Is targeted chemotherapy an alternative to immunotherapy in chronic lymphocytic leukemia?
Although molecular remission is now detected, it is still unknown whether we have the tools to cure B cell chronic lymphocytic leukemia (referred to as CLL). Nonetheless, several new therapeutic approaches have been introduced in cancer therapy during the last decade, including antiangiogenic therapy, apoptosis-inducing treatment and inhibition of heat shock proteins, farnesyl transferase, tyrosine kinases and proteasomes. These modalities may also be considered in CLL, but additional experimental characterization is required. Further characterization and development of CLL animal models should be a part of this preclinical work (especially xenografting in NOD/SCID animals, but also murine leukemia) to allow a more extensive evaluation prior to clinical trials. Animal models are particularly important for preclinical comparison of pharmacological effects between different disease compartments and for in vivo evaluation of antileukemic immune reactivity. However, T cell targeting therapy seems to have several advantages in comparison to other approaches: (1) based on the current clinical experience one would expect low toxicity for several of these strategies, especially vaccine treatment; (2) several studies have demonstrated that autologous T cells can recognize CLL cells; (3) experimental and clinical evidence suggests that immunotherapy can be combined with chemotherapy. Thus, T cell therapy has a relatively strong scientific basis that justifies further clinical studies of immunotherapy in CLL. Although several of the new pharmacological agents seem to have immunosuppressive effects, at least some of them (e.g. heat shock protein 90 inhibitors, proteasome inhibitors, inhibition of angiogenesis) appear to affect T cells only at relatively high concentrations and may thus be used in combination with immunotherapy.


Intra- and inter-rater reliability of urethral mobility measurement by ultrasound in women: a cross-section study.
To verify the intra- and inter-rater reliability of urethral mobility measurement evaluated by ultrasound (US). This is a reliability study realized according to Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) recommendations. Twenty-one nulliparous women (25.5 ± 3.3 SD years) were volunteers. Two examiners (E1 and E2) performed the measurement of urethral mobility at rest and Valsalva on the same day. Three measurements were recorded for each moment and the mean of them were used for analysis. To perform the analysis, bladder mobility was calculated using the following equation: [Formula: see text], where "x" is the vertical distance, "y" is the horizontal distance from the dorsocaudal margin of the pubic symphysis, "V" is the Valsalva maneuver, and "R" means rest. The intraclass correlation coefficient (ICC) was calculated considering: ICC ≥ 0.75, excellent; 0.40 ≤ ICC <0.75, satisfactory; ICC < 0.40, poor, with a significance level of 5% and 95% confidence interval. The intra-rater reliabilities of E1 and E2 were considered excellent between the two evaluations, with ICC 0.98 (p < 0.0001) for the E1 and 0.84 (p < 0.0001) for E2. The inter-rater reliability was considered excellent (ICC = 0.83). Both intra- and inter-rater reliabilities of urethral mobility measurement were considered to have excellent agreement.


Expression of hypoxia inducible factor-1 alpha, macrophage migration inhibition factor, matrix metalloproteinase-2 and -9, and their inhibitors in hemodialysis grafts and arteriovenous fistulas.
It is well recognized that arteriovenous fistulas (AVFs) used for hemodialysis access have better primary patency rates with less restenosis than polytetrafluoroethylene (PTFE) grafts; however, the mechanism responsible for this is not known. Recent data suggest that hypoxia inducible factor-1 alpha (HIF-1 alpha) is associated with vascular restenosis, possibly through mechanisms that increase the production of macrophage migration inhibition factor (MIF), matrix metalloproteinase-2 (MMP-2) and MMP-9, and their inhibitors (tissue inhibitor of MMPs; TIMP). The present study tested the hypothesis that there are differences in the expression patterns of HIF-1 alpha, MIF, MMP-2, MMP-9, and TIMPs in specimens removed from patients with AVFs and PTFE grafts. Whole-vessel tissue samples were obtained from the vein distal to the vein-to-PTFE graft anastomosis and the proximal outflow vein (within 6 cm of the arteriovenous anastomosis) of AVFs from 17 patients who required a surgical revision for thrombosis and stenosis. Nonstenotic veins of four patients undergoing hemodialysis vascular access placement were used as controls. PTFE grafts (n = 6), AVFs (n = 6), and control samples (n = 3) underwent Western blot analysis and zymography. A separate group of five patients with PTFE hemodialysis grafts and one control subject were used for immunohistochemical analysis. Specimens from patients with PTFE grafts had significantly higher expression of HIF-1 alpha (P = .03), MIF (P = .02), TIMP-1 (P = .0006), pro-MMP-2 (P = .02), and pro-MMP-9 (P = .046) compared with control veins. The expression of only pro-MMP-9 was significantly higher in AVFs compared with control samples (P = .004). There was a significant increase in the expression of MIF (P = .007) and TIMP-1 (P < .0001) in PTFE graft specimens compared with AVFs. MIF and TIMP-1 were localized to the adventitia of the vein distal to the vein-to-PTFE graft anastomosis. There were major differences in the expression patterns of hypoxia (ie, HIF-1 alpha) and proteins regulated by HIF-1?, including MIF, pro-MMP-2, pro-MMP-9, and TIMP-1, in specimens removed from patients with PTFE grafts and AVFs. Understanding the role of HIF-1 alpha and these proteins in hemodialysis access failure can help improve outcomes.


Experimental esophagitis induced by acid and pepsin in rabbits mimicking human reflux esophagitis.
The lack of appropriate animal models might explain the paucity of information on the mechanisms of mucosal damage and defense in reflux esophagitis. The aim of this study was to develop a model of esophagitis in rabbits mimicking human reflux esophagitis. New Zealand white rabbits underwent surgery for placement of a plastic tube into the cervical esophagus. Acidified pepsin (AP) was intermittently perfused for different periods. Esophageal injury was assessed by macroscopic and microscopic examination, including the cell proliferation immunohistochemical parameter mib1. Rabbit losses (20%) were attributable mostly to postsurgical mortality and tube displacement. Perfusion of AP for 60 min/12 h or 45 min/12 h induced high-grade esophagitis by days 3 and 5, respectively, characterized by diffuse erosion/ulceration, inflammation, bleeding, and reactive epithelial changes. Perfusion of acidified pepsin for 60 min/day, especially at 30 min/12 h, induced low-grade esophagitis characterized by superficial epithelial loss, mild/absent inflammation, and epithelial reactive changes including increased cell proliferation, basal hyperplasia, and papillomatosis, which reached maximal expression by day 7. This perfusion regimen induced mucosal adaptation to damage. Different and highly reproducible esophageal mucosal lesions mimicking human reflux esophagitis can be induced in rabbits with repetitive acid and pepsin exposure.


Insulin resistance and impaired glucose tolerance in obese children and adolescents.
In developed countries, obesity prevalence has strongly increased in the last decades. This has also been observed in children and adolescents. Until recently, type 2 diabetes mellitus was considered very rare among children and adolescents; however, in the last decades, some cases have been observed mainly in obese adolescents of some minority populations. The aim of our study was to assess the prevalence of type 2 diabetes, impaired glucose tolerance (IGT) and insulin resistance, and the metabolic features, in obese children and adolescents. We have studied 95 obese children and adolescents, 53 males and 42 females, aged 4-16 years. The prevalence of IGT in obese children and adolescents studied was 7.4%; there was not any child with type 2 diabetes. Fasting glucose and insulin serum concentrations did not show significant differences between obese children with or without IGT; however, 120 minutes after an oral glucose tolerance test, glucose and insulin serum concentrations showed statistically significant differences between both groups. Insulin resistance is defined as a HOMA index higher than 4. The prevalence of insulin resistance in obese children studied was 35.8%. Trygliceride serum concentrations were higher and HDL-C serum concentrations were lower in obese children with IGT than in those without IGT, but the differences were not statistically significant. IGT and insulin resistance are frequent in obese children and adolescents; early treatment in obese children and adolescents with IGT constitutes a strategy of reversing progression to beta-cell failure and in preventing type 2 diabetes.


Transcriptome Sequencing and iTRAQ of Different Rice Cultivars Provide Insight into Molecular Mechanisms of Cold-Tolerance Response in Japonica Rice.
Rice (Oryza sativa L.) is one of the most important crops cultivated in both tropical and temperate regions. However, it has a high sensitivity to cold stress and chilling stress limits its nitrogen uptake and metabolism. To identify the genes and pathways involved in cold tolerance, specifically within nitrogen metabolism pathways, we compared gene and protein expression differences between a cold-tolerant cultivar, Dongnong428 (DN), and a cold-sensitive cultivar, Songjing10 (SJ). Using isobaric tags for relative or absolute quantification (iTRAQ) with high-throughput mRNA sequencing (RNA-seq) techniques, we identified 5549 genes and 450 proteins in DN and 6145 genes and 790 proteins in SJ, which were differentially expressed during low water temperature (Tw) treatments. There were 354 transcription factor (TF) genes (212 downregulated, 142 upregulated) and 366 TF genes (220 downregulated, 146 upregulated), including 47 gene families, differentially expressed in DN under control (CKDN) vs. DN under low-Tw (D15DN) and SJ under control (CKSJ) vs. SJ under low-Tw D15SJ, respectively. Genes associated with rice cold-related biosynthesis pathways, particularly the mitogen-activated protein kinase (MAPK) signaling, zeatin biosynthesis, and plant hormone signal transduction pathways, were significantly differentially expressed in both rice cultivars. Differentially expressed proteins (DEPs) associated with rice cold-related biosynthesis pathways, and particularly glutathione metabolism, were significantly differentially expressed in both rice cultivars. Transcriptome and proteome analysis of the nitrogen metabolism pathways showed that major genes and proteins that participated in γ-aminobutyric acid (GABA) and glutamine synthesis were downregulated under cold stress. Cold stress conditions during reproductive growth, resulted in genes and proteins related to cold stress biosynthesis pathways being significantly differentially expressed in DN and SJ. The present study confirmed the known cold stress-associated genes and identified new putative cold-responsive genes. We also found that translational regulation under cold stress plays an important role in cold-tolerant DN. Low-Tw treatments affected N uptake and N metabolism in rice, as well as promoted Glu metabolism and the synthesis of ornithine and proline in cold-sensitive SJ.


Effects of taurine on basal and stimulated luteinizing hormone (LH) and LH-releasing hormone secretion in ovariectomized rats: in vitro studies.
Taurine (Tau), a putative inhibitory amino acid neurotransmitter, has been shown to inhibit luteinizing hormone (LH) release in vivo. We investigated the effect of this amino acid on LH secretion by cultured anterior pituitary cells. A 5-h incubation with Tau (10(-3)-10(-8) M) did not affect basal or LH-releasing hormone (LHRH)-stimulated LH release. Basal LHRH release from superfused mediobasal hypothalamic fragments was not affected by Tau (10(-3) M). However, this substance clearly diminished LHRH release after stimulation with KCl (50 mM) or N-methyl-D-aspartate (10(-4) M). It is concluded that Tau may exert an inhibitory effect on LH secretion acting at the hypothalamic level.


