Robotic follicular unit extraction in hair transplantation.
In recent years, there has been a shift toward minimally invasive procedures. In hair transplantation surgery, this trend has manifested with the emergence of follicular unit extraction (FUE). Recently, a robot has been introduced for FUE procedures. To determine the transection rate of a robotic FUE device. The authors discuss the procedure, technical requirements, optimal candidates, advantages, and disadvantages of robotic FUE compared with the standard ellipse. Optimal candidates for robotic FUE are those with dark hair color who can sit for 45 to 120 minutes and are willing to shave a large area for donor harvesting. The main advantages of robotic FUE compared with the standard ellipse are its minimally invasive nature and the lack of a linear scar. The average transection rate with the robot to date is 6.6% (range, 0.4%-32.1%). The robot is a new and innovative method for FUE hair transplantation of which hair transplant surgeons should be aware.


Glutathione suppresses TGF-beta-induced PAI-1 expression by inhibiting p38 and JNK MAPK and the binding of AP-1, SP-1, and Smad to the PAI-1 promoter.
Transforming growth factor (TGF)-beta upregulates plasminogen activator inhibitor type 1 (PAI-1) in a variety of cell types, and PAI-1 is considered to be an essential factor for the development of fibrosis. Our previous studies demonstrated that TGF-beta decreased intracellular glutathione (GSH) content in murine embryonic fibroblasts (NIH/3T3 cells), whereas treatment of the cells with GSH, which restored intracellular GSH concentration, inhibited TGF-beta-induced collagen accumulation by blocking PAI-1 expression and enhancing collagen degradation. In the present study, we demonstrate that GSH blocks TGF-beta-induced PAI-1 promoter activity in NIH/3T3 cells, which is associated with an inhibition of TGF-beta-induced JNK and p38 phosphorylation. Interestingly, although exogenous GSH does not affect phosphorylation and/or nuclear translocation of Smad2/3 and Smad4, it completely eliminates TGF-beta-induced binding of transcription factors to not only AP-1 and SP-1 but also Smad cis elements in the PAI-1 promoter. Decoy oligonucleotides (ODN) studies further demonstrate that AP-1, SP-1, and Smad ODNs abrogate the inhibitory effect of GSH on TGF-beta-induced PAI-1 promoter activity and inhibit TGF-beta-induced expression of endogenous PAI-1. Furthermore, we show that GSH reduces TGF-beta-stimulated reactive oxygen species (ROS) signal. Blocking ROS production with diphenyleneiodonium or scavenging ROS with a superoxide dismutase and catalase mimetic MnTBaP dramatically reduces TGF-beta-induced p38 and JNK phosphorylation as well as PAI-1 gene expression. In composite, these findings suggest that GSH inhibits TGF-beta-stimulated PAI-1 expression in fibroblasts by blocking the JNK/p38 pathway, probably by reducing ROS, which leads to an inhibition of the binding of transcription factors to the AP-1, SP-1, and Smad cis elements in the PAI-1 promoter.


The effects of denturism: New Zealand dentists' response to competition.
The New Zealand Dental Act of 1988 allowed clinical dental technicians to deal directly with the public in fitting and supplying dentures. This study tested the hypothesis that dentists responded to competition from dental technicians by lowering their fees. The results indicate that there was no significant change in the fees charged by dentists for dentures. The apparent failure of deregulation to produce the expected outcome could be due to the competitive pressure imposed by dental technicians practicing illegally prior to 1988, to consumers' lack of information, or to barriers to "consumer search" imposed by the act itself.


Superhard properties of rhodium and iridium boride films.
Very recently, the superhard properties of rhenium and ruthenium boride films were reported, this research being inspired by the discovery of the ReB(2) bulk superhardness. In this paper, we report the first successful deposition and characterization of rhodium and iridium boride films, other possible candidates for superhard materials. The films were prepared, applying the pulsed laser deposition technique, and studied by X-ray diffraction, scanning electron and atomic force microscopies, and Vickers microhardness. The refined structural parameters for RhB(1.1) and IrB(1.1) films were obtained. The RhB(1.1) film is characterized by the submicrometer crystallite size, whereas for the IrB(1.1) film, the crystallite size is in the tens of nanometers range, and this latter film presents a slightly preferred orientation along the [004] direction. Both the films exhibit very similar morphology, being composed of dense globular aggregate texture. The RhB(1.1) film presents a homogeneously textured surface with an average roughness of 20-50 nm, whereas the IrB(1.1) film possesses a finer texture with an average roughness of 20-30 nm. The intrinsic hardness of both films lies in the superhardness range: the 1.0 microm thick RhB(1.1) film possesses a hardness of 44 GPa, whereas the 0.4 microm thick IrB(1.1) film has a hardness of 43 GPa.


Effect of adenosine A2A receptor agonist (CGS) on ischemia/reperfusion injury in isolated rat liver.
Ischemia/reperfusion injury during liver transplantation is a major cause of primary nonfunctioning graft for which there is no effective treatment other than retransplantation. Adenosine prevents ischemia-reperfusion-induced hepatic injury via its A2A receptors. The aim of this study was to investigate the role of A2A receptor agonist on apoptotic ischemia/reperfusion-induced hepatic injury in rats. Isolated rat livers within University of Wisconsin solution were randomly divided into four groups: (1) continuous perfusion of Krebs-Henseleit solution through the portal vein for 165 minutes (control); (2) 30-minute perfusion followed by 120 minutes of ischemia and 15 minutes of reperfusion; (3) like group 2, but with the administration of CGS 21680, an A2A receptor agonist, 30 microg/100 ml, for 1 minute before ischemia; (4) like group 3, but with administration of SCH 58261, an A2A receptor antagonist. Serum liver enzyme levels were measured by biochemical analysis, and intrahepatic caspase-3 activity was measured by fluorometric assay; apoptotic cells were identified by morphological criteria, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) fluorometric assay, and immunohistochemistry for caspase-3. Results showed that at 1 minute of reperfusion, there was a statistically significant reduction in liver enzyme levels in the animals pretreated with CGS (p < 0.05). On fluorometric assay, caspase-3 activity was significantly decreased in group 3 compared to group 2 (p < 0.0002). The reduction in postischemic apoptotic hepatic injury in the CGS-treated group was confirmed morphologically, by the significantly fewer apoptotic hepatocyte cells detected (p < 0.05); immunohistochemically, by the significantly weaker activation of caspase-3 compared to the ischemic group (p < 0.05); and by the TUNEL assay (p < 0.05). In conclusion, the administration of A2A receptor agonist before induction of ischemia can attenuate postischemic apoptotic hepatic injury and thereby minimize liver injury. Apoptotic hepatic injury seems to be mediated through caspase-3 activity.


Detection of extended spectrum beta-lactamase production in clinical isolates of Klebsiella spp.
Clinical laboratories need to develop quick screening methods for detection of extended spectrum beta-lactamase (ESBL) producing strains, so that the appropriate medication can be started without delay. In this study, we report the screening sensitivity of four representative antimicrobial agents i.e., cefpodoxime, cefotaxime, ceftazidime and aztreonam, commonly used for ESBL detection in Klebsiella spp. A total of 100 clinical isolates of Klebsiella spp. from the cases of neonatal septicaemia at a tertiary care hospital from north India, were screened for ESBL production by Kirby- Bauer's disc diffusion (cefpodoxime, cefotaxime, ceftazidime and aztreonam) and minimum inhibitory concentration (MIC) test by agar dilution methods. Confirmation was done by double disc method. Results showed that 58 of the 100 isolates tested were ESBL positive by confirmatory test and cefpodoxime was more efficient ESBL screening antimicrobial agent than ceftazidime, cefotaxime and aztreonam. Using the standard disk diffusion as screening test for identifying ESBL producers, cefpodoxime was found to be the most efficient antimicrobial agent in screening isolates as potential ESBL producers followed by ceftazidime in Klebsiella spp. isolates.


Comparison of pharmacokinetics of the sirolimus-eluting stent in Japanese patients with those in American patients.
The aim of this study was to evaluate the pharmacokinetics of the sirolimus-eluting stent (SES) implanted in 20 Japanese patients with angina pectoris and compare it with that in US study. Bx VELOCITY stent loaded with a total sirolimus dose of 150 mug was used in this study. Ten patients were treated by single-SES (group 1) and 10 patients were treated by double-SES (group 2). Sirolimus levels in whole blood were serially measured in the 2 groups after the SES implantation and compared with the pharmacokinetics in US study. We also evaluated the side effect of sirolimus, major adverse clinical events, and binary angiographic restenosis at 8 months after the SES implantation. Peak concentrations were observed approximately 4 hours after the SES implantation, and sirolimus half-lives were approximately 120 hours in each group. Mean peak sirolimus levels were 0.86 and 2.00 ng/mL for the group 1 and group 2, respectively. The peak concentrations of sirolimus in this study were twice higher in Japanese than in Americans, but they were much lower than effective concentration of sirolimus when orally administrated as an immunosuppressive agent. There were no side effects of sirolimus and no binary angiographic restenosis in any patients. One patient had target vessel revascularization at 8 months after the SES implantation. Although blood concentrations of sirolimus in Japanese patients after SES implantation are somewhat higher than those in American patients, its level is extremely low compared with the systemic administration, indicating the same clinical benefits by the SES could be safely expected in Japanese patients.


Dabigatran reduces thrombin-induced platelet aggregation and activation in a dose-dependent manner.
Dabigatran is an oral anticoagulant and a reversible inhibitor of thrombin. Further, dabigatran might affect platelet function through a direct effect on platelet thrombin receptors. The aim was to investigate the effect of dabigatran on platelet activation and platelet aggregation. Healthy donor blood was incubated with dabigatran 0, 50, 500 ng/mL, corresponding to the therapeutic range of dabigatran peak plasma concentrations, and 10,000 ng/mL comprising a supra-therapeutic dabigatran plasma level. Platelet aggregation was tested with 96-well aggregometry. Flow cytometry was used to test platelet activation and platelet thrombin receptor expression (SPAN-12 and WEDE-15 expression). Agonists were thrombin, thrombin receptor-activating peptide, protease-activated receptor-4 agonist, collagen, collagen-related peptide, arachidonic acid, and adenosine diphosphate. All concentrations of dabigatran fully inhibited platelet aggregation for thrombin up to 2 IU/mL, while dabigatran did not affect platelet aggregation by other agonists. Platelet activation (percentage of platelets positive for activated GPIIb/IIIa, CD63, P-selectin) was reduced after thrombin stimulation in samples with dabigatran levels ≥500 ng/mL. After stimulation with thrombin, the percentage of activated GPIIb/IIIa-positive platelets was 99.8 ± 0.2% without dabigatran, 14.7 ± 4.7% with 500 ng/mL dabigatran, and 4.2 ± 0.2% with 10,000 ng/mL dabigatran, both p < 0.001 when compared to samples without dabigatran. Also, the receptor expression of GPIIb/IIIa, CD63, and P-selectin were reduced after dabigatran treatment. The expression of thrombin receptors was reduced at dabigatran on ≥ 500 ng/mL. In conclusion, dabigatran exclusively inhibits thrombin-induced platelet activation and aggregation with a dose-dependent response. Platelet stimulation with other agonists was not affected by dabigatran.


