Genetic Polymorphism of CAT C-262 T and Susceptibility to Breast Cancer, a Case-Control Study and Meta-Analysis of the Literatures.
Catalase (CAT) activity is likely to be affected by functional polymorphism of C-262 T (rs1001179) in the CAT gene (OMIM: 115500). It is hypothesized that individuals with the lower expressing forms of the CAT polymorphism may be more susceptible to breast cancer. Therefore, the present case-control study and meta-analysis were carried out. The present case-control study consisted of 407 females with breast cancer and a total of 395 healthy female from population matched with patients according to age. Genotypic analysis for the CAT C-262 T polymorphism was determined by PCR. We identified 7 eligible studies, including 10,471 subjects (4,959 patients, and 5,512 healthy controls) in relation to the CAT C-262 T polymorphism and breast cancer risk. Based on the present case-control study, the CT (OR = 0.90, 95% CI: 0.66-1.22, P = 0.484) and TT (OR = 0.68, 95% CI: 0.35-1.30, P = 0.245) genotypes were not associated with breast cancer risk compared to the CC genotype. For meta-analysis including all studies, there was significant heterogeneity between studies. The overall ORs of the breast cancer risk were not associated with the CT (Q-statistic = 14.90, df = 6, P < 0.05; OR = 1.01, 95% CI: 0.92-1.09, P = 0.862) and TT (Q-statistic = 2.57, df = 6, P > 0.05; OR = 1.03, 95% CI: 0.85-1.24, P = 0.770) genotypes. There was no association between C-262 T polymorphism of the CAT and risk of breast cancer.


Longitudinal assessment of immunological status and rate of immune recovery following treatment in children with ALL.
We prospectively evaluated the immunological status, immune recovery and risk of infection in pediatric ALL patients treated on the BFM 95 protocol. Humoral and cellular immunity were evaluated in 72 children with ALL at the end of intensive therapy and values were compared to those at the completion of therapy and 6-monthly. Parameters investigated included lymphocyte subpopulation by flow cytometry, immunoglobulin levels by nephelometry, antibody titers to previous immunizations and delayed hypersensitivity with skin testing. Immune responses were correlated to duration of therapy, CNS radiotherapy, age and sex. Humoral immunity was severely depressed by the end of intensive therapy with low immunoglobulin levels and CD19, improved after therapy cessation. Cellular immune responses were normal at the end of intensive treatment but declined significantly by the end of therapy and both CD4 and CD8 remained low at later evaluation points whereas CD4/CD8 ratio was increasing. Duration of therapy and CNS radiotherapy did not affect the rate of immune recovery whereas female had higher CD19, CD45RO, and IgM and children >7 years had higher CD19 and lower CD16 and CD3DR. Among immunized children, 86.7% maintained protective antibodies to MMR and 63% to polio. Despite impairment of immunity, infections outside the neutropenic periods were common viral illnesses. Humoral immunity was depressed in children with ALL at the end of intensive therapy but began to recover after cessation of therapy. In contrast, cellular immunity declined significantly by the end of therapy and remained abnormal for at least 1 year post-therapy.


Multiple chemiluminescence immunoassay detection of the concentration ratio of glycosylated hemoglobin A1c to total hemoglobin in whole blood samples.
The concentration ratio of glycosylated hemoglobin A1c (HbA1c) to total hemoglobin (Hb) has long been used to accurately determine stagewise diabetes because this parameter represents a reliable and accurate biomarker of mean 90-day blood glucose values. In this paper, we report a time-resolved chemiluminescence assay that can detect both Hb and HbA1c. For the determination of Hb, the interaction of heme in Hb with H2O2 in NaOH solution was performed to generate a chemiluminescence peak. HbA1c was detected using a sandwich immunoassay based on an acridine ester-labeling method using the same Hb chemiluminescence trigger system. The results showed that the repeatability %CV of the proposed method for multiple detections of HbA1c and Hb ranged from 1.22 to 2.21%, with a median value of 1.73%, while the within-site reproducibility %CV ranged from 2.13 to 3.27%, with a median value of 2.81%. Compared with the conventional HPLC method (BIO-RAD D10 system), the correlation coefficient was 0.9959. In conclusion, a time-resolved multiple chemiluminescence immunoassay biosensor for HbA1c/Hb detection was established, and the method has excellent reproducibility and accuracy, thus demonstrating great potential for clinical application.


Identification and characterization of a novel carboxylesterase EstQ7 from a soil metagenomic library.
A novel lipolytic gene, estq7, was identified from a fosmid metagenomic library. The recombinant enzyme EstQ7 consists of 370 amino acids with an anticipated molecular mass of 42 kDa. Multiple sequence alignments showed that EstQ7 contained a pentapeptide motif GHSMG, and a putative catalytic triad Ser174-Asp306-His344. Interestingly, EstQ7 was found to have very little similarity to the characterized lipolytic enzymes. Phylogenetic analysis revealed that EstQ7 may be a member of a novel family of lipolytic enzymes. Biochemical characterization of the recombinant enzyme revealed that it constitutes a slightly alkalophilic, moderate thermophilic and highly active carboxylesterase against short-chain fatty acid esters with optimum temperature 50 ℃ and pH 8.2. The Km and kcat values toward p-nitrophenyl acetate were determined to be 0.17 mM and 1910s-1, respectively. Moreover, EstQ7 was demonstrated to have acyltransferase activity by GC-MS analysis. Structural modeling of the three-dimensional structure of this new enzyme showed that it exhibits a typical α/β hydrolase fold, and the catalytic triad residues are spatially close. Molecular docking revealed the interactions between the enzyme and the ligand. The high levels of lipolytic activity of EstQ7, combined with its moderate thermophilic property and acyltransferase activity, render this novel enzyme a promising candidate biocatalyst for food, pharmaceutical and biotechnological applications.


Redox regulation of differentiation in symbiotic nitrogen fixation.
Nitrogen-fixing symbiosis between Rhizobium bacteria and legumes leads to the formation of a new organ, the root nodule. The development of the nodule requires the differentiation of plant root cells to welcome the endosymbiotic bacterial partner. This development includes the formation of an efficient vascular tissue which allows metabolic exchanges between the root and the nodule, the formation of a barrier to oxygen diffusion necessary for the bacterial nitrogenase activity and the enlargement of cells in the infection zone to support the large bacterial population. Inside the plant cell, the bacteria differentiate into bacteroids which are able to reduce atmospheric nitrogen to ammonia needed for plant growth in exchange for carbon sources. Nodule functioning requires a tight regulation of the development of plant cells and bacteria. Nodule functioning requires a tight regulation of the development of plant cells and bacteria. The importance of redox control in nodule development and N-fixation is discussed in this review. The involvement of reactive oxygen and nitrogen species and the importance of the antioxidant defense are analyzed. Plant differentiation and bacterial differentiation are controlled by reactive oxygen and nitrogen species, enzymes involved in the antioxidant defense and antioxidant compounds. The establishment and functioning of nitrogen-fixing symbiosis involve a redox control important for both the plant-bacteria crosstalk and the consideration of environmental parameters. This article is part of a Special Issue entitled Redox regulation of differentiation and de-differentiation.


Unilateral enlargement of the testis in childhood: does it need exploration?
Unilateral testicular enlargement in the pubertal boy is not an indication for exploration and biopsy, if the clinical features and investigations show no evidence of malignancy. In the prepubertal boy, unilateral testicular enlargement is not necessarily an indication for exploration if there are no clinical or investigational grounds for suspicion of neoplasia. Close follow-up is essential.


Metabolism of metandienone in man: identification and synthesis of conjugated excreted urinary metabolites, determination of excretion rates and gas chromatographic-mass spectrometric identification of bis-hydroxylated metabolites.
After oral administration of metandienone (17 alpha-methyl-androsta-1,4-dien-17 beta-ol-3-one) to male volunteers conjugated metabolites are isolated from urine via XAD-2-adsorption, enzymatic hydrolysis and preparative high-performance liquid chromatography (HPLC). Four conjugated metabolites are identified by gas chromatography-mass spectrometry (GC/MS) with electron impact (EI)-ionization after derivatization with N-methyl-N-trimethyl-silyl-trifluoroacetamide/trimethylsilyl-imidazole (MSTFA/TMS-Imi) and comparison with synthesized reference compounds: 17 alpha-methyl-5 beta-androst-1-en-17 beta-ol-3-one (II), 17 alpha-methyl-5 beta-androst-1-ene-3 alpha,17 beta-diol (III), 17 beta-methyl-5 beta-androst-1-ene-3 alpha,17 alpha-diol (IV) and 17 alpha-methyl-5 beta-androstane-3 alpha,17 beta-diol (V). After administration of 40 mg of metandienone four bis-hydroxy-metabolites--6 beta,12-dihydroxy-metandienone (IX), 6 beta,16 beta-dihydroxy-metandienone (X), 6 beta,16 alpha-dihydroxy-metandienone (XI) and 6 beta,16 beta-dihydroxy-17-epimetandienone (XII)--were detected in the unconjugated fraction. The metabolites III, IV and V are excreted in a comparable amount to the unconjugated excreted metabolites 17-epimetandienone (VI), 6 beta-hydroxy-metandienone (VII) and 6 beta-hydroxy-17-epimetandienone (VIII). Whereas the unconjugated excreted metabolites show maximum excretion rates between 4 and 12 h after administration the conjugated metabolites III, IV and V are excreted with maximum rates between 12 and 34 h.


Quantitative bone SPECT/CT applications for cartilaginous bone neoplasms.
To evaluate the ability of quantitative values obtained with bone single photon emission computed tomography/computed tomography (SPECT/CT) to differentiate benign from malignant cartilaginous bone neoplasms. Bone SPECT/CT scans of 10 patients with 8 benign cartilaginous bone neoplasms (4 enchondromas, 1 periosteal chondroma, 1 osteochondroma, 1 bizarre parosteal osteochondromatous proliferation, 1 chondroblastoma) and 2 malignant cartilaginous bone neoplasms (1 periosteal chondrosarcoma, 1 chondrosarcoma) were retrospectively analyzed with maximum standardized uptake value (SUVmax), mean SUV (SUVmean), metabolic bone volume (MBV), and total bone uptake (TBU) of primary lesions. Mean SUVmax of 8 benign and 2 malignant cartilaginous bone neoplasms were 1.93±1.02 (range 0.59-3.41) and 6.07±0.86 (5.46-6.67), respectively with no overlap (P=0.028). Mean SUVmean of those were 1.24±0.71 (range 0.36-2.36) and 4.05±0.30 (3.84-4.26), respectively with no overlap (P=0.00036). Mean MBV of those were 7.17±4.19 (range 3.17-13.77) and 10.29±10.05 (3.19-17.4), respectively with no significant difference (P=0.74). Mean TBU of those were 9.22±8.31 (range 1.15-23.61) and 43.19±43.7 (12.26-74.13), respectively with no significant difference (P=0.47). Standardized uptake value obtained with bone SPECT/CT may be useful to differentiate benign from malignant cartilaginous bone neoplasms, thus helping the orthopedic surgeon towards the most appropriate treatment procedure.


