Use of new media by Turkish fans in sport communication: facebook and twitter.
This research examines the use of Facebook and Twitter, two social networks, for sportive reasons in Turkey. To this end, the literature was surveyed and a 5 Likert type data collection tool consisting of 21 questions was developed by the researcher based on the expert views. The sample of the research included 460 sport fans who are college students at Abant İzzet Baysal University and Sakarya University. It was found in the research that 91.7% of the participants had a profile on Facebook and 13.3% had a profile on Twitter. The rate of opening an account on Twitter, which still has no version in Turkish language, was low. It was found that the fans mostly followed the official site of their favorite team on Facebook, got informed about the sports activities through Facebook and learned news, which they did not hear from other sources. It was also ascertained that male fans used social networks for sportive reasons more than female fans did (p<.05). It is possible to state that social networks such as Facebook and Twitter have become a rapidly-developing alternative medium in sports against traditional media such as newspaper and television.


Galectin-3 regulates intracellular trafficking of EGFR through Alix and promotes keratinocyte migration.
The EGFR-mediated signaling pathways are important in a variety of cellular processes, including cell migration and wound re-epithelialization. Intracellular trafficking of EGFR is critical for maintaining EGFR surface expression. Galectin-3, a member of an animal lectin family, has been implicated in a number of physiological and pathological processes. Through studies of galectin-3-deficient mice and cells isolated from these mice, we demonstrated that the absence of galectin-3 impairs keratinocyte migration and skin wound re-epithelialization. We have linked this pro-migratory function to a crucial role of cytosolic galectin-3 in controlling intracellular trafficking and cell surface expression of EGFR after EGF stimulation. Without galectin-3, the surface levels of EGFR are markedly reduced, and the receptor accumulates diffusely in the cytoplasm. This is associated with reduced rates of both endocytosis and recycling of the receptor. We have provided evidence that this previously unreported function of galectin-3 may be mediated through interaction with its binding partner Alix, which is a protein component of the ESCRT (endosomal sorting complex required for transport) machinery. Our results suggest that galectin-3 is potentially a critical regulator of a number of important cellular responses through its intracellular control of trafficking of cell surface receptors.


Lactacystin-Induced Model of Hypertension in Rats: Effects of Melatonin and Captopril.
Lactacystin is a proteasome inhibitor that interferes with several factors involved in heart remodelling. The aim of this study was to investigate whether the chronic administration of lactacystin induces hypertension and heart remodelling and whether these changes can be modified by captopril or melatonin. In addition, the lactacystin-model was compared with NG-nitro-l-arginine-methyl ester (L-NAME)- and continuous light-induced hypertension. Six groups of three-month-old male Wistar rats (11 per group) were treated for six weeks as follows: control (vehicle), L-NAME (40 mg/kg/day), continuous light (24 h/day), lactacystin (5 mg/kg/day) alone, and lactacystin with captopril (100 mg/kg/day), or melatonin (10 mg/kg/day). Lactacystin treatment increased systolic blood pressure (SBP) and induced fibrosis of the left ventricle (LV), as observed in L-NAME-hypertension and continuous light-hypertension. LV weight and the cross-sectional area of the aorta were increased only in L-NAME-induced hypertension. The level of oxidative load was preserved or reduced in all three models of hypertension. Nitric oxide synthase (NOS) activity in the LV and kidney was unchanged in the lactacystin group. Nuclear factor-kappa B (NF-κB) protein expression in the LV was increased in all treated groups in the cytoplasm, however, in neither group in the nucleus. Although melatonin had no effect on SBP, only this indolamine (but not captopril) reduced the concentration of insoluble and total collagen in the LV and stimulated the NO-pathway in the lactacystin group. We conclude that chronic administration of lactacystin represents a novel model of hypertension with collagenous rebuilding of the LV, convenient for testing antihypertensive drugs or agents exerting a cardiovascular benefit beyond blood pressure reduction.


Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia.
The powerful 'graft versus leukemia' effect thought partly responsible for the therapeutic effect of allogeneic hematopoietic cell transplantation in acute myeloid leukemia (AML) provides rationale for investigation of immune-based therapies in this high-risk blood cancer. There is considerable preclinical evidence for potential synergy between PD-1 immune checkpoint blockade and the hypomethylating agents already commonly used for this disease. We report here the results of 17 H-0026 (PD-AML, NCT02996474), an investigator sponsored, single-institution, single-arm open-label 10-subject pilot study to test the feasibility of the first-in-human combination of pembrolizumab and decitabine in adult patients with refractory or relapsed AML (R-AML). In this cohort of previously treated patients, this novel combination of anti-PD-1 and hypomethylating therapy was feasible and associated with a best response of stable disease or better in 6 of 10 patients. Considerable immunological changes were identified using T cell receptor β sequencing as well as single-cell immunophenotypic and RNA expression analyses on sorted CD3+ T cells in patients who developed immune-related adverse events (irAEs) during treatment. Clonal T cell expansions occurred at irAE onset; single-cell sequencing demonstrated that these expanded clones were predominately CD8+ effector memory T cells with high cell surface PD-1 expression and transcriptional profiles indicative of activation and cytotoxicity. In contrast, no such distinctive immune changes were detectable in those experiencing a measurable antileukemic response during treatment. Addition of pembrolizumab to 10-day decitabine therapy was clinically feasible in patients with R-AML, with immunological changes from PD-1 blockade observed in patients experiencing irAEs.


A comparison of free-stall barns used by modernized Wisconsin dairies.
A primary objective of the Wisconsin Dairy Modernization Survey was to compare features of free-stall barns available to dairy producers. This study used data from a large random sample of expanding dairy farms to determine whether the theoretical benefits of particular free-stall configurations bear out under on-farm conditions. Comparisons were made among herds using free-stall barns as their primary housing for new versus remodeled facilities, barn design, bedding used, feed-delivery design, manure removal strategies, animal restraint, maternity areas, overcrowding, and cooling methods. Producers who made the transition from tie-stall housing to free-stall housing were satisfied with this decision. New free-stall barns provided a more desirable environment for the herds than remodeled free-stall barns, although initial investments were higher. When new free-stall barns were compared, herds with four-row barns had higher production, lower somatic cell count, and higher stocking rates than herds with six-row barns. Respondents were more satisfied with four- and six-row barns than with two- and three-row barns. Respondents felt sand provided some advantages for cow comfort, while satisfaction with bedding cost and manure handling was higher with mattresses. Dairy Herd Improvement data showed no difference in milk production or somatic cell count for producers who chose sand or mattress-based free stalls. Respondents were more satisfied with the use of drive-through feeding than other feed-delivery designs. Most producers chose to use tractor scrapers to remove manure; however, producers who used automated systems were more satisfied with manure management. Few differences were observed when comparing self-locking head gates to palpation rails. Overcrowding did not have any adverse affect on production or user satisfaction with feed intake or cow comfort. Using supplemental cooling appeared to facilitate higher production.


Applications of DNA tiling arrays to experimental genome annotation and regulatory pathway discovery.
Microarrays have become a popular and important technology for surveying global patterns in gene expression and regulation. A number of innovative experiments have extended microarray applications beyond the measurement of mRNA expression levels, in order to uncover aspects of large-scale chromosome function and dynamics. This has been made possible due to the recent development of tiling arrays, where all non-repetitive DNA comprising a chromosome or locus is represented at various sequence resolutions. Since tiling arrays are designed to contain the entire DNA sequence without prior consultation of existing gene annotation, they enable the discovery of novel transcribed sequences and regulatory elements through the unbiased interrogation of genomic loci. The implementation of such methods for the global analysis of large eukaryotic genomes presents significant technical challenges. Nonetheless, tiling arrays are expected to become instrumental for the genome-wide identification and characterization of functional elements. Combined with computational methods to relate these data and map the complex interactions of transcriptional regulators, tiling array experiments can provide insight toward a more comprehensive understanding of fundamental molecular and cellular processes.


Oceanirhabdus sediminicola gen. nov., sp. nov., an anaerobic bacterium isolated from sea sediment.
A novel anaerobic bacterium, designated NH-JN4(T) was isolated from a sediment sample collected in the South China Sea. Cells were Gram-stain-positive, spore-forming, peritrichous and rod-shaped (0.5-1.2×2.2-7 µm). The temperature and pH ranges for growth were 22-42 °C and pH 6.0-8.5. Optimal growth occurred at 34-38 °C and pH 6.5-7.0. The NaCl concentration range for growth was 0.5-6 % (w/v) with an optimum of 2.5 %. Catalase and oxidase were not produced. Substrates which could be utilized were peptone, tryptone, yeast extract, beef extract and glycine. Main fermentation products from PYG medium were formate, acetate, butyrate and ethanol. Strain NH-JN4(T) could utilize sodium sulfite as an electron acceptor. No respiratory quinone was detected. The predominant fatty acids were anteiso-C15 : 0, C16 : 0, iso-C15 : 0, anteiso-C17 : 0 and C16 : 0 DMA. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipids. The DNA G+C content was 35.8 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain NH-JN4(T) was a member of family Clostridiaceae, and was most closely related to Clostridium limosum ATCC 25620(T), Clostridium proteolyticum DSM 3090(T), Clostridium histolyticum ATCC 19401(T) and Clostridium tepidiprofundi SG 508(T), showing 94.0, 93.0, 92.9 and 92.3 % sequence similarity, respectively. On the basis of phenotypic, genotypic and chemotaxonomic properties, strain NH-JN4(T) represents a novel species of a new genus in the family Clostridiaceae, for which the name Oceanirhabdus sediminicola gen. nov., sp. nov. is proposed. The type strain of the type species is NH-JN4(T) ( = JCM 18501(T) = CCTCC AB 2013103(T) = KCTC 15322(T)).