Transplantation is a risk factor for acute kidney injury in patients undergoing total hip replacement arthroplasty for avascular necrosis: an observational study.
The increased number of patients undergoing transplantation has increased the number of transplant recipients undergoing total hip replacement arthroplasty (THRA). We have evaluated the association between transplantation and acute kidney injury (AKI) in patients undergoing THRA. Patients who underwent THRA from May 2004 to February 2012 were retrospectively assessed. Their demographic and clinical characteristics, the results of perioperative laboratory tests, the amounts of fluids transfused during surgery, and anesthesia time were evaluated. Patients were divided into 2 groups: transplant (n = 222) and nontransplant (n = 2,044) patients. With use of the maximal Acute Kidney Injury Network criteria, AKI was evaluated by changes in creatinine concentration within 48 hours of THRA. Propensity analyses and logistic regression were performed to evaluate the association between transplantation and postoperative AKI. Postoperative AKI was significantly associated with transplantation (P < .0001), and transplantation was an independent factor predictive of postoperative AKI (P < .0001). Transplant recipients are at risk for AKI following THRA. The mechanism by which organ transplantation enhances postoperative AKI warrants further evaluation.


Silencing of microRNA-375 affects immune function in mice with liver failure by upregulating astrocyte elevated gene-1 through reducing apoptosis of Kupffer cells.
This study aims to investigate how microRNA-375 (miR-375) improves immune function by regulating liver macrophages (Kupffer cells) in mice with liver failure. Forty mice were divided into ConA-1h, ConA-3h, ConA-6h, and control groups, with 10 mice in each group. Mice models of liver failure were established by injecting concanavalin A (ConA) solution via the tail veins of mice, and then primary Kupffer cells were isolated and cultured. Reverse transcription quantitative polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay were conducted to examine the expressions of miR-375, astrocyte elevated gene-1 (AEG-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β in Kupffer cells of mice with liver failure as well as after silencing of miR-375. Flow cytometry was used to determine cell apoptosis. During the liver failure process, miR-375, IL-6, TNF-α, and IL-1β expressions were increased over time, while AEG-1 expression decreased over time in the control, ConA-1h, ConA-3h, and ConA-6h groups. Opposite alternations were observed after silencing of miR-375. Dual-luciferase reporter gene assay showed that AEG-1 was a target gene of miR-375. Flow cytometry determination showed that the ratio of apoptotic Kupffer cells decreased after silencing of miR-375. Overexpression of AEG-1 could rescue the suppression of IL-6, TNF-α, and IL-1β expressions in Kupffer cells after the short-term induction of ConA and further inhibit cell apoptosis. Our study provides evidence that miR-375 could regulate Kupffer cells to improve immune function in mice with liver failure.


Mutational analysis and a structural model of methyl-directed restriction enzyme Mrr.
The Mrr protein of Escherichia coli K12 is a cryptic Type IV restriction endonuclease whose activity appears to be triggered by high pressure stress. In this report we used high pressure to isolate and analyze several Mrr mutants, and generated a new structural model of the Mrr protein. The activity of a number of spontaneous and strategically constructed Mrr mutants is discussed in the light of this model, providing a first insight into the structure-function relationships of the Mrr enzyme.


Improving protein secretion of a transglutaminase-secreting Corynebacterium glutamicum recombinant strain on the basis of 13C metabolic flux analysis.
Corynebacterium glutamicum is known as a host species for amino acid production. This microorganism was recently noticed as a host that produces secreted proteins. In this study, we performed (13)C metabolic flux analysis ((13)C-MFA) on a recombinant C. glutamicum strain that secretes a heterologous transglutaminase (TGase) to improve TGase secretion. For the (13)C-MFA of a TGase-secreting C. glutamicum strain in batch cultivation, a (13)C-labeling experiment and measurement of mass isotopomer distributions of proteinogenic amino acids were performed, and metabolic fluxes were determined considering the changes in fractional (13)C-labeling of proteinogenic amino acids with respect to culture time. The TGase yield increased at the stationary phase but decreased toward its end. The results of (13)C-MFA revealed that the flux from glycolysis to the TCA cycle gradually increased during TGase secretion. We speculate that the NADH/NAD(+) ratio in the cells increases and that as a result, the specific glucose uptake rate decreases in the stationary phase because of the increased flux of the TCA cycle. Since it is expected that a decrease in the NADH/NAD(+) ratio would improve the TGase yield, we tried to enhance lactate production in a TGase-secreting C. glutamicum strain to decrease cellular NADH levels by increasing the pH level in the culture. The TGase yield increased in 1.4-fold by increasing the pH from 6.7 to 7.2, indicating that the TGase yield was successfully improved on the basis of the (13)C-MFA.


The effect of fecapentaenes on nuclear aberrations in murine colonic epithelial cells.
Fecapentaenes, human fecal mutagens of bacterial origin, were intrarectally administered to mice in suppository form. Despite the strong, positive mutagenic response of fecanpentaenes using Ames tester strains TA 98 and TA 100, no increase in nuclear aberrations, taken as a measure of genotoxicity in colonic epithelial cells, was observed over control levels. In fecapentaene treated animals, however, the incidence of mitotic figures was increased above control levels to values comparable to those observed in mice treated with the known colon carcinogen, N-ethyl-N-nitrosourea. Thus, it would appear that fecapentaenes are not cytotoxic to murine colonic epithelia as judged by the nuclear aberration assay.


Electrical stimulation of the rectal ampulla causing reflex voiding.
Electrical stimulation of the rectal ampulla resulted in a desire to void and defecate in 11 patients with an intact nervous system. There was a contraction of the detrusor and the rectal ampulla with relaxation of the anal sphincter. Electrical stimulation of the rectal ampulla and anal sphincter has clinical applications in patients with incontinence of, or inability to empty, the lower urinary tract or fecal system.


Interaction of quaternary ammonium compounds with acetylcholinesterase: characterization of the active site.
The relation of the structure of 31 quaternary ammonium compounds (28 inhibitors; 3 substrate analogues) with their effects on the activity of acetylcholinesterase (EC 220.127.116.11; AChE) was studied. The compounds were structurally related to the natural substrate acetylcholine (ACh). All bear a trimethylammonium moiety as cationic head. The inhibitors include a variety of functional groups instead of an electrophilic ester group, making these substances suitable to probe the esteratic subsite. The inhibition constants and Km values were determined in kinetic experiments under steady state conditions (pH-stat method). Most of the substances acted as reversible, competitive inhibitors with KI in the range of 10(-6)-10(-3) M. The substrate analogues had Km values between (1.2-2.2) X 10(-4) M. The data allow the following main conclusions: (1) The quaternary trimethylammonium group of ACh is of high importance for substrate binding to AChE. It mediates association at the anionic site. (2) A poorer contribution to binding (two orders of magnitude lower) is attributable to the apolar methylene chain in ACh. It can be related to a hydrophobic interaction of the hydrocarbon chain at a region neighbouring the anionic site. (3) The ester group (both C = O and O) does not contribute to substrate binding. It is only responsible for reactivity.


Low-Coordination Single Au Atoms on Ultrathin ZnIn2 S4 Nanosheets for Selective Photocatalytic CO2 Reduction towards CH4.
Selective CO2 photoreduction to hydrocarbon fuels such as CH4 is promising and sustainable for carbon-neutral future. However, lack of proper binding strengths with reaction intermediates makes it still a challenge for photocatalytic CO2 methanation with both high activity and selectivity. Here, low-coordination single Au atoms (Au1 -S2 ) on ultrathin ZnIn2 S4 nanosheets was synthesized by a complex-exchange route, enabling exceptional photocatalytic CO2 reduction performance. Under visible light irradiation, Au1 /ZnIn2 S4 catalyst exhibits a CH4 yield of 275 μmol g-1 h-1 with a selectivity as high as 77 %. As revealed by detailed characterizations and density functional theory calculations, Au1 /ZnIn2 S4 with Au1 -S2 structure not only display fast carrier transfer to underpin its superior activity, but also greatly reduce the energy barrier for protonation of *CO and stabilize the *CH3 intermediate, thereby leading to the selective CH4 generation from CO2 photoreduction.


Psoriasis vulgaris and genetic markers.
In a sample of n = 160 nonrelated male and female patients suffering from psoriasis Vulgaris, blood serum protein, and enzyme group typings have been carried out and compared with healthy controls from the same area (Rheinland-Pfalz). Marked statistically significant differences between patients and controls were found in none of the genetic blood polymorphisms considered here. However, combining previously published data from various authors with our own, significant associations between this skin disease and genetic polymorphisms such as MN, Gc, Gm (2), red cell acid phosphatase, and red cell phosphoglucomutase (PGM1) were seen. The possible reasons for these associations are discussed.


The bioactive amide alkaloids from the stems of Piper nigrum.
Piper nigrum is an important aromatic plant, and its fruits (black and white pepper) are commonly used as food additives and spices. However, its stems were disposed as wastes. This research comprehensively investigated bioactive alkaloids of the stems, eight new dimeric amide alkaloids and eight known compounds were obtained. All obtained compounds showed excellent anti-inflammatory activity. Additionally, the dimeric amide alkaloids enhanced the anticancer effect of paclitaxel against cervical cancer cells. These results demonstrate that the stems of P. nigrum could be the sustainable source of bioactive alkaloids for development and utilization in the food and health fields.


Growth hormone bioactivity, insulin-like growth factors (IGFs), and IGF binding proteins in obese children.
In obese children, both spontaneous and stimulated growth hormone (GH) secretion are impaired but a normal or increased height velocity is usually observed. This study was undertaken to explain the discrepancy between impaired GH secretion and normal height velocity. We evaluated the GH bioactivity (GH-BIO), GH serum level by immunofluorimetric assay (GH-IFMA), insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in 21 prepubertal obese children (13 boys and eight girls) aged 5.7 to 9.4 years affected by simple obesity and in 32 (22 boys and 10 girls) age- and sex-matched normal-weight controls. The results were as follows (obese versus [v] controls): GH-IFMA, 4.84 +/- 3.54 v 23.7 +/- 2.04 microg/L (P < .001); GH-BIO, 0.60 +/- 0.45 v 1.84 +/- 0.15 U/mL (P < .001); IGF-I, 173.8 +/- 57.2 v 188.6 +/- 132.6 ng/mL (nonsignificant); IGF-II, 596.1 +/- 139.7 v 439.3 +/- 127.4 ng/mL (P < .001); IGFBP-1, 23.25 +/- 14.25 v 107 +/- 165.7 ng/mL (P < .05); IGFBP-2, 44.37 +/- 62.18 v 385.93 +/- 227.81 ng/mL (P < .001); IGFBP-3, 3.31 +/- 0.82 v 2.6 +/- 0.94 microg/mL (P < .05); and IGFs/IGFBPs, 1.32 +/- 0.32 v 1.07 +/- 0.34 (P < .05). In conclusion, in prepubertal obese children, not only immunoreactive but also bioactive GH concentrations were low. In these subjects, therefore, nutritional factors and insulin may contribute to sustain normal growth also by modulating several components of the IGF-IGFBP system.


