum who had undergone Aβ ([18F]AZD4694) and tau ([18F]MK6240) position emission tomography (PET) and clinical assessment FINDINGS: All CSF p-tau biomarkers were accurate predictors of cognitive impairment but CSF p-tau217 demonstrated the largest fold-changes in AD patients in comparison to non-AD dementias and cognitively unimpaired individuals. CSF p-tau231 and p-tau217 predicted Aβ and tau to a similar degree but p-tau231 attained abnormal levels first. P-tau231 was sensitive to the earliest changes of Aβ in the medial orbitofrontal, precuneus and posterior cingulate before global Aβ PET positivity was reached INTERPRETATION: We demonstrate that CSF p-tau231 increases early in development of AD pathology and is a principal candidate for detecting incipient Aβ pathology for therapeutic trial application FUNDING: Canadian Institutes of Health Research (CIHR), Canadian Consortium of Neurodegeneration and Aging, Weston Brain Institute, Brain Canada Foundation, the Fonds de Recherche du Québec.


National Education Progression in Nursing (NEPIN): Developing Leadership Capacity for Organizations.
In 2011, the Robert Wood Johnson Foundation and the Center to Champion Nursing in America set a course to address the recommendations of the Institute of Medicine's Future of Nursing report. In response, the Academic Progression in Nursing (APIN) provided national leadership for advancing nursing academic progression. A new entity, the National Progression in Nursing Education Collaborative, has formed to continue the important work started by APIN.


Management and outcome of spinal implant-associated surgical site infections in patients with posterior instrumentation: analysis of 176 cases.
The management of implant-associated surgical site infections (SSI) in patients with posterior instrumentation is challenging. Evidence regarding the most appropriate treatment and the need for removal of implants is equivocal. We sought to evaluate the management and outcome of such patients at our institution. We searched our prospectively documented databases for eligible patients with posterior spinal instrumentation, excluding the cervical spine (January 2008-June 2018). Patient files were reviewed, demographic data and treatment details were recorded. Patient-reported outcome (PRO) was assessed with the Core Outcome Measures Index (COMI) preoperatively and postoperatively at 3 and 12 months. A total of 170 patients underwent 210 revisions for 176 SSIs. Two-thirds presented within four weeks (105/176, 59.7%, median 22.5d, 7d-11.1y). The most common pathogens were Staphylococcus aureus (n = 79/210, 37.6%) and Staphylococcus epidermidis (n = 56/210, 26.7%). Debridement and implant retention was performed in 135/210 (64.3%) revisions and partial replacement in 62/210 (29.5%). In 28/176 SSI (15.9%), persistent infection required multiple revisions (≤ 4). Surgery was followed by intravenous and oral antimicrobial treatment (10-12w). In 139/176 SSIs (79%) with ≥ 1y follow-up, infection was cured in 115/139 (82.7%); relapse occurred in 9 (relapse rate: 5.1%). Two patients (1.4%) died. COMI decreased significantly (8.2 ± 1.5 vs. 4.8 ± 2.9, p < 0.0001) over 12 months. 72.7% of patients were (very) satisfied with their care. Patients with SSI after posterior (thoraco-)lumbo(-sacral) instrumentation can be successfully treated in most cases with surgical and specific antibiotic treatment. An interdisciplinary approach is recommended. Loose implants should be replaced. In some cases, multiple revisions may be necessary. Patient outcomes were satisfactory.


A fatal case of Ortner's syndrome and dysphagia aortica secondary to rapidly expanding mycotic thoracic aortic aneurysm in a chronic kidney disease patient.
Ortner's syndrome or cardiovocal syndrome is a rare condition and refers to the association between cardiovascular conditions, usually cardiac enlargement from mitral stenosis, and recurrent laryngeal nerve palsy. We reported an interesting case of a patient with end-stage renal disease on regular dialysis who developed both Ortner's syndrome and dysphagia aortica as a result of an aortic arch aneurysm. The aneurysm underwent a rapid increase in size, likely as a result of Staphylococcus aureus infection (mycotic aneurysm) from an internal jugular dialysis catheter. This case highlighted the importance of cardiovascular conditions as rarer causes of dysphonia and dysphagia, particularly with the existence of an extrinsic infective source.


Anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft: comparison of autograft, fresh-frozen allograft, and γ-irradiated allograft.
To compare clinical follow-up results of anterior cruciate ligament (ACL) reconstruction using (1) autologous, (2) fresh-frozen allogeneic, and (3) γ-irradiated allogeneic bone-patellar tendon-bone (BPTB). From February 2002 to January 2006, 187 patients received BPTB ACL reconstruction at our center. One hundred forty-two consecutive patients who had received single-bundle BPTB ACL reconstruction were included in this study. Of these patients, 41 had autografts, 33 had fresh-frozen allografts, and 68 had γ-irradiated allografts. Clinical results were evaluated with the KT-1000 maximum displacement test (MEDmetric, San Diego, CA), Lachman test, and Lysholm, Irrgang, and Larson activity scales. The mean duration of follow-up was 6.7 ± 1.5 years (range, 4.2 to 8.2 years). There were 3 cases of acute synovitis due to immunologic rejection (fresh-frozen allografts) and 6 cases of failure (γ-irradiated allografts). KT-1000 examination showed more anterior laxity in the γ-irradiated allograft group compared with the autograft and fresh-frozen allograft groups (P < .05). The Lysholm, Irrgang, and Larson activity scales showed no difference among the 3 groups (P > .05). The study showed a statistically poorer KT-1000 result and higher failure rate in the γ-irradiated allograft group compared with the autograft and fresh-frozen allograft groups. This may suggest that γ-irradiated allograft is not a good candidate graft for ACL reconstruction. Power analysis showed that the study was underpowered, so further research and longer follow-up study are needed to make this point clearer. Level III, retrospective comparative study.


Feasibility of an implantable bioreactor for renal cell therapy using silicon nanopore membranes.
The definitive treatment for end-stage renal disease is kidney transplantation, which remains limited by organ availability and post-transplant complications. Alternatively, an implantable bioartificial kidney could address both problems while enhancing the quality and length of patient life. An implantable bioartificial kidney requires a bioreactor containing renal cells to replicate key native cell functions, such as water and solute reabsorption, and metabolic and endocrinologic functions. Here, we report a proof-of-concept implantable bioreactor containing silicon nanopore membranes to offer a level of immunoprotection to human renal epithelial cells. After implantation into pigs without systemic anticoagulation or immunosuppression therapy for 7 days, we show that cells maintain >90% viability and functionality, with normal or elevated transporter gene expression and vitamin D activation. Despite implantation into a xenograft model, we find that cells exhibit minimal damage, and recipient cytokine levels are not suggestive of hyperacute rejection. These initial data confirm the potential feasibility of an implantable bioreactor for renal cell therapy utilizing silicon nanopore membranes.


Association of in vitro fertilization with maternal and perinatal outcomes among pregnant women with active tuberculosis: A retrospective hospital-based cohort study.
Study on effect of fertilization methods on maternal and perinatal outcomes with respect to TB during pregnancy was scarce. This study aimed to analyze maternal and perinatal outcomes in active TB cases after in vitro fertilization (IVF) treatment vs. normal pregnancy. Clinical data of 80 pregnant women with active TB hospitalized at Shanghai Public Health Clinical Center between June 1st, 2014 and November 30th, 2020 were extracted and retrospectively analyzed. History of receiving IVF was recorded at admission and its association with maternal and perinatal outcomes were assessed using multivariable logistic regression models with adjustment for potential confounders. Of the 80 pregnant women with active TB, 28 (35.0%) received IVF treatment and 52 (65.0%) did not receive IVF treatment. After adjusting for potential confounders, receiving IVF was associated with worse maternal and perinatal outcomes, including maternal criticality (21.4 vs. 2.0%, adjusted OR = 28.3, P = 0.015), miliary TB (89.3 vs. 13.5%, adjusted OR = 75.4, P < 0.001), TB meningitis (32.1 vs. 7.7%, adjusted OR = 6.2, P = 0.010), and perinatal mortality (64.3 vs. 28.8%, adjusted OR = 9.8, P = 0.001). The additional risk of TB to women receiving IVF treatment is a public health challenge specific to countries with a high tuberculosis burden. Increased awareness of latent tuberculosis infection in women receiving IVF treatment is needed.


