Copper nanoparticles decorated inside or outside carbon nanotubes used for methyl acetate hydrogenation.
Copper nanoparticles loaded inside or outside carbon nanotubes (CNTs) were prepared by a simple wet chemistry method. The structures and physicochemical properties of the obtained materials were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Methyl acetate (MA) hydrogenation forming methanol and ethanol was chosen as the application to explore the catalytic performances of copper inside and outside CNTs. The reaction results indicated that the catalytic activity of Cu-inside-CNTs catalyst was significantly higher than that of Cu-outside-CNTs because of the space confined effects. Furthermore, the influences of Cu content on CNTs to the catalytic performance were also investigated.


Endothelial cells stimulate T cell NFAT nuclear translocation in the presence of cyclosporin A: involvement of the wnt/glycogen synthase kinase-3 beta pathway.
T cells resistant to the immunosuppressive drug cyclosporin A (CsA) may be important mediators of chronic graft rejection. We previously reported that T cells activated in the presence of endothelial cells (EC) develop resistance to CsA, and initiate IL-2 secretion within 8-12 h of triggering. CsA normally blocks the phosphatase, calcineurin, thus preventing nuclear translocation of the transcription factor, NFAT. We find that in the presence but not the absence of EC, NFAT1 can be detected in the nuclei of CsA-treated T cells within 8 h of triggering, reaching a maximal level of 60% of control by 24 h. Glycogen synthase kinase-3beta (GSK-3beta), which rephosphorylates NFAT and promotes nuclear export, is inhibited by EC costimulation. GSK-3beta is a component of the wnt signaling pathway, and EC express wnt-5a and T cells express frizzled-5, a wnt-5a receptor. Wnt-5a promotes T cell NFAT nuclear accumulation in the presence of CsA, an effect mimicked by Li(+), a potent inhibitor of GSK-3beta. The protein kinase C agonist PMA dramatically synergizes with both EC and wnt-5a in stimulating T cell IL-2 synthesis, and inhibition of either protein kinase C by Ro-31-8425 or G-proteins by pertussis toxin effectively blocks the actions of wnt-5a on T cells. Finally, a secreted, dominant-negative form of frizzled-5 blocks EC-mediated CsA resistance. Thus, EC promote CsA-resistant nuclear localization of NFAT and subsequent IL-2 synthesis through a noncanonical wnt-dependent pathway.


Genetic voltage indicators.
As a "holy grail" of neuroscience, optical imaging of membrane potential could enable high resolution measurements of spiking and synaptic activity in neuronal populations. This has been partly achieved using organic voltage-sensitive dyes in vitro, or in invertebrate preparations yet unspecific staining has prevented single-cell resolution measurements from mammalian preparations in vivo. The development of genetically encoded voltage indicators (GEVIs) and chemogenetic sensors has enabled targeting voltage indicators to plasma membranes and selective neuronal populations. Here, we review recent advances in the design and use of genetic voltage indicators and discuss advantages and disadvantages of three classes of them. Although genetic voltage indicators could revolutionize neuroscience, there are still significant challenges, particularly two-photon performance. To overcome them may require cross-disciplinary collaborations, team effort, and sustained support by large-scale research initiatives.


In vivo imaging of differences in early donor cell proliferation in graft-versus-host disease hosts with different pre-conditioning doses.
Graft-versus-host disease (GVHD) results from immunemediated attacks on recipient tissues by donor-originated cells through the recognition of incompatible antigens expressed on host cells. The pre-conditioning irradiation dose is a risk factor influencing GVHD severity. In this study, using newly generated luciferase transgenic mice on a B6 background (B6.Luc(Tg)) as bone marrow and splenocyte donors, we explored the effects of irradiation doses on donor cell dynamics in major histocompatibility complex (MHC)-matched allogeneic GVHD hosts via bioluminescence imaging (BLI). Results from BLI of GVHD hosts showed higher emission intensities of luminescence signals from hosts irradiated with 900 cGy as compared with those irradiated with 400 cGy. In particular, BLI signals from target organs, such as the spleen, liver, and lung, and several different lymph nodes fluctuated with similar time kinetics soon after transplantation, reflecting the synchronous proliferation of donor cells in the different organs in hosts irradiated with 900 cGy. The kinetic curves of the BLI signals were not synchronized between the target organs and the secondary organs in hosts irradiated with 400 cGy. These results demonstrate that pre-conditioning doses influence the kinetics and degree of proliferation in the target organs soon after transplantation. The results from this study are the first describing donor cell dynamics in MHC-matched allogeneic GVHD hosts and the influence of irradiation doses on proliferation dynamics, and will provide spatiotemporal information to help understand GVHD pathophysiology.


In search of the elusive U-shaped performance-turnover relationship: are high performing Swiss bankers more liable to quit?
This project revisits the perennial debate over the relationship between job performance and turnover. Disputing traditional findings, C. Trevor, B. Gerhart, and J. Boudreau (1997) observed that high and low performers quit more than do average performers. They further challenged received wisdom by showing that promotions can induce turnover, especially among poor performers, by signaling ability. The authors sought to replicate and extend these unconventional findings by exploring curvilinear and moderating effects on the performance-exit relationship among 11,098 Swiss nationals employed in a bank. Survival regression revealed that performance is curvilinearly related to quits and that bonus pay deterred superior performers from leaving more than did pay increases. Further, the average number of job levels advanced per promotion rather than promotion rate increased quit risks. Cultural and organizational moderators of performance-termination associations and effective strategies for retaining top performers are discussed.