Developmental expression of MMP-9 (gelatinase B) mRNA in mouse embryos.
Considerable remodeling of the extracellular matrix as well as cellular migration takes place during embryogenesis. Since the metalloproteinase MMP-9 is implicated in these functions in cancer cells, we studied the patterns of expression of MMP-9 mRNA during the development of post-implantation mouse embryos. MMP-9 mRNA was detected using the ribonuclease protection assay in poly A+RNA from 13 to 17 day embryos, but not at 11 days. In order to localize these transcripts, in situ hybridization was performed on sections of murine embryos from 7.5 to 15 days of gestation. At the time of implantation, MMP-9 mRNA was localized to the invading trophoblast cells. Strong signals were also seen in the yolk sac. No signal for MMP-9 mRNA was seen by in situ hybridization in the embryo until day 11 when detectable reaction was seen in the central nervous system. By day 15 strong signals were seen in the liver, in the developing bronchial epithelium of the lungs and in the primordial alveoli, in the epithelium of the thyroid gland, in the thymus, in the endochondrial plates of the bone, and in neural cells. The liver from day 15 embryos contained gelatinase activity at 105 kDa consistent with MMP-9. Thus, MMP-9 expression appears to be expressed in specific organs in a precise temporal sequence during development.


Identity of victims from fragmented and decomposed remnants by DNA profiling in a case of serial killings.
A 28-year-old man, Surinder Koli, from a Nithari village adjoining Delhi, India committed serial murder. This case was of paramount importance in medico-legal investigations, as it was a landmark case of a serial killer reported from India. The skeletal remains (627 pieces) including skull/skull portions (19) were recovered from the nearby sewer drain, sump and the backyard of the house in which this man was residing. In addition, soft tissues (51) were also recovered from the same sewer drain. The victims were killed over a two-year period. The establishment of identity of the victims was crucial to prove the case in the court of law as well as for the claimants. Nineteen sets were prepared by radiology/anatomical examination from the exhibits recovered. DNA profiling confirmed the correctness of these sets and also short tandem repeat typing of nuclear DNA successfully identified eight individuals. Both DNA profiling and radiography/anatomical examination played an important role in solving this complicated case.


Sodium-dependent, concentrative nucleoside transport in cultured intestinal epithelial cells.
In a simple salts medium, monolayers of IEC-6 intestinal cells achieved concentrations of unmetabolized formycin B (an analog of inosine) about 6-fold higher than in the medium. Rates of formycin B influx were a saturable function of Na+ concentrations in the medium. Although IEC-6 cells possess sites with high affinity for nitrobenzylthioinosine, a potent inhibitor of equilibrative (facilitated diffusion) nucleoside transport systems in certain cell types, the inhibitor had only minor effects on formycin B uptake in IEC-6 cells, but reduced efflux of the analog from these cells. These findings indicate the joint presence in IEC-6 cells of nucleoside transporters of two types, one that is concentrative and Na+-dependent, and another that is sensitive to nitrobenzylthioinosine and apparently equilibrative.


Sex differences in neuropsychological function in non-psychotic relatives of schizophrenic probands.
Some recent studies suggest that men with schizophrenia may have greater neuropsychological deficits than women. It is not known, however, whether similar sex differences may be present in biological relatives of schizophrenic patients. We evaluated neuropsychological functioning of 54 relatives of schizophrenic patients and 72 normal volunteers. It was hypothesized that, if sex differences were present, they would be accounted for largely by deficits in male relatives. We were particularly interested in three neuropsychological functions that we previously identified as putative neuropsychological vulnerability indicators for schizophrenia: (1) abstraction/executive function; (2) verbal memory; and (3) auditory attention. There were significant group x sex interactions for verbal memory and motor function, and trends toward significant interactions for auditory attention and mental control/encoding. However, with the exception of motor function, it was the female relatives who accounted for most of the impairment. A speculative explanation for the findings is that women may have a higher threshold than men for developing schizophrenia. If so, female relatives might be able to withstand greater impairments than men before developing psychotic symptoms. Consequently, in a sample that was limited to non-psychotic relatives--as in the present study--there could be over-representation of both less impaired men and more impaired women. Alternative explanations and limitations of the study are also discussed.


Processing and assembly of the integrin, glycoprotein IIb-IIIa, in HEL cells.
We examined the biosynthetic processing and assembly of the platelet glycoprotein (GP) IIb-IIIa complex in [35S]methionine-labeled HEL cells, a human cell line with features of megakaryocytes. Both GPIIb and GPIIIa were synthesized as single-chain precursors to which high mannose N-linked oligosaccharides were added in the endoplasmic reticulum (ER). A 5-fold excess of the major IIb precursor, preIIb, was synthesized relative to GPIIIa. Two smaller proteins immunologically related to GPIIb were synthesized in smaller amounts. Assembly of the GPIIb and GPIIIa precursors required 4-6 h for completion. All GPIIIa molecules were eventually assembled; the excess GPIIb precursors were degraded without reaching the cell surface. Following assembly, preIIb-IIIa complexes were rapidly transported to the Golgi apparatus where preIIb underwent modification of high mannose chains into complex oligosaccharides and proteolytic cleavage to yield disulfide-linked heavy and light chains. Pretreating cells with the ionophore monensin blocked cleavage of preIIb but not its carbohydrate modification or its assembly with GPIIIa. These studies suggest that 1) assembly of the precursors of GPIIb and GPIIIa in the ER is a slow process requiring conformational maturation of one or both subunits, and 2) only heterodimers assembled in the ER are transported to the Golgi apparatus for additional processing and, ultimately, expression on the cell surface.


A novel approach for latent print identification using accurate overlays to prioritize reference prints.
A novel approach to automated fingerprint matching and scoring that produces accurate locally and nonlinearly adjusted overlays of a latent print onto each reference print in a corpus is described. The technology, which addresses challenges inherent to latent prints, provides the latent print examiner with a prioritized ranking of candidate reference prints based on the overlays of the latent onto each candidate print. In addition to supporting current latent print comparison practices, this approach can make it possible to return a greater number of AFIS candidate prints because the ranked overlays provide a substantial starting point for latent-to-reference print comparison. To provide the image information required to create an accurate overlay of a latent print onto a reference print, "Ridge-Specific Markers" (RSMs), which correspond to short continuous segments of a ridge or furrow, are introduced. RSMs are reliably associated with any specific local section of a ridge or a furrow using the geometric information available from the image. Latent prints are commonly fragmentary, with reduced clarity and limited minutiae (i.e., ridge endings and bifurcations). Even in the absence of traditional minutiae, latent prints contain very important information in their ridges that permit automated matching using RSMs. No print orientation or information beyond the RSMs is required to generate the overlays. This automated process is applied to the 88 good quality latent prints in the NIST Special Database (SD) 27. Nonlinear overlays of each latent were produced onto all of the 88 reference prints in the NIST SD27. With fully automated processing, the true mate reference prints were ranked in the first candidate position for 80.7% of the latents tested, and 89.8% of the true mate reference prints ranked in the top ten positions. After manual post-processing of those latents for which the true mate reference print was not ranked first, these frequencies increased to 90.9% (1st rank) and 96.6% (top ten), respectively. Because the computational process is highly parallelizable, it is feasible for this method to work with a reference corpus of several thousand prints.


Prolonged Mechanical Ventilation in Children: Review of the Definition.
To review existing definitions of prolonged mechanical ventilation in children. Review of the literature. Not applicable. Pediatric patients under mechanical ventilation. Not applicable. We searched the literature for original research on prolonged mechanical ventilation in children using the PubMed, Embase, and Cochrane Library databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed, and we extracted patient characteristics, duration of mechanical ventilation, outcomes, and associated complications. We identified 30 articles for qualitative analysis and found a wide variety of definitions, varying from 48 hours to 6 months. The most frequently used definitions of prolonged mechanical ventilation were greater than 7 days, greater than 14 days, and greater than 21 days. There was no high-quality evidence of a definition for prolonged mechanical ventilation in children. There is limited evidence to determine the definition of prolonged mechanical ventilation in children. The variety of definitions is a sign of the need for a consensus definition of pediatric prolonged mechanical ventilation.


Inhibition of macrophage migration inhibitory factor reduces diabetic nephropathy in type II diabetes mice.
Macrophage migration inhibitory factor (MIF) plays a critical role in inflammation and is elevated in diabetic kidney. However, whether MIF plays a causative role in diabetic nephropathy (DN) remains unclear. In the present study, we have demonstrated that after treatment of 8-week-old diabetic db/db and nondiabetic db/m mice with the MIF inhibitor ISO-1 (20 mg/kg) for 8 weeks, there was a significant decrease in blood glucose, albuminuria, extracellular matrix accumulation, epithelial-mesenchymal transition (EMT), and macrophage activation in the kidney of db/db mice. Incubation of macrophages with MIF induced the production of proinflammatory cytokines, including interleukin (IL) 6, IL-1β, tumor necrosis factor α (TNF-α). The conditioned media (CM) of MIF-activated macrophages and TNF-α induced by MIF caused podocyte damage. Moreover, CM from MIF-activated macrophages induced EMT of renal tubular cells, and this effect was blocked by ISO-1. Thus, MIF inhibition may be a potential therapeutic strategy for DN. This effect may be attributable to its inhibitory effect on macrophage activation in the diabetic kidney.


Controlled trial of the effect of cycloalliin on the fibrinolytic activity of venous blood.
Cycloalliin is a natural constituent of onion, sulphur-containing but odourless. It was synthesised for this randomised double-blind study; its effect on fibribolytic activity and platelet aggregability was tested in venous blood from 18 male volunteers. It increased the former to a highly significant degree but had no effect on the latter. It was well tolerated and harmless in the single oral dosage used.