Effective Actions of Ion Release from Mesoporous Bioactive Glass and Macrophage Mediators on the Differentiation of Osteoprogenitor and Endothelial Progenitor Cells.
Due to their specific mesoporous structure and large surface area, mesoporous bioactive glasses (MBGs) possess both drug-delivery ability and effective ionic release to promote bone regeneration by stimulating osteogenesis and angiogenesis. Macrophages secrete mediators that can affect both processes, depending on their phenotype. In this work, the action of ion release from MBG-75S, with a molar composition of 75SiO2-20CaO-5P2O5, on osteogenesis and angiogenesis and the modulatory role of macrophages have been assessed in vitro with MC3T3-E1 pre-osteoblasts and endothelial progenitor cells (EPCs) in monoculture and in coculture with RAW 264.7 macrophages. Ca2+, phosphorous, and silicon ions released from MBG-75S were measured in the culture medium during both differentiation processes. Alkaline phosphatase activity and matrix mineralization were quantified as the key markers of osteogenic differentiation in MC3T3-E1 cells. The expression of CD31, CD34, VEGFR2, eNOS, and vWF was evaluated to characterize the EPC differentiation into mature endothelial cells. Other cellular parameters analyzed included the cell size and complexity, intracellular calcium, and intracellular content of the reactive oxygen species. The results obtained indicate that the ions released by MBG-75S promote osteogenesis and angiogenesis in vitro, evidencing a macrophage inhibitory role in these processes and demonstrating the high potential of MBG-75S for the preparation of implants for bone regeneration.


A novel Data and Model Centric artificial intelligence based approach in developing high-performance Named Entity Recognition for Bengali Language.
Named Entity Recognition (NER) plays a significant role in enhancing the performance of all types of domain specific applications in Natural Language Processing (NLP). According to the type of application, the goal of NER is to identify target entities based on the context of other existing entities in a sentence. Numerous architectures have demonstrated good performance for high-resource languages such as English and Chinese NER. However, currently existing NER models for Bengali could not achieve reliable accuracy due to morphological richness of Bengali and limited availability of resources. This work integrates both Data and Model Centric AI concepts to achieve a state-of-the-art performance. A unique dataset was created for this study demonstrating the impact of a good quality dataset on accuracy. We proposed a method for developing a high quality NER dataset for any language. We have used our dataset to evaluate the performance of various Deep Learning models. A hybrid model performed with the exact match F1 score of 87.50%, partial match F1 score of 92.31%, and micro F1 score of 98.32%. Our proposed model reduces the need for feature engineering and utilizes minimal resources.


Successful interventions for smoking cessation in pregnancy.
The purpose of this article is to evaluate research regarding beneficial approaches to smoking cessation interventions during pregnancy. Research about nicotine replacement, nurse-managed counseling sessions, hypnosis, and behavioral modifications are presented. One of the most useful types of program for smoking cessation in pregnancy (as measured by cotinine-validated abstinence) described in the literature thus far has been the nurse-managed smoking cessation program, which includes a 15-minute individualized counseling session combined with a telephone contact 7-10 days after the prenatal visit. More research is needed in this important area of nursing practice.


Tumor infiltrating lymphocytes and continuous infusion interleukin-2 after metastasectomy in 61 patients with melanoma, colorectal and renal carcinoma.
Adoptive immunotherapy with tumor infiltrating lymphocyte (TIL) reinfusion plus continuous interleukin-2 (IL-2) infusion could represent an innovative way of treating immunogenic tumors. This study therefore recruited melanoma, colorectal and renal carcinoma patients whose metastases had been surgically removed. The treatment was initially given to 22 patients with advanced disease and more recently to 39 disease-free (DF) patients after radical metastasectomy. The latter group was selected in view of a theoretically better lymphocyte/tumor cell ratio and with the aim to improve disease-free and overall survival (DFS-OS) in very high risk patients. The starting IL-2 dose was 12 MIU/day (West's schedule); doses were modulated on the bases of toxicity parameters. Even though patients received different total amounts of IL-2, all of them completed the treatment. The treatment was offered to 22 advanced-stage cancer patients (12 melanomas, 9 colorectal carcinomas, 1 kidney carcinoma). Few and short stabilizations were observed with a median survival of 12 months (range, 3-29). Subsequently, another 39 patients were treated in an adjuvant setting after radical metastasectomy (18 melanomas, 19 colorectal carcinomas, 2 kidney cancers). Eleven out of 17 DF melanoma patients (64.7%) are still free of disease after a median of 37+ months (range, 5+ - 69+). In the group of DF colorectal cancer patients eight (44.4%) are still DF after a median of 21+ months (range, 7+ - 67+ months). One of the two patients with kidney cancer is still DF after 28+ months. Two patients (1 melanoma and 1 colorectal cancer) had just been treated and were therefore not evaluable. Severe toxicity occurred in three cases but was rapidly resolved. There was a great diversity in IL-2 doses administered; comparison of the total IL-2 dose administered between the patients who are still DF and those who progressed revealed no difference between the two groups of colorectal cancer patients, whereas melanoma patients who progressed received an average IL-2 dose of 6.5 MIU/day versus 15.8 MIU/day in DF patients. No differences were observed in any of the groups between the number of TILs reinfused and clinical response. The study is still ongoing; it has been decided to focus on DF melanoma patients after radical metastasectomy, for whom the data seem to be encouraging. Further endpoints of the study are the role of IL-2 dosage in the adjuvant setting, and the possibility to make correlations between biological parameters and clinical results.


Incorrect DNA methylation of the DAZL promoter CpG island associates with defective human sperm.
Successful gametogenesis requires the establishment of an appropriate epigenetic state in developing germ cells. Nevertheless, an association between abnormal spermatogenesis and epigenetic disturbances in germline-specific genes remains to be demonstrated. In this study, the DNA methylation pattern of the promoter CpG island (CGI) of two germline regulator genes--DAZL and DAZ, was characterized by bisulphite genomic sequencing in quality-fractioned ejaculated sperm populations from normozoospermic (NZ) and oligoasthenoteratozoospermic (OAT) men. OAT patients display increased methylation defects in the DAZL promoter CGI when compared with NZ controls. Such differences are recorded when analyzing sperm fractions enriched either in normal or defective germ cells (P< 0.001 in both cases). Significant differences in DNA methylation profiles are also observable when comparing the qualitatively distinct germ cell fractions inside the NZ and OAT groups (P= 0.003 and P= 0.007, respectively). Contrastingly, the unmethylation pattern of the DAZ promoter CGI remains correctly established in all experimental groups. An association between disrupted DNA methylation of a key spermatogenesis gene and abnormal human sperm is described here for the first time. These results suggest that incorrect epigenetic marks in germline genes may be correlated with male gametogenic defects.


Haploinsufficiency of ZNF238 is associated with corpus callosum abnormalities in 1q44 deletions.
A variety of candidate genes have been proposed to cause corpus callosum abnormalities (CCAs) in patients with terminal chromosome 1q deletions. Recent data excluded AKT3 and implicated ZNF238 and/or CEP170 as genes causative of corpus callosum anomalies in patients with 1q43-1q44 deletions. We report on a girl with dysmorphic features, seizures beginning in infancy, hypotonia, marked developmental delay, and dysgenesis of the corpus callosum. Chromosomal microarray analysis detected a de novo 1.47 Mb deletion at 1q44. The deleted interval encompasses the ZNF238 gene but not the CEP170 or AKT3 genes, thus providing additional evidence for the former and against the latter as being causative of corpus callosum anomalies in patients with such deletions.


Regulatory RNAs and the HptB/RetS signalling pathways fine-tune Pseudomonas aeruginosa pathogenesis.
Bacterial pathogenesis often depends on regulatory networks, two-component systems and small RNAs (sRNAs). In Pseudomonas aeruginosa, the RetS sensor pathway downregulates expression of two sRNAs, rsmY and rsmZ. Consequently, biofilm and the Type Six Secretion System (T6SS) are repressed, whereas the Type III Secretion System (T3SS) is activated. We show that the HptB signalling pathway controls biofilm and T3SS, and fine-tunes P. aeruginosa pathogenesis. We demonstrate that RetS and HptB intersect at the GacA response regulator, which directly controls sRNAs production. Importantly, RetS controls both sRNAs, whereas HptB exclusively regulates rsmY expression. We reveal that HptB signalling is a complex regulatory cascade. This cascade involves a response regulator, with an output domain belonging to the phosphatase 2C family, and likely an anti-anti-sigma factor. This reveals that the initial input in the Gac system comes from several signalling pathways, and the final output is adjusted by a differential control on rsmY and rsmZ. This is exemplified by the RetS-dependent but HptB-independent control on T6SS. We also demonstrate a redundant action of the two sRNAs on T3SS gene expression, while the impact on pel gene expression is additive. These features underpin a novel mechanism in the fine-tuned regulation of gene expression.


Does adversity early in life affect general population suicide rates? A cross-national study.
Adversity early in life has been suggested as a protective factor for elderly suicides. However, studies examining this relationship in general population suicide rates are scarce. The relationship between general population suicide rates and four proxy measures of adversity earlier in life was examined using data from the World Health Organization and the United Nations data banks. General population suicide rates were negatively correlated with the percentage of children under the age of 5 years who were underweight, the percentage of children under the age of 5 years who were under height, the percentage of infants with low birth weight babies, and the percentage of the general population that was undernourished. The only independent predictor general population suicide rates in both sexes, on multiple regression analysis, was the Gini coefficient (a measure of income inequality). Income inequality may lead to low birth weight, undernourishment, underweight and under height because income inequality results in poor access to healthcare and nutrition. These adversities may increase child mortality rates and reduce life expectancy. Those surviving into adulthood in countries with greater adversity early in life may be at reduced risk of suicide because of selective survival of those at reduced risk of suicide due to constitutional or genetic factors and development of greater tolerance to hardship in adulthood.


[Research progress on breeding standard of medicinal animals and discussion on several key problems].
Medicinal animal breeding standards is regarded as the law to normalize relevant production that can guarantee the quality of traditional Chinese medicine of animal category. The article summarized the medicinal animal resources in our country and the present condition of medicinal animal breeding standards. It considered the current animal breeding standards system was in adequate, not only the quantity of breeding standards, the standard content and index were also uncomprehensive, which is not conducive to the scientific and orderly development and utilization of medicinal animal resources. The article pointed out that the development of the basic standards, environmental control, feed quality, raising management, inspection and quarantine should be included into the medicinal animal breeding standards, and the medicinal animal breeding standards content framework was introduced. Meanwhile, animal welfare, biological safety and file management should be concerned during the process of research. Hope the article has good reference value to medicinal animal breeding standards establishment and production management.


