Flexural strength, biocompatibility, and antimicrobial activity of a polymethyl methacrylate denture resin enhanced with graphene and silver nanoparticles.
The study evaluates the effect of adding graphene-Ag nanoparticles (G-AgNp) to a PMMA auto-polymerizing resin, with focus on antibacterial activity, cytotoxicity, monomer release, and mechanical properties. Auto-polymerizing acrylic resin (M) was loaded with 1 wt% G-AgNp (P1) and 2 wt% G-AgNp (P2). Methyl methacrylate monomer release (MMA) was measured after immersion of the samples in chloroform and cell medium respectively. Cell viability was assessed on dysplastic oral keratinocytes (DOK) and dental pulp stem cells. Oxidative stress and inflammatory response following exposure of dysplastic oral keratinocytes to the experimental resins was evaluated. Antibacterial activity against Staphylococcus aureus, Streptococcus mutans and Escherichia coli and also flexural strength of the resins were assessed. Residual monomer: For samples immersed in chloroform, MMA concentration reached high levels, 10.27 μg/g for sample P1; MMA increased at higher G-AgNp loading; 0.63 μg/g MMA was found in medium for P1, and less for sample P2. Cell viability: Both cell lines displayed a viability decrease, but remained above 75%, compared to controls, when exposed to undiluted samples. Inflammation: proinflammatory molecule TNF-α decreased when DOK cultures were exposed to G-AgNp samples. MDA levels indicated increased oxidative stress damage in cells treated with PMMA, confirmed by the antioxidant mechanism activation, while samples containing G-AgNp induced an antioxidant effect. All tested samples showed antibacterial properties against Gram-positive bacteria. Samples containing G-AgNp also exhibited bactericide action on E. coli. Mechanical properties: both samples containing G-AgNp improved flexural strength compared to the sample resin, measured through elastic strength parameters. PMMA resin loaded with G-AgNp presents promising antibacterial activity associated with minimal toxicity to human cells, in vitro, as well as improved flexural properties. These encouraging results obtained in vitro support further in vivo investigation, to thoroughly check whether the PMMA loaded with graphene-silver nanoparticles constitute an improvement over current denture materials.


Purification of baculovirus vectors using heparin affinity chromatography.
Baculoviruses are commonly used for recombinant protein and vaccine production. Baculoviruses are nonpathogenic to vertebrates, have a large packaging capacity, display broad host and cell type tropism, infect both dividing and nondividing cells, and do not elicit strong immune or allergic responses in vivo. Hence, their use as gene delivery vehicles has become increasingly popular in recent years. Moreover, baculovirus vectors carrying mammalian regulatory elements can efficiently transduce and express transgenes in mammalian cells. Based on the finding that heparan sulfate, which is structurally similar to heparin, is an attachment receptor for baculovirus, we developed a novel scalable baculovirus purification method using heparin-affinity chromatography. Baculovirus supernatants were loaded onto a POROS heparin column, washed to remove unbound materials, and eluted with 1.5 mol/l NaCl, which yielded a recovery of purified baculovirus of 85%. After ultracentrifugation, baculovirus titers increased from 200- to 700-fold with overall yields of 26-29%. We further show that baculovirus particles were infectious, normal in morphology and size, despite high-salt elution and shear forces used during purification and concentration. Our chromatography-based purification method is scalable and, together with ultracentrifugation and/or tangential flow filtration, will be suitable for large-scale manufacturing of baculovirus stocks for protein and vaccine production and in gene therapy applications.


Absence of relationship between UV-induced reversion frequency and nucleotide sequence at the CYC1 locus of yeast.
The UV induced mutation frequency of a given base pair located at different sites within the CYC1 gene of Saccharomyces cerevisiae was found to vary by more than fifty fold, indicating the existence of hotspots and coldspots typical of those found in other organisms. We were unable, however, to find any feature of the nucleotide sequence at or near the sites of mutation that explains this variability. These and other data suggest that hotspots are not located within regions particularly susceptible to the formation of premutational lesions. More probably the variation in mutability depends on differences in the activity of enzymes responsible for producing mutations, though the reasons for these differences are not understood and may depend on factors not directly related to nucleotide sequence.


Chitosan scaffold enhances nerve regeneration within the in vitro reconstructed bladder wall: an animal study.
The function of reconstructed bladder depends on the contracting bladder wall. This can be obtained with a proper innervating segment. Polyglycolic acid (PGA) is used as cell vehicle. Chitosan supported the adhesion and differentiation of neurons. The aim of the study was to compare PGA with PGA/chitosan 'sandwich' grafts for bladder regeneration. 3T3 fibroblasts were seeded on 6 PGA and on 3 chitosan scaffolds and incubated for 3 days at 37 degrees C in 5% CO(2) before implantation. Three rats underwent bladder reconstruction with PGA cell-seeded grafts and 3 with PGA grafts covered with chitosan cell-seeded grafts ('sandwich' graft). Three rats in the control group were not operated. After 6 months, reconstructed tissue was stained with hematoxylin and eosin. Neurons were identified by synaptophysin and neuron-specific enolase staining. No complications were noticed. PGA/chitosan grafts were evaluated as (+++) and (++), while PGA grafts were evaluated as (++) and (+) with use of synaptophysin antibody. The control group was evaluated as (+). PGA/chitosan grafts were evaluated as (++) and (+), while PGA grafts were evaluated as (++) and (+) in neuron-specific enolase staining. The control group was evaluated as (+). Chitosan improved PGA's abilities as a cell matrix and in guiding neurons into the graft.


Immunologic monitoring during and after OKT3 therapy.
Immunologic monitoring should be undertaken during and for 6 weeks after OKT3 treatment. CD3 absolute cell determinations should be obtained three times per week during therapy. A progressive increase of the absolute CD3 cell count above 10/microL is suggestive of an inadequate OKT3 serum level, most often due to an early antimurine response. Weekly posttherapy antimurine response should be determined. The presence or absence of an antimurine response can be suggestive of a successful response to a second therapeutic course of OKT3.


A general approach to desalting oligosaccharides released from glycoproteins.
Desalting of sugar samples is essential for the success of many techniques of carbohydrate analysis such as mass spectrometry, capillary electrophoresis, anion exchange chromatography, enzyme degradation and chemical derivatization. All desalting methods which are currently used have limitations: for example, mixed-bed ion-exchange columns risk the loss of charged sugars, precipitation of salt by a non-aqueous solvent can result in co-precipitation of oligosaccharides, and gel chromatography uses highly crosslinked packings in which separation of small oligosaccharides is difficult to achieve. We demonstrate that graphitized carbon as a solid phase extraction cartridge can be used for the purification of oligosaccharides (or their derivatives) from solutions containing one or more of the following contaminants: salts (including salts of hydroxide, acetate, phosphate), monosaccharides, detergents (sodium dodecyl sulfate and Triton X-100), protein (including enzymes) and reagents for the release of oligosaccharides from glycoconjugates (such as hydrazine and sodium borohydride). There is complete recovery of the oligosaccharides from the adsorbent which can also be used to fractionate acidic and neutral glycans. Specific applications such as clean-up of N-linked oligosaccharides after removal by PNGase F and hydrazine, desalting of O-linked glycans after removal by alkali, on-line desalting of HPAEC-separated oligosaccharides and beta-eliminated alditols prior to electrospray mass spectrometry, and purification of oligosaccharides from urine are described.


Changes in blood cholesterol awareness: final results from the South Carolina Cardiovascular Disease Prevention Project.
We examined changes in five indicators of blood cholesterol awareness in two comparable biracial communities in South Carolina. One community received three years of cholesterol education and intervention activities implemented by a state health department and the other served as a comparison. Cross-sectional, interviewer-administered, random digit-dialed telephone surveys of 11,070 adults 18 years and older were conducted in 1987, 1988, 1989, and 1991. Changes in community levels of knowledge, preventive behavior, risk awareness, and treatment were assessed and compared between the two communities with analysis of covariance techniques that adjusted for age, race, and sex. Significant increases in knowledge, behavior, and risk awareness were observed for most groups defined by race, sex, or age in both communities. Significant net intervention increases between 1987 and 1991 were seen for knowledge of good cholesterol level (+16.4%, P < .001); behavioral action of ever having blood cholesterol checked (+18.6%, P < .001); and knowledge of personal level of blood cholesterol (+16.0%, P < .01). These results suggest that a community-wide blood cholesterol screening and education program can be effective in increasing blood cholesterol knowledge, risk awareness, and preventive behavior, thus serving as part of a public health strategy to lower and treat high blood cholesterol levels in a community.


Serotonin 3 receptor signaling regulates 5-fluorouracil-mediated apoptosis indirectly via TNF-α production by enhancing serotonin release from enterochromaffin cells.
Antagonists of the 5-hydroxytryptamine (serotonin) 3 receptor (5-HT3R) have anti-inflammatory and anti-apoptotic activities, but the detailed, underlying mechanisms are not well understood. We focused on anti-apoptotic activities via 5-HT3R signaling to clarify the underlying mechanisms. Mice were administered 5-fluorouracil (5-FU), which induced apoptosis in intestinal epithelial cells. Coadministration with 5-HT3R antagonists or agonists tended to decrease or increase the number of apoptotic cells, respectively. In serotonin 3A receptor (5-HT3AR) null (HTR3A-/-) mice, the number of apoptotic cells induced by 5-FU was decreased compared with that in wild-type (WT) mice. Bone marrow (BM) transplantation was performed to determine if BM-derived immune cells regulated 5-FU-induced apoptosis, but they were found to be unrelated to this process. Data from 5-HT3AR/enhanced green fluorescent protein reporter mice revealed that 50% of enterochromaffin (EC) cells expressed 5-HT3AR, but the number of apoptotic cells induced by 5-FU in the intestinal crypt organoids of HTR3A-/- mice was not altered compared with WT mice. In contrast, plasma 5-HT concentrations in WT mice but not in HTR3A-/- mice administered 5-FU were increased significantly. In conclusion, 5-HT3R signaling may enhance 5-HT release, possibly from EC cells intravascularly, or paracrine, resulting in increases in plasma 5-HT concentration, which in turn, enhances apoptotic activities induced by 5-FU.-Mikawa, S., Kondo, M., Kaji, N., Mihara, T., Yoshitake, R., Nakagawa, T., Takamoto, M., Nishimura, R., Shimada, S., Ozaki, H., Hori, M. Serotonin 3 receptor signaling regulates 5-fluorouracil-mediated apoptosis indirectly via TNF-α production by enhancing serotonin release from enterochromaffin cells.