[Consequences of insulin resistance on lipid profile in type2 diabetics group: study of 118 cases].
Insulin is a hormone which has an essential role in lipids metabolism by modulating the activity of many key enzymes and by its intervention on the production and the catabolism of lipoproteins. The aim of this study was to determine the influence of insulin resistance on lipid profile in a diabetic group. The study group consists of 118 diabetic patients. We assayed for each patient total cholesterol, high density lipoprotein cholesterol, triglycerides and insulin. Insulin resistance was determined by HOMA index. Insulin was found correlated to body mass index, triglycerides, waist circumference, and glycated haemoglobin. Triglycerides and glycated haemoglobin were significantly more elevated in insulin resistant group than in insulin sensitive group. Insulin resistance may be the initial anomaly in type 2 diabetes and incite us to search on molecular anomalies in the insulin action.


[Effects of antisense transforming growth factor beta receptor-I expressing plasmid on pig serum-induced rat liver fibrosis].
To observe the effects of antisense transforming growth factor beta receptor-I (TbetaRI) expressing plasmid on rat liver fibrosis. RT-nested-PCR and gene recombinant techniques were used to construct the rat antisense TbetaRI recombinant plasmid which can be expressed in eucaryotic cells. The recombinant plasmid and blanx vector (pcDNA3) were encapsulated by glycosyl-poly-L-lysine and then transducted into rats of pig serum-induced liver fibrosis model respectively. Expression of exogenous transfected plasmid was assessed by Northern blot, RT-PCR, Western blot and immunohistochemistry. Serum TGF-beta(1) was determined by ELISA. The content of hepatic hydroxyproline was tested. Immunohistochemistry was used to test type I and III collagen. VG staining was used for pathological study. The exogenous antisense TbetaRI could be expressed in vivo, and could block the mRNA and protein expression of TbetaRI in the fibrotic liver induced by pig serum. Its expression also reduced the level of TGF-beta(1) (P < 0.05) and decreased the the contents of hepatic hydroxyproline and the deposition of collagens type I and type III (P < 0.01). And its expression also improved the pathologic classification of liver fibrosis models (P < 0.01). The results demonstrate that the antisense TbetaRI recombinant plasmid has certain extern reverse effect on liver fibrosis and make it as a possible candidate for use in future gene therapy.


Modification of the existing maximum residue level for oxathiapiprolin in kales/radish leaves.
In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant DLR-Rheinpfalz submitted a request to the competent national authority in Germany to modify the existing maximum residue level (MRL) for the active substance oxathiapiprolin in kales, with the specific intention to derive an MRL in radish leaves (classified under the subgroup of kales), based on an intended NEU use on radishes. The residue data in radish leaves submitted in support of the request were found to be sufficient to derive MRL proposal for this commodity which could be applicable also for kales. Adequate analytical methods for enforcement are available to control the residues of oxathiapiprolin in radishes at the validated LOQ of 0.01 mg/kg. Based on the risk assessment results, EFSA concluded that the long-term intake of residues resulting from the use of oxathiapiprolin on radishes according to the reported agricultural practice is unlikely to present a risk to consumer health.


Development of new atom transfer radical polymerization system by iron (III)-metal salts without using any external initiator and reducing agent.
Atom transfer radical polymerization (ATRP) catalyzed by high oxidation state metal salts of FeX3 is developed for the first time in the absence of both external initiator and reducing agent. Methyl methacrylate (MMA) and styrene are polymerized successfully using FeX3 /Phosphorous ligands with well-controlled molecular weight distributions (=1.5). The molecular weight of the polymers increases with monomer consumption with the progress of time and the polymerization behaviors show a decent ATRP trend. Activators and initiators are suggested to generate in situ by the addition reaction of MMA and one equivalent of FeX3 . The PMMA synthesized from without-initiator system is characterized by (1) H, (13) C and DEPT (distortionless enhancement by polarization transfer nuclear magnetic resonance) nuclear magnetic resonance spectroscopy. Chain extension and copolymerization experiments prove the livingness of the obtained polymer.


Sex acts, sex partners, and sex budgets: implications for risk factor analysis and estimation of HIV transmission probabilities.
Many epidemiological studies have identified the number of sex partners as a risk factor for the acquisition of HIV, but few studies have identified the number of sex acts as a risk factor. The seeming lack of importance of the number of sex acts as a risk factor has yet to be explained. In this report we conduct an exploratory data analysis to evaluate the relationship between the number of sex acts and the number of sex partners for heterosexuals. Our results indicate that it may be most appropriate to view sexual activity within a sex budget and resource allocation framework. We use the results (a) to suggest an explanation for why the results from some of the risk factor analysis studies have identified a per partnership but not a per act risk, and (b) to assess the implications of the relationship for the estimation of heterosexual transmission probabilities for HIV.