[Histological studies on the roots of eighteen species of sect. microdiscus of the genus Adenophora].
The Chinese materia medica "Nanshasheng" (Radix Adenophorae) specified in Chinese Pharmacopoeia (1995) is the dried root of Adenophora tetraphylla (Thunb.) Fisch. or A. stricta Miq. (Fam. Campanulaceae). Results of an investigation on the botanical origin of the drug showed that the roots of 30 species (subspecies, varieties) of the genus Adenophora are also used in certain districts in China. Thus, it is necessary to study and compare the histological characters of these roots. In this paper, the root structure of 18 species from Sect. Microdiscus are reported, viz. Adenophora brevidiscifera Hong, A. coelestis Diels, A. stricta Miq., A. stricta Miq. var. qinglongshanica P. F. Tu et G. J. Xu, A. stricta Miq. var. nanjingensis P. F. Tu et G. J. Xu, A. stricta Miq. subsp. henanica P. F. Tu et G. J. Xu, A. stricta Miq. subsp. sessilifolia Hong, A. longipedicellata Hong, A. gmelinii (Spreng.) Fisch., A. polyantha Nakai, A. micrantha Hong, A. stenophylla Hemsl., A. potaninii Korsh., A. bockiana Diels, A. wawreana Zahlbr., A. tricuspidata (Fisch. ex Roem. et Schult.) A. DC., A. pereskiifolia (Fisch. ex Roem. et Schult.) G. Don and A. divaricata Franch. et Sav.. According to the presence, arrangement and thickening of cell walls of sclerified cork cell (SCC) in cork tissue and the rate of secondary and anomalous structures, the histological structures of Adenophora roots are classified into types A, B and C. In type A, SCC are arranged in ring shape. Type A can be further classified into subtypes A1 and A2. Only the outer and anticlinal walls of SCC are thickened in subtype A1, and all cell walls of SCC are thickened in subtype A2. In type B, SCC are arranged scatteredly, not in ring shape. In type C, there is no SCC. Type C can be classified into subtypes C1, C2 and C3. In type C1, the secondary structure occupies more than 50% of the root diameter. In type C2, the anomalous structure is more than 50% of the root diameter, and the anomalous vascular bundles are in band form. The anomalous structure occupies more than 50% of the root diameter in subtype C3, and the anomalous vascular bundles are branched.


Carbon nanomaterials sensitize prostate cancer cells to docetaxel and mitomycin C via induction of apoptosis and inhibition of proliferation.
We have previously shown that carbon nanofibers (CNFs) and carbon nanotubes (CNTs) can sensitize prostate cancer (PCa) cells to platinum-based chemotherapeutics. In order to further verify this concept and to avoid a bias, the present study investigates the chemosensitizing potential of CNFs and CNTs to the conventional chemotherapeutics docetaxel (DTX) and mitomycin C (MMC), which have different molecular structures and mechanisms of action than platinum-based chemotherapeutics. DU-145 PCa cells were treated with DTX and MMC alone or in combination with the carbon nanomaterials. The impact of the monotreatments and the combinatory treatments on cellular function was then systematically analyzed by using different experimental approaches (viability, short-term and long-term proliferation, cell death rate). DTX and MMC alone reduced the viability of PCa cells to 94% and 68%, respectively, whereas a combined treatment with CNFs led to less than 30% remaining viable cells. Up to 17- and 7-fold higher DTX and MMC concentrations were needed in order to evoke a similar inhibition of viability as mediated by the combinatory treatments. In contrast, the dose of platinum-based chemotherapeutics could only be reduced by up to 3-fold by combination with carbon nanomaterials. Furthermore, combinatory treatments with CNFs led mostly to an additive inhibition of short- and long-term proliferation compared to the individual treatments. Also, higher cell death rates were observed in combinatory treatments than in monotreatments, e.g., a combination of MMC and CNFs more than doubled the cell death rate mediated by apoptosis. Combinations with CNTs showed a similar, but less pronounced impact on cellular functions. In summary, carbon nanomaterials in combination with DTX and MMC evoked additive to partly synergistic anti-tumor effects. CNFs and CNTs possess the ability to sensitize cancer cells to a wide range of structurally diverse chemotherapeutics and thus represent an interesting option for the development of multimodal cancer therapies. Co-administration of chemotherapeutics with carbon nanomaterials could result in a reduction of the chemotherapeutic dosage and thus limit systemic side effects.


THE PATHOLOGY OF LIVER CIRRHOSIS IN PATIENTS WITH CYSTIC FIBROSIS OF THE PANCREAS.
The peculiarities of the type of liver cirrhosis that occurs in patients with cystic fibrosis of the pancreas depend on a number of factors. Two such factors, which have received little attention in the past, became apparent during a study of the livers of patients dying of this disease at the Henry Ford Hospital, Detroit. Firstly, the onset of the disease in fetal life may disturb the development of the bile duct system whose normal development is essential for normal structural relationships to be maintained in the liver. Focal lesions of intrahepatic biliary atresia will then complicate the histologic picture of "multi-lobular biliary cirrhosis". Secondly, scars formed in an infantile liver will considerably distort the subsequent growth of the liver, resulting in bizarre nodularity. Despite massive deformation large portions of the liver will still be composed of primary parenchyma that will enable normal liver functions as revealed by laboratory tests.


Belayer: Modeling discrete and continuous spatial variation in gene expression from spatially resolved transcriptomics.
Spatially resolved transcriptomics (SRT) technologies measure gene expression at known locations in a tissue slice, enabling the identification of spatially varying genes or cell types. Current approaches for these tasks assume either that gene expression varies continuously across a tissue or that a tissue contains a small number of regions with distinct cellular composition. We propose a model for SRT data from layered tissues that includes both continuous and discrete spatial variation in expression and an algorithm, Belayer, to learn the parameters of this model. Belayer models gene expression as a piecewise linear function of the relative depth of a tissue layer with possible discontinuities at layer boundaries. We use conformal maps to model relative depth and derive a dynamic programming algorithm to infer layer boundaries and gene expression functions. Belayer accurately identifies tissue layers and biologically meaningful spatially varying genes in SRT data from the brain and skin.


Fine needle aspiration compared with scintigraphy for detection of liver neoplasia.
The diagnostic accuracy of fine needle aspiration and scintigraphy was compared prospectively in a series of cases of suspected liver neoplasm. The results of both techniques showed a close correlation to final diagnosis. Biopsy, easily and rapidly performed with simple equipments, is a cost-saving procedure with as good a sensitivity as scintigraphy. Furthermore, the possible finding of specific cytological pictures of primary liver carcinoma or tumours of the amino precursor uptake decarboxylating cell series lend further weight to the biopsy technique.


Pre-pregnancy BMI-specific optimal gestational weight gain for women in Japan.
The Institute of Medicine (IOM) guidelines are the most widely used guidelines on gestational weight gain; however, accumulation of evidence that body composition in Asians differs from other races has brought concern regarding whether their direct application is appropriate. We aimed to study to what extent optimal gestational weight gain among women in Japan differs by pre-pregnancy body mass index (BMI) and to compare estimated optimal gestational weight gain to current Japanese and Institute of Medicine (IOM) recommendations. We retrospectively studied 104,070 singleton pregnancies among nulliparous women in 2005-2011 using the Japanese national perinatal network database. In five pre-pregnancy BMI sub-groups (17.0-18.4, 18.5-19.9, 20-22.9, 23-24.9, and 25-27.4 kg/m2), we estimated the association of the rate of gestational weight gain with pregnancy outcomes (fetal growth, preterm delivery, and delivery complications) using multivariate regression. Weight gain rate associated with the lowest risk of adverse outcomes decreased with increasing BMI (12.2 kg, 10.9 kg, 9.9 kg, 7.7 kg, and 4.3 kg/40 weeks) for the five BMI categories as described above, respectively. Current Japanese guidelines were lower than optimal gains, with the lowest risk of adverse outcomes for women with BMI below 18.5 kg/m2, and current IOM recommendations were higher than optimal gains for women with BMI over 23 kg/m2. Optimal weight gain during pregnancy varies largely by pre-pregnancy BMI, and defining those with BMI over 23 kg/m2 as overweight, as proposed by the World Health Organization, may be useful when applying current IOM recommendations to Japanese guidelines.


Does environmental regulation caused by air pollution reduce shadow banking for non-financial companies? Based on the exit perspective of implicit government guarantee.
As China's economy enters the stage of high-quality development, the sustainability of development becomes increasingly important. Therefore, this study takes air quality index as the explanatory variable, the level of shadow banking as the explained variable, and environmental regulation as the intermediary variable to empirically study whether environmental regulation caused by air pollution will affect the shadow banking of non-financial enterprises. The findings suggest that air pollution is likely to strengthen environmental regulation, thereby reducing the level of shadow banking, as air pollution strengthens environmental regulation, leading to the reduction of implicit government guarantees, while enterprises tend to abandon or minimize reliance on these guarantees and reduce leverage. The mechanism test shows that the ESG performance of non-financial firms weakens the process by which air pollution reduces the degree of shadow banking of non-financial firms, while the short-sightedness of management enhances this process. Heterogeneity analysis shows that this process is more significant under the effect of market-driven environmental regulation and in private enterprises and enterprises in regions with large industrial scale. Therefore, the policy implication is that government should continue to strengthen environmental law enforcement in future supervision, as this can not only reduce pollution levels but also reduce systemic financial risks. Enterprises should also increase their sense of social responsibility.