Implications of Chronic Opioid Therapy on Perioperative Complications and Long-Term Surgical Recovery.
With chronic opioid use becoming an increasingly common occurrenceamong the general population, perioperative specialties must adapt to the physiologic changes caused by long-term opioids. However, data on the clinicalanesthetics implications of long-term opioid use is scarce. This review intends to survey the literature addressing the molecular mechanisms of long-term opioid use as well as their interaction with various organ systems.


Ethnic disparities in preventable hospitalisation in England: an analysis of 916 375 emergency admissions.
To study ethnic inequalities in ambulatory care sensitive conditions (ACSC) in England. Observational study of inpatient hospital admission database enhanced with ethnicity coding of patient surnames. The primary diagnosis of the first episode in spells with emergency admission were coded with definitions for acute ACSC, chronic ACSC and vaccine-preventable diseases. National Health Service England. 916 375 ACSC emergency admissions in 7 39 618 patients were identified between April 2011 and March 2012. ORs of ACSC for each ethnic group relative to the White British majority group adjusted for age, sex and area deprivation. Acute ACSC admission risk adjusted for age and sex was particularly high among Other (OR 1.73; 95% CI 1.69 to 1.77) and Pakistani (1.51; 95% CI 1.48 to 1.54) compared with White British patients. For chronic ACSC, high risk was found among Other (2.02; 95% CI 1.97 to 2.08), Pakistani (2.07; 95% CI 2.02 to 2.12) and Bangladeshi (1.36; 95% CI 1.30 to 1.42). For vaccine-preventable diseases, other (2.42; 95% CI 2.31 to 2.54), Pakistani (1.94; 95% CI 1.85 to 2.04), Bangladeshi (1.48; 95% CI 1.36 to 1.62), Black African (1.45; 95% CI 1.36 to 1.54) and white other (1.38; 95% CI 1.33 to 1.43) groups. Elevated risk was only partly explained in analyses also adjusting for area deprivation. ACSC admission was especially high among individuals of Bangladeshi, Pakistani, Black African, white other or other background with up to twofold differences compared with the white British group. This suggests that these ethnic groups are not receiving optimal primary care.


Prevalence and the factors influencing soil-transmitted helminths among school age children (5-14 years age) in a rural area of Coimbatore district.
Highest intensity of soil-transmitted helminthiasis (STH) is seen among school age children. The aim of this study is to find out the prevalence and factors associated with soil-transmitted helminthic infection among school age children (5-14 years) in a rural area of Coimbatore district. The study was conducted in the field practice area of the Rural Health Training Centre (RHTC) Vedapatti, Coimbatore. RHTC caters to a total population of 23,841 distributed in 14 villages. After getting ethical clearance, five of the 14 villages of Vedapatti were selected by the cluster sampling method. Totally, 819 participated in the survey conducted between November 2015 and July 2016 in the field practice area. Structured questionnaire was used to collect the information. Consent from parents and assent from child were obtained. Totally, 610 gave one adequate stool sample. Early morning samples were collected and transported to the laboratory within four hours. Formal ether concentration method was performed, and examination was done. Data analysis was performed with the SPSS version 19 software. The prevalence is expressed in percentage with 95% confidence interval (CI). Univariate and multivariate analyses were performed. Strength of association was expressed in terms of odds ratio (OR) and adjusted OR with 95% CI. P < 0.05 was considered as statistically significant. The prevalence of STH was 7.70% (95% CI: 5.58-9.82). Ascaris lumbricoides was highly prevalent 6.9% (4.89%-8.91%) followed by Hook worm 0.7% (0.04%-1.36%), and Trichuris trichura 0.2% (0.15%-0.55%). Mulitivariate logistic regression analysis showed that pucca houses offered protection against STH. The prevalence of STH in a rural area of Coimbatore is 7.7% (95% CI: 5.58-9.82), and is continuing as a public health problem.


Adolescents' perceptions of risk for HIV infection: implications for future research.
Few studies have investigated adolescents' perceptions of their risk for HIV infection. Findings from two studies of adolescents in Massachusetts indicate that there are differences in the knowledge, beliefs, behaviors, and perceptions of risk among adolescents and suggest the need for understanding the differences among adolescents from different racial or ethnic backgrounds. In both studies, white students were the most knowledgeable about casual, sexual, and drug use transmission of HIV followed by black, Hispanic, and Asian students. In both studies more black adolescents than other racial or ethnic groups were sexually active, and black and Hispanic adolescents began having sexual intercourse at an earlier age than white or Asian adolescents. Asian and Hispanic adolescents were most worried about getting AIDS. Although more Hispanics than other groups reported changing their behavior because of AIDS, fewer of them who had changed their sexual or contraceptive behavior were using effective methods. Despite clear differences in the perceived risk of getting AIDS among these adolescents, the underlying reasons remain to be explicated, using, among other data collection methods, ethnographic techniques to probe adolescents' risk perceptions, their understandings of sickness, and their explanatory models of AIDS. Life events affect risk taking behaviors and also shape perceptions of risk. To understand what it is that adolescents consider 'risky' requires seeing their life options as they do in the larger context of their aspirations and worries about how 'to fit in'.


Co-expression gene network analysis reveals novel regulatory pathways involved in porto-sinusoidal vascular disease.
Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD. We obtained liver tissue samples from 20 consecutive patients with PSVD and 21 sex- and age-matched patients with cirrhosis and 13 histologically normal livers (HNL) (initial cohort) and performed transcriptomic analysis. Microarray data were analyzed using weighted gene correlation network analysis to identify clusters of highly correlated genes differently expressed in patients with PSVD. We next evaluated the molecular pathways enriched in patients with PSVD and the core-related genes from the most significantly enriched pathways in patients with PSVD. Our main findings were validated using RNA sequencing in a different cohort of PSVD, cirrhosis and HNL (n = 8 for each group). Patients with PSVD have a distinctive genetic profile enriched mainly in canonical pathways involving hemostasis and coagulation but also lipid metabolism and oxidative phosphorylation. Serpin family (SERPINC1), the apolipoproteins (APOA, APOB, APOC), ATP synthases (ATP5G1, ATP5B), fibrinogen genes (FGB, FGA) and alpha-2-macroglobulin were identified as highly connective genes that may have an important role in PSVD pathogenesis. PSVD has a unique transcriptomic profile and we have identified deregulation of pathways involved in vascular homeostasis as the main pathogenic event of disease development. Porto-sinusoidal vascular disease is a rare but life-shortening disease that affects mainly young people. Knowledge of the disrupted pathways involved in its development will help to identify novel therapeutic targets and new treatments. Using a systems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease.


Euphorbia helioscopia a Putative Plant Reservoir of Pathogenic Curtobacterium flaccumfaciens.
The endophyte EHF3 strain was isolated in Algeria from an Euphorbia helioscopia plant growing in a fallow field. The strain was characterized by biochemical and physiological tests and assayed for the production of secondary metabolites involved in biocontrol, for plant growth promotion ability and for pathogenicity. The strain was identified by BIOLOG test as Curtobacterium flaccumfaciens. Biochemical and physiological characterization revealed that the strain was able to secrete protease, caseinase and amylase enzymes, to grow up to 37 °C and at pH values 5 to 9. C. flaccumfaciens EHF3 strain was incapable of solubilizing phosphorus and to produce IAA, HCN siderophores and phenazine compounds. The strain showed a moderate swimming and swarming motility and produced biofilm. EHF3 strain was positive at the hypersensitivity test on tobacco plants and induced symptoms on three varieties of bean resembling to those of the bacterial wilt disease induced by C. flaccumfaciens pv. flaccumfaciens. The preliminary data reported in this study, regarding the detection of a pathogenic C. flaccumfaciens strain, as endophyte of a E. helioscopia plant, highlight the role of non-host plants as reservoir of this bacterial pathogen.


Semiquantitative assessment of cardiovascular disease markers in multislice computed tomography of the chest: interobserver and intraobserver agreements.
To investigate the interobserver and intraobserver agreements for the semiquantitative assessment of markers of subclinical cardiovascular disease as identified by routine care, diagnostic computed tomography (CT) of the chest, to improve the quality of reporting of these incidental findings. Two observers independently evaluated 109 consecutive chest CT scans in routine care, clinical patients from one tertiary referral center. All nongated, contrast-enhanced scans were acquired on a 16-slice CT scanner. Images were scored for the presence of aortic wall abnormalities and calcifications of the coronary artery, the heart valves, the thoracic aorta, and the proximal supraaortic arteries. Furthermore, the presence of left ventricular scarring and elongation of the aorta were recorded. All markers were scored on a semiquantitative scale. Interobserver and intraobserver agreements are presented as weighted kappa and intraclass correlation coefficients. Interobserver and intraobserver agreements for individual markers were good to excellent, with weighted kappa coefficients of 0.54 to 0.89 for interobserver agreement and 0.55 to 0.96 for intraobserver agreement. Semiquantitative assessment of subclinical cardiovascular disease markers in routine care, diagnostic chest CT scans is possible with good to excellent interobserver and intraobserver agreements. Use of these definitions in clinical practice will enable a more standardized assessment and reporting of incidental findings in diagnostic chest CT.


Twelve-month Durability of a Fully-implanted, Nickel-sized and Shaped Tibial Nerve Stimulator for the Treatment of Overactive Bladder Syndrome with Urgency Urinary Incontinence: A Single-Arm, Prospective Study.
To evaluate the safety and efficacy of the eCoin - a nickel-sized, primary battery-powered, neuromodulation device for the treatment of urgency urinary incontinence which is implanted in the lower leg in a 20-minute procedure under local anesthesia. A feasibility clinical trial was conducted and the results after 1 year of treatment with the eCoin are presented. A total of 46 participants with refractory urgency urinary incontinence were included in this prospective, single-arm, open-label study. This study was conducted at 7 sites in the United States and New Zealand. Participants in this study were implanted with the eCoin in the lower leg over the tibial nerve and activated after 4 weeks. Bladder diary data and validated quality-of-life instruments, collected at 3, 6, and 12 months' post-activation, were compared to baseline values. Responders were defined as those who had a ≥50% reduction in reported episodes of urgency urinary incontinence. At 12 months', 65% of participants were considered responders with 26% of participants achieving complete continence. The median number of urgency urinary incontinence episodes per day decreased from 4.2 at baseline to 1.7 at 12 months'. Seventy percent of participants reported feeling "better", "much better", or "very much better" on the Likert 7-point maximum scale. One participant experienced a related serious adverse event. The eCoin is a safe and effective treatment for urgency urinary incontinence associated with overactive bladder syndrome, with significant reduction or complete resolution of symptoms and no significant safety concerns.