A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development.
MELK is a serine/threonine kinase involved in several cell processes, including the cell cycle, proliferation, apoptosis and mRNA processing. However, its function remains elusive. Here, we explored its role in the Xenopus early embryo and show by knockdown that xMELK (Xenopus MELK) is necessary for completion of cell division. Consistent with a role in cell division, endogenous xMELK accumulates at the equatorial cortex of anaphase blastomeres. Its relocalization is highly dynamic and correlates with a conformational rearrangement in xMELK. Overexpression of xMELK leads to failure of cytokinesis and impairs accumulation at the division furrow of activated RhoA - a pivotal regulator of cytokinesis. Furthermore, endogenous xMELK associates and colocalizes with the cytokinesis organizer anillin. Unexpectedly, our study reveals a transition in the mode of cytokinesis correlated to cell size and that implicates xMELK. Collectively, our findings disclose the importance of xMELK in cytokinesis during early development and show that the mechanism of cytokinesis changes during Xenopus early development.


Fatal cytomegalovirus bronchiolitis in a patient with Nezelof's syndrome.
A 4-year-old girl who had received a fetal thymus gland by intraperitoneal transplantation 41 months previously sustained acute, fatal bronchiolitis due to culture-proven cytomegalovirus despite the fact that a specific antibody response to this organism was detected. While the thymic transplantation had increased the number of circulating T lymphocytes and had permitted immune sensitization to delayed-hypersensitivity skin test antigens, there was still an incomplete state of T lymphocyte function. In particular, isolated lymphocytes failed to respond to stimulation with phytohemagglutinin at several concentrations and, more important, the pathologic examination demonstrated a severe anatomic deficiency of lymphoid tissue associated with T lymphocyte function. The unusual infection that caused the death of this child emphasized the necessity of acquiring sufficient T lymphocyte function in immunologic reconstitution attempts.


[Legal and medico-legal issues in adolescent medicine. A critical review of the present regulation and legislation].
During the last years the Italian Government has taken many different initiatives to protect the adolescents rights to benefit from physical, psychical and social well-being. In particular, various projects concerning the promotion and the support of the school, the family, sport, mass-media, judicial and medical infrastructures, have been organised, promoted and financed. However, it is not always possible to assure a real safeguarding of teenagers rights; this especially happens because the problem concerning the autonomous capacity of minors to consent (or non consent) to the medical treatment is much debated. However, many contradictions still persist about the effective duration of the pediatric age. All the same, it must be noted that the Legislator apparently realised that not only the physical, psychological and social maturity proceed by steps, but also the legal capacity.


Companion animals and the elderly: a state-of-the-art summary.
The human/animal relationship exhibited by the elderly and their pets has limitations as well as potentials. The functions of a pet as a companion and social facilitator in pet-facilitated psychotherapy include serving as a cotherapist for facilitation of rapport, providing companionship, substituting for close interpersonal relationships (ie, significant others), enhancing the health status of a variety of target groups, increasing opportunity for sensory stimulation, and providing emotional support and a sense of well-being. Available information was limited because few studies have been replicated, data were not validated, and previous studies were restricted mainly to institutionalized or therapeutic environments. Implications for future research include use of animals for companionship and to promote the physical, social, and emotional health of the elderly.


[Thrombosis of the hepatic artery and portal vein secondary to invasive aspergillosis following liver transplantation].
Thrombosis of the main hepatic vessels is a severe, frequent complication in patients requiring liver transplantation. It is usually a cause of emergency retransplantation. Two cases of hepatic vascular thrombosis secondary to disseminated aspergillosis are presented. Both patients demonstrated a septic state and required a second transplantation despite which they died within a few days. Necropsy showed disseminated aspergillosis with invasion of the portal venous system and the hepatic artery. The risk factors associated with this infection and the possible pathogenic mechanisms are discussed.


The multiple cantilever system: a solution for a failed precision attachment denture case.
Multiple-cantilevered pontic bridges can be a great alternative to dental implants and distal extension prostheses. Dental hygiene must be considered the most important factor in preserving the status quo of the permanent restoration. Traumatic occlusion, which can occur because of the widened periodontal space and greater mobility of a multiple-cantilever bridge, is not automatically a sign of failure. As long as the mobility of the fixed bridge does not increase and the patient can function and feel comfortable with it, a successful therapy can be concluded. If marginal periodontitis exists, destruction of the cervical ligaments, bone resorption, and apical migration of the epithelium will occur. Through loss of the supportive structures, hypermobility will increase. If the destructive factors of marginal periodontitis are not eliminated, the hypermobility can interfere with masticatory function. It is important that patients be made aware of this possibility. Regular recalls in the beginning of the maintenance program will emphasize the importance of the home-care system.


Acupuncture and moxibustion for primary osteoporosis: An overview of systematic review.
Primary osteoporosis (PO) is a common disease that was characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures and constitutes a pressing public health problem. But the effect of acupuncture or moxibustion treatment for PO is controversial.To provide a comprehensive systematic overview of current evidence from systematic reviews (SR)/Meta-analysis of acupuncture treatment for PO pertaining to risk of bias, quality of evidence and report quality.A total of 9 international and Chinese databases were searched for SR/meta-analysis of randomized controlled trials (RCTs). The risk of bias of SR/meta-analysis was appraised using the risk of bias in systematic reviews (ROBIS) instrument, the quality of the evidence was evaluated via Grading of Recommendations Assessment, Development and Evaluation (GRADE), and the report quality of the included studies are estimated by Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA).According to ROBIS, only 2 articles were with risk of low bias; according to PRISMA, and most articles were reported incomplete, mainly in Q2, Q7, Q24, and Q27; according to GRADE, a total of 28 outcome indicators were evaluated under 4 different interventions of experimental group and control group: the evidence quality of bone mineral density (BMD) from treatment of acupuncture and moxibustion/acupuncture and moxibustion plus was high or moderate; Visual Analogue Score (VAS) of acupuncture plus moxibustion or acupuncture plus moxibustion plus other was low or very low; clinical effectiveness of acupuncture plus moxibustion or acupuncture plus moxibustion plus other was uncertain.Acupuncture and moxibustion can improve the BMD of PO patients according to high-quality evidence, and may benefit VAS, pain score, clinical efficacy based on moderate or low-quality evidence. Further research that provides higher quality evidence of SR/RCTs of acupuncture and moxibustion treatment for PO is required.


Fuzzy vector quantization algorithms and their application in image compression.
This paper presents the development and evaluation of fuzzy vector quantization algorithms. These algorithms are designed to achieve the quality of vector quantizers provided by sophisticated but computationally demanding approaches, while capturing the advantages of the frequently used in practice k-means algorithm, such as speed, simplicity, and conceptual appeal. The uncertainty typically associated with clustering tasks is formulated in this approach by allowing the assignment of each training vector to multiple clusters in the early stages of the iterative codebook design process. A training vector assignment strategy is also proposed for the transition from the fuzzy mode, where each training vector can be assigned to multiple clusters, to the crisp mode, where each training vector can be assigned to only one cluster. Such a strategy reduces the dependence of the resulting codebook on the random initial codebook selection. The resulting algorithms are used in image compression based on vector quantization. This application provides the basis for evaluating the computational efficiency of the proposed algorithms and comparing the quality of the resulting codebook design with that provided by competing techniques.


B. infantis EVC001 Is Well-Tolerated and Improves Human Milk Oligosaccharide Utilization in Preterm Infants in the Neonatal Intensive Care Unit.
Not all infants carry specialized gut microbes, meaning they cannot digest human milk oligosaccharides and therefore do not receive complete benefits from human milk. B. infantis EVC001 is equipped to convert the full array of complex oligosaccharides into compounds usable by the infant, making it an ideal candidate to stabilize gut function and improve nutrition in preterm infants. A prospective, open-label study design was used to evaluate the tolerability of B. infantis EVC001 and its effects on the fecal microbiota in preterm infants in a Neonatal Intensive Care Unit. Thirty preterm infants <1,500 g and/or <33 weeks gestation at birth were divided into two matched groups, and control infants were enrolled and discharged prior to enrolling EVC001 infants to prevent cross-colonization of B. infantis: (1) fifteen control infants received no EVC001, and (2) fifteen infants received once-daily feedings of B. infantis EVC001 (8.0 x 109 CFU) in MCT oil. Clinical information regarding medications, growth, nutrition, gastrointestinal events, diagnoses, and procedures was collected throughout admission. Infant stool samples were collected at baseline, Study Days 14 and 28, and 34-, 36-, and 38-weeks of gestation. Taxonomic composition of the fecal microbiota, functional microbiota analysis, B. infantis, and human milk oligosaccharides (HMOs) in the stool were determined or quantified using 16S rRNA gene sequencing, metagenomic sequencing, qPCR, and mass spectrometry, respectively. No adverse events or tolerability issues related to EVC001 were reported. Control infants had no detectable levels of B. infantis. EVC001 infants achieved high levels of B. infantis (mean = 9.7 Log10 CFU/μg fecal DNA) by Study Day 14, correlating with less fecal HMOs (ρ = -0.83, P < 0.0001), indicating better HMO utilization in the gut. In this study, B. infantis EVC001 was shown to be safe, well-tolerated, and efficient in colonizing the preterm infant gut and able to increase the abundance of bifidobacteria capable of metabolizing HMOs, resulting in significantly improved utilization of human milk. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03939546, identifier: NCT03939546.


Identification of a bile acid response element in the cholesterol 7 alpha-hydroxylase gene CYP7A.
The transcriptional activity of the cholesterol 7 alpha-hydroxylase gene CYP7A is repressed by bile acids. Taurine conjugates of chenodeoxycholate and deoxycholate, but not cholate and ursodeoxycholate, inhibited the CYP7A promoter/luciferase reporter activity in transient transfection assays in Hep G2 cells. A region from nucleotide (nt) -74 to -55 was found to mediate bile acid response. However, deletion of this bile acid response element (BARE-I) enhanced reporter activity but did not eliminate the bile acid response. This is due to the presence of another BARE-II located in a conserved region between nt -149 and -128. Deletion or mutations of these sequences reduced promoter activity and abolished bile acid repression. This BARE-II shares an identical AGTTCAAG core sequence with BARE-I. Electrophoretic mobility shift assays of BARE-I and BARE-II probes using Hep G2 nuclear extract and the partially purified binding activity of nt -65/-54 DNA-affinity column revealed that the same or a similar nuclear protein might bind to both BAREs. BARE-II is the major BARE involved in the transcriptional repression of the CYP7A gene by hydrophobic bile acids.