Human cytomegalovirus infection alters the expression of cellular microRNA species that affect its replication.
The human genome encodes over 500 microRNAs (miRNAs), small RNAs (19 to 26 nucleotides [nt]) that regulate the expressions of diverse cellular genes. Many cellular processes are altered through a variety of mechanisms by human cytomegalovirus (HCMV) infection. We asked whether HCMV infection leads to changes in the expression of cellular miRNAs and whether HCMV-regulated miRNAs are important for HCMV replication. Levels of most miRNAs did not change markedly during infection, but some were positively or negatively regulated. Patterns of miRNA expression were linked to the time course of infection. Some similarly reregulated miRNAs share identical or similar seed sequences, suggesting coordinated regulation of miRNA species that have shared targets. miRNAs miR-100 and miR-101 were chosen for further analyses based on their reproducible changes in expression after infection and on the basis of having predicted targets in the 3' untranslated regions (3'-UTR) of genes encoding components of the mammalian target of rapamycin (mTOR) pathway, which is important during HCMV infection. Reporter genes that contain the 3'-UTR of mTOR (predicted targets for miR-100 and miR-101) or raptor (a component of the mTOR pathway; predicted site for miR-100) were constructed. Mimics of miR-100 and miR-101 inhibited expression from the mTOR construct, while only miR-100 inhibited the raptor construct. Together, miR-100 and miR-101 reduced mTOR protein levels. While the miR-100 and miR-101 mimics individually modestly inhibited production of infectious progeny, much greater inhibition was achieved with a combination of both (33-fold). Our key finding is that HCMV selectively manipulates the expression of some cellular miRNAs to help its own replication.


[A study on the correlation between HLA-DR genes and susceptibility to pulmonary tuberculosis in a population of Han nationality from southern China].
To analyze the association between HLA-DR genes and pulmonary tuberculosis and to explore susceptible genes associated with pulmonary tuberculosis in a population of Han nationality from southern China. Using case-control study, we detected by polymerase chain reaction-sequence specific primers (PCR-SSP) technique the 23 alleles of HLA-DR gene sites in 110 tuberculosis cases and 101 controls from Guangdong, Guangxi, Hunan, Hubei, Jiangxi and Fujian provinces. Gene frequency (GF) and odds ratio (OR) were calculated and compared. The frequency of DR16 allele in pulmonary tuberculosis cases was strikingly higher than that in the healthy controls (chi2=5.915, Pc< 0.05). Their GFs were 12.62% and 5.60% respectively, and the OR was 2.53. Significantly decreased frequency of DR1 and DR13.3 alleles in cases were found (chi2 values were 17.847 and 14.258 respectively, Pc < 0.01). Their ratios of GFs were 8.08% vs. 23.57% and 29.29% vs. 50.24%, and their ORs were 0.26 and 0.33 respectively. The results suggest that DR16 allele is closely correlated to incidence of pulmonary tuberculosis in this population of Han nationality from southern China, or linked to susceptible genes which are functional. It is also suggested that expression of DR1 and DR13.3 alleles may be associated with an antagonist effect in the pathogenesis of pulmonary tuberculosis in this population.


On-line prediction of the glucose concentration of CHO cell cultivations by NIR and Raman spectroscopy: Comparative scalability test with a shake flask model system.
In this study, near-infrared (NIR) and Raman spectroscopy were compared in parallel to predict the glucose concentration of Chinese hamster ovary cell cultivations. A shake flask model system was used to quickly generate spectra similar to bioreactor cultivations therefore accelerating the development of a working model prior to actual cultivations. Automated variable selection and several pre-processing methods were tested iteratively during model development using spectra from six shake flask cultivations. The target was to achieve the lowest error of prediction for the glucose concentration in two independent shake flasks. The best model was then used to test the scalability of the two techniques by predicting spectra of a 10l and a 100l scale bioreactor cultivation. The NIR spectroscopy based model could follow the trend of the glucose concentration but it was not sufficiently accurate for bioreactor monitoring. On the other hand, the Raman spectroscopy based model predicted the concentration of glucose in both cultivation scales sufficiently accurately with an error around 4mM (0.72g/l), that is satisfactory for the on-line bioreactor monitoring purposes of the biopharma industry. Therefore, the shake flask model system was proven to be suitable for scalable spectroscopic model development.


Tumor cell-intrinsic CD274/PD-L1: A novel metabolic balancing act with clinical potential.
Tumor expression of the immune co-signaling molecule CD274/PD-L1 was originally described as impeding antitumor immunity by direct engagement of its receptor, PDCD1/PD-1, on antitumor T cells. Melanoma-intrinsic PDCD1 was recently shown to promote tumor growth and MTOR signals in cooperation with tumor CD274, and sarcoma-intrinsic CD274 signaling promotes glucose metabolism to impede antitumor immunity. Our recent report shows that tumor cell-intrinsic CD274 promotes MTORC1 signaling in mouse melanoma and mouse and human ovarian cancer, inhibits autophagy and sensitizes some tumors to clinically available pharmacological autophagy inhibitors and confers resistance to MTOR inhibitors. Tumor CD274 could be a biomarker of autophagy or MTOR inhibitor response in selected tumors, and these inhibitors could improve anti-CD274 or anti-PDCD1 cancer immunotherapy. As we found that distinct tumor types exhibit this CD274-driven phenotype, it could be widely applicable.


A Personalized and Interactive Web-Based Health Care Innovation to Advance the Quality of Life and Care of Patients With Heart Failure (ACQUIRE-HF): A Mixed Methods Feasibility Study.
Heart failure (HF) is a progressive, debilitating, and complex disease, and due to an increasing incidence and prevalence, it represents a global health and economic problem. Hence, there is an urgent need to evaluate alternative care modalities to current practice to safeguard a high level of care for this growing population. Our goal was to examine the feasibility of engaging patients to use patient-centered and personalized tools coupled with a Web-based, shared care and interactive platform in order to empower and enable them to live a better life with their disease. We used a mixed methods, single-center, pre-post design. Patients with HF and reduced left ventricular ejection fraction (n=26) were recruited from the outpatient HF clinic at Odense University Hospital (Svendborg Hospital), Denmark, between October 2015 and March 2016. Patients were asked to monitor their health status via the platform using the standardized, disease-specific measure, the Kansas City Cardiomyopathy Questionnaire (KCCQ), and to register their weight. A subset of patients and nursing staff were interviewed after 3-month follow-up about their experiences with the platform. Overall, patients experienced improvement in patient-reported health status but deterioration in self-care behavior between baseline and 3-month follow-up. The mean score reflecting patient expectations toward use prior to start of the study was lower (16 [SD 5]) than their actual experiences with use of the platform (21 [SD 5]) after 3-month follow-up. Of all patients, 19 completed both a baseline and follow-up KCCQ. A total of 9 experienced deterioration in their health status (range from 3-34 points), while 10 experienced an improvement (range from 1-23 points). The qualitative data indicated that the majority of patients found the registration and monitoring on the platform useful. Both nursing staff and patients indicated that such monitoring could be a useful tool to engage and empower patients, in particular when patients are just diagnosed with HF. The use of patient tracking and monitoring of health status in HF using a standardized and validated measure seems feasible and may lead to insights that will help educate, empower, and engage patients more in their own disease management, although it is not suitable for all patients. Nursing staff found the patient-centered tool beneficial as a communication tool with patients but were more reticent with respect to using it as a replacement for the personal contact in the outpatient clinic.


Emotional adaptation during a crisis: decline in anxiety and depression after the initial weeks of COVID-19 in the United States.
Crises such as the COVID-19 pandemic are known to exacerbate depression and anxiety, though their temporal trajectories remain under-investigated. The present study aims to investigate fluctuations in depression and anxiety using the COVID-19 pandemic as a model crisis. A total of 1512 adults living in the United States enrolled in this online study beginning April 2, 2020 and were assessed weekly for 10 weeks (until June 4, 2020). We measured depression and anxiety using the Zung Self-Rating Depression scale and State-Trait Anxiety Inventory (state subscale), respectively, along with demographic and COVID-related surveys. Linear mixed-effects models were used to examine factors contributing to longitudinal changes in depression and anxiety. We found that depression and anxiety levels were high in early April, but declined over time. Being female, younger age, lower-income, and previous psychiatric diagnosis correlated with higher overall levels of anxiety and depression; being married additionally correlated with lower overall levels of depression, but not anxiety. Importantly, worsening of COVID-related economic impact and increase in projected pandemic duration exacerbated both depression and anxiety over time. Finally, increasing levels of informedness correlated with decreasing levels of depression, while increased COVID-19 severity (i.e., 7-day change in cases) and social media use were positively associated with anxiety over time. These findings not only provide evidence for overall emotional adaptation during the initial weeks of the pandemic, but also provide insight into overlapping, yet distinct, factors contributing to depression and anxiety throughout the first wave of the pandemic.


An update on atrial fibrillation: focus on stroke risk reduction strategies.
Atrial fibrillation (AF) currently affects approximately 2% of the general adult population, and the number of patients suffering from AF constantly increases. Although the occurrence of AF rarely poses an immediate threat to patient's survival, the arrhythmia is associated with significant cardiovascular morbidity and mortality mostly resulting from ischemic stroke or systemic thromboembolism, or heart failure. Overall, patients with AF have a 5-fold greater risk of stroke compared to individuals in sinus rhythm, but individual stroke risk depends on the presence of various stroke risk factors, and optimal stroke prevention is essential for AF patients. Several major advances in AF-related stroke prevention have been achieved recently, including the refinements in stroke and bleeding risk assessment with an essential shift in the recognition of AF patients who should be offered oral anticoagulant (OAC) therapy, the advent of non-vitamin K antagonist oral anticoagulants (NOACs) which are increasingly used in the "real-world" setting, as well as the development of non-pharmacological means of thromboprophylaxis in AF patients (e.g., left atrial appendage [LAA] occluding devices). In this review article, we summarize these recent developments in stroke risk reduction strategies and discuss the main principles of decision-making regarding OAC therapy in AF patients.


Improving Prediction of High-Cost Health Care Users with Medical Check-Up Data.
Studies found that a small portion of the population spent the majority of health care resources, and they highlighted the importance of predicting high-cost users in the health care management and policy. Most prior research on high-cost user prediction models are based on diagnosis data with additional cost and health care utilization data to improve prediction accuracy. To further improve the prediction of high-cost users, researchers have been testing various new data sources such as self-reported health status data. In this study, we use three categories of medical check-up data, laboratory tests, self-reported medical history, and self-reported health behavior data to build high-cost user prediction models, and to assess the medical check-up features as predictors of high-cost users. Using three data-mining models, logistic regression, random forest, and neural network models, we show that under the diagnosis-based approach, medical check-up data marginally improve diagnosis-based prediction models. Under the cost-based approach, we find that medical check-up data improve cost-based prediction models marginally and medical check-up data can be a viable alternate data source to diagnosis data in predicting high-cost users.


