Effects of re-infection with Neospora caninum in bulls on parasite detection in semen and blood and immunological responses.
Three bulls with experimentally induced primary infection with Neospora caninum were re-infected intravenously with 10(8) live N. caninum tachyzoites of the NC-1 isolate at 300 days post-infection to investigate the presence of N. caninum in semen and blood, and the associated immune responses. In parallel, three bulls with experimentally induced primary infection with N. caninum and three non-infected bulls were also monitored. Re-infected and infected bulls showed an intermittent presence of N. caninum DNA in semen with a parasite load ranging from 0.1 to 15.6 (mean 4.4) and 0.1 to 11.1 (mean 4.1) parasites/ml, respectively. Re-infected bulls showed significant and persistent serum-specific IgM and IgG antibody responses. Specific IgG levels were detected in seminal plasma of all infected bulls, but the magnitude of the response was significantly higher in re-infected rather than in chronically infected animals. The mean specific IFN-gamma levels in re-infected bulls were significantly increased as early as 3 and 7 days after experimental infection when compared to bulls in other groups. This study showed that the intermittent presence and parasite load of N. caninum in the semen of re-infected bulls is very similar to that reported in chronically infected animals. The protozoa could not be isolated from BALB/c nu/nu mice inoculated with PCR-positive semen samples and inseminated heifers with pooled semen samples did not show seroconversion. Plasma IFN-gamma level seems to be a good indicator of a recent N. caninum infection.


Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.
Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.


Transformation of vesicular into cubic nanoparticles by autoclaving of aqueous monoolein/poloxamer dispersions.
The ultrastructure of aqueous colloidal dispersions of the cubic monoolein/poloxamer 407/water phase, in particular the particle size distribution and presence of an additional vesicular fraction, highly depends on composition and preparation parameters. Therefore, the effect of autoclaving on such dispersions was investigated. Before autoclaving at 121 degrees C, a dispersion of 4.6% monoolein/0.4% poloxamer predominantly consists of cubic particles beside a fraction of non-cubic particles. The small vesicular particles disappear almost completely upon autoclaving whereas larger particles with cubic structure remain in the sample. In contrast, a 4.4% monoolein/0.6% poloxamer dispersion contains predominantly small vesicular particles before heat treatment. After autoclaving, the majority of the particles is larger and of cubic structure and only a few small non-cubic particles remain. The effect can already be observed at short autoclaving times (e.g., 5 min) but a temperature of at least 90 degrees C is required to induce a major change in the ultrastructure. Results from temperature dependent small angle X-ray diffraction investigations indicate that temperatures corresponding to an isotropic phase are required for particle transformation. Heat treatment of monoolein/poloxamer dispersions can thus be used to transform vesicular dispersions into dispersions of cubic phase or to improve the cubic/non-cubic particle ratio in dispersions already containing particles with cubic internal structure.


AR-Q640X, a model to study the effects of constitutively active C-terminally truncated AR variants in prostate cancer cells.
A recently identified mechanism allowing prostate cancer (PCa) cells to grow in the absence of androgens is the expression of constitutively active, C-terminally truncated androgen receptor (AR) variants lacking vast parts of the ligand-binding domain. These AR variants termed ARΔLBD are either products of alternative splicing, point mutations leading to premature stop codons or proteolytic cleavage of the AR. Some controversies exist about the requirement of additional full-length AR for the full transcriptional activity of the ARΔLBD. On basis of a mutated, C-terminally truncated AR termed Q640X, we developed an experimental model for the study of ARΔLBD in PCa cells. Activation of AR-dependent promoters was analyzed by reporter gene assays. Dimerization studies were conducted using a mammalian two-hybrid system. Although Q640X/Q640X homodimers were able to induce the expression of certain AR target genes, Q640X/AR heterodimers were necessary to activate the full panel of androgen-dependent genes under androgen-deprived conditions. The following study supports the hypothesis that castration-resistant prostate cancer (CRPC) cells are able to activate specific androgen-dependent genes by selective modulation of the ratio between ARΔLBD and their putative dimerization partners like the full-length AR or other ARΔLBD in the absence of androgens. The present data suggest that AR-mutant Q640X is a powerful experimental tool for the functional analysis of ARΔLBD in CRPC.


Phytochemical and genetic characterization of styles of wild Crocus species from the island of Crete, Greece and comparison to those of cultivated C. sativus.
The aim of this study was to contribute to the characterization of Crocus taxa using morphological, phytochemical and genetic analysis. The styles of C. cartwrightianus, C. oreocreticus and C. laevigatus, collected in the island of Crete were compared to those of C. sativus cultivated at the region of Western Macedonia (Greece). Phytochemical analysis was done using GC-MS and HPLC methods, while ISSR markers were used for their genetic characterization. Safranal was the major volatile component of the styles of C. sativus, 4-hydroxy-2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde of C. cartwrightianus and C. oreocreticus, and isophorone of C. laevigatus. C. sativus had the highest content of crocins and picrocrocin, while C. laevigatus the lowest (only 5% of C. sativus' quantity) and negligible amount of picrocrocin. According to both the genetic and the chemical analysis, C. cartwrightianus is more related to C. oreocreticus, while C. sativus and C. laevigatus are more distinct. Concordance between the two different types of data was also confirmed by the Mantel test (r = 0.932, P = .68). This is the first thorough screening of secondary metabolites (volatile and non-volatile) and also genetic and morphological characters of wild Crocus styles simultaneously, that contributes to the identification and valorisation of genotypes with similar to C. sativus traits which may be introduced as new cultivars through breeding.


Plasma prostaglandin levels in fed and starved lean, normal and obese women.
The plasma obtained from fed and starved lean, normal and obese women was estimated, by a radio-immunoassay method, for prostaglandins, owing to their implication in the regulation of adipose tissue lipolysis and the development of obesity. No significant differences were found due to nutritional status or body-build. However, a significantly higher plasma concentration of prostaglandins of the E-type than of the F-type, was found consistently. The very low levels of prostaglandins observed (a range of 0.10--0.15 ng ml-1 for E-type and a range of 0.05--0.07 ng ml-1 for the F-type) may be due, in part, to the activity of a plasmatic prostaglandin metabolizing system.


Variables related to health-related quality of life among breast cancer survivors after participation in an interdisciplinary treatment combining mindfulness and physiotherapy.
Breast cancer diagnosis and treatment increase the potential psychological impact on breast cancer survivors (BCS). The objective of this study was to assess the effects of an interdisciplinary intervention during follow-up in BCS and identify variables related to improvements in HRQoL. In a non-randomised quasi-experimental design performed on an outpatient basis in a hospital gynaecology and oncology unit, 60 BCS were assigned to an interdisciplinary experimental group (EG) or a usual care group (CG). The EG underwent 12 sessions of an interdisciplinary program which included Mindfulness and physiotherapy, for 120 min per day, once a week for 6 weeks. At baseline, at 6 weeks and at 3 months after the intervention, participants of EG and CG completed an assessment of HRQoL (EuroQol and EORTC-QLQ-C30) and symptomatology of anxiety and depression. Additionally, EG completed an assessment of satisfaction with the treatment. For data analysis, we used descriptive statistics, Wilcoxon test, Kruskal-Wallis test, Chi-square and Fisher tests and generalised linear models. After 6 weeks, statistically significant differences were apparent in global and cancer-related health symptoms such as fatigue and pain in the EORTC QLQ-C30 and in anxiety and depression, among the EG (n = 30) compared with the CG (n = 30). Patients receiving the intervention reported a high degree of satisfaction with the treatment. Three months after the intervention, patients in the EG continued to show statistically significant improvements compared with the CG. In addition, allocation to the EG was identified as a variable related to improvement of HRQoL (EORTC QLQ-C30) in the multivariable model. The results of our study suggest that a 6-week interdisciplinary intervention may improve HRQoL and symptomatology of anxiety and depression in BCS patients at 3 months. The study presents data that the intervention for BCS appears promising and warrants further study in a randomised controlled trial.


Purification and characterization of an F-actin-bundling 55-kilodalton protein from HeLa cells.
An F-actin-bundling protein with Mr of 55,000 has been purified from HeLa cells by a simple method using its affinity to F-actin. Briefly, muscle actin was mixed with supernatants of HeLa cell homogenates, and the resultant actin gel was precipitated by low speed centrifugation. The 55-kDa protein in the actin gel was dissociated by depolymerization of F-actin and purified sequentially by chromatography on DEAE-cellulose and hydroxylapatite. The Stokes radius and sedimentation coefficient of the 55-kDa protein were 32 A and 4.35 (S20,w), respectively. These results suggest that the 55-kDa protein is a monomeric globular protein with a native molecular weight of 57,000. The globular form of the protein was confirmed by electron microscopy of rotary shadowed specimens. The binding of the protein to actin was saturated at an approximate stoichiometry of 4 actin monomers to one 55-kDa molecule. The protein made F-actin aggregate side-by-side into bundles as has been reported for other F-actin-bundling proteins such as fimbrin (Mr = 68,000) and fascin (Mr = 58,000). The 55-kDa protein is a new actin-binding protein based on biochemical, morphological, and immunological characterization. Skeletal muscle tropomyosin inhibited the actin-bundling activity of 55-kDa protein by competitive binding to actin, suggesting that the 55-kDa protein binding site on F-actin is in the vicinity of the tropomyosin-binding site.


Effect of various solubilizers on angiotensinII receptors in bovine adrenocortical plasma membranes.
3 nonionic detergents, Triton X-100, Lubrol WX and NP-40, inhibited binding of [3H]-ATII to bovine adrenocortical plasma membranes. This effect appeared to be direct and not due to solubilization of the ATII receptor by these agents. Sodium deoxycholate and the chaotropic ions, ClO4- and Br-, produced effects similar to the nonionic detergents.