[Protecting adolescents during migration, a difficult task for parents].
Going through adolescence during migration carries risks, especially when parents must discover their new world at the same time as passing on their values. Teenagers in search of their identity and creativity can endanger themselves as well as their family. A mixed approach is therefore necessary to give meaning to the passing on of traditions.


Effect of preoperative radiological treatment of hepatocellular carcinoma before liver transplantation: a retrospective study.
To assess the results of radiological treatment of patients with hepatocellular carcinoma (HCC) performed before orthotopic liver transplantation (OLT). Sixty-two transplanted patients with a total of 89 HCC nodules were studied; 50 lesions in 38 patients had been treated prior to OLT with transcatheter arterial chemoembolization (TACE; n = 29), percutaneous ethanol injection (PEI; n = 10), or combined therapy (TACE + PEI; n = 11). The induced necrosis was pathologically evaluated. The recurrence rate after OLT in the treated group of patients (n = 38) was compared with that in the non-treated group (n = 24). After TACE, necrosis was complete in 7 of 29 lesions (24.1%), partial in 11 of 29 (37.9%), and absent in 11 of 29 (37.9%). After PEI, necrosis was complete in 8 of 10 lesions (80%), and partial in 2 of 10 (20%). Using combined therapy, necrosis was complete in 11 of 11 lesions (100%). Four of 24 untreated and 4 of 38 treated patients did not survive OLT from causes not related to the HCC; 3 of 20 non-treated patients (15%) and 4 of 34 treated patients (11.8%) had post-OLT recurrence (these last four patients had undergone only TACE and did not have tumor necrosis at pathological examination). TACE of HCC prior to OLT had no influence on the recurrence rate. PEI and combined therapy (TACE + PEI) may be recommended in patients awaiting OLT.


Cerebral norepinephrine: influence on cortical oxidative metabolism in situ.
Unilateral lesion of the locus coeruleus and the resultant norepinephrine depletion in the ipsilateral cerebrum alters the relationship between cerebral metabolic demands and local delivery of oxygen and substrates. This effect of norepinephrine depletion is demonstrated by slower recovery of the redox ratio of cytochrome a,a3 during increased metabolic demands induced by local cortical stimulation.


Efficacy study of recycling materials by lemon peels as novel lead adsorbents with comparing of material form effects and possibility of continuous flow experiment.
Lead contamination in the industrial wastewater is a major concern because of human health effects, so wastewater treatment is required before uses. Adsorption is an effective method with a reasonable cost, and natural wastes are an interesting choice as low-cost adsorbent. Lemon peels were chosen with their proper chemical properties for lead removal. This study is aimed at synthesizing lemon peel adsorbents; analyzing adsorbent characterizations; investigating affecting factors on dose, contact time, pH, and concentration; examining adsorption isotherms and kinetics; and exploring desorption experiments and fixed-bed column experiments. This study was successful synthesized adsorbents of lemon peel powder (LP) and beads (LPB) and was characterized through XRD, FESEM-FIB, EDS, BET, and FTIR. The optimum conditions of LP and LPB of 50 mg L-1 lead concentration were 4 g, 6 h, and pH 5 and 3 g, 5 h, and pH 5, respectively. Both adsorbents were corresponded to Freundlich and pseudo-second-order kinetic model. Fixed-bed column experiments which represented LPB had high lead removal efficiency with the adsorption capacity of 1.67 mg g-1, and it was also a good reusability more than 2 cycles. Therefore, LPB is a potential adsorbent to possibly apply for wastewater treatment.


