Bactericidal and anti-inflammatory effects of Moquilea tomentosa Benth. flavonoid-rich leaf extract.
Natural products are an important source of bioproducts with pharmacological properties. Here we investigate the components of leaves from M. tomentosa Benth. (Fritsch) (Chrysobalanaceae) and its effects on bacterial cell growth, biofilm production and macrophage activity. The effect of the different leaf extracts against bacterial cell growth was performed using the microdilution method. The most active extract was analyzed by mass spectrometry, and its effect on bacterial biofilm production was evaluated on polystyrene plates. The extract effect on macrophage activity was tested in the RAW264.7 cell line, which was stimulated with different concentrations of the extract in the presence or absence of LPS. We show that the ethyl acetate (EtOAc) extract was the most effective against bacterial cell growth. EtOAc extract DI-ESI (-)MSn analysis showed the presence of a glycosylated flavonoid tentatively assigned as myricetin 3-O-xylosyl-rhamnoside (MW 596). Also, the EtOAc extract increased biofilm formation by S. aureus and inhibited cytokine and NO production induced by LPS in RAW macrophages. M. tomentosa flavonoid-enriched EtOAc extract presented a bactericidal and anti-inflammatory pharmacological potential.


AP-1-directed human T cell leukemia virus type 1 viral gene expression during monocytic differentiation.
Human T cell leukemia virus type 1 (HTLV-1) has previously been shown to infect antigen-presenting cells and their precursors in vivo. However, the role these important cell populations play in the pathogenesis of HTLV-1-associated myelopathy/tropical spastic paraparesis or adult T cell leukemia remains unresolved. To better understand how HTLV-1 infection of these important cell populations may potentially impact disease progression, the regulation of HTLV-1 viral gene expression in established monocytic cell lines was examined. U-937 promonocytic cells transiently transfected with a HTLV-1 long-terminal repeat (LTR) luciferase construct were treated with phorbol 12-myristate 13-acetate (PMA) to induce cellular differentiation. PMA-induced cellular differentiation resulted in activation of basal and Tax-mediated transactivation of the HTLV-1 LTR. In addition, electrophoretic mobility shift analyses demonstrated that PMA-induced cellular differentiation induced DNA-binding activity of cellular transcription factors to Tax-responsive element 1 (TRE-1) repeat II. Supershift analyses revealed that factors belonging to the activator protein 1 (AP-1) family of basic region/leucine zipper proteins (Fra-1, Fra-2, JunB, and JunD) were induced to bind to TRE-1 repeat II during cellular differentiation. Inhibition of AP-1 DNA-binding activity by overexpression of a dominant-negative c-Fos mutant (A-Fos) in transient expression analyses resulted in severely decreased levels of HTLV-1 LTR activation in PMA-induced U-937 cells. These results have suggested that following infection of peripheral blood monocytes, HTLV-1 viral gene expression may become up-regulated by AP-1 during differentiation into macrophages or dendritic cells.


Disc height loss after anterior cervical microdiscectomy with titanium intervertebral cage fusion.
The use of a graft in cervical inter-vertebral disc repair is still a controversial procedure. The aim of the treatment is to restore the physiological disc height and to achieve fusion. This study was performed to determine the rate of narrowing of the cervical intervertebral disc after using a titanium cervical intervertebral cage (BAK-C; Sulzer Spine Tech, Minneapolis, MN). 43 patients were included in the study. Each had a cervical disc protrusion, resulting in radiculopathy. All underwent surgery involving an anterior one level cervical microdiscectomy and fusion with a cylindrical titanium cage. The mean follow-up time was 18+/-5 months. The extent of the mean narrowing rate of disc space was 35.6+/-9%. The fusion rate was 98% and the mean time to fusion was 6 months. The use of a cervical intervertebral cage in anterior cervical microdiscectomy does not prevent the loss of the height of the cervical disc space after the operation.


Recruitment and retention of speech-language pathologists: putting home healthcare on the radar.
The problems that home health managers experience in hiring speech-language pathologists (SLPs) are not surprising. The surveys of the profession show that insufficient numbers of SLPs exist in the workforce to fill all the available positions. In competing with schools and other healthcare settings, home health recruiters also must overcome SLPs' lack of exposure to home health during their formative student experiences. This article provides some tips about where to find SLPs and how to excite them about home healthcare--and once having hired them, how to keep them.


Equine arteritis virus: an overview.
The causative agent of the respiratory disease equine viral arteritis is a small, single-stranded RNA virus with a genome organization and replication strategy related to that of coronaviruses and toroviruses. Clinical signs of infection in horses vary widely and severe infection can lead to pregnant mares aborting. Infected horses generally make good recoveries but stallions may become semen shedders of equine arteritis virus (EAV). These carrier stallions play an important role in the dissemination and perpetuation of EAV. Laboratory tests exist to detect virus and the equine immune response to infection. However, vaccines are not currently licensed in the UK to combat viral arteritis, the incidence of which may increase due to changes in European legislation.


Cytogenetic effect of malathion in in vitro culture of human peripheral blood.
Chromosomal aberrations, sister-chromatid exchanges and mitotic indices were observed in human peripheral leukocytes, treated with four different concentrations of malathion (0.02, 0.2, 2 and 20 micrograms/ml), an organophosphate pesticide, added to the culture medium at 0, 24 and 48 h after culture initiation. These cultures showed a dose-dependent increase in the frequency of chromosomal aberration as well as sister-chromatid exchanges. There was a significant decrease in mitotic index at all concentrations.


Fine-tuning genomic and pedigree inbreeding rates in equine population with a deep and reliable stud book: the case of the Pura Raza Española horse.
Estimating inbreeding, which is omnipresent and inevitable in livestock populations, is a primary goal for management and animal breeding especially for those interested in mitigating the negative consequences of inbreeding. Inbreeding coefficients have been historically estimated by using pedigree information; however, over the last decade, genome-base inbreeding coefficients have come to the forefront in this field. The Pura Raza Española (PRE) horse is an autochthonous Spanish horse breed which has been recognised since 1912. The total PRE population (344,718 horses) was used to estimate Classical (F), Ballou's ancestral, Kalinowski's ancestral, Kalinowski's new and the ancestral history coefficient values. In addition, genotypic data from a selected population of 805 PRE individuals was used to determine the individual inbreeding coefficient using SNP-by-SNP-based techniques (methods of moments -FHOM-, the diagonal elements of the genomic -FG-, and hybrid matrixes -FH-) and ROH measures (FRZ). The analyse of both pedigree and genomic based inbreeding coefficients in a large and robust population such as the PRE horse, with proven parenteral information for the last 40 years and a high degree of completeness (over 90% for the last 70 years) will allow us to understand PRE genetic variability better and the correlations between the estimations will give the data greater reliability. The mean values of the pedigree-based inbreeding coefficients ranged from 0.01 (F for the last 3 generations -F3-) to 0.44 (ancestral history coefficient) and the mean values of genomic-based inbreeding coefficients varied from 0.05 (FRZ for three generations, FH and FHOM) to 0.11 (FRZ for nine generations). Significant correlations were also found between pedigree and genomic inbreeding values, which ranged between 0.58 (F3 with FHOM) and 0.79 (F with FRZ). In addition, the correlations between FRZ estimated for the last 20 generations and the pedigree-based inbreeding highlight the fact that fewer generations of genomic data are required when comparing total inbreeding values, and the opposite when ancient values are calculated. Ultimately, our results show that it is still useful to work with a deep and reliable pedigree in pedigree-based genetic studies with very large effective population sizes. Obtaining a satisfactory parameter will always be desirable, but the approximation obtained with a robust pedigree will allow us to work more efficiently and economically than with massive genotyping.


Long-term survival in patients with ovarian metastases from colorectal carcinoma.
Ovarian metastases (OM) are a relatively uncommon consequence of primary colorectal carcinoma (CRC). The authors present a retrospective review of the impact of elective and therapeutic oophorectomy on the natural history of CRC. Patients with primary CRC from January 1964 through March 1996 were reviewed. Survival from the time of OM diagnosis was estimated by the Kaplan-Meier method; differences between groups were based on the log-rank test. A total of 155 patients were studied. Synchronous OM occurred in 90 patients (58.1%); metachronous OM occurred in 65 patients (41.9%). Estimated 5-year survival for patients with synchronous OM was 9%, versus 20% for metachronous OM (P < .0001). Resection of metastatic disease was associated with an improved 5-year survival for synchronous OM (15% vs. 0%, P=.0001) and metachronous OM (24% vs. 0%, P < .0001) if patients were disease-free postoperatively. Other clinical characteristics, including age, menopausal status, stage, and location of primary tumor, had no significant impact on survival. Ovarian metastases from colorectal carcinoma are associated with a poor outcome. Although there is no survival advantage associated with resection of occult microscopic disease, long-term survival is possible if patients are rendered surgically disease-free.


Overexpression of NCAPG in ovarian cancer is associated with ovarian cancer proliferation and apoptosis via p38 MAPK signaling pathway.
Non-SMC condensin I complex subunit G (NCAPG), a member of the subunit of condensin complex, is significantly overexpressed in various cancers and involved in the pathogenesis of cancers. However, the roles of NCAPG in ovarian cancer remain unclear. The mRNA expression, overall survival, and disease-free survival of NCAPG in ovarian cancer were analyzed by GEPIA and KM plotter database, and the expression levels of NCAPG in OC tissues and cell lines were determined by qPCR and immunohistochemistry analysis. shRNA targeting NCAPG gene (sh-NCAPG) was utilized to knock down NCAPG expression in OVCAR3 and SKOV3 cells. Subsequently, CCK-8 assay, colony formation assay, transwell invasion assay and flow cytometric analysis were performed to detect the effect of NCAPG on OC cell proliferation, apoptosis, and invasion. Finally, western blot assays were performed to detect the mechanism of NCAPG in ovarian cancer. Analysis using GEPIA and KM plotter database showed NCAPG was upregulated in ovarian cancer and negatively associated with the survival of OC patients. qPCR and immunohistochemistry analysis confirmed it was highly expressed in both ovarian cancer tissues and cells. The silencing of NCAPG inhibited OC cell proliferation and invasion, and induced cell apoptosis. Additionally, flow cytometric analysis revealed that NCAPG knockdown arrested the cell cycle at G2 and S phases. Furthermore, we also found that downregulation of NCAPG could suppress OC cell proliferation and invasion via activating the p38 MAPK signaling pathway. Our results suggest that NCAPG exhibits an important role in the development and progression of ovarian cancer and implicates NCAPG as a potential therapeutic target in ovarian cancer.