Differential expression of PTEN-targeting microRNAs miR-19a and miR-21 in Cowden syndrome.
Germline mutations in the gene encoding phosphatase and tensin homolog deleted on chromosome ten (PTEN [MIM 601728]) are associated with a number of clinically distinct heritable cancer syndromes, including both Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). Seemingly identical pathogenic PTEN mutations have been observed in patients with CS and BRRS, as well as in patients with incomplete features of CS, referred to as CS-like (CSL) patients. These observations indicate that additional, unidentified, genetic and epigenetic factors act as phenotypic modifiers in these disorders. These genetic factors could also contribute to disease in patients with CS, CSL, or BRRS without identifiable PTEN mutations. Two potential modifiers are miR-19a and miR-21, which are previously identified PTEN-targeting miRNAs. We investigated the role of these miRNAs by characterizing their relative expression levels in PTEN-mutation-positive and PTEN-mutation-negative patients with CS, CSL, or BRRS. Interestingly, we observed differential expression of miR-19a and miR-21 in our PTEN-mutation-positive patients. Both were found to be significantly overexpressed within this group (p < 0.01) and were inversely correlated with germline PTEN protein levels. Similarly, the relative expression of miR-19a and miR-21 was differentially expressed in a series of PTEN-mutation-negative patients with CS or CSL with variable clinical phenotypes and decreased full-length PTEN protein expression. Among PTEN-mutation-positive patients with CS, both miRNAs were significantly overexpressed (p = 0.006-0.013). Taken together, our study results suggest that differential expression of PTEN-targeting miR-19a and miR-21 modulates the PTEN protein levels and the CS and CSL phenotypes, irrespective of the patient's mutation status, and support their roles as genetic modifiers in CS and CSL.


Presenilins mutated at Asp-257 or Asp-385 restore Pen-2 expression and Nicastrin glycosylation but remain catalytically inactive in the absence of wild type Presenilin.
The Presenilins are part of the gamma-secretase complex that is involved in the regulated intramembrane proteolysis of amyloid precursor protein and other type I integral membrane proteins. Nicastrin, Pen-2, and Aph1 are the other proteins of this complex. The Presenilins probably contribute the catalytic activity to the protease complex. However, several investigators reported normal Abeta-peptide generation in cells expressing Presenilins mutated at the putative catalytic site residue Asp-257, contradicting this hypothesis. Because endogenously expressed wild type Presenilin could contribute to residual gamma-secretase activity in these experiments, we have reinvestigated the problem by expressing mutated Presenilins in a Presenilin-negative cell line. We confirm that Presenilins with mutated Asp residues are catalytically inactive. Unexpectedly, these mutated Presenilins are still partially processed into amino- and carboxyl-terminal fragments by a "Presenilinase"-like activity. They are also able to rescue Pen-2 expression and Nicastrin glycosylation in Presenilin-negative cells and become incorporated into large approximately 440-kDa complexes as assessed by blue native gel electrophoresis. Our study demonstrates that the catalytic activity of Presenilin and its other functions in the generation, stabilization, and transport of the gamma-secretase complex can be separated and extends the concept that Presenilins are multifunctional proteins.


Appropriate real-time PCR reference genes for fluoride treatment studies performed in vitro or in vivo.
Quantitative real-time PCR (qPCR) is routinely performed for experiments designed to identify the molecular mechanisms involved in the pathogenesis of dental fluorosis. Expression of reference gene(s) is expected to remain unchanged in fluoride-treated cells or in rodents relative to the corresponding untreated controls. The aim of this study was to select optimal reference genes for fluoride experiments performed in vitro and in vivo. Five candidate genes were evaluated: B2m, Eef1a1, Gapdh, Hprt and Tbp. For in vitro experiments, LS8 cells derived from mouse enamel organ were treated with 0, 1, 3 and/or 5mM sodium fluoride (NaF) for 6 or 18 h followed by RNA isolation. For in vivo experiments, six-week old rats were treated with 0 or 100 ppm fluoride as NaF for six weeks at which time RNA was isolated from enamel organs. RNA from cells and enamel organs were reverse-transcribed and stability of gene expression for the candidate reference genes was evaluated by qPCR in treated versus non-treated samples. The most stably expressed genes in vitro according to geNorm were B2m and Tbp, and according to Normfinder were Hprt and Gapdh. The most stable genes in vivo were Eef1a1 and Gapdh. Expression of Ddit3, a gene previously shown to be induced by fluoride, was demonstrated to be accurately calculated only when using an optimal reference gene. This study identifies suitable reference genes for relative quantification of gene expression by qPCR after fluoride treatment both in cultured cells and in the rodent enamel organ.


Characterization of N-acetyltryptophan degradation products in concentrated human serum albumin solutions and development of an automated high performance liquid chromatography-mass spectrometry method for their quantitation.
N-acetyltryptophan (NAT) has long been used as a stabilizer in some protein solutions, such as human serum albumin, to prevent oxidative protein degradation. However, the fate of NAT has not been discussed in literature. Two NAT degradation products have been observed in concentrated albumin solutions (20% and 25%) and identified as 1-acetyl-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid and 1-acetyl-3a,8a-dihydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid. To monitor the levels of these two previously unidentified NAT degradation products in concentrated albumin solutions, a fully automated method, incorporating online size exclusion chromatography (SEC) trapping and reversed-phase high performance liquid chromatography-mass spectrometry (HPLC-MS) with multiple reaction monitoring (MRM) analysis, has been developed and validated for their quantitative analysis. The method does not require an internal standard. The only sample manipulation is to obtain an albumin concentration of 4% in all standards and test HPLC samples. A limit of quantitation (LOQ) as low as 20 ng/mL has been achieved for both compounds. This method can readily be adopted for the quantitative determination of other small molecules in concentrated protein solutions.


Risk of age-related fractures in patients with unprovoked seizures.
The incidence of age-related fractures was determined in a cohort of 467 Rochester, Minnesota residents with unprovoked seizures. The 30 initial hip fractures observed were significantly more than the 13.19 expected [standardized morbidity ratio (SMR) = 2.3; 95% confidence interval (CI) 1.5-3.3]. The overall incidence of distal forearm (Colles) fractures was not significantly increased (SMR = 1.6; 95% CI 0.9-2.5), based on 17 cases. Hip fracture incidence was increased during the first 10 years after seizure diagnosis but was not related to anti-epileptic drug (AED) use. In contrast, the increase in Colles' fracture incidence was associated with duration of therapy, as the SMR for greater than or equal to 10 years of AED use was 2.4 (95% CI 1.0-5.0). The incidence of vertebral fractures was slightly higher among treated patients but was not associated with duration of AED use. Thus, there was no consistent pattern to support the contention that fracture incidence is greatly increased by long-term AED use.


Association between Short Maternal Height and Low Birth Weight: a Hospital-based Study in Japan.
Anthropometry measurements, such as height and weight, have recently been used to predict poorer birth outcomes. However, the relationship between maternal height and birth outcomes remains unclear. We examined the effect of shorter maternal height on low birth weight (LBW) among 17,150 pairs of Japanese mothers and newborns. Data for this analysis were collected from newborns who were delivered at a large hospital in Japan. Maternal height was the exposure variable, and LBW and admission to the neonatal intensive care unit were the outcome variables. Logistic regression models were used to estimate the associations. The shortest maternal height quartile (131.0-151.9 cm) was related to LBW (OR 1.91 [95% CI 1.64, 2.22]). The groups with the second (152.0-157.9 cm) and the third shortest maternal height quartiles (158.0-160.9 cm) were also related to LBW. A P trend with one quartile change also showed a significant relationship. The relationship between maternal height and NICU admission disappeared when the statistical model was adjusted for LBW. A newborn's small size was one factor in the relationship between shorter maternal height and NICU admission. In developed countries, shorter mothers provide a useful prenatal target to anticipate and plan for LBW newborns and NICU admission.


Survival rate of total hip replacements with matched and with mixed components with 10.7 years mean follow-up.
Mixing and matching components from different manufacturers in total hip arthroplasty is a frequently used off-label praxis. The clinical consequences of this procedure have not been studied in detail. 860 patients with matched and 1067 patients with mixed primary total hip replacement (THR) components carried out between 1 January 2002 and 31 December 2004, were selected from our Institution registry. The analysis endpoint was set at 1 January 2016. THRs with poorly performing components were excluded from study groups. Kaplan-Meier survival curves for both groups were calculated and compared using the Log-Rank test and the demographic data using the chi-square test. Correlations between demographic data and revisions were calculated using bivariate correlation. 28 revisions were carried out in the matched group and 67 in the mixed group. The 14-year overall survival probability was significantly better in the former (96.0%) than in the mixed group (92.7%) (p = 0.002). Survival, free of aseptic and septic failures, was statistically, significantly higher in the matched group (p = 0.026 and p = 0.007, respectively).The survival of the mixed subgroup with heads and stems from the same manufacturer did not differ statistically from that of the matched group (p = 0.079). In contrast to the results listed in the National Joint Registry and the New Zealand Joint Registry, the survival probability in our study was, statistically, significantly higher in total hip replacements using components of the same manufacturer. Importantly, mixing and matching the components of different manufacturers led to similar survival providing the head and the stem were from the same manufacturer.


IPOM plus versus IPOM standard in incisional hernia repair: results of a prospective multicenter trial.
Laparoscopic ventral hernia repair is a well-established technique with satisfying outcomes even at long term for the treatment of incisional and ventral hernia. However, the literature debate is still ongoing regarding the preferred surgical technique. Nowadays, two approaches are commonly adopted: the intraperitoneal onlay mesh repair (sIPOM) and the intraperitoneal onlay mesh reinforcement with defect closure before mesh placement (pIPOM). The aim of this prospective analysis is to compare the postoperative outcomes of patients treated for incisional hernia (IH) with sIPOM and pIPOM after 36 months follow-up in terms of recurrence, quality of life and wound events. Patients receiving pIPOM and sIPOM for IH were actively followed up for 36 months. At the outpatient clinic, hernia recurrence (HR), mesh bulging (MB), quality of life with the Gastrointestinal Quality of Life Index (GIQLI) and wound events were assessed. Between January 2015 and January 2019, 98 patients underwent a pIPOM and 89 underwent an sIPOM. At 36 months, nine patients (4 in pIPOM and 5 in sIPOM) experienced an HR, while MB was recorded in four patients in pIPOM and nine in sIPOM. No statistically significant difference could be identified also in terms of final GIQLI score and wound events. LVHR with or without fascial closure, also in our study, provides satisfactory results in terms of safety and efficacy. The discordant results in the literature are probably related to independent variables such as the type of mesh, the type of suture and closure technique. Therefore, was the funeral of sIPOM done too early? STUDY DATASET IS AVAILABLE ON CLINICALTRIALS. NCT05712213.