Kinematic analysis of a functional and sequential bimanual task in patients with left hemiparesis: intra-limb and interlimb coordination.
To characterise upper limb performance of each hand (intra-limb coordination) and interlimb coordination on a functional, sequential bimanual task in patients with left hemiparesis and age-matched controls. Fourteen patients with left hemiparesis (age: 60.01 +/- 9.09 years) and 13 adults without neurological impairments (age: 59.14 +/- 10.59 years) were instructed to reach-to-grasp a jar with the affected/left limb and to unscrew the jar cap with the unaffected/right limb. Reaching and grasping kinematics were analysed for intra-limb coordination and bimanual synchronisation and temporal correlation for interlimb coordination. The patients showed significantly less efficient, less smooth, and less forceful movement and spent significantly more time for on-line error correction with the affected hand than the healthy controls. Interlimb coordination was disrupted at movement onset but was preserved at movement end in the hemiparetic patients. The major deficits of the left hemiparetic patients involved heavy reliance on feedback control with the affected hand, and poor bimanual coordination at movement onset, which might be specifically retrained during stroke rehabilitation. Preservation ofinterlimb coordination at movement end in stroke patients suggested that they retained flexibility in response to the impaired temporal performance of the affected hand to achieve the end goal.


A biotinylated peptide, BP21, alleviates hypotension in anaphylactic mice.
Platelet-activating factor (PAF) is known as an important mediator of anaphylaxis and, therefore, may possibly serve as a direct target for anti-anaphylactic drugs. We recently reported that a synthetic N-terminally biotinylated peptide, BP21, alleviates hypothermia and vascular hyperpermeability during anaphylactic reactions in a mouse model of anaphylaxis via the direct binding of a Tyr-Lys-Asp-Gly sequence in the peptide to PAF. In this study, we investigated the effect of BP21 on in vivo anaphylactic hypotension. Results showed that BP21 significantly inhibited anaphylactic hypotension in a dose-dependent manner, with peak severity being reached within 20 minutes. Adrenaline, which is the recommended first line treatment for anaphylactic patients, did not inhibit anaphylactic hypothermia. The combined administration of BP21 with adrenaline inhibited both hypotension and hypothermia, even at both low doses, more effectively compared with solo administration of BP21 or adrenaline. These results suggested that BP21 could potentially be a novel anti-anaphylactic agent for targeting PAF in vivo.


Personality and Hypothalamic-Pituitary-Adrenal Axis in Older Men and Women.
Personality has been related to health and mortality risk, which has created interest in the biological pathways that could explain this relationship. Although a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been associated with health outcomes and aging, few studies have explored the association between personality and HPA axis functioning in older adults. In addition, it has been suggested that sex could moderate the relationship between personality and HPA axis functioning. Thus, our aim was to analyze the relationship between the big five personality traits and the diurnal cortisol pattern in older adults, as well as sex differences in this relationship. To do so, 79 older people (40 men and 39 women) from 59 to 81 years old (M = 69.19, SD = 4.60) completed the NEO-Five-Factor Inventory (FFI) to measure neuroticism, conscientiousness, extraversion, openness, and agreeableness. Saliva samples were provided on three consecutive days (awakening; 15, 30, and 45 min post-awakening; and bedtime) in order to analyze the diurnal cortisol pattern and, specifically, two cortisol indexes: the cortisol awakening response (CAR) and the diurnal cortisol slope (DCS). Results showed that neuroticism and conscientiousness moderated the diurnal cortisol pattern. Thus, individuals with higher neuroticism and lower conscientiousness scores showed higher bedtime cortisol levels, suggesting a less healthy diurnal cortisol pattern. Regarding the cortisol indexes, higher neuroticism and lower conscientiousness were related to greater CAR and DCS. Sex moderated the association between extraversion and the DCS. Specifically, higher extraversion was related to a lower DCS only in women. Openness and agreeableness were not related to the diurnal cortisol pattern. In conclusion, our results show that in older adults, neuroticism is a vulnerability factor for HPA axis dysregulation, with possible adverse effects on health. By contrast, conscientiousness, and extraversion only in women, appear to be protective factors of HPA axis functioning, with potential beneficial effects on health.


[Straightening operations in juvenile kyphosis. Results in 31 cases using Harrington's dorsal compression spondylodesis or its combination with ventral osteodiskectomy and clip insertion].
Results of operative treatment in 31 cases of juvenile kyphosis are presented. In 23 cases a posterior Harrington spondylodesis, in 6 cases a combined staged anterior and posterior spondylodesis, in two cases an anterior spondylodesis alone were performed. The average preoperative angle in the first group was 50 degrees (15 degrees-83 degrees), the average postop, angle was 22 degrees representing an 56% average improvement of the initial angle. At reevaluation, however, an average loss of correction of 13.9 degrees or 49.6% reduction of the initial improvement was registered. The combined procedures started with an average preoperative angle of 60 degrees, the postsurgery value was 22 degrees representing 63% of improvement. In 6 cases the average loss of correction at reevaluation was only 7% or 18.9% of early improvement was lost. The results favor strongly a combined staged anterior and posterior procedure for correction. When the behaviour of the wedge vertebrae is included as well, this study offers clear indications for a differentiated treatment of choice in each case of severe juvenile kyphosis.


kappa B-like motifs regulate the induction of immune genes in Drosophila.
The mammalian transcription factor NF-kappa B regulates a number of genes involved in immune and acute phase responses, by interacting with a nucleotide sequence element, the kappa B-motif. In this work we demonstrate the participation of similar motifs in the immune response of insects as well: kappa B-like motifs have a regulatory role in the synthesis of cecropins, a set of anti-bacterial peptides, triggered by the presence of bacterial cell wall components in the insect blood. We show that the upstream region of the Cecropin gene CecA1 contains elements responsible for inducible and tissue-specific expression. Furthermore, a trimer of kappa B-like motif confers high levels of inducible expression from the reporter gene, after transfection in a Drosophila blood cell line. As in the moth Hyalophora cecropia, stimulation with bacterial lipopolysaccharide induces a nuclear factor that specifically binds to the kappa B-like motif. Our data suggest a functional and evolutionary relationship between these insect immune response factors and the mammalian NF-kappa B.


Novel modular enzymes encoded by a cellulase gene cluster in Cellvibrio mixtus.
Hydrolysis of plant cell wall polysaccharides, a process which is of intrinsic biological and biotechnological importance, requires the concerted action of an extensive repertoire of microbial cellulases and hemicellulases. Here, we report the identification of the gene cluster unk16A, regA and cel5B in the aerobic soil bacterium Cellvibrio mixtus, encoding a family 16 (CmUnk16A) glycoside hydrolase (GH), an AraC/XylS transcription activator (CmRegA) and a family 5 (CmCel5B) endo-glucanase, respectively. CmUnk16A is a modular enzyme comprising, in addition to the catalytic domain, two family 32 carbohydrate-binding modules (CBMs), termed CBM32-1 and CBM32-2, a CBM4 and a domain of unknown function. We show that CBM32-2 binds weakly to laminarin and pustulan. CmRegA is also a modular protein containing a highly hydrophobic N-terminal domain and a C-terminal DNA-binding domain of the AraC/XylS family. The role of the identified enzymes in the hydrolysis of cell wall polysaccharides by aerobic bacteria is discussed.


Development of skin-humanized mouse models of pachyonychia congenita.
Molecular characterization and assessment of therapeutic outcomes for inherited cutaneous disorders requires faithful preclinical models. In this study we report the establishment of two different skin-humanized pachyonychia congenita (PC) model systems, based on permanent engraftment of bioengineered skin equivalents generated from patient skin cells onto immunodeficient mice. Using keratinocytes and fibroblasts isolated from unaffected skin biopsies of two PC patients carrying the p.Asn171Lys mutation of the keratin 6a gene (KRT6A), we were able to regenerate PC-derived human skin that appeared phenotypically normal, but developed sustained PC features after the use of an acute hyperproliferative stimulus (i.e., tape stripping). In contrast, the use of keratinocytes from an affected area (i.e., plantar callus) from a different patient carrying the KRT6A mutation p.Asn171Asp led to a full recapitulation of the phenotype that included marked acanthosis and epidermal blistering after minor trauma. The ability to generate large numbers of PC skin-engrafted mice will enable the testing of novel pharmacological or gene-based therapies for this as yet untreatable disease.


The role of alveolar epithelium in radiation-induced lung injury.
Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13 Gy) and fractionated doses (24-36 Gy) of (137)Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c(+) cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis.


Using genetically encoded fluorescent biosensors to interrogate ovarian cancer metabolism.
Epithelial ovarian cancer (OC) is the most lethal gynecological malignancy and patients present with significant metastatic burden, particularly to the adipose-rich microenvironment of the omentum. Recent evidence has highlighted the importance of metabolic adaptations in enabling this metastasis, leading to significant interest in evolving the arsenal of tools used to study OC metabolism. In this study, we demonstrate the capability of genetically encoded fluorescent biosensors to study OC, with a focus on 3D organoid models that better recapitulate in vivo tumor microenvironments. Plasmids encoding the metabolic biosensors HyPer, iNap, Peredox, and Perceval were transfected into 15 ovarian cancer cell lines to assay oxidative stress, NADPH/NADP+, NADH/NAD+, and ATP/ADP, respectively. Fluorescence readings were used to assay dynamic metabolic responses to omental conditioned media (OCM) and 100 μM carboplatin treatment. SKOV3 cells expressing HyPer were imaged as 2D monolayers, 3D organoids, and as in vivo metastases via an intravital omental window. We further established organoids from ascites collected from Stage III/IV OC patients with carboplatin-resistant or carboplatin-sensitive tumors (n = 8 total). These patient-derived organoids (PDOs) were engineered to express HyPer, and metabolic readings of oxidative stress were performed during treatment with 100 μM carboplatin. Exposure to OCM or carboplatin induced heterogenous metabolic changes in 15 OC cell lines, as measured using metabolic sensors. Oxidative stress of in vivo omental metastases, measured via intravital imaging of metastasizing SKOV3-HyPer cells, was more closely recapitulated by SKOV3-HyPer organoids than by 2D monolayers. Finally, carboplatin treatment of HyPer-expressing PDOs induced higher oxidative stress in organoids derived from carboplatin-resistant patients than from those derived from carboplatin-sensitive patients. Our study showed that biosensors provide a useful method of studying dynamic metabolic changes in preclinical models of OC, including 3D organoids and intravital imaging. As 3D models of OC continue to evolve, the repertoire of biosensors will likely serve as valuable tools to probe the metabolic changes of clinical importance in OC.