Familial colorectal cancer.
The introduction of average-risk colorectal cancer (CRC) screening programs means that many subjects with family history of CRC and without well-described inherited syndromes can benefit from these public health policies. Therefore, the definition of which individuals should be named under the umbrella of the term "familial CRC" should be reconsidered to include only those who are outside of the protection of population-based screening and need to be moved towards a more intensive surveillance strategy. Two subgroups have been reported as having a high enough CRC risk to be included within the term "familial risk of CRC": individuals who have ≥1 first degree relative (FDR) with CRC diagnosed at age <50 years, and those who have ≥2 FDRs with CRC. Colonoscopy-based screening starting at age 40 years is proposed as the most accepted recommendation for these individuals. Finally, the evolution of Lynch syndrome screening from clinical criteria to tumor tissue analysis and new tools for screening pathogenic gene mutations associated with cancer susceptibility in individuals with early-onset CRC might help to reduce misclassification of familial CRC.


Evidence in duck for supporting alteration of incubation temperature may have influence on methylation of genomic DNA.
Incubation temperature has an immediate and long-term influence on the embryonic development in birds. DNA methylation as an important environment-induced mechanism could serve as a potential link between embryos' phenotypic variability and temperature variation, which reprogrammed by DNA (cytosine-5)-methyltransferases (DNMTS) and Methyl-CpG binding domain proteins (MBPS) 3&5 (MBD3&5). Five genes in DNMTS and MBPS gene families were selected as target genes, given their important role in epigenetic modification. In this study, we aimed to test whether raising incubation temperature from 37.8°C to 38.8°C between embryonic days (ED) 1-10, ED10-20 and ED20-27 have effect on DNA methylation and whether DNMTS, MBPS play roles in thermal epigenetic regulation of early development in duck. Real-time quantitative PCR analysis showed that increased incubation temperature by 1°C has remarkably dynamic effect on gene expression levels of DNMTS and MBPS. Slight changes in incubation temperature significantly increased mRNA levels of target genes in breast muscle tissue during ED1-10, especially for DNMT1, DNMT3A and MBD5. In addition, higher temperature significantly increased enzyme activities of DNMT1 in leg muscle during ED10-20, liver tissue during ED1-10, ED20-27 and DNMT3A in leg muscle and breast muscle tissue during ED10-20. These results suggest that incubation temperature has an extended effect on gene expression levels and enzyme activities of DNMTS and MBPS, which provides evidence that incubation temperature may influence DNA methylation in duck during early developmental stages. Our data indicated that DNMTS and MBPS may involved in thermal epigenetice regulation of embryos during the early development in duck. The potential links between embryonic temperature and epigenetic modification need further investigation.


Post-graduation Plans of Undergraduate BME Students: Gender, Self-efficacy, Value, and Identity Beliefs.
This study investigates career intentions and students' engineering attitudes in BME, with a focus on gender differences. Data from n = 716 undergraduate biomedical engineering students at a large public research institution in the United States were analyzed using hierarchical agglomerative cluster analysis. Results revealed five clusters of intended post-graduation plans: Engineering Job and Graduate School, Any Job, Non-Engineering Job and Graduate School, Any Option, and Any Graduate School. Women were evenly distributed across clusters; there was no evidence of gendered career preferences. The main findings in regard to engineering attitudes reveal significant differences by cluster in interest, attainment value, utility value, and professional identity, but not in academic self-efficacy. Yet, within clusters the only gender differences were women's lower engineering academic self-efficacy, interest and professional identity compared to men. Implications and areas of future research are discussed.


Pharmacokinetics, Pharmacodynamics, Safety, and Clinical Activity of Multiple Doses of RCT-18 in Chinese Patients With Systemic Lupus Erythematosus.
RCT-18 is a novel recombinant fusion protein that blocks the activity of a B-lymphocyte stimulator and a proliferation-inducing ligand. This was a randomized, single-blind, and placebo-controlled phase 1 study in 12 patients with systemic lupus erythematosus. Eligible patients were randomized 3:1 to receive multiple subcutaneous doses of RCT-18 for 4 weeks (180 mg, once weekly) or placebo and monitored over an 84-day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety, and clinical activity. After multiple-dose RCT-18, the maximal serum concentration (Cmax ) of total and free RCT-18 was reached within 1 to 2 days. Mean elimination half-life for total RCT-18 and free RCT-18 was 11.4 to 26.4 days and 2.4 to 26.5 days, respectively. Slight accumulation was found after multiple subcutaneous administrations. The average accumulation ratios of AUC and Cmax after the fourth administration of RCT-18 were 2.0 and 1.7 for total RCT-18, and 1.8 and 1.6 for free RCT-18. The formation and elimination of BLyS-RCT-18 complex were much slower, with a time to Cmax of 14 to 46 days. Pharmacokinetic characteristics of RCT-18 in SLE patients were similar to those in patients with rheumatoid arthritis. No positive reaction was detected in the immunogenicity assessments. RCT-18 was biologically active, according to serum immunoglobulin and B-cell levels. Treatment-related IgM and IgA reduction was found during this study. CD19(+) , IgD(+) , and CD27(+) B-cell counts were increased after administration and decreased subsequently. SLE patients treated with RCT-18 were more prone to infections, including moderate and severe infections. Lower dosages of RCT-18 should be considered in further clinical development.


Establishing a low-expression renalase gene model in cardiac tissue of Sprague-Dawley rats.
Renalase is a novel secretory amino oxidase expressed in the kidney and heart. To study the protective mechanism of renalase in local heart tissue, we established a low-expression renalase model with lentivirus (LV)-mediated RNA interference technology. Three renalase-targeting oligonucleotides were designed after analyzing the mRNA of renalase. LV particles were prepared with LV expression systems (using the Trono 3 plasmid component system), after which LV-RNLS-shRNAs and LV-NC-shRNA were transfected into H9C2 cells in different cell culture plates. The optimal oligonucleotide was screened by real-time PCR and Western blot. These techniques were also used to detect renalase gene expression in the heart tissue. In the cell screening experiment, the efficacy of the inhibition of renalase mRNA expression was 93.7 % and that of renalase protein expression was 83.1 % in H9C2 cells. When the oligonucleotide was injected into the pericardial cavities of the SD rats on the 10th day, it inhibited 63.9 % of the expression of renalase protein in the heart tissue. LV-RNLS-RNAi (19813-1) can be used to establish an optimal renalase low-expression model for further research on the renalase system.


Calibration of the response of 9-amino acridine fluorescence to transmembrane pH differences in bacterial chromatophores.
The spectral characteristics of absorption and fluorescence emission of 9-amino acridine are not altered by the interaction with bacterial chromatophores, except for the attenuation of both the absorption and emission following the formation of a protonic gradient. The lifetime of fluorescence of the dye is significantly affected in the presence of membranes, and even more following illumination. The shortening of the lifetime induced by light is reversible and prevented by nigericin and K+. The onset kinetics of the fluorescence quenching following the generation of an artificial transmembrane pH difference is temperature dependent, with an activation energy of 17 +/- 3 kcal/mol. The effect of pH on the rate constants is consistent with a model assuming that the diffusion of the unprotonated species is the limiting step in the quenching phenomenon. The response of 9-amino acridine to artificially imposed delta pH's has been utilized as a calibration method for the measurements of the light-induced protonic gradient. The apparent inner volume of chromatophores, evaluated from the extraplation of the response at delta pH = 0, was found to be much larger (15- to 40-fold) than the true osmotic volume, indicating that most of the dye is bound to the membrane when accumulated into the inner lumen.


Nuclear export as a key arbiter of "mRNA identity" in eukaryotes.
Over the past decade, various studies have indicated that most of the eukaryotic genome is transcribed at some level. The pervasiveness of transcription might seem surprising when one considers that only a quarter of the human genome comprises genes (including exons and introns) and less than 2% codes for protein. This conundrum is partially explained by the unique evolutionary pressures that are imposed on species with small population sizes, such as eukaryotes. These conditions promote the expansion of introns and non-functional intergenic DNA, and the accumulation of cryptic transcriptional start sites. As a result, the eukaryotic gene expression machinery must effectively evaluate whether or not a transcript has all the hallmarks of a protein-coding mRNA. If a transcript contains these features, then positive feedback loops are activated to further stimulate its transcription, processing, nuclear export and ultimately, translation. However if a transcript lacks features associated with "mRNA identity", then the RNA is degraded and/or used to inhibit further transcription and translation of the gene. Here we discuss how mRNA identity is assessed by the nuclear export machinery in order to extract meaningful information from the eukaryotic genome. In the process, we provide an explanation of why certain sequences that are enriched in protein-coding genes, such as the signal sequence coding region, promote mRNA nuclear export in vertebrates. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing.


Prey selection by an intertidal beetle: field test of an optimal diet model.
Adult beetles Thinopinus pictus LeConte (Staphlyinidae) live on sand beaches in temporary burrows from which they emerge at night to prey on amphipods Orchestoidea calforniana (Brandt). I constructed models of amphipod size selection by beetles, using the size distributions of amphipods measured on the beach, and the results of laboratory experiments on capture success, reaction distance and feeding rates. Capture success decreased and the probability that an amphipod was detected increased with increasing amphipod size. Beetles observed during beach searches selected larger sizes of amphipods than predicted from availability and vulnerability of different sizes. To apply an optimal foraging model, I estimated the profitability of different sizes of amphipods from the number of amphipods of a given size required to satiate a beetle in the laboratory. Profitability was highest for large amphipods and lowest for small amphipods and isopods. However, amphipod abundance on the beach was always below the threshold at which specialization on larger sizes was predicted to occur.