Rotavirus A, C, and H in Brazilian pigs: potential for zoonotic transmission of RVA.
Rotaviruses (RVs) have been identified as one of the main infectious causes of diarrhea in young pigs. We determined the prevalence of rotavirus A (RVA), C (RVC), and H (RVH) in pigs on a Brazilian farm. Samples were screened by reverse-transcription (RT)-PCR, and samples positive for RVA were genotyped by PCR amplification and sequencing analysis. Of the 329 fecal samples analyzed, 102 (30.9%) were positive for RV, 25 (7.6%) contained RVA only, 32 (9.7%) contained RVC only, and 31 (9.4%) contained RVH only. Co-circulation, the presence of ≥ 2 RVs in a sample, was detected in 14 (4.2%) samples. Of the 15 animals with diarrhea, 6 (40%) were positive for RV, and of the 314 asymptomatic animals, 96 (30.6%) were positive for RV; there was no statistically significant difference between the 2 groups (p = 0.441). Genotyping of RVA strains showed co-circulation of genotypes G1, G3, G9-P[8]-I1, and I2-E1. Phylogenetic analysis showed that some of the RVA genotypes found in pigs had high percentages of identity when compared with reference strains from humans, which suggests interspecies transmission. Because RVs may be zoonotic, excretion of RVs into the environment can result in transmission to agricultural workers causing interspecies infections and allowing the emergence of new reassorted viruses.


Vital Conversations: An Interactive Conflict Resolution Training Session for Fourth-Year Medical Students.
The AAMC has recognized the importance of effective teamwork and collaboration. One core Entrustable Professional Activity emphasizes creating a climate of mutual respect and trust and prioritizing team needs over personal needs, which leads to safe, timely, effective, efficient, and equitable patient care. Relationship conflicts, specifically, are associated with decreased productivity, complex information processing, and work satisfaction. Given the prevalence of conflict and its impact on health care workers, the lack of conflict resolution curricula in undergraduate medical education is surprising. We developed a curriculum formally introducing these skills and allowing practice in a simulated environment before students entered residency. Fourth-year medical students completed a conflict resolution exercise in a mandatory transition-to-residency course. Students completed online prework including reflection on teamwork and information on conflict resolution styles, participated in a simulated conflict with a standardized patient acting as a nurse, and afterward completed a self-evaluation with video review by the students' assigned coach and feedback on the session. We collected complete responses from 108 students. We evaluated the curriculum for feasibility and acceptability by faculty and students. Most students agreed with faculty on their entrustment and milestone levels. Students found that the session prompted self-reflection and was a good review of conflict resolution. The standardized patient and faculty feedback was found to be the most useful by the students. We successfully implemented a simulated but realistic conflict resolution exercise. Students found the exercise helpful in their preparation for residency.


[The Comparison of Clinical Effect of Rh-endostar on Retreated Non-Small Cell Lung Cancer and Colorectal Cancer.].
Antiangiogenesis has become the fourth module of cancer therapy nowadays. However, its clinical effect varies from cancer to cancer. The aim of this study is to compare the clinical efficacy of rh-endostatin (YH-16, Endostar) on retreated non-small cell lung cancer and colorectal cancer. The patients including 17 cases of retreated non-small cell lung cancer (NSCLC) and 15 cases of retreated colorectal cancer were confirmed by histopathology or cytopathology. All the cases were administrated with rh-endostatin combining chemotherapy and radiotherapy. 7.5 mg/m(2) rhendostatin solved in 500 mL of normal saline was slow intravenously dropped from day 1 to day 14. The efficacy was evaluated strictly according to RECIST criteria and the quality of life (QOL) was based on the Karnofsky performance (KPS). The response rate (RR) of 17 cases of retreated NSCLC was 11.8% (2/17), and the disease control rate (DCR) was 41.2% (7/17). However, the RR and DCR of the 15 cases of retreated colorectal cancer were up to 40% (6/15) and 86.6% (13/15). There was significant difference between these two tumors (P<0.05). Moreover, significant difference was also found on the QOL of these two tumors [The improving and stable QOL was 41.2% (7/17) and 86.6% (13/15), respectively (P<0.05)]. The clinical efficacy of rh-endostatin on retreated colorectal cancer was better than on retreated non-small cell lung cancer, which suggested that it was necessary to perform more clinical observations on the digestive tumors.


Coxiella burnetii in central Italy: novel genotypes are circulating in cattle and goats.
Genotyping of bacteria is critical for diagnosis, treatment, and epidemiological surveillance. Coxiella burnetii, the etiological agent of Q fever, has been recognized to have a potential for bioterrorism purposes. Because few serosurveys have been conducted in Italy, there is still limited information about the distribution of this pathogen in natural conditions. In this paper, we describe the genotyping of C. burnetii strains by multispacer sequence typing (MST) detected in cattle and goat farms in the Abruzzi region of Italy. Biological samples (milk, aborted fetus) positive for C. burnetii DNA were sequenced in the spacer regions and compared with those already publicly available ( http://ifr48.timone.univ-mrs.fr/MST_Coxiella/mst/group_detail ). The MST profile of C. burnetii detected in milk samples demonstrated the presence of a new allele, whereas the C. burnetii spacer sequences from fetus and milk goat samples displayed a new allelic combination. The results suggest the circulation of novel genotypes of C. burnetii in Italy.