The power of Drosophila in modeling human disease mechanisms.
Six years ago, DMM launched a subject collection called 'Drosophila as a Disease Model'. This collection features Review-type articles and original research that highlight the power of Drosophila research in many aspects of human disease modeling. In the ensuing years, Drosophila research has further expanded to capitalize on genome editing, development of resources, and further interest in studying rare disease mechanisms. In the current issue of DMM, we again highlight the versatility, breadth, and scope of Drosophila research in human disease modeling and translational medicine. While many researchers have embraced the power of the fly, many more could still be encouraged to appreciate the strengths of Drosophila and how such research can integrate across species in a multi-pronged approach. Only when we truly acknowledge that all models contribute to our understanding of human biology, can we take advantage of the scope of current research endeavors.


Improving performance and cyclability of zinc-silver oxide batteries by using graphene as a two dimensional conductive additive.
In this article, the use of reduced graphene oxide (rGO) as a high-surface-area conductive additive for enhancing zinc-silver oxide (Zn-Ag2O) batteries is reported for the first time. Specific capacity, rate capability and cyclability are all improved with the addition of 5% thermally reduced graphene oxide to the electrode. It is shown that the rGO morphology becomes more beneficial as the active materials tend toward the nanoscale. The combination results in a better utilization of the active material, which in turn improves the specific capacity of the zinc-silver oxide batteries by ca. 50%, as a result of the more intimate contact with the nano (∼50 nm) electrode particles. The resulting rGO network also creates a high-surface-area conducting template for ZnO electrodeposition upon discharge, significantly reducing the overall particle size of the ZnO deposit, thus inhibiting the formation of dendrites, and increasing the number of achievable cycles from 4 to >160 with a basic cellulose separator. The morphology of the electrodes and its electrochemical parameters are studied as a function of cycling.


Temporal Dynamics of Rituals in Obsessive Compulsive Disorder.
Obsessive-compulsive disorder (OCD) is characterized by obsessions, defined as intrusive and persistent thoughts, and compulsions, defined as repetitive ritualistic behaviors that attempt to neutralize the anxiety associated with the obsessions. The present study investigated the patterns of symptoms as they occur over time in order to generate new insights about the triggers to symptoms. Fourteen adult participants who met the DSM-5 criteria for OCD completed 7-day logbooks of daily activities including the times when they engaged in compulsive rituals. Orbital Decomposition (ORBDE) was used to extract symptom patterns and revealed a wide range of symptom cycle lengths, some of which were hierarchically organized in time and some were not. Furthermore the results of the ORBDE analysis were logically consistent with those of a previously reported nonlinear regression analysis. Both analytic techniques supported a turbulence model for OCD onset: Combinations of cognition, emotion, and behavioral responses that would occur randomly for nonclinical samples self-organize into deterministic and chaotic patterns for clinical samples. It is speculated that knowledge of the individuals' temporal dynamics could inform effective treatment strategies, allowing a therapist to develop an individualized yet empirically supported treatment plan.


Molecular targeting of VEGF/VEGFR signaling by the anti-VEGF monoclonal antibody BD0801 inhibits the growth and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo.
Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related deaths with 750,000 newly diagnosed cases each year. Surgery, radiotherapy, and chemotherapy constitute the main treatment modalities for HCC, but liver cirrhosis and damage often occur. Molecular targeted drugs have been recently developed to treat HCC. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) autocrine signaling is closely related to the growth, progression, and metastasis of HCC, making the VEGF/VEGFR axis an ideal target for the development of molecular targeted agents. Here, we report the effects of the novel anti-VEGF humanized monoclonal antibody BD0801 on the growth of HCC cells in vitro and in vivo as well as the underlying mechanisms. BD0801 significantly inhibited the proliferation of HepG2, SMMC-7721, and Bel7402 cells in vitro, accompanied with an induction of apoptosis and cell cycle arrest at the G1 phase. BD0801 potently suppressed AKT, Erk1/2, and retinoblastoma (Rb) phosphorylation, while increasing p21 and decreasing cyclin D1 protein levels. BD0801 significantly inhibited growth in mouse tumor xenografts and induced cell apoptosis of HepG2 and SMMC-7721 tumor xenografts. Furthermore, BD0801 effectively reduced the vascular density and tumor tissue microvessel density (MVD). Similarly, BD0801 decreased AKT, Erk1/2, and Rb phosphorylation and cyclin D1 expression whereas it increased p21 protein expression in mouse HCC tumor xenografts. Importantly, BD0801 showed a better effect than Bevacizumab (Bev) on the inhibition of cell growth and induction of apoptosis in HCC cells in vitro and in vivo. These findings suggest that BD0801 is a potent anti-VEGF monoclonal antibody for the treatment of HCC.


Development and implementation of a continuing care program for patients with intellectual and developmental disabilities in family medicine.
In the United States, individuals with intellectual and developmental disabilities (IDD) consistently experience health disparities. One factor is limited access to quality healthcare services equipped to meet the needs of those with IDD, particularly as they transition to adulthood. The purpose of this work is to describe the development and implementation of Jefferson's Continuing Care Program (JCCP), which was designed to address this care gap. We share how the idea, logistics, and support for the clinic were developed; how JCCP was designed to be uniquely accessible both via physical space and clinic flow; and how those challenges encountered have been crucial for fine-tuning optimal patient care. Since its inception in 2019, JCCP has made large strides towards educating the next generation of medical providers to care for patients with IDD. Looking to the future, JCCP plans to broaden its impact by serving more patients, continuing our advocacy and education work, and continuing to adapt to the needs of our community.


Congenital Guillain-Barré syndrome associated with maternal inflammatory bowel disease is responsive to intravenous immunoglobulin.
A 34-week floppy preterm infant born to a mother with acute ulcerative colitis presented with a progressive reduction in spontaneous limb movements, severe generalized hypotonia, areflexia, autonomic dysfunction and respiratory failure. Electromyography revealed pronounced denervation activity and markedly slow nerve conduction velocity (3 m/s) with evidence of conduction block. These findings indicated demyelination with additional axonal features. The infant was diagnosed with congenital Guillain-Barré syndrome, was treated with intravenous immunoglobulin and showed clinical improvement within 48 hours of treatment. The relationship between inflammatory bowel syndrome and inflammatory demyelinating polyneuropathy is discussed.


The development and use of a universal model to predict tree crop harvester pesticide exposure.
A simple regression model is presented for predicting the transfer of residual foliar applied pesticide to the body of a Florida citrus harvester. This model is dependent on work rate and residue concentration and agrees with an earlier model derived from similar data taken from a California study. This suggests that observed regional differences in the morbidity of harvesters in treated fields may be due to regional differences in foliar pesticide residue levels rather than regional differences in transport mechanisms of pesticide from foliage to worker. Eventual metabolite output in worker urine is also predicted.


Amantadine and rimantadine for influenza A in children and the elderly.
Influenza is an acute respiratory illness caused by influenza A and B viruses. Complications may occur, especially among children and the elderly. To assess the effectiveness and safety of amantadine and rimantadine in preventing, treating and shortening the duration of influenza A in children and the elderly. We searched CENTRAL (2014, Issue 9), MEDLINE (1966 to September week 4, 2014) and EMBASE (1980 to October 2014). Randomised controlled trials (RCTs) or quasi-RCTs comparing amantadine and/or rimantadine with no intervention, placebo, other antivirals or different doses or schedules of amantadine or rimantadine in children and the elderly with influenza A. Two review authors independently assessed the search results. We extracted and analysed data using the standard Cochrane methodology. We identified 12 studies (2494 participants: 1586 children and 908 elderly) comparing amantadine and rimantadine with placebo, paracetamol (one trial: 69 children) or zanamivir (two trials: 545 elderly) to treat influenza A.Amantadine was effective in preventing influenza A in children (773 participants, risk ratio (RR) 0.11; 95% confidence interval (CI) 0.04 to 0.30). The assumed risk of influenza A in the control group was 10 per 100. The corresponding risk in the rimantadine group was one per 100 (95% CI 0 to 3). Nevertheless, the quality of the evidence was low and the safety of the drug was not well established.For treatment, rimantadine was beneficial in abating fever on day three of treatment in children: one selected study with low risk of bias, moderate evidence quality and 69 participants (RR 0.36; 95% CI 0.14 to 0.91). The assumed risk was 38 per 100. The corresponding risk in the rimantadine group was 14 per 100 (95% CI 5 to 34).Rimantadine did not show any prophylactic effect in the elderly. The quality of evidence was very low: 103 participants (RR 0.45; 95% CI 0.14 to 1.41). The assumed risk was 17 per 100. The corresponding risk in the rimantadine group was 7 per 100 (95% CI 2 to 23).There was no evidence of adverse effects caused by treatment with amantadine or rimantadine.We found no studies assessing amantadine in the elderly. The quality of the evidence combined with a lack of knowledge about the safety of amantadine and the limited benefits of rimantadine, do not indicate that amantadine and rimantadine compared to control (placebo or paracetamol) could be useful in preventing, treating and shortening the duration of influenza A in children and the elderly.


C3 requirements for formation of alternative pathway C5 convertase.
Although alternative pathway C3 and C5 convertases both have active proteolytic sites dependent on the same protein, Bb, the quantitative requirements for the expression of these activities are sufficiently different to permit their delineation in terms of B input an cell-bound C3b. That the labile component of each active site is Bb was established by their parallel decay rates, regeneration of the original specificities with B in the presence of D, and stabilization of each convertase by C3NeF. The evidence that the spatial relationships of Bb and C3b on the cell surface for C3 and C5 convertase activities are distinct is based not only upon the decay and regeneration of each original convertase but more so upon their interconversion. C3 convertase is converted to C5 convertase by interaction with additional C3 whereas C5 convertase reverts to a C3 convertase by treatment with C3 INA. The capacity of C3 INA treatment to abolish C5 convertase sites without affecting C3 convertase sites indicates the existence of two functional species of C3b, one of which is protected in the C3bBb complex whereas the other is exposed.