In-silico modeling of the interplay between APOE4, NLRP3, and ACE2-SPIKE complex in neurodegeneration between Alzheimer and SARS-CoV: implications for understanding pathogenesis and developing therapeutic strategies.
The multifaceted interplay between neurodegenerative pathologies, including Alzheimer's disease (AD), and the highly virulent severe acute respiratory syndrome coronavirus (SARS-CoV), is implicated in various conditions. AD and SARS-CoV pathogenesis involve the APOE4 allele, NLRP3 inflammasome, and ACE2-SPIKE complex. APOE4, a genetic polymorphism of the APOE gene, is associated with an increased susceptibility to AD. NLRP3, an inflammatory protein of the innate immune system, plays a pivotal role in immune response cascades. In SARS-CoV, the ACE2 receptor serves as the principal portal for cellular entry, while APOE4 intricately interacts with the ACE2-spike protein complex, enhancing viral internalization process. The interaction of NLRP3 with the ACE2-spike protein complex leads to increased inflammatory signaling. The convergence of APOE4/NLRP3 and ACE2-spike protein complex interactions suggests a possible link between SARS and AD. Therefore, the current research centralizes the association between by utilizing SARS-CoV datasets to explore possible mechanisms that account for the pathogenesis of SARS-CoV and AD. The work is further extended to unveil the molecular interactions of APOE4 and NLRP3 with the ACE2-Spike protein complex at the molecular level by employing molecular dynamics simulation techniques. The therapeutic efficacy of Chyawanprash nutraceuticals is evaluated as their inhibitory potential towards APOE4-ACE2-Spike protein and NLRP3-ACE2-Spike protein complexes. Notably, our simulations unequivocally demonstrate the robust and enduring binding capability of the compound Phyllantidine with the target complexes throughout the simulation period. The findings of the studies further corroborate the primary hypothesis of APOE4 and NLRP3 as driver factors in the pathogenesis of both SARS-CoV and AD. Therefore, this research establishes a paradigm for comprehending the complex interaction between AD and SARS-CoV and lays the groundwork for further study in this domain.Communicated by Ramaswamy H. Sarma.


Granulocyte and monocyte adsorptive apheresis ameliorates sepsis in rats.
Overwhelming activation of granulocytes and monocytes is central to inflammatory responses during sepsis. Granulocyte and monocyte adsorptive apheresis (GMA) is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads and selectively adsorbs granulocytes and monocytes from the peripheral blood. In this study, septic rats received the GMA treatment for 2 h at 18 h after cecal ligation and puncture. GMA selectively adsorbed activated neutrophils and monocytes from the peripheral blood, reduced serum inflammatory cytokine expression, and seemed to improve organ injuries and animal survival. GMA potentially reduced lung injury by alleviating the infiltration of inflammatory cells and the secretion of cytokines. This study showed that selective granulocyte and monocyte adsorption with cellulose acetate beads might ameliorate cecal ligation and puncture (CLP)-induced sepsis and improve survival and organ function.


Regulation of the Inflammatory Synovial Fibroblast Phenotype by Metastasis-Associated Lung Adenocarcinoma Transcript 1 Long Noncoding RNA in Obese Patients With Osteoarthritis.
To identify long noncoding RNAs (lncRNAs) associated with the inflammatory phenotype of synovial fibroblasts from obese patients with osteoarthritis (OA), and to explore the expression and function of these lncRNAs. Synovium was collected from normal-weight patients with hip fracture (non-OA; n = 6) and from normal-weight (n = 8) and obese (n = 8) patients with hip OA. Expression of RNA was determined by RNA-sequencing and quantitative reverse transcription-polymerase chain reaction. Knockdown of lncRNA was performed using LNA-based GapmeRs. Synovial fibroblast cytokine production was measured by enzyme-linked immunosorbent assay. Synovial fibroblasts from obese patients with OA secreted greater levels of interleukin-6 (IL-6) (mean ± SEM 162 ± 21 pg/ml; P < 0.001) and CXCL8 (262 ± 67 pg/ml; P < 0.05) compared to fibroblasts from normal-weight patients with OA (IL-6, 51 ± 4 pg/ml; CXCL8, 78 ± 11 pg/ml) or non-OA patients (IL-6, 35 ± 3 pg/ml; CXCL8, 56 ± 6 pg/ml) (n = 6 patients per group). RNA-sequencing revealed that fibroblasts from obese OA patients exhibited an inflammatory transcriptome, with increased expression of proinflammatory messenger RNAs (mRNAs) as compared to that in fibroblasts from normal-weight OA or non-OA patients (>2-fold change, P < 0.05; n = 4 patients per group). A total of 19 lncRNAs were differentially expressed between normal-weight OA and non-OA patient fibroblasts, and a further 19 lncRNAs were differentially expressed in fibroblasts from obese OA patients compared to normal-weight OA patients (>2-fold change, P < 0.05 for each), which included the lncRNA for metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1 was rapidly induced upon stimulation of OA synovial fibroblasts with proinflammatory cytokines, and was up-regulated in the synovium from obese OA patients as compared to normal-weight OA patients (1.6-fold change, P < 0.001) or non-OA patients (6-fold change, P < 0.001). MALAT1 knockdown in OA synovial fibroblasts (n = 4 patients) decreased the levels of mRNA expression and protein secretion of CXCL8 (>1.5-fold change, P < 0.01), whereas it increased expression of mRNAs for TRIM6 (>2-fold change, P < 0.01), IL7R (<2-fold change, P < 0.01), HIST1H1C (>1.5-fold change, P < 0.001), and MAML3 (>1.5-fold change, P < 0.001). In addition, MALAT1 knockdown inhibited the proliferation of synovial fibroblasts from obese patients with OA. Synovial fibroblasts from obese patients with hip OA exhibit an inflammatory phenotype. MALAT1 lncRNA may mediate joint inflammation in obese OA patients.


Responsivity to familiar versus unfamiliar social reward in children with autism.
In autism spectrum disorders (ASD), social motivation theories suggest that the core social communication problems seen in children with ASD arise from diminished responsiveness to social reward. Although clinical and experimental data support these theories, the extent to which the reward deficit in ASD is unique for social rewards remains unclear. With the present investigation, we aimed to provide insight into the degree to which sociality as well as familiarity of reward incentives impact motivated goal-directed behavior in children with ASD. To do so, we directly compared the influence of familiar versus unfamiliar social reward relative to nonsocial, monetary reward in children with ASD relative to age- and IQ-matched typically developing controls (TDC) using a visual and auditory incentive go/nogo task with reward contingencies for successful response inhibitions. We found that children with ASD responded stronger to visual familiar and unfamiliar social reward as well as to nonsocial, monetary reward than TDC. While the present data are at odds with predictions made by social motivation theories, individual variations beyond clinical diagnosis, such as reward exposure across various social settings, help explain the pattern of results. The findings of this study stress the necessity for additional research on intra-individual as well as environmental factors that contribute to social reward responsiveness in individuals with ASD versus other neuropsychiatric disorders such as ADHD or conduct disorder.


Experimental oxalate urolith formation in rats.
Urinary calculi composed of calcium oxalate were produced in male hooded Wistar rats fed a vitamin B6 deficient diet over 16 weeks. This basic diet was modified by doubling the phosphate content or loading with vitamin C or D3 in three treatment groups. The number of rats developing oxalate stones was not altered by the addition of vitamin D3 or phosphate, but there was a significant increase in total weight of stone formed and histological evidence of extensive renal damage in rats on the high vitamin D3 diet. The addition of vitamin C to the vitamin B6 deficient rats resulted in a reduction in the number of rats with uroliths and a fall in urinary oxalate excretion, while similarly loaded vitamin B6 supplemented controls were free of oxalate calculi. It is concluded that the oxalate urolithiasis induced by vitamin B6 deficiency was exacerbated by added vitamin D3 and reduced by vitamin C.


Molecular and cellular defects in nephrogenic diabetes insipidus.
Nephrogenic diabetes insipidus is a rare genetic disorder characterized by insensitivity of the distal nephron to the antidiuretic effect of arginine vasopressin. Two different molecular defects underlying this disease have so far been identified. Mutations in the gene encoding the vasopressin type-2 receptor cause the X-chromosomal form of the disease, whereas mutations in the gene encoding the vasopressin-dependent water channel aquaporin-2 are responsible for the autosomal recessive, and (in some cases) an autosomal dominant type of the disease. Functional analysis of naturally occurring mutations in the vasopressin type-2 receptor and aquaporin-2 have increased the insight into the structure and function of both proteins and have led to substantial progress in understanding the cellular mechanisms underlying the concentrating ability of the kidney. Some female carriers of a vasopressin type-2 receptor mutation may show complete manifestation of nephrogenic diabetes insipidus, probably as a result of skewed X-inactivation. The recent findings in nephrogenic diabetes insipidus research have considerable impact for diagnosis of and genetic counselling for this disease.


Malaria, climate variability, and interventions: modelling transmission dynamics.
Assessment of the relative impact of climate change on malaria dynamics is a complex problem. Climate is a well-known factor that plays a crucial role in driving malaria outbreaks in epidemic transmission areas. However, its influence in endemic environments with intensive malaria control interventions is not fully understood, mainly due to the scarcity of high-quality, long-term malaria data. The demographic surveillance systems in Africa offer unique platforms for quantifying the relative effects of weather variability on the burden of malaria. Here, using a process-based stochastic transmission model, we show that in the lowlands of malaria endemic western Kenya, variations in climatic factors played a key role in driving malaria incidence during 2008-2019, despite high bed net coverage and use among the population. The model captures some of the main mechanisms of human, parasite, and vector dynamics, and opens the possibility to forecast malaria in endemic regions, taking into account the interaction between future climatic conditions and intervention scenarios.


Quantifying Tropical Plant Diversity Requires an Integrated Technological Approach.
Tropical biomes are the most diverse plant communities on Earth, and quantifying this diversity at large spatial scales is vital for many purposes. As macroecological approaches proliferate, the taxonomic uncertainties in species occurrence data are easily neglected and can lead to spurious findings in downstream analyses. Here, we argue that technological approaches offer potential solutions, but there is no single silver bullet to resolve uncertainty in plant biodiversity quantification. Instead, we propose the use of artificial intelligence (AI) approaches to build a data-driven framework that integrates several data sources - including spectroscopy, DNA sequences, image recognition, and morphological data. Such a framework would provide a foundation for improving species identification in macroecological analyses while simultaneously improving the taxonomic process of species delimitation.


[Intraspecies animal behavior in a model of experimental cerebral ischemia].
Specifics of intraspecies behaviour following ligation of both or either one of the two carotid arteries, were studied in rats. Certain behavioural features are altered in different ways depending on ligation of the right or left carotid artery. The approach can be applied to evaluation of graveness of the brain ischemic lesion.