Iconic gestures prime words: comparison of priming effects when gestures are presented alone and when they are accompanying speech.
Previous studies have shown that iconic gestures presented in an isolated manner prime visually presented semantically related words. Since gestures and speech are almost always produced together, this study examined whether iconic gestures accompanying speech would prime words and compared the priming effect of iconic gestures with speech to that of iconic gestures presented alone. Adult participants (N = 180) were randomly assigned to one of three conditions in a lexical decision task: Gestures-Only (the primes were iconic gestures presented alone); Speech-Only (the primes were auditory tokens conveying the same meaning as the iconic gestures); Gestures-Accompanying-Speech (the primes were the simultaneous coupling of iconic gestures and their corresponding auditory tokens). Our findings revealed significant priming effects in all three conditions. However, the priming effect in the Gestures-Accompanying-Speech condition was comparable to that in the Speech-Only condition and was significantly weaker than that in the Gestures-Only condition, suggesting that the facilitatory effect of iconic gestures accompanying speech may be constrained by the level of language processing required in the lexical decision task where linguistic processing of words forms is more dominant than semantic processing. Hence, the priming effect afforded by the co-speech iconic gestures was weakened.


Hepatocellular carcinoma surveillance: An evidence-based approach.
Hepatocellular carcinoma (HCC) makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. Chronic liver disease is the most significant risk factor for HCC with 80%-90% of new cases occurring in the background of cirrhosis. Studies have shown that early diagnosis of HCC through surveillance programs improve prognosis and availability of curative therapies. All patients with cirrhosis and high-risk hepatitis B patients are at risk for HCC and should undergo surveillance. The recommended surveillance modality is abdominal ultrasound (US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with non-alcoholic fatty liver disease (NAFLD). With the current obesity epidemic and rise in the prevalence of NAFLD, abdominal computed tomography or magnetic resonance imaging may be indicated as the primary screening modality in these patients. The addition of alpha-fetoprotein to a surveillance regimen is thought to improve the sensitivity of HCC detection. Further investigation of serum biomarkers is needed. Semiannual screening is the suggested surveillance interval. Surveillance for HCC is underutilized and low adherence disproportionately affects certain demographics such as non-Caucasian race and low socioeconomic status.


Space-Confined Earth-Abundant Bifunctional Electrocatalyst for High-Efficiency Water Splitting.
Hydrogen generation from water splitting could be an alternative way to meet increasing energy demands while also balancing the impact of energy being supplied by fossil-based fuels. The efficacy of water splitting strongly depends on the performance of electrocatalysts. Herein, we report a unique space-confined earth-abundant electrocatalyst having the bifunctionality of simultaneous hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), leading to high-efficiency water splitting. Outperforming Pt/C or RuO2 catalysts, this mesoscopic, space-confined, bifunctional configuration is constructed from a monolithic zeolitic imidazolate framework@layered double hydroxide (ZIF@LDH) precursor on Ni foam. Such a confinement leads to a high dispersion of ultrafine Co3O4 nanoparticles within the N-doped carbon matrix by temperature-dependent calcination of the ZIF@LDH. We demonstrate that the OER has an overpotential of 318 mV at a current density of 10 mA cm-2, while that of HER is -106 mV @ -10 mA cm-2. The voltage applied to a two-electrode cell for overall water splitting is 1.59 V to achieve a stable current density of 10 mA cm-2 while using the monolithic catalyst as both the anode and the cathode. It is anticipated that our space-confined method, which focuses on earth-abundant elements with structural integrity, may provide a novel and economically sound strategy for practical energy conversion applications.


Functional Analysis of the Photosynthetic Apparatus of Prochlorothrix hollandica (Prochlorales), a Chlorophyll b Containing Procaryote.
Light-shade adaptation of the chlorophyll a/b containing procaryote Prochlorothrix hollandica was studied in semicontinuous cultures adapted to 8, 80 and 200 mumole quanta per square meter per second. Chlorophyll a contents based on dry weight differed by a factor of 6 and chlorophyll b by a factor of 2.5 between the two extreme light conditions. Light utilization efficiencies determined from photosynthesis response curves were found to decrease in low light grown cultures due to lower light harvesting efficiencies; quantum requirements were constant at limiting and saturating irradiances for growth. At saturating growth irradiances, changes in light saturated oxygen evolution rate originated from changes in chlorophyll a antenna relative to the number of reaction centers II. At light-limiting conditions both the number of reaction centers II and the antenna size changed. The amount of chlorophyll b relative to reaction center II remained constant. As in cyanobacteria, the ratio of reaction center I to reaction center II was modulated during light-shade adaptation. On the other hand, time constants for photosynthetic electron transport (4 milliseconds) were low as observed in green algae and diatoms. The occurrence of state one to two and state two to one transitions is reported here. Another feature linking photosynthetic electron transport in P. hollandica to that in the eucaryotic photosynthetic apparatus was blockage of the state one to two transition by 3-(3,4-dichlorophenyl)-1,1-dimethylurea. Although chlorophyll b was reported in association with photosystem I, the 630 nanometer light effect does not exclude that chlorophyll b is the photoreceptor for the state one to two transition.


From Scheme to System (Part 1): Notes on Conceptual and Methodological Innovations in the Multicountry Research Program on Scaling Up Results-Based Financing in Health Systems.
Abstract-This article presents conceptual and methodological developments made in analyzing the scale up of results-based financing (RBF) as part of a multicountry research program supported by the Alliance for Health Policy and Systems Research. Following a brief overview of the research process, the article proposes a new five-dimensional conceptualization of scale-up (population coverage, service coverage, health system integration, cross-sectoral diffusion, and knowledge expansion) to capture various facets of RBF scale-up. It also presents how Walt and Gilson's health policy triangle framework was modified to identify the enablers and barriers to scale-up in the country case studies included in this research program. The article then puts forth a four-phase model of scale-up, including phases of generation, adoption, institutionalization, and expansion, developed for the purpose of this research program. The article concludes by providing some lessons learned on the use of the methods and theoretical frameworks developed for this multicountry research program.