Decision support system for NPK fertilization: a solution method for minimizing the impact on human health, climate change, ecosystem quality and resources.
Sugarcane cultivation requires correct fertilizer rates. However, when nutrients are not available, or there is over-fertilization, the yields are significantly reduced and the environmental burden increase. In this study, it is proposed a decision support system (DSS) for the correct NPK (nitrogen, phosphorus and potassium) fertilization. The DSS consists of two fuzzy models; the edaphic condition model (EDC-M) and the NPK fertilization model (NPK-M). The DSS using parameters from soil analysis and is based on the experience of two groups of experts to avoid the bias to the reality of a single group of professionals. The results of the DSS are compared with the results of soil analysis and those of the group of experts. One hundred and sixty tests were developed in the NPK-M. The N rate shows R 2=0.981 for the DSS and R 2=0.963 for soil analyzes. The P rate shows R 2=0.9702 for the DSS and R 2=0.9183 for the soil analyzes. The K rate shows R 2=0.9691 for the DSS and R 2=0.9663 for the soil analyzes. Environmental results indicate that the estimated rates with the DSS do reduce the environmental impact on the tests performed.


Evaluation of Dose Uncertainty to the Target Associated With Real-Time Tracking Intensity-Modulated Radiation Therapy Using the CyberKnife Synchrony System.
We investigated the dose uncertainty caused by errors in real-time tracking intensity-modulated radiation therapy (IMRT) using the CyberKnife Synchrony Respiratory Tracking System (SRTS). Twenty lung tumors that had been treated with non-IMRT real-time tracking using CyberKnife SRTS were used for this study. After validating the tracking error in each case, we did 40 IMRT planning using 8 different collimator sizes for the 20 patients. The collimator size was determined for each planning target volume (PTV); smaller ones were one-half, and larger ones three-quarters, of the PTV diameter. The planned dose was 45 Gy in 4 fractions prescribed at 95% volume border of the PTV. Thereafter, the tracking error in each case was substituted into calculation software developed in house and randomly added in the setting of each beam. The IMRT planning incorporating tracking errors was simulated 1000 times, and various dose data on the clinical target volume (CTV) were compared with the original data. The same simulation was carried out by changing the fraction number from 1 to 6 in each IMRT plan. Finally, a total of 240 000 plans were analyzed. With 4 fractions, the change in the CTV maximum and minimum doses was within 3.0% (median) for each collimator. The change in D99 and D95 was within 2.0%. With decreases in the fraction number, the CTV coverage rate and the minimum dose decreased and varied greatly. The accuracy of real-time tracking IMRT delivered in 4 fractions using CyberKnife SRTS was considered to be clinically acceptable.


Sulfation of phenylephrine by the human cytosolic sulfotransferases.
Previous studies had demonstrated that sulfation constituted a major pathway for the metabolism of phenylephrine in vivo. The current study was designed to identify the major human SULT(s) responsible for the sulfation of phenylephrine. Of the twelve human SULTs analyzed, SULT1A3 displayed the strongest sulfating activity toward phenylephrine. The enzyme exhibited a pH optimum spanning 7 - 10.5. Kinetic analysis revealed that SULT1A3- mediated sulfation of phenylephrine occurred in the same order of magnitude compared with that previously reported for SULT1A3-mediated sulfation of dopamine. Moreover, sulfation of phenylephrine was shown to occur in HepG2 cells under metabolic setting. Collectively, these results provided useful information concerning the biochemical basis underlying the metabolism of phenylephrine in vivo as previously reported.


Cell Polarity in Cerebral Cortex Development-Cellular Architecture Shaped by Biochemical Networks.
The human cerebral cortex is the seat of our cognitive abilities and composed of an extraordinary number of neurons, organized in six distinct layers. The establishment of specific morphological and physiological features in individual neurons needs to be regulated with high precision. Impairments in the sequential developmental programs instructing corticogenesis lead to alterations in the cortical cytoarchitecture which is thought to represent the major underlying cause for several neurological disorders including neurodevelopmental and psychiatric diseases. In this review article we discuss the role of cell polarity at sequential stages during cortex development. We first provide an overview of morphological cell polarity features in cortical neural stem cells and newly-born postmitotic neurons. We then synthesize a conceptual molecular and biochemical framework how cell polarity is established at the cellular level through a break in symmetry in nascent cortical projection neurons. Lastly we provide a perspective how the molecular mechanisms applying to single cells could be probed and integrated in an in vivo and tissue-wide context.


Parental knowledge and attitudes about human papilloma virus in Iran.
Infection by human papillomavirus (HPV) is one of common sexually transmitted diseases leading to cervical cancer. Evaluation of parental knowledge and attitudes toward HPV were aims of present study to provide an appropriate method to decrease burden of this infection on society. During this study, 358 parents were assessed for knowledge about HPV and its related disorders. Some 76% of parents had no information about HPV infection and among the informed parents 36% had obtained their information via internet and others from studying medical resources. The average score of mothers information about HPV infection was higher than that of fathers, and also educational level and age had significant impact on knowledge of parents about HPV. Parent knowledge about the hazards of HPV was higher than their knowledge about modes of transmission. Lack of awareness about HPV infection was high in this study, underlining the urgency of education among all adult people in our society.


[The effect of the increase in the calcium concentration induced by action of the ionophore A-23187 on mitosis in cultured ESK cells].
After addition of 20 mM calcium ionophore A23187 to cultured PK (pig kidney embryo) cells, [Ca++] in cytosol increased by more than 10 times. The maximum [Ca++] concentration was observed 1-2 min after drug introduction. Later on [Ca++] gradually decreased, and after 30 min of incubation with A23187 [Ca++] its concentration was 3-5 times higher than in the norm. 1 min after introduction of the calcium ionophore, mitotic spindles shortened for 1/3 and the angle of divergence of spindle microtubules from the centrosome extended. These changes remained for 5 min of treatment. After nocodazole treatment the length of the mitotic spindle reduced (2 min), then mitotic spindle and the metaphase plate were disrupted. The rate of mitotic spindle shortening after addition of the ionophore is about the same as after addition of nocodazole, but after ionophore treatment the metaphase plate remained for more than 5 min. Based on the results obtained we suggest that the maximum distance between spindle poles at metaphase is in the intact cell, and after any perturbation of normal microtubule dynamics the spindle may rapidly collapse. The collapsed mitotic spindle becomes more stable and its size is determined predominantly by kinetochore fibers. The metaphase spindle is completely and rapidly destroyed when the microtubule growth is prohibited, but it is preserved when this growth is restricted.


[Pulmonary hypertension in chronic myeloproliferative disorders].
We report on three autopsy cases with clinical and morphological evidence of pulmonary hypertension and concurrent myeloproliferative disorders. Massive accumulations of pleomorphic, atypical megakaryocytes and thrombotic material are found within the pulmonary capillary beds. Morphometrical studies allowed us to identify on average 1,293.4 (1,145.8-1,401) megakaryocytes per one square centimetre lung tissue (standard value: 25 megakaryocytes/cm(2) lung tissue). The lungs of the controls with unaffected parenchyma show smaller numbers of megakaryocytes. It seems highly unlikely that these haematopoietic cells originate in lung capillaries in the absence of morphological correlates. Recurrent chronic microemboli consisting of megakaryocytes and thrombocytes could be held responsible for the development of secondary chronic pulmonary hypertension. Our observations suggest that pulmonary hypertension associated with chronic myeloproliferative disorders should be classified into the fourth group of the EVIAN-classification of pulmonary hypertension.


Wound infection after cataract surgery: a report of two cases.
This is a report of 2 cases of fungal wound infection after cataract surgery (phacoemulsification). Both patients were noticed to have the fungal wound infection at the one-month follow-up after the surgery. Although both patients had been advised to taper steroid containing antibiotic eye drops, they failed to do so. Despite intensive treatment with antifungal eye drops and oral antifungal agents, visual outcome was poor. Fungal infection of the wound may occur in cataract patients in the post-operative period. This infection is probably more common in patients who have had a temporal incision and who are from an agricultural background living in a hot and humid climate.


Mist1-null mice are resistant to streptozotocin-induced beta cell damage.
Streptozotocin (STZ), a pancreatic beta cell toxin, is used to induce diabetic conditions by targeting the Glut-2 transporter. We have recently identified decreased Glut-2 expression in beta cells of mice lacking the transcription factor Mist1 (Mist1(KO)). Given the loss in Glut-2 expression, we examined whether Mist1(KO) beta cells have an increased resistance to STZ. Mist1(KO) and wild-type (WT) female mice received a single 100 or 200 mg/kg injection of STZ, and resting glucose levels and islet morphology were assayed 3-7 days after injection. Ten-month-old Mist1(KO) mice have less beta cell damage when exposed to high levels of STZ while 2-month-old Mist1(KO) mice exhibit a dose-dependent resistance. Surprisingly, Mist1(KO) mice still have elevated fasting glucose levels when compared to WT mice. These results suggest that while Mist1(KO) islets have increased resistance to STZ, additional effects outside of beta cell loss alter blood glucose homeostasis.


HE4: a new potential early biomarker for the recurrence of ovarian cancer.
Human epididymis protein 4 (HE4) has recently been described as a new marker for the early diagnosis of ovarian cancer (OC). The objective of this study was to evaluate (a) the expression of HE4 vs. OC mucin CA125 in 32 patients with OC compared to 163 patients with other malignant or benign pathologies (b) HE4 as indicator of the recurrence of the disease in eight patients followed-up for 20 months after OC diagnosis. Serum HE4 and CA 125 levels were determined by ELISA and IRMA, respectively. At diagnosis, the patients with OC demonstrated high levels of both biomarkers with 96.9% sensitivity for HE4 and 85.7% for CA125. In the other pathologies there was 3.7% positivity for HE4 and 21.0% for CA125. The follow-up study showed an increase of HE4 5-8 months before CA125 increment in five of the eight patients, this early expression being strictly associated to a relapse of the disease. In conclusion, this study showed that HE4, compared to CA125, potentially is a better marker for the diagnosis of OC and could be an important early indicator of the recurrence of the disease.