Oxytocin Administration Increases Proactive Control in Men with Overweight or Obesity: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.
Preclinical and clinical evidence suggests that oxytocin administration decreases food intake and weight. The mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown but critical to study to consider oxytocin as a neurohormonal weight loss treatment. Complementing ongoing research into metabolic and food motivation mechanisms of oxytocin, this study hypothesized that in humans, oxytocin improves cognitive control over behavior. In a randomized, double-blind, placebo-controlled crossover study of 24-IU single-dose intranasal oxytocin, 10 men with overweight or obesity completed a stop-signal task assessing ability and strategy to suppress behavioral impulses, in which they performed a choice-reaction task (go task) but had to withhold their response when prompted (stop task). It was hypothesized that oxytocin would improve suppression of behavioral impulses. After receiving oxytocin, compared with placebo, participants showed increased reaction times in the go task (mean [M] = 936 milliseconds vs. 833 millseconds; P = 0.012; 95% CI: 29 to 178) and displayed fewer stop errors (M = 36.41% vs. 41.15%; P = 0.049; 95% CI: -9.43% to -0.03%). Oxytocin triggers increased proactive control over behavior. Future studies need to further characterize the impact of oxytocin on cognitive control and investigate its potential role in the anorexigenic effects of oxytocin in human obesity.


Validation and Reference Scores of the Transition Readiness Assessment Questionnaire in Adolescent and Young Adult IBD Patients.
Transition readiness can predict a successful transition from pediatric to adult care. This study aimed to validate and develop age-dependent reference scores for the (Dutch version of) Transition Readiness Assessment Questionnaire (TRAQ), in adolescents and young adults (AYAs) with inflammatory bowel disease (IBD). TRAQ has 20 items (score 1-5) distributed over 5 domains (total sum score 100) and is completed by AYAs. Following the COnsensus-based Standards for the selection of health Measurement INstruments methodology, we conducted the translation, back-to back translation, pretesting, and validation of the final Dutch version of TRAQ (TRAQ-NL) questionnaire. We used a Rasch model for structural validation, hypothesis testing for construct validity, and Cronbach alpha to demonstrate reliability. Reference scores were calculated using percentiles. Two hundred fifty TRAQ questionnaires were evaluated in 136 AYAs with IBD [56% Crohn disease, 58% male, median age 17.5 years (range 15.7-20.4)]. The overall mean item score was 3.87 (range 1.45-5). With good reliability (Cronbach alpha 0.87), TRAQ-NL discriminated well between knowledge levels, especially in the lower levels. Transition readiness was defined as low, moderate, adequate, or excellent in patients with TRAQ percentile scores (PC) <25th (<3.375 mean item score), 25th-50th (3.375-3.9), 50th-90th (3.91-4.7), or >90th (>4.7). Younger patients, concomitant illness, fewer visits to the transition clinic, and parental dependence were associated with significantly lower TRAQ scores. TRAQ(-NL) is reliable and valid, with age-dependent PC to identify (in)adequate transfer readiness. TRAQ can now be more easily used as a patient-reported outcome measure to monitor transition readiness longitudinally in routine care for AYAs IBD patients.


Design of double sampling inspection plans for life tests under time censoring based on Pareto type IV distribution.
Sampling inspection plans for life tests, called reliability sampling plans, are generally employed to determine the acceptance or non-acceptance of the lot(s) of finished products by performing tests on the sampled items, measuring the lifetime of the items and observing the number of failures of items. Lifetime of individual items is a prime quality characteristic that can be treated as a continuous random variable and can be modeled by an appropriate probability distribution. In this article, double sampling plans for life tests under time censoring with a provision to draw two random samples and to admit a maximum of one failure in the combined samples are formulated assuming that the lifetime random variable follows a Pareto type IV distribution. A methodical procedure for the selection of the plan parameters using reliable life criterion with the desired discrimination protecting the interests of the producer and the consumer in terms of the acceptable reliable life and unacceptable reliable life is evolved. The operating ratio is used as a measure of discrimination in designing the proposed reliability sampling plans.


[Use of rifampicin for directed modification of the nucleotide composition of the cells of Bacillus megaterium and Candida utilis].
The object of this work was to study the effect of rifampicin on the physiological state of Bacillus megaterium and Candida utilis in chemostat and batch cultures. When B. megaterium is cultivated in a medium containing 1 microgram of rifampicin per litre, its metabolism changes, the pool of free nucleotides rises, and the content of RNA drops in response to the specific action of the inhibitor. The modified state is observed throughout many generations. The action of the inhibitor is also non-specific: protein content falls and polyhydroxybutyric acid is accumulated. The morphology of B. megaterium cells changes: they become larger, their cell wall thickens, and the separation of cells from one another is complicated. At a high concentration (5 mg/l), rifampicin decelerates the growth of C. utilis and causes merely a minor non-specific inhibition.


Association between Style of Living and General Health in Suburban Women: A Cross-sectional Study in South East of Iran.
In developing countries, suburban population is increasing. However, their health issues are rarely considered in studies. Socioeconomic and environmental factors in their neighbourhood can affect their lifestyle and health. Compared to men, women have fewer social resources and are more susceptible to an unfavourable environment, in general. To investigate the association between lifestyle and general health status in suburban women. This correlation, cross-sectional study assessed the lifestyle and general health, among suburban women living in Shirabad neighbourhood, Zahedan, Iran. Randomized one stage cluster sampling was used and 132 people participated in the study. Lifestyle Questionnaire (LSQ) and General Health Questionnaire-28 (GHQ-28) were used for data collection. For data analysis, descriptive statistical methods, Pearson's correlation coefficient and multivariate regression analysis were performed. Mean score of LSQ was 100.23±20.45 and mean GHQ-28 score was 28.46±16.41. There was a significant negative relationship between lifestyle and GHQ-28 total score (r=-0.619, p=0.01). Multivariate regression analysis showed that among predictor variables, education, sports and fitness and psychological health components had a significant relationship with GHQ-28 (p<0.001, p=0.01, p=0.002 respectively). This study demonstrated that suburban women have poor lifestyle and health status. Also, it showed a significant relationship between education, sports and fitness and psychological health components and health. As a result, implementation of programs to modify lifestyle especially in the field of sports and improving the educational level could be useful in promoting women's health.


Subacute reactions to intrathecal amipaque (metrizamide), conray and dimer X: a structural and ultrastructural study.
Adult New Zealand rabbits were injected intrathecally with 200 or 300 mgI/ml of metrizamide, meglumine iocarmate or meglumine iothalamate. They were placed in the Trendelenburg position for 20 min and allowed to survive for 1, 2 or 3 weeks. Sacrifice was by intraarterial perfusion of aldehydes under anesthesia followed by preparation of brain and major venous sinuses for light and electron microscopy. Major findings were subpial edema and inflammatory reaction of superficial brain, leptomeninges, subarachnoid space and arachnoid granulations. They were most severe after iothalamate and milder after metrizamide. The severity decreased with time. It is of significance that severe reactions occurred after 300 mgI/ml concentration of metrizamide.


Comparison and optimization of DNA Isolation protocols for high throughput genomic studies of Acacia pachyceras Schwartz.
We describe the optimization and validation of six DNA isolation protocols from fresh leaves of the rare tree Acacia pachyceras. The first four protocols employed three commercial kits (Sigma, Nucleospin1, Nucleospin 2, Promega) whereas the remaining two were based on the traditional sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide CTAB methods. Each protocol provided significantly different results concerning DNA concentration (p < 0.032), yield (p < 0.000), contaminant carry over, protocol duration, cost per sample, and comprehensive cost. We demonstrated the applicability of all the tested protocols in DNA barcoding. The protocol yielded maximum amounts (92.85 µg) of DNA in a rapid turnaround time (8 h). The quantity and purity surpassed all the other tested methods. DNA extracted by the CTAB method was the best for NGS (Phred score >Q30). These protocols will be useful tools for molecular research of Acacia pachyceras and other closely related tree species.


Cell-free translation of the vitamin K-dependent bone protein osteocalcin.
The primary gene product of the vitamin K-dependent bone matrix protein, osteocalcin, has been identified by immunoprecipitation of cell-free translated proteins from 4 week rat calvariae mRNA preparations. Peptides of 9.8kd and 12kd, precipitated with a polyclonal affinity selected species specific antibody raised to purified rat osteocalcin, accounted for 1-2% of labelled proteins and were displaced by rat osteocalcin. These studies demonstrate that the 5800 molecular weight osteocalcin is synthesized as a precursor of approximately twice its size. The size of the propeptide, with a molecular weight of 4.3kd, is consistent with other known secreted vitamin K-dependent blood proteins.


Adverse effects of E150d on zebrafish development.
E150d is a food additive used to increase palatability and impart colour to foods and drinks. Known as 'caramel dye', it contains 4-methylimidazole, a cytotoxic molecule for animal models and human. Recently, the growing consumption of E150d causes an increasing release of this additive into the environment, particularly in water bodies. For this reason, in this study it was assessed the toxic effect of E150d on zebrafish embryos, a conventional aquatic model organism. Six hours post fertilization embryos were treated with two different concentrations of E150d (0.3 g/L and 0.6 g/L) for 72 h and their embryonic development was studied. It emerged that this food additive induced toxic effects on hatching, survival, embryos phenotype and cardiac beat with a dose-dependent trend. Furthermore, it impaired swimming performance and induced damages in skeletal muscles and pericardial cavity. Data obtained showed the risk associated with the dispersion of E150d in water bodies suggesting that a greater attention should be paid in avoiding an unnecessary use so to preserve human and environmental health.


Complete laryngotracheoesophageal cleft: complicated management issues.
Laryngotracheoesophageal clefts are rare developmental anomalies of the upper aerodigestive tract. They range in severity from being virtually asymptomatic throughout life (type I) to being incompatible with life (type IV). The timing of diagnosis is crucial to the successful treatment of severe clefts. Treatment is complicated and requires a multi-team approach. The case report discusses the elements involved in diagnosing and treating this severe airway anomaly. Case report. Review of a case at a tertiary care center. A case of a complete laryngotracheoesophageal cleft with left-side pulmonary agenesis in a newborn is reported. Rigid bronchoscopy revealed a common tracheoesophageal lumen from the larynx to the stomach with a single bronchus supplying the right-side lung. Management of this patient included establishment and maintenance of a tenuous airway, maintenance of nutrition, and anesthetic and surgical planning for upper aerodigestive tract reconstruction. Although severe laryngotracheoesophageal clefts are rare, they require prompt, team-oriented management for the best outcome possible. The diagnosis, sustenance, and treatment options of these patients depend on varied and complicated factors, which are discussed.