Survival factors in patients of high fall - A 10-year level-I multi-trauma center study.
This study aims to investigate the characteristics of patients after free falls at the Level-I trauma centers. The factors associated with survival were differentiated. This retrospective study was conducted at the National Taiwan University Hospital, the Hsin-Chu branch, and the Yun-Lin branch, all accredited as Level-I trauma centers between January 2010 and September 2020. Adult patients with falls from height of more than one story (i.e. 3.6 m) were included. Clinical data were obtained from electronic medical records. Odds ratios (OR) were computed with 95% confidence intervals (CIs) for significant parameters for survival. A total of 371 patients were included. Only 2 survived to discharge with poor neurologic outcomes in 101 patients with OHCA. The overall mortality rate was 98% and 11% in patients with and without OHCA. A higher falling height with a one-meter increase (OR, 1.14, 95% CI, 1.10-1.19) was significantly related to OHCA, especially the height over 6 m (OR, 3.07, 95% CI, 1.19-7.94). A higher trauma injury severity score (TRISS) was significantly related to survival among patients without OHCA (OR, 1.07, 95% CI, 1.04-1.11), especially TRISS≧0.945 (OR, 5.21, 95% CI, 1.28-21.24). Patients without severe head/neck injury of Abbreviated Injury Scale (AIS)≧3 (OR, 0.17, 95% CI, 0.07-0.42) were positively associated with survivors among patients without OHCA. Patients with traumatic OHCA following falls had a high mortality rate of 98% and dismal outcomes, compared with non-traumatic OHCA. Falling heights, especially over 6 m was associated with OHCA. Patients without OHCA had a mortality rate of 11%. Patients with a higher TRISS, especially more than 0.945, or without severe head injury had more chances to survive in the non-OHCA group. The study provided the evidence to guide termination of high futility resuscitation for traumatic OHCA secondary to falls to conserve the clinical resources.


[Examination of condylomatous lesions of the uterine cervix in 468 anatomic specimens. Retrospective study].
On the basis of 468 anatomical specimens, we intended to look for histological signs of an HPV (human papilloma virus) infestation. This study has enabled to calculate the true incidence of this pathology, to correlate the histo-clinical aspects as well as the association severe lesions-condylomatous lesions. Our conclusions confirm the close connection between viral lesions and malignant pathology of the cervix.


Heart-lung transplantation in a patient with pulmonary atresia and ventricular septal defect.
Operation for pulmonary atresia and ventricular septal defect is challenging, as in most patients the pulmonary arteries are hypoplastic, nonconfluent, or in part absent. In these cases, combined heart-lung transplantation may be the surgical treatment of choice. In the described case, the morphology of pulmonary atresia and ventricular septal defect was present in combination with completely atretic main, left, and right pulmonary arteries. In this patient, successful heart-lung transplantation was performed.


Depletion of cellular glycogen during the early logarithmic growth phase of human fibroblasts.
Human diploid fibroblasts deplete 50% of their cellular glycogen by day 4 after subcultivation in 100 mg% glucose medium. The glycogen content increases again as the cells approach confluency. Growth of cells in low glucose medium results in rapid glycogen depletion and indicates that stored glycogen has a limited potential as an energy source.


Mycotoxins in cereal grain. Part VI. The effect of ochratoxin A on growth and tissue residues of the mycotoxin in broiler chickens.
Eight weeks experiment on effects of continuous feeding of mycotoxin graded levels (0; 9.5; 1.0; .5; 2.0 mg ochratoxin A (OA) per kilogram of feed) to male and female broiler chickens was carried out. Birds' mortality was similar in all groups including control. Macroscopical veterinary examination did not reveal any changes in livers and kidneys. Males were found to be more sensitive to OA than females. The depression of body weight was found to be proportional to level of OA. The reduction of body weight of males (30%) was more significant than that of females (20%). Feed consumption per one kilogram of body weight was dependent on OA concentration in feed. In livers and white muscles of birds fed 1.0; 1.5 and 2.0 mg OA/kg feed and in red muscles of birds fed 1.5 and 2.0 mg OA/kg feed residues of OA were observed. OA disappeared completely from all mentioned tissues after 4 days when birds were fed with OA free feed.


[Serous otitis: long-term efficacy of transtympanic drainage].
The A. has followed for a whole year (1982), 50 patients chosen at random who underwent transtympanic ventilation, with the goal of assessing the long-term results (both audiometric and tympanometric) linked with the previous pathology.


Partitioning the transplant site effect in reciprocal transplant experiments with Impatiens capensis and Impatiens pallida.
Modified reciprocal transplant experiments were conducted with the annual plant species Impatients capensis and I. pallida to partition the influence of environment on fitness into two components; that of (1) conspecific neighbours occupying each transplant site, and (2) the abiotic and biotic features of each site exclusive of the conspecific neighbours. In the within-species reciprocal transplant series, differences in survivorship and fruit production by cleistogamous flowers were attributable primarily to the effect of conspecific neighbours. In addition, plants surrounded by neighbours from the site of origin produced significantly more fruit from chasmogamous flowers compared with plants surrounded by neighbours from the alien site. In the between-species reciprocal transplant series, one transplant site was consistently associated with greater survivorship and fruit production regardless of the identity of neighbouring plants. The results suggest that different aspects of the environment in these reciprocal transplant experiments (conspecific neighbours, other species, physical factors) determine fitness in different situations.


Opportunistic yeast infections: candidiasis, cryptococcosis, trichosporonosis and geotrichosis.
Opportunistic yeast infections are diseases caused by fungi which normally are saprophytic and do not cause disease in humans or animals. The prevalence of these diseases has been increasing due to immunosuppressive, corticosteroid, and long-term antibiotic treatment following organ transplantation or after serious metabolic, hematological, or immunological diseases. We review epidemiological, clinical, diagnostic, and therapeutic aspects of the four "big" opportunistic yeast infections: candidiasis, cryptococcosis, trichosporonosis, and geotrichosis.


Genetic analysis of developmental mechanics in hydra. XI. Mechanism of sex reversal by heterosexual parabiosis.
Sex change from female to male occurs at a high rate in hydra when a female polyp is exposed to a male polyp by parabiosis for a limited length of time. The mechanism of this masculinization process was investigated. When a male strain which produces immotile sperm was used to masculinize female strains, the resultant masculinized animals produced only immotile sperm. Evidence was also obtained which indicated that the original female interstitial cells remained in large numbers in the masculinized animals but did not differentiate into gametic cells. These observations suggest that masculinization is achieved not by the hypothetical "masculinizing factor" but by the migration of the male interstitial cells from the male to the female tissue during parabiosis.


Acquisition of chromosome 1q duplication in parental and genome-edited human-induced pluripotent stem cell-derived neural stem cells results in their higher proliferation rate in vitro and in vivo.
Genetic engineering of human-induced pluripotent stem cell-derived neural stem cells (hiPSC-NSC) may increase the risk of genomic aberrations. Therefore, we asked whether genetic modification of hiPSC-NSCs exacerbates chromosomal abnormalities that may occur during passaging and whether they may cause any functional perturbations in NSCs in vitro and in vivo. The transgenic cassette was inserted into the AAVS1 locus, and the genetic integrity of zinc-finger nuclease (ZFN)-modified hiPSC-NSCs was assessed by the SNP-based karyotyping. The hiPSC-NSC proliferation was assessed in vitro by the EdU incorporation assay and in vivo by staining of brain slices with Ki-67 antibody at 2 and 8 weeks after transplantation of ZFN-NSCs with and without chromosomal aberration into the striatum of immunodeficient rats. During early passages, no chromosomal abnormalities were detected in unmodified or ZFN-modified hiPSC-NSCs. However, at higher passages both cell populations acquired duplication of the entire long arm of chromosome 1, dup(1)q. ZNF-NSCs carrying dup(1)q exhibited higher proliferation rate than karyotypically intact cells, which was partly mediated by increased expression of AKT3 located on Chr1q. Compared to karyotypically normal ZNF-NSCs, cells with dup(1)q also exhibited increased proliferation in vivo 2 weeks, but not 2 months, after transplantation. These results demonstrate that, independently of ZFN-editing, hiPSC-NSCs have a propensity for acquiring dup(1)q and this aberration results in increased proliferation which might compromise downstream hiPSC-NSC applications.


Extracorporeal Membrane Oxygenation in Postcardiotomy Cardiogenic Shock.
Postcardiotomy extracorporeal membrane oxygenation (PC-ECMO), the most frequent indication for ECMO in the United States, is increasingly used as the first-line mechanical circulatory support in patients who are refractory to conventional treatment. Despite increasing use of PC-ECMO, limited evidence is available regarding its safety, efficacy, and optimal timing for initiation and weaning. The decision to use PC-ECMO often is made in the absence of robust clinical data, leading to variability in patient selection, management, and outcomes across different institutions. This article summarizes current evidence on ECMO use in postcardiotomy cardiogenic shock and discusses its potential benefits, management, complications, and outcomes.


Structure-activity relationships for unsaturated dialdehydes. 3. Mutagenic, antimicrobial, cytotoxic, and phytotoxic activities of merulidial derivatives.
The mutagenic activity in the Ames' Salmonella assay, the antimicrobial activities against bacteria, fungi, and algae, the cytotoxic activities against Ehrlich ascitic tumor cells and L1210 cells, and the phytotoxic activities against Lepidium sativum and Setaria italica, of the unsaturated dialdehyde merulidial and six acetylated, hydroxylated, and cyclopropane ring isomerized derivatives of merulidial, are compared. Some possible structure-activity relationships are discussed.