[Postoperative recurrence in Crohn's disease].
Intestinal resection in the natural history of Crohn's disease is a forced step. Unfortunately surgery is not curative as disease inexorably recurs. The frequency of recurrence varies according to the definitions adopted, being high when endoscopical criteria are used (70-90% at one year). Among risk factors, the most convincing is a smoking habit. The pathogenesis of recurrence is still unknown. Particular attention was paid to colo-ileal reflux which occurs after the resection of the ileocecal valve. The diagnosis should always be based on morphological criteria (endoscopy or radiology). In fact symptoms occur late and are often uncharacteristic. A particular problem in the management of patients with Crohn's disease is the prevention of post-operative recurrence. Recent randomized, controlled trials of which the first has been published by the authors of this article, demonstrated that the administration of 5-ASA early after resection may prevent, delay or attenuate such recurrences. Cessation of smoking also plays a central role in prevention. The final message is that in active Crohn's disease surgery should not be excessively delayed. Early resection followed by prophylactic treatment seems to improve the quality of life in patients with more severe Crohn's disease.


Predictors of performance and perceived fatigability in people with multiple sclerosis.
Fatigability is a distinct construct from fatigue that has been reported to contribute to activity limitations in people with multiple sclerosis (PwMS). Identifying predictors of performance and perceived fatigability may guide the development of interventions to mitigate fatigability. This study investigated predictors of performance and perceived fatigability among PwMS. PwMS (N = 51) completed self-report measures of demographics, clinical history, symptoms severity (Modified Fatigue Impact Scale), and functioning (PROMIS Physical Function and PROMIS Cognitive Function Abilities). Performance fatigability measures included Ambulatory Fatigue Index (AFI), Deceleration Index (DI), and Distance Walking Index (DWI). Perceived fatigability measures included Pittsburgh Fatigability Scale (PFS), Perceived Physical Exertion, and Perceived Fatigue Intensity. Performance and perceived fatigability measures were calculated based on the Timed 25-Foot Walk Test and the 6-Minute Walk Test. Multivariable linear regression analyses indicated that PROMIS Cognitive Function was a significant independent predictor of performance fatigability measured with AFI (β = -0.515, p = 0.007), DI (β = -0.511, p = 0.008), and DWI (β = -0.516, p = 0.007). Regarding perceived fatigability, PROMIS Pain Intensity predicted Perceived Fatigue Intensity (β = 0.325, p = 0.035). PROMIS Physical Function predicted PFS Mental fatigability (β = -0.503, p < 0.001). PROMIS Physical Function (β = -0.619, p < 0.001) and Cognitive Function (β = -0.249, p = 0.037) predicted PFS Physical fatigability. Preliminary findings suggest that self-reported functioning levels, including physical and perceived cognitive function, are potential predictors of performance and perceived fatigability in MS. Notably, perceived fatigue impact showed no association with performance or perceived fatigability. Future studies are warranted to confirm and extend our findings.


Effect of prolonged and neonatal capsaicin treatments on the substance P immunoreactive nerves in the rabbit eye and spinal cord.
Substance-P (SP) immunoreactivity was demonstrated in the rabbit eye and spinal cord using monoclonal SP antibody and an indirect immunofluorescence technique. Norves containing SP immunoreactive material were found in the cornea, iris and ciliary body of which the iridic sphincter had the densest innervation. Neither prolonged subcutaneous treatment (up to 280 mg/kg) augmented by intracameral capsaicin injection nor neonatal treatment with drug 70 mg/kg eliminated this immunoreactivity, though both blocked the miotic effect of intracameral SP. It is concluded that capsaicin is not specific SP depleting agent but rather a neurotocic substance that affects noxious pathways and probably prevents the release of the SP retained by the nerve following the treatment used.


Behavioral evaluation of GH treatment in short statured children and adolescents: findings from a pilot study.
A cohort of 93 short-statured children and adolescents undergoing GH treatment were evaluated with respect to behavior, emotions, and attitudes. The sample consisted of patients suffering from either idiopathic GH deficiency or neurosecretory dysfunction (no.=47), Turner syndrome (no.=20), organic GH deficiency due to brain tumors (no.=10), or other etiologies (no.=16). The Child Behavior Checklist (CBCL) together with a brief Evaluation of Treatment Questionnaire (ETQ) were filled out by the patient's parents. These evaluations were performed at onset and after 12 and 24 months of GH treatment, respectively. There was a highly significant but clinically small decline of behavioral abnormalities over time and parents saw major benefits of GH treatment in the total group of patients. The behavioral changes over time were independent of diagnostic category, gender, height velocity, puberty and age.


What is speciation and how should we study it?
To understand speciation, we first need to know what species are. Yet debates over species concepts have seemed endless, with little obvious relevance to the study of speciation. Recently, there has been progress in resolving these debates, favoring a lineage-based, evolutionary species concept. This progress calls for reconsideration of the study of speciation. Traditional speciation research based on the biological species concept has led to great advances in understanding how nonallopatric speciation occurs and how species diverge and remain separate from each other. However, this research has neglected the question of how new species arise in the first place for the most common geographic mode (allopatric). A new and very different research program is needed to understand the ecological and evolutionary processes that split an ancestral species into new allopatric lineages. This research program will connect speciation to many other fundamental questions in evolutionary biology, ecology, biogeography, and conservation biology.


Influence of Load Carriage on High-Intensity Running Performance Estimation.
Load carriage is a necessary burden for tactical athletes. A combination of training modes, including aerobic conditioning and progressive load carriage, may lead to improved performance. The critical speed (CS) concept enables the practitioner to prescribe high-intensity interval training (HIIT) time limits (TLIMs) from a single 3-minute all-out exercise test (3 MT). We sought to examine the effect of a standard load carriage (18.86 kg) on CS and the finite running capacity > CS (D'). A group of trained subjects (age: 26 ± 5 years, height: 181 ± 4 cm, body mass [BM]: 90 ± 14 kg) completed a loaded and unloaded (UL) 3 MT. The CS was reduced by 0.66 ± 0.24 m·s (p < 0.01) in the loaded condition. There was a small nonsignificant increase in D' (21.25 ± 39.53 m, p = 0.07). The higher the % load carriage relative to BM is, the greater decline in CS (r = 0.83, p < 0.01). A revised CS with load carriage from the UL 3 MT may be calculated using: adjusted CS = original CS + ([-0.0638 × %load]) + 0.6982. Our results indicate that revised CS and TLIMs for fixed distance, fixed time, or fixed speed HIIT prescriptions may be derived from a UL 3 MT. Such calculations would enable more expeditious training for tactical athletes. We recommend further research involving implementation of HIIT using this new method.


Rheumatoid Arthritis in Sickle-Cell Population: Pathophysiologic Insights, Clinical Evaluation and Management.
The advent of hydroxyurea and advanced medical care, including immunizations has led to improved survival among patients with Sickle Cell Disease (SCD). This prolonged survival however, introduces a chronic inflammatory disorder, Rheumatoid Arthritis (RA), which presents at a relatively older age and is rarely reported among SCD patients. In this review, we highlight the epidemiological association of SCD-RA and discuss the underlying common pathogenetic mechanisms, such as endothelial dysfunction, the role of inflammatory cytokines and oxidative stress. We also point to the difficulties in ascertaining the clinical diagnosis of RA in SCD patients. Finally, we provide rationale for therapeutic options available for RA and the challenges in the management of these patients with agents that are known to increase the risk of infection and immunosuppression such as steroids, disease modifying anti-rheumatic drugs and biologics.


Impact of mechanical ventilation on the pathophysiology of progressive acute lung injury.
The earliest description of what is now known as the acute respiratory distress syndrome (ARDS) was a highly lethal double pneumonia. Ashbaugh and colleagues (Ashbaugh DG, Bigelow DB, Petty TL, Levine BE Lancet 2: 319-323, 1967) correctly identified the disease as ARDS in 1967. Their initial study showing the positive effect of mechanical ventilation with positive end-expiratory pressure (PEEP) on ARDS mortality was dampened when it was discovered that improperly used mechanical ventilation can cause a secondary ventilator-induced lung injury (VILI), thereby greatly exacerbating ARDS mortality. This Synthesis Report will review the pathophysiology of ARDS and VILI from a mechanical stress-strain perspective. Although inflammation is also an important component of VILI pathology, it is secondary to the mechanical damage caused by excessive strain. The mechanical breath will be deconstructed to show that multiple parameters that comprise the breath-airway pressure, flows, volumes, and the duration during which they are applied to each breath-are critical to lung injury and protection. Specifically, the mechanisms by which a properly set mechanical breath can reduce the development of excessive fluid flux and pulmonary edema, which are a hallmark of ARDS pathology, are reviewed. Using our knowledge of how multiple parameters in the mechanical breath affect lung physiology, the optimal combination of pressures, volumes, flows, and durations that should offer maximum lung protection are postulated.


RhoA and cytoskeletal disruption mediate reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity.
Spaceflight, aging, and disuse lead to reduced BMD. This study shows that overexpression of constitutively active RhoA restores actin cytoskeletal arrangement, enhances the osteoblastic phenotype, and suppresses the adipocytic phenotype of human mesenchymal stem cells cultured in modeled microgravity. Reduced BMD during spaceflight is partly caused by reduced bone formation. However, mechanisms responsible for this bone loss remain unclear. We have previously shown reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells (hMSCs) cultured in modeled microgravity (MMG). The small GTPase, RhoA, regulates actin stress fiber formation and has been implicated in the lineage commitment of hMSCs. We examined the effects of MMG on actin cytoskeletal organization and RhoA activity and the ability of constitutively active RhoA to reverse these effects. hMSCs were seeded onto plastic microcarrier beads at a density of 10(6) and allowed to form aggregates in DMEM containing 10% FBS for 7 days. Aggregates were incubated in DMEM containing 2% FBS for 6 h with or without an adenoviral vector containing constitutively active RhoA at a multiplicity of infection (moi) of 500 and allowed to recover in 10% FBS for 24 h. Cells were transferred to the rotary cell culture system to model microgravity or to be maintained at normal gravity for 7 days in DMEM, 10% FBS, 10 nM dexamethasone, 10 mM beta-glycerol phosphate, and 50 muM ascorbic acid 2-phosphate. F-actin stress fibers are disrupted in hMSCs within 3 h of initiation of MMG and are completely absent by 7 days, whereas monomeric G-actin is increased. Because of the association of G-actin with lipid droplets in fat cells, the observed 310% increase in intracellular lipid accumulation in hMSCs cultured in MMG was not unexpected. Consistent with these changes in cellular morphology, 7 days of MMG significantly reduces RhoA activity and subsequent phosphorylation of cofilin by 88+/-2% and 77+/-9%, respectively. Importantly, introduction of an adenoviral construct expressing constitutively active RhoA reverses the elimination of stress fibers, significantly increases osteoblastic gene expression of type I collagen, alkaline phosphatase, and runt-related transcription factor 2, and suppresses adipocytic gene expression of leptin and glucose transporter 4 in hMSCs cultured in MMG. Suppression of RhoA activity during MMG represents a novel mechanism for reduced osteoblastogenesis and enhanced adipogenesis of hMSCs.