Symptoms of Sternal Nonunion Late after Cardiac Surgery.
Background A cohort of patients having symptoms of sternal nonunion late after sternotomy was studied to find out whether the complaints were related to true sternal nonunion or decreased bone density. Methods A survey was mailed to 2,053 cardiac surgical patients operated in our institution between July 2007 and June 2010. The patients were requested about symptoms referring to sternal instability. A group of symptomatic individuals as well as 1:1 age- and time-matched asymptomatic controls were examined with sternal palpation, ultrasound during standardized sternal pressure provocation, and computed tomography (CT). Results The number of patients replied in the survey was 1,918 (93.4%); 2.3% (44 patients) reported sensation of movement or clicking in sternum during body movements and during coughing. Symptomatic patients living within 200 km to the hospital (21) and their asymptomatic controls (21) were selected for further clinical and imaging studies. Mean period between the initial operation and the examinations was 36 (22-56) months. Sternal palpation pain was significantly associated with reported symptoms suggestive of sternal nonunion (odds ratio [OR] 22.0; 95% confidence interval [CI] 2.5-195); however, none of the patients had clinically unstable sternum or nonunion in the sternal imaging. The symptoms of sternal instability were more frequent in patients whose bone mineralization rate (as measured with T-scores) was higher. Conclusion Symptoms suggestive of sternal nonunion were experienced by 2.3%. However, their symptoms did not correlate with CT scans or provocation ultrasound although palpation pain was evident. Thus the pain is derived from nonmechanical etiologies. Higher bone mineralization rate correlated with abnormal symptoms of sternal wound.


Epidemic Vulnerability Index for Effective Vaccine Distribution against Pandemic.
COVID-19 vaccine distribution route directly impacts the community's mortality and infection rate. Therefore, optimal vaccination dissemination would appreciably lower the death and infection rates. This paper proposes the Epidemic Vulnerability Index (EVI) that quantitatively evaluates the subject's potential risk. Our primary aim for the suggested index is to diminish both infection rate and death rate efficiently. EVI was accordingly designed with clinical factors determining the mortality and social factors incorporating the infection rate. Through statistical COVID-19 patient dataset analysis and social network analysis with an agent-based model that is analogous to a real-world system, we define and experimentally validate the capability of EVI. Our experiments consist of nine vaccination distribution scenarios, including existing indexes which estimate the risk and stochastically proliferate the contagion and vaccine in a 300,000 agent-based graph network. We compared the outcome and variation of the three metrics in the experiments: infection case, death case, and death rate. Through this assessment, vaccination by the descending order of EVI has shown to have a significant outcome with an average of 5.0% lower infection cases, 9.4% lower death cases, and 3.5% lower death rate than other vaccine distribution routes.


Comparison between 4.0-mm stainless steel and 4.75-mm titanium alloy single-rod spinal instrumentation for anterior thoracoscopic scoliosis surgery.
Retrospective review of a consecutive, single surgeon case series. To compare minimum 2-year postoperative outcomes between 4.0-mm stainless steel and 4.75-mm titanium alloy single-rod anterior thoracoscopic instrumentation for the treatment of thoracic idiopathic scoliosis. Advances in anterior thoracoscopic spinal instrumentation for scoliosis have attempted to mitigate the postoperative complications of rod failure, pseudarthrosis, and deformity progression. Biomechanical data suggest that the 4.75-mm titanium construct has a lower risk of fatigue failure compared to the 4.0-mm stainless steel construct. Sixty-four consecutive anterior thoracoscopic spinal instrumentation cases in patients with thoracic scoliosis performed by a single surgeon and with minimum 2-year follow-up were retrospectively reviewed. The first 34 cases used a 4.0-mm stainless steel (SS) construct, whereas the subsequent 30 cases used a 4.75-mm titanium (Ti) alloy instrumentation system. The first 10 SS cases and the first 5 Ti cases were excluded from the statistical comparison to account for a potential learning curve effect. A multivariate analysis of variance (P < 0.05) was used to compare radiographic, perioperative, and postoperative complication data between patients surgically treated with the 2 different instrumentation systems. Patients in the SS group (n = 24) underwent surgery from 2000 to 2001, whereas patients in the Ti group (n = 25) underwent surgery from 2002 to 2004. The mean age at surgery, gender ratio, length of hospitalization, estimated blood loss, and operative time were not statistically different between the 2 patient groups (P > 0.13). The average follow-up in the SS group was, however, significantly longer than in the Ti group (4.0 +/- 1.4 years vs. 2.3 +/- 1.0 years; P = 0.001). Preop main thoracic Cobb angles were similar between the 2 groups (P = 0.62); however, the 2-year main thoracic Cobb was significantly smaller (P = 0.03) and the 2-year percent correction was significantly greater in the Ti group (P = 0.03). Five patients (21%) in the SS group had a pseudarthrosis, 3 (13%) experienced rod failure, and 2 (8%) required a revision posterior spinal fusion. In the Ti group, 2 patients (8%) had a pseudarthrosis, and no patient experienced rod failure or required a revision procedure. Although the average follow-up in the Ti group was significantly shorter than in the SS group, the 4.75-mm titanium alloy construct resulted in improved maintenance of deformity correction at 2-years postop and a lower incidence of instrumentation-related complications (pseudarthrosis, rod breakage, and surgical revisions) compared to the 4.0-mm stainless steel construct. Improved outcomes with the titanium alloy construct are likely because of the mechanical properties of the implant, refined patient selection criteria, and greater surgical experience gained with time.


Perseveration in left spatial neglect: drawing and cancellation tasks.
Perseveration in target cancellation tasks and in drawing by copy and from memory was investigated in 21 right-brain-damaged patients, seven with no evidence of left visuo-spatial neglect, and 14 with neglect. Eight such neglect patients showed perseveration in both cancellation and drawing tasks, although no correlation was found with the severity of neglect. Patients with perseveration were not disproportionately impaired in tasks assessing executive (fluency, Stroop colour-word interference, and Weigl's sorting test), and visuo-spatial short-term memory function. In the context of a two-component hypothesis, graphic perseveration (the first component) is a specific disorder that manifests in a variety of tasks, particularly those requiring serial graphic production. Unilateral spatial neglect (the second component) may trigger and facilitate the production of perseveration errors, with a contra-ipsilateral gradient of increasing severity.


Effects of balloon angioplasty and stent implantation on intrarenal echo-Doppler velocimetric indices.
This study was aimed at examining whether four intrarenal echo-Doppler velocimetric indices (pulsatility and resistive indices, acceleration and acceleration time) can be useful for assessing the effects of renal artery dilation obtained with either angioplasty or stent implantation. Echo-Doppler studies were performed in 63 hypertensive patients with 68 renal artery stenoses (39 atherosclerotic and 29 fibromuscular) prior to and within five days after the dilation procedures (55 angioplasties, 13 stent implantations), which resulted in an average reduction of arterial narrowing from 79% to 20%. In 24 patients, the velocimetric indices were also examined in relationship to the venoarterial differences of plasma renin activity and of angiotensin II across the stenotic kidneys. We found that after dilation the values of the four indices had returned within the normal range in all but three arteries (one false negative for resistive index and two for acceleration time). However, decrements in acceleration time was the only factor to be significantly correlated with the reduction of arterial narrowing. Moreover, postdilation values of this index were, on average, slightly but significantly higher in arteries that at follow-up developed restenosis rather than in those that remained patent. For similar reductions in arterial narrowing the absolute changes of all indices were similar in atherosclerotic and fibromuscular stenotic arteries and, in a subset of the atheromatous arteries, were also similar after angioplasty and stent implantation. No relationship was found with the changes in the venoarterial differences of plasma renin activity and angiotensin II. It appears that these intrarenal velocimetric indices and, in particular, acceleration time reliably reflect the technical success of renal artery dilation. The acceleration time index may also be valuable for predicting the restenosis of the dilated vessel. None of the indices, however, mirrors the functional consequences of removal of renal artery stenosis as expressed through the changes in transrenal gradients of the components of the renin-angiotensin system.


Familism, family environment, and suicide attempts among Latina youth.
In this study, we examined the relationship between familism and family environment type as well as the relationship between family environment type and suicide attempts among Latina youth. Latina teen attempters (n = 109) and nonattempters (n = 107) were recruited from the New York City area. Latent class analysis revealed three family environment types: tight-knit, intermediate-knit, and loose-knit. Tight-knit families (high cohesion and low conflict) were significantly less likely to have teens who attempted suicide as compared with intermediate-knit families or loose-knit families. Moreover, familism increased the odds of being in a tight-knit family versus a loose-knit family and the odds of being in a tight-knit family versus a intermediate-knit. The results suggest that familism may protect against suicide behavior among Latinas via its influence on family environment.


The effect of reference microphone placement on sound pressure levels at an ear level hearing aid microphone.
The present study was designed to investigate the effects of reference microphone location on probe tube microphone measures of hearing aid response. The reference microphone of a clinical probe tube microphone system was located either at a position on the cheek (position A) or in close proximity to the microphone of an ear level hearing aid (position B). With sound pressure level (SPL) held constant at the reference microphone, the SPL at the position of the hearing aid microphone was measured at 14 test frequencies using a 1/8-inch condenser microphone. Measures were obtained on ten male and ten female subjects. Results indicated large frequency-dependent deviations in SPL at the hearing aid microphone, compared to that measured at the reference microphone, when the reference microphone was at position A. In the 1200 to 2000 Hz range, the SPL at the hearing aid microphone was as much as 9.5 dB higher than at the reference microphone. There were no large frequency-dependent variations with the reference microphone in position B, but the SPL at the hearing aid microphone location was approximately 3 dB higher than at the reference microphone. Results suggest that estimates of hearing aid output can be affected markedly by the reference microphone location. Clinical implications of the impact of reference microphone location on probe microphone measures of hearing aid gain and saturation sound pressure levels are discussed.


Gray-scale perceptions calculated: optimum display background luminance.
The following questions motivated this study, which summarizes and illustrates the answers. How can the number of gray levels visible on a display be maximized? How can a designer maximize the discriminability of a set of gray symbols that use only a part of the luminance range available from the display technology? Can we calculate whether particular shades of gray will be discriminable from each other? How big should successive gray-scale steps be (in luminance, reflectance, or optical density) to make them appear equal? How many discriminable shades of gray can be seen with a particular display technology in a particular light environment? What is the probability that two specified shades of gray will be mistaken for each other at a glance? How does the luminance of the screen background affect the visibility of gray symbols? Is there a single principle that describes the appearances of areas more luminous than the background (positive contrasts) and less luminous areas (negative contrasts)? Limitations on the answers are discussed, issues for further research are suggested, and applications are described.