A case of a maintenance hemodialysis patient in whom a change of sensitivity to acetate was suspected.
Sodium acetate, which is a buffering agent in dialysates, has a vasodilatation effect as well as effects for depression of myocardial contractility even in low dosages. Also, it is presumed to be one of the causes of hypotension during hemodialysis (HD). In recent years, acetate-free dialysates [A(-)D] have been developed. In this case, although it was possible to maintain a relatively stable hemodynamic condition during HD using 10 mEq/L of acetate-containing dialysate [A(+)D], after HD using A(-)D for 4 months and then switched back to A(+)D, the patient complained of several symptoms such as nausea, vomiting, and headache, and severe hypotension episodes increased during HD. Furthermore, stabilization of the hemodynamic condition was obtained after switching back to A(-)D. Moreover, the nutritional state and anemia were improved. Conventionally, it has been considered that cases referred to as acetate intolerance have various symptoms with increasing blood acetate levels; however, this case suggests the possibility that tolerance to acetate was acquired by using the A(+)D over time, and the tolerance dissipated after using the A(-)D for 4 months. The number of cases involving broadly defined acetate intolerance as in this case was higher than expected. These findings suggest that using A(-)D for such cases, it may therefore be possible to maintain stable hemodynamic conditions during HD and improve the nutritional state and anemia.


[Prevention of peritoneal dissemination after colorectal surgery--significance of MMC administration in abdominal cavity].
Peritoneal lavage cytology during surgery was done in 287 patients with colorectal cancer. Positive cytologic specimens were obtained from 21 patients. Of 13 patients who had free cancer cells in peritoneal cavity but no peritoneal dissemination macroscopically, 5 patients received intraperitoneal administration of 20 mg of MMC dissolved in 500 ml of saline. Peritoneal dissemination occurred in 0/5 (0%) of the MMC treated group and in 5/8 (63%) of the untreated group (p less than 0.05). Our results indicate that intraperitoneal administration of MMC (20 mg) is an effective method of preventing peritoneal dissemination after resection of colorectal cancer.


Commitment to physical activity and anxiety about physique among college women.
This study involved a comparison of scores on the Commitment to Physical Activity Scale and the Social Physique Anxiety Scale by 258 women athletes, kinesiology majors, and a control group. Mean commitment to physical activity of the control group was significantly lower than the means of the other groups; the mean on anxiety about social physique was significantly higher.


Glial cell loss in the hippocampus of alcoholics.
Alcohol abuse is often accompanied by cognitive impairment. Memory and concentration problems, especially, are described in neuropsychologically tested abstinent alcoholics. This impairment seems to be reversible, because a neuropsychological study has reported that after >5 years of abstinence, former alcoholics performed normally compared with a control group. The neuropathological correlate to the cognitive impairment associated with alcoholism is still under debate. Hippocampus is an area of the brain primarily involved in learning and memory, and the hippocampus is affected in several demential diseases. Over recent years, it has become evident that the glial cells in the brain, especially the astrocytes, play a central part in many activities that are critical to the normal functions of the brain. The total number of neuron and glial cells in the hippocampus was estimated in five severely affected alcoholics and five controls with an unbiased stereological technique: the optical fractionator. A statistically significant loss of 37% of the glial cells was found globally in the hippocampus of the alcoholics compared with controls. A reduction of astrocytes and oligodendrocytes and, to a lesser degree, microglial cells accounted for this loss. No loss of neurons was found in the hippocampus from alcoholics. The loss of glial cells and the potential for regeneration of these cells after cessation of alcohol abuse is discussed in the light of the results of clinical studies of former alcoholics.


Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin.
Urokinase (uPA) and the urokinase receptor (uPAR) form a multifunctional system capable of concurrently regulating pericellular proteolysis, cell-surface adhesion, and mitogenesis. The role of uPA and uPAR in directed proteolysis is well established and its function in cellular adhesiveness has recently been clarified by numerous studies. The molecular mechanisms underlying the mitogenic effects of uPA and uPAR are still unclear, however. We identified mechanisms that might participate in uPA-related mitogenesis in human vascular smooth muscle cells and demonstrated that uPA induces activation of a unique signaling complex. This complex contains uPAR and two additional proteins, nucleolin and casein kinase 2, which are implicated in cell proliferation. Both proteins were isolated by affinity chromatography on uPA-conjugated cyanogen-bromide-activated Sepharose 4B and were identified using nano-electrospray mass spectrometry and immunoblotting. We used laser scanning and immunoelectron microscopy studies to further demonstrate that nucleolin and casein kinase 2 are located on the cell surface where they colocalize with the uPAR. Moreover, the proteins were co-internalized into the cell as an entire complex. Immunoprecipitation experiments in combination with an in vitro kinase assay demonstrated a specific association of uPAR with nucleolin and casein kinase 2 and revealed a uPA-induced activation of casein kinase 2, which presumably led to phosphorylation of nucleolin. Blockade of nucleolin and casein kinase 2 with specific modulators led to the inhibition of uPA-induced cell proliferation. We conclude that in human vascular smooth muscle cells, uPA induces the formation and activation of a newly identified signaling complex comprising uPAR, nucleolin, and casein kinase 2, that is responsible for the uPA-related mitogenic response. The complex is not a unique feature of vascular smooth muscle cells, as it was also found in other uPAR-expressing cell types.