An efficient extraction method for quantitation of adenosine triphosphate in mammalian tissues and cells.
Firefly bioluminescence is widely used in the measurement of adenosine 5'-triphosphate (ATP) levels in biological materials. For such assays in tissues and cells, ATP must be extracted away from protein in the initial step and extraction efficacy is the main determinant of the assay accuracy. Extraction reagents recommended in the commercially available ATP assay kits are chaotropic reagents, trichloroacetic acid (TCA), perchloric acid (PCA), and ethylene glycol (EG), which extract nucleotides through protein precipitation and/or nucleotidase inactivation. We found that these reagents are particularly useful for measuring ATP levels in materials with relatively low protein concentrations such as blood cells, cultured cells, and bacteria. However, these methods are not suitable for ATP extraction from tissues with high protein concentrations, because some ATP may be co-precipitated with the insolubilized protein during homogenization and extraction, and it could also be precipitated by neutralization in the acid extracts. Here we found that a phenol-based extraction method markedly increased the ATP and other nucleotides extracted from tissues. In addition, phenol extraction does not require neutralization before the luciferin-luciferase assay step. ATP levels analyzed by luciferase assay in various tissues extracted by Tris-EDTA-saturated phenol (phenol-TE) were over 17.8-fold higher than those extracted by TCA and over 550-fold higher than those in EG extracts. Here we report a simple, rapid, and reliable phenol-TE extraction procedure for ATP measurement in tissues and cells by luciferase assay.


Vectorial total generalized variation for accelerated multi-channel multi-contrast MRI.
To develop and implement an efficient reconstruction technique to improve accelerated multi-channel multi-contrast MRI. The vectorial total generalized variation (TGV) operator is used as a regularizer for the sensitivity encoding (SENSE) technique to improve image quality of multi-channel multi-contrast MRI. The alternating direction method of multipliers (ADMM) is used to efficiently reconstruct the data. The performance of the proposed method (MC-TGV-SENSE) is assessed on two healthy volunteers at several acceleration factors. As demonstrated on the in vivo results, MC-TGV-SENSE had the lowest root-mean-square error (RMSE), highest structural similarity index, and best visual quality at all acceleration factors, compared to other methods under consideration. MC-TGV-SENSE yielded up to 17.3% relative RMSE reduction compared to the widely used total variation regularized SENSE. Furthermore, we observed that the reconstruction time of MC-TGV-SENSE is reduced by approximately a factor of two with comparable RMSEs by using the proposed ADMM-based algorithm as opposed to the more commonly used Chambolle-Pock primal-dual algorithm for the TGV-based reconstruction. MC-TGV-SENSE is a better alternative than the existing reconstruction methods for accelerated multi-channel multi-contrast MRI. The proposed method exploits shared information among the images (MC), mitigates staircasing artifacts (TGV), and uses the encoding power of multiple receiver coils (SENSE).


Systematic reviews: Separating fact from fiction.
The volume of scientific literature continues to expand and decision-makers are faced with increasingly unmanageable volumes of evidence to assess. Systematic reviews (SRs) are powerful tools that aim to provide comprehensive, transparent, reproducible and updateable summaries of evidence. SR methods were developed, and have been employed, in healthcare for more than two decades, and they are now widely used across a broad range of topics, including environmental management and social interventions in crime and justice, education, international development, and social welfare. Despite these successes and the increasing acceptance of SR methods as a 'gold standard' in evidence-informed policy and practice, misconceptions still remain regarding their applicability. The aim of this article is to separate fact from fiction, addressing twelve common misconceptions that can influence the decision as to whether a SR is the most appropriate method for evidence synthesis for a given topic. Through examples, we illustrate the flexibility of SR methods and demonstrate their suitability for addressing issues on environmental health and chemical risk assessment.


Clinic and genetic predictors in response to erenumab.
Erenumab (ERE) is the first anticalcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. A proportion of patients do not adequately respond to ERE. Prospective multicenter study involving 110 migraine patients starting ERE 70 mg monthly. Baseline socio-demographics and migraine characteristics, including mean monthly migraine days (MMDs), migraine-related burden (MIDAS [Migraine Disability Assessment scale] and Headache Impact Test-6), and use of abortive medications, during 3 months before and after ERE start were collected. Real-time polymerase chain reaction was used to determine polymorphic variants of calcitonin receptor-like receptor and receptor activity-modifying protein-1 genes. Logistic regression models were used to identify independent predictors for 50% responder patients (50-RESP) and 75% responder patients (75-RESP). At month 3, MMDs decreased from 17.2 to 9.2 (p < 0.0001), 59/110 (53.6%) patients were 50-RESP, and 30/110 (27.3%) were 75-RESP. Age at migraine onset (odds ratio [OR] [95% confidence interval (95% CI)]: 1.062 [1.008-1.120], p = 0.024), number of failed preventive medications (0.753 [0.600-0.946], p = 0.015), and MIDAS score (1.011 [1.002-1.020], p = 0.017) were associated with 75-RESP. Among the genetic variants investigated, RAMP1 rs7590387 was found associated with a lower probability of being 75-RESP (per G allele OR [95% CI]: 0.53 [0.29-0.99], p = 0.048]), but this association did not survive adjustment for confounding clinical variables (per G allele, 0.55 [0.28-1.10], p = 0.09]). In this real-word study, treatment with ERE significantly reduced MMDs. The number of failed preventive medications, migraine burden, and age at migraine onset predicted response to ERE. Larger studies are required to confirm a possible role of RAMP1 rs7590387 as genetic predictor of ERE efficacy.


Relationship between fetal weight, placental growth and litter size in mice from mid- to late-gestation.
In mammals, the placenta, which consists of maternal and fetal components, is important in fetal development because it supplies the fetus with the nourishment it needs. We investigated the effects of placental growth and litter size on mouse fetal weights from mid- to late-gestation. The mean weight of male fetuses at 13.5 days post coitum (dpc) was larger than that of females. Although there was a significant correlation between fetal and placental weights in both males and females during mid-gestation (P<0.05), there was no correlation during late-gestation. However, a significant correlation was observed between litter size and fetal weights in both males and females at 17.5 dpc (P<0.05). These findings suggest that fetal weight is regulated by placental growth during mid-gestation, while the effects of litter size are more prominent towards late-gestation.


Allogeneic haematopoietic stem-cell transplantation for relapsed and refractory aggressive histology non-Hodgkin lymphoma.
Forty-four patients with relapsed or refractory aggressive histology non-Hodgkin lymphoma (NHL) (diffuse large B cell, n = 23; peripheral T cell, n = 5; transformed B cell, n = 16) proceeded to allogeneic stem cell transplant (allo-SCT) between 1987 and 2003. Median age at transplant was 40 years (range 19-56 years). At the time of transplant, 35 were chemosensitive and nine were chemorefractory. Thirty-three patients had matched sibling donors and 11 had unrelated donors. Forty-two patients (95%) received radiation-based conditioning regimens. Event-free survival (EFS) and overall survival (OS) at 5 years was 43% [95% confidence interval (CI): 27-58%] and 48% (95% CI: 32-63%) respectively. Treatment-related mortality was 25% at 1 year. Grade III-IV acute graft-versus-host disease (GVHD) was the only significant variable affecting OS and EFS, and had a negative impact. Chronic GVHD did not influence survival. Lymphoma relapse <12 months after initial therapy predicted for increased risk of relapse post-transplant (P = 0.02). Patients with chemorefractory lymphoma were not at increased risk of relapse (P = 0.20) with four of nine patients remaining alive without disease 12-103 months post-transplant. In conclusion, allo-SCT for relapsed or refractory aggressive histology NHL results in long-term EFS and OS of 40-50%. Patients with chemorefractory disease can have a durable remission post-transplant.


Contamination of joints with tissue debris and hair after arthrocentesis: the effect of needle insertion angle, spinal needle gauge, and insertion of spinal needles with and without a stylet.
To assess fetlock joint contamination with tissue debris and hair after arthrocentesis. Experimental. Fetlock joint tissues (n = 10 horses). Soft tissue flaps including the joint capsule were dissected from the dorsal fetlock joints of 7 anesthetized horses leaving an intact proximal base. Needles inserted through the tissue flaps were flushed into tissue cell culture plates and examined for debris. Studies were repeated on excised fetlock tissue preparations after being stored for 5 days. Variables included gauge and type of needle, insertion of spinal needles with and without a stylet, angle of insertion, length of hair, and ante- and postmortem needle insertion. Tissue fragments collected from 3 horses were cultured for bacteria. Compared to 20 g disposable needles inserted perpendicularly through unclipped skin, the odds ratios (ORs) for hair contamination were significantly greater for 20 g spinal needles without a stylet, and significantly less for 22 g spinal needles inserted with a stylet and for angled insertion of disposable needles. Tissue contamination OR was significantly less for 20 g spinal needles inserted without a stylet, angled insertion, and clipped hair. Bacteria were isolated from 2.6% of tissue fragments. Angled needle insertion reduces joint contamination with tissue and hair. Spinal needles should be inserted with a stylet in place and 22 g spinal needles are preferable to 20 g spinal needles. Joints may be contaminated with bacteria after routine surgical preparation of skin.


Infrared divergences and quantum coherence.
In theories with long-range forces like QED or perturbative gravity, only rates that include emitted soft radiation are non-vanishing. Independently of detector resolution, finite observables can only be obtained after integrating over the IR-component of this radiation. This integration can lead to some loss of quantum coherence. In this note, however, we argue that it should in general not lead to full decoherence. Based on unitarity, we suggest a way to define non-vanishing off-diagonal pieces of the IR-finite density matrix. For this IR-finite density matrix, we estimate the dependence of the loss of quantum coherence, i.e. of its purity, on the scattering kinematics.


The role of miR-19b in the inhibition of endothelial cell apoptosis and its relationship with coronary artery disease.
The biological effects of microRNAs (miRNAs) and TNF-α in atherosclerosis have been widely studied. The circulating miR-17-92 cluster has been recently shown to be significantly downregulated in patients with injured vascular endothelium. However, it remains unclear whether the miR-17-92 cluster plays a significant role in vascular endothelial repair. The aim of this study was to investigate the relationship between the miR-17-92 cluster and TNF-α-induced endothelial cell apoptosis. We determined that the down-regulation of miR-19b level among patients with coronary artery disease was consistent with miRNA expression changes in endothelial cells following 24 h of TNF-α treatment. In vitro, the overexpression of miR-19b significantly alleviated the endothelial cells apoptosis, whereas the inhibition of miR-19b significantly enhanced apoptosis. The increased levels of Afap1 and caspase7 observed in our apoptosis model could be reduced by miR-19b, and this effect could be due to miR-19b binding 3'-UTRs of Afap1 and caspase7 mRNA. Therefore our results indicate that miR-19b plays a key role in the attenuation of TNF-α-induced endothelial cell apoptosis and that this function is closely linked to the Apaf1/caspase-dependent pathway.