Marfan's syndrome: combined composite valve graft replacement of the aortic root and transaortic mitral valve replacement.
Echocardiographic studies in patients with Marfan's syndrome indicate that 95% eventually have aortic root dilatation, mitral valve prolapse, or a combination of these. Both lesions can progress and require operation for aortic root aneurysm, aortic valve insufficiency, and mitral valve insufficiency. This report reviews the simplified treatment of 6 patients by combined composite valve graft replacement of the aortic root and transaortic mitral valve replacement at one operation. All patients survived and are well for periods extending from 1 month to 12 months.


Selective extraction and column separation for 16 kinds of rare earth element ions by using N, N-dioctyl diglycolacid grafted silica gel particles as the stationary phase.
The selective extraction and column separation rear earth elements (REEs) were investigated in the present work. Herein, the functional ligand of N, N-dioctyldiglycolic acid (DODGA) was synthesized and chemically grafted on the silica gel (SG) particles to give the novel material SG@DODGA. The obtained SG@DODGA was fully characterized by NMR, BET (Brunauer-Emmett-Teller) N2 physisorption analysis, atom force microscopy (AFM), scanning electronic microscopy (SEM), Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). After investigating the adsorption capability of the SG@DODGA towards 16 kinds of REEs (La, Ce, Pr, Nd, Sm, Eu, Gd, Td, Dy, Ho, Er, Tm, Yb, Lu, Y and Sc), the results showed that the adsorption kinetic data was better fitted with pseudo-second-order model and Elovich model, the adsorption isotherms data was suitable for Freundlich model. The above result also indicated that the adsorption mechanism between the SG@DODGA and REEs was chemical ion exchange. Moreover, choose SG@DODGA as the column chromatography stationary phase and packed in a glass column for the column studies to obtain breakthroughs profile of each REEs. Furthermore, the column was used to try to separate the mixed 16 kinds of REEs. The first attempt to preliminary separate REEs result showed that this column could be applied for simply separating REEs. The light REEs La, Ce, Pr, Nd exhibited better separation effect than the other REEs.


Cancer-Related Dysfunctional Beliefs About Sleep Mediate the Influence of Sleep Disturbance on Fear of Progression Among Patients With Surgically Resected Lung Cancer.
Lung cancer is associated with significant psychological distress, including fear of progression (FoP). Because insomnia and depression are highly prevalent and associated with FoP, we examined the association between FoP, insomnia, and depression in cancer patients. Furthermore, we tested the mediation effect of cancer-related dysfunctional beliefs about sleep (C-DBS) on this association. We analyzed data collected from patients with surgically resected non-small cell lung cancer from a single-center randomized controlled study investigating digital healthcare applications. Baseline demographic and clinical variables were collected. In addition, self-reported questionnaires including the Fear of Progression Questionnaire-Short Form, Patients Health Questionnaire-9 items (PHQ-9), Insomnia Severity Index, and C-DBS were administered. Among the 320 enrolled patients with lung cancer, a regression model showed that FoP was predicted by age (β = -0.13, P = 0.007), PHQ-9 (β = 0.35, P < 0.001), and C-DBS (β = 0.28, P < 0.001). Insomnia did not directly influence FoP, but C-DBS mediated the association. Depression directly influenced FoP, but C-DBS did not mediate this association. Among patients with surgically resected lung cancer, C-DBS mediated the effects of severity of insomnia on FoP. Depression directly influenced FoP, but C-DBS did not influence this association. To reduce FoP among patients with lung cancer, C-DBS should be addressed in the cognitive behavioral therapy module.


Sonographic findings of transvaginal color Doppler ultrasound in ectopic pregnancy.
The objective of this study was to retrospectively assess whether the sonographic findings from transvaginal color Doppler ultrasound (TV-CDU) are helpful in the diagnosis of ectopic pregnancy. Thirty-four patients who received surgery for ectopic tubal pregnancies were preoperatively evaluated using TV-CDU. The presence or absence of color vascularity within the ectopic masses was examined. The relationship between the presence or absence of blood flow in the tubal mass and the corpus luteum cyst, or the serum β-hCG values, was evaluated. Color vascularity within the adnexal mass was detected in 27 of 34 (79.4%) patients with ectopic pregnancies by TV-CDU. Color vascularity within the mass was observed in 18 of 24 (75.0%) patients with a questionable adnexal mass that had no obvious gestational sac in B-mode images. Moreover, color vascularity was seen in all four patients with a serum β-human chorionic gonadotropin (β-hCG) value of less than 500 mIU/ml. However, it was difficult to identify the blood flow of the adnexal mass in six of the nine (66.7%) patients with a corpus luteum cyst in the ipsilateral ovary. No relationship was observed between the serum β-hCG concentrations and the resistance indices, or the peak systolic velocity. The detection of color vascularity by TV-CDU in patients with an ectopic pregnancy is helpful for diagnosis, especially for patients with either a questionable adnexal mass in B-mode images or lower serum β-hCG concentrations.


Glucose metabolism by lymphocytes, macrophages, and tumor cells from Walker 256 tumor-bearing rats supplemented with fish oil for one generation.
Here we investigated the effect of lifelong supplementation of the diet with coconut fat (CO, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids) on tumor growth and lactate production from glucose in Walker 256 tumor cells, peritoneal macrophages, spleen, and gut-associated lymphocytes. Female Wistar rats were supplemented with CO or FO prior to mating and then throughout pregnancy and gestation and then the male offspring were supplemented from weaning until 90 days of age. Then they were inoculated subcutaneously with Walker 256 tumor cells. Tumor weight at 14 days in control rats (those fed standard chow) and CO supplemented was approximately 30 g. Supplementation of the diet with FO significantly reduced tumor growth by 76%. Lactate production (nmol h(-1) mg(-1) protein) from glucose by Walker 256 cells in the group fed regular chow (W) was 381.8 +/- 14.9. Supplementation with coconut fat (WCO) caused a significant reduction in lactate production by 1.6-fold and with fish oil (WFO) by 3.8-fold. Spleen lymphocytes obtained from W and WCO groups had markedly increased lactate production (553 +/- 70 and 635 +/- 150) when compared to non-tumor-bearing rats ( approximately 260 +/- 30). FO supplementation reduced significantly the lactate production (297 +/- 50). Gut-associated lymphocytes obtained from W and WCO groups increased lactate production markedly (280 +/- 31 and 276 +/- 25) when compared to non-tumor-bearing rats ( approximately 90 +/- 18). FO supplementation reduced significantly the lactate production (168 +/- 14). Lactate production by peritoneal macrophages was increased by tumor burden but there was no difference between the groups fed the various diets. Lifelong consumption of FO protects against tumor growth and modifies glucose metabolism in Walker tumor cells and lymphocytes but not in macrophages.


Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response, Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma.
To identify predictive factors of tumor response, progression-free survival (PFS), overall survival (OS), and toxicity using three-dimensional (3D) voxel-based dosimetry in patients with intermediate and advanced stage hepatocellular carcinoma (HCC) treated by yttrium-90 (90Y) resin microspheres radioembolization (RE). From February 2012 to December 2015, 45 90Y resin microspheres RE procedures were performed for HCC (Barcelona Clinic Liver Cancer stage B/C; n = 15/30). Area under the dose-volume histograms (AUDVHs) were calculated from 3D voxel-based dosimetry to measure 90Y dose deposition. Factors associated with tumor control (ie, complete/partial response or stable disease on Modified Response Evaluation Criteria in Solid Tumors) at 6 months were investigated. PFS and OS analyses were performed (Kaplan-Meier). Toxicity was assessed by occurrence of radioembolization-induced liver disease (REILD). Tumor control rate was 40.5% (17/42). Complete tumor targeting (odds ratio = 36.97; 95% confidence interval, 1.83-747; P < .001) and AUDVHtumor (odds ratio = 1.027; 95% confidence interval, 1.002-1.071; P = .033) independently predicted tumor control. AUDVHtumor ≥ 61 Gy predicted tumor control with 76.5% sensitivity and 75% specificity. PFS and OS in patients with incomplete tumor targeting were significantly shorter than in patients with complete tumor targeting (median PFS, 2.7 months [range, 0.8-4.6 months] vs 7.9 months [range, 2.1-39.5 months], P < .001; median OS, 4.5 months [range, 1.4-23 months] vs 19.2 months [range, 2.1-46.9 months], P < .001). Patients with incomplete tumor targeting and AUDVHtumor < 61 Gy, incomplete tumor targeting and AUDVHtumor > 61 Gy, complete tumor targeting and AUDVHtumor < 61 Gy, and AUDVHtumor > 61 Gy had median PFS of 2.7, 1.8, 6.3, and 12.1 months (P < .001). REILD (n = 4; 9.5%) was associated with higher dose delivered to normal liver (P = .04). Complete tumor targeting and 90Y dose to tumor are independent factors associated with tumor control and clinical outcomes.


Effects of cell phone use on semen parameters: Results from the MARHCS cohort study in Chongqing, China.
Epidemiological and experimental evidence for detrimental effects of cell phone use on semen quality is still equivocal. And that recruiting participants from infertility clinic not from general population may raise the possibility of a selection bias. To investigate effects of cell phone use on semen parameters in a general population,We screened and documented the cell phone use information of 794 young men from the Male Reproductive Health in Chongqing College students (MARHCS) cohort study in 2013, followed by 666 and 568 in 2014 and 2015, respectively. In the univariate regression analyses, we found that the daily duration of talking on the cell phone was significantly associated with decreased semen parameters, including sperm concentration [β coefficient=-6.32% per unit daily duration of talking on the cell phone (h); 95% confidence interval (CI), -11.94, -0.34] and total sperm count (-8.23; 95% CI, -14.38, -1.63) in 2013; semen volume (-8.37; 95% CI, -15.93, -0.13) and total sperm count (-16.59; 95% CI, -29.91, -0.73) in 2015]. Internet use via cellular networks was also associated with decreased sperm concentration and total sperm counts in 2013 and decreased semen volume in 2015. Multivariate analyses were used to adjust for the effects of potential confounders, and significant negative associations between internet use and semen parameters remained. Consistent but nonsignificant negative associations between talking on the cell phone and semen parameters persisted throughout the three study years, and the negative association was statistically significant in a mixed model that considered all three years of data on talking on the cell phone and semen quality. Our results showed that certain aspects of cell phone use may negatively affect sperm quality in men by decreasing the semen volume, sperm concentration, or sperm count, thus impairing male fertility.