Transmission characteristics of a tee-junction in a rectangular duct at higher-order modes.
Numerical and experimental studies were undertaken to characterize the noise transmission and scattering properties in higher-order modes across the tee-junction of a rectangular duct used in ventilation and air-conditioning systems. To measure these properties, a formulation of a transmission matrix based on the transfer function and a two-microphone method was devised. The measurement of modal sound transmission and scattering coefficients is demonstrated for a duct element in a rectangular duct. The results of numerical simulations were verified by experiments. The results show that sound transmissions of fundamental mode and higher-order modes across the main duct are high at the eigen-frequencies of the main duct and sidebranch. Weak modal coupling of the branch-modes and the traveling wave in the main duct is observed at or very close to the eigen-frequencies of the sidebranch, which shifts excitation of the higher-order branch-modes at higher frequencies. A decrease in sound transmission and increase in sound scattering into higher-order modes occur with excitation of the axial branch-mode. Excitation of the longitudinal branch-mode due to branch-end reflection also results in lower sound transmission of higher-order modes across the junction along the main duct.


Antimicrobial susceptibility profiles associated with bacterial meningitis among children: a referral hospital-based study in Iran.
Bacterial meningitis continues to be associated with high morbidity and mortality rate worldwide, especially in the pediatric age group. This study was performed to identify the microbial etiologies of meningitis among 31 children, who were admitted in the Emergency Ward of a referral pediatric hospital in Iran. Culture identification showed that Streptococcus pneumoniae (12 subjects), Haemophilus influenzae (11 subjects) were the most common bacteria, followed by Escherichia coli (7 cases) and Neisseria meningitidis (only one case). Antibiotic susceptibility tests revealed that vancomycin had the best effect on S. pneumoniae in comparison with other antibiotics, whereas H. influenzae and E. coli were more susceptible to ceftriaxone, ceftazidime, and ceftizoxime than other antibiotics. In conclusion, despite the advances in antibiotic therapy and vaccine development, bacterial meningitis still is a health problem. S. pneumoniae, H. influenzae, and N. meningitidis are the main sources of bacterial meningitis, but other organisms such as E. coli should also be suspected, when a case is admitted to a referral pediatric hospital.


Heavy metal (Pb, Zn, Cd, Fe, and Cu) contents of plant foliage near the Anvil Range lead/zinc mine, Faro, Yukon Territory.
Mining and processing of lead (Pb)/zinc (Zn) ore at the Anvil Range mine occurred near the town of Faro in the Yukon Territory, Canada, for approximately 30 years, beginning in 1968. A study was undertaken to examine whether the mining activities had left a detectable "footprint" on the environment in the way of heavy metal phytoaccumulation. Foliage of three native plant species was sampled: bog blueberry (Vaccinium uliginosum), Labrador tea (Ledum groenlandicum), and willow (Salix sp.), at approximately 0.25, 2.5, 12, 30, and 200 (control) km distant from the mill (ore-processing facility at the mine). Foliage samples were oven-dried, wet- or dry-ashed, and analyzed for metal content using ICP-AES. In addition to Pb and Zn, the primary ore constituents, copper (Cu), iron (Fe), and cadmium (Cd), were also assayed. As expected, foliar Pb and Zn concentrations were elevated in plants at the sites closest to the mill, i.e., 0.25 and 2.5 km from the mine facility. Copper and Fe, both essential nutrients for plants, were also elevated in foliage at the sites closest to the mill, but not to a level that would be of concern. Foliar Cd levels were highest in Salix relative to the other species but were not affected by proximity to the mill. Results suggest that Ledum may be the best indicator of high environmental concentrations of Pb, while Salix may be the best indicator of elevated Zn and Cd.


Financial Incentives to Encourage Value-Based Health Care.
This article reviews the literature on the use of financial incentives to improve the provision of value-based health care. Eighty studies of 44 schemes from 10 countries were reviewed. The proportion of positive and statistically significant outcomes was close to .5. Stronger study designs were associated with a lower proportion of positive effects. There were no differences between studies conducted in the United States compared with other countries; between schemes that targeted hospitals or primary care; or between schemes combining pay for performance with rewards for reducing costs, relative to pay for performance schemes alone. Paying for performance improvement is less likely to be effective. Allowing payments to be used for specific purposes, such as quality improvement, had a higher likelihood of a positive effect, compared with using funding for physician income. Finally, the size of incentive payments relative to revenue was not associated with the proportion of positive outcomes.


Migrant information, job search and the remigration decision.
"Labor force migration poses two important questions for the economist. The first concerns the nature, magnitude and direction of labor force response to perceived earnings differentials over space. The latter and more complex question concerns the effectiveness, or efficiency, of this response--namely migration--and other market mechanisms in reducing these earnings differentials over time." Both questions are addressed in this paper "by examining relationships among: (1) quality of information obtained prior to a move, (2) search duration at the migration destination, and (3) the likelihood of subsequent (perhaps corrective) remigration." These relationships are analyzed using the human capital model of migration-remigration and data from the 1970 U.S. census.