Detection and verification of malting quality QTLs using wild barley introgression lines.
A malting quality quantitative trait locus (QTL) study was conducted using a set of 39 wild barley introgression lines (hereafter abbreviated with S42ILs). Each S42IL harbors a single marker-defined chromosomal segment from the wild barley accession 'ISR 42-8' (Hordeum vulgare ssp. spontaneum) within the genetic background of the elite spring barley cultivar 'Scarlett' (Hordeum vulgare ssp. vulgare). The aim of the study was (1) to verify genetic effects previously identified in the advanced backcross population S42, (2) to detect new QTLs, and (3) to identify S42ILs exhibiting multiple QTL effects. For this, grain samples from field tests in three different environments were subjected to micro malting. Subsequently, a line x phenotype association study was performed with the S42ILs in order to localize putative QTL effects. A QTL was accepted if the trait value of a particular S42IL was significantly (P < 0.05) different from the recurrent parent as a control, either across all tested environments or in a particular environment. For eight malting quality traits, altogether 40 QTLs were localized, among which 35 QTLs (87.5%) were stable across all environments. Six QTLs (15.0%) revealed a trait improving wild barley effect. Out of 36 QTLs detected in a previous advanced backcross QTL study with the parent BC(2)DH population S42, 18 QTLs (50.0%) could be verified with the S42IL set. For the quality parameters alpha-amylase activity and Hartong 45 degrees C, all QTLs assessed in population S42 were verified by S42ILs. In addition, eight new QTL effects and 17 QTLs affecting two newly investigated traits were localized. Two QTL clusters harboring simultaneous effects on eight and six traits, respectively, were mapped to chromosomes 1H and 4H. In future, fine-mapping of these QTL regions will be conducted in order to shed further light on the genetic basis of the most interesting QTLs.


Identification of potent epitopes on hexon capsid protein and their evaluation as vaccine candidates against infections caused by members of Adenoviridae family.
Adenoviruses cause economically important diseases in vertebrates. Effective vaccines against adenoviral diseases are currently lacking. Here, we report a highly conserved epitopic region on hexon proteins of adenoviruses that generate a strong immune response when used as a virus-like-particle (VLP) vaccine, produced by inserting the epitopic region into the core protein of hepatitis B virus. For evaluation of its protective efficacy, the epitopic region from a representative adenovirus, fowl adenovirus serotype 4 (FAdV-4), was tested as a VLP vaccine which conferred 90% protection against challenge with a virulent FAdV-4 isolate in chickens. Importantly, such a high level of protection is not achieved when the epitopic region is employed as a part of a subunit vaccine. As the sequence and the structure of the epitopic region are highly conserved in hexon proteins of adenoviruses, the epitopic region could be employed as a promising VLP vaccine candidate against adenoviral diseases, in general.


Oral anticoagulant prescribing among patients with cancer and atrial fibrillation in England, 2009-2019.
Anticoagulation of patients with atrial fibrillation (AF) and cancer is challenging because of their high risk for stroke and bleeding. Little is known of the variations of oral anticoagulant (OAC) prescribing in patients with AF with and without cancer. Patients with first-time AF during 2009-2019 from the Clinical Practice Research Datalink were included. Cancer diagnosis was defined as a history of breast, prostate, colorectal, lung, or hematological cancer. Competing-risk analysis was used to assess the risk of OAC prescribing in patients with AF and cancer adjusted for clinical and sociodemographic factors. Of 177,065 patients with AF, 11.7% had cancer. Compared to patients without cancer, patients with cancer were less likely to receive OAC: prostate cancer (subhazard ratio [SHR], 0.95; 95% CI, 0.91-0.99), breast cancer (SHR, 0.93; 95% CI, 0.89-0.98), colorectal cancer (SHR, 0.93; 95% CI, 0.88-0.99), hematological cancer (SHR, 0.70; 95% CI, 0.65-0.75), and lung cancer (SHR, 0.44; 95% CI, 0.38-0.50). The cumulative incidence function (CIF) of OAC prescribing was lowest for patients with lung cancer and hematological cancer compared with patients without cancer. The difference between the CIF of OAC prescribing in patients with and without cancer becomes narrower in the most deprived areas. Elderly patients (aged ≥85 years) overall had the lowest CIF of OAC prescribing regardless of cancer status. In patients with AF, underprescribing of OAC is independently associated with certain cancer types. Patients with hematological and lung cancer are the least likely to receive anticoagulation therapy compared with patients without cancer. Underprescribing of OAC in cancer is linked to old age. Further studies of patients with AF and cancer are warranted to assess the net clinical benefit of anticoagulation in certain cancer types.


Understanding Causes of Hair Loss in Women.
Hair loss affects millions of people worldwide and can have devastating effects on an individual's psychoemotional well-being. Today hair restoration technologies through hair transplantation have advanced with the use of robots and follicular unit extraction and grafting that it is possible to offer to patient's excellent clinical results. Adjuvant modalities such as platelet-rich plasma injections, lasers, and stem cells can further enhance the durability, health, and appearance of hair transplants.


Quantities of Yersinia pestis in fleas (Siphonaptera: Pulicidae, Ceratophyllidae, and Hystrichopsyllidae) collected from areas of known or suspected plague activity.
We used a quantitative competitive polymerase chain reaction (PCR) (QC-PCR) to determine bacterial loads in 669 fleas collected in areas of confirmed and suspected plague epizootics. Fleas were collected out of rodent burrows (67.9%) and off of captured animals (24.1%) and rodent carcasses (8.1%). An initial PCR screening assay indicated that 12.1% (81/669) of all fleas were positive for Yersinia pestis. Fleas collected from burrows had significantly lower (chi2 = 264.9, P < 0.0001) infection rates (6.8%) but significantly higher (Student t-test, P < 0.0001) bacterial loads (mean = 10(5.6) Y. pestis per flea) than fleas collected off of rodent carcasses (infection rate = 92.6%; mean bacterial load = 10(4.8) Y. pestis per flea). None of the fleas collected off of captured animals were positive for Y. pestis by PCR, although seven of the 176 captured animals were serologically positive for Y. pestis.


Prediction, mapping and validation of tick glutathione S-transferase B-cell epitopes.
In search of ways to address the increasing incidence of global acaricide resistance, tick control through vaccination is regarded as a sustainable alternative approach. Recently, a novel cocktail antigen tick-vaccine was developed based on the recombinant glutathione S-transferase (rGST) anti-sera cross-reaction to glutathione S-transferases of Rhipicephalus appendiculatus (GST-Ra), Amblyomma variegatum (GST-Av), Haemaphysalis longicornis (GST-Hl), Rhipicephalus decoloratus (GST-Rd) and Rhipicephalus microplus (GST-Rm). Therefore, the current study aimed to predict the shared B-cell epitopes within the GST sequences of these tick species. Prediction of B-cell epitopes and proteasomal cleavage sites were performed using immunoinformatics algorithms. The conserved epitopes predicted within the sequences were mapped on the homodimers of the respective tick GSTs, and the corresponding peptides were independently used for rabbit immunization experiments. Based on the dot blot assay, the immunogenicity of the peptides and their potential to be recognized by corresponding rGST anti-sera raised by rabbit immunization in a previous work were investigated. This study revealed that the predicted conserved B-cell epitopes within the five tick GST sequences were localized on the surface of the respective GST homodimers. The epitopes of GST-Ra, GST-Rd, GST-Av, and GST-Hl were also shown to contain a seven residue-long peptide sequence with no proteasomal cleavage sites, whereas proteasomal digestion of GST-Rm was predicted to yield a 4-residue fragment. Given that a few proteasomal cleavage sites were found within the conserved epitope sequences of the four GSTs, the sequences could also contain a T-cell epitope. Finally, the peptide and rGST anti-sera reacted against the corresponding peptide, confirming their immunogenicity. These data support the claim that the rGSTs, used in the previous study, contain conserved B-cell epitopes, which elucidates why the rGST anti-sera cross-reacted to non-homologous tick GSTs. Taken together, the data suggest that the B-cell epitopes predicted in this study could be useful for constituting epitope-based GST tick vaccines.


Serum level of phenobarbital or/and diphenylhydantoin in epileptics with some preexisting serum lipid alterations. Correlations with the treatment efficiency in epilepsy.
In a group of 38 epileptics, 13.1 % had alterations of serum lipids before administration of antiepileptic therapy. An inverse relation was found between the level of serum lipids and that of drug concentration : on minimal daily doses, phenobarbital attained disproportionally high concentrations in a patient with hypocholesterolemia + hypotriglyceridemia, while on large daily doses phenobarbital and/or diphenylhydantoin attained low concentrations in the patients with hypercholesterolemia alone or accompanied by hypertriglyceridemia.


Through the looking glass: understanding non-inferiority.
Non-inferiority trials test whether a new product is not unacceptably worse than a product already in use. This paper introduces concepts related to non-inferiority, and discusses the regulatory views of both the European Medicines Agency and the United States Food and Drug Administration.


The impact of a multifaceted intervention including sepsis electronic alert system and sepsis response team on the outcomes of patients with sepsis and septic shock.
Compliance with the clinical practice guidelines of sepsis management has been low. The objective of our study was to describe the results of implementing a multifaceted intervention including an electronic alert (e-alert) with a sepsis response team (SRT) on the outcome of patients with sepsis and septic shock presenting to the emergency department. This was a pre-post two-phased implementation study that consisted of a pre-intervention phase (January 01, 2011-September 24, 2012), intervention phase I (multifaceted intervention including e-alert, from September 25, 2012-March 03, 2013) and intervention phase II when SRT was added (March 04, 2013-October 30, 2013) in a 900-bed tertiary-care academic hospital. We recorded baseline characteristics and processes of care in adult patients presenting with sepsis or septic shock. The primary outcome measures were hospital mortality. Secondary outcomes were the need for mechanical ventilation and length of stay in the intensive unit and in the hospital. After implementing the multifaceted intervention including e-alert and SRT, cases were identified with less severe clinical and laboratory abnormalities and the processes of care improved. When adjusted to propensity score, the interventions were associated with reduction in hospital mortality [for intervention phase II compared to pre-intervention: adjusted odds ratio (aOR) 0.71, 95% CI 0.58-0.85, p = 0.003], reduction in the need for mechanical ventilation (aOR 0.45, 95% CI 0.37-0.55, p < 0.0001) and reduction in ICU LOS and hospital LOS for all patients as well as ICU LOS for survivors. Implementing a multifaceted intervention including sepsis e-alert with SRT was associated with earlier identification of sepsis, increase in compliance with sepsis resuscitation bundle and reduction in the need for mechanical ventilation and reduction in hospital mortality and LOS.