Cardiopulmonary changes in the crying neonate.
To determine hemodynamic effects of crying, 12 newborn infants recovering from the respiratory distress syndrome (RDS) were studied. When crying, the range of inspiratory esophageal pressure was -18.8 to -32.5 cm H2O and the range of espiratory pressure was +6.2 to 34.4 cm H2O. The esophageal pressure remained positive for a mean value of 66% of the respiratory cycle. There was a mean significant increase in heart rate of 19 beats/min. The systolic and diastolic blood pressures increased significantly at the beginning of strain to 115 and 135% of the respective control values. There was a progressive decrease in systolic and diastolic pressures during the period of strain and the systolic pressures reached values significantly less than control. With the decrease in systolic and diastolic pressures, there were pronounced reductions in pulse pressures. Three infants reached pulse pressure values less than 1% of control when cries were sustained for nine cardiac cycles. There was a significant mean decrease in arterial oxygen tension (PaO2) of 16.8 mm Hg. There were no changes in arterial carbon dioxide tension (PaCO2), pH, or base excess.


Mammography visual enhancement in CAD-based breast cancer diagnosis.
This paper presents a novel approach to detect and discriminate abnormal and cueing signatures in mammography through enhancing the imaging contrast. Partial gland and adipose tissues are removed, and thus, the visual effect of mammography will be enhanced. Inspired by single image haze removal, we remove the majority of background tissues by introducing the idea of image matting. Experimental results show the feasibility and performance on distinguishing focuses from healthy tissues in the enhanced mammography. The method has potential applications on breast cancer diagnosis in computer-aided detection.


Arm Squeeze Test: a new clinical test to distinguish neck from shoulder pain.
Objective of this study is to evaluate the diagnostic values of the Arm Squeeze Test. The test consists in squeezing the middle third of the upper arm. 1,567 patients were included in this study. Diagnosis of cervical nerve root compression or shoulder disease was clinically formulated and confirmed with imaging before performing test. 350 healthy volunteers were recruited as controls. The test was positive when score on a VAS Scale was 3 points or higher on squeezing the middle third of the upper arm compared to acromioclavicular (AC) joint and anterolateral-subacromial area. Patients were subdivided as follows: 903 with rotator cuff tear, 155 with shoulder adhesive capsulitis, 101 with AC joint arthropathy, 55 with calcifying tendonitis, and 48 affected by glenohumeral arthritis. The study sample included 305 patients with cervical nerve root compression from C5 to T1 with shoulder radicular pain. The test was positive in 295/305 (96.7%) of patients with cervical nerve root compression, compared to 35/903 (3.87%), 3/155 (1.93%), 0/101 (0%), 1/55 (1.81%) and 4/48 (8.33%) of those with rotator cuff tear, adhesive capsulitis, AC arthropathy, calcifying tendonitis and glenohumeral arthritis, respectively. A positive result was obtained in 14/350 asymptomatic subjects (4%). If patients with cervical nerve root compression were compared to controls and patients with shoulder diseases, the test had sensitivity of 0.96 and specificity from 0.91 to 1. The Arm Squeeze Test may be useful to distinguish cervical nerve root compression from shoulder disease in case of doubtful diagnosis. A positive result to this test may lead to cervical etiology of the shoulder pain.


Identification of two divergently transcribed genes centromere-proximal to the ARG4 locus on chromosome VIII of Saccharomyces cerevisiae.
We have sequenced a 3296 bp segment of the chromosome VIII adjacent to the 3' end of the ARG4 gene. This segment contains two divergently oriented open reading frames (YSC83 and YSC84). Northern blot analysis showed the presence of transcripts corresponding to these two open reading frames in vegetative cells. Levels of these transcripts increase five to ten-fold during sporulation. These two genes are not essential for vegetative growth or sporulation. Analysis of the putative protein products on the SwissProt database revealed that the C-terminal region of the Ysc84 protein contains a putative SH3 domain.


Regulation of septin organization and function in yeast.
Septins are a conserved eukaryotic family of GTP-binding filament-forming proteins with functions in cytokinesis and other processes. In the budding yeast Saccharomyces cerevisiae, septins initially localize to the presumptive bud site and then to the cortex of the mother-bud neck as an hourglass structure. During cytokinesis, the septin hourglass splits and single septin rings partition with each of the resulting cells. Septins are thought to function in diverse processes in S. cerevisiae, mainly by acting as a scaffold to direct the neck localization of septin-associated proteins.