Platelet-activating factor receptor.
Platelet-activating factor (PAF) is a pro-inflammatory lipid mediator possessing a unique 1-O-alkyl glycerophospholipid (GPC) backbone (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholin). Cloned PAF receptor, which belongs to the G protein-coupled receptor superfamily, transduces pleiotropic functions including cell motility, smooth muscle contraction, and synthesis and release of mediators and cytokines via multiple heterotrimeric G proteins. Pharmacological studies have suggested that PAF functions in a variety of settings including allergy, inflammation, neural functions, reproduction, and atherosclerosis. Establishment of PAFR(-/-) mice confirmed that the PAF receptor is responsible for pro-inflammatory responses, but that its roles in other settings remain to be clarified.


Electron-Transferred Donor/Acceptor Ferrimagnet with T(C) = 91 K in a Layered Assembly of Paddlewheel [Ru2] Units and TCNQ.
The donor (D)/acceptor (A) assembly reaction of the paddlewheel-type diruthenium(II,II) complex [Ru2(2,4,6-F3PhCO2)4(THF)2] (2,4,6-F3PhCO2(-) = 2,4,6-trifluorobenzoate; abbreviated hereafter as [Ru2]) with 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) in a p-xylene/CH2Cl2 solvent system led to the formation of a two-dimensional layered compound, [{Ru2(2,4,6-F3PhCO2)4}2(TCNQ)]·2(p-xylene)·2CH2Cl2 (1). As expected from this D/A combination, 1 has a one-electron-transfer ionic state with the D(0.5+)2A(-) formulation. This state formally derives a heterospin state composed of S = 1 for [Ru(II,II)2], S = 3/2 for [Ru(II,III)2](+), and S = ½ for TCNQ(•-), possibly causing intralayer ferrimagnetic spin ordering. Most of these types of compounds have an antiferromagnetic ground state because of the coupling of ferrimagnetically ordered layers in dipole antiferromagnetic interactions. However, 1 became a three-dimensional ferrimagnet with T(C) = 91 K because of the presence of interlayer ferromagnetic interactions.


Ruptured Medullary Hemangioblastoma Mimicking a Craniocervical Junction Dural Arteriovenous Fistula with a Pseudoaneurysm.
Hemangioblastomas (HBMs) are rare vascular tumors commonly located in the posterior fossa of adults. A mid-50s patient presented with sudden unconsciousness. Computed tomography scans revealed acute hemorrhages around the posterior fossa, predominantly in the subarachnoid space. Digital subtraction angiography (DSA) revealed an 8-mm round lesion filled with contrast agent, fed by the C1 segmental artery of the left vertebral artery (VA), showing early venous drainage to the spinal cord and brainstem. Emergent embolization was attempted under suspicion of a ruptured dural arteriovenous fistula, resulting in parent artery occlusion due to feeder selection failure. Follow-up DSA after a month depicted a persistent aneurysm via collaterals from both VAs. Consequently, the decision was made to proceed with surgical intervention, leading to the resection of the lesion, confirming its diagnosis as a HBM through histological examination. This case underscores the potential for misdiagnosis when HBMs with an intratumoral shunt mimic vascular shunt lesions.


Phylogenetic analysis of the mycoplasmas.
The phylogenetic relationships between the mycoplasmas and bacteria have been established from a comparative analysis of their 16S rRNA oligonucleotide catalogs. The genera Mycoplasma, Spiroplasma, and Acholeplasma arose by degenerative evolution, as a deep branch of the subline of clostridial ancestry that led to Bacillus and Lactobacillus. Thermoplasma has no specific relationship to the other mycoplasmas; it belongs with the archaebacteria.


Studies on the quality nutrition in women with polycystic ovary syndrome (PCOS)
Polycystic ovary syndrome (PCOS) manifests itself with various symptoms, therefore it interests representatives of many medical specializations: general practitioners, gynecologists, endocrinologists, dermatologists, cardiologists and those who deal with metabolic disorders, such as dieticians. The aim of this study was perform the qualitative assessment of components of diets of women with PCOS as one of the major factor contributing to the disease. The study was performed on 54 women of childbearing age with PCOS diagnosed according to on the Rotterdam criteria. Qualitative assessment of the diets on the basis of 216 menus was performed based on the analysis of 3-day food diaries and food records taken from the last 24-hour dietary interview. Diets quality assessment was made using three types of point tests: Szewczyński's Diets' classification (SDC), Bielińska's Test with Kulesza's modification (BTK), Healthy Diet Indicator (HDI). Average waist-hip ratio (WHR) and body mass index (BMI) was above the standard 0.91± 0.08 and 29.16 ± 5.8 kg/m2. Qualitative analysis performed with point tests SDC, BT-K and HDI revealed that the majority of the diets were composed inappropriately, containing many mistakes. Statistically significant correlations (Pearson's) were determined between HDI test and the body weight and BMI. When analyzing the type of the meals also the correlations (Spearman's) between BMI and BMI category in BT-K test. Mistakes in diets of women with PCOS are the cause of metabolic disorders related to improper function of ovaries. Native test BT-K seems to be a better method then test SDC and probably HDI of assessing diet in women with PCOS from Poland.


Perceptions of Cancer Care and Clinical Trials in the Black Community: Implications for Care Coordination Between Oncology and Primary Care Teams.
Despite efforts to ameliorate disparities in cancer care and clinical trials, barriers persist. As part of a multiphase community-engaged assessment, an exploratory community-engaged research partnership, forged between an academic hospital and a community-based organization, set out to explore perceptions of cancer care and cancer clinical trials by black Bostonians. Key informant interviews with health care providers and patient advocates in community health centers (CHCs), organizers from grassroots coalitions focused on cancer, informed the development of a focus group protocol. Six focus groups were conducted with black residents in Boston, including groups of cancer survivors and family members. Transcripts were coded thematically and a code-based report was generated and analyzed by community and academic stakeholders. While some participants identified clinical trials as beneficial, overall perceptions conjured feelings of fear and exploitation. Participants describe barriers to clinical trial participation in the context of cancer care experiences, which included negative interactions with providers and mistrust. Primary care physicians (PCPs) reported being levied as a trusted resource for patients undergoing care, but lamented the absence of a mechanism by which to gain information about cancer care and clinical trials. Confusion about cancer care and clinical trials persists, even among individuals who have undergone treatment for cancer. Greater coordination between PCPs and CHC care teams and oncology care teams may improve patient experiences with cancer care, while also serving as a mechanism to disseminate information about treatment options and clinical trials. Inequities in cancer care and clinical trial participation persist. The findings of this study indicate that greater coordination with primary care physicians (PCPs) and community health center (CHC) providers may be an important step for both improving the quality of cancer care in communities and increasing awareness of clinical trials. However, PCPs and CHCs are often stretched to capacity with caring for their communities. This leaves the oncology community well positioned to create programs to bridge the communication gaps and provide resources necessary to support oncologic care along the cancer continuum, from prevention through survivorship.


[The problems of mastitis in mares].
Based on a group of 33 mares infected with mastitis, data regarding the time of appearance, the clinical symptoms and the bacteriological causes of the disease were evaluated. The cases were distributed as follows: 27.3% before delivery, 24.2% immediately after delivery (until the third day), 12.1% during the middle and late stages of lactation, 9.1% immediately after the weaning of the foal and 27.3% outside the lactation period of non-pregnant mares. The clinical picture is described. In the majority of the cases, both halves of the udder were infected. The analysis of the bacteriological results showed that from 70 isolated germ types no less than 36 were streptococci (in 25 cases beta-haemolytic streptococci). Compared to this, E. coli (3 cases), coliform germs (6 cases) and klebsiella (2 cases) were found rather seldom. The additional examination of milk samples taken from healthy mares during the first seven days after delivery showed that 13 (= 41.9%) of the mares, or 21.0% of the milk samples (n = 62), were bacterially contaminated. Here, too, the streptococci formed the majority of the germs.


Prognostic factors for survival after transarterial chemoembolization combined with microwave ablation for hepatocellular carcinoma.
To analyze prognostic factors for survival after transarterial chemoembolization (TACE) combined with microwave ablation (MWA) for hepatocellular carcinoma (HCC). Clinical data of 86 patients who underwent TACE combined with MWA between January 2006 and December 2013 were retrospectively analyzed in this study. Survival curves were detected using log-rank test. Univariate analysis was performed using log-rank test with respect to 13 prognostic factors affecting survival. All statistically significant prognostic factors identified by univariate analysis were entered into a Cox proportion hazards regression model to identify independent predictors of survival. P values were two-sided and P < 0.05 was considered statistically significant. Median follow-up time was 47.6 mo, and median survival time of enrolled patients was 21.5 mo. The 1-, 2-, 3- and 5-year overall survival rates were 72.1%, 44.1%, 31.4% and 13.9%, respectively. Tumor size(χ(2) = 14.999, P = 0.000), Barcelona Clinic Liver Cancer (BCLC) stage (χ(2) = 29.765, P = 0.000), Child-Pugh class (χ(2) = 51.820, P = 0.000), portal vein tumor thrombus (PVTT) (χ(2) = 43.086, P = 0.000), arterio-venous fistula (χ(2) = 29.791, P = 0.000), MWA therapy times (χ(2) = 12.920, P = 0.002), Eastern Cooperative Oncology Group (ECOG) score (χ(2) = 28.660, P = 0.000) and targeted drug usage (χ(2) = 10.901, P = 0.001) were found to be significantly associated with overall survival by univariate analysis. Multivariate analysis identified that tumor size (95%CI: 1.608-4.962, P = 0.000), BCLC stage (95%CI: 1.016-2.208, P = 0.020), PVTT (95%CI: 2.062-9.068, P = 0.000), MWA therapy times (95%CI: 0.402-0.745, P = 0.000), ECOG score (95%CI: 1.012-3.053, P = 0.045) and targeted drug usage (95%CI: 1.335-3.143, P = 0.001) were independent prognostic factors associated with overall survival. Superior performance status, MWA treatment and targeted drug were favorable factors, and large HCC, PVTT and advanced BCLC stage were risk factors for survival after TACE-MWA for HCC.