Principles in treating pediatric patients with pilonidal disease - An expert perspective.
Pilonidal disease is common amongst adolescent males and females and often leads to recurrent symptoms and life-altering morbidity. Traditionally, surgery included wide excision of the involved area with primary closure. Post-operative complication rates were high and recurrence of disease common, leading to a search for alternative approaches for treating pilonidal disease. A minimally invasive (trephination) approach was described by Gips in 2008 and has since been adopted by many surgeons. Although the trephination procedure is less morbid than total excision, the risk of wound complications is not insignificant and post-operative recurrence has been reported in more than 10% of patients. The lack of a clear advantage for any single treatment strategy has led a wide variation in provider approach. To standardize the care for pediatric patients with pilonidal disease, a dedicated clinic was created at our institution in 2018. The aim of this paper is to describe an approach to treating pediatric patients with pilonidal disease that has been established through the experience of treating hundreds of adolescent males and females per year. Given the impact on quality of life for those that are affected by pilonidal disease, it is important that future research be directed toward discovery of the best practices for treating this challenging disease.


YTHDF1 phase separation triggers the fate transition of spermatogonial stem cells by activating the IκB-NF-κB-CCND1 axis.
N6-methyladenosine (m6A) modification controls cell fate determination. Here, we show that liquid-liquid phase separation (LLPS) of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), a pivotal m6A "reader" protein, promotes the transdifferentiation of spermatogonial stem cells (SSCs) into neural stem cell-like cells by activating the IκB-nuclear factor κB (NF-κB)-CCND1 axis. The inhibition of IκBα/β mRNA translation mediated by YTHDF1 LLPS is the key to the activation of the IκB-NF-κB-CCND1 axis. Disrupting either YTHDF1 LLPS or NF-κB activation inhibits transdifferentiation efficiency. Moreover, overexpression of the YTH domain of YTHDF1 inhibits the activation of the IκB-NF-κB-CCND1 axis by promoting IκBα/β mRNA translation. Overexpression of the tau-YTH fusion protein reactivates IκB-NF-κB-CCND1 axis by inhibiting the translation of IκBα/β mRNAs, and tau LLPS is observed, which can restore transdifferentiation efficiency. Our findings demonstrate that the protein-RNA LLPS plays essential roles in cell fate transition and provide insights into translational medicine and the therapy of neurological diseases.


Effect of parental morphine addiction on hippocampal long-term potentiation in rats offspring.
Attention to addiction of women alone for fetus and infant's health has caused the possible role of father's status was less considered, while some developmental impairments including decrease of liter size, weight loss, congenital deficiencies, behavioral disorders, and learning and memory impairments in offspring with addicted father have been reported. In this study the effects of addiction of one or both parents to morphine on male and female offspring hippocampal long-term potentiation (LTP), were assessed. One hundred twenty female and 48 male rats (4-5 months, 250-270 g) were used. Forty females and 16 males were addicted by oral administration of morphine (32 mg/kg twice daily) for 5 days before mating. Then each two males with five females were housed (coupled) per cage as five groups for coupling: (A) addicted females+5% dextrose males (add.F); (B) addicted males+5% dextrose females (add.M); (C) addicted females+addicted males (add.MF); (D) 5% dextrose females+intact males (dex.F); (E) 5% dextrose males+intact females (dex.M). In puberty offspring LTP was induced in hippocampal dentate gyrus by stimulation of perforant path (pp). Changes of population spikes (PS) amplitude and LTP slope at 0, 5, 30, 60 and 120 min were evaluated. Slope of LTP at 30, 60 and 120 min, and amplitude of PS at 60 and 120 min in add.F and add.M offspring were significantly lower than dextrose groups (P<0.01). LTP slope and PS amplitude of male and female offspring did not different between add.F and add.M groups. Our results suggest that both parental and paternal addiction to morphine may cause memory deficiency through reduction of LTP in hippocampus.


Induction of c-fos gene and protein by growth factors precedes activation of c-myc.
Stimulation of fibroblasts with serum or purified growth factors leads to a dramatic induction of expression of both c-fos mRNA and protein within a few minutes, followed by activation of c-myc. This suggests that c-fos induction is a primary event and the earliest known effect on gene expression by growth factors.


The effects of interleukins 4 and 5 on the differentiation of B cells from (NZB x NZW)F1 mice.
We describe here that IL-4 and IL-5 together can induce the production of high amounts of IgG1 polyclonal antibodies by B cells from old (NZB x NZW)F1 mice even in the absence of LPS. The effect was less marked in young mice from the same strain or in normal Balb/c mice. The cells sensitive to the treatment with the interleukins were the large B cells. Old mice had higher proportions of such cells than young mice or normal Balb/c mice. Synthesis of anti-DNA antibodies of the IgM class was induced. Although IL-4 plus IL-5 induced a strong polyclonal IgG1 production, there were no IgG1 anti-DNA antibodies.


Evidence for a lack of functional receptors for nerve growth factor (NGF) in chick bone cells in vitro.
Nerve growth factor (NGF) is essential for the development and differentiation of sympathetic and sensory neurons. Recently, NGF receptors were demonstrated in non-neural cells, and several mesenchymal cell types including lymphocytes and skeletal myotubes were shown to be stimulated to proliferate by NGF. Our purpose was to examine for the presence of functional NGF receptors in osteoblasts. Bone cells from chick calvaria were used as a model; PC-12 cells derived from rat adrenal pheochromocytoma were used as positive controls. NGF was examined for functions in chick bone cells by studying effects on (1) [3H]-thymidine incorporation; (2) alkaline phosphatase (ALP) activity; and (3) protein tyrosine phosphorylation. Effects of NGF on thymidine incorporation and protein tyrosine phosphorylation by PC-12 cells were also measured. A radioreceptor assay was used to test for the presence of receptors. In chick calvarial cells, NGF had no effect on thymidine incorporation, ALP activity or protein tyrosine phosphorylation. Radioreceptor assay with bone cells showed no evidence of NGF receptors. In contrast, in PC-12 cells, NGF (1) decreased thymidine incorporation; (2) increased protein tyrosine phosphorylation; and (3) showed receptor activity by radioreceptor assay. In conclusion, unlike several other mesenchymal cell types, chick bone cells show no evidence of NGF receptors or functional responses to NGF in vitro.


Biosynthesis of marine toxins.
Throughout history, humans have encountered natural toxic chemicals from the ocean environment, often through contaminated seafood. Although marine toxins can be harmful to human health and devastate local environments when they are produced during algal bloom events, they are also important biochemical research reagents and drug leads in medicine. In spite of their long history, the biosynthetic origin of many well-known marine toxins has remained elusive. New biosynthetic insights have shed light on the chemical transformations that create the complex structures of several iconic oceanic toxins. To that end, this review highlights advances made in the biosynthetic understanding of five important environmental toxins of marine origin: domoic acid, kainic acid, saxitoxin, tetrodotoxin, and polyether polyketides such as brevetoxin.


AI Ethics, Ethics Washing, and the Need to Politicize Data Ethics.
Many commercial actors in the tech sector publish ethics guidelines as a means to 'wash away' concerns raised about their policies. For some academics, this phenomenon is reason to replace ethics with other tools and methods in an attempt to make sure that the tech sector does not cross any moral Rubicons. Others warn against the tendency to reduce a criticism of 'ethics washing' into one of ethics simpliciter. In this essay, I argue firstly that the dominant focus on principles, dilemmas, and theory in conventional ethical theories and practices could be an explanation of it lacking resistance to abuse by dominant actors, and hence its rather disappointing capacity to stop, redirect, or at least slow down big tech's course. Secondly, drawing from research on casuistry and political philosopher Raymond Geuss, this essay will make a case for a question, rather than theory or principle-based ethical data practice. The emphasis of this approach is placed on the acquisition of a thorough understanding of a social-political phenomenon like tech development. This approach should be replenished with one extra component to the picture of the repoliticized data ethics drawn so far: the importance of 'exemplars,' or stories. Precisely the fact that one should acquire an in-depth understanding of the problem in practice will also allow one to look in the past, present, or future for similar and comparable stories from which one can learn.


ANRIL Genetic Variants in Iranian Breast Cancer Patients.
The genetic variants of the long non-coding RNA ANRIL (an antisense noncoding RNA in the INK4 locus) as well as its expression have been shown to be associated with several human diseases including cancers. The aim of this study was to examine the association of ANRIL variants with breast cancer susceptibility in Iranian patients. In this case-control study, we genotyped rs1333045, rs4977574, rs1333048 and rs10757278 single nucleotide polymorphisms (SNPs) in 122 breast can- cer patients as well as in 200 normal age-matched subjects by tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR). The TT genotype at rs1333045 was significantly over-represented among pa- tients (P=0.038) but did not remain significant after multiple-testing correction. In addi- tion, among all observed haplotypes (with SNP order of rs1333045, rs1333048 rs4977574 and rs10757278), four haplotypes were shown to be associated with breast cancer risk. However, after multiple testing corrections, TCGA was the only haplotype which remained significant. These results suggest that breast cancer risk is significantly associated with ANRIL variants. Future work analyzing the expression of different associated ANRIL haplotypes would further shed light on the role of ANRIL in this disease.


Characterization of the polyphenol oxidase gene family reveals a novel microRNA involved in posttranscriptional regulation of PPOs in Salvia miltiorrhiza.
Salvia miltiorrhiza is a well-known material of traditional Chinese medicine. Understanding the regulatory mechanisms of phenolic acid biosynthesis and metabolism are important for S. miltiorrhiza quality improvement. We report here that S. miltiorrhiza contains 19 polyphenol oxidases (PPOs), forming the largest PPO gene family in plant species to our knowledge. Analysis of gene structures and sequence features revealed the conservation and divergence of SmPPOs. SmPPOs were differentially expressed in plant tissues and eight of them were predominantly expressed in phloem and xylem, indicating that some SmPPOs are functionally redundant, whereas the others are associated with different physiological processes. Expression patterns of eighteen SmPPOs were significantly altered under MeJA treatment, and twelve were yeast extract and Ag+-responsive, suggesting the majority of SmPPOs are stress-responsive. Analysis of high-throughput small RNA sequences and degradome data showed that miR1444-mediated regulation of PPOs existing in P. trichocarpa is absent from S. miltiorrhiza. Instead, a subset of SmPPOs was posttranscriptionally regulated by a novel miRNA, termed Smi-miR12112. It indicates the specificity and significance of miRNA-mediated regulation of PPOs. The results shed light on the regulation of SmPPO expression and suggest the complexity of SmPPO-associated phenolic acid biosynthesis and metabolism.