[Prophylactic Appendectomy: Yes or No?]
Background At more than 50%, appendicitis is the leading cause of acute intra-abdominal disease requiring surgery. In the course of various other operations, prophylactic appendectomy (PA) is frequently performed. Objectives This study examines to what extent PA is justified. Patients and Methods A prospective study was performed in all patients (n = 173) undergoing prophylactic appendectomy in Katharinen Hospital Unna between January 2010 and October 2013. The following variables were analysed: age, gender, type of primary surgery, emergency or elective surgery, complications, lethality, intraoperative and histopathological evaluation of the appendix. In addition, patients were contacted postoperatively with the request to complete a questionnaire. Results Prophylactic appendectomy was carried out without any specific complications. 117 patients (68%) participated in the survey. 15% of these patients had suffered symptoms that could be attributable to irritation of the appendix. With only one exception, all appendectomy specimens revealed pathological findings in the histopathological examination. PA allowed the early diagnosis of 4 adenomas, one neuroendocrine tumour and 6 metastases or manifestations of peritoneal carcinomatosis. Conclusion PA is ethically justifiable, as there are few complications. Moreover, it can help to avoid future appendicitis and allows early detection of malignancies.


Computational study of the intermolecular interactions and their effect on the UV-visible spectra of the ternary liquid mixture of benzene, ethanol and propylene glycol.
Quantum chemical calculations are well-equipped to provide answers to the questions regarding the different aspects of intermolecular interactions. We investigate the benzene, ethanol and 1,2 propanediol ternary mixture with theoretical as well as experimental UV-Vis spectroscopy. An extensive theoretical study on the molecular structure and UV-Vis spectral analysis was undertaken using density functional theory (DFT) method. Structural parameter analysis and the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) energy gap help to describe the possible interaction between molecules in dimer and in combination. Interaction energy has been calculated from topological study. Time-dependent density functional theory (TDDFT) calculations on dimer/cluster in gas phase help to understand the effect of the molecular interaction on the overall spectral shift and related intensity variation. Our results show that in the ternary mixture, the interaction energies of the interactions are π-π interaction: 0.52-2.57 kcal/mol, Hp-π interaction: 1.15 kcal/mol and H-bonding: 2.49 to 4.46 kcal/mol. The π-π interaction and H-bonding cause red shift in absorption spectra while Hp-π interaction causes blue shift. In the ternary mixture, the strength of different kinds of interaction depends on the concentration, and as each interaction has its own effect on spectral shift, the overall experimental spectra get broader and distorted from the Gaussian shape.


Edaravone Dexborneol Alleviates Neuroinflammation by Reducing Neuroglial Cell Proliferation and Suppresses Neuronal Apoptosis/Autophagy in Vascular Dementia Rats.
More and more evidence shows that the pathological mechanism of vascular dementia (VD) is closely related to oxidative stress injury, cell apoptosis, autophagy, inflammatory response, excitatory amino acid toxicity, synaptic plasticity change, calcium overload, and other processes. Edaravone dexborneol (EDB) is a new type of neuroprotective agent that can improve the neurological damage caused by an ischemic stroke. Previous studies showed that EDB has effects on synergistic antioxidants and induces anti-apoptotic responses. However, it remains unclear whether EDB can affect apoptosis and autophagy by activating the PI3K/Akt/mTOR signaling pathway and its impact on the neuroglial cells. In this study, we established the VD model of rats by bilateral carotid artery occlusion to explore the neuroprotective effect of EDB and its mechanism. Morris Water Maze test was applied to assess the cognitive function of rats. H&E and TUNEL staining were applied to observe the cellular structure of the hippocampus. Immunofluorescence labeling was used to observe the proliferation of astrocytes and microglia. ELISA was applied to examine the levels of TNF-α, IL-1β and IL-6, and RT-PCR was applied to examine their mRNA expression levels. Western blotting was applied to examine apoptosis-related proteins (Bax, Bcl-2, Caspase-3), autophagy-related proteins (Beclin-1, P62, LC3B), PI3K/Akt/mTOR signaling pathway proteins and their phosphorylation levels. The results indicated that EDB ameliorates learning and memory in rats subjected to the VD model, alleviates neuroinflammatory response by reducing the proliferation of the neuroglial cell and inhibits apoptosis and autophagy, which may be mediated by the PI3K/Akt/mTOR signaling pathway.


An evidence-based review and guidelines for patient self-testing and management of oral anticoagulation.
There is a limited evidence base for self-testing and -management for oral anticoagulation management. Available data suggest that these are credible models for a significant minority of patients if underpinned by structured training and follow-up. The guidelines presented are necessarily consensual and outline procedures for patient selection, training, product procurement, product maintenance, quality assurance procedures, dosage adjustment and clinical supervision. The cost-effectiveness of these models remains to be elucidated within the UK. Further data on both health economic and clinical outcomes are required from UK based studies before widespread implementation of self-testing and management can be recommended on a wider scale.


Risk Factors for Major Complications Following Minimally Invasive Surgeries for Endometriosis in the United States.
To study the rate and risk factors for short-term postoperative complications of patients undergoing minimally invasive surgery (MIS) for endometriosis in the United States. Retrospective cohort study. American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2020. Patients with endometriosis diagnosis. Laparoscopic surgery for endometriosis. We compared women with and without 30-day postoperative major complications, defined according to the Clavien-Dindo classification. A total of 28 697 women underwent MIS during the study period, of which 2.6% had major postoperative complications. Organ space surgical site infection and reoperation were the most common complications (47.0% and 39.8%, respectively). In multivariable regression analysis, African American race (adjusted odds ratio [aOR] 95% confidence interval [CI] 1.61 [1.29-2.01], p <.001), hypertension (aOR 95% CI 1.23 [1.01-1.50], p = .036), bleeding disorders (aOR 95% CI 1.96 [1.03-3.74], p = .041), bowel procedures (aOR 95% CI 1.93 [1.37-2.72], p <.001) and hysterectomy (aOR 95% CI 2.09 [1.67-2.63], p <.001) were independently associated with increased risk of major complications. In multivariable regression analysis of laparoscopies without bowel procedures, African American race, bleeding disorders, and hysterectomy were independently associated with increased major complication risk. Among cases with bowel procedures, African American race and colectomy were independently associated with increased major complication risk. In multivariable regression analysis of women who underwent hysterectomy, African American race, bleeding disorders, and lysis of adhesions were independently associated with increased major complications risk. Among women who underwent uterine-sparing surgery, African American race, hypertension, preoperative blood transfusion, and bowel procedures were independently associated with increased major complications risk. Among women undergoing MIS for endometriosis, African American race, hypertension, bleeding disorders, and bowel surgery or hysterectomy are risk factors for major complications. African American race is a risk factor for major complications among women undergoing surgeries with and without bowel procedures or hysterectomy.


Isolation and characterization of a butyrylesterase from human erythrocytes.
Human erythrocytes contain a butyrylesterase which, judging from the ease with which it can be solubilized, is present in the cytoplasm of these cells. This enzyme has been isolated and a number of its properties characterized. The purified enzyme hydrolyzed butyryl esters with both a lower Km and higher V than is seen with esters containing longer or shorter acyl groups. It has a molecular weight of 320 000 and an isoelectric point of 4.1. This low isoelectric point is apparently a result of the relatively high content of glutamic and aspartic acids. The stability of the isolated butyrylesterase has been examined under a number of different conditions. The enzyme is inhibited by low concentrations of Hg2+, Cd2+, Zn2+ and the organophosphorus compound Mipafox, but is insensitive to eserine. The properties of this butyrylesterase, including its ability to hydrolyze thiocholine esters at a relatively rapid rate (albeit with a high Km), are a mixture of those expected for an arylesterase and a cholinesterase.


Psychometric Assessment of Pilot Language and Communication Items on the 2018 and 2019 National Survey of Children's Health.
Until recently, normative data on language and communication development among children in the United States have not been available to inform critical efforts to promote language development and prevent impairments. This study represents the first psychometric assessment of nationally representative data derived from a National Survey of Children's Health (NSCH) pilot measure of language and communication development among children ages 1 to 5 years. We analyzed 14,573 parent responses to language and communication items on the 2018 and 2019 NSCH to evaluate whether the newly added 11 items represent a single latent trait for language and communication development and to determine normative age of success on each item. We applied weighted, one-parameter Item Response Theory to rate and cluster items by difficulty relative to developmental language ability. We examined differential item functioning (DIF) using weighted logistic regression by demographic factors. Together, exploratory factor analysis resulting in a single factor > 1 and explaining 93% of the variance and positive correlations indicated unidimensionality of the measure. Item characteristic curves indicated groupings were overall concordant with proposed milestone ages and representative of an approximate 90% success cut-point by child age. Indicated normative age cut-points for 3 of the items differed slightly from proposed milestone ages. Uniform DIF was not observed and potential nonuniform DIF was observed across 5 items. Results have the potential to enhance understanding of risk and protective factors, inform efforts to promote language and communication development, and guide programmatic efforts on early detection of language delays.


Analysis of variations and controls of evapotranspiration over major Indian River Basins (1982-2014).
This study analyses long-term (1982-2014) estimates of evapotranspiration (ET) over four major river basins of India with the primary objective of understanding the factors controlling its space-time variability. Here we utilize terrestrial water storage change (TWSC) estimates, computed from WaterGAP Global Hydrology Model (WGHM) simulations, in monthly water balance computations to obtain the best available estimates of long-term ET for the study region. Trend analysis shows significant increase in annual ET over Ganga (2.72 mm/year) and Krishna (3.90 mm/year) River Basins, while in Godavari and Mahanadi River Basins the observed trends are insignificant. The relative contribution of potential factors (represented by precipitation, soil moisture, temperature and Normalized Difference Vegetation Index (NDVI)) that affect the variability of monthly ET is assessed using Hierarchical Partitioning Analysis (HPA). Results reveal that ET variance is largely controlled by the availability of water (represented by precipitation and soil moisture) in all the river basins. Precipitation (soil moisture) accounts for 65% (16%), 70% (20%), 77% (15%) and 67% (18%) of the variability in monthly ET over the Ganga, Godavari, Krishna and Mahanadi River Basins, respectively. Similarly, highest contributions from precipitation are also observed in annual scale variations of ET in all the river basins. Multiple regression analysis performed to assess the overall influence of controlling variables demonstrate that precipitation, soil moisture, temperature and NDVI explain 84% (Ganga), 86% (Godavari), 91% (Krishna) and 82% (Mahanadi) of variations observed in monthly ET over the respective basins. Results presented in this study have major implications for the understanding of ET variability, appropriateness and discrepancies in different ET products and compliment the contemporary efforts of extending GRACE-based ET estimates in space and time.