Using Non-immersive VR Simulations in Conjunction with Priming to Enhance Conceptualizing Radiation and Risk.
Radiation is present daily and used throughout many industries for beneficial purposes. Safety professionals and workers need a general understanding of radiation identification techniques and associated risks to manage the work environment with radiation protection practices. This is especially important in workplaces where the radiation source is ancillary to the primary activities of the industry. The elusive nature of radiation makes learners understanding in an educational setting a challenge. Furthermore, delivering a hands-on experience to support learning and training of radiation, its assessment, and protection measures is quite difficult, given its hazardous nature. Virtual reality, even using non-immersive environments, offers significant benefits through simulating sources of radiation. A non-immersive simulator titled AssessRadVR, facilitated the radiation experience and presented dynamically the effects of the trainees' interactions with shielding materials, detection equipment, and the working environment. Yet, interaction with simulation alone may not trigger effective encoding of these critical aspects in long-term memory. This paper discusses using the AssessRadVR simulator in conjunction with a procedure for subliminally priming the long-term memory encoding to enhance radiation's activated representation. Students in an introductory industrial hygiene class were divided into two groups and primed with either alarming or non-alarming words following the Bargh, Chen, & Borrows procedure (1996). Results demonstrated that students primed with alarming words were more open to objectively evaluating the radiation sources due to their overall perception that the risk was manageable. Why is this of interest to the community: The results provided that even with limited prior knowledge in radiation, after engaging with the simulator, most students were able to recognize and apply radiation principles, which indicates they could apply key principles in a real-world radiation workplace. Further, the impact of activating with alarming words led to a statistically significantly higher perception that working in the radiation environment was manageable.


Arousal Effects on Pupil Size, Heart Rate, and Skin Conductance in an Emotional Face Task.
Arousal level changes constantly and it has a profound influence on performance during everyday activities. Fluctuations in arousal are regulated by the autonomic nervous system, which is mainly controlled by the balanced activity of the parasympathetic and sympathetic systems, commonly indexed by heart rate (HR) and galvanic skin response (GSR), respectively. Although a growing number of studies have used pupil size to indicate the level of arousal, research that directly examines the relationship between pupil size and HR or GSR is limited. The goal of this study was to understand how pupil size is modulated by autonomic arousal. Human participants fixated various emotional face stimuli, of which low-level visual properties were carefully controlled, while their pupil size, HR, GSR, and eye position were recorded simultaneously. We hypothesized that a positive correlation between pupil size and HR or GSR would be observed both before and after face presentation. Trial-by-trial positive correlations between pupil diameter and HR and GSR were found before face presentation, with larger pupil diameter observed on trials with higher HR or GSR. However, task-evoked pupil responses after face presentation only correlated with HR. Overall, these results demonstrated a trial-by-trial relationship between pupil size and HR or GSR, suggesting that pupil size can be used as an index for arousal level involuntarily regulated by the autonomic nervous system.


Oxidative DNA base modifications and polycyclic aromatic hydrocarbon DNA adducts in squamous cell carcinoma of larynx.
Tobacco smoke, recognized as a major etiological factor for cancers of the upper aerodigestive tract, represents an abundant source of reactive oxygen species (ROS), which are believed to play a significant role in mutagenesis and carcinogenesis. An additional source of ROS in tissues exposed to tobacco smoke may be metabolic oxidation of polycyclic aromatic hydrocarbons (PAH). To investigate the relationships between oxidative DNA lesions and aromatic DNA adducts, six modified DNA bases 5-hydroxyuracil, 5-hydroxycytosine, 7,8-dihydro-8-oxoguanine, 7,8-dihydro-8-oxoadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine and 4,6-diamino-5-formamidopyrimidine and the total level of PAH-related DNA adducts were measured in cancerous and the surrounding normal larynx tissues (68 subjects), using gas chromatography/isotope-dilution mass spectroscopy with selected ion monitoring and the 32P-postlabeling-HPLC assay, respectively. The levels of oxidative DNA lesions in cancerous and adjacent tissue were comparable; the differences between the two types of tissue were significant only for 5-hydroxypyrimidines (slightly higher levels were observed in the adjacent tissue). Comparable levels of DNA lesions in cancerous and the surrounding normal tissues observed in the larynx tumors support a field cancerization theory. The surrounding tissues may still be recognized as normal by histological criteria. However, molecular alterations resulting from the chronic tobacco smoke exposure, which equally affects larynx epithelia, may lead to multiple premalignant lesions. Thus, a demonstration of similar levels of DNA damage in cancerous and the adjacent tissue could explain a frequent formation of secondary tumors in the larynx and the frequent recurrence in this type of cancer. A weak, but distinct effect of tumor grading and metastatic status was observed in both kinds of tissue in the case of 5-hydroxyuracil, 5-hydroxycytosine, 7,8-dihydro-8-oxoguanine, 7,8-dihydro-8-oxoadenine. This effect was displayed as a gradual shift in the data distribution toward high values from G1 through G2-G3 and from non-metastatic to metastatic tumors. Since the levels of oxidative DNA base modifications tended to increase with the tumor aggressiveness, we postulate that the oxidative DNA lesions increase genetic instability and thus contribute to tumor progression in laryngeal cancer. No associations between aromatic adduct levels and oxidative DNA lesions were present, suggesting that the metabolism of PAH does not contribute significantly to the oxidative stress in larynx tissues, remaining the tobacco smoke ROS as a major source of oxidative DNA damage in the exposed tissue.


[Early diagnosis of alcohol abuse and alcohol dependence in general practice].
The doctor's office offers the best chance of an early diagnosis of alcohol-related disorders. The physician can make the most of his opportunity by always taking this possibility into account in patients with unspecific symptoms. Since so-called low-risk alcohol consumption may develop into damaging drinking and finally addictive drinking leading to dependence, the physician must be familiar with the features of these different drinking patterns to be able to intervene prophylactically in the early forms, and therapeutically in later stages. Diagnostic talks with the patient should always contain elements of motivational interviewing so as to enable the physician to react appropriately to the degree of readiness of the patient to make necessary changes in his lifestyle.


Intellectual Property Rights and Access in Crisis.
The importance of access to intellectual property rights (IPR) protected subject-matter in two crucial areas - public health, and educational and cultural engagement - has been extensively demonstrated during the COVID-19 pandemic. Although they involve separate legal areas, patent and copyright, the common thread linking the two is intellectual property's difficult relationship with access in the public interest. This paper examines the tensions caused by access barriers, the tools used to reduce them and their effectiveness. It is clear that the access barriers magnified by COVID-19 are not restricted to narrow or specific contexts but are widespread. They are created by, and are a feature of, our existing IPR frameworks. Open movements provide limited remedies because they are not designed to, nor can adequately address the wide range of access barriers necessary to promote the public interest. Existing legislative mechanisms designed to remove access barriers similarly fail to effectively remedy access needs. These existing options are premised on the assumption that there is a singular "public" motivated by homogenous "interests", which fails to reflect the plurality and cross-border reality of the public(s) interest(s) underpinning the welfare goals of IPR. We conclude that a systemic re-evaluation is required and call for positive and equitable legal measures protective of the public(s) interest(s) to be built within IPR frameworks that also address non-IPR barriers. The current pandemic and development of a "new normal" provides a crucial opportunity to comprehensively consider the public(s) interest(s), not just during a global health crisis, but on an ongoing basis.


Nutrition and lipidomic profile in colorectal cancers.
Adherence to a healthy diet has been reported to be essential for the primary prevention of colorectal cancer, through a reduction of tissue inflammation, a low concentration of circulating lipoproteins and lower levels of serum cholesterol. Since an altered expression of the fatty acids pattern has been demonstrated to be a crucial event in colorectal carcinogenesis, lipidomic analysis is considered able to identify early diagnostic and prognostic biomarkers of complex diseases such as colorectal cancer. cell membrane fatty acid profile and serum lipoproteins pattern were evaluated by gas chromatography and electrophoresis method respectively. There is a close association between diet and lipidomic profile in colorectal cancer, both in pre-clinical and clinical studies. A modified serum lipoproteins pattern has been demonstrated to be predominant in intestinal tumors. The study of fatty acids profile in cell membrane and the evaluation of serum lipoproteins subfractions could be useful to have an integrate vision on the interactions between lipids and the pathogenesis of colorectal cancer and to understand the mechanisms of action and the consequences of these interactions on human health status.


Tacrolimus-based triple-drug immunosuppression minimizes serum lipid elevations in pediatric cardiac transplant recipients.
Immunosuppression with corticosteroids and cyclosporine has been associated with hyperlipidemia, a risk factor for post-transplant coronary artery disease. The recent development of tacrolimus has created an alternative to cyclosporine-based triple drug immunotherapy. One potential benefit that has been reported in patients receiving tacrolimus is a minimization of elevation of both total and LDL cholesterol, compared to those increases observed in patients receiving cyclosporine-based immunosuppression. It is unclear in previous studies whether this beneficial effect is related to tacrolimus directly or to its corticosteroid sparing potential. To study this relationship, we compared lipid profiles from pediatric cardiac transplant recipients treated with corticosteroids, and either cyclosporine or tacrolimus. The study group consisted of 23 patients (mean age = 12.3 years) with pre-transplant and serial post-transplant determinations of total cholesterol, LDL, HDL, and triglycerides. Patients were separated into 4 study groups, defined by immunosuppressive regimen (cyclosporine vs. tacrolimus) and prednisone dose (>0.10 mg/kg/day vs. < or =0.10 mg/kg/day). Patients who received cyclosporine and higher doses of prednisone experienced a mean 74 mg/dl increase from baseline in total cholesterol (p = .0001). None of the other 3 treatment groups demonstrated a statistically significant elevation. Similar trends were observed in LDL and triglyceride alterations between the 4 study groups. Interestingly, patients treated with tacrolimus and higher doses of prednisone demonstrated a significant rise in HDL from baseline (p = .0001), although those who received cyclosporine and higher dose prednisone failed to exhibit this rise. The minimal degree of lipid alteration seen in patients receiving tacrolimus and higher doses of prednisone indicates that this effect was not solely based upon the steroid-sparing properties of tacrolimus therapy. The data also suggests a possible synergistic effect between cyclosporine and higher doses of prednisone on hyperlipidemia. Therefore, in pediatric patients requiring higher corticosteroid doses late after transplantation, use of tacrolimus rather than cyclosporine may lead to more favorable lipid profiles and help minimize the risk of post-transplant coronary arteriopathy.