GSPE is superior to NAC in the prevention of contrast-induced nephropathy: might this superiority be related to caspase 1 and calpain 1?
Our study was intended to evaluate the role of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), caspases 1 and 3 and calpain 1 in the pathogenesis of contrast-induced nephropathy (CIN) and to compare the protective effects of N acetyl cysteine (NAC) and grape seed proanthocyanidin extract (GSPE) against the development of CIN. 32 rats were divided into four groups; control, contrast media (CM), CM+NAC and CM+GSPE. CIN was induced by administration of 7 ml/kg diatrizoate. The experiment was discontinued on the ninth day. Blood was collected for blood urea nitrogen (BUN) and creatinine measurement. Rat kidney tissues were removed for histopathological evaluation and the investigation of caspases 1 and 3, iNOS, eNOS, TUNEL and calpain 1. A significant increase in BUN, creatinine, renal histopathological injury, TUNEL, caspases 1, 3, calpain 1, iNOS and eNOS was observed in the CM group compared to the control group. There was amelioration in all these parameters in the CM+GSPE group, while there was no significant amelioration in BUN, creatinine and renal histopathological injury in the CM+NAC group. In addition, calpain 1 staining and creatinine were significantly lower in the CM+GSPE group compared to the CM+NAC group. Our study showed, for the first time in the literature, that GSPE has a greater renoprotective effect compared with NAC and that this effective protection may be related to decrease in calpain 1 levels.


Transcriptional regulation and O-GlcNAcylation activity of zebrafish OGT during embryogenesis.
Zebrafish OGT (zOGT) sequence was identified in zebrafish (Danio rerio) genome and six different transcriptional variants of zOGT, designated var1 to var6, were isolated. Here we describe the developmental regulation of zOGT variants at transcriptional level and characterization of their OGT activities of protein O-GlcNAcylation. OGT transcriptional variants in zebrafish were differentially generated by alternative splicing and in particular, var1 and var2 were contained by 48 bp intron as a novel exon sequence, demonstrating that this form of OGT was not found in mammals. Transcript analysis revealed that var1 and var2 were highly expressed at early phase of development including unfertilized egg until dome stage whereas var3 and var4 were begins to be expressed at sphere stage until late phase of development. Our data indicate that var1 and var2 are likely to be maternal transcripts. The protein expression assay in Escherichia coli-p62 system showed that OGT activities of var3 and var4 were found to be only active whereas those of other variants were inactive.


ANS fluorescence: Potential to discriminate hydrophobic sites of proteins in solid states.
In the current study, ANS fluorescence was established as a powerful tool to study proteins in solid-state. Silk fibroin from Bombyx mori cocoons was used as a paradigm protein. ANS incorporated into the films of silk fibroin exhibits fluorescence with two-lifetime components that can be assigned to the patches and/or cavities with distinct hydrophobicities. Decay associated spectra (DAS) of ANS fluorescence from both sites could be fit to the single log-normal component indicating their homogeneity. ANS binding sites in the protein film are specific and could be saturated by ANS titration. ANS located in the binding site that exhibits the long-lifetime fluorescence is not accessible to the water molecules and its DAS stays homogeneously broadened upon hydration of the protein film. In contrast, ANS from the sites demonstrating the short-lifetime fluorescence is accessible to water molecules. In the hydrated films, solvent-induced fluctuations produce an ensemble of binding sites with similar characters. Therefore, upon hydration, the short-lifetime DAS becomes significantly red-shifted and inhomogeneously broadened. The similar spectral features have previously been observed for ANS complexed with globular proteins in solution. The data reveal the origin of the short-lifetime fluorescence component of ANS bound to the globular proteins in aqueous solution. Findings from this study indicate that ANS is applicable to characterize dehydrated as well as hydrated protein aggregates, amyloids relevant to amyloid diseases, such as Alzheimer's, Parkinson, and prion diseases.


Frequency content and characteristics of ventricular conduction.
The spectrum of frequencies producing the QRS complex has not been fully explored. In this manuscript we review previous studies of QRS frequency content, and discuss our novel method of the conjoint analysis of the ECG signal in six dimensions: in the domain of three space dimensions, in time domain, and in frequency domain. Orbital frequency of QRS loop is introduced as a six-dimensional characteristic of ventricular conduction, which helped to reveal inapparent ventricular conduction, and to characterize electrophysiological substrate. In this paper, we review our novel method in the historical context.


[Our experience of the sural flap with distal pedicle in the repair of foot plantar and heel of foot lesions].
The sural flap has often been used to cover the weight-bearing and non-weight-bearing areas of the foot and ankle. This study reports our experience in the coverage of these defects in the foot in weight-bearing areas. This is a retrospective and descriptive study of 70 months. This study includes 16 patients presenting a loss of plantar substance and/or heel of the foot covered by a sural flap with a distal pedicle. The sampling technique described by Masquelet served as our reference. An increase in the length of the pedicle of at least two centimeters during the dissection made it possible to avoid any stretching or compression for the most distal lesions. The average age was 35 years with a sex ratio of three in favor of men. Traumatic lesions predominated (n=10) with an average area of lesions of 68.8cm2. The average partial and total support times were 1.8 and 3.6 months respectively. We noted one case of flap necrosis. The natural evolution of the flap took place in three progressive stages: regeneration, keratinization and squamous metaplasia. Normal bipodal support and stable gait without footwear anomaly were noted in 15 cases. The distal pedicle sural flap technique is accessible. Its reliability makes it an ideal choice for distal loss of substance to the leg and foot.


Further evidence for a hypothalamus-parotid gland endocrine axis in the rat.
The existence of a hypothalamus-parotid gland endocrine axis that stimulates intradentinal dye penetration (IDDP) in rat teeth was suggested in earlier studies and IDDP-stimulating factors were isolated or purified from porcine parotid glands and hypothalamic tissues, respectively. In the present study, infusion of carbamyl-DL-aspartic acid (CAA) into rats was used to demonstrate the role of the endogenous hormones of the hypothalamus-parotid gland endocrine axis in stimulating IDDP, as observed by fluorescence microscopy of longitudinal sections of molar teeth. Intra-arterial infusion of CAA into intact rats stimulated IDDP in a dose-related fashion (between 49-390 nmol/100 g body weight); however, infusion of 390 nmol into parotidectomized rats was ineffective. Infusion of plasma from CAA-treated rats was equally effective in stimulating IDDP in intact and in parotidectomized animals. In contrast, plasma obtained from parotidectomized, CAA-treated rats stimulated IDDP in intact recipient animals but not in parotidectomized ones. Moreover, plasma from adult rats treated with CAA after an electrolytic lesion of the hypothalamus, and infused back into young intact rats, was ineffective in stimulating IDDP. These results indicate that: (1) CAA requires the functional integrity of the parotid gland to express its IDDP-stimulating activity, (2) a hormonal factor is secreted by the parotids in response to CAA stimulation and is directly responsible for IDDP stimulation, (3) release of the endocrine parotid IDDP-stimulating factor after infusion of CAA involves a second endocrine factor that appears to originate from the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)


A different aspect of corrosive ingestion in children: socio-demographic characteristics and effect of family functioning.
Corrosive ingestion is thoroughly investigated in terms of its complications and treatment modalities but to date family functioning, behavior, attitude and knowledge of mothers of children who ingested corrosives has not been investigated and socio-demographic data has rarely been mentioned. Therefore a study was planned to investigate the socio-demographic data, family functioning, knowledge, behavior and attitude of mothers of children who ingested corrosive materials. The mothers of 50 children who ingested corrosive materials and 60 controls were asked to answer a questionnaire which included socio-demographic data and questions about their attitude, behavior and knowledge of corrosive ingestion. The mothers were also asked to reply family assessment device (FAD) and parental attitude research instrument (PARI). The average ages of the children were 5.31+/-2.32 in the corrosive group with an M:F ratio of 1:1. The level of education of both mothers (p=0.000) and fathers (p=0.000) in the corrosive group were lower than that of the controls. There was no difference between the two groups in terms of number of working mothers (p=0.085). In the corrosive group the families used to have three or more children (42%) and the socioeconomic status of this group was lower than the controls (p=0.001). In the corrosive group these substances were purchased unlabeled (64%) and kept mainly in coke bottles. The affective involvement dimension of the FAD and the attitude of over-parenting and democratic attitude dimensions of the PARI tests were significantly different in the corrosive group among mothers from lower educational level whereas no difference was detected among mothers from higher educational level in this regard. It was found that both level of education of the parents and socioeconomic factors played important role in shaping the habits that might lead to corrosive ingestion in children. For the prevention of corrosive ingestion broad based strategies including education are required.


B cell increases and ex vivo IL-2 production as secondary endpoints for the detection of sensitizers in non-radioisotopic local lymph node assay using flow cytometry.
Non-radioisotopic local lymph node assay (LLNA) using 5-bromo-2'-deoxyuridine (BrdU) with flow cytometry (FCM) is gaining attention since it is free from the regulatory issues in traditional LLNA (tLLNA) accompanying in vivo uses of radioisotope, (3)H-thymidine. However, there is also concern over compromised performance of non-radioisotopic LLNA, raising needs for additional endpoints to improve the accuracy. With the full 22 reference substances enlisted in OECD Test Guideline No. 429, we evaluated the performance of LLNA:BrdU-FCM along with the concomitant measurements of B/T cell ratio and ex vivo cytokine production from isolated lymph node cells (LNCs) to examine the utility of these markers as secondary endpoints. Mice (Balb/c, female) were topically treated with substances on both ears for 3 days and then, BrdU was intraperitoneally injected on day 5. After a day, lymph nodes were isolated and undergone FCM to determine BrdU incorporation and B/T cell sub-typing with B220+ and CD3e+. Ex vivo cytokine production by LNCs was measured such as IL-2, IL-4, IL-6, IL-12, IFN-γ, MCP-1, GM-CSF and TNFα. Mice treated with sensitizers showed preferential increases in B cell population and the selective production of IL-2, which matched well with the increases in BrdU incorporation. When compared with guinea pig or human data, BrdU incorporation, B cell increase and IL-2 production ex vivo could successfully identify sensitizers with the accuracy comparable to tLLNA, suggesting that these markers may be useful for improving the accuracy of LLNA:BrdU-FCM or as stand-alone non-radioisotopic endpoints.


Surgeon Volume and Social Disparity are Associated with Postoperative Complications After Lumbar Fusion.
To characterize the volume dependence of both facilities and surgeons on postoperative complications after lumbar fusion and characterize the role of socioeconomic status. Adults who underwent lumbar fusion from 2011 to 2015 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for lumbar disc degeneration or spondylolisthesis and procedure codes for lumbar fusion in the New York Statewide Planning and Research Cooperative System database. Complications were compared across surgeon and facility volumes using multivariable Cox proportional hazards regression, controlling for patient demographic and clinical factors. Surgeon and facility volumes were compared between the lowest and highest 20%. Of the 26,211 patients identified with a lumbar fusion, 16,377 patients were treated at a high-volume or low-volume facility or by a high-volume or low-volume surgeon. Low-volume facilities had higher 3-month and 12-month rates of readmission, pneumonia, and cellulitis; lower 1-month, 3-month, and 12-month rates of deep vein thrombosis; and lower 1-month rates of wound complications. Low-volume surgeons had higher 1-month, 3-month, and 12-month rates of readmission, acute renal failure, surgical site infection, and wound complications; high 1-month and 3-month rates of urinary tract infection and pulmonary embolism; and a lower 12-month rate of revision. Patients who were treated by low-volume surgeons and had complications were more concentrated to ZIP codes with high social deprivation. Both high-volume facilities and high-volume surgeons show lower rates of complications and readmission. There are significant socioeconomic disparities regarding which patients can access high-volume surgeons.