CD4/GP120mac251 interaction induces phospholipase A2 (PLA2) activation in cynomolgus monkey lymphocytes.
Cynomolgus monkey are susceptible to infection with select simian immunodeficiency virus (SIV). We investigated the early interactions between SIV envelope glycoproteins (gp120mac251) and macaque lymphocytes. Our results demonstrate that the soluble viral glycoprotein induce a specific phospholipase A2 (PLA2) activation in lymphocytes through CD4. This PLA2 activation, induced after envelope glycoprotein-CD4 interaction, because of its locally destabilizing membrane effect, may have important implications for preparing the lymphocyte membrane for fusion with the viral particle. However, this effect is not sufficient to accomplish fusion. These data indicate that the specific step of fusion may be downstream from PLA2 activation.


Distribution and abundance of microplastics in the water column of Vembanad Lake-A Ramsar site in Kerala, India.
The study focuses on the occurrence, abundance and characteristics of microplastics (MPs) in the subsurface and bottom waters of Vembanad Lake, a Ramsar site in the state of Kerala. Even though several studies elucidate the prevalence of microplastic pollution in the surface waters of aquatic ecosystems, a little is known about the vertical distribution of MPs in the water column. Vembanad Lake water is greatly affected by microplastic pollution compared to other Indian lakes as it receive discharges from six rivers; a number of sewage canals and run-off. Ubiquitous distribution of MPs was found in the lake with a mean abundance of 26.79 ± 3.74 items L-1 and 52.70 ± 5.43 items L-1 in subsurface and bottom waters respectively. Fibers, constitute more than half of the total MPs in both subsurface and bottom waters. The dominance of polyamide and polypropylene with most of the MPs being fibers indicate that they originate probably from fishing activities and laundry wastewater. The particles with in the size range 100-500 μm were in excess in the water samples. Further fragmentation, increasing the number of MPs in the lake water was envisaged from the SEM images of MPs showing cracks and crevices. These MPs along with adsorbed contaminants upon ingestion by the aquatic organisms become a threat to the food web of the lake. The local population which depends mainly on the fishes and mussels of the lake for their dietary needs would be greatly affected by the contamination of the lake with MPs. Further research on MPs contamination in edible biota would give more insights on the extent and risks of MPs pollution in the lake.


The metabolism of aldosterone in kidney.
Slices of kidney cortex and medulla from adrenalectomized male rats metabolized aldosterone to at least 4 peaks of polar metabolites as well as reduced metabolites. The majority of the products were ring A-reduced and shown chromatographically to consist of 5 alpha-reduced metabolites; significant quantities of 5 beta-reduced metabolites were also synthesized. Approximately half of the 5 alpha-reduced products cochromatographed with 3 beta,5 alpha-THA and the remainder with 5 alpha-DHA and/or 3 alpha,5 alpha-THA. The anti-mineralocorticoids, spironolactone and progesterone, inhibited renal synthesis of 5 alpha-reduced products of aldosterone by 80%. 5 beta-Reduction was also slightly inhibited. Corticosterone slightly inhibited synthesis of the 5 alpha- and 5 beta-reduced products. Corticosterone and progesterone significantly inhibited the renal synthesis of the polar metabolites of aldosterone, but the inhibition was not significant at this dosage of spironolactone. Interestingly, the nuclei and plasma membranes were shown to be the most active fractions for these aldosterone transformations. Importantly significant quantities of 5 alpha-DHA and/or 3 alpha,5 alpha-THA, which possess 1/10 and 1/30, respectively, of the antinatriuretic activity of aldosterone, were synthesized at these subcellular locations.


Differentiation of Caco-2 cells requires both transcriptional and post-translational down-regulation of Myc.
Caco-2 cancer cell line is widely used to reproduce in vitro the differentiation of absorptive enterocytes of human intestinal epithelium. This cell line, when cultured over confluence for 21 days, spontaneously undergoes cell cycle arrest and differentiates with the formation of a polarized enterocyte-like monolayer. During this process, Myc protein is completely down-regulated, as occurs in normal enterocytes. Caco-2 cells differ from normal enterocytes for mutations of APC and β-catenin genes, factors known to be involved in the transcriptional control of MYC gene during enterocyte differentiation. In this paper, we investigated how Myc regulation could be achieved during Caco-2 differentiative process, notwithstanding the APC and β-catenin mutations. We highlighted the post translational regulation of Myc protein as one of the essential mechanisms that allows the exit from cell cycle and onset of differentiation of Caco-2 cells. Moreover, we found a strong correlation between Myc protein downregulation and the expression of the transcription factor Cdx2, suggesting the existence of a regulative link between these two proteins.


Two new triterpenoid estersaponins and biological activities of Pittosporum tobira 'Variegata' (Thunb.) W. T. Aiton leaves.
Two new triterpenoid estersaponins (1, 2) were isolated from the leaves of Pittosporum tobira 'Variegata' (Thunb.) W. T. Aiton, along with one known saponin (3) and one known flavonoid glycoside (4). Their structures were established by different spectroscopic methods including 1D and 2D NMR, UV, as well as ESI-MS analysis. The investigated 80% aqueous methanol extract showed significant dose dependent inhibition of acetic acid induced abdominal writhing in mice. The n-butanol fraction exerted moderate antimicrobial activity against Staphylococcus aureus and Escherichia coli. In addition, it showed in vitro antioxidant activity with IC50 value (7.3 μg/ml) lower than that of the positive control ascorbic acid (11.2 μg/ml), using DPPH free radical scavenging activity method. Evaluation of its in vitro cytotoxicity showed strong activity against breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and colon carcinoma (HCT) cell lines.


Evaluating TB diagnosis and care in the Union of the Comoros.
The Union of the Comoros has experienced a persistent notification gap in TB cases despite several strategic changes, including molecular diagnosis and contact investigation. We therefore performed a TB patient pathway analysis (PPA) under the National Tuberculosis Programme (NTP). To assess the alignment of healthcare-seeking behaviour and TB service availability to clarify the reasons for these missing cases. Three primary data sources, including a national list of health facilities, TB surveillance data and care-seeking behaviour data, were analysed at the national and regional levels to determine access to TB diagnosis and the initial point of care-seeking. Summary data were visualised using the standardised PPA Wizard programme, and the analysis was completed using demographic and socio-economic data. At the initial point of care-seeking, 18% of patients had access to TB services, available only in nine centralised public health facilities. Furthermore, 30% of patients initially consulted in the informal sector and 45% in the formal public or private sector in health facilities, both of which lacked the capacity for TB diagnosis or first-line treatment. The concentration of and limited access to TB services at the intermediate and central levels of care indicate a need for decentralisation efforts.


Evaluation of the long-term imprecision of the Capillarys 2 Flex Piercing® with serial differences in patient Hemoblogin A1c data: A comparison with two common immunoassays.
Since HbA1c became a diagnostic criterion for type 2 diabetes, assays measuring this analyte were required to be analytically stronger. Although precision of Sebia Capillarys 2 Flex Piercing® was previously evaluated with standard methods and material, we wanted to document the long-term performance of this analyzer in two different centers. In this study, we evaluated, with a non-conventional methodology, the analytical precision of the Sebia Capillarys 2 Flex Piercing® using HbA1c patient data and compared it with two different common commercial immunoassays. CV of 1.33% and 1.32% was obtained in the two centers for the electrophoretic technique compared to 2.66% and 3.92% for the Roche Cobas Integra 800® and Beckman Synchron DxC® immunoassays technique respectively. Our results show that capillary electrophoresis is more robust than the 2 immunoassays tested for long-term precision and even exceeds minimal requirements recommended.


Chemometrics-based approach to enhancing the usefulness of time domain reflectometry in investigating properties of granular materials.
Sets of time domain reflectometry waveforms analyzed with appropriate chemometric methods, instead of typical single waveform analysis, enable one to detect and quantify differences between waveforms, even if they appear at the level of several orders of magnitude below the scale of the measurements. Typical applications of such an approach to samples of healthy and damaged grain showed that differences contributing five orders of magnitude below the scale are still detectable. Under more rigorous experimental conditions, the level of detectable differences can be expected to be even lower.


Defining and characterizing drug/compound function.
The receptor concept, now more than century old, remains the core concept in understanding the mechanisms of disease causality and drug action. Originally formulated in the early 1900s, receptor theory has evolved in both detail and complexity as the tools of molecular biology and increasingly sophisticated research technologies have facilitated the study of drug/ligand receptor interactions at the molecular level. The result has been a more detailed and nuanced understanding of the parameters of drug action that together with knowledge of the pleotropic nature of cellular targets and associated signaling pathways has reshaped the receptor concept. Added to the basic agonist/antagonist view of drug/ligand function, concepts like allosterism, inverse agonism, biased signaling and compound residence time have provided a broader understanding of compound-target interactions to better inform drug discovery efforts. The iteration of descriptive data from pharmacological experiments to provide generic indices of affinity and efficacy can now be used to predict expected drug/compound effects in other cell/organ systems where the sensitivity of the latter to drug effects (either via expression levels of cell surface receptors or variances in the efficiency with which those receptors are coupled to cytosolic metabolic processes) can be accommodated.


Characterization and Gas Sensitivity of Polyaniline/Coral-Like SnO2 Hybrid Material Prepared by In Situ Polymerization.
A PANI/coral-like mesoporous SnO2 hybrid material was fabricated using in situ polymerization method at 0-5 degrees C. The coral-like mesoporous SnO2 was synthesized by controlling the hydrolysis of SnCl4 and subsequent removal of the templates by calcination in air. The obtained PANI/coral-like mesoporous SnO2 hybrid material was characterized by FT-IR, XRD, TEM and SEM. The XRD pattern suggested that PANI did not modify the crystal structure of SnO2, but SnO2 affect the crystallization of PANI to some extents. The SEM and TEM pattern suggested that coral-like mesoporous SnO2 was enwrapped by PANI. The gas-sensing property of PANI/coral-like SnO2 hybrid material was also studied to NH3, trimethylamine (TMA), and SO2 at room temperature. It was found that the sensor based on PANI/coral-like SnO2 hybrid material had higher response and faster response/recovery to NH3, TMA and SO2 than that based on PANI. The sensing mechanism of the hybrid material was also investigated.


Trigeminal nerve: the possible origin of substance p-nergic response in isolated rabbit iris sphincter muscle.
We determined the effects of trigeminal nerve denervation on the noncholinergic, nonadrenergic response to electrical transmural stimulation of the isolated rabbit iris sphincter muscle. The left ophthalmic nerve (first branch of the trigeminal nerve) was cut at the intracranial, peripheral site of the trigeminal ganglion and five to ten days later, the iris sphincter muscle isolated from the left eye (operated side) was found to produce a fast cholinergic contraction in response to electrical transmural stimulation and there was no evidence of noncholinergic, nonadrenergic contractions. On the other hand, in the iris sphincter muscle isolated from the right eye (control side), electrical transmural stimulation produced both cholinergic and noncholinergic, nonadrenergic contractile responses. Capsaicin and bradykinin produced noncholinergic, nonadrenergic contractile responses in the muscle from the control side, while in the iris sphincter from the trigeminally denervated eye there was no such response to application of these drugs. Exogenous substance P (SP) and carbachol produced a strong contractile response in both the trigeminally innervated and denervated sphincter muscles. Somatostatin, vasoactive intestinal polypeptide (VIP) and enkephalin were without effects. These observations suggest that the noncholinergic, nonadrenergic responses to electrical transmural stimulation are derived from the trigeminal nerve and that the mediator involved is probably SP or a related peptide.