Cysteine-Rich Antifungal Proteins from Filamentous Fungi are Promising Bioactive Natural Compounds in Anti-Candida Therapy.
The emerging number of life-threatening invasive fungal infections caused by drug-resistant Candida strains urges the need for the development and application of fundamentally new and safe antifungal strategies in the clinical treatment. Recent studies demonstrated that the extracellular cysteine-rich and cationic antifungal proteins (crAFPs) originating from filamentous fungi, and de novo designed synthetic peptide derivatives of these crAFPs provide a feasible basis for this approach. This mini-review focuses on the global challenges of the anti-Canidia therapy and on the crAFPs as potential drug candidates to overcome existing problems. The advantages and limitations in the use of crAFPs and peptide derivatives compared to those of conventional antifungal drugs will also be critically discussed.


Pediatric Asthma Is Associated With Poorer 3-Year Academic Achievement in Urban Elementary and Middle-School Students.
Asthma has been associated with worse academic performance in a single school year, yet this association may be magnified over time as students with asthma continue to fall behind. This study examined the relationship between asthma and standardized test performance aggregated across 3 school years, including whether performance varied by likelihood of having significant asthma. Data were from students in grades K-8 at 2 urban public schools in the Northeastern United States (2015-2018). Asthma was based on parent- and self-report and school health center records. Standardized test performance was assessed using Measures of Academic Progress (MAP) and Partnership for Assessment of Readiness for College and Careers (PARCC). Mixed effects linear and logistic regression models were used to evaluate the relationship between asthma and performance during 3 school years. Any asthma was associated with worse MAP performance across the 3 academic years. Students with the most significant asthma demonstrated worse performance on MAP and PARCC. Aggregating across 3 school years, students scored 3.17 points worse on MAP reading (95% confidence interval [CI]: 0.7-5.63; P = .012) and 3.56 points worse on MAP mathematics (95% CI: 0.52-6.6; P = .022); they had 48.8% (95% CI: 1.9%-73.2%; P = .044) and 58.0% (95% CI: 21%-78%; P = .007) lower odds of proficiency on PARCC English/Language Arts and Mathematics, respectively compared to those without asthma. The relationship between asthma and poorer academic achievement in 1 school year may be magnified over multiple years, particularly among those with more significant asthma. School-based asthma interventions may support academic growth and more equitable health outcomes.


The nucleoskeleton as a genome-associated dynamic 'network of networks'.
In the cytosol, actin polymers, intermediate filaments and microtubules can anchor to cell surface adhesions and interlink to form intricate networks. This cytoskeleton is anchored to the nucleus through LINC (links the nucleoskeleton and cytoskeleton) complexes that span the nuclear envelope and in turn anchor to networks of filaments in the nucleus. The metazoan nucleoskeleton includes nuclear pore-linked filaments, A-type and B-type lamin intermediate filaments, nuclear mitotic apparatus (NuMA) networks, spectrins, titin, 'unconventional' polymers of actin and at least ten different myosin and kinesin motors. These elements constitute a poorly understood 'network of networks' that dynamically reorganizes during mitosis and is responsible for genome organization and integrity.


Location of anterior knee pain affects load tolerance in isometric single leg knee extension.
To investigate relationships between load tolerance of single leg isometric knee extension and athlete reported knee pain location and severity during the single leg decline squat. Cross-sectional study. 175 college basketball athletes (99 women, 76 men) in Alberta, Canada participated at the start of the 2018-19 season. Knee pain location (dichotomized into focal/diffuse pain), and severity (numerical rating scale 0-10) were collected during the single leg decline squat. Athletes completed a standardized single leg isometric knee extension to determine load tolerance (defined by pain or reduced form). A quantile regression model was used to examine the association between load tolerance and pain location adjusting for sex, years played, body mass index and team. Athletes with diffuse pain had a significantly lower median load tolerance (-0.89 kg) than athletes without pain (95% confidence interval [-1.49, -0.29]; p = 0.003). Athletes with focal pain tolerated similar median loads (-0.42 kg) to those without pain (95% confidence interval [-1.17, 0.33]; p = 0.26). Higher knee pain severity was associated with a non-linear but consistent reduction in load tolerance (p < 0.001). Athlete-reported knee pain location during the single leg decline squat influenced load tolerance to isometric knee extension. Athletes with focal pain tolerated similar isometric loads to their pain free teammates. Clinicians should consider load selection of isometric knee extension for athletes with diffuse pain given their lower load tolerance. Future research should consider reporting pain location in addition to pain severity to differentiate clinical presentations and response to exercise.


Performance of discrete wavelet transform-based method in the detection of influenza outbreaks in Iran: An ecological study.
Timely detection of outbreaks is one of the main purposes of the health surveillance system. The presence of appropriate methods in the detection of outbreaks can have an important role in the timely detection of outbreaks. Because of the importance of this issue, this study aimed to assess the performance of discrete wavelet transform (DWT) based methods in detecting influenza outbreaks in Iran from January 2010 to January 2020. All registered influenza-positive virus cases in Iran from January 2010 to January 2010 were obtained from the FluNet web base tool, the World Health Organization website. The combination method that includes DWT and Shewhart control chart was used in this study. All analyses were performed using MATLAB software version 2018a Stata software version 15. The Mean ± SD and median of reported influenza cases from January 2010 to January 2020 was 36 ± 108 and four cases per week. The combination of the DWT and Shewhart control chart with K = 0.25 had the most sensitivity. The most specificity in the detection of nonoutbreak days was seen in the combination of DWT and Shewhart control chart with K = 1.5, K = 1.75, and K = 2, respectively. The combination of DWT and Shewhart control chart with K = 0.5 had the best performance in the detection of outbreaks (sensitivity = 0.64, specificity: 0.90, Youden index: 0.54, and area under the curve [AUC]: 0.77). The DWT-based method in detecting influenza outbreaks has acceptable performance, but it is recommended that this method's performance be assessed in detecting outbreaks of other infectious diseases.


A two-session psychological intervention for siblings of pediatric cancer patients: a randomized controlled pilot trial.
Since siblings of pediatric cancer patients are at risk for emotional, behavioral, and social problems, there is considerable interest in development of early psychological interventions. This paper aimed at evaluating the effectiveness of a two-session psychological intervention for siblings of newly diagnosed pediatric cancer patients. Thirty siblings age 6-17 years were randomly assigned to an intervention group or an active control group with standard psychosocial care. The manualized intervention provided to siblings in the first 2 months after the cancer diagnosis of the ill child included medical information, promotion of coping skills, and a psychoeducational booklet for parents. At 4 to 6 weeks, 4 months, and 7 months after the diagnosis, all siblings and their parents completed measures (from standardized instruments) of social support, quality of life, medical knowledge, posttraumatic stress symptoms, and anxiety. At follow-up siblings in the intervention group showed better psychological well-being, had better medical knowledge, and reported receiving social support from more people. However, the intervention had no effects on posttraumatic stress symptoms and anxiety. The results of this pilot trial suggest that a two-session sibling intervention can improve siblings' adjustment, particularly psychological well-being, in the early stage after a cancer diagnosis. ClinicalTrials.gov NCT00296907.


Overexpression of metabolic markers HK1 and PKM2 contributes to lymphatic metastasis and adverse prognosis in Chinese gastric cancer.
Hexokinase 1 (HK1) and pyruvate kinase M2 (PKM2) are two key regulators in glycosis and oncogenic markers in cancers. In the present study, we investigated the expression profile by Western blotting and immunohistochemistry and determined their prognostic values in the gastric cancer. Expression of HK1 and PKM2 was remarkably increased in gastric cancer tissues and was significantly associated lymphatic metastasis and advanced TNM staging. In the COX regression model, HK1 and TNM stage were analyzed as adverse prognostic indicators in gastric cancer. Furthermore, patients with HK1 expression showed remarkable shorter survival duration in both lymphatic metastasis cohort and advanced staging cohort. Our results suggest that overexpression of PKM2 and HK1, especially the latter, significantly associates with lymphatic metastasis, advanced clinical staging and unfavorable prognosis in gastric cancer.


A screening method for detecting iron reducing wood-rot fungi.
A plate assay using the Fe(II) selective dye, ferrozine, for detecting wood-rot fungi with Fe(III) reductive abilities, was developed. The assay is fast, simple and, in most cases, more sensitive than the corresponding liquid medium test. The brown rot fungi, Gloeophyllum trabeum and Laetiporeus sulphureus, displayed higher iron reductive capabilities than white rot fungi, Trametes versicolor, Ganoderma australe and Ceriporiopsis subvermispora.


Mechanistic insight into the RNA-stimulated ATPase activity of tick-borne encephalitis virus helicase.
The helicase domain of nonstructural protein 3 (NS3H) unwinds the double-stranded RNA replication intermediate in an ATP-dependent manner during the flavivirus life cycle. While the ATP hydrolysis mechanism of Dengue and Zika viruses NS3H has been extensively studied, little is known in the case of the tick-borne encephalitis virus NS3H. We demonstrate that ssRNA binds with nanomolar affinity to NS3H and strongly stimulates the ATP hydrolysis cycle, whereas ssDNA binds only weakly and inhibits ATPase activity in a noncompetitive manner. Thus, NS3H is an RNA-specific helicase, whereas DNA might act as an allosteric inhibitor. Using modeling, we explored plausible allosteric mechanisms by which ssDNA inhibits the ATPase via nonspecific binding in the vicinity of the active site and ATP repositioning. We captured several structural snapshots of key ATP hydrolysis stages using X-ray crystallography. One intermediate, in which the inorganic phosphate and ADP remained trapped inside the ATPase site after hydrolysis, suggests that inorganic phosphate release is the rate-limiting step. Using structure-guided modeling and molecular dynamics simulation, we identified putative RNA-binding residues and observed that the opening and closing of the ATP-binding site modulates RNA affinity. Site-directed mutagenesis of the conserved RNA-binding residues revealed that the allosteric activation of ATPase activity is primarily communicated via an arginine residue in domain 1. In summary, we characterized conformational changes associated with modulating RNA affinity and mapped allosteric communication between RNA-binding groove and ATPase site of tick-borne encephalitis virus helicase.