Effect of nitaxozanide and pyrimethamine on astrocytes infected by Toxoplasma gondii in vitro.
T. gondii is a causal agent of encephalitis in immunocompromised patients. Pyrimethamine (PYR) has been the treatment of choice for toxoplasmosis. The aim of this study was to analyze the effect of nitazoxanide and pyrimethamine on astrocytes infected with T. gondii in vitro. Rat astrocytes were cultured and infected with T. gondii. The effect of nitazoxanide (10, 20 and 30 μg/mL) and pyrimethamine (7, 10 and 13 μg/mL) on astrocytes infected was evaluated at 24 and 48 h post-infection. Tachyzoites and astrocytes were detected by the immunocytochemical method. T. gondii viability in astrocytes infected and treated with NTZ and PYR as well as NTZ and PYR cytotoxicity on astrocytes in vitro were evaluated by the MTT assay. The number of parasites in astrocytes treated with the drugs was significantly reduced when compared to control (p <0.001) at 24 and 48 h. Nitazoxanide produced 97% T. gondii death in a concentration of 10 μg/mL in 48 h infected astrocytes. At 48 h, the death rate of T. gondii was higher when treated with nitazoxanide than with pyrimethamine. A higher toxicity rate in astrocyte was observed when using pyrimethamine at 40 μg/mL. Nitazoxanide reduced T. gondii infection more efficiently than pyrimethamine and is not cytotoxic to astrocytes at the administered dose.


Clinicopathologic Factors Associated With Occult Lymph Node Metastasis in Patients With Clinically Diagnosed N0 Lung Adenocarcinoma.
In some patients, clinical N0 (cN0) lung adenocarcinoma diagnosed by preoperative computed tomography scanning and positron emission tomography scanning was staged as pathologic N1 (pN1) or N2 (pN2) postoperatively. The aim of this study was to determine the preoperative and postoperative clinicopathologic factors related to nodal upstaging after a surgical operation. We conducted a retrospective chart review of 350 patients treated for cN0 lung adenocarcinoma by curative resection. We analyzed clinicopathologic findings, comparing pN0 patients with the nodal upstaging group. Of 350 patients treated for cN0 tumors, 305 (87.1%) were confirmed postoperatively as having pN0 tumors, and 45 (12.9%) were confirmed as having pN1 or pN2 tumors. The mean maximum standardized uptake value (SUVmax) was higher in the nodal upstaging group than in the pN0 group (6.9 versus 3.8, p = 0.004); the upstaging group also included more cases in which SUVmax was greater than 5 (70.5% versus 24.8%, p < 0.001). Pleural invasion, lymphatic invasion, and vascular invasion were all more frequently seen in the nodal upstaging group than in the pN0 group (all p < 0.001). The presence of tumors with a micropapillary component was higher in the nodal upstaging group (p < 0.001). Multivariate logistic regression analysis identified SUVmax greater than 5, lymphatic invasion, vascular invasion, and a micropapillary component as significant risk factors for nodal upstaging. In lung adenocarcinoma diagnosed as clinical N0 by chest computed tomography and positron emission tomography scanning, the possibility of occult lymph node metastasis increases with SUVmax greater than 5 and when lymphatic invasion, vascular invasion, and a micropapillary component are present.


Renaissance natural philosophy, brain, and epilepsy (and some ideas about science).
Renaissance was a period full of religious and supernatural concepts and practices distant from the contemporary scientific world. Some erratic behaviors were considered demonic possessions and treated by exorcisms. It is supported by many sources. However, some important sources of the Renaissance point to a different picture. They show trends towards naturalistic explanations of many diseases, including epilepsy. This critical review discusses this approach, using texts by Mondino de' Luzzi and Leonardo da Vinci. However, more than an historical study, this review considers the passage from religious and supernatural practices to modern science. Contemporary consequences of that passage are considered, considering this Special Issue of Epilepsy & Behavior.