AFM study of hippocampal cells cultured on silicon wafers with nano-scale surface topograph.
The rat hippocampal cells were selected as model to study the interaction between the neural cells and silicon substrates using atomic force microscopy (AFM). The hippocampal cells show tight adherence on silicon wafers with nano-scale surface topograph. The lateral friction force investigated by AFM shows significant increase on the boundary around the cellular body. It is considered to relate to the cytoskeleton and cellular secretions. After ultrasonic wash in ethanol and acetone step by step, the surface of silicon wafers was observed by AFM sequentially. We have found that the culture leftovers form tight porous networks and a monolayer on the silicon wafers. It is concluded that the leftovers overspreading on the silicon substrates are the base of cell adherence on such smooth inert surfaces.


ATP-dependent protein kinase activities in the oral pathogen Streptococcus mutans.
ATP-dependent protein kinase activities were detected in both membrane and cytoplasmic fractions from the oral pathogen Streptococcus mutans. Different polypeptides were phosphorylated by endogenous kinase(s) in the two fractions. In membranes, five phosphoproteins were detected with apparent masses of 82, 37, 22, 12, and 10 kilodaltons (KD). In cytoplasm, two major acid-stable phosphoproteins were found. One was identified as HPr of the phosphoenolpyruvate (PEP)-dependent phosphotransferase system (PTS), while the other had an apparent mass of 61 KD. Both of these proteins were phosphorylated on a seryl residue. Fructose 1,6-bisphosphate stimulated phosphorylation of HPr by the kinase and inhibited phosphorylation of the 61-KD protein. In contrast, fructose 1-phosphate, 2-phosphoglycerate, 3-phosphoglycerate, and dihydroxyacetone phosphate inhibited phosphorylation of HPr and stimulated phosphorylation of the 61-KD protein. Several other glycolytic intermediates as well as inorganic phosphate inhibited phosphorylation of either or both proteins. Preincubation of cytoplasm with PEP prior to incubation with ATP reduced the amount of phospho-(seryl)-HPr formed, but not that of the 61-KD phosphoprotein. The latter protein has not yet been identified but has properties that suggest that it may be the protein kinase itself. These results provide evidence for one or more soluble ATP-dependent protein kinases in S mutans that are regulated by glycolytic intermediates and that may play a role in the modulation of carbohydrate uptake and metabolism in this organism. A model for feedback regulation of sugar transport in S mutans, mediated by an allosterically regulated kinase, is presented.


Association of human T-cell leukaemia/lymphoma virus with the Tac antigen marker for the human T-cell growth factor receptor.
Certain adult T-cell lymphoproliferative disorders are associated with human T-cell leukaemia virus (HTLV), a unique human type C retrovirus. (The strains of HTLV used in these studies belong to the subgroup HTLV-I.) HTLV is not an endogenous agent in man, but rather is an acquired virus with T-cell tropism. Neoplastic cells from patients infected with HTLV generally express receptors for T-cell growth factor (TCGF) (interleukin-2), and do not require prior activation with antigens or lectins to undergo TCGF-induced proliferation. Furthermore, neoplastic T-cell lines originating from such patients may constitutively produce TCGF, TCGF receptors and HTLV virions. HTLV is transmissible from cell to cell, and the infection of human T cells in vitro is associated with the expression of TCGF receptors, which can be identified by the monoclonal antibody termed anti-Tac. In our experience to date, T-cell populations that produce HTLV without exception also express epitopes found on TCGF receptors. Recognition of an association between HTLV virions and the Tac antigen would have clinical and theoretical implications. We now present evidence that during the replication or release of HTLV, the virion becomes preferentially associated with the Tac antigen.


Measuring the levels of noise at the İstanbul Atatürk Airport and comparisons with model simulations.
Airport noise and its impact on the surrounding areas are major issues in the aviation industry. The İstanbul Atatürk Airport is a major global airport with passenger numbers increasing rapidly per annum. The noise levels for day, evening and night times were modeled around the İstanbul Atatürk Airport according to the European Noise Directive using the actual data records for the year 2011. The "ECAC Doc. 29-Interim" method was used for the computation of the aircraft traffic noise. In the setting the noise model for the local airport topography was taken into consideration together with the noise source data, the airport loadings, features of aircraft and actual air traffic data. Model results were compared with long-term noise measurement values for calibration. According to calibration results, classifications of the aircraft type and flight tracks were revised. For noise model validation, the daily noise measurements at four additional locations were used during the verification period. The input data was re-edited only for these periods and the model was validated. A successful model performance was obtained in several zones around the airport. The validated noise model of the İstanbul Atatürk Airport can be now utilized both for determining the noise levels in the future and for producing new strategies which are about the land use planning, operational considerations for the air traffic management and the noise abatement procedures.


Heterogeneous regional endocardial repolarization is associated with increased risk for ischemia-dependent ventricular fibrillation after myocardial infarction.
Repolarization Heterogeneity and Sudden Death Risk. The aim of this study was to investigate whether the characteristics of endocardial ventricular repolarization are associated with differential risk for sudden death. Prolonged surface QT interval is associated with increased arrhythmic risk after myocardial infarction (MI), but the underlying mechanism of QT prolongation and its relation to lethal arrhythmias are unclear. Ventricular fibrillation (VF) risk was assessed in 12 dogs 1 month after anterior MI during an exercise test coupled with brief circumflex coronary occlusion. Susceptible dogs (n = 5) developed VF during the brief ischemic episode, whereas resistant dogs did not (n = 7). Surface QT interval was measured at rest. Endocardial electroanatomic catheter maps of left ventricular repolarization were obtained in four unique regions identified by echocardiography and compared between groups. Compared to resistant dogs, susceptible dogs were characterized by prolonged surface QT intervals (240 +/- 10 msec vs 222 +/- 7 msec, P = 0.04). In addition, they had lower baroreflex sensitivity (9.7 +/- 1.5 msec/mmHg vs 28 +/- 9.8 msec/mmHg, P < 0.01) and a tachycardic response to acute ischemia suggesting higher propensity for stronger sympathetic reflexes. Surface QT interval prolongation in susceptible dogs was due to a marked heterogeneity of endocardial left ventricular repolarization (239 +/- 42 msec, basal anterior wall vs 197 +/- 35, lateral wall; P < 0.001). Resistant animals had no regional differences in endocardial repolarization. Sympathetic activation following MI not only produces adverse structural remodeling but also contributes to adverse electrophysiologic remodeling resulting in heterogeneous ventricular repolarization and in a myocardial substrate conducive to lethal reentrant arrhythmias.


Risk of cutaneous adverse events in cancer patients treated with phosphatidylinositol-3-kinase inhibitors: A systematic review and meta-analysis of randomized controlled trials.
Cutaneous adverse effects (AEs) are common following the phosphoinositide-3-kinase (PI3K) inhibitors treatment. We aim to estimate the incidence and risk of PI3K inhibitor-related cutaneous AEs. The protocol was submitted to the PROSPERO registry. We searched ClinicalTrials.gov and international databases up to July 29, 2022. Meta-analysis was conducted by using risk ratios (RRs) with 95% confidence intervals (CIs). Fourteen randomized controlled trials (RCTs) comprising 3877 patients were analyzed in this study. Compared with control arms, PI3K inhibitors showed a significant increase in the risk of all-grade rash, high-grade rash, and serious rash events (RR 2.29, 95% CI 1.58-3.31, p < 0.00001; RR 9.34, 95% CI 4.21-20.69, p < 0.00001; RR 5.11, 95% CI 2.11-12.36, p = 0.0003). The overall incidences of all-grade rash and high-grade rash were 26.2% (592/2257) and 4.4% (66/1487). Subgroup analyses of all-grade rash according to cancer types and PI3K inhibitor assignations identified the significant associations. PI3K inhibitors also significantly increased the risk of pruritus and dry skin (RR 1.63, 95% CI 1.14-2.33, p = 0.007; RR 3.34, 95% CI 2.30-4.85, p < 0.00001), with incidences of 13.4% (284/2115) and 9.8% (141/1436) in the treatment group. There is a significantly increased risk of some cutaneous AEs in patients using PI3K inhibitors. Advance intervention is recommended in case of severe and life-threatening events. Further research is required to investigate the risk factors and pathogenesis.


Trends in the surgical management of duodenal ulcer. A fifteen year study.
The number of patients undergoing definitive duodenal ulcer operation at Charlotte Memorial Hospital and Medical Center declined by 75 percent from 1971 to 1985. The percentage of women making up the total study population increased to 40 percent in the period from 1981 through 1985. Average patient age also increased. Fewer gastric resections are now being performed and emergency operations are becoming more frequent, with bleeding being the most common indication. Splenic lacerations requiring splenectomy in patients undergoing vagotomy occurred in 3.1 percent of the study population during the 15 year study. The overall mortality rate for elective operations was 1.5 percent and for emergency operations, 17.2 percent. The incidence of acute duodenal ulcer perforation increased during this 15 year study. Duodenal ulcer operations have changed in number and in type as the manifestations of the disease have become altered by trends that began in the mid 1950s and became exaggerated by more effective ulcer therapy.


Aflatoxins in hazelnuts and dried figs: Occurrence and exposure assessment.
A total of 300 samples of hazelnuts and dried fig were analysed for the incidence of any aflatoxins (AFs). High-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) method was used to quantify the amounts of AFs. The limit of quantification varied from 0.21 to 0.30μgkg(-1). No AFs were detected in shells of the hazelnuts, while six raw hazelnut kernel samples (12%) and five roasted hazelnut kernel samples (8.3%) contained AFs ranging from 0.09 to 11.3μgkg(-1) and from 0.17 to 11.2μgkg(-1), respectively. Sixteen dried fig samples (12.3%) contained AFs ranging from 0.1 to 28.2μgkg(-1) and a mean value of 3.8μgkg(-1). Three hazelnuts and six dried fig samples exceeded the European maximum limits (MLs) of 5 and 2μgkg(-1) for aflatoxin B1 (AFB1), respectively. The contribution of hazelnuts to AFs exposure is higher than that of dried figs.