[Clinical diagnosis of thromboembolic complications. 125I fibrinogen test, thermography, ultrasound (author's transl)].
Early diagnosis of deep vein thrombosis (DVT) in all patients operated upon does not make sense. Prevention is better. Should dvt occur, phlebography is mandatory. The only other reliable objective method is the fibrinogen test, which is ideal for clinical research. Peripheral pulmonary emboli (pe) are more common than most people assume. Many are asymptomatic and lyse spontaneously, but often they are precursors of dangerous pe. Combined perfusion-ventilation scintigrams are often diagnostic. The combination of dyspnea, tachypnea, low pO2, and low pCO2 in the presence of a nearly normal chest X-ray makes a diagnosis of massive pe most likely. In all unclear situations pulmonary angiography is important.


A registry study of very low birthweight liveborn infants in Sweden, 1973-1988.
Very low birthweight liveborn infants (less than 1,500 g, VLBW) born in Sweden 1973-88 were identified from the Medical Birth Registry and efforts were made to remove wrongly recorded birthweights--9% of infants with a registered birth weight below 1,500 g were removed. Some VLBW infants were not recorded in the register and the estimate of the prevalence at birth of VLBW infants is therefore slightly underestimated. It increased from about 5.5 per 1,000 during the period 1973-84 to 6.7 per 1,000 during 1987-88. 18% of VLBW infants were involved in multiple births. Median Apgar score at 5 min increased for each 100 g birthweight class. Even at a birthweight between 1,400 and 1,499 g, a low Apgar score at 5 min was seen in 20%. The rate of cesarean section increased between 1973 and 1983 from about 10% to 60%. One-year survival for infants with a birthweight less than 1,000 g increased from less than 20% in 1973-75 to 50% in the 1986-88 cohorts. Corresponding figures for infants with a birthweight between 1,000 and 1,499 g were 60% and 90%. A markedly better one-year survival is already evident in the 600-699 g class. On stratifying for 100 g birthweight class, perinatal death risk was higher in boys than in girls and higher in multiple births than in singletons. An increased rate of congenital malformations was seen in the 1,000-1,499 g class but not in the less than 1,000 g class.


Delayed onset of insulin activation of the insulin receptor kinase in vivo in human skeletal muscle.
During the infusion of insulin in vivo, the rate of activation of glucose disposal lags significantly behind the rate of increase in serum insulin levels. To determine whether this delay was related to transcapillary transport of insulin, we determined increments in serum insulin levels, glucose disposal rates (GDR), and insulin receptor (IR) kinase activity measured during continuous infusions of insulin (40 and 120 mU.m-2.min-1) administered to 8 nondiabetic males; similar studies were done at 1,200.m-2.min-1 in 2 of the subjects. Half-maximal insulin levels were achieved at a mean of 4.9 and 7.2 min during the 40 and 120 mU.m-2.min-1 clamps, respectively, with corresponding half-maximal GDR stimulation at a mean of 59 and 47 min. Unlike the rise in insulin levels, IR kinase activation was much slower with half-maximal activity occurring at approximately 40-60 min in the 2 clamps. Thus, the rise in serum insulin levels in each clamp was much faster than the increment in either kinase activity or glucose disposal. Insulin infusion increased both IR kinase and GDR maximally approximately 10-fold, with half-maximal stimulation at approximately 3,600 and approximately 700 pM, indicating spare kinase for glucose disposal. These results demonstrate that the delay in stimulation of glucose disposal by insulin is related to a rate-limiting step between the intravascular space and the cell-surface of skeletal muscle. This may involve delayed transendothelial transport of insulin.


Vangl2 interaction plays a role in the proteasomal degradation of Prickle2.
The PET and LIM domain-containing protein, Prickle, plays a key role in planar cell polarity (PCP) in Drosophila. It has been reported that mutations in the PRICKLE2 gene, which encodes one of the human orthologues of Prickle, are associated with human diseases such as epilepsy and autism spectrum disorder. To develop preventive and therapeutic strategies for these intractable diseases, we studied the regulation of Prickle2 protein levels in transfected HEK293T cells. Prickle2 levels were negatively regulated by a physical interaction with another PCP protein, Van Gogh-like 2 (Vangl2). The Vangl2-mediated reduction in Prickle2 levels was, at least in part, relieved by proteasome inhibitors or by functional inhibition of the Cullin-1 E3 ubiquitin ligase. Furthermore, the expression of Vangl2 enhanced the polyubiquitination of Prickle2. This ubiquitination was partially blocked by co-expression of a ubiquitin mutant, which cannot be polymerised through their Lys48 residue to induce target proteins toward proteasomal degradation. Together, these results suggest that Prickle2 is polyubiquitinated by the Vangl2 interaction in a Cullin-1-dependent manner to limit its expression levels. This regulation may play a role in the local and temporal fine-tuning of Prickle protein levels during PCP signal-dependent cellular behaviours.


Studies on tRNA adaptation, tRNA turnover, precursor tRNA and tRNA gene distribution in Bombyx mori by using two-dimensional polyacrylamide gel electrophoresis.
Eighteen out of twenty amino acids have been used for identifying tRNAs from the silkworm Bombyx mori L. fractionated on two-dimensional polyacrylamide gel electrophoresis. 43 spots out of 53 have been identified. This mapping confirms previous results and brings new answers to some questions on the regulation of tRNA biosynthesis. 1. In addition to quantitative adaptation of tRNAs to the composition of silk proteins (fibroin from the posterior silk gland, sericin from the middle part) and of iso-tRNAs from posterior silk gland to the major codons of fibroin mRNA, we also observe adaptation of tRNA from various tissues to the average amino acid content of proteins from fat body, gut, gonads and carcass of the silkworm. 2. In the silk gland, turnover rates of several tRNA species are similar. The selective accumulation of tRNAs needed for decoding fibroin and sericin mRNAs which takes place during the Vth larval instar, cannot be explained by the occurrence of a preferential degradation of some tRNA species. 3. Under given conditions for incubating silk glands, it is possible to obtain an accumulation of precursor tRNA species, which are enriched in pre-tRNAAla and pre-tRNAGly in the posterior silk gland and pre-tRNASer in the middle part. 4. The distribution of tRNA genes is not random. tRNA genes for glycine, alanine and serine are prominent. Selective transcription of batteries of iso-tRNA genes could explain our data.


Catalase active metal-organic framework synthesized by ligand regulation for the dual detection of glucose and cysteine.
Mimic enzymes greatly improve the inherent insufficiencies of natural enzymes. Therefore, mimic enzyme sensors attract increasing research interest. Metal-organic framework (MOF) is emerging in the field of mimic enzyme catalysis due to its remarkable structural properties. In this paper, a colorimetric method is designed for rapid and sensitive detection of glucose and cysteine levels. The MOF Eu-pydc (pydc-2,5-pyridinedicarboxylic acid) is synthesized by a new strategy which is regulated by ligands at room temperature and found to have peroxidase activity. Then, the MOF is used as a mimic enzyme to catalyze chromogenic substrate (3,3',5,5'-tetramethylbenzidine, TMB) for colorimetric sensing of glucose. The developed method can accurately detect glucose in the range of 10 μM-1 mM (R2 = 0.9958) with a relatively low detection limit about 6.9 μM. Moreover, a cysteine sensor with a detection limit of 0.28 μM is also established based on the disappearance of the color of oxTMB. Additionally, the proposed glucose sensor exhibits excellent selectivity and is successfully applied to blood glucose detection. At the same time, the detection of cysteine is also highly sensitive. In short, the dual sensor is fast, low cost, and convenient, and has great application potential in the diagnosis of disease.


Three newly delimited species of Saccharomyces sensu stricto.
Deoxyribonucleic acid reassociation studies of 24 different wine and beer-associated strains of Saccharomyces confirmed the presence of three separate species. S. cerevisiae and S. bayanus strains had only 22% of their genomes in common. S. pastorianus, with intermediate hybridization values between S. cerevisiae and S. bayanus (52 and 72%, respectively) could possibly be a natural hybrid of the two species. S. pastorianus replaces S. carlsbergensis with which it is homologous for 93% of its genome, since the former species was described first by Hansen in 1904. These data do not agree with the results of traditional physiological tests.


The presence of persistent symptoms 12 months following a first lateral ankle sprain: A systematic review and meta-analysis.
A lateral ankle sprain (LAS) is the most common musculoskeletal injury in the physically active population. It is uncertain what percentage of these patients develop persisting symptoms including pain, recurrent sprains and subjective instability. This systematic review was conducted to assess the presence and duration of persistent symptoms after a first LAS. A systematic review of the Medline, Web of Sciences, Embase, CINAHL and Pedro databases was performed to identify peer-reviewed articles concerning the occurrence and duration of remaining symptoms after a first LAS. Inclusion criteria focused on selection of patients without previous ankle injuries and study quality. One of the following outcomes had to be described: subjective instability, resprains, remaining symptoms. In total, 15 studies were included. The occurrence of patients with subjective instability decreased from 37.9% (95%CI [6.0-69.7]) at 3 months to 16.1% (95%CI [7.8-24.3]) at 6 months and 8.1% (95%CI [3.3-13.3]) at 12 months. The occurrence of patients with a recurrent LAS was 15.8% (95%CI [6.3-25.3]) at 12 months. The occurrence of patients with residual pain decreased from 48.6% (95%CI [23.6-73.5]) at 3 months, to 21.5% (95%CI [2.8-40.2]) at 6 months and 6.7% (95%CI [3.2-10.1]) at 12 months. This study offers new insights in the presence of remaining symptoms after a first LAS and the development of chronic ankle instability. Twelve months following an initial LAS, a significant number of patients may still have symptoms. The incidence of subjective instability, and pain, continues to decrease until 12 months post-injury. This new information may suggest that a longer period of non-operative treatment may be warranted before recommending surgical intervention in patients with a first LAS.