Non-invasive hemoglobin concentration measurements with multi-wavelength reflectance mode PPG sensor and CNN data processing.
Possibility of non-invasive hemoglobin concentration measurements with wearable devices have been evaluated. The proposed solution is based on the assumption that PPG waveform shape measured at various wavelengths in the reflectance mode carries information about in-depth distribution of optical pathlength in the tissue. Decomposition of temporal and spectral features of PPG signal have been applied to correct estimation of hemoglobin concentration. The dataset including 840 PPG waveforms from 170 volunteers have been collected for the purpose of neural network training and validation. The achieved performance (MAE~13.6 g/l, R~0.62) is confirmed with the invasive blood test.Clinical Relevance - This paper establishes possibility of non-invasive real time hemoglobin concentration measurements by means of low-cost wearable sensor with accuracy comparable to non-invasive clinical instruments.


[Increase in access to SH-groups of membrane proteins in Ehrlich ascites carcinoma cells upon purinergic receptor activation].
The effect of ATP on SH-groups accessibility of the surface membrane proteins in Ehrlich ascites tumor cells has been studied using a fluorescent nonpenetrating reagent Thiolyte MQ. No accessible protein SH-groups in plasma membrane of unstimulated cells have been found. The accessibility of SH-groups in proteins with molecular masses 82 and 23 kDa was increased in 10 s after the ATP addition. The data are interpreted as a result of the conformational transition or vertical translocation of certain thiol-bearing membrane proteins at purinoreceptor activation. The effect may apparently be coupled to the changes in the membrane potential and calcium concentration in the cytoplasm occurring in the same time interval.


Cuproptosis-related lncRNA scoring system to predict the clinical outcome and immune landscape in pancreatic adenocarcinoma.
Cuproptosis is a recently discovered novel programmed cell death pathway that differs from traditional programmed cell death and has an important role in cancer and immune regulation. Long noncoding RNA (lncRNA) is considered new potential prognostic biomarkers in pancreatic adenocarcinoma (PAAD). However, the prognostic role and immune landscape of cuproptosis-related lncRNA in PAAD remain unclear. The transcriptome and clinical data of PAAD were obtained from The Cancer Genome Atlas (TCGA) database. Cuproptosis-related lncRNA was identified using Pearson correlation analysis. The optimal lncRNA was screened by Cox and the Least Absolute Shrinkage and Selection Operator (LASSO) regression mode, and for the construction of risk scoring system. PAAD patients were divided into high- and low-risk groups according to the risk score. Clinicopathological parameter correlation analysis, univariate and multivariate Cox regression, time-dependent receiver operating characteristic (ROC) curves, and nomogram were performed to evaluate the model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore differences in biological function between different risk groups. Single-sample gene set enrichment analysis (ssGSEA) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm were used to analyze the differences in tumor immune microenvironment (TIME) in different risk groups of PAAD. Additionally, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict immunotherapy response and identify potential immune beneficiaries. Immune checkpoints and tumor mutation burden (TMB) were also systematically analyzed. Finally, drug sensitivity analysis was used to explore the reactivity of different drugs in high- and low-risk groups to provide a reference for the selection of precise therapeutic drugs. Six cuproptosis-related lncRNAs (AL117335.1, AC044849.1, AL358944.1, ZNF236-DT, Z97832.2, and CASC8) were used to construct risk model. Survival analysis showed that overall survival and progression-free survival in the low-risk group were better than those in the high-risk group, and it is suitable for PAAD patients with different clinical characteristics. Univariate and multifactorial Cox regression analysis showed that risk score was an independent prognostic factor in PAAD patients. ROC analysis showed that the AUC values of the risk score in 1 year, 3 years and 5 years were 0.707,0.762 and 0.880, respectively. Nomogram showed that the total points of PAAD patients at 1 year, 3 years, and 5 years were 0.914,0.648, and 0.543. GO and KEGG analyses indicated that the differential genes in the high- and low-risk groups were associated with tumor proliferation and metastasis and immune regulatory pathway. Immune correlation analysis showed that the amount of pro-inflammatory cells, including CD8+ T cells, was significantly higher in the low-risk group than in the high-risk group, and the expression of immune checkpoint genes, including PD-1 and CTLA-4, was increased in the low-risk group. TIDE analysis suggests that patients in the low-risk group may benefit from immunotherapy. Finally, there was significant variability in multiple chemotherapeutic and targeted drugs across the risk groups, which informs our clinical drug selection. Our cuproptosis-related lncRNA scoring system (CRLss) could predict the clinical outcome and immune landscape of PAAD patients, identify the potential beneficiaries of immunotherapy, and provide a reference for precise therapeutic drug selection.


Editing the Sickle Cell Disease Mutation in Human Hematopoietic Stem Cells: Comparison of Endonucleases and Homologous Donor Templates.
Site-specific correction of a point mutation causing a monogenic disease in autologous hematopoietic stem and progenitor cells (HSPCs) can be used as a treatment of inherited disorders of the blood cells. Sickle cell disease (SCD) is an ideal model to investigate the potential use of gene editing to transvert a single point mutation at the β-globin locus (HBB). We compared the activity of zinc-finger nucleases (ZFNs) and CRISPR/Cas9 for editing, and homologous donor templates delivered as single-stranded oligodeoxynucleotides (ssODNs), adeno-associated virus serotype 6 (AAV6), integrase-deficient lentiviral vectors (IDLVs), and adenovirus 5/35 serotype (Ad5/35) to transvert the base pair responsible for SCD in HBB in primary human CD34+ HSPCs. We found that the ZFNs and Cas9 directed similar frequencies of nuclease activity. In vitro, AAV6 led to the highest frequencies of homology-directed repair (HDR), but levels of base pair transversions were significantly reduced when analyzing cells in vivo in immunodeficient mouse xenografts, with similar frequencies achieved with either AAV6 or ssODNs. AAV6 also caused significant impairment of colony-forming progenitors and human cell engraftment. Gene correction in engrafting hematopoietic stem cells may be limited by the capacity of the cells to mediate HDR, suggesting additional manipulations may be needed for high-efficiency gene correction in HSPCs.


Multi-omics analysis identifies IgG2b class-switching with ALCAM-CD6 co-stimulation in joint-draining lymph nodes during advanced inflammatory-erosive arthritis.
Defective lymphatic drainage and translocation of B-cells in inflamed (Bin) joint-draining lymph node sinuses are pathogenic phenomena in patients with severe rheumatoid arthritis (RA). However, the molecular mechanisms underlying this lymphatic dysfunction remain poorly understood. Herein, we utilized multi-omic spatial and single-cell transcriptomics to evaluate altered cellular composition (including lymphatic endothelial cells, macrophages, B-cells, and T-cells) in the joint-draining lymph node sinuses and their associated phenotypic changes and cell-cell interactions during RA development using the tumor necrosis factor transgenic (TNF-Tg) mouse model. Popliteal lymph nodes (PLNs) from wild-type (n=10) and TNF-Tg male mice with "Early" (5 to 6-months of age; n=6) and "Advanced" (>8-months of age; n=12) arthritis were harvested and processed for spatial transcriptomics. Single-cell RNA sequencing (scRNAseq) was performed in PLNs from the TNF-Tg cohorts (n=6 PLNs pooled/cohort). PLN histopathology and ELISPOT along with ankle histology and micro-CT were evaluated. Histopathology of human lymph nodes and synovia was performed for clinical correlation. Advanced PLN sinuses exhibited an increased Ighg2b/Ighm expression ratio (Early 0.5 ± 0.1 vs Advanced 1.4 ± 0.5 counts/counts; p<0.001) that significantly correlated with reduced talus bone volumes in the afferent ankle (R2 = 0.54, p<0.001). Integration of single-cell and spatial transcriptomics revealed the increased IgG2b+ plasma cells localized in MARCO+ peri-follicular medullary sinuses. A concomitant decreased Fth1 expression (Early 2.5 ± 0.74 vs Advanced 1.0 ± 0.50 counts, p<0.001) within Advanced PLN sinuses was associated with accumulation of iron-laden Prussian blue positive macrophages in lymph nodes and synovium of Advanced TNF-Tg mice, and further validated in RA clinical samples. T-cells were increased 8-fold in Advanced PLNs, and bioinformatic pathway assessment identified the interaction between ALCAM+ macrophages and CD6+ T-cells as a plausible co-stimulatory mechanism to promote IgG2b class-switching. Collectively, these data support a model of flare in chronic TNF-induced arthritis in which loss of lymphatic flow through affected joint-draining lymph nodes facilitates the interaction between effluxing macrophages and T-cells via ALCAM-CD6 co-stimulation, initiating IgG2b class-switching and plasma cell differentiation of the expanded Bin population. Future work is warranted to investigate immunoglobulin clonality and potential autoimmune consequences, as well as the efficacy of anti-CD6 therapy to prevent these pathogenic events.


Novel PCR-restriction fragment length polymorphism method for determining serotypes or serogroups of Streptococcus pneumoniae isolates.
Serotyping Streptococcus pneumoniae is a technique generally confined to reference laboratories, as purchasing pneumococcal antisera is a huge investment. Many attempts have been made to modify serological agglutination techniques to make them more accessible, and more recently developments in serotyping have focused on molecular techniques. This paper describes a PCR assay which amplifies the entire capsulation locus between dexB and aliA. Amplicons are digested to produce serotype-specific patterns. We have shown, using 81 epidemiologically unrelated strains representing 46 different serotypes, that the patterns correlate with a 90 to 100% similarity range for the same serotype or serogroup. Prospective testing of 73 isolates of unknown serotype confirmed reliable serotype attribution, and serotype profiles are reproducible on repeated testing. Once our database contains all 90 serotypes, this technique should be fully portable, cost-effective, and useful in any laboratory with sufficient molecular experience.