The epidemiology of injury in a rural state: 5,322 cases over 6 years.
Presently, descriptions of rural trauma are complications of national sample statistics and local data from states projected to rural areas. This study reviews all hospital discharges (36,866) for children (aged 0 to 18 years) from January 1985 through December 1990 in an entirely rural state. Fourteen percent of admissions (5,322) were due to traumatic injury and 63% of these occurred in boys. Injury rates were age dependent with children 15 to 18 years experiencing an incidence of 110/10,000; 10 to 14 years 55/10,000; 5 to 9 years 39/10,000; 1 to 4 years 35/10,000; and < 1 year 39.5/10,000. Mean age for the entire population was 11.4 +/- 5.7 years. Thirty-five percent of children had more than one major site of injury. Sixty-three percent of admissions were for blunt trauma and only 4.8% were penetrating. The remainder were due to burns, hanging, ingestion, and other toxic agents. Falls constituted the most prevalent cause of injury in this population occurring in 25.9%, motor vehicle accidents 22.9%, struck by an object 9.6%, suicide attempts 8.5%, poisoning 4.7%, fire 1.2%, drowning 0.7%, and farm machinery 0.3%. The vast majority of motor vehicle accidents involved the child as an operator or occupant of the vehicle. Less than 10% involved a pedestrian being struck and less than 5% involved a child being struck while on a bicycle. Less than 6% of all injuries involved a bicycle. Child maltreatment was recorded in less than 2% of this population. Only 3.3% of injured children required transfer to another acute care facility (1/3 because of a motor vehicle accident and 1/4 because of a fall).(ABSTRACT TRUNCATED AT 250 WORDS)


Helicobacter pylori infection induces cyclooxygenase-2 expression in human gastric mucosa.
Recent studies indicate that expression of mitogen-inducible cyclooxygenase-2 (COX-2) occurs in gastrointestinal tumors. We investigated the effects of Helicobacter pylori (H. pylori) infection, a class I carcinogen for the human stomach, on gastric COX-2 expression using immunohistochemistry. Human subjects without macroscopic lesions, as determined by endoscopic screening, were biopsied for H. pylori infection. The biopsy samples were immunohistochemically examined for COX-2 expression. COX-2 was expressed in gastric epithelia and subepithelial inflammatory cells in all H. pylori-infected subjects. There was no expression of COX-2 in the gastric mucosa of H. pylori-negative subjects. COX-2 expression has been reported in gastrointestinal carcinomas, gastrointestinal cancer cell-lines, and in the gut after carcinogenic treatment. The present study demonstrates that H. pylori infection leads to gastric mucosal expression of COX-2, indicating that the enzyme is involved in H. pylori-related gastric pathology in humans.


A rapid and quantitative assay for measuring neutralizing antibodies of Coxsackievirus B3.
Coxsackievirus B3 (CVB3) infection has been found to account for an increasing proportion cases of hand, foot and mouth disease (HFMD) in recent epidemiology studies. CVB3 is a single stranded, non-enveloped RNA virus and the infection can cause prominent health threat to pre-school children. Here, by taking approaches of reverse genetics, we established a single-round infection system for CVB3. The pseudovirus was produced by sequential transfection of CVB3 capsid expresser plasmid and CVB3 replicon RNA bearing firefly luciferase as a reporter. The CVB3 pseudovirus system was used for quantifying neutralizing antibody (NtAb) levels of 720 human serum samples and showed superior specificity and sensitivity comparing traditional cytopathic effect (CPE) assay. Furthermore, we compared the seroprevalence of CVB3 NtAbs in pre-school children and healthy adults, and found that only 11.94% of pre-school children were NtAbs positive which suggested that most children were naive to CVB3 infection; while there is much higher positive rate in adults (60%) indicating that most adults have experienced CVB3 infection during childhood. This rapid and quantitative assay greatly facilitates evaluating the level of NtAbs against CVB3 in populations and will help to advance CVB3 vaccine development.


Survival analysis for the missing censoring indicator model using kernel density estimation techniques.
This article concerns asymptotic theory for a new estimator of a survival function in the missing censoring indicator model of random censorship. Specifically, the large sample results for an inverse probability-of-non-missingness weighted estimator of the cumulative hazard function, so far not available, are derived, including an almost sure representation with rate for a remainder term, and uniform strong consistency with rate of convergence. The estimator is based on a kernel estimate for the conditional probability of non-missingness of the censoring indicator. Expressions for its bias and variance, in turn leading to an expression for the mean squared error as a function of the bandwidth, are also obtained. The corresponding estimator of the survival function, whose weak convergence is derived, is asymptotically efficient. A numerical study, comparing the performances of the proposed and two other currently existing efficient estimators, is presented.


Predictive factors of failure in management of ectopic pregnancy with single-dose methotrexate: a general population-based analysis from the Auvergne Register, France.
In a general population setting, the existence of a learning curve for treatment of ectopic pregnancy with single-dose methotrexate has been demonstrated, because a significant decrease in failure rate can be achieved over time. Despite this finding, the risk of single-dose methotrexate failure increases significantly in patients with initial hCG levels>1,300 IU/L and/or in women who report having ever used combined oral contraception before pregnancy.


Utility of thin-layer preparations in endometrial cytology: immunocytochemical expression of PTEN, beta-catenin and p53 for benign endometrial lesions.
This article focuses on the characteristic features of morphology and molecular biology of PTEN, beta-catenin, and p53 immunocytochemistry in normal endometrium (proliferative, secretory, and atrophic) and endometrial glandular and stromal breakdown (EGBD) using thin-layer specimens. During a 6-month period, 120 endometrial samples were collected directly using the Uterobrush and a thin-layer specimen was prepared. Immunocytochemical expression of PTEN, beta-catenin, and p53 were investigated using 30 cases each of proliferative endometrium (PE), secretory endometrium (SE), atrophic endometrium (AE), and EGBD.PTEN expression of normal endometrial glandular epithelial cells changes with the hormonal status; PE produce very high expression, SE creates attenuation or disappearance of PTEN expression and AE diminished more in comparison with SE. PTEN expression of EGBD showed a tendency towards attenuation compared with PE, but showed high expression in comparison with SE and AE. As for the immunoreactivity of beta-catenin, in all phases (PE, SE, AE, and EGBD), it was observed in the cytoplasm of glandular epithelial cells, but not nuclei, and showed strong membranous staining. As for the p53 immunoreactivity, p53 positivity was not observed in the glandular epithelial cells in all phases (PE, SE, AE, and EGBD) with the exception of some metaplastic cells. The presence of p53 immunoreactivity of a weak, low ratio in metaplastic cells was unexpected. In the current study, the expression manner of PTEN, beta-catenin, and p53 immunocytochemistry was observed in the normal endometrium (PE, SE, and AE) and EGBD.


Financial deepening, financial innovation, and education as new determinants of green growth in China.
To address the issue of global warming, the agreed solution is to reduce GHG emissions. The plausible solution to reduce GHG emissions is to follow a green growth strategy that refers to the complete decoupling of economic growth from its environmental impact through the sustainable utilization of natural resources. Consistent with this view, this study investigates the impact of financial deepening, financial innovation, and education on green growth in China from 1996 to 2020. The empirical analysis of the model is conducted through quantile ARDL. The long-run estimated coefficients of financial institution deepening are positively significant across most quantiles, whereas the estimated coefficients of financial market deepening are positively significant in almost half quantiles. These results imply that the financial deepening of both financial markets and institutions can positively contribute to green growth. However, the estimates of financial innovations are significant and positive in higher quantiles, implying that financial innovation only contributes to the green when the rate of financial innovation is too high. The estimates of education are positively significant at higher quantiles. Our study highlights various policy suggestions that are aimed at instigating sustainable green growth in China.


An innovative sandwich ELISA system based on an antibody cocktail for gluten analysis.
A cocktail sandwich ELISA based on the employ of two monoclonal antibodies (MAbs) as coating antibodies and a third MAb conjugated to horseradish peroxidase has been developed for the analysis of gluten in foods. Given that each MAb displays a wide specificity spectrum for wheat, barley, rye and oats prolamins, their combination for ELISA ensures a high crossreactivity with most of the potentially toxic gliadin, hordein, secalin and avenin protein family. One of the unprecedented features of the cocktail sandwich ELISA is that it permits for the first time analysis of barley hordeins in foods, which is unattainable using conventional or commercial ELISA kits. Besides, gliadins, hordeins and secalins are recognised to the same extent. The system provides a high detection sensitivity for gliadins, hordeins, secalins and avenins (1.5, 0.05, 0.15 and 12 ng/ml, respectively). The working linear range comprises 3-100 ng/ml with a gliadin detection limit of 1.5 ppm. This limit of detection is even better than that demanded in the latest Codex recommendation, 10 ppm. Cocktail ELISA data were contrasted with those of commercial ELISA kits and confirmed by mass spectrometry, a non-immunological technique which provides evidence for the occurrence of false positive results with the commercial kits.


Inequalities in access to paid sick leave among workers in England and Wales.
It is poorly understood which workers lack access to sick pay in England and Wales. This evidence gap has been of particular interest in the context of the Covid-19 pandemic given the relationship between presenteeism and infectious disease transmission. This cross-sectional analysis (n = 8874) was nested within a large community cohort study based across England and Wales (Virus Watch). An online survey in February 2021 asked participants in work if they had access to paid sick leave. We used logistic regression to examine sociodemographic factors associated with lacking access to sick pay. Only 66% (n = 5864) of participants reported access to sick pay. South Asian workers (adjusted odds ratio [OR] 1.40, 95% confidence interval [CI] 1.06-1.83) and those from Other minority ethnic backgrounds (OR 2.93, 95% CI 1.54-5.59) were more likely to lack access to sick pay compared to White British workers. Older workers (OR range 1.72 [1.53-1.93]-5.26 [4.42-6.26]), workers in low-income households (OR 2.53, 95% CI 2.15-2.98) and those in transport, trade, and service occupations (OR range 2.03 [1.58-2.61]-5.29 [3.67-7.72]) were also more likely to lack access to sick pay compared respectively to workers aged 25-44, those in high income households and managerial occupations. Unwarranted age and ethnic inequalities in sick pay access are suggestive of labour market discrimination. Occupational differences are also cause for concern. Policymakers should consider expanding access to sick pay to mitigate transmission of Covid-19 and other endemic respiratory infections in the community, and in the context of pandemic preparation.