Clinical trial of a low-cost external fixator for global surgery use.
A low-cost modular external fixator for the lower limb has been developed for global surgery use. The purpose of this study is to assess outcome measures in the first clinical use of the device. A prospective cohort study was conducted with patients recruited in two trauma hospitals. Initial clinical procedure data were collected, and patients were followed up every two weeks until 12 weeks or definitive fixation. Follow-up assessed infection, stability, and radiographic outcomes. In addition, patient-reported outcomes and surgeons' feedback on device usability were collected by questionnaires. The external fixator was used on 17 patients. Ten were mono-lateral, five were joint spanning, and two were delta configuration. One patient had a pin site infection at 12-week follow-up. All were stable when tested mechanically and using radiographic assessment, and 53% were converted to definitive fixation. The low-cost external fixator developed is appropriate for use in global surgery trauma centres with good clinical outcomes. SLCTR/2021/025 (06 Sep 2021).


Richter's syndrome presenting as a facial swelling.
In a small percentage of cases, patients suffering from chronic lymphocytic leukemia undergo a preterminal dedifferentiation or transformation of their disease with the development of diffuse histiocytic lymphoma. The transformation, which is often accompanied clinically by pyrexia, lymphadenopathy, weight loss, and abdominal pain, has been termed Richter's syndrome. A case is reported wherein the patient came with a facial swelling that was initially thought to be due to dental infection. Richter's syndrome does not appear to have been reported in the oral surgery literature previously.


Stressors, Psychological States, and Relationship Quality among East Malaysian Adults with Partners Amid the COVID-19 Lockdown.
The COVID-19 pandemic has had a huge impact not only on healthcare systems and economic threats but also on relationships. Due to the massive measures of the Movement Control Order, such as social distancing, strictly limited physical activities, and making adjustments to working from home-merged with the pandemic's fear-romantic partners may face challenges that affect the quality of their relationships. The purpose of this study was to (i) identify stressors experienced by participants during the COVID-19 lockdown, (ii) evaluate participants'psychological well-being before and during the lockdown, and (iii) see if participants' perceived relationship quality differed before and during the lockdown. An online self-report questionnaire was used to recruit 334 adults (58.1 percent female, 41.9 percent male) with partners (married = 304, engaged = 12, and in committed relationships = 17). Participants were asked about stressors they encountered as a result of COVID-19 using an open-ended question. The Depression Anxiety Stress Scales (DASS-21) were used to assess mental health, and the Perceived Relationship Quality Component (PRQC) Inventory was used to assess relationship quality. According to the findings, the top three common stressors reported by participants were financial problems, restricted movement, and fear of COVID-19 infection. Participants reported significantly higher levels of stress, anxiety, and depression during the lockdown than before. The findings also revealed that participants' relationship quality improved during the lockdown compared to before the lockdown. The current study contributes by providing information on the impact of the COVID-19 pandemic on mental health and the quality of couples' relationships during the pandemic.


Status of major hemostatic components in the setting of COVID-19: the effect on endothelium, platelets, coagulation factors, fibrinolytic system, and complement.
The coagulation, fibrinolytic, anticoagulation, and complement systems are in delicate balance with the vessel wall endothelium ensuring appropriate hemostasis. Coagulopathy in coronavirus disease 2019 (COVID-19) is not a simple disorder of one hemostatic component but a complicated process affecting most of the hemostasis system. COVID-19 disturbs the balance between the procoagulant systems and the regulatory mechanisms. Here, we investigate the effect of COVID-19 on key hemostatic components, including platelets, endothelial cells, coagulation factors, fibrinolytic system, anticoagulant protein system, and complement system, to improve our understanding of the pathophysiological processes underlying COVID-19 coagulopathy based on evidence.


Prognostic impact of final kissing balloon technique after crossover stenting for the left main coronary artery: from the AOI-LMCA registry.
It is still uncertain whether the final kissing balloon technique (FKBT) is mandatory after crossover stenting for the left main coronary artery (LMCA). Assessing Optimal Percutaneous Coronary Intervention for LMCA (AOI-LMCA) registry, a 6-center retrospective registry, enrolled 1809 consecutive patients for LMCA stenting in Japan. In the present analysis, 5-year clinical outcomes were compared between non-FKBT (n = 160) and FKBT (n = 578) groups in patients treated with crossover stenting with drug-eluting stents from the LMCA to the left anterior descending artery. Propensity score-matched analysis was also performed in 160 patient pairs. In the entire study population as well as in the propensity-matched population, the cumulative 5-year incidence of the primary outcome measure (target lesion revascularization: TLR) was not significantly different between the FKBT and non-FKBT groups (10.7 versus 14.3%, P = 0.49, and 11.8 versus 14.3%, P = 0.53, respectively). In the sensitivity analysis by the multivariable Cox proportional hazard model, the effect of FKBT relative to non-FKBT for TLR remained insignificant (adjusted HR 0.89, 95% CI 0.47-1.69, P = 0.72). Regarding the TLR location, there were no significant differences in the cumulative incidences of TLR for LMCA-only, for the main branch, and for the side branch between the 2 groups (2.2 versus 1.3%, P = 0.93, 11.8 versus 9.1%, P = 0.71, and 8.2 versus 7.6%, P = 0.82, respectively). FKBT after a 1-stent strategy for LMCA crossover stenting did not affect TLR and other clinical outcomes during 5-year follow-up.Clinical Trial Registration: Assessing Optimal Percutaneous Coronary Intervention for Left Main Coronary Artery Stenting Registry (AOI LMCA Stenting Registry). http://www.umin.ac.jp/ctr/index/htm/ . Unique Identifier: UMIN000014706.


Long-term vascular access for hemodialysis using silicon dual-lumen catheters with guidewire replacement of catheters for technique salvage.
Difficulties in creating vascular access in patients on hemodialysis are encountered in most dialysis centers. This is usually due to a lack of suitable peripheral vessels due to previous access surgery in patients on long-term hemodialysis, but also may be seen in some patients de novo, particularly diabetics and patients with peripheral vascular disease. Surgical techniques used to overcome this problem vary depending on patient characteristics and, to a certain extent, on local expertise/preference. We report our experience of using silicon dual-lumen hemodialysis catheters over a 3-year period; during this time, 54 catheters were inserted into 32 hemodialysis patients. The indication for this procedure in 52 catheters (31 patients) was either exhausted vascular access or obvious difficulty identifying a suitable peripheral blood vessel. Of the catheters inserted, 20 were placed into subclavian veins by primary insertion (ie, patients did not have existing subclavian catheter); 34 were replaced over a guidewire (a procedure used to allow technique salvage). The catheter survival rate was 72.7% at 90 days and 48.7% at 1 year. Corresponding rates at 90 days and 1 year for technique survival were 93.3% and 81.8%, respectively. The mean catheter and technique survival was 387 (95% confidence intervals [CIs], 273, 502) and 844 (95% CIs, 684, 1,005) days, respectively. Poor flow accounted for 70.4% of catheter failures and, despite 18 episodes of catheter-related sepsis, no catheters were lost due to infection. Factors identified as leading to reduced catheter survival were left-sided placement and catheter tip placement in the superior vena cava (as opposed to right atrial placement). We did not observe poorer survival or increased sepsis in catheters replaced over a guidewire, and would advocate this technique as a means of salvage in this group of patients.


Delayed outcome from surgically treated patients with benign nerve associated tumors of the extremities larger than 5 cm.
The purpose of this work was to analyse the surgical procedure used and the outcome from patients with solitary nerve associated benign tumors of the extremities (SNABTE) >5 cm. A 15 year review was performed for all patients with SNABTE treated in our department. The surgical procedures used (complete or incomplete tumor removal, with or without nerve preservation), the needs for grafting techniques as well as the outcome were analysed. Nine (9.5%) of 94 patients with SNABTE met the study requirements. The histological diagnosis revealed a schwannoma in four cases, a neurofibroma in three cases, one lipoma and one lipofibroma. Seven lesions could be completely excised. Preservation of the nerve bundles with complete neurological recovery was possible in five cases. The resection of a 22 cm neurofibroma without preservation of the nerve did not add measurable residual neurological deficits. One patient with a peroneal neurofibroma required a grafting procedure. Intentional incomplete tumor excisions were performed in two patients with well preserved nerve functions where a median nerve lipofibroma and a radial nerve neurofibroma were diagnosed. All patients showed different degrees of improved outcome. We conclude that the complete resection of large SNABTE, excepting lipofibromas and some neurofibromas, is always possible and associated with an improved outcome. The nerve preservation should be attempted in all cases, particularly in those with conserved functionality of a major nerve trunk.


The Dwyer procedure in the treatment of idiopathic scoliosis. A 10-year follow-up review of 21 patients.
Despite the well-known Dwyer procedure, developed in 1969, comprehensive reports on its use, with long-term follow-up, are relatively scarce. The purposes of this study were to detect eventual late complications and to compare late results with postoperative angular curve correction. This article reports on 21 children operated on between October 1972 and October 1975 and reviewed with a minimum follow-up of 10 years (10 other patients were lost to follow-up after 5 years). Patients had idiopathic lumbar or thoracolumbar curves (average curve, 56 degrees). Results are discussed with a special reference to longitudinal observation. There is a great correction of the instrumented curve (postoperative, 5 degrees), but a loss of correction of 10 degrees is generally observed, prevented by a complete immediate correction or even hypercorrection. The upper curve, noninstrumented, also shows improvement (mean preoperative, 38 degrees; postoperative, 22 degrees; 10 years, 22 degrees) but re-equilibration cannot be predicted. Pseudarthrosis of one intervertebral space occurs frequently, and may cause failure of the cable with a loss of correction of 10-20 degrees. Kyphosis (or simple loss of lumbar lordosis) is commonly observed but should be balanced with correction of rotation. The following conclusions were made: morbidity is not severe, despite the advanced surgical technique. The technique is difficult and has a direct consequence on the quality of results; pseudarthrosis is a frequent complication, followed by important loss of correction; indications should be discussed carefully in idiopathic lumbar and thoracolumbar curves. It is still too early to advocate either anterior instrumentation of Zielke (VDS) or segmental posterior instrumentation (C. D. Luque) because of short-term follow-up.