Inhibition of nocturnal prolactin surges in the pregnant rat by incubation medium containing placental lactogen.
Rats hysterectomized on Day 7 or 8 of pregnancy continued to have nocturnal prolactin surges 1 day later. Conditioned medium obtained from incubation of Day 11 placentas infused via the jugular vein completely blocked this nocturnal surge, indicating a negative feedback of placental secretions on prolactin. Infusion of an ultrafiltrate of the conditioned medium which only contained molecules with Mr above 10,000 also blocked the prolactin surge. Next, it was determined whether this feedback of placental secretions on prolactin may work by way of hypothalamic dopamine. Levels of dopamine in hypophysial stalk blood from pregnant rats on Day 12, a time when secretion of placental lactogen is high, were not different from those in rats in which placental lactogen was absent. It is concluded that termination of prolactin surges at midpregnancy may be due to feedback of placental secretions, possibly placental lactogen, on the hypothalamus and/or pituitary. However, these experiments do not support the hypothesis that this inhibition is mediated by alteration in hypothalamic dopamine secretion.


Can the sagittal lumbar curvature be closely approximated by an ellipse?
For the sagittal lumbar curvature, existing spinal models are based only on the anthropomorphic radiographic characteristics of one individual, or, at best, of only a few individuals. This raises questions of applicability of the modeling results to clinical situations. Because spinal coupling and loads on spinal tissues have been shown to be functions of the initial static posture, a rigorously derived neutral lumbar lordosis would be important for clinicians and spine researchers. This study presents modeling of the sagittal lumbar spine in the shape of an ellipse. Vertebral body and disc heights, derived from digitized lateral lumbar radiographs of 50 normal subjects, were used to create an ellipse along the posterior body margins from the inferior of T12 to the superior sacral base. Additional data to create an elliptical lumbar model were determined from a least-squares analysis of passing ellipses through the digitized posterior body points. This confirmed that an elliptical model closely fit the lumbar curvature with a least-squares error of 1.2 mm per digitized point. The elliptical model is approximately an 85 degrees portion of a quadrant. The semi-major and semi-minor axes, a and b, are parallel to the posterior body margin of T12 and parallel to the inferior body endplate of T12, respectively, with a semi-minor to semi-major radio of b/a=0.39. The elliptic model has a height-to-length ratio of H/L=0.963, where height is the vertical distance from inferior T12 to superior S1 and length is the arc length along George's line (along the posterior longitudinal ligament) from T12 to S1.


No barrier breakdown between human and cattle schistosome species in the Senegal River Basin in the face of hybridisation.
Schistosomiasis is widely distributed along the Senegal River Basin (SRB), affecting both the human population and their livestock. Damming of the Senegal River for irrigation purposes in the 1980s induced ecological changes that resulted in a large outbreak of Schistosoma mansoni, followed a few years later by an increase and spread of Schistosoma haematobium infections. The presence of hybrid crosses between the human and cattle schistosomes, S. haematobium and Schistosoma bovis, respectively, is adding complexity to the disease epidemiology in this area, and questions the strength of the species boundary between these two species. This study aimed to investigate the epidemiology of S. haematobium, S. bovis and their hybrids along the Senegal River basin using both microsatellite genetic markers and analysis of mitochondrial and nuclear DNA markers. Human schistosome populations with a S. haematobium cox1 mtDNA profile and those with a S. bovis cox1 mtDNA profile (the so-called hybrids) appear to belong to a single randomly mating population, strongly differentiated from the pure S. bovis found in cattle. These results suggest that, in northern Senegal, a strong species boundary persists between human and cattle schistosome species and there is no prolific admixing of the populations. In addition, we found that in the SRB S. haematobium was spatially more differentiated in comparison to S. mansoni. This may be related either to the presence and susceptibility of the intermediate snail hosts, or to the colonisation history of the parasite.


Utilizing a Homecare Platform for Remote Monitoring of Patients with Idiopathic Pulmonary Fibrosis.
Homecare and home telemonitoring are a focal point of emerging healthcare schemes, with proven benefits for both patients, caregivers and providers, including reduction of healthcare costs and improved patients' quality of life, especially in the case of chronic disease management. Studies have evaluated solutions for remote monitoring of chronic patients based on technologies that allow daily symptom and vital signs monitoring, tailored to the needs of specific diseases. In this work, we present an affordable home telemonitoring system for patients with idiopathic pulmonary fibrosis (IPF), based on an application for mobile devices and Bluetooth-enabled sensors for pulse oximetry and blood pressure measurements. Besides monitoring of vital signs, the system incorporates communication via videoconferencing and emergency response, with support from a helpdesk service. A pilot study was conducted, in order to verify the proposed solution's feasibility. The results support the utilization of the system for effective monitoring of patients with IPF.


Abnormal IgG galactosylation in MRL-lpr/lpr mice: pathogenic role in the development of arthritis.
MRL-lpr/lpr (MRL/lpr) mice spontaneously develop arthritis by an increase in the incidence of agalactosylated oligosaccharides in serum IgG, similar to rheumatoid arthritis patients. However, whether this association has a pathogenic significance is still unknown. In this study, we analyzed the oligosaccharide structure of serum IgG in various MRL mice with or without arthritis, to clarify the relationship between the oligosaccharide abnormality and the development of arthritis. The level of agalactosylation in serum IgG was comparable in both arthritis-free MRL/lpr and MRL-+/+ (MRL/+) mice at 6 weeks of age. In contrast, the incidence of IgG lacking galactose markedly increased in MRL/lpr mice at 6 months of age (the age at which arthritis occurred), compared with that from age-matched MRL/+ mice without arthritis. However, the proportion of agalactosylated IgG increased similarly in anti-CD4 monoclonal antibody-treated MRL/lpr mice at 6 months of age, despite the absence of the development of arthritis, because of depletion of CD4+ T cells. These results suggest that the abnormality in IgG galactosylation of MRL/lpr mice developed in an age-dependent manner, but it did so independently of CD4+ T cell-dependent B-cell activation and is not a consequence of the development of arthritis.


Establishment of a genomic bank of bovine herpesvirus 1 using a novel positive selection plasmid vector.
A small positive selection cloning vector, designated pSiig1, suitable for the construction of genomic banks in E. coli is described and used for the establishment of a bank of the bovine herpesvirus 1 genome. Hybrid transformants are directly selected on agar plates containing ampicillin. The vector is based on the replicon of R1 and has a lambda PR promotor inserted upstream of the replication control genes. The vector has an uncontrolled (runaway) replication and is lethal to the host cell unless the PR promotor is brought under trans-acting control of the lambda cI repressor or runaway replication is blocked by an insertion between the PR promotor and the replicon. The vector contains a unique Bg/II site between PR and the replicon which is suitable for insertion of genomic DNA.


Synthesis and pharmacological activity of 1,2,4-triazolo[4,3-a]quinolines.
The synthesis of a series of 1,2,4-triazolo[4,3-a]quinoline derivatives is described; their structures were assigned by 1H NMR and analytical data. The new compounds were tested in vivo for their antiinflammatory and analgesic activities, as well as for their ulcerogenic action. Some of the tested triazoles showed an analgesic activity in the acetic acid writhing test and antiinflammatory properties on carrageenan paw edema assay.


The PLOD2/succinate axis regulates the epithelial-mesenchymal plasticity and cancer cell stemness.
Aberrant accumulation of succinate has been detected in many cancers. However, the cellular function and regulation of succinate in cancer progression is not completely understood. Using stable isotope-resolved metabolomics analysis, we showed that the epithelial mesenchymal transition (EMT) was associated with profound changes in metabolites, including elevation of cytoplasmic succinate levels. The treatment with cell-permeable succinate induced mesenchymal phenotypes in mammary epithelial cells and enhanced cancer cell stemness. Chromatin immunoprecipitation and sequence analysis showed that elevated cytoplasmic succinate levels were sufficient to reduce global 5-hydroxymethylcytosinene (5hmC) accumulation and induce transcriptional repression of EMT-related genes. We showed that expression of procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) was associated with elevation of cytoplasmic succinate during the EMT process. Silencing of PLOD2 expression in breast cancer cells reduced succinate levels and inhibited cancer cell mesenchymal phenotypes and stemness, which was accompanied by elevated 5hmC levels in chromatin. Importantly, exogenous succinate rescued cancer cell stemness and 5hmC levels in PLOD2-silenced cells, suggesting that PLOD2 promotes cancer progression at least partially through succinate. These results reveal the previously unidentified function of succinate in enhancing cancer cell plasticity and stemness.


Expression of sonic hedgehog signaling components in hepatocellular carcinoma and cyclopamine-induced apoptosis through Bcl-2 downregulation in vitro.
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Aberrant activation of sonic hedgehog (Shh) signaling pathway plays important roles in tumorigenesis and progression of several tumors. Cyclopamine, an important inhibitor of Shh signaling pathway, can induce cell apoptosis. However, the mechanisms underlying cyclopamine-induced apoptosis are not well understood. The aim of this study is to determine the expression of the Shh signaling pathway components in HCC and to investigate the mechanisms underlying cyclopamine-induced apoptosis in HCC cells. Shh signaling components (Shh, Ptch, Smo and Gli-1) expression levels were evaluated by immunohistochemistry on tissue microarrays containing 98 HCCs with paired adjacent noncancerous liver tissues. The relationships between sonic hedgehog signal pathway and clinicopathological factors were analyzed in HCC. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis was detected by flow cytometry. mRNA and protein levels were analyzed by RT-PCR and Western blot, respectively. Shh, Ptch, Smo and Gli-1 were overexpressed in HCC tissues compared with paired adjacent noncancerous liver tissue. Activated Shh signaling pathway was associated with tumor size, capsular invasion and vascular invasion in HCC. Cyclopamine remarkably decreased cell viability, induced apoptosis and downregulated Bcl-2 expression in HCC cells. Shh signaling pathway plays an important role in HCC tumorigenesis and progression, indicating that Shh signaling pathway is a potential therapeutic target for HCC. Cyclopamine induces apoptosis through downregulating Bcl-2 in HCC.