Acute Gastroenteritis Disease Burden in Infants With Medical Risk Conditions in the Netherlands.
Infants with medical risk conditions are vulnerable to childhood infections including acute gastroenteritis (AGE). To guide prevention programs, we quantified AGE incidence, severity and virus prevalence among medical risk infants in the Netherlands. This prospective cohort-study was part of the RIVAR-project recruiting infants with prematurity, low birth weight or severe congenital conditions in 13 hospitals. Follow-up included 18 monthly health questionnaires detailing AGE symptoms and healthcare usage. Parents were also instructed to notify when an infant developed AGE, to collect a stool sample and complete a daily severity score (Modified Vesikari Severity). Stool samples were analyzed by real-time polymerase chain reaction for rotavirus, norovirus, adenovirus and astrovirus. Between November 2014 and October 2017, 631 infants participated during 9125 person-months of observation. In total, 559 episodes were identified. The mean AGE incidence rate was 73.5 per 100 person-years (PY) (95% confidence interval: 67.6-79.9) and increased with age [incidence rate: 48.3 (39.8-58.3) vs. 80.2 (73.0-88.1)/100 PY for ages 1-5 vs. 6-18 months, respectively]. Healthcare was attended for 38.1% (213/559) and 26.8% (68/254) were classified as severe based on the Modified Vesikari Severity. Stool samples were obtained from 254 AGE episodes. Norovirus was identified in 65 (25.6%) and rotavirus in 44 (17.7%). Adenovirus and astrovirus together accounted for 8.3% (N = 21). Severe AGE occurred most frequently in rotavirus positive episodes. The observed AGE incidence, severity and healthcare usage among medical risk infants confirms substantial disease burden. Norovirus and rotavirus are the dominant pathogens and severe episodes occurred most frequently in children with rotavirus infection. AGE prevention in medical risk infants should be prioritized.


Global organization of metabolic fluxes in the bacterium Escherichia coli.
Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalysed biochemical reactions, is the most investigated complex intracellular web of molecular interactions. Although the topological organization of individual reactions into metabolic networks is well understood, the principles that govern their global functional use under different growth conditions raise many unanswered questions. By implementing a flux balance analysis of the metabolism of Escherichia coli strain MG1655, here we show that network use is highly uneven. Whereas most metabolic reactions have low fluxes, the overall activity of the metabolism is dominated by several reactions with very high fluxes. E. coli responds to changes in growth conditions by reorganizing the rates of selected fluxes predominantly within this high-flux backbone. This behaviour probably represents a universal feature of metabolic activity in all cells, with potential implications for metabolic engineering.


Management of intra-abdominal organ injury following blunt abdominal trauma in children.
To evaluate the strategy of a combined diagnostic and therapeutic approach in children with intra-abdominal organ injury following blunt abdominal trauma. Retrospective clinical study. Pediatric intensive care unit of an university hospital. 38 children with documented intra-abdominal injury. Initial non-surgical treatment by a team of pediatric intensivists, radiologists and surgeons. Physical examination, oriented blood and urine tests, plain abdominal film, abdominal ultrasound (US) and computed tomography (CT) with contrast. US documented intra-abdominal fluid in 30 and initial organ lesion in 14 out of 31 patients evaluated. Abdominal CT demonstrated the precise organ lesion in 34 out of 36 patients examined with solid organ lesion. Early laparotomy was needed in 7 because of severe shock, pneumoperitoneum and ruptured diaphragm, and delayed surgery in 6 patients. All 38 patients regained a normal life. The stepped diagnostic approach combined with initial non-surgical treatment by a team provided accurate diagnosis and appropriate treatment. Abdominal US, by demonstrating free intra-abdominal fluid is very sensitive to detect patients with intra-abdominal organ injury, CT scan with contrast is needed to give precise information of specific organ lesions.


Molecular and phenotypic variation in the achaete-scute region of Drosophila melanogaster.
Variation in quantitative characters underlies much adaptive evolution and provides the basis for selective improvement of domestic species, yet the genetic nature of quantitative variation is poorly understood. Many loci affecting quantitative traits have been identified by the segregation of mutant alleles with major qualitative effects. These alleles may represent an extreme of a continuum of allelic effects, and most quantitative variation could result from the segregation of alleles with subtle effects at loci identified by alleles with major effects. The achaete-scute complex in Drosophila melanogaster plays a central part in bristle development and has been characterized at the molecular level. The hypothesis that naturally occurring quantitative variation in bristle number could be associated with wild-type alleles of achaete-scute was tested by correlating phenotypic variation in bristle number with molecular variation in restriction maps in this region among chromosomes extracted from natural populations. DNA insertion variation in the achaete-scute region was found to be strongly associated with variation in bristle number.


A prospective study of BCG given to young children in Agra, India--a region of high contact with environmental mycobacteria.
A multiple skin test survey of school children (aged 5-15 years) living in Agra, India showed very high levels of sensitisation to numerous species of mycobacteria and little difference in tuberculin positivity between those with and without BCG scars. A total of 136 children aged 3 months to 8 years, living in Agra, were skin tested with Tuberculin and Leprosin A and examined for scars of previous BCG vaccination. Of those who had not previously received BCG and who had responses to Tuberculin of zero or less than 5 mm induration, 109 were offered BCG vaccination: 107 accepted and as many of them as possible were followed up with repeat skin testing 1 and 2 years later. The results are discussed in relation to the background of environmental sensitisation. A comparison is made with the data obtained from other places, particularly the Lebanon, where there is little sensitisation from the environment. Although the high level of Tuberculin conversion achieved after BCG suggested that the vaccine might have an important protective effect, the large size of Tuberculin responses in comparison with those obtained in the UK was worrying. Evidence was obtained suggesting that sensitisation to mycobacteria may occur in very young children which is not detected by the Tuberculin test, but which influences responses to BCG vaccination.


Sign in, time out, sign out checklist-changing practice through interdepartmental teamwork to improve safety at caesarean section.
Three similar clinical incidences over a three-month period highlighted an issue with the readiness and availability of neonatal resuscitation personnel and equipment at the time of caesarean section (CS). This identified a potential risk to the wellbeing of the mother and baby that had to be addressed. A joint venture was undertaken with the maternity and theatre directorates. A maternity-specific checklist in use in the UK maternity services was sourced, adapted and implemented. No further incidents have been reported since with resulting overall enhanced safety of pregnant women and newborn babies in the unit.


Parent-collected respiratory specimens--a novel method for respiratory virus and vaccine efficacy research.
Population-based respiratory research and vaccine efficacy studies have previously required clinic or home visits when a subject had an acute respiratory illness. This method may mean parents are unwilling to enroll their child or report an illness of interest. We conducted a community-based cohort study into respiratory illnesses in 234 pre-school aged children using parent-collected specimens. Between January 2003 and January 2004 there were 563 specimens collected from 730 identified illnesses and these were tested using a panel of respiratory virus polymerase chain reaction (PCR) assays; 409 (73%) were positive for any virus. Specimens were not more likely to be positive when collected by a healthcare worker parent, when they included a throat swab, or when a very good collection technique was reported. A delay from illness onset to specimen collection of up to 5 days did not appear to impact on sensitivity of virus identification, but a delay of six or more days with minor delays in testing saw positivity fall. Combined with daily symptom diary completion and PCR testing, parent-collected specimens are an efficient and acceptable method for the conduct of future vaccine efficacy studies and other community-based respiratory virus research.


A 4-base pair deletion in the mitochondrial cytochrome b gene associated with parkinsonism/MELAS overlap syndrome.
Five patients with diminished activity of complex III of the mitochondrial respiratory chain have been screened for mutations in the mitochondrial cytochrome b (cyt b) gene. In 1 patient, a young boy with an akinetic rigid syndrome and a mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), a novel 4-base pair deletion was identified. This mutation in this highly conserved gene is considered to be pathogenic since it is a heteroplasmic frame shift mutation predicted to lead to a truncated protein.


Development of valid pulmonary function equations for trained athletes.
The validity of commonly recommended pulmonary function prediction equations (Bulletin Européen de Physiopathologie Respiratoire, Clinical Respiratory Physiology) was tested with two samples (n1 = 156; n2 = 218) of well-trained athletes. Pulmonary function measures (FVC, TLC, RV, FEF25%-75%, FEV1.0, PEF, RV/TCL ratio, FEV1.0/FVC ratio) were typically very reliable but inaccurately predicted with recommended equations based upon anthropometric characteristics. Newly developed "unisex" regression equations were developed with "dummy" coding of gender (i.e., 0 = female; 1 = male), age, height, weight, and various interactions. The new equations were validated with a subsample of group one, cross-validated with the remaining portion of group one, and then cross-validated again with the 218 subjects from sample two. The newly created pulmonary function prediction equations are more valid for well-trained athletes than the equations in use for the general population.


Insights into the degradation of chlorimuron-ethyl by Stenotrophomonas maltophilia D310-3.
In this study, the effects of cultivation conditions on the degradation of chlorimuron-ethyl by Stenotrophomonas maltophilia D310-3, which exhibits a high chlorimuron-ethyl-degrading capability, were investigated. To improve the biodegradation efficiency, the cultivation conditions were optimized using response surface methodology (RSM) based on Box-Behnken design (BBD). The maximum biodegradation rate (89.9%) was obtained at the optimal conditions (culture time, 6 d; substrate concentration, 50.21 mg L(-1); pH, 5.95; temperature, 30.15 °C). The Andrews model was used to describe the dynamic change regularity of the specific degradation rate as the substrate concentration increased, and the values of the maximum specific degradation rate (q(max)), half-saturation constant (K(S)) and inhibition constant (K(i)) were 78.87 d(-1), 9180.97 mg L(-1) and 0.28 mg L(-1), respectively. Eight degradation products were captured and identified by liquid chromatography-mass spectrometry (LC-MS) and Fourier transform infrared (FTIR) spectrometry, and three possible degradation pathways are proposed based on the results of high-performance liquid chromatography (HPLC), LC-MS and FTIR analyses as well as results reported in relevant literature. To the best of our knowledge, this is the first systematic study of the degradation pathway of chlorimuron-ethyl by S. maltophilia D310-3. This study provides valuable information for further exploration of the microbial degradation of other sulfonylurea herbicides.