Unexpected exit of a cochlear implant electrode through the wall of the basal turn of the cochlea - a report on two patients.
We describe the unusual complication of the cochlear implant electrode eroding through the lateral bony wall of the cochlear basal turn in 2 different patients. This complication, occurring during life, has not been previously described in the literature. Radiological investigations were vital in making this diagnosis. We also discuss the likely pathophysiology behind this complication.


Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling.
The JAK2V617F mutation is associated with distinct myeloproliferative neoplasms, including polycythemia vera (PV) and essential thrombocythemia (ET), but it remains unclear how it generates disparate disorders. By comparing clonally-derived mutant and wild-type cells from individual patients, we demonstrate that the transcriptional consequences of JAK2V617F are subtle, and that JAK2V617F-heterozygous erythroid cells from ET and PV patients exhibit differential interferon signaling and STAT1 phosphorylation. Increased STAT1 activity in normal CD34-positive progenitors produces an ET-like phenotype, whereas downregulation of STAT1 activity in JAK2V617F-heterozygous ET progenitors produces a PV-like phenotype. Our results illustrate the power of clonal analysis, indicate that the consequences of JAK2V617F reflect a balance between STAT5 and STAT1 activation and are relevant for other neoplasms associated with signaling pathway mutations.


Validation of questionnaires on physical function.
Data-gathering instruments were used in a randomized controlled trial, designed to assess a structured preoperative educational program for elective surgical patients. The key dependent variable was the physical functional capacity of patients following surgery. Questionnaires were developed to measure physical functioning in the immediate postoperative period, after discharge from hospital, and 10 days and 33 days after surgery. Statistical techniques used to measure interobserver agreement and bias were worker's chi square, Cicchett's statistic, the contingency coefficient, Kendall's Taub, and Kendall's coefficient of concordance W. The standardized questionnaires permitted classification of patients's postoperative physical functions with results that agreed highly with the classification done by experienced clinicians who cared for the same patients.


Capillary electrophoresis with electrospray mass spectrometry detection for low-molecular-mass compounds.
Mass spectrometry (MS) detection using electrospray ionization (ESI) has been explored for the separation by capillary electrophoresis (CE) of a number of sample mixtures containing low-molecular-mass species. Optimal sheath liquid composition has been determined using a peptide mixture in which femtomolar quantities of analyte were easily observed. Effects of CE buffer choice were studied in detail. Also, a separation of basic drugs in cough syrup has been successfully detected by ESI-MS. Using negative ionization, a mixture of alkyl sulfonates and a mixture of food dyes were analyzed. All components were easily resolved and identified by molecular weight.


Hummingbird contribution to plant reproduction in the rupestrian grasslands is not defined by pollination syndrome.
Floral traits mediate the roles of distinct animals as effective pollinators along a generalization/specialization continuum. Many plant species are visited by different pollinator functional groups and the specific contribution of each group is expected to reflect the set of floral characteristics defined by pollination syndromes. Although considered a highly specialized nectarivorous group, hummingbirds frequently visit flowers lacking apparent specialization to bird pollination. How they contribute to the reproduction of these plants, however, has not been evaluated through field experiments considering multiple non-related plant species simultaneously. Here, we investigated hummingbirds' contributions to the pollination of ten plant species comprising a gradient of adaptation to bird pollination in the Brazilian rupestrian grasslands. We excluded hummingbirds from flowers and evaluated their relative contribution in comparison to insects (mainly bees) on conspecific/heterospecific pollen deposition and fruit set. Floral traits that are typically associated with bird pollination were associated with increased pollen deposition, but not with fruit set in the presence of hummingbirds. With hummingbirds, conspecific and heterospecific pollen deposition increased in most species, while fruit set increased in four plant species with varying degrees of fit to ornithophily. Our results show that assessing the relative contribution of specific pollinator groups may depend on when this contribution is measured, i.e. pollen deposition or fruit set. Considering fruit set, our results indicate that hummingbirds contributed to plant reproduction independently of the fit to bird pollination syndrome. This emphasizes their importance as under-appreciated generalized pollinators in some communities.


A preliminary study for a slantwise-placed electroglottography.
Slantwise-placed electroglottography (EGG) was proposed for synchronous use with an ultrasound machine in a previous work. The objective was to confirm the feasibility of this slant EGG, differentiate it from conventional EGG, and give suggestions for its applications. A synchronized system composed of an EGG device, a high-speed video, a sound level meter, and a headset was established. The same phonation conditions were acquired by training subjects to reach the target phonation frequency and intensity. Electrode position was designed, and vocal fold vibration parameters were measured from EGG waveforms recorded in each electrode position. Comparison showed that the characteristic points identified in slant EGG waveforms were consistent with the vibration phase shown by high-speed video images. Phonation frequency measured from slant EGG was highly accurate. EGG amplitude nonlinearly decreased with the increase of electrode distance. Compared with conventional EGG parameters, velocity ratio and glottal closed quotient measured from slant EGG were accurate when electrodes were placed symmetrically and the electrode distance was within a proper length. Slant EGG was proved feasible and can be considered as a useful tool to obtain comprehensive information in investigating the in vivo vocal fold dynamics when synchronized with other detecting equipment.


Electoral rewards for political grandstanding.
Many assumed that legislators send political messages or even grandstand in expectation of gaining electoral rewards. However, largely due to a lack of proper data and measurements, this assumption has not been tested. Publicized committee hearings provide a unique environment to consistently observe changes in legislators' speech patterns and test this assumption. Using House committee hearing transcripts from 1997 to 2016 and Grandstanding Scores-which capture the intensity of political messages conveyed in members' statements in hearings-I find that an increase in a member's messaging efforts in a given Congress leads to increased vote share in the following election. This suggests that legislators' grandstanding remarks, often regarded as cheap talk, can be an effective electoral strategy. Additional findings suggest that PAC donors respond differently to members' grandstanding behavior. Specifically, while voters react to members' grandstanding positively but are ignorant about their legislative effectiveness, PAC donors are unmoved by members' grandstanding behaviors and reward members' effective law-making activities instead. These asymmetric reactions from voters and donors may provide members with a twisted incentive to appeal to voters merely by making impressive, political speeches while legislating in favor of organized interests, which raises concerns about how representative democracy works.


Evaluating whole-genome expression differences in idiopathic and diabetic adhesive capsulitis.
Diabetic patients have a greater incidence of adhesive capsulitis (AC) and a more protracted disease course than patients with idiopathic AC. The purpose of this study was to compare gene expression differences between AC with diabetes mellitus and AC without diabetes mellitus. Shoulder capsule samples were prospectively obtained from diabetic or nondiabetic patients who presented with shoulder dysfunction and underwent arthroscopy (N = 16). Shoulder samples of AC with and without diabetes (n = 8) were compared with normal shoulder samples with and without diabetes as the control group (n = 8). Shoulder capsule samples were subjected to whole-transcriptome RNA sequencing, and differential expression was analyzed with EdgeR. Only genes with a false discovery rate < 5% were included for further functional enrichment analysis. The sample population had a mean age of 47 years (range, 24-62 years), and the mean hemoglobin A1c level for nondiabetic and diabetic patients was 5.18% and 8.71%, respectively. RNA-sequencing analysis revealed that 66 genes were differentially expressed between diabetic patients and nondiabetic patients with AC whereas only 3 genes were differentially expressed when control patients with and without diabetes were compared. Furthermore, 286 genes were differentially expressed in idiopathic AC patients, and 61 genes were differentially expressed in diabetic AC patients. On gene clustering analysis, idiopathic AC was enriched with multiple structural and muscle-related pathways, such as muscle filament sliding, whereas diabetic AC included a greater number of hormonal and inflammatory signaling pathways, such as cellular response to corticotropin-releasing factor. Whole-transcriptome expression profiles demonstrate a fundamentally different underlying pathophysiology when comparing diabetic AC with idiopathic AC, suggesting that these conditions are distinct clinical entities. The new genes expressed explain the differences in the disease course and suggest new therapeutic targets that may lead to different treatment paradigms in these 2 subsets.


Blood manganese concentration is elevated in iron deficiency anemia patients, whereas globus pallidus signal intensity is minimally affected.
To determine whether blood manganese (Mn) concentration is elevated in patients with iron deficiency anemia (IDA), and whether this affects signal intensities in the globus pallidus. Twenty-seven patients with IDA and 10 control subjects were tested for blood Mn, and brain magnetic resonance images (MRI) were also examined. Seventeen of the 27 patients were followed-up after iron therapy. IDA patients had a mean blood Mn concentration of 2.05 +/- 0.44 microg/dl, which was higher than controls. The mean pallidal index (PI) of anemic patients was not different from that of controls. There was a correlation between log blood Mn and PI (rho = 0.384, P = 0.048; n = 27) in IDA patients. None of the patients showed increased signals in the globus pallidus in T1-weighted MRI. Blood Mn levels decreased and hemoglobin levels increased after iron therapy (P < 0.05). Although blood Mn is elevated in IDA patients, there is no increase in globus pallidus MRI signal intensity. These findings stand in contrast to those of our other studies showing patients with chronic liver disease or occupational Mn exposure have elevated signal intensities remarkably.


Species variation and the mechanism of pressure-anaesthetic interactions.
The mechanism of general anaesthesia has proved difficult to elucidate (see ref. 1 for a review), although the relative potencies of anaesthetic agents have been used to establish that the site at which anaesthetics act is hydrophobic in nature. One further clue to their mode of action is that the effects of anaesthetics on vertebrates can be eliminated by pressures of approximately 100 atm (refs 3, 4). However, the effects of anaesthetics are not always reversed in model systems, where there is evidence that the pattern of pressure reversal varies significantly. We now find that pressure fails to reverse the effects of anaesthetics on the freshwater shrimp (Gammarus pulex), although the sensitivity of these crustaceans to anaesthetics is comparable with that of higher animals. This is hard to reconcile with traditional bio-physical mechanisms and indicates that anaesthetics may act at a specific protein site rather than having a general effect on cell membranes. The pharmacology of pressure in mammals seems to be more similar to that of strychnine than of any other central stimulant. As glycine, whose action is blocked by strychnine, is absent as a neurotransmitter in the arthropod central nervous system, we believe that this substance may be involved in determining pressure-anaesthetic interactions in vertebrates.