Genetic polymorphisms of genes involved in DNA repair and metabolism influence micronucleus frequencies in human peripheral blood lymphocytes.
The cytokinesis-block micronucleus cytome (CBMNCyt) assay is a widely used technique for measuring DNA damage in human populations. The formation of micronuclei (MN) in dividing cells can result from chromosome breakage due to unrepaired or mis-repaired DNA lesions or chromosome malsegregation due to mitotic malfunction. The sensitivity of the MN assay to polymorphisms in various genes involved in DNA repair, activation/deactivation of carcinogens/chemicals/drugs/alcohol, folate metabolism pathway and micronutrient transport has been extensively reported in the literature. MN frequency is also an important index for determining DNA repair efficiency phenotype (including mis-repair), response to environmental exposure and identifying various dietary factors required for optimal genome stability. The aim of the present study is to review the reported in vivo associations between genotype and MN frequency in humans taking into considerations the presence of interactions with nutrients levels and/or exposure to genotoxins. One hundred and eleven publications linking MN frequency in peripheral blood lymphocytes to gene polymorphism were retrieved from PubMed. After applying exclusion criteria, only 37 studies were evaluated in the present review. Polymorphisms in XRCC1 (Arg280His), ERCC2 (Lys751Gln), CYP2E1 (c1/c2) and MTR (A2756G) were consistently associated with the MN formation. These results contribute substantial evidence to the hypothesis that genotype may influence MN frequency in human cells.


Age-related changes in the aortic valve affect leaflet stress distributions: implications for aortic valve degeneration.
The degeneration of aortic valve leaflets occurs primarily due to high mechanical stresses in zones of leaflet flexion. Aging, which has been identified as a risk factor for degenerative aortic stenosis, is associated with reductions in stretch and in compliance, and an increase in tissue thickness of the leaflet and root. The study aim was to investigate the effects of age-related tissue changes on valve opening dynamics and leaflet stress patterns, and its implications for valve degeneration. A three-dimensional finite element model of the aortic valve and root was developed in Ansys. A transient, non-linear analysis was carried out of the valve opening phase. Three age groups were identified based on leaflet and root tissue properties: group I age <35 years; group II aged 33-55 years; and group III aged >55 years. The valve opening dynamics was studied and von Mises stresses in various regions of the leaflet were computed. Maximum leaflet stresses occurred along the leaflet-root attachment, analogous to the spatial distribution of calcific deposits in the aortic valve. With increasing age, the rate of valve opening decreased, and the magnitude of leaflet tip displacement in both radial and axial directions reduced progressively. At the leaflet-root attachment, groups II and III showed 19% and 32.7% increases in average stress over group I, respectively. At the free edge, the stresses in group III increased 2.7% over group I; however, the average stress at the free edge in group II decreased 3.5% over group I. In the leaflet belly, groups II and III showed 27.6% and 60.9% increases in stresses over group I, respectively. Changes in leaflet and root tissue properties lead to altered leaflet dynamics and increased stresses. This not only emphasizes the role of aging on the development and progression of degenerative aortic valve disease, but also has implications in the design of bioprosthetic heart valves.


Antibacterial, anti-inflammatory and peroxidase-mediated cyclooxygenase-1 inhibitory properties of Fusarium solani extract.
Context: Nigerian soil fungi population is unexplored. It is hypothesized that they harbour new bioactive chemicals. This hypothesis is based on the large percentage of currently approved medicines that originated from soil-inhabiting micro-organisms Objectives: To investigate the antimicrobial and anti-inflammatory properties of Fusarium solani ethyl acetate (EtOAc) extract selected based on its broad spectrum of antimicrobial potential in an overlay experiment with seven other soil fungi strains. Materials and methods: Fungus number 6 (F6), identified by molecular characterization as Fusarium solani (Mart.) Sacc (Nectriaceae) was selected for studies from eight purified soil fungi due to its superior broad-spectrum antibiotics producing potential following agar overlay experiment. F6 was fermented for 21 d and the minimum inhibitory concentration (MIC) of its EtOAc fermentation extract (dose range: 12.5-100 µg/mL) was determined using agar dilution method for Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhi and anti-inflammatory properties determined using rat-paw (250-500 mg/kg) and xylene induced oedema (250-500 µg/kg) (in Swiss albino rats and mice) models, respectively. The ability of the extract to inhibit cyclooxygenase (COX) enzyme was also determined in vitro using Cayman test kit-760111. Result: The MIC of the EtOAc extract was <12.5 µg/mL for S. aureus, P. aeruginosa and Escherichia coli. It inhibited xylene induced oedema by 65% compared with 61% observed for diclofenac and was significantly (p < 0.05) better than diclofenac in rat-paw-oedema model within the first phase of inflammation. The extract inhibited COX-1 peroxidase-mediated activities with an IC50 below 5 µg/mL. Conclusions: The extract exhibited strong antibacterial and anti-inflammatory properties, warranting further investigations into therapeutic potential of this fungus. This study design can be adapted in soil fungi metabolomic investigations. We report for the first time the potent anti-inflammatory property of the ethyl acetate extract of soil strain of F. solani with a possible mechanism of action that involves the inhibition of COX enzyme.


Infrared thermography in children: a reliable tool for differential diagnosis of peripheral microvascular dysfunction and Raynaud's phenomenon?
Infrared Thermography (IRT) has been used for over 30 years in the assessment of Raynaud Phenomenon (RP) and other peripheral microvascular dysfunctions in adults but, to date, very little experience is available on its use in children for this purpose. The first aim of the study was to assess reproducibility of thermographic examination after cold exposure by comparing inter-observer agreement in thermal imaging interpretation. The secondary aim was to evaluate whether IRT is reliable to diagnose and differentiate peripheral circulation disturbances in children. Children with clinical diagnosis of primary Raynaud's phenomenon (PRP), secondary RP (SRP), acrocyanosis (AC) and age-matched controls underwent sequential measurements of skin temperature at distal interphalangeal (DIP) and metacarpophalangeal (MCP) joints with IRT at baseline and for 10 min after cold challenge test. Intraclass correlation coefficient (ICC) was calculated for inter-rater reliability in IRT interpretation, then temperature variations at MCP and DIP joints and the distal-dorsal difference (DDD) were analysed. Fourteen PRP, 16 SRP, 14 AC and 15 controls entered the study. ICC showed excellent agreement (> 0.93) for DIPs and MCPs in 192 measures for each subject. Patients with PRP, SRP and acrocyanosis showed significantly slower recovery at MCPs (p < 0.05) and at DIPs (p < 0.001) than controls. At baseline, higher temperature at DIPs and lower at MCPs was observed in PRP compared with SRP with significantly lower DDD (p < 0.001). Differently from AC, both PRP and SRP showed gain of temperature at DIPs and less at MCPs after cold challenge. PRP but not SRP patients returned to DIPs basal temperature by the end of re-warming time. Analysis of DDD confirmed that controls and PRP, SRP and AC patients significantly differed in fingers recovery pattern (p < 0.05). IRT appears reliable and reproducible in identifying children with peripheral microvascular disturbances. Our results show that IRT examination pointed out that PRP, SRP and AC patients present significant differences in basal extremities temperature and in re-warming pattern after cold challenge therefore IRT can be suggested as an objective tool for diagnosis and monitoring of disease.


Deleterious effect of ultraviolet-B radiation on accessory function of human blood adherent mononuclear cells.
The effects of ultraviolet-B radiation (UV-B) on accessory function of human blood adherent mononuclear cells (ADH) for antigen and mitogen-induced responses, and production by ADH of the amplifying cytokine interleukin 1 (IL-1) were examined. Responder lymphocytes were rendered accessory cell dependent by treatment of nonadherent cells with OKIal+complement. UV-B depressed accessory function of ADH in a dose-dependent manner. UV-B at 5 mJ/cm2 decreased accessory function of 2 x 10(4) ADH for tetanus toxoid-induced responses (measured as incorporation of 3H-thymidine) by 84% (P less than 0.001, n = 6) and phytohaemagglutinin-induced responses 91% (P less than 0.001, n = 4). UV-B also decreased accessory activity of peripheral blood mononuclear cells but not Epstein-Barr virus-transformed B cells for a PPD-reactive T cell line. Viability was approximately 90% 0-72 h after exposure of ADH to 5 mJ/cm2 of UV-B. Interleukin 1 (IL-1) activity of supernatants of ADH was assayed on C3H/HeJ mouse thymocytes. Pretreatment of ADH with 5 mJ/cm2 UV-B decreased lipopolysaccharide-stimulated IL-1 activity from 169 +/- 34 (mean U/ml +/- s.e.) to 4 +/- 1 (P less than 0.01, n = 4). Lysates of UV-B irradiated. LPS-stimulated ADH had no discernible IL-1 activity. Addition of IL-1 partially restored accessory activity of UV-B irradiated ADH for lymphocyte responses to TT. Exposure of ADH to TT or PHA for 30 min before irradiation blocked the inhibitory effect of UV-B on accessory activity. Thus, low doses of UV-B are deleterious to accessory function and to production of IL-1 by ADH. Interference with production of cytokines and with initial interactions of accessory cells with antigen and mitogen may be critical to the effects of UV-B on immunoregulatory function of ADH.


Integrated autonomic and behavioral responses to L/N Ca2(+)-channel blocker omega-conotoxin in conscious rats.
omega-Conotoxin (omega-ctx) was used as a probe for studying the putative role of brain L/N-type Ca2+ channels in regulation of autonomic functions. Rats were injected intracerebroventricularly (icv) with omega-ctx, and hemodynamic, biochemical and behavioral variables were monitored. omega-Ctx (0.032-10 nmol/kg) caused a persistent, dose-dependent shaking behavior, complex thermoregulatory changes, and motor deficits lasting up to 48 h. Cardiovascular responses to omega-ctx included tachycardia (+71 +/- 16%, P less than 0.01) and elevated arterial blood pressure (+16 +/- 1%, P less than 0.05) associated with increased circulating levels of norepinephrine and epinephrine. Higher doses, 1 or 10 nmol/kg, resulted in circulatory shock and death. Central administration of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), diltiazem (100 or 1,000 nmol/kg), neomycin (100 nmol/kg, each), nifedipine (10 nmol/kg), and CdCl2 (100 nmol/kg), which represent intracellular, non-specific N-, L-, and L/N-type Ca2(+)-channel blockers, respectively, did not cause any behavioral or hemodynamic effects, whereas the L-channel agonist BAY K 8644 (100 nmol/kg icv) caused a mild transient pressor response. Pretreatment with the gamma-aminobutyric acid (GABA) agonist muscimol (icv) or a combined intravenous pretreatment with propranolol and N-methylatropine blocked the omega-ctx effects. Our data suggest that omega-ctx actions in the brain involve central GABAergic mechanisms modulated by yet a different type of Ca2+ channels not characterized by any of the known voltage-operated Ca2+ channels.