Trace elements and human health risks assessment of finer aerosol atmospheric particles (PM1).
The present study investigated PM1 (aerosol particles with an aerodynamic diameter ≤ 1.0 μm) mass concentrations and sixteen (Al, Ca, Cd, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni, Pb, S, Ti, and Zn) PM1-related trace elements. PM1 samples were collected in an anthropized area of international attention close to oil/gas pre-treatment plants in Agri Valley (Southern Italy). The PM1 mass concentrations varied from 3 to 16 μg/m3. The decreasing pattern of the trace element concentrations was S > Ca > Na > K ≈ Mg ≈ Fe> Al > Li > Cr > Zn > Ti> Cu > Ni ≈ Mn > Pb ≈ Cd. Anthropogenic local emissions such as biomass burning, vehicular traffic, and industrial sources mainly related to oil/gas pre-treatment plants were identified by the principal component analysis. Further, air mass back-trajectory analyses suggest an important contribute to the long-range transport on PM1 at Agri Valley. The carcinogenic (Cd, Cr(VI), Ni, and Pb) and non-carcinogenic (Cd, Cr(VI), Cu, Mn, Ni, Pb, and Zn) health risks both for children and for adults were assessed using the United State Environmental Protection Agency (USEPA) methods considering inhalation, ingestion, and dermal contact pathway. Chromium (VI) posed the highest carcinogenic risk for both children and adults. The integrated carcinogenic risks were respectively 3.45 × 10-5 and 1.38 × 10-4 for children and adults indicating that attention should be paid for carcinogenic health effects. Nickel posed the highest non-carcinogenic risk for children through inhalation pathway. The integrated non-carcinogenic risk showed a value higher than 1 highlighting that Cd, Cr(VI), Cu, Mn, Ni, Pb, and Zn may cause cumulative non-carcinogenic health effect for children from inhalation exposure.


Antibiotic Resistance of Acinetobacter baumannii in Iran: A Systemic Review of the Published Literature.
Acinetobacter baumannii is a bacterium responsible for health care-associated infections, and it frequently develops multiple drug resistance (MDR). The prevalence of antibiotic-resistant A. baumannii in Iran has increased, and this may cause significant clinical problems. Therefore, in order to elucidate the development of antibiotic resistance, we performed a systematic review of the literature published on antibiotic-resistant A. baumannii reported in Iran. Thirty-six publications that met the criteria for inclusion were reviewed from an initial 87 papers. Selected papers published between 2008 and September 2014, were categorized on the basis of the sample collecting year been between 2001 and 2013. Analysis of data revealed that, in general, there was an increase in antimicrobial resistance. During the initial time point of these studies (2001-2007) there was a high rate of resistance to all antibiotics, with the exception of carbapenems, lipopeptides, and aminoglycosides that had a low resistance rate in comparison with the others. Also, the resistance rate was increased in one group of these three antimicrobial groups from 2010 to 2013. In particular, there was an increase in resistance to carbapenems (imipenem and meropenem) from 2010-2011 and 2012-2013, whereas no significant change in the resistance rate of the other two antimicrobial groups (lipopeptides and aminoglycosides) during the study time was observed, although we did observe certain trends in amikacin (aminoglycoside group antibiotic) between 2011-2012 and 2012-2013. These findings indicate that antimicrobial resistance of A. baumannii in Iran has increased, which may very well affect the antimicrobial resistance of this organism worldwide. Based on these results, novel prevention and treatment strategies against A. baumannii infections are warranted. Furthermore, these data may assist in revising treatment guidelines and regional policies in care units to slow the emergence of antimicrobial resistance.


Open-to-Air RAFT Polymerization on a Surface under Ambient Conditions.
Oxygen (O2)-mediated controlled radical polymerization was performed on surfaces under ambient conditions, enabling on-surface polymer brush growth under open-to-air conditions at room temperature in the absence of metal components. Polymerization of zwitterionic monomers using this O2-mediated surface-initiated reversible addition fragmentation chain-transfer (O2-SI-RAFT) method yielded hydrophilic surfaces that exhibited anti-biofouling effects. O2-SI-RAFT polymerization can be performed on large surfaces under open-to-air conditions. Various monomers including (meth)acrylates and acrylamides were employed for O2-SI-RAFT polymerization; the method is thus versatile in terms of the polymers used for coating and functionalization. A wide range of hydrophilic and hydrophobic monomers can be employed. In addition, the end-group functionality of the polymer grown by O2-SI-RAFT polymerization allowed chain extension to form block copolymer brushes on a surface.


Prevalence of and prevention for work-related upper limb disorders among physical therapists: a systematic review.
Physical therapists (PTs) are at increased risk for development of work-related upper limb disorders (WRULDs) due to the physically intensive, constant hands-on nature of the profession. The objectives of this systematic review were to examine the literature on WRULDs among PTs, specifically the (1) 1-year prevalence, (2) workplace risk factors, (3) consequences, and (4) coping strategies utilized to mitigate WRULDs. A comprehensive search of the literature was performed using PubMed, CINHAL, EMBASE, and Google Scholar. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for conducting this systematic review. Studies that reported the 1-year prevalence of WRULDs among PTs, workplace risk factors for WRULDs, consequences of WRULDs, and coping strategies utilized by PTs were included. Twelve studies met the inclusion criteria. The 1-year WRULDs prevalence rates varied widely, with thumb disorders having the highest prevalence (7.6-52.5%), followed by wrist and hand disorders (5-66.2%), shoulder disorders (3.2-45.2%), and elbow disorders (4-16%). Reported risk factors included treating a high volume of patients and frequent performance of manual therapy techniques. Consequences included interference with PTs' personal and professional activities while coping strategies involved alterations to the work environment, techniques used, and workload. WRULDs remain a persistent threat to the PT workforce, likely due to the hands-on, physically intensive nature of professional activities. An essential strategy to reduce WRULDs is to improve clinicians' awareness of WRULDs, workplace risk factors, and subsequent consequences of WRULDs. Effective coping strategies are critical to preserve, protect, and prolong PTs' use of the upper limbs.


Sourdough microbial community dynamics: An analysis during French organic bread-making processes.
Natural sourdoughs are commonly used in bread-making processes, especially for organic bread. Despite its role in bread flavor and dough rise, the stability of the sourdough microbial community during and between bread-making processes is debated. We investigated the dynamics of lactic acid bacteria (LAB) and yeast communities in traditional organic sourdoughs of five French bakeries during the bread-making process and several months apart using classical and molecular microbiology techniques. Sourdoughs were sampled at four steps of the bread-making process with repetition. The analysis of microbial density over 68 sourdough/dough samples revealed that both LAB and yeast counts changed along the bread-making process and between bread-making runs. The species composition was less variable. A total of six LAB and nine yeast species was identified from 520 and 1675 isolates, respectively. The dominant LAB species was Lactobacillus sanfranciscensis, found for all bakeries and each bread-making run. The dominant yeast species changed only once between bread-making processes but differed between bakeries. They mostly belonged to the Kazachstania clade. Overall, this study highlights the change of population density within the bread-making process and between bread-making runs and the relative stability of the sourdough species community during bread-making process.


Allogeneic stem cell transplantation.
Allogeneic stem cell transplantation (HSCT) requires the harvest of an adequate number of stem cells (SC) from a histocompatible donor and their infusion into a patient following a conditioning regimen. During the past 35 years, the role of HSCT has changed from an experimental procedure for terminally ill patients to a curative treatment. In 2003, 1170 procedures were registered in Italy (Italian Group for Blood and Marrow Transplantation). The main reported indications were as follows: leukemia, lymphoproliferative diseases, myelodysplasia, and nonmalignant diseases such as thalassemia and severe aplastic anemia. Important changes have been observed in the last 5 years: the shift from bone marrow to peripheral blood as the SC source, the increasing number of alternative donors such as unrelated, partially matched family donors and cord blood SC, and the new extra-hematological indications including solid tumors. Moreover, the development of nonmyeloablative conditioning regimens have allowed physicians to perform HSCT in patients with advanced age or important comorbidities. In contrast, the availability of the Tyrosine kinase inhibitor (STI-571) for treatment of patients affected by chronic myelogenous leukemia, which was formerly the main indication for HSCT, has produced a dramatic decrease in the number of transplantations in this setting. HSCT performed in the early phases of disease and in young patients offers more than a 50% cure rate. The transplant-related mortality still represents the greatest obstacle, ranging from 20%-30%, despite the less toxic conditioning regimens, high-resolution HLA typing, and better supportive care. GvHD and infections remain the main causes of morbidity. As regards relapses, they correlate with disease status at the time of transplantation. Promising results have been recently obtained with haploidentical and with cord blood SC transplantation also in adult patients.


Medical management of osteoarthritis of the knee and hip joints.
Osteoarthritis is a common, chronic condition which requires an individualised management plan involving multiple kinds of treatment. Exercise programs and the Arthritis Self-Management Program reduce pain and disability associated with osteoarthritis. Paracetamol is the most appropriate first-line analgesic. Non-steroidal anti-inflammatory drugs may be used as second-line analgesia on an as-needed basis (including continuous use), but must be used with caution. Cyclo-oxygenase-2-specific inhibitors are used if there are risk factors for upper-gastrointestinal complications, but only after considering cardiovascular risk. Glucosamine sulfate is a safe and effective over-the-counter treatment. Intra-articular therapies are used when others have failed.


Antibody response elicited against empty reticuloendotheliosis virus particles in two inbred lines of chicken.
Immunisation of Houghton White Leghorn line 15I and 6(1) chickens with empty reticuloendotheliosis virus particles elicited a primary antibody response which is probably directed against the viral envelope glycoproteins gp73/71 and gp22. Antibodies in line 15I birds were shown to be non-neutralising and did not protect against the tumourigenic effects of reticuloendotheliosis virus, strain T. However, immunised line 6(1) chicks did not exhibit the runting syndrome associated with reticuloendotheliosis virus infection, suggesting that antibody against viral coat proteins may play a role in modulating pathogenesis in certain lines of chicken.


Lung function at one month of age as a risk factor for infant respiratory symptoms in a high risk population.
Abnormal premorbid lung function is a risk factor for subsequent wheezing in children with one or no atopic parent. This study was undertaken to establish whether early lung function in high risk infants (both parents atopic) was a risk factor for respiratory symptoms in infancy and to examine the influence of maternal asthma, smoking, and allergen exposure during pregnancy on any association. Infants were recruited from the NAC Manchester Asthma and Allergy Study cohort at birth. Partial forced expiratory flow volume technique under sedation was carried out to determine maximal flow at FRC (V'maxFRC). Children were followed prospectively and parents completed a standard respiratory questionnaire at one year of age. Sixty nine term infants (34 boys; 88% mothers non-smokers; no household pets) underwent respiratory function testing. Size adjusted V'maxFRC was significantly lower in infants who had recurrent wheeze during the first year of life (mean 1.3 ml/s/cm, 95% CI 0.99 to 1.60) than in those who did not (mean 2.03 ml/s/cm, 95% CI 1.71 to 2.36; p=0.01). V'maxFRC was also significantly lower in infants who had recurrent cough symptoms. In multivariate regression analysis, when adjusted for age at test, sex, maternal asthma, smoking and maternal mattress Der 1 levels, a lower size adjusted V'maxFRC score remained strongly associated with wheezing (OR 0.37, 95% CI 0.18 to 0.77, p=0.007). Maternal smoking also remained an independent risk factor (OR 29.85, 95% CI 2.46 to 362.5, p=0.008). Significantly diminished lung function was present in high risk infants who subsequently wheezed and coughed. This was independent of maternal exposure to mite allergen, asthma, and smoking during pregnancy.