Synthesis of 2,5,8,11,14,17-hexafluoro-hexa-peri- hexabenzocoronene for n-type organic field-effect transistors.
A fluorine-substituted hexa-peri-hexabenzocoronene was synthesized as a thermostable active material for n-type semiconductors. The LUMO and HOMO energy levels, estimated by UV-vis and photoelectron spectroscopy, were lower by 0.5 eV than those of hexa-peri-hexabenzocoronene. A field-effect transistor fabricated by vacuum sublimation showed n-type performance with a field-effect mobility of 1.6 x 10(-2) cm(2)/Vs and an on/off ratio of 10(4). The electron-withdrawing effect of the fluorine substituents changed the polarity from p-type to n-type.


Why a mechanical disc?
Low back pain secondary to degenerative disc disease is an overwhelming and growing problem in the United States and Western countries. Most degenerative disc disease can be treated nonoperatively. There are, however, substantial numbers of patients who have not benefited from exhaustive nonoperative treatments and subsequently seek surgical solutions to their incapacitating back pain. Lumbar fusion for back pain and/or leg pain associated with degenerative disc disease is considered the gold standard by which other treatments are judged. A challenge to spinal fusion for degenerative disc disease is now being offered in the form of the artificial disc. The implantation of an artificial lumbar disc allows for maintenance or restoration of physiologic movement at affected segments. A major long-term complication of spinal fusion is degeneration of a disc adjacent to the fused segments. Theoretically, the maintenance of motion could minimize development of adjacent disc degeneration as seen with spinal fusion. It is interesting to note that fusion of the hip or knee is not considered a primary procedure, but fusion is a primary procedure for the lumbar spine. Four artificial lumbar discs are discussed in this article. Early results are promising in terms of clinical results and movement, but long-term follow-up clinical trials must be done in order to gain an accurate comparison with spinal fusion. Trials are currently ongoing. The clinical results up to now and the potential for maintaining lumbar mobility throughout life warrant continuation of this surgical procedure.


[Progress in Single-cell RNA Sequencing of Lung Adenocarcinoma].
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and one of the main causes of cancer-related deaths. In the past decade, with the widespread use of computed tomography (CT) in routine screening for lung cancer, the incidence of LUAD presenting as small pulmonary nodules radiologically, has increased remarkably. The mechanisms of the occurrence and progression of LUADs are complex, and the prognoses of patients with LUAD vary significantly. Although significant progress has been made in targeted therapy and immunotherapy for LUADs in recent years, the drug resistance of tumor cells has not been effectively overcome, which limits the benefits of patients. With the accomplishment of the Human Genome Project, sequencing-based genomic and transcriptomics have come into the field of clinical and scientific researches. Single-cell sequencing, as a new type of sequencing method that has captured increasing attention recently, can perform specific analysis of cell populations at single-cell level, which can reveal the unique changes of each cell type. Single-cell sequencing can also provide accurate assessment on heterogeneous stromal cells and cancer cells, which is helpful to reveal the complexity of molecular compositions and differences between non- and malignant tissues. To sum up, it is an urgent need for clinicians and basic scientists to deeply understand the pathogenesis and development of LUAD, the heterogeneity of tumor microenvironment (TME) and the mechanism of drug resistance formation through single-cell sequencing, so as to discover new therapeutic targets. In this paper, we reviewed and summarized the application and progress in single-cell sequencing of LUADs. .


Transaldolase is part of a supramolecular complex containing glucose-6-phosphate dehydrogenase in human neutrophils that undergoes retrograde trafficking during pregnancy.
Previous studies have shown that glucose-6-phosphate dehydrogenase (G6PDase) and 6-phosphogluconate dehydrogenase form a supramolecular complex in human neutrophils that undergoes retrograde trafficking in cells from pregnant women, but anterograde trafficking in cells from nonpregnant individuals. Using fluorescence resonance energy transfer techniques, we now demonstrate that transaldolase (TALase), a key regulatory enzyme in the nonoxidative branch of the hexose monophosphate shunt, is in close physical proximity with G6PDase, but not with lactate dehydrogenase, thus suggesting the formation of a TALase-G6PDase complex. Moreover, immunofluorescence microscopy demonstrated that TALase undergoes anterograde trafficking in neutrophils from nonpregnant individuals, whereas retrograde trafficking is found during pregnancy. However, pregnancy did not affect lactate dehydrogenase distribution. Colchicine treatment blocked the retrograde distribution of TALase, suggesting that microtubules are involved in TALase trafficking. We suggest that TALase is part of a supramolecular hexose monophosphate shunt complex, which likely increases the efficiency of the shunt via substrate channeling. We further suggest that TALase's retrograde motion contributes to uncoupling the shunt from its source of glucose-6-phosphate at the plasma membrane, thereby blunting nicotinamide adenine dinucleotide phosphate (reduced form) production and downstream oxidant production by neutrophils.


From carpet bombing to cruise missiles: the 'second-order' mechanisms used by transcription factors to ensure specific DNA binding in vivo.
Transcription factors generally have only modest specificity for their target sites, yet must find them in a sea of non-specific DNA. Some transcription factors are expressed at very high levels, to ensure that, despite losses to non-specific binding, the promoter is still occupied (the carpet-bombing strategy). Others increase their binding specificity by collaborating with other factors in a variety of ways.


Improving the intein-mediated, site-specific protein biotinylation strategies both in vitro and in vivo.
One of the critical issues in the generation of a protein microarray lies in the choice of immobilization strategies, which ensure proteins are adhered to the glass surface while properly retaining their native biological activities. We previously developed intein-mediated strategies for protein biotinylation and site-specific protein microarray generation. Herein, we report new findings of these strategies, which improve the biotinylation efficiency of proteins by up to 10-folds.


[Hypoxemia after general anesthesia].
Studies conducted shortly after the implementation of pulse oximetry (PO) into clinical practice 20-25 years ago revealed that many patients breathing room air during transfer from the operating room (OR) to the post-anesthesia care unit (PACU) directly after general anesthesia (GA) had a peripheral oxygen saturation (S(p)O(2)) below 90%. Moreover, it was shown that the detection of hypoxemia by clinical criteria is extremely unreliable. Meanwhile, the use of PO has become part of the obligatory standard monitoring during GA in Germany and many other countries. Likewise, the use of PO is standard care in the PACU although there are no official recommendations. However, for the time period in between, i.e. immediately after GA during transportation of patients from the OR to the PACU, monitoring of the S(p)O(2) in patients breathing room air is neither obligatory in Germany nor are there any official recommendations or guidelines in this respect. Given the introduction of shorter acting anesthetic agents within the last 25 years, the main goal of this study was to explore whether the incidence of hypoxemia in the immediate period after GA is still so high. Additional aims of this study were to examine whether the detection of hypoxemia based on clinical criteria can be confirmed to be very unreliable, what the risk factors for hypoxemia following GA are and how common it is in Germany to transport patients from the OR to the PACU without PO and supplemental oxygen. In a prospective observational study 970 patients who underwent a broad spectrum of elective surgery under GA in a university hospital setting were included. The S(p)O(2) was measured at the end of the transfer from the OR to the PACU immediately after the anesthetist who had taken care of the patient during the operation had estimated the S(p)O(2). The association between biometric, surgical and anesthesiological variables on the one hand and hypoxemia as well as a decrease of S(p)O(2) on the other hand were studied using multivariate methods. Finally, a survey including all university hospitals was carried out to find out about the use of PO and oxygen during patient transfer from the OR to the PACU. Of the 959 patients who were eligible for analysis 17% had a S(p)O(2) < 90% and 6.6% a S(p)O(2) < 85%. Hypoxemia was not recognized in 82% of the patients in whom an assessment based on clinical grounds was carried out. Variables with an independent influence on hypoxemia and decrease of S(p)O(2) were as follows: saturation before induction of GA, body mass index, age, American Society of Anesthesiologists (ASA) physical status, difference between maximum and minimum inspiratory pressure, mode of ventilation, the choice of opioid and muscle relaxant as well as the use of nitrous oxide. Patient-dependent risk factors had the strongest impact on hypoxemia. In about 80% of the university hospitals neither PO nor supplemental oxygen is used during transportation of the patient from the OR to the PACU. The use of opioids and relaxants with short duration of action may have favorable effects on preventing hypoxemia and decreases of S(p)O(2). These measures will, however, not be sufficient to solve this problem because the highest risk factors for hypoxemia are patient-related. Despite knowing risk factors for oxygen desaturation, it is currently not possible to reliably predict which patients will become hypoxemic or have a decrease of S(p)O(2). Therefore, transportation of patients breathing room air from the OR to the PACU directly after GA without use of PO or supplemental oxygen seems to be questionable in terms of patient safety.


Effects of tandem cognitive behavioral therapy and healthy lifestyle interventions on health-related outcomes in cancer survivors: a systematic review.
Healthy lifestyle (HL) behaviors and cognitive behavioral therapy (CBT) have been individually shown to improve adverse effects of cancer treatment. Little is known about how such programs in tandem affect health-related outcomes. This review evaluates extant literature on tandem CBT/HL interventions on health-related outcomes in cancer survivors. A comprehensive search of PubMed, PsychINFO, CINAHL, and Embase databases revealed numerous studies involving CBT and HL tandem interventions in cancer survivors in the last 20 years. Studies meeting the inclusion criteria were examined and assessed by the authors. The 36 studies included 5199 participants. Interventions involved the use of CBT in combination with a HL condition (stress reduction, increasing physical activity, etc.). These tandem conditions were compared against no intervention, usual care, and/or CBT alone or HL alone. Interventions were delivered by a variety of interventionists, and over different durations. The most common HL target outcomes were stress, and insomnia. Most studies (31 of 36) reported a reduction in adverse treatment and/or cancer-related effects. Findings were biased with the overrepresentation of breast cancer survivors, and underrepresentation of minority groups, and those with advanced cancer. Thus, this review highlights the need for further research to test tandem interventions against CBT alone and HL alone, and toward identifying the most efficacious interventions for dissemination and implementation across diverse groups of cancer survivors. Implications for cancer survivors Tandem CBT/HL interventions can improve health-related outcomes for cancer survivors when compared to usual care, but there is a paucity of knowledge to suggest differential outcomes when compared to CBT or HL alone.