A possible mechanism contributing to the synergistic action of vasotocin (VT) and corticotropin-releasing hormone (CRH) receptors on corticosterone release in birds.
Arginine vasotocin (AVT) and corticotropin-releasing hormone (CRH) are two neuronal regulators in the hypothalamic-pituitary-adrenal (HPA) axis that modulate biological responses to stress in avian species. When AVT and CRH are administered together in vitro or in vivo, levels of adrenocorticotropic hormone (ACTH) or plasma corticosterone (CORT) are released, respectively, in a synergistic manner. The underlying mechanism of this greater than additive stress response was investigated by expressing the vasotocin receptor type 2 (VT2R) and CRH receptor type 1 (CRH-R1), both G-protein coupled receptors, in HeLa cells. Fluorescence resonance energy transfer (FRET) analysis provided the evidence for heterodimerization of the VT2R/CRH-R1 in the presence of their respective ligands, AVT and CRH. The VT2R and CRH-R1 were tagged at the C-terminal ends with either cyan fluorescent protein (CFP) or yellow fluorescent protein (YFP), and a VT2R chimera was constructed by replacing the fourth transmembrane region (TM4) of the VT2R with TM-IV of the β2-adrenergic receptor (β2AR). When VT2R/β2AR chimera and CRH-R1 were expressed in HeLa cells, heterodimerization was partly disrupted. Taken together, these data indicate that TM-IV of the VT2R may provide an important interface for effective receptor dimerization, suggesting that direct molecular interaction between VT2R and CRH-R1 receptors plays a role in mediating an enhanced interaction between these two receptors. Their interaction at the anterior pituitary level may potentiate the endocrine output of the avian HPA system.


Theoretical studies of structure, energetics and properties of Ca²⁺ complexes with alizarin glucoside.
The effective dissolution of calcium oxalate, the main component of kidney stones, is important in the treatment of nephrolithisis. Polyphenol glycosides constitute compounds supporting dissolution and inhibition of formation of stones. These moieties possess oxygen atoms which can interact with calcium cations. Density functional theory studies of interactions of polyphenol glycosides and Ca(2+) were performed to determine preferred structures and the role of polyphenol and carbohydrate parts in the formation of complexes. The determination of these properties may be useful in designing new complexes, effectively interacting with calcium compounds. In the present study we try to define factors influencing interaction energies and stabilization. The determined structures were divided according to coordination numbers. Obtained data indicate that for stronger interactions complexes maximize the number of O-Ca(2+) contacts.


The effects of working memory on brain-computer interface performance.
The purpose of the present study is to evaluate the relationship between working memory and BCI performance. Participants took part in two separate sessions. The first session consisted of three computerized tasks. The List Sorting Working Memory Task was used to measure working memory, the Picture Vocabulary Test was used to measure general intelligence, and the Dimensional Change Card Sort Test was used to measure executive function, specifically cognitive flexibility. The second session consisted of a P300-based BCI copy-spelling task. The results indicate that both working memory and general intelligence are significant predictors of BCI performance. This suggests that working memory training could be used to improve performance on a BCI task. Working memory training may help to reduce a portion of the individual differences that exist in BCI performance allowing for a wider range of users to successfully operate the BCI system as well as increase the BCI performance of current users.


Characterization of the binding epitope of ciprofloxacin bound to human serum albumin.
Aqueous solutions of ciprofloxacin in phosphate buffer were measured by NMR under physiological conditions. The chemical shifts differ substantially compared to earlier investigations at low pH or in DMSO. Protein binding experiments using saturation transfer were optimized to measure proton resonances of ciprofloxacin that are in close proximity to human serum albumin. The relative intensities were mapped on the molecule to define the binding epitope. According to this methodology the cyclopropane ring and the chinolon ring constitute the binding epitope. Competition experiments with increasing amounts of salicylic acid did not change the saturation transfer to the ciprofloxacin protons indicating at least two different binding sites.


Weekly and yearly rhythms in plasma fibrinogen in hospitalized male military veterans.
The variation in plasma fibrinogen level demonstrating prominent circaseptan and circannual cycles is clinically relevant. There is a correlation between increasing level of fibrinogen and other hemostatic factors and risk of myocardial infarction and sudden death. The circaseptan and circannual cycles in fibrinogen concentration described in this study may help to explain further the variation in frequency of coronary events. Furthermore, the recent demonstration of a circadian pattern in the efficacy of tissue plasminogen activator, with peak efficacy occurring at 2000 hours--10 hours after the peak incidence of myocardial infarction--implies that further patterns to coronary artery syndromes may be predicted and the treatment efficacy may rely on demonstrated circaseptan and circannual cycles of these events.


Glutathione-S-transferase profiles in the emerald ash borer, Agrilus planipennis.
The emerald ash borer, Agrilus planipennis Fairmaire is a recently discovered invasive insect pest of ash, Fraxinus spp. in North America. Glutathione-S-transferases (GST) are a multifunctional superfamily of enzymes which function in conjugating toxic compounds to less toxic and excretable forms. In this study, we report the molecular characterization and expression patterns of different classes of GST genes in different tissues and developmental stages plus their specific activity. Multiple sequence alignment of all six A. planipennis GSTs (ApGST-E1, ApGST-E2, ApGST-E3, ApGST-O1, ApGST-S1 and ApGST-μ1) revealed conserved features of insect GSTs and a phylogenetic analysis grouped the GSTs within the epsilon, sigma, omega and microsomal classes of GSTs. Real time quantitative PCR was used to study field collected samples. In larval tissues high mRNA levels for ApGST-E1, ApGST-E3 and ApGST-O1 were obtained in the midgut and Malpighian tubules. On the other hand, ApGST-E2 and ApGST-S1 showed high mRNA levels in fat body and ApGST-μ1 showed constitutive levels in all the tissues assayed. During development, mRNA levels for ApGST-E2 were observed to be the highest in feeding instars, ApGST-S1 in prepupal instars; while the others showed constitutive patterns in all the developmental stages examined. At the enzyme level, total GST activity was similar in all the tissues and developmental stages assayed. Results obtained suggest that A. planipennis is potentially primed with GST-driven detoxification to metabolize ash allelochemicals. To our knowledge this study represents the first report of GSTs in A. planipennis and also in the family of wood boring beetles.


Population-based assessment of the risk of primary cesarean delivery due to excess prepregnancy weight among nulliparous women delivering term infants.
To estimate the risk of cesarean delivery due to excess prepregnancy body mass index (BMI) in a multistate, US population-based sample. We analyzed data from the population-based Pregnancy Risk Assessment Monitoring System (PRAMS) on 24,423 nulliparous women with single, term infants delivered between 1998 and 2000 in 19 states. We calculated BMI from self-reported weight and height. We assessed interactions between prepregnancy BMI and other risk factors. We estimated weighted relative risks and 95% confidence intervals for the association between prepregnancy BMI and cesarean section from multiple logistic regression models adjusting for demographic and medical risk factors from the PRAMS questionnaire or birth certificates. The incidence of cesarean delivery increased with increased prepregnancy BMI, from 14.3% (0.8 standard error (SE)) for lean women (BMI < 19.8) to 42.6% (2.0 SE) for very obese women (BMI > or = 35). The risk of cesarean section differed by presence of any medical, labor and/or delivery complication. Among women with any complication, the estimated adjusted RR for cesarean delivery was 1.1 (95% confidence interval (CI) 1.0-1.2) among overweight women, 1.3 (95% CI 1.1-1.4) among obese women, and 1.4 (95% CI 1.2-1.6) among very obese women compared with normal weight women. Among women without any complications, the estimated adjusted RR was 1.4 (95% CI 1.0-1.8) among overweight women, 1.5 (95% CI 1.1-2.1) among obese women, and 3.1 (95% CI 2.3-4.8) among very obese women. Excess prepregnancy weight increases the risk of cesarean delivery among nulliparous women giving birth to single, term infants, especially among very obese women without any complications.


Synthesis and anti-CVB3 activity of 4-amino acid derivative substituted pyrimidine nucleoside analogues.
Seven novel 4-amino acid derivative substituted pyrimidine nucleoside analogues were designed, synthesized, and tested for their anti-CVB3 activity. Initial biological studies indicated that among these 4-amino acid derivative substituted pyrimidine nucleoside analogues, 4-N-(2'-amino-glutaric acid-1'-methylester)-1-(2'- deoxy-2'-β-fluoro-4'-azido)-furanosyl-cytosine 2 exhibited the most potent anti-CVB activity (IC50 = 9.3 μM). The cytotoxicity of these compounds has also been assessed. The toxicity of compound 2 was similar to that of ribavirin.


Aging and osteoarthritis: Central role of the extracellular matrix.
Osteoarthritis (OA), is a major cause of severe joint pain, physical disability and quality of life impairment in the aging population across the developed and developing world. Increased catabolism in the extracellular matrix (ECM) of the articular cartilage is a key factor in the development and progression of OA. The molecular mechanisms leading to an impaired matrix turnover have not been fully clarified, however cellular senescence, increased expression of inflammatory mediators as well as oxidative stress in association with an inherently limited regenerative potential of the tissue, are all important contributors to OA development. All these factors are linked to and tend to be maximized by aging. Nonetheless the role of aging in compromising joint stability and function in OA has not been completely clarified yet. This review will systematically analyze cellular and structural changes taking place in the articular cartilage and bone in the pathogenesis of OA which are linked to aging. A particular emphasis will be placed on age-related changes in the phenotype of the articular chondrocytes.


Histoplasmosis capsulati and duboisii in Europe: the impact of the HIV pandemic, travel and immigration.
The present report describes a fatal case of imported AIDS-related disseminated histoplasmosis capsulati infection associated with multiple coexisting infections, diagnosed with cultural recovery of Histoplasma capsulatum var. capsulatum with a commercial radiometric Mycobacterium medium. The epidemiological and clinical features of histoplasmosis capsulati and duboisii in Europe are reviewed by examining also 69 documented cases of Histoplasma capsulatum var. capsulatum infection (25 in AIDS patients) and 17 cases of Histoplasma capsulatum var. duboisii infection (3 in HIV-infected patients), described since 1980. This draws special attention to the role played during recent years by the emergence of the HIV pandemic and the progressive intensification of travel and immigration as risk factors for this disease in our continent. AIDS patients, who are prone to multiple concurrent opportunistic infections which may share clinical and laboratory features with each other and with other HIV-associated diseases, represent the most relevant current group at risk for severe disseminated histoplasmosis, which may come to medical attention far from their place of origin.