Optimizing the performance of Fe-based metal-organic frameworks in photo-Fenton processes: Mechanisms, strategies and prospects.
Contaminants in water pose a significant challenge as they are harmful and difficult to treat using conventional methods. Therefore, various new methods have been proposed to degrade organic pollutants in water, among which the photo-Fenton process is considered promising. In recent years, Fe-based metal-organic frameworks (Fe-MOFs) have gained attention and found applications in different fields due to their cost-effectiveness, non-toxic nature, and unique porous structure. Many researchers have applied Fe-MOFs to the photo-Fenton process in recent years and achieved good results. This review focuses on describing different strategies for enhancing the performance of Fe-MOFs in the photo-Fenton process. Also, the mechanism of MOF in the photo-Fenton process is described in detail. Finally, prospects for the application of Fe-MOFs in photo-Fenton systems for the treatment of organic pollutants in water are presented. This study provides information and ideas for researchers to use Fe-MOFs to remove organic pollutants from water by photo-Fenton process.


Autoubiquitination of feline E3 ubiquitin ligase BCA2.
BCA2/RNF115/Rabring7 is a RING type E3 ubiquitin ligase that is overexpressed in human breast tumors and is important for regulating breast cancer cell migration. In the present investigation, feline BCA2 (fBCA2) was identified and characterized. Compared with its human counterpart, the fBCA2 cDNA was confirmed to be 918 base pairs in length showing 92.6% consensus and identity positions, encoding a protein of 305 amino acids with 96.7% consensus and 93.1% identity positions. The fBCA2 protein contains a RING domain at the C-terminus, which was found to be essential for its autoubiquitination.


The fowl adenovirus type 1 (CELO) virus-associated RNA-encoding gene: a new ribozyme-expression vector.
A new system for hammerhead ribozyme (Rz) expression was examined in which fowl adenovirus type 1 (CELO) virus-associated RNA (CELO VA RNA) was used as a vector for the incorporation of Rz to target the mRNA of secreted alkaline phosphatase (SEAP) both in vitro and in vivo. The Rz gene was integrated into the CELO VA RNA between the internal promoter boxes A and B; apparently this did not interfere with its transcription. Rz integrated into CELO VA RNA and, lacking the viral sequences, exhibited the same activity in vitro, Consequently, CELO VA RNA sequences did not inhibit the integrated Rz activity in vitro. In vivo experiments were carried out with human 293 cells by co-transfection with plasmids containing Rz and SEAP. Inhibition of enzyme activity was 50% in 48 h. We conclude that CELO VA RNA may be used for effective expression of hammerhead Rz.


Use of an oral exam in an internal medicine clerkship.
Scores from an oral exam used to evaluate student performance at the end of an Internal Medicine clerkship are analyzed to assess inter-examiner consistency. Design aspects of the oral exam procedure are discussed.


Profile of patients with tuberculosis: evaluation of the Brazilian national tuberculosis control program in Bagé, Brazil.
To present epidemiological data on patients diagnosed with tuberculosis, as well as on associated factors, and to determine the efficacy of the National Tuberculosis Control Program in Bagé, Brazil. A retrospective study was carried out at the Pablo Barcellos Center, analyzing cases of tuberculosis reported from January 2001 to December 2004. Data were collected through the review of clinical charts and from the National Case Registry database. During this period, of the 4468 sputum smear microscopies performed, 131 were positive, with higher prevalence among males aged 26 to 35 years old. Prevalence was lower among those aged 65 and above. Over 50% of the patients were Caucasian, had only 1 to 3 years of schooling and worked in low-income jobs (mean salary, 265 Brazilian reals/month). There was no significant difference between smokers and former smokers/nonsmokers, and only one of the 131 cases was HIV positive. The number of sputum smear microscopies performed in Bagé increased in the past four years. In 2003 and 2004, it exceeded the goal of the National Tuberculosis Control Program. However, the number of new cases decreased, demonstrating the efficacy of the active search for tuberculosis cases in the city.


Effect of feed strategy on methane production and performance of an AnSBBR treating effluent from biodiesel production.
The aim of this work was to investigate the effect of different feeding times (2, 4 and 6 h) and applied volumetric organic loads (4.5, 6.0 and 7.5 gCOD L(-1) day(-1)) on the performance of an anaerobic sequencing batch biofilm reactor (AnSBBR) treating effluent from biodiesel production. Polyurethane foam cubes were used as inert support in the reactor, and mixing was accomplished by recirculating the liquid phase. The effect of feeding time on reactor performance showed to be more pronounced at higher values of applied volumetric organic loads (AVOLs). Highest organic material removal efficiencies achieved at AVOL of 4.5 gCOD L(-1) day(-1) were 87 % at 4-h feeding against 84 % at 2-h and 6-h feeding. At AVOL of 6.0 gCOD L(-1) day(-1), highest organic material removal efficiencies achieved with 4-h and 6-h feeding were 84 %, against 71 % at 2-h feeding. At AVOL of 7.5 gCOD L(-1) day(-1), organic material removal efficiency achieved with 4-h feeding was 77 %. Hence, longer feeding times favored minimization of total volatile acids concentration during the cycle as well as in the effluent, guaranteeing process stability and safety.


Sequence specificities in the interactions of chemicals and radiations with DNA.
Sequence specificities in the interactions of chemicals and radiations with DNA are reviewed. Emphasis is placed on information which has been obtained by adapting DNA sequencing techniques to the detection of DNA damage and modifications. The actions of anti-tumor drugs, non-covalent DNA binders and UV irradiation are discussed in terms of both modifications induced in DNA and the subsequent response of DNA polymerase and repair enzymes. Particular attention is paid to the evidence for 'sequence-specific' interactions of these agents with DNA. It is concluded that while most agents exhibit 'warm' or even 'hot' spots in their interactions with DNA there is not, as yet, compelling evidence for extreme selectivity down to say the gene level in their actions. There does, however, appear to be some affinity, particularly in the case of non-covalent binders, for certain tertiary structures rather than primary sequences per se. In addition, both misincorporation opposite DNA damage and the bypass of damage by polymerases are important phenomena which, to some extent, exhibit sequence specificities. The idea is advanced that DNA structures such as hairpins or cruciforms maybe important in vivo targets for many agents giving rise to specific biological effects.


MRI appearances of hepatic epithelioid hemangioendothelioma: a retrospective study of 57 patients.
Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare and the MRI features have never been investigated in a large group of patients. A retrospective study was designed to review the MRI images of HEH patients. Two radiologists separately evaluated signal intensity (SI) on unenhanced imaging, morphological features, contrast-enhancement pattern at dynamic study. The MRI features were compared between patients with HEH and hepatic metastatic tumor (HMT). Fifty-seven HEH patients were included in this study and a total of 412 lesions were evaluated. On per-lesion analysis, the rate of coalescent lesion and subcapsular lesion were 18.2% and 39.8%, respectively. Capsular retraction and lollipop sign were observed in 47 lesions (11.4%) and 60 lesions (14.6%), respectively. Large lesions (> 5 cm) had the highest rate of coalescent lesion, subcapsular lesion, capsular retraction and lollipop sign. Target sign appeared in 196 lesions (47.6%) on T2 weighted (T2W) and 146 lesions (35.4%) on portal phase. Medium lesions (2-5 cm) had the highest rate of target sign on both T2W (72.9%) and portal phase (55.2%). On per-patient analysis, compare with HEH patients, HMT patients seldom had the appearance of lollipop sign (66.7% versus 6.4%, p < 0.01), capsular retraction (59.6% versus 3.2%, p < 0.01) and target appearance on both T2Wand portal phase (64.9% versus 12.7%, p < 0.01). MRI features of HEH correlated with the lesion size. Capsular retraction, lollipop sign and coexistence of target sign on both T2W and portal phase were relatively specific MRI features of HEH, which could be helpful in suggesting the diagnosis.


Endothelial dysfunction in patients with angina and non-obstructed coronary arteries is associated with an increased risk of mayor cardiovascular events. Results of the Spanish ENDOCOR registry.
Coronary endothelial dysfunction and vasospasm are potential causes of ischemia in patients without obstructive coronary stenoses (INOCA). To evaluate the prevalence of endothelial dysfunction and the clinical profile of patients with INOCA in Spain, as well as to identify the predictors and the prognostic impact of endothelial dysfunction in this scenario. A total of 438 consecutive patients with INOCA in whom the acetylcholine test was performed were prospectively enrolled. Patients were followed up at 1 and 2 years. Mean age was 62 ± 11 years with 60% female. Clinical presentation comprised 52.6% angina at rest, 61.2% exertional angina, and 31.7% dyspnea. There were no major complications of the acetylcholine test. Endothelial dysfunction was observed in 198 (45%) of patients, with severe vasoconstriction (defined as over 70% constriction), being observed in 101 (23%). Multivariable regression analysis showed that endothelial dysfunction was predicted by the presence of exertional angina (OR 2.2; CI95%1.01-2.55; p = 0.02), prior coronary disease (OR 2.46; CI95% 1.57-3.89; p < 0.01), and coronary intramyocardial bridging (2.35; CI95% 1.02-5.60; p = 0.04). Patients with endothelial dysfunction presented with worsening angina compared to those without endothelial dysfunction (25.6% vs. 12.8%) and also presented with increased levels of minimal effort angina (40% vs. 26,7%, p = 0.03) more frequently during the follow up than those without endothelial dysfunction. Endothelial dysfunction was also an independent predictor of the occurrence of myocardial infarction or unstable angina at one year (OR 2.85, CI 95% 1.01-9.25; p = 0.03). Endothelial dysfunction is present in almost half of patients with INOCA and is associated with worsening symptoms, as well as with a higher rate of adverse events.


Myopathy with core-like structures in a dog.
Core-like structures were seen histologically in many of the fibres of the triceps and biceps femoris muscles of an 18-months-old male Great Dane with muscle weakness and moderate proximal muscular atrophy. The structures were lightly staining and lacked cross-striations. Some contained vacuoles and nuclei. Scattered necrotic and presumably regenerating fibres were also present. Ultrastructurally, the cores contained disarrayed filament bundles attached to thickened Z-lines which were compatible with the rods of rod myopathies. The condition was not fully characterized, but has certain similarities to a group of rare human congenital muscular disorders which includes central core disease.


Genome-wide characterization of the relationship between essential and TATA-containing genes.
Essential genes are involved in most survival-related housekeeping functions. TATA-containing genes encode proteins involved in various stress-response functions. However, because essential and TATA-containing genes have been researched independently, their relationship remains unclear. The present study classified Saccharomyces cerevisiae genes into four groups: non-essential non-TATA, non-essential TATA, essential non-TATA, and essential TATA genes. The results showed that essential TATA genes have the most significant codon bias, the highest level of expression, and unique characteristics, including a large number of transcription factor binding sites, a higher degree in protein interaction networks, and significantly different amino acid usage patterns compared with the other gene groups. Notably, essential TATA genes were uniquely involved in functions such as unfolded protein binding, glycolysis, and alcohol and steroid-related processes.