Kits for the diagnosis of infectious mononucleosis compared with the Paul-Bunnell test.
We compared the results obtained with six different test kits for infectious mononucleosis with those obtained with the Paul-Bunnell test. The investigation was carried out in one laboratory using 149 selected pools of patient sera. Each pool was tested three times with the Paul-Bunnell test and once with each kit. The results obtained with the kits were grouped according to the titre found with the Paul-Bunnell test. The percentage of positive results within each group was calculated for each kit. The Paul-Bunnell titre, which would have classified 50% of the specimens as positive, was estimated for each kit and this was designated the 50% cut off value. In general, there was good agreement. However, false positive test results were found rather frequently with one kit (19%) and the 50% cut off values differed. One kit showed a 50% cut off value at about 8, another at about 16, and the rest at between 16 and 32. We suggest the introduction of improved internal quality control combined with external quality assessment.


Relationship between eye preference and binocular rivalry, and between eye-hand preference and reading ability in children.
One goal of the experiment presented here was to check, in children, the relationship between eye preference when sighting at different angles and eye dominance in binocular rivalry. In addition, since it is sometimes argued that a crossed pattern of eye-hand preference might put children at risk of difficulties in learning to read, we evaluated the relationship between this pattern and reading achievement in first and sixth graders. Results showed that a majority of children are right-eyed for monosighting, and that intrinsic preference and spatial factor influence the choice of eye. As many children were right- or left-eye dominant, and eye dominance was not related to eye preference. We found no relationship between eye-hand preference and reading proficiency, thus not confirming that a crossed pattern of eye-hand preference might put children at risk of difficulties in learning to read. Consistent handers were more advanced in reading than inconsistent handers.


Patient Perceptions on Receiving Vaccination Services through Community Pharmacies.
(1) Introduction: Pharmacists are medical professionals who play an active role in the protection of public health. Since 2021, pharmacists with an appropriate certification have been authorised to administer vaccines against COVID-19. (2) Objective: The objective of this study was to ascertain the perceptions of patients about receiving vaccinations through community pharmacies. (3) Material and methods: This study was conducted in 2021. The research tool was an anonymous questionnaire published on the websites of patient organisations. Ultimately, 1062 patients participated in this study. (4) Results: This study shows that most of the respondents find community pharmacies more accessible than outpatient clinics (85.3%). Sixty-one percent of the respondents stated that getting vaccinated at pharmacies would be less time consuming than at outpatient clinics. Nearly every third respondent (29.5%) declared that they would get vaccinated if they received such a recommendation from a pharmacist. Fifty-six percent of the respondents were of the opinion that the administration of vaccines by pharmacists would relieve the burden on medical staff and the healthcare system. (5) Conclusions: Polish patients participating in the study have a positive attitude towards the implementation of vaccination services in community pharmacies as an effective way of combating infectious diseases.


Bafilomycins produced in culture by Streptomyces spp. isolated from marine habitats are potent inhibitors of autophagy.
Five new bafilomycins, F (1) to J (5), have been isolated from laboratory cultures of two Streptomyces spp. obtained from marine sediments collected in British Columbia, and their structures have been elucidated by detailed analysis of spectroscopic data and the synthesis of model compounds. The new bafilomycins F (1), G (2), H (3), and J (5) along with several co-occurring known analogues showed potent inhibition of autophagy in microscopy and biochemical assays. The thiomorpholinone fragment present in bafilomycin F (1) has not previously been found in a natural product.


Self-consistent field approach for cross-linked copolymer materials.
A generalized self-consistent field approach for polymer networks with a fixed topology is developed. It is shown that the theory reproduces the localization of cross-links, which is characteristic for gels. The theory is then used to study the order-disorder transition in regular networks of end-linked diblock copolymers. Compared to diblock copolymer melts, the transition is shifted towards lower values of the incompatibility parameter χ (the Flory-Huggins parameter). Moreover, the transition becomes strongly first order already at the mean-field level. If stress is applied, the transition is further shifted and finally vanishes in a critical point.


Bone morphogenetic proteins: The anomalous molecules.
Bone is unique of all the tissues in the vertebrate organism. When injured, it heals by formation of new bone. Bone morphogenetic proteins (BMPs) are powerful inductors of the osteogenic activity during the embryologic bone formation phase and in cases of bone healing. They have proliferative effects on different cellular types, showing chemotactic properties and are able to induce mesenchymal cells differentiation into osteoblastic and chondroblastic line cells. Both primary cells and cell lines have been shown to respond to BMPs. Further the ability of embryonic cells to respond to BMPs by differentiating into cartilage and bone cells suggests that they are involved in the development of embryonic skeletal system. In addition, these proteins can also promote the angiogenesis, regulate the activity of some growth factors, and affect the production of these growth factors, which is helpful for the osteogenesis. BMPs have been considered as the most potent growth factors that can promote the bone regeneration. Thus, the aim of this review is to emphasize on the unique nature of the BMP molecules regarding their structure, classification, signaling mechanism, etc., as BMPs are the only molecules which show such deviation from the normal order, type. This will further help in understanding the role of BMPs and their potential advances which are necessary to facilitate the process of regeneration in periodontics.