Shifts in flowering phenology in response to spring temperatures in eastern Tennessee.
Plant phenological shifts are among the clearest indicators of the effects of climate change. In North America, numerous studies in the northeastern United States have demonstrated earlier spring flowering compared to historical records. However, few studies have examined phenological shifts in the southeastern United States, a highly biodiverse region of North America characterized by dramatic variations in abiotic conditions over small geographic areas. We examined 1000+ digitized herbarium records along with location-specific temperature data to analyze phenological shifts of 14 spring-flowering species in two adjacent ecoregions in eastern Tennessee. Spring-flowering plant communities in the Blue Ridge and the Ridge and Valley ecoregions differed in their sensitivity to temperature; plants in the Ridge and Valley flower 0.73 days earlier/°C on average compared to 1.09 days/°C for plants in the Blue Ridge. Additionally, for the majority of species in both ecoregions, flowering is sensitive to spring temperature; i.e., in warmer years, most species flowered earlier. Despite this sensitivity, we did not find support for community-level shifts in flowering within eastern Tennessee in recent decades, likely because increases in annual temperature in the southeast are driven primarily by warming summer (rather than spring) temperatures. These results highlight the importance of including ecoregion as a predictor in phenological models for capturing variation in sensitivity among populations and suggest that even small shifts in temperature can have dramatic effects on phenology in response to climate in the southeastern United States.


Bee visitation rates to trees of Prockia crucis differing in flower number.
Annual flower production ranged over four orders of magnitude among individuals of the tropical tree Prockia crucis (Flacourtiaceae), but the number of visits per flower by bees did not increase with flower number. In a population in Jalisco, México, the trees flower for about one week each year, offering only pollen to the bees (mostly solitary species). In a small group of trees, the number of visits per flower was less on trees with greater flower production but in a large group visitation did not vary between trees. Pollen flow probably was not directed from large to small trees or vice versa, because the number of flowers per tree did not determine the schedule of visits. The ratio of pollinators to pollen thieves decreased rapidly through the day, while individuals of both groups foraged more rapidly. Most bee species were rare, and only a small subset of medium-sized to large bees were effective pollinators. Large and small groups of trees differed in the relationship between individual flower crop and abundance and diversity of both pollinators and thieves.


Prevalence and effects of suicidal ideation diagnosis code position in claims on readmission rate estimates.
Suicidal ideation (SI) is a major health concern in children, adolescents, and young adults (CAYA) population. Inaccurate estimates of SI-related hospital readmission rates may contribute to inappropriate allocation of resources for the prevention of future readmissions. The estimation of these readmission rates using claims data may be sensitive to the diagnosis code position used to establish analytic cohorts. To examine the prevalence and effects of SI diagnosis code position in claims on 30-day readmission rates using the Nationwide Readmissions Database (NRD). This was a cross-sectional study using the NRD (2010-2015). We established six cohorts of hospitalized CAYA (5-24 years old) with a diagnosis of SI based on different combinations of SI diagnosis code (ICD-9 code V62.84) positions in claims. Thirty-day hospital readmission rates following an index SI discharge were estimated for each cohort. We tested the null hypothesis that hospital readmission rates following an index SI discharge are not sensitive to diagnosis code positions using a test for equality of proportions between the predefined SI cohorts. The prevalence of SI diagnosis codes increased yearly from 2.9% in 2010 to 5.8% in 2015. SI hospital readmission rates ranged from 0 to 41.1 per 1000 index events based on cohort definitions (i.e. diagnosis code positions). We rejected the null hypothesis that SI-related readmission rates are not sensitive to diagnosis code positions. SI-related readmission rate estimates are sensitive to SI diagnosis code positions. Determining appropriate diagnostic positions can further improve readmission analyses for SI and its applications in healthcare policies.


Impact of bone mineral density in reducing fracture risk in patients receiving alendronate plus alfacalcidol therapy.
Changes in bone mineral density (BMD) are a potential surrogate marker for fracture endpoints in clinical trials. However little is known whether the increase in BMD in response to combination treatment with alendronate plus alfacalcidol is associated with fracture risk reduction. We aimed to evaluate the impact of BMD on fracture risk in osteoporosis patients, using the data from the randomized clinical trial comparing alendronate plus alfacalcidol with alendronate alone. We selected 412 patients with two or more prevalent vertebral fractures and who had BMD measurements at baseline and after 6, 12, and/or 24 months out of 2022 patients from the database of the Japanese Osteoporosis Intervention Trial. Patients in this subset who received combination treatment with alendronate plus alfacalcidol had shown a lower risk of fracture than patients treated with alendronate alone. We used Poisson regression model analysis to calculate the proportion of treatment effect (PTE) that was attributable to BMD increases in patients receiving combination treatment. The highest PTE attributable to changes in BMD was 1.2% in patients with a BMD increase of 3% or more in the lumbar spine. For BMD measurements of the radius, the highest PTE was 2.8% with a BMD increase of 0% or more. For BMD measurements of the metacarpal bone, the highest PTE was 1.2% with a BMD increase of 3% or more. In patients with a BMD greater than or equal to 70% of the young adult mean in the lumbar spine, the PTE attributable to BMD was 0.2%. In patients with a BMD greater than or equal to 70% of the young adult mean in the radius, the PTE attributable to BMD was 0.3%. The additional effects of alfacalcidol in reducing fracture risk do not likely result from increased BMD; other mechanisms remain a possibility.


Study on the process of intervertebral disc disease by the theory of continuum damage mechanics.
Recently, more and more people suffer from low back pain triggered by lumbar degenerative disc disease. The mechanical factor is one of the most significant causes of disc degeneration. This study aims to explore the biomechanical responses of the intervertebral disc, and investigate the process of disc injury by the theory of continuum damage mechanics. A finite element model of the L4-L5 lumbar spine was developed and validated. The model not only considered changes in permeability coefficient with strain, but also included physiological factors such as osmotic pressure. Three loading conditions were simulated: (A) static loads, (B) vibration loads, (C) injury process. The simulation results revealed that the facet joints shared massive stresses of the intervertebral discs, and prevented excessive lumbar spine movement. However, their asymmetrical position may have led to degeneration. The von Mises stress and pore pressure of annulus fibrosus showed significantly different trends under static loads and vibration loads. The von Mises stress of nucleus pulposus was not sensitive to vibration loads, but its pore pressure was conspicuously influenced by vibration loads. The injury first appeared at the posterior centre, and then, it gradually expanded along the edge of the intervertebral disc. With an increase in the loading steps, the damage rate of the intervertebral disc increased logarithmically. The variation in the biomechanical performance of the intervertebral disc could be attributed to the periodic movement of internal fluids. This study might be helpful for understanding the mechanism of intervertebral disc degeneration.


Peripheral nerve damage associated with administration of taxanes in patients with cancer.
Peripheral neuropathy is a well recognized toxicity of taxanes, usually resulting to dose modification and changes in the treatment plan. Taxanes produce a symmetric, axonal predominantly sensory distal neuropathy with less prominent motor involvement. A "dying back" process starting from distal nerve endings followed by effects on Schwann cells, neuronal body or axonal transport changes and a disturbed cytoplasmatic flow in the affected neurons is the most widely accepted mechanism of taxanes neurotoxicity. The incidence of taxanes-induced peripheral neuropathy is related to causal factors, such as single dose per course and cumulative dose and risk factors including treatment schedule, prior or concomitant administration of platinum compounds or vinca alcaloids, age and pre-existing peripheral neuropathy of other causes. The most reliable method to assess taxanes neurotoxicity is by clinical examination combined with electrophysiological evaluation. There is currently no effective symptomatic treatment for paclitaxel-associated pain, myalgias and arthralgias. Tricyclic antidepressants and anticonvulsants have been used as symptomatic treatment of neurotoxicity with some measure of success. Therefore, new approaches for prophylaxis against taxanes-induced peripheral neuropathy are needed. Several neuroprotective agents including, thiols, neurotrophic factors, and antioxidants hold promise for their ability to prevent neurotoxicity resulting from taxanes exposure. However, further confirmatory trials are warranted on this important clinical topic. This review critically looks at the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of taxanes-induced peripheral neuropathy. We also highlight areas of future research.


Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage.
To examine the effects of dydrogesterone on the production of Th1 and Th2 cytokines by lymphocytes from women undergoing unexplained recurrent spontaneous miscarriage (RSM). Controlled prospective, clinical study conducted in a maternity hospital and a university-based immunology laboratory. Faculty of Medicine, Kuwait University and Kuwait Maternity Hospital. Thirty women with unexplained RSM. Peripheral blood mononuclear cells (PBMC) from women with unexplained RSM were isolated from venous blood by density gradient sedimentation and stimulated with phytohaemagglutinin (PHA). Culture supernatants assayed for interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-6 and IL-10 by ELISA. Levels of the progesterone-induced blocking factor (PIBF) were also measured. Cytokine production in the presence and absence of progesterone and dydrogesterone. Dydrogesterone significantly inhibited the production of the Th1 cytokines IFN-gamma (P= 0.0001) and TNF-alpha (P= 0.005) and induced an increase in the levels of the Th2 cytokines IL-4 (P= 0.03) and IL-6 (P= 0.017) resulting in a substantial shift in the ratio of Th1/Th2 cytokines. The effect of dydrogesterone was blocked by the addition of the progesterone-receptor antagonist mifepristone, indicating that dydrogesterone was acting via the progesterone receptor. Dydrogesterone induced the production of PIBF. Dydrogesterone inhibits the production of the Th1 cytokines IFN-gamma and TNF-alpha from lymphocytes and up-regulates the production of the Th2 cytokines IL-4 and IL-6, inducing a Th1 to Th2 cytokine shift.


Segmental ("floating") lumbar spine fusions.
A traditional teaching in orthopaedic surgery has been that, in cases of fusion for L4-5 discopathy or instability, one must include the lumbosacral joint. There is nothing in the literature to support this time-honored dictum. The senior author, among others, has rejected this concept; and, the authors are, therefore, in a position to present a 32-year experience with segmental or "floating" fusion. Two hundred six floating fusions were performed, of which 184 were available for follow-up. Of these, 83.7% achieved "Excellent" or "Good" results; 15.2% were rated "Fair"; and 2% were rated "Poor." Only five patients (2.7%) had subsequent disc herniation at the lumbosacral level necessitating discectomy and extension of fusion to incorporate the sacrum.