The prognostic value of high-density lipoprotein cholesterol in patients with decompensated cirrhosis: a propensity score matching analysis.
Emerging evidence has implicated that high-density lipoprotein cholesterol (HDL-C) as a prognostic surrogate in the context of cirrhosis. However, an exact cutoff has not been fully elucidated. We aimed to clarify optimal cutoff of HDL-C for short-term mortality based on time-to-event analysis and validated this association by performing propensity score matching (PSM) analysis. A total of 238 patients with decompensated cirrhosis were enrolled. The optimal cutoff of HDL-C was initially determined by X-tile program. Independent risk factors for 180-day mortality were identified by multiple Cox regression. The Kaplan-Meier method was implemented to generate survival curves. A 1:2 ratio PSM was performed to diminish selection bias and potential confounders. The X-tile implied that the difference in survival was most significant for HDL <0.4mmol/L (<16mg/dL). Circulating HDL <0.4mmol/L exhibited an independent risk factor both in the entire cohort and PSM subset (HR 2.696, 95% CI 1.082-6.791, P = 0.033; HR 2.735, 95% CI 1.027-7.734, P = 0.048). Furthermore, HDL-C combined with conventional scoring systems had higher AUCs associated with poor prognosis than Child-Pugh classification or model for end-stage liver disease (MELD) in isolation (0.78 vs 0.66; 0.74 vs 0.54, P < 0.05 for both). HDL-C <0.4 mmol/L may serve as a readily available and robust cutoff for stratifying cirrhotic patients at high 180-day mortality risk. The incorporation of HDL-C to Child-Pugh classification or MELD has the potentials to provide substantially clinical relevance without extra economic cost.


Charcoal burning and maternal filicide-suicide trends in Taiwan: the impact of accessibility of lethal methods.
Charcoal burning has emerged as a novel suicide method in Taiwan and its impact on maternal filicide-suicide (MFS) remains unexplored. Using official national mortality data and reports of MFS cases from electronic newspaper archives, the authors aimed to examine whether the newly available charcoal burning was associated with an increase in MFS incidents during the period from 1999 to 2006. The trends for changes in age/gender/method-specific suicide rates and MFS incidence were analyzed and then correlated with each other. The results indicated that charcoal burning was the leading method of filicide in reported MFS incidents. The increase in MFS incidents paralleled that of charcoal burning-specific suicide rates in females aged 25-44 years, while suicide rates by other methods did not change significantly. Easy accessibility and perceived painlessness as conveyed by the media might account for the choices of charcoal burning for MFS. Restricting access to charcoal burning should therefore be prioritized for further prevention strategies.


Bombyx batryticatus extract activates coagulation factor Ⅻ to promote angiogenesis in rats with cerebral ischemia/reperfusion injury.
Bombyx batryticatus is traditionally used to treat patients with stroke, but its mechanism remains unclear. To explore the interventional effect of Bombyx batryticatus extract as an activator of FⅫ on angiogenesis of rats with cerebral ischemia/reperfusion injury. Firstly, the mechanism of Bombyx batryticatus interfering with IS was predicted by systematic pharmacology method, and then it was further verified by animal experiments. The effects of Bombyx batryticatus extract on plasma coagulation were detected, and the activation of coagulation factor Ⅻ (FⅫ) and its downstream substrate kallikrein kinase (KK) was detected in vitro. The brain morphology and expressions of FXII, KK, vascular endothelial growth factors (VEGF), CD31, Brdu/von Willebrand Factor (vWF) were detected. The morphological changes, cell proliferation and VEGF expression of brain microvascular endothelial cells were detected by oxygen glucose deprivation model. The pharmacodynamic substances of Bombyx batryticatus extract were identified by Liquid Chromatography - Mass Spectrometry (LC-MS). The results of systematic pharmacology found that the treatment of IS by Bombyx batryticatus may be related to blood coagulation and other processes. In vitro, Bombyx batryticatus extract prolonged the activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) (P < 0.05), activated FⅫ and promoted the production of downstream substrate KK, with dose-dependent (P < 0.05). Bombyx batryticatus extract improved the neuronal damage of rats, activated FXII and increased the production of KK and the expressions of VEGF, CD31, Brdu/vWF (P < 0.05). Bombyx batryticatus extract also increased the proliferation of brain microvascular endothelial cells and expression of VEGF in rats (P < 0.05). A total of 809 metabolites in Bombyx batryticatus extract were identified by LC-MS. Bombyx batryticatus extract may ameliorate the injury of nerve function in rats with cerebral ischemia/reperfusion injury.


WOANet: Whale optimized deep neural network for the classification of COVID-19 from radiography images.
Coronavirus Diseases (COVID-19) is a new disease that will be declared a global pandemic in 2020. It is characterized by a constellation of traits like fever, dry cough, dyspnea, fatigue, chest pain, etc. Clinical findings have shown that the human chest Computed Tomography(CT) images can diagnose lung infection in most COVID-19 patients. Visual changes in CT scan due to COVID-19 is subjective and evaluated by radiologists for diagnosis purpose. Deep Learning (DL) can provide an automatic diagnosis tool to relieve radiologists' burden for quantitative analysis of CT scan images in patients. However, DL techniques face different training problems like mode collapse and instability. Deciding on training hyper-parameters to adjust the weight and biases of DL by a given CT image dataset is crucial for achieving the best accuracy. This paper combines the backpropagation algorithm and Whale Optimization Algorithm (WOA) to optimize such DL networks. Experimental results for the diagnosis of COVID-19 patients from a comprehensive COVID-CT scan dataset show the best performance compared to other recent methods. The proposed network architecture results were validated with the existing pre-trained network to prove the efficiency of the network.


A woman's build and the risk of breast cancer.
A woman's build and the risk of breast cancer seem to be related. While relative overweight, as described by the body mass index, seems to be associated with increased breast cancer risk in postmenopausal women, overweight in premenopausal women seems slightly protective. Papers from a MEDLINE search are reviewed regarding the association between build and the development of breast cancer. Different aspects of build, such as height, weight, body mass index and body shape, are discussed. The more prominent associations found through this search are a positive association between height and breast cancer risk both in pre- and postmenopausal women. Regarding body mass index, the association is negative in premenopausal women and positive in postmenopausal women. Body shape described as masculine versus feminine seems to have no impact on breast cancer risk in premenopausal women, but seems to be positively associated with breast cancer in postmenopausal women. Possible biological mechanisms responsible for the associations with breast cancer risk are discussed, including endogenous oestrogens, androgens and glucose metabolic substances. Avoiding or reducing postmenopausal overweight may modify breast cancer risk indicators in a more favourable direction.


Characteristics of cathepsin members and expression responses to poly I:C challenge in Pacific cod (Gadus macrocephalus).
Cathepsins are major lysosomal enzymes that participate in necessary physiological processes, including protein degradation, tissue differentiation, and innate or adaptive immune responses. According to their proteolytic activity, vertebrate cathepsins are classified as cysteine proteases (cathepsins B, C, F, H, K, L, O, S, V, W, and X or Z), aspartic proteases (cathepsin D and E), and serine proteases (cathepsin A and G). Several cathepsins were reported in teleosts, however, no cathepsin gene has been identified from Pacific cod so far. In the present study, a total of 13 cathepsin genes were identified for Pacific cod. The evolutionary path of each cathepsin gene was demonstrated via analysis of phylogenetic trees, multiple alignments, conserved domains, motif compositions, and tertiary structures. Tissue distribution analysis showed that all cathepsin genes were ubiquitously expressed in eight healthy tissues but they exhibited diverse levels of expression. Several cathepsin genes were found to be highly expressed in the kidney, spleen, head kidney and liver, whereas low or modest levels were detected in the gills, skin, intestines, and heart. Temporal-specific expression of cathepsins in early developmental stages of Pacific cod were also conducted. CTSK, S, F, and Z were highly expressed at 1 dph and 5 dph and decreased later, while CTSL, L1, and L.1 transcript levels gradually increased in a time-dependent manner. Additionally, the expression profiles of cathepsin genes in Pacific cod were evaluated in the spleen and liver after poly I:C challenge. The results indicated that all cathepsin genes were significantly upregulated upon poly I:C stimulation, suggesting that they play key roles in antiviral immune responses in Pacific cod. Our findings establish a foundation for future exploration of the molecular mechanisms of cathepsins in modulating antiviral immunity in Pacific cod.


Nectar source distribution as a determinant of oviposition host species in Euphydryas chalcedona.
The distribution of nectar sources is shown to affect both the distribution of adult Euphydryas chalcedona and their offspring. We suggest that nectar sources thereby influence the selection of oviposition host plant species in habitats where those species are spacially separated.


Organotin compounds: an ionophore system for fluoride ion recognition.
Ion-selective properties were established for membrane electrodes prepared by using organotin compounds of type (L(CN)RSnF2)n, (R=n-Bu (I),=Ph (II)) and (L(CN)SnF3)n (III) (L(CN)=C(6)H4(CH2NMe2)-2). Electrodes formulated with the optimized membranes containing the organotin compounds I-III as ionophores and sodium tetraphenylborate (10-30%) exhibited high selectivity for fluoride over other anions. An electrode prepared with ionophore II using dibutyl phthalate as the plasticizer and 15% sodium tetraphenylborate (NaTPB) as anion additive, possesses the best potentiometric response characteristics. It shows a detection limit of 7.9 x 10(-7) M with a slope of 62.7 mV decade(-1) of activity in buffer solutions of pH 5.5. The interference from other anions is suppressed under this optimized measurement conditions. An entirely non-Hofmeister selectivity sequence (F->CH3COO->Cl->I- approximately Br->ClO4->NO2->NO3->SCN-) with remarkable preference towards fluoride is obtained. The influence on the electrode performances by anion additive was studied, and the possible response mechanism was investigated by UV-vis spectra. The electrode has been used for direct determination of fluoride in drinking mineral water with satisfactory results.