Assessment of COVID-19 prevention and protection measures in hospitals.
This paper aims to develop an assessment framework for the Covid-19 prevention and protection measures in hospitals. The conceptual model is developed by using fifty-four attributes, fifteen criteria, and three enablers. The multi-grade fuzzy approach is used to develop the assessment framework, and Importance Performance Analysis (IPA) identifies the weaker attributes in the case organization. The case hospital's preventive and safety measures assessment level is 8.05, which is 'very highly focused on protection measures,' and fourteen weaker attributes were identified. The case hospital management should focus on the guidelines of Covid-19 preventive and protection measures, strict protocols, regular audits, education and training of the staff, and active surveillance. Case hospital managers should also focus on staffing and timings, the formulation of policies, and abiding by those policies without any fail. This proposed assessment model is a new initiative in-hospital assessment in preventive and safety measures in the healthcare sector during the Covid-19 era. This framework will enable hospital managers as a continuous assessment tool to improve their Covid-19 prevention operations.


Incidence and patterns of recurrence after intersphincteric resection for very low rectal adenocarcinoma.
The aim of this study was to evaluate the incidence and patterns of recurrence, or oncologic safety, after intersphincteric resection (ISR) without radiotherapy for very low rectal adenocarcinoma. One hundred eight consecutive patients with T1-T3 rectal cancers located 1 to 5 cm (median 3 cm) from the anal verge underwent ISR. A retrospective analysis of prospectively recorded data from the 106 patients not receiving radiotherapy was performed. There were 23 T1, 40 T2, and 43 T3 tumors. Morbidity and mortality rates were 33% and 1%, respectively. The 3-year rates of overall local recurrence and survival were 5.7% and 95%, respectively. The 3-year cumulative local recurrence rate was 0% for the patients with T1-T2 tumors as compared with 15% for those with T3 tumors (p=0.0012). In T3 tumors, the 2-year local recurrence rate was 5% for patients with negative surgical margins as compared with 33% for those with positive margins (p=0.0001). The incidences of distant recurrence for stages I, II, III, and IV disease were 4%, 5%, 18%, and 33%, respectively. ISR does not increase local or distant recurrences. For T1-T2 tumors, meticulous dissection and irrigation after closure of the distal stump allows local control without radiotherapy. With T3 tumors, preoperative therapy should be considered if resection margins are estimated to be insufficient.


Revising the Belgian Nursing Minimum Dataset: from concept to implementation.
The process of revising the Belgian Nursing Minimum Dataset (B-NMDS) started in 2000 and entailed four major phases. The first phase (June-October 2002) involved the development of a conceptual framework based on a literature review and secondary data analysis. The Nursing Interventions Classification (NIC) was selected as a framework for the revision of the original B-NMDS. The second phase (November 2002-September 2003) focused on language development for six care programs evaluated by panels of clinical experts (N=75). These panels identified the following items as priorities for the revised B-NMDS: hospital financing, nurse staffing allocation, assessment of the appropriateness of hospitalisation, and quality management. During this period, we developed a draft instrument with 92 variables using the NIC. This led to an alpha version of a revised B-NMDS. The third phase (October 2003-December 2004) focused on data collection and validation of the new tool. The revised B-NMDS (alpha version) was tested in 158 nursing wards in 66 Belgian hospitals from December 2003 until March 2004. This test generated data for some 95,000 in-patient days. The interrater reliability of the revised B-NMDS was assessed. The criterion-related validity of the revised B-NMDS was compared to that of the original B-NMDS. The discriminative power of the revised B-NMDS was also assessed to select the most relevant variables for data collection. This resulted in a beta version of the revised B-NMDS in December 2004. The records of the revised B-NMDS were linked to the Hospital Discharge Dataset and other mandatory datasets to integrate the revised B-NMDS into the overall healthcare management system. The fourth phase (January 2005-December 2005) is presently focusing on information management. Nationwide implementation is foreseen by January 2007.


Pluripotency state of mouse ES cells determines their contribution to self-organized layer formation by mesh closure on microstructured adhesion-limiting substrates.
Assembly of pluripotent stem cells to initiate self-organized tissue formation on engineered scaffolds is an important process in stem cell engineering. Pluripotent stem cells are known to exist in diverse pluripotency states, with heterogeneous subpopulations exhibiting differential gene expression levels, but how such diverse pluripotency states orchestrate tissue formation is still an unrevealed question. In this study, using microstructured adhesion-limiting substrates, we aimed to clarify the contribution to self-organized layer formation by mouse embryonic stem cells in different pluripotency states: ground and naïve state. We found that while ground state cells as well as sorted REX1-high expression cells formed discontinuous cell layers with limited lateral spread, naïve state cells could successfully self-organize to form a continuous layer by progressive mesh closure within 3 days. Using sequential immunofluorescence microscopy to examine the mesh closure process, we found that KRT8+ cells were particularly localized around unfilled holes, occasionally bridging the holes in a manner suggestive of their role in the closure process. These results highlight that compared with ground state cells, naïve state cells possess a higher capability to contribute to self-organized layer formation by mesh closure. Thus, this study provides insights with implications for the application of stem cells in scaffold-based tissue engineering.


Defining "natural product" between public health and business, 17th to 21st centuries.
The historical definition of a natural product stands at the crossroads of business, health, and the symbolic order of things. Until the end of the 19th century, "natural product" was a synonym of perishable. The emergency of organic chemistry made perishability be replaced with "toxicity". Nowadays, genetics is provoking a radical change in the notion and practises of "natural product". However, these concerns are never entirely opposed to "naturality" as a synonym for sacred and symbolic order. Traceability is largely based upon kosher practices and the association between organic and good for health is hardly based upon sound scientific arguments.


Exonuclease TREX1 also Has a Sweet Tooth.
TREX1 regulates innate immune responses by counteracting DNA accumulation in the cytosol. In this issue of Immunity, Hasan et al. (2015) show that TREX1 also safeguards the cell against free glycan build-up in the endoplasmic reticulum, thereby preventing glycan-induced inflammation.


Inhibition of epidermal growth factor-induced cell transformation and Akt activation by caffeine.
We found that caffeine significantly inhibited epidermal growth factor (EGF)- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation in the JB6 mouse epidermal cell line. The tumor promoter-induced cell transformation was also blocked by treatment with an adenosine A1 receptor antagonist, 8-phenyltheophylline (8-PTH). Caffeine slightly attenuated activation of EGF-induced activator protein 1 (AP-1) activation, which play important roles in cell transformation, but only at the highest concentration examined (1 mM). Interestingly, pretreatment with caffeine suppressed EGF-induced phosphorylation and activation of Akt and ribosomal p 70 S6 protein kinase (p 70 S 6 K), a target of Akt, without inhibiting phosphatidylinositol 3-kinase (PI 3 K) activation. The inhibition of Akt activation of caffeine was not a result of its adenosine receptor antagonism. Because Akt plays a key role in signal transduction pathways leading to cell proliferation and apoptosis, our results provide novel insight into possible mechanisms of the chemotherapeutic effect of caffeine.


The Risk Factors of COVID-19 Infection and Mortality among Older Adults in South Korea.
This study aimed to identify the risk factors associated with coronavirus disease 2019 (COVID-19) infection and mortality among older adults in South Korea. Using Korean National Health Insurance data from January 1, 2020, to March 31, 2022, we analyzed the impact of various factors, including age, comorbidity burden, and insurance type, on COVID-19 infection and mortality rates. Age was the most significant risk factor for mortality in older adults. A higher comorbidity burden was also associated with increased infection (odds ratio [OR]=1.33 for Charlson Comorbidity Index [CCI] ≥2, 95% confidence interval [CI] 1.321-1.339) and mortality (OR=1.537 for CCI ≥2, 95% CI 1.459-1.618) rates. While Medical Aid recipients exhibited lower infection rates (OR=0.898, 95% CI 0.89-0.906) than National Health Insurance beneficiaries, they had higher mortality rates (OR=1.692, 95% CI 1.623-1.763). These results emphasized the need to prioritize vaccination and allocate healthcare resources for older adults, particularly those with multiple comorbidities. Addressing socioeconomic disparities and ensuring equitable access to testing and healthcare services are crucial for mitigating the impact of COVID-19 on older adults.


Concurrent drug therapy in patients undergoing surgery.
In a retrospective study of 57,176 patients and a prospective study of 216 patients undergoing surgery, 24-32% of patients were receiving some concurrent medication. Between 10 and 16% were taking drugs for cardiovascular disease. Of these, only 71% had their normal medication prescribed before surgery and only 41% received their drugs on the day of surgery.


Is oseltamivir suitable for fighting against COVID-19: In silico assessment, in vitro and retrospective study.
Oseltamivir is a first-line antiviral drug, especially in primary hospitals. During the ongoing outbreak of coronavirus disease 2019 (COVID-19), most patients with COVID-19 who are symptomatic have used oseltamivir. Considering its popular and important role as an antiviral drug, it is necessary to evaluate oseltamivir in the treatment of COVID-19. To evaluate the effect of oseltamivir against COVID-19. Swiss-model was used to construct the structure of the N-terminal RNA-binding domain (NRBD) of the nucleoprotein (NC), papain-like protease (PLpro), and RNA-directed RNA polymerase (RdRp) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). TM-align program was performed to compare the structure of the viral proteins with the structure of the neuraminidase of influenza A. Molecular docking was used to analyze the theoretical possibility of effective binding of oseltamivir with the active centers of the viral proteins. In vitro study was used to evaluate the antiviral efficiency of oseltamivir against SARS-CoV-2. By clinical case analysis, we statistically evaluated whether the history of oseltamivir use influenced the progression of the disease. The structures of NRBD, PLpro, and RdRp were built successfully. The results from TM-align suggested that the S protein, NRBD, 3C-like protease (3CLpro), PLPrO, and RdRp were structurally similar to the influenza A neuraminidase, with TM-scores of 0.30077, 0.19254, 0.28766, 0.30666, and 0.34047, respectively. Interestingly, the active center of 3CL pro was found to be similar to the active center from the neuraminidase of influenza A. Through an analysis of molecular docking, we discovered that oseltamivir carboxylic acid was more favorable to bind to the active site of 3CLpro effectively, but its inhibitory effect was not strong compared with the positive group. Finally, we used in vitro study and retrospective case analysis to verify our speculations. We found that oseltamivir is ineffective against SARS-CoV-2 in vitro study and the clinical use of oseltamivir did not improve the patients' symptoms and signs and did not slow the disease progression. We consider that oseltamivir isn't suitable for the treatment of COVID-19. During the outbreak of novel coronavirus, when oseltamivir is not effective for the patients after they take it, health workers should be highly vigilant about the possibility of COVID-19.