A new hybrid fuzzy time series model with an application to predict PM10 concentration.
Fuzzy time series (FTS) forecasting models show a great performance in predicting time series, such as air pollution time series. However, they have caused major issues by utilizing random partitioning of the universe of discourse and ignoring repeated fuzzy sets. In this study, a novel hybrid forecasting model by integrating fuzzy time series to Markov chain and C-Means clustering techniques with an optimal number of clusters is presented. This hybridization contributes to generating effective lengths of intervals and thus, improving the model accuracy. The proposed model was verified and validated with real time series data sets, which are the benchmark data of actual trading of Taiwan Stock Exchange Capitalization Weighted Stock Index (TAIEX) and PM10 concentration data from Melaka, Malaysia. In addition, a comparison was made with some existing fuzzy time series models. Furthermore, the mean absolute percentage error, mean squared error and Theil's U statistic were calculated as evaluation criteria to illustrate the performance of the proposed model. The empirical analysis shows that the proposed model handles the time series data sets more efficiently and provides better overall forecasting results than existing FTS models. The results prove that the proposed model has greatly improved the prediction accuracy, for which it outperforms several fuzzy time series models. Therefore, it can be concluded that the proposed model is a better option for forecasting air pollution parameters and any kind of random parameters.


Type III mixed cryoglobulinemia associated with digital necrotic ulcer successfully treated with intermittent intravenous pulse cyclophosphamide--a case report.
Cryoglobulinemic vasculitis is an immune complex-mediated vasculitis predominantly affecting small vessels. The authors report an 18-year-old woman with painful digital necrotic ulcer due to type III cryoglobulinemic vasculitis on the basis of systemic lupus erythematosus. Serum protein electrophoresis and immunoelectrophoresis demonstrated a polyclonal peak of the immunoglobulin Glambda (IgGlambda) and IgMlambda type. The patient was successfully treated with intermittent intravenous pulse cyclophosphamide.


Guide RNA-binding complex from mitochondria of trypanosomatids.
In the mitochondria of trypanosomatids, the majority of mRNAs undergo massive uracil-insertion/deletion editing. Throughout the processes of pre-mRNA polyadenylation, guide RNA (gRNA) uridylylation and annealing to mRNA, and editing reactions, several multiprotein complexes must engage in transient interactions to produce a template for protein synthesis. Here, we report the identification of a protein complex essential for gRNA stability. The gRNA-binding complex (GRBC) interacts with gRNA processing, editing, and polyadenylation machineries and with the mitochondrial edited mRNA stability (MERS1) factor. RNAi knockdown of the core subunits, GRBC1 and GRBC2, led to the elimination of gRNAs, thus inhibiting mRNA editing. Inhibition of MERS1 expression selectively abrogated edited mRNAs. Homologous proteins unique to the order of Kinetoplastida, GRBC1 and GRBC2, form a stable 200 kDa particle that directly binds gRNAs. Systematic analysis of RNA-mediated and RNA-independent interactions involving the GRBC and MERS1 suggests a unified model for RNA processing in the kinetoplast mitochondria.


Olfaction: it makes a world of scents.
Mutations in odorant receptor genes predict olfactory perception of common compounds in foods and flowers. Through recombination they can generate extensive combinatorial variation in sensory ability among individuals.


Cell cycle-dependent Adriamycin uptake in Chinese hamster cells.
Adriamycin fluorescence was measured by flow cytometry after exposing synchronized Chinese hamster (line CHO) cells to a fixed dose of adriamycin (ADR). Three synchrony methods were used: mitotic selection, isoleucine-deficient culture and pretreatment with low doses of ADR. Approximately a 1.6- to 2-fold increase in ADR fluorescence intensity was observed for cells in G2 + M compared to cells in G1. An increase in ADR fluorescence was also noted for cell populations exhibiting a G2 block after pretreatment with low-dose ADR. No significant difference in fluorescence intensity was observed for G1 cell populations with two different volume distributions. Results suggest that the magnitude of ADR fluorescence is affected by the cell cycle distribution and that cellular susceptibility to drug-induced cytokinetic changes during exposure must also be taken into consideration when measuring ADR uptake.


Prospective analysis of liver biopsies before and after methotrexate therapy in rheumatoid patients.
The significance of hepatic changes in methotrexate-treated RA patients is unclear at this time. In our group of RA patients, there was a slight increase in the incidence of triaditis and fat during methotrexate therapy. Disease duration greater than or equal to 10 years was associated with increased hepatic triaditis before treatment. Age greater than 50 years was associated with increased hepatic fat before and after treatment. It appears that patients' ages and duration of underlying RA account for some changes, independent of methotrexate therapy. Several of our patients changed from higher to lower histologic grade or had an apparent decrease in fibrosis, fat, or triaditis on the pathologists' reports and the blind readings of the repeat biopsies. This may be explained by sampling error. More importantly, some of these changes may not be of clinical significance. One report of methotrexate-induced cirrhosis in patients with psoriasis demonstrated that in all but one of 14 patients who continued receiving methotrexate the cirrhosis decrease or did not progress. This may also be true of the hepatic fibrosis seen in RA after methotrexate treatment. In this study, there did not appear to be changes seen on pretreatment liver biopsy that were predictive of subsequent fibrosis or cirrhosis. Our data indicate that pretreatment biopsy is unwarranted in a population similar to ours. However, our practice has been to try to avoid methotrexate in patients with diabetes, prior liver disease, alcoholism, or obesity because of previous reports suggesting that these patients are at increased risk for the development of cirrhosis. Only the above-mentioned patient, eventually diagnosed as having cirrhosis, might have been handled differently. Including the study, none of the approximately 700 RA patients in the literature having liver biopsies after methotrexate therapy have developed cirrhosis consequent to its use. Most of these had received a total dose of approximately 1,500 mg in small weekly doses, and alcohol was prohibited. Below this cumulative dose the risk of clinically significant liver damage in carefully selected patients is very low. In view of this experience, the recommendation that RA patients have liver biopsies after 1,500 mg of methotrexate (a holdover from the psoriasis literature) may be too conservative in low-risk RA patients, provided methotrexate is administered weekly and alcohol is prohibited. Recognizing that the absolute need for biopsy is unproven, a more realistic milestone for those choosing biopsy might be after each 2,000 to 2,500 mg.(ABSTRACT TRUNCATED AT 400 WORDS)


[Angiotensin II-acetylcholine interaction on the mechanical response of the isolated rat stomach].
This research was carried on denervated isolated rat stomach. Mechanical response to Ach treated with three different ATN II concentrations was recorded. No competitive antagonism was observed so that no common receptor can be supposed. The apparent noncompetitive antagonism may be ascribed to the action of ATN II on P and T Ca++ activating systems.


Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. Intravenous or intramuscular/subcutaneous naloxone in opioid overdose.
A short cut review was carried out to establish whether intramuscular/subcutaneous naloxone is better than intravenous naloxone in opioid overdose. Altogether 185 papers were found using the reported search, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.


Hodgkin's disease in children.
Fifty-nine children with Hodgkin's disease were seen over a 34-year period. Compared with Hodgkin's disease in adults, there was an increased male incidence, especially in the younger children. This was associated with an increased male incidence of lymphocyte-predominant histology. Forty-six patients underwent lymphography as part of their staging, and 13 had staging laparotomies. The 5-year survival for the entire group was 85%, with a median survival of 10 years. Response to radiotherapy in children with Stages I-IIIA disease was: 12 children treated with involved-field radiotherapy after inadequate clinical staging had a 3-year remission rate of 13%, and a median length of remission of 18 months; 24 children treated with extended-field radiotherapy after adequate clinical staging, including lymphography, had a 3-year remission rate of 72%, and a median duration of remission not yet reached; 3 children treated with elective local radiotherapy for Stage IA disease after intensive clinical staging remain in complete remission for periods of up to 34 months. Eight out of 10 children with Stages IIIB-IV disease, treated with combination chemotherapy, achieved complete remission with a 3-year remission rate of 70%; 7 children treated with combination chemotherapy following relapse after radiotherapy all achieved complete remission with a 3-year complete remission rate of 66%. Thirteen children underwent laparotomy and splenectomy as a staging procedure. Five were found to have intra-abdominal disease, including 4 with splenic involvement. These results show that there is no place for involved-field radiotherapy after inadequate clinical staging, in the management of childhood Hodgkin's disease. Extended-field radiotherapy after adequate staging, and combination chemotherapy, produce results which are as good as those for adults, but the benefits of these treatments and of staging laparotomy must be balanced against the possible complications when they are used in children. These problems are discussed and a scheme of management is proposed.


Treatment of Extensive Gluteus Muscle Tears With Transosseous Fixation and a Nonresorbable Collagen Patch.
Extensive tearing of the gluteus muscles (spontaneous or subsequent to hip arthroplasty) is difficult to treat. We are carrying out osseous fixation with securement of the suture anchor by a nonresorbable collagen patch. The objective of this study is to examine the follow-up data of 30 patients and to assess whether the clinical outcomes depended on the extent of the fatty degeneration of the gluteus medius. Thirty patients (28 female and 2 male) with a mean age of 76.8 ± 4.3 years (68-83 years) were followed for a mean of 46.8 ± 23.1 months (24-101 months). Pain improved significantly from a preoperative visual analog scale score of 7.0 ± 1.52 (6-10) to 0.83 ± 0.77 (0-3) 24-month postoperative. The gluteus medius muscle force increased from 2.09 ± 0.81 to 3.3 ± 0.78 using the British Medical Research Council Scale. All patients exhibited a severe limp before the operation. Postoperatively, only 5 patients had a severe limp, while 14 exhibited a mild limp and 11 no limp at all. The modified Harris Hip Score increased from a preoperative value of 44.5 ± 4.2 (26-66) to a value of 81.1 ± 7.79 (60-100) 24-month postoperative. The functional results were dependent on the level of fatty degeneration of the muscle. The first results for this surgical technique appear to be very promising for the treatment of extensive tearing of the gluteus musculature that has a degree of fatty degeneration less than 75%.