Xenopus meiotic microtubule-associated interactome.
In metazoan oocytes the assembly of a microtubule-based spindle depends on the activity of a large number of accessory non-tubulin proteins, many of which remain unknown. In this work we isolated the microtubule-bound proteins from Xenopus eggs. Using mass spectrometry we identified 318 proteins, only 43 of which are known to bind microtubules. To integrate our results, we compiled for the first time a network of the meiotic microtubule-related interactome. The map reveals numerous interactions between spindle microtubules and the newly identified non-tubulin spindle components and highlights proteins absent from the mitotic spindle proteome. To validate newly identified spindle components, we expressed as GFP-fusions nine proteins identified by us and for first time demonstrated that Mgc68500, Loc398535, Nif3l1bp1/THOC7, LSM14A/RAP55A, TSGA14/CEP41, Mgc80361 and Mgc81475 are associated with spindles in egg extracts or in somatic cells. Furthermore, we showed that transfection of HeLa cells with siRNAs, corresponding to the human orthologue of Mgc81475 dramatically perturbs spindle formation in HeLa cells. These results show that our approach to the identification of the Xenopus microtubule-associated proteome yielded bona fide factors with a role in spindle assembly.


Survival and toxicity of radical radiotherapy (with or without brachytherapy) for FIGO stage I and II cervical cancer: a mono-institutional analysis.
To add to the existing outcome data regarding radical radiotherapy (RT) for FIGO Stage I and II cervical cancer in a mono-institutional series and to evaluate the cost-benefit ratio of the addition of brachytherapy (BRA) to external-beam radiotherapy (EBRT). The authors report on 240 patients (pts) with FIGO Stage I and II cervical cancer, consecutively treated with radical RT from 1990 through 2009 at the Istituto del Radio "O. Alberti" (EBRT alone, 32, EBRT and BRA, 189, BRA alone, 19). BRA was delivered with low dose rate (LDR, 133.64%) until 2003 and then with high dose rate (HDR, 75.36%). RT was associated with concomitant chemotherapy (CHT), mainly weekly cisplatin 40 mg/m2, in 87 pts, mostly after 2000. The Chi-square test was used to compare the different variables, the Log-Rank test to compare the actuarial survival values, and the Cox-model for the multivariate analysis. Five-year actuarial overall survival (OS) equalled 65%, disease specific survival (DSS) 77%. Regardless of disease stage, better DSS was evident in pts treated with EBRT and BRA compared with those treated with EBRT alone (82% and 58% respectively, p = 0.005); pts treated with concomitant CHT (dose intensity > or = 50%) and higher RT doses (RT cumulative EQD2 > or = 75 Gy) obtained better DSS. Complete response (CR) rate approached 88.4% (206/233 evaluable pts) and more than half of the subsequent failures (21/36) were in distant sites. Older patients and those given BRA had better OS and DSS, while BRA dose rate did not result related with these outcomes. Chronic G3/G4 toxicity involved more frequently the intestinal/rectal tract than other organs at risk. Rectal and vaginal serious chronic sequelae developed mainly in pts treated with EBRT and BRA and suggest the need for more advanced treatment techniques. the present mono-institutional analysis confirms the efficacy of radical RT for the treatment of cervical cancer and provides support to the role of BRA to obtain better outcomes. An effort to reduce long-term toxicity of the treatment is needed.


A novel Bacillus thuringiensis gene encoding a Spodoptera exigua-specific crystal protein.
Only one of the four lepidoptera-specific crystal protein subclasses (CryIC) Bacillus thuringiensis was previously shown to be highly toxic against several Spodoptera species. By using a cryIC-derived nucleotide probe, DNA from 25 different strains of B. thuringiensis was screened for the presence of homologous sequences. A putative crystal protein gene, considerably different from the cryIC gene subclass, was identified in the DNA of strain 4F1 (serotype kenyae) and cloned in Escherichia coli. Its nucleotide sequence was determined and appeared to contain several features typical for a crystal protein gene. Furthermore, the region coding for the N-terminal part of the putative toxic fragment showed extensive homology to subclass cryIA sequences derived from gene BtII, whereas the region coding for the C-terminal part appeared to be highly homologous to the cryIC gene BtVI. With an anti-crystal protein antiserum, a polypeptide of the expected size could be demonstrated in Western immunoblots, onto which a lysate of E. coli cells harboring the putative gene, now designated as BtXI, had been transferred. Cells expressing the gene appeared to be equally toxic against larvae of Spodoptera exigua as recombinant cells expressing the BtVI (cryIC)-encoded crystal protein. However, no toxicity against larvae of Heliothis virescens, Mamestra brassicae, or Pieris brassicae could be demonstrated. The nucleotide sequence analysis and the toxicity studies showed that this novel crystal protein gene falls into a new cryl gene subclass. We propose that this subclass be referred to as cryIE.


Understanding barriers to organized breast cancer screening in France: women's perceptions, attitudes, and knowledge.
The participation rate in organized breast cancer screening in France is lower than recommended. Non-participants either use opportunistic screening or do not use either screening modality. To assess any differences in perceptions, attitudes and knowledge related to breast cancer screening between users of opportunistic screening and non-users of any screening mammograms and to identify potential barriers to participation in organized screening. Six focus groups were conducted in May 2010 with 34 French non-participants in organized screening, 15 who used opportunistic screening (OpS group) and 19 who used no screening (NoS group). The guide used for both groups explored perceptions and attitudes related to health, cancer and screening; perceptions of femininity; and knowledge about breast cancer screening. Thematic content analysis was performed. Perceptions, attitudes and knowledge differed between the two groups. Women in the OpS group perceived a high susceptibility to breast cancer, visited their gynaecologist regularly, were unfamiliar with organized screening modalities and had doubts about its quality. NoS women had very high- or low-perceived susceptibility to breast cancer, knew about screening modalities, had doubts about its usefulness and expressed negative opinions of mammograms. Differences in perceptions and attitudes related to breast cancer screening partially explain why some women choose opportunistic screening or no screening. General practitioners and gynaecologists are in a unique position to provide individually tailored preventative messages to improve participation in organized screening.


Actin-dependent activation of presynaptic silent synapses contributes to long-term synaptic plasticity in developing hippocampal neurons.
Developing neurons have greater capacity in experience-dependent plasticity than adult neurons but the molecular mechanism is not well understood. Here we report a developmentally regulated long-term synaptic plasticity through actin-dependent activation of presynaptic silent synapses in cultured hippocampal neurons. Live FM 1-43 imaging and retrospective immunocytochemistry revealed that many presynaptic boutons in immature neurons are functionally silent at resting conditions, but can be converted into active ones after repetitive neuronal stimulation. The activation of presynaptic silent synapses is dependent on L-type calcium channels and protein kinase A (PKA)/PKC signaling pathways. Moreover, blocking actin polymerization with latrunculin A and cytochalasin B abolishes long-term increase of presynaptic functional boutons induced by repetitive stimulation, whereas actin polymerizer jasplakinolide increases the number of active boutons in immature neurons. In mature neurons, however, presynaptic boutons are mostly functional and repetitive stimulation did not induce additional enhancement. Quantitative immunostaining with phalloidin revealed a significant increase in axonal F-actin level after repetitive stimulation in immature but not mature neurons. These results suggest that actin-dependent activation of presynaptic silent synapses contributes significantly to the long-term synaptic plasticity during neuronal development.


The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome.
White blood cell (WBC) count is a known risk factor for atherosclerotic vascular disease in adult women. Polycystic ovary syndrome (PCOS) is potentially a risk factor for atherosclerosis and cardiovascular disease. The aim of the present study was to investigate leukocyte count in PCOS. One hundred and fifty PCOS women matched for age and body mass index with 150 healthy women were enrolled. WBC count, C-reactive protein, and a complete anthropometrical, metabolic, and hormonal evaluation were performed in both groups. Serum insulin, glucose level, and lipid profile were also measured in each subject. WBC count was significantly higher (P < 0.0001) in PCOS with (interquartile range in parentheses) 7260 (393) cells/mm(3), compared with controls with 5220 (210) cells/mm(3). C-reactive protein levels were significantly increased (P < 0.0001) in PCOS with 2 (1) mg/liter compared with healthy women with 0.7 (0.8) mg/liter. In both groups, there was a significant (P < 0.0001) linear correlation between WBC count and homeostasis model assessment score (PCOS, r = 0.94; controls, r = 0.91). Multiple linear regression analysis showed that other hormone levels are not predictors of leukocyte count both in PCOS and control women. In conclusion, our data demonstrate that PCOS women have an increased WBC count that correlates with homeostasis model assessment values.


Reduction of aflatoxin level in aflatoxin-induced rats by the activity of probiotic Lactobacillus casei strain Shirota.
Aflatoxin B1 (AFB1 ) is considered as the most toxic food contaminant, and microorganisms, especially bacteria, have been studied for their potential to reduce the bioavailability of mycotoxins including aflatoxins. Therefore, this research investigated the efficacy of oral administration of Lactobacillus casei Shirota (LcS) in aflatoxin-induced rats. Sprague Dawley rats were divided into three groups of untreated control, the group induced with AFB1 only, and the group given probiotic in addition to AFB1. In the group induced with AFB1 only, food intake and body weight were reduced significantly. The liver and kidney enzymes were significantly enhanced in both groups induced with AFB1 , but they were lower in the group given LcS. AFB1 was detected from all serum samples except for untreated control group's samples. Blood serum level of AFB1 in the group induced with AFB1 only was significantly higher than the group which received probiotic as a treatment (P < 0·05), and there was no significant difference between the control group and the group treated with probiotic. LcS supplementation could improve the adverse effect of AFB1 induction on rats' body weight, plasma biochemical parameters and also could reduce the level of AFB1 in blood serum. This study's outcomes contribute to better understanding of the potential of probiotic to reduce the bioavailability ofAFB1 . Moreover, it can open an opportunity for future investigations to study the efficacy of oral supplementation of probiotic LcS in reducing aflatoxin level in human.