[Review and analysis of the evidence on the role and the impact of pharmacists' activities: Development of an online tool].
Considering the increase in healthcare expenses, stakeholders need to make choices, including healthcare program funding, and professional activities to prioritise. The main objective was to list evidences about the role and impact of pharmacists. Themes were chosen according to three dimensions of the pharmacist profession: (1) activities, (2) healthcare programs and (3) disorders. A literature search was conducted for each theme. A bibliographic data sheet was completed for each article. An analytic data sheet, consisting of descriptive and impact outcomes, was also completed for the most relevant articles. For each theme, a synthesis was elaborated. The website Impact Pharmacie (http://impactpharmacie.org) was developed. A total of 70 synthesis were written. A total of 1442 articles were included with a bibliographic data sheet, and 914 with an analytic data sheet. Six hundred and fifty articles had positive outcomes on the role of the pharmacist, representing 803 different positive outcome markers. Pharmacists had positive outcomes on morbidity (n=212), adherence (n=92), costs (n=36), adverse effects (n=26), drug errors (n=31) and mortality (n=13). This descriptive study presents the review of the evidence on the role and the impact of pharmacists activities, which led to the Impact Pharmacie website. This francophone website can contribute to support clinical pharmacy development, and to a better use of pharmacists in healthcare.


A type III polyketide synthase from Wachendorfia thyrsiflora and its role in diarylheptanoid and phenylphenalenone biosynthesis.
Chalcone synthase (CHS) related type III plant polyketide synthases (PKSs) are likely to be involved in the biosynthesis of diarylheptanoids (e.g. curcumin and polycyclic phenylphenalenones), but no such activity has been reported. Root cultures from Wachendorfia thyrsiflora (Haemodoraceae) are a suitable source to search for such enzymes because they synthesize large amounts of phenylphenalenones, but no other products that are known to require CHSs or related enzymes (e.g. flavonoids or stilbenes). A homology-based RT-PCR strategy led to the identification of cDNAs for a type III PKS sharing only approximately 60% identity with typical CHSs. It was named WtPKS1 (W. thyrsiflora polyketide synthase 1). The purified recombinant protein accepted a large variety of aromatic and aliphatic starter CoA esters, including phenylpropionyl- and side-chain unsaturated phenylpropanoid-CoAs. The simplest model for the initial reaction in diarylheptanoid biosynthesis predicts a phenylpropanoid-CoA as starter and a single condensation reaction to a diketide. Benzalacetones, the expected release products, were observed only with unsaturated phenylpropanoid-CoAs, and the best results were obtained with 4-coumaroyl-CoA (80% of the products). With all other substrates, WtPKS1 performed two condensation reactions and released pyrones. We propose that WtPKS1 catalyses the first step in diarylheptanoid biosynthesis and that the observed pyrones are derailment products in the absence of downstream processing proteins.


Glucose tolerance and insulin secretion, morbidity, and death in patients with cystic fibrosis.
To describe the history, mechanisms, and consequences of cystic fibrosis (CF)-related diabetes, from childhood to early adulthood. Pancreatic beta-cell function was estimated from the plasma insulin/glucose ratios during oral glucose tolerance test (total area under the curve and deltaI(30-0min)/G(30min), homeostasis model assessment [HOMA]%B), insulin sensitivity with the HOMA%S index, in 237 children with CF (109 boys, 128 girls). Progression of glucose metabolism abnormalities was evaluated by analysis for interval censored data; rates of pulmonary transplantation and death by Kaplan-Meier analysis. Impaired glucose tolerance was found in 20% of patients at 10 years, 50% at 15 years, 75% at 20 years, 82% at 30 years; for diabetes, >20% at 15 year, 45% at 20 years, 70% at 30 years; for insulin treatment, 30% at 20 years, 40% at 30 years. Early impairment was associated with lower survival rates and higher rates of lung transplantation. The area under the curve(glucose) correlated with decreased body mass index and height. Decrease in early insulin secretion (deltaI(30-0min)/G(30min)) was associated with impaired glucose tolerance, in all estimates of insulin secretion with diabetes. HOMA%S did not differ between the groups. Increased inflammation correlated with insulin resistance and impaired glucose tolerance. CF-related diabetes, mainly because of beta-cell deficiency, is frequent early in life and associated with impaired nutritional state and growth, increased rates of terminal respiratory failure, and death.


Monoclonal antibodies to mitochondrial F1-ATPase and oligomycin sensitivity conferring protein (OSCP). Tools for recognition of well conserved and essential antigenic sites.
The preparation of anti-OSCP monoclonal antibodies is described for the first time. One of these antibodies prevents the activating effect of OSCP in reconstitution experiments. These antibodies and antibodies previously obtained against the alpha- and beta-subunits of pig heart mitochondrial F1-ATPase have been used to look for well conserved epitopes in various species. One anti-beta antibody can recognize all species tested while the anti-OSCP antibodies only recognize the pig or beef enzyme. The above anti-beta antibody inhibits ATP synthesis without modifying the rate of ATP hydrolysis. This antibody also prevents the ADP-induced hysteretic inhibition of F1-ATPase.


Risk factors for African swine fever incursion in Romanian domestic farms during 2019.
African swine fever (ASF) entered Georgia in 2007 and the EU in 2014. In the EU, the virus primarily spread in wild boar (Sus scrofa) in the period from 2014-2018. However, from the summer 2018, numerous domestic pig farms in Romania were affected by ASF. In contrast to the existing knowledge on ASF transmission routes, the understanding of risk factors and the importance of different transmission routes is still limited. In the period from May to September 2019, 655 Romanian pig farms were included in a matched case-control study investigating possible risk factors for ASF incursion in commercial and backyard pig farms. The results showed that close proximity to outbreaks in domestic farms was a risk factor in commercial as well as backyard farms. Furthermore, in backyard farms, herd size, wild boar abundance around the farm, number of domestic outbreaks within 2 km around farms, short distance to wild boar cases and visits of professionals working on farms were statistically significant risk factors. Additionally, growing crops around the farm, which could potentially attract wild boar, and feeding forage from ASF affected areas to the pigs were risk factors for ASF incursion in backyard farms.


Effects of epichlorohydrin on male and female reproduction in Long-Evans rats.
Male and female Long-Evans rats were treated with epichlorohydrin (ECH) by oral gavage (males: 12.5, 25, and 50 mg/kg/day; females: 25, 50, and 100 mg/kg/day) for 21 and 14 days, respectively, prior to mating trials with untreated animals. Treated females were further dosed until delivery. Fertility was assayed in the high-dose males only and was found to be totally impaired. No measured parameters of female reproduction were changed relative to controls. Treated males showed normal copulatory behavior. Sperm morphology and percentage motile sperm were not statistically different from control values in both ejaculated and cauda epididymal samples from ECH-treated animals. The number of sperm in ejaculates was normal while cauda epididymal sperm count was slightly decreased in males at the 50 mg ECH/kg dose level. Mean curvilinear velocity, straight-line velocity, and amplitude of lateral head displacement of cauda epididymal sperm were significantly reduced by ECH at 12.5 mg/kg/day and above. Sperm track linearity was also reduced, but only at 50 mg/kg/day. Beat/cross frequency of sperm was significantly increased at 12.5 mg/kg/day and above. All of the above sperm motion parameters showed dose-dependent trends. These effects are consistent with the spermatozoal metabolic lesions reported for alpha-chlorohydrin, a metabolite of ECH.


Daidzein causes cytochrome c-mediated apoptosis via the Bcl-2 family in human hepatic cancer cells.
Daidzein, which belongs to the group of isoflavones from soybeans, has been extensively researched prostate, cervix, brain, breast, and colon cancer cell lines. However, daidzein has not been thoroughly investigated in human hepatic cancer cells; therefore, we investigated whether it inhibits hepatic cancer cell growth. Decreased cell proliferation was measured in daidzein-treated hepatic cancer cells (SK-HEP-1) upon real-time cell electronic sensing analysis however, it was not affected on normal human hepatocytes (Chang). Daidzein-induced apoptosis was demonstrated by comet and TUNEL assay. Moreover, we conducted two-dimensional electrophoresis to study the mechanism of daidzein-induced apoptosis in daidzein-treated SK-HEP-1 cells. Expression of peroxiredoxin-3 (Prdx-3), which modulates redox homeostasis of cells, was increased in protein analysis. Additionally, we measured the levels of reactive oxygen species and it was decreased in daidzein-treated SKHEP-1 cells. Daidzein-induced apoptosis in SK-HEP-1 cells was also associated with the up-regulation of Bak and down-regulation of Bcl-2 and Bcl-xL proteins. Moreover, daidzein treatment increased in the release of mitochondrial cytochrome c and activation of APAF-1, caspase 9 and caspase 3. Overall, these result indicate that daidzein is a potent inducer of apoptosis in hepatic cancer cells via mitochondrial pathway.


Activity regulation of a Hox protein and a role for the homeodomain in inhibiting transcriptional activation.
Hox proteins are transcription factors that assign positional identities along the body axis of animal embryos. Different Hox proteins have similar DNA-binding functions in vitro and require cofactors to achieve their biological functions. Cofactors can function by enhancement of the DNA-binding specificity of Hox proteins, as has been shown for Extradenticle (Exd). We present results supporting a novel mechanism for Hox cofactor function: regulation of transcriptional activation function. First, we provide evidence that the Hox protein Deformed (Dfd) can interact with simple DNA-binding sites in Drosophila embryos in the absence of Exd, but this binding is not sufficient for transcriptional activation of reporter genes. Secondly, either Dfd or a Dfd-VP16 hybrid mediate much stronger activation in embryos on a Dfd-Exd composite site than on a simple Dfd-binding site, even though the two sites possess similar Dfd-binding affinities. This suggests that Exd is required to release the transcriptional activation function of Dfd independently of Exd enhancement of Dfd-binding affinity on the composite site. Thirdly, transfection assays confirmed that Dfd possesses an activation domain, which is suppressed in a manner dependent on the presence of the homeodomain. The regulation of Hox transcriptional activation functions may underlie the different functional specificities of proteins belonging to this developmental patterning family.