IL23R haplotypes provide a large population attributable risk for Crohn's disease.
The IL-23 pathway plays a pivotal role in the development of chronic mucosal inflammation seen in the inflammatory bowel diseases. Multiple studies have now established the contribution of the interleukin 23 receptor gene (IL23R) to Crohn's disease (CD) risk in general and of the IL23R R381Q variant in particular. The aim of this work was to estimate the total contribution of this gene to CD risk test using a haplotype approach. In all, 763 CD subjects and 254 controls were genotyped for single nucleotide polymorphisms in the IL23R gene using Illumina and ABI methods. Haplotypes were assigned using PHASEv2 and tested for association with CD by chi-square and permutation. Haplotypes with both increased and decreased risk for CD were observed in 2 of the 4 observed blocks (Block 2 H1: 55.4% control, 64% CD, P = 0.019; H2: 64.5% control, 54.4% CD, P = 0.006; Block 3 H1: 55.8% control, 64.4% CD, P = 0.013; H2: 47.0% control, 36.6% CD, P = 0.001). The population attributable risk for these haplotypes was substantially larger than that estimated for the IL23R R381Q variant (Block 2 H1 and block 3 H1 approximately 20%, compared with approximately 4% for Block 3 H6, containing the variant). These observations suggest that IL23R makes a substantial contribution to CD susceptibility, larger than that estimated from the population frequency of the R381Q variant. These observations also support the expectation that finding "hits" from genomewide association studies will be but an important chapter in the story of unraveling the genetic contribution to CD, rather than the final chapter that brings clarity to all the plot twists of a complicated story.


Tachykinins mediate non-adrenergic, non-cholinergic excitatory neurotransmission to the hamster ileum via NK1 and NK2 receptors.
The present study was designed to investigate Substance P (SP) and a related tachykinin, Neurokinin A (NKA), contributions to the excitatory neurotransmission to the circular smooth muscle of the hamster ileum. In the presence of atropine (0.5 microM), guanethidine (3 microM) and NG-nitro-L-arginine methyl ester (L-NAME) (200 microM), electrical field stimulation (EFS) evoked a non-adrenergic, non-cholinergic (NANC) excitatory junction potential (EJP) and contraction of circular smooth muscle. Applications of SP and NKA produced depolarizing and contractile responses in a concentration-dependent fashion. The EJP and contraction were almost abolished by the non-specific tachykininergic antagonist, spantide (3 microM). Application of SP antagonist, L-732,138, (1 microM) markedly inhibited EJP (82.5%) and contraction (68.9%) and completely blocked excitatory responses produced by exogenous application of SP. While application of NKA antagonist, SR48968 (1 microM) completely blocked the depolarising and contractile responses to NKA, it only slightly inhibited those to EFS (17.2% and 31.4% respectively). These results provide evidence that, in the circular muscle of hamster ileum, endogenous tachykinins are the main NANC excitatory neurotransmitters and their action is mediated by both NK1 and NK2 receptors.


CryoGrid-PIXUL-RNA: high throughput RNA isolation platform for tissue transcript analysis.
Disease molecular complexity requires high throughput workflows to map disease pathways through analysis of vast tissue repositories. Great progress has been made in tissue multiomics analytical technologies. To match the high throughput of these advanced analytical platforms, we have previously developed a multipurpose 96-well microplate sonicator, PIXUL, that can be used in multiple workflows to extract analytes from cultured cells and tissue fragments for various downstream molecular assays. And yet, the sample preparation devices, such as PIXUL, along with the downstream multiomics analytical capabilities have not been fully exploited to interrogate tissues because storing and sampling of such biospecimens remain, in comparison, inefficient. To mitigate this tissue interrogation bottleneck, we have developed a low-cost user-friendly system, CryoGrid, to catalog, cryostore and sample tissue fragments. TRIzol is widely used to isolate RNA but it is labor-intensive, hazardous, requires fume-hoods, and is an expensive reagent. Columns are also commonly used to extract RNA but they involve many steps, are prone to human errors, and are also expensive. Both TRIzol and column protocols use test tubes. We developed a microplate PIXUL-based TRIzol-free and column-free RNA isolation protocol that uses a buffer containing proteinase K (PK buffer). We have integrated the CryoGrid system with PIXUL-based PK buffer, TRIzol, and PureLink column methods to isolate RNA for gene-specific qPCR and genome-wide transcript analyses. CryoGrid-PIXUL, when integrated with either PK buffer, TRIzol or PureLink column RNA isolation protocols, yielded similar transcript profiles in frozen organs (brain, heart, kidney and liver) from a mouse model of sepsis. RNA isolation using the CryoGrid-PIXUL system combined with the 96-well microplate PK buffer method offers an inexpensive user-friendly high throughput workflow to study transcriptional responses in tissues in health and disease as well as in therapeutic interventions.


Cognitive behavioral therapy combined with "empathy nursing" model on recurrent depressive disorder.
To explore the effects of cognitive behavioral therapy combined with "empathy nursing" model on recurrent depressive disorder. The clinical data of 80 patients with recurrent depressive disorder were analyzed retrospectively. Among them, 40 patients receiving routine treatment and nursing were regarded as the control group, and 40 patients receiving additional cognitive behavioral therapy combined with "empathy nursing" on the basis of routine treatment and nursing were considered as the observation group. Total nursing compliance of the observation group was much higher than that of the control group throughout the intervention. After the intervention, the SES and GQOL scores were both increased, and the observation group had a more obvious increase. The SDSS, Pittsburgh sleep quality index (PSQI), Hamilton Depression (HAMD) and LOTCA scores were all decreased after the intervention, and the observation group had much lower scores. Total nursing satisfaction of the observation group was markedly higher than that of the control group. Additional cognitive behavioral therapy combined with "empathy nursing" model can effectively promote the self-esteem and cognitive function, enhance nursing compliance, improve adverse emotions, restore sleep quality, reduce social function defects, and improve the quality of life.


Influence of cavity preparation with Er:YAG Laser on enamel adjacent to restorations submitted to cariogenic challenge in situ: a polarized light microscopic analysis.
Er:YAG laser has been used for caries removal and cavity preparation, using ablative parameters. Its effect on the margins of restorations submitted to cariogenic challenge has not yet been sufficiently investigated. The aim of this study was to assess the enamel adjacent to restored Er:YAG laser-prepared cavities submitted to cariogenic challenge in situ, under polarized light microscopy. Ninety-one enamel slabs were randomly assigned to seven groups (n = 13): I, II, III-Er:YAG laser with 250 mJ, 62.5 J/cm2, combined with 2, 3, and 4 Hz, respectively; IV, V, VI-Er:YAG laser with 350 mJ, 87.5 J/cm(2), combined with 2, 3, and 4 Hz, respectively; VII-High-speed handpiece (control). Cavities were restored and the restorations were polished. The slabs were fixed to intra-oral appliances, worn by 13 volunteers for 14 days. Sucrose solution was applied to each slab six times per day. Samples were removed, cleaned, sectioned and ground to polarized light microscopic analysis. Demineralized area and inhibition zone width were quantitatively assessed. Presence or absence of cracks was also analyzed. Scores for demineralization and inhibition zone were determined. No difference was found among the groups with regard to demineralized area, inhibition zone width, presence or absence of cracks, and demineralization score. Inhibition zone score showed difference among the groups. There was a correlation between the quantitative measures and the scores. Er:YAG laser was similar to high-speed handpiece, with regard to alterations in enamel adjacent to restorations submitted to cariogenic challenge in situ. The inhibition zone score might suggest less demineralization at the restoration margin of the irradiated substrates. Correlation between the quantitative measures and scores indicates that score was, in this case, a suitable complementary method for assessment of caries lesion around restorations, under polarized light microscopy.


Characteristics of the original patient navigation programs to reduce disparities in the diagnosis and treatment of breast cancer.
Patient navigation is an intervention developed to reduce disparities in cancer care that is being widely replicated and receiving considerable support for demonstration projects and research to test its effectiveness. In the current study, the authors present an in-depth descriptive analysis of the original patient navigation programs to inform current and future program development. A qualitative multistakeholder case study using interviews and site visits of the first patient navigation site and 2 sites subsequently developed by the leadership of the original site were evaluated. At these sites, patient navigation is a system, as opposed to a person, comprised primarily of navigators and directors that work together to remove barriers and facilitate access in a well-defined course of care; navigators were from the community or were culturally similar to the patient population served but were also paid employees of the clinical care site with detailed knowledge of the clinical course patients must traverse to complete care plans. Directors had administrative authority over the clinical facility and social capital across institutions, and communicated regularly and openly with navigators to implement system level changes to remove barriers to care. Contextual factors such as policies supporting breast cancer care also influenced the implementation of these programs. The first patient navigation programs combined community and culturally sensitive care-coordination with aspects of disease management programs to reduce racial, ethnic, and poverty-driven disparities in care. Future efforts to replicate and evaluate patient navigation should take into account these unique aspects of the original patient navigation programs.


A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow.
By employing multiparameter sorting, we identified in murine bone marrow (BM) a homogenous population of rare (approximately 0.02% of BMMNC) Sca-1(+)lin(-)CD45- cells that express by RQ-PCR and immunohistochemistry markers of pluripotent stem cells (PSC) such as SSEA-1, Oct-4, Nanog and Rex-1. The direct electronmicroscopical analysis revealed that these cells are small (approximately 2-4 microm), posses large nuclei surrounded by a narrow rim of cytoplasm, and contain open-type chromatin (euchromatin) that is typical for embryonic stem cells. In vitro cultures these cells are able to differentiate into all three germ-layer lineages. The number of these cells is highest in BM from young (approximately 1-month-old) mice and decreases with age. It is also significantly diminished in short living DBA/2J mice as compared to long living B6 animals. These cells in vitro respond strongly to SDF-1, HGF/SF and LIF and express CXCR4, c-met and LIF-R, respectively, and since they adhere to fibroblasts they may be coisolated with BM adherent cells. We hypothesize that this population of Sca-1(+)lin(-)CD45- very small embryonic-like (VSEL) stem cells is deposited early during development in BM and could be a source of pluripotent stem cells for tissue/organ regeneration.


Stabilization of soybean oil-in-water emulsions using polypeptide multilayers: Cationic polylysine and anionic polyglutamic acid.
Oil-in-water emulsions are used as delivery systems for non-polar functional ingredients in various industries, including foods, cosmetics, personal care products, agrochemicals, and pharmaceuticals. Emulsions, however, tend to breakdown under the conditions found in many commercial products. In this study, the functional performance of the lipid droplets in emulsions was tailored by sequential layer-by-layer electrostatic deposition of oppositely charged polypeptides onto their surfaces. Cationic poly-L-lysine (PLL) and anionic poly-glutamic acid (PGA) were used as a pair of oppositely charged polypeptides (pH 4.0). First, a primary emulsion (10% w/w soybean oil-in-water emulsion) was formed consisting of small lipid droplets (d32 = 500 µm) coated by a natural surfactant (0.05% w/w quillaja saponin). Second, cationic PLL was deposited onto the surfaces of the anionic saponin-coated droplets. Third, anionic PGA was deposited onto the surfaces of the cationic PLL-saponin-coated droplets. We then assessed the ability of the coatings to protect the lipid droplets from aggregation when the pH (2.0-9.0), ionic strength (0-350 mM), or temperature (30-90 °C) were altered. The properties of the primary, secondary, and tertiary emulsions were monitored by measuring the mean particle diameter (d32), electrical characteristics (ζ-potential), and microstructure of the lipid droplets. The electrical characteristics of the droplets could be modulated by controlling the number and type of layers used. The primary emulsion had the best resistance to varying environmental conditions, while the secondary emulsion had the worst, suggesting electrostatic deposition should only be used to obtain specific functionalities. Interestingly, PLL detached from the surfaces of the secondary emulsions at high salt concentrations due to electrostatic screening, which improved their salt stability. This phenomenon may be useful for some food applications, e.g., having cationic droplets during food storage, but anionic ones inside the human body.


Influence of different inhibitors on the activity of the RAD54 dependent step of DNA repair in Saccharomyces cerevisiae.
The recombinagenic pathway of DNA repair in yeast was characterized by the effect of different inhibitors on the temperature-dependent survival after gamma-irradiation in haploid cells of the thermoconditional mutant rad54-3. Blocking protein synthesis with cycloheximide in replicating cells caused partial inhibition of the RAD54 dependent function but some repair activity remained detectable. This indicates that gamma-rays can induce RAD54 activity above some constitutive level of function. Inhibition of DNA replication by hydroxyurea efficiently blocked the RAD54 dependent function in stationary-phase cells but not in logarithmic-phase cells. In logarithmic-phase cells, we found a strong inhibitory effect of caffeine on the RAD54 mediated repair process.


Determination of cardiac output with dynamic contrast-enhanced computed tomography.
Cardiac output (CO) is an important diagnostic and prognostic factor in the haemodynamic evaluation of patients. The gold standard for CO measurement, thermodilution, requires an invasive right-heart catheterisation (RHC). In this pilot study we aimed to determine the accuracy of non-invasive CO determination from dynamic contrast-enhanced computed tomography (CT) compared to thermodilution. Patients who underwent diagnostic or follow-up RHC due to suspected or known pulmonary vascular disease at our department and required a thoracic CT between June 2011 and August 2012 were included. CO was determined from CT attenuation-time curves in the pulmonary artery and the ascending aorta using a dynamic contrast-enhanced CT sequence. CO determined in N = 18 patients by dynamic CT in the pulmonary artery was in very good agreement with thermodilution data (r = 0.84). Bland-Altman analysis showed a systematic overestimation of 0.7 ± 0.6 l/min compared to thermodilution. Data from the ascending aorta also showed a good correlation, but with a larger scattering of the values. The average effective dose for the dynamic investigation was 1.2 ± 0.7 mSv. CO determined with dynamic contrast-enhanced CT in the main pulmonary artery reliably predicts the values obtained by thermodilution during RHC. This non-invasive technique might provide an alternative for repeated invasive right-heart catheter investigations in the follow-up of pulmonary arterial hypertension patients.


Continuous vagal nerve stimulation affects atrial neural remodeling and reduces atrial fibrillation inducibility in rabbits.
The effects of continuous vagal nerve stimulation (VNS) on atrial neural remodeling during atrial fibrillation (AF) remain unclear. To test the hypothesis that VNS affects atrial neural remodeling and reduces AF inducibility. Twenty rabbits were randomly divided into two groups: rapid atrial pacing (RAP) group and RAP with VNS group. AF inducibility studies and atrial histologic analyses were performed after 4 weeks. Five rabbits of RAP group (5/10) in the RAP group developed sustained AF. None of rabbits in RAP with VNS group had developed AF. The incidence of sustained AF in VNS group was significant lower than that in rapid pacing group (P<.01). Treatment with VNS resulted in a significant reduction in atrial neural remodeling and AF duration (P<.01). Atrial neural remodeling plays an important role in the initiation and maintenance of AF. Modulating autonomic nerve function with VNS can contribute to AF control.


The impact of COVID-19 on the number of active small primary care businesses by severity of the pandemic: evidence from South Korea.
Health systems have become financially fragile owing to the economic recession caused by the COVID-19 pandemic. However, small primary care businesses have received less policy attention than public health and secondary care. We aimed to estimate the impact of COVID-19 on the number of active small primary care businesses in South Korea. We selected clinics, dental clinics, oriental clinics, and pharmacies as primary care businesses. Our estimation took advantage of regional variations in COVID-19 cases in South Korea. We determined the number of active primary care businesses from 2019 1Q to 2021 1Q on a quarterly basis, and conducted interrupted time series analysis to estimate the effects of COVID-19 on this sector. This study found no significant increase or decrease in the number of clinics, dental clinics, and oriental clinics immediately after the pandemic began or in the time trends after the pandemic. However, there was a significant increase in the number of pharmacies immediately after the pandemic. The most affected area presented different trends in the number of pharmacies, dental clinics, and oriental clinics. Impact of the pandemic on the number of active small primary care business were low in South Korea. However, the impact varied according to the type of primary care setting and severity of the pandemic. The additional public health role of primary care could be associated with the sustenance of primary care businesses.


[What does a thorough personality questionnaire, the MMPI-2, tell us about psychological aspects of recurrent miscarriage?].
Try to analyse the experience of couples undergoing repeated miscarriages by answering the following questions: what can we learn from these men and women who suffered from repeated miscarriages? A thorough personality questionnaire, the MMPI-2, presented to 50 couples who have had repeated miscarriages. Through a hierarchical classification, different profiles appear in the men's group as well as in the women's group, revealing a somatization of psychological suffering. It is also revealing acute defensive personality profiles showing restricted affects in a lot of these men whose partners have suffered from multiple procreation failures. Such a narrower range of emotions can be a cause of additional pain for their partner and for themselves. We can therefore establish that, in these circumstances, the medical and/or psychological treatment should include both couple members to improve the marital adjustment and ease the couple towards another pregnancy which is always apprehended with the fear of another failure. A few etiological hypothesis may be evoked.


Specific binding of vasculotropin to bovine brain capillary endothelial cells.
Recently, a new growth factor was purified to homogeneity; its biological activity appeared to be restricted to vascular endothelial derived cells. As it was also angiogenic in vivo, it was provisionally named vasculotropin. An iodination procedure used to label vasculotropin did not damage the molecule; it was thus possible to undertake binding studies. The binding of iodinated vasculotropin to bovine brain capillary endothelial cells reached saturation at 7 ng/ml and half maximal binding occurred at 1.5 ng/ml. Scatchard analysis of the data demonstrated 2 classes of binding sites with apparent dissociation constants of 4 and 41 pM and 600 and 4,100 sites per cell respectively. The interaction was specific since an excess of unlabelled vasculotropin, but no Fibroblast Growth Factor or Transforming Growth Factor Beta almost totally abolished the binding of the tracer. A sensitive radioreceptor-assay convenient for measuring vasculotropin in biological samples is described.


HPV vaccination and sexual health in France: Empowering girls to decide.
Vaccination coverage against HPV in France is among the lowest in the industrialized world, although the public authorities have recently become aware of this issue. Few studies have looked at teenaged girls' representations of this vaccination, even though they are the most concerned by it. This qualitative study explored the experiences and representations of HPV vaccination by adolescent girls seeing doctors at least occasionally. We used a written essay question to explore this issue among 101 adolescent girls at six urban medical centers and a semi-structured interview to discuss it in further depth with five of them. The analysis was lexicometric (ALCESTE®) and phenomenological (Interpretative Phenomenological Analysis). These results are organized around four superordinate themes: the teenage girls' factual knowledge about this vaccine, their motives for and obstacles to vaccination, their involvement in this decision, and finally the need for information about and solutions to this issue. Teenage girls know little about this vaccine and are more sensitive to the emotional discourse that surrounds it than to rational knowledge about it. The requirement for parental authorization for this vaccine reinforces the girls' lack of investment. Vaccination programs should integrate the HPV vaccine more thoroughly into general prevention concerning sexual health and should send a strong signal by offering minors anonymous vaccination free of charge, as is already the case in France for requests for contraception, the morning-after pill, elective abortion, and screening and treatment of sexually transmitted infections.


Persistent organic pollutants and polycyclic aromatic hydrocarbons in penguins of the genus Pygoscelis in Admiralty Bay - An Antarctic specially managed area.
Persistent organic pollutants were assessed in fat samples of the Gentoo (Pygoscelis papua), Chinstrap (Pygoscelis antarcticus) and Adélie (Pygoscelis adeliae) penguins collected during the austral summers of 2005/06 and 2006/07 in Admiralty Bay, King George Island, Antarctica. The predominant organic pollutants were PCB (114 to 1115), polycyclic aromatic hydrocarbons (PAHs) (60.1 to 238.7), HCB (<0.3 to 132.2) and BDE-47 (<1.0 to 10.7) in ng g(-1) wet weight. The mean concentrations of the majority of organic pollutants were similar among the three species of penguins. Chicks of all three species showed similar profiles of PCB congeners, with predominance of lower chlorinated compounds. The distribution of PAHs was similar in all birds, with a predominance of naphthalene and alkyl-naphthalene, which are the main constituents of arctic diesel fuel. These data contribute to the monitoring of the continued exposure to organic pollutants in the Antarctic biota.


Breastfeeding in Byzantine icon art.
The Mary Galaktotrophousa is a representation of the Virgin breastfeeding the infant Jesus. The origin of this theme goes back to Antiquity when images of gods feeding humans were considered as an example that should be imitated by human. In the early days of Christianity, the Fathers of the Church recognized on the feature of Mary the ideal exemplary of maternity. The image of the Virgin breastfeeding the Holy Child, except the theological interpretation of the gesture, underline the fact that breastfeeding represents one of the most substantial gestures in the woman nature.