Factors influencing pregnancy rates in intrauterine insemination cycles.
To identify the predictors of pregnancy rate (PR) among women undergoing intrauterine insemination (IUI) cycles. Two hundred thirty-two women undergoing 255 IUI cycles were retrospectively evaluated according to clinical and semen characteristics in terms of PRs. The overall PR was 9.4%. The PR was 7.9% in the primary infertility group, whereas the rate was 21.4% in the secondary infertility group (p < 0.05). The pregnancy rate was 3.1% for 1 preovulatory follicle, 9.3% for 2 follicles, 16.9% for 3 and 23.1% for 4 (p < 0.05). The PR increased in accordance with the total motile sperm count before sperm preparation (p > 0.05); however, the PR was significantly higher in sperm morphology of >4% (according to Kruger criteria) than in the < or = 4% group (6.7% vs. 22.2%, respectively; p = 0.003). Using binary logistic regression analysis, the number of preovulatory follicles and the percentage of normal sperm morphology in processed sperm had the maximum power to predict the PR following IUI. Other than clinical and laboratory characteristics, only the number of preovulatory follicles and the percentage of normal sperm morphology in processed sperm can be used in the prediction of a favorable IUI outcome.


Response mechanism of Chlamydomonas reinhardtii to nanoscale bismuth oxyiodide (nano-BiOI): Integrating analysis of mineral nutrient metabolism and metabolomics.
Nanoscale bismuth oxyiodide (nano-BiOI) is widely studied and applied in environmental applications and biomedical fields, with the consequence that it may be deposited into aquatic environments. However, the impact of nano-BiOI on aquatic ecosystems, especially freshwater microalga, remains limited. Herein, the nano-BiOI was synthesized and its response mechanism towards microalga Chlamydomonas reinhardtii was evaluated. Results showed that a low concentration of nano-BiOI (5 mg/L) could stimulate algal growth at the early stage of stress. With the increase in concentration, the growth rate of algal cells was inhibited and showed a dose effect. Intracellular reactive oxygen species (ROS) were significantly induced and accompanied by enhanced lipid peroxidation, decreased nonspecific esterase activity, and significantly upregulated glutathione S-transferase activity (GST) activity. Mineral nutrient metabolism analysis showed that nano-BiOI significantly interfered with the mineral nutrients of the algae. Non-targeted metabolomics identified 35 different metabolites (DEMs, 22 upregulated, and 13 downregulated) under 100 mg/L BiOI stress. Metabolic pathway analysis demonstrated that a high concentration of nano-BiOI significantly induced metabolic pathways related to amino acid biosynthesis, lipid biosynthesis, and glutathione biosynthesis, and significantly inhibited the sterol biosynthesis pathway. This finding will contribute to understanding the toxicological mechanisms of nano-BiOI on C. reinhardtii.


A quantitative headspace-solid-phase microextraction-gas chromatography-flame ionization detector method to analyze short chain free fatty acids in rat feces.
This study sought to develop and validate a quantitative method to analyze short chain free fatty acids (SCFAs) in rat feces by solid-phase microextraction and gas chromatography (SPME-GC) using the salt mixture ammonium sulfate and sodium dihydrogen phosphate as salting out agent. Conditioning and extraction time, linearity, limits of detection and quantification, repeatability, and recovery were evaluated. The proposed method allows quantification with improved sensitivity as compared with other methods exploiting SPME-GC. The method has been applied to analyze rat fecal samples, quantifying acetic, propionic, isobutyric, butyric, isopentanoic, pentanoic, and hexanoic acids.


microRNA-221 Inhibits Latent TGF-β1 Activation through Targeting Thrombospondin-1 to Attenuate Kidney Failure-Induced Cardiac Fibrosis.
Kidney failure (KF) is associated with cardiac fibrosis and significantly increased mortality in heart failure. Thrombospondin-1 (TSP1), a key regulator of latent transforming growth factor-β1 (L-TGF-β1) activation, is a predicted target of miR-221. We hypothesized miR-221 attenuates severe KF-associated cardiac fibrosis via targeting of Thbs1 with subsequent inhibition of L-TGF-β1 activation. Rat cardiac fibroblasts (cFB) were isolated and transfected with microRNA-221 (miR-221) mimics or mimic control (miR-221 and MC) with or without exposure to L-TGF-β1. We demonstrate miR-221 downregulates Thbs1 via direct 3' untranslated region (3' UTR) targeting with consequent inhibition of L-TGF-β1 activation in cFB as proven by the significant reduction of myofibroblast activation, collagen secretion, TGF-β1 signaling, TSP1 secretion, and TGF-β1 bioactivity measured by Pai1 promoter reporter. The 5/6 nephrectomy (Nx) model of cardiac fibrosis was used to test the in vivo therapeutic efficacy of miR-221 (i.v. 1 mg/kg ×3). miR-221 significantly inhibited Nx-induced upregulation of TSP1 and p-SMAD3 in the heart at day-7 and reduced cardiac fibrosis (picro-sirius), improved cardiac function (±dP/dt), and improved 8-week survival rate (60% versus 36%; p = 0.038). miR-221 mimic treatment improved survival and reduced cardiac fibrosis in a model of severe KF. miR-221 is a therapeutic target to address cardiac fibrosis originating from renal disease and other causes.


Antineoplastic activity of azacarbazoles. III. Synthesis and antitumor evaluation of selected 2-, 3- aza- and diazaanalogues of carbazole.
Preliminary screening of the antitumor properties of selected azacarbazoles revealed that of all the compounds tested only 2,7-diazacarbazole (compound IX) and 3,6-diazacarbazole (compound XI) caused the inhibition of Sarcoma 180 growth up to 70%. beta- and gamma-Carbolines and their derivatives in presented testing system were inactive. None of the tested compounds displayed marked activity against murine leukemias and was active in the cytotoxicity test of KB cells.


Establishing a multidisciplinary taskforce to improve anticoagulation safety at a large health system.
To describe the development of a multidisciplinary anticoagulant safety taskforce (ASTF) to address anticoagulation-related issues across the medication-use system. Oral and parenteral anticoagulants have been classified as high-alert medications because of their potential for harm. Errors at the point of prescribing, monitoring, and administering therapy have been noted in safety literature. Our hospital system, which includes 1 academic medical center, 6 community hospitals, and 1 long-term care facility, designed a multidisciplinary ASTF to address anticoagulation-related issues. The ASTF used the 2017 Institute for Safe Medication Practices (ISMP) Medication Safety Self-Assessment for Antithrombotic Therapy as the primary tool for reviewing current practices, performing gap analyses, and identifying our greatest areas of opportunity. The top 8 best practice elements related to anticoagulant use were identified for initial efforts of ASTF activity. Meetings were led by a medication safety pharmacist who reviewed process opportunities and actions to address gaps. The hospital chief quality and patient safety officer and the vice president of quality were the executive sponsors of the ASTF. Key stakeholders such as the medication safety committee chair and the president of the medical staff were instrumental in leading the initiative. Recommendations from the ASTF were reviewed and approved by the system medication safety committee and the system pharmacy and therapeutics committee to support system-wide implementation. The ASTF accomplished more than initially planned within its first year. Error mitigation occurred through policy revisions, order set development and modification, and implementation of practice changes to comply with each best practice. The ISMP antithrombotic self-assessment score improved from 67% to 87%, surpassing the initially targeted score of 75%. To overcome implementation barriers with the electronic health record, we enlisted support from our informatics leadership to leverage information technology. Overall, the success of the taskforce was attributed to the teamwork and leadership of key individuals within the organization. Leveraging interest from key stakeholders across multiple disciplines with an established assessment tool was key in developing a productive and successful ASTF. The group came together to evaluate anticoagulant-related issues and implement sustainable changes to decrease anticoagulation error potential.


[Nonspecific indices of cellular and humoral immunity in viral hepatitis A and B patients].
The article deals with the comparative study of the state of phagocytosis, as manifested by the ingestion of bacterial cells and by the results of the specific lupus erythematosus test, in 65 patients with acute viral hepatitis A and 45 patients with acute viral hepatitis B; these patients were also compared with respect to the presence of the markers of antigenemia and the state of their nonspecific immunity, determined by the level of serum immunoglobulins.


Balance control and adaptation during vibratory perturbations in middle-aged and elderly humans.
The objective was to investigate if healthy elderly people respond and adapt differently to postural disturbances compared to middle-aged people. Thirty middle-aged (mean age 37.8 years, range 24-56 years) and forty healthy elderly subjects (mean age 74.6 years, range 66-88 years) were tested with posturography. Body sway was evoked by applying pseudorandom vibratory stimulation to the belly of the gastrocnemius muscles of both legs simultaneously. The tests were performed both with eyes open and eyes closed. The anteroposterior body sway was measured with a force platform and analyzed with a method that considers the adaptive changes of posture and stimulation responses. The results showed that middle-aged people generally used a different postural control strategy as compared to the elderly. The elderly responded more rapidly to vibratory perturbation, used more high-frequency (>0.1 Hz) motions and the motion dynamics had a higher degree of complexity. Moreover, the elderly had diminished ability to use visual information to improve balance control. Altogether, despite having an effective postural control adaptation similar to that of middle-aged people, the elderly had more difficulty in withstanding balance perturbations. These findings suggest that the balance control deterioration associated with aging cannot be fully compensated for by postural control adaptation.


Fluorescent probes to evaluate the physiological state and activity of microbial biocatalysts: a guide for prokaryotic and eukaryotic investigation.
Many fluorescent techniques are employed to evaluate the viability and activity of microbial cells used in biotechnology. These techniques are sometimes complex and the interpretation of results opened to misunderstanding. Moreover, new developments are constantly proposed especially concerning a more accurate evaluation of the state of the cells including eukaryotic microorganisms. This paper aims at presenting to biotechnologists unfamiliar with fluorescence the principles of these methods and the related possible pitfalls. It focuses on probes of the physical (integrity and fluidity) and energetical (intracellular pH and membrane potential) state of the cell membrane (bacterial and yeast cells) and presents also other probes (nucleic acids, respiration...) and new technical trends. The specificities of Gram-negative bacterial cells are also discussed.