Haemophilic pseudotumour presenting with large bowel obstruction.
Osseous haemophilic pseudotumours are uncommon. The commonest sites of involvement are the femur and the pelvis. Trauma is the initiating factor in most reported cases and repeated bleeding into the lesion contributes to their growth. Most lesions grow slowly and are often asymptomatic. Complications include massive haemorrhage, infection and pathological fracture. We present an extremely unusual presentation where a large haemophilic pseudotumour of the pelvis extended to impinge the adjacent colon, resulting in large bowel obstruction.


A Prospective Study and Single-Center Experience: Effectivity of Fusion Prostate Biopsy in Biopsy-Naïve Patients.
Objective Fusion prostate biopsy (FPB) has become a popular technique in biopsy-naïve patients, though not accepted as a standard approach (yet). In this study, we aimed to present the clinical outcomes of biopsy-naïve patients who underwent FPB. Material and methods The study included 400 biopsy-naïve patients aged 45-75 years who had a prostate-specific antigen (PSA) level of 2-10 ng/ml and were detected with a Prostate Imaging-Reporting and Data System (PIRADS) ≥3 lesion on multiparametric prostate magnetic resonance imaging (mpMRI)-guided FPB. A combined biopsy (CB) was performed in each patient, in which 2-4 cores were obtained for suspicious lesions by targeted biopsy (TB) and then 12-core standard prostate biopsy (SPB) was conducted in the same session. Cancer detection rates, clinically significant prostate cancer (csPCa) detection rates, histological upgrading rates, and false negative rates were determined. Results The 400 patients had a mean age of 62.01±7.00 years and a mean PSA value of 6.84±1.87 ng/ml. Overall PCa detection rate was 50% (200/400). The csPCa detection rates for TB, SPB, and CB were 25.0%, 31.8%, and 44.0%, respectively (p<0.001). In PIRADS 3, 4, and 5 lesions, CB had a csPCa detection rate of 29.2%, 54%, and 64.8%, respectively (p<0.001). The ratio of false negativity was significantly higher for TB compared to SPB (43.2% vs. 27.8%, p=0.003), whereas no significant difference was found between these two techniques with regard to upgrading rates although TB had a higher rate (19.6% vs. 13.7%, p=0.144). Conclusion FPB, a combined approach involving TB and SPB, was revealed as the most successful technique in biopsy-naïve patients with PSA<10 ng/ml due to its high cancer detection rates and low false negative rates.


Blood viscosity studies in native and reconstituted polycythemic blood.
In twelve subjects with Polycythemia vera (P.V.) whole blood, plasma and relative viscosities and the main factors capable of influencing such parameters (Hct, RBCs, WBCs and platelet count, total proteins, gamma-globulins and fibrinogen) were investigated. Ten normal subjects of similar age and sex were studied as control. Whole blood viscosity was determined both in basal conditions and after reconstitution of Hct to normal values by adding some autologous plasma. After the reconstitution of Hct the subjects studied were divided into two groups on the basis of the correlation between Hct and whole blood viscosity. The first group (group A) had a good correlation between Hct and whole blood viscosity; on the other hand the second group (group B) did not show any significant correlation between these two parameters after reconstitution. In basal conditions none of the parameters capable of influencing whole blood viscosity or plasma viscosity permitted any discrimination between the two groups. The relative viscosity, which represents an indirect index of red blood cell deformability, appears to be more elevated in group B. Therefore, the different behaviour of polycythemic blood after reconstitution of Hct might be conceived to be due to a difference in red cell deformability.


Race/Ethnicity and Perception of Care: Does Patient-Provider Concordance Matter?
We determine whether racial concordance between postpartum patients and obstetric providers (dyads) impacts the perception of quality of care among people undergoing intrapartum obstetrical procedures. This is a prospective cohort study of postpartum people who underwent operative vaginal or cesarean deliveries in the second stage of labor. Participants were asked to identify the race of their primary provider and complete the Interpersonal Processes of Care (IPC) survey, which assesses communication, patient-centered decision-making, and interpersonal style. The association of participant-identified patient-provider racial concordance with IPC scores was determined. The primary outcome was the IPC subdomain related to discrimination, and secondary outcomes included other IPC subdomains and IPC results by participant racial identity (Black, LatinX vs. White). Sociodemographic and biomedical data were extracted from the medical record. Bivariable analyses were performed. Of 168 patients who were approached, 107 (63.6%) agreed to participate and 87 (81.3%) completed the survey. The majority (n=49) identified a racially discordant provider. Participants in racially concordant dyads were more likely to be older, White, use English as a primary language, complete a higher degree of education, and have a higher household income when compared with racially discordant dyads. Intrapartum outcomes were not significantly different between groups. Median IPC subtest scores were not significantly different between groups or between racial/ethnic identities. There were no significant differences in perceptions of IPC between racially concordant versus discordant dyads. However, there is an ongoing need to further clarify measures of quality of care in high-acuity obstetrical situations to remediate ongoing racial and ethnic disparities in adverse health outcomes. · Racial concordance between patient and clinician has been associated with improved quality of care.. · There are limited data on racial concordance and perceptions of operative obstetrical care (e.g., operative vaginal delivery).. · Racial concordance was not associated with differences in patient-perceived quality of care associated with operative obstetrics..


Maternal expression and function of the Drosophila sox gene Dichaete during oogenesis.
Members of the Sox family of DNA-binding HMG domain proteins have been shown to regulate gene transcription in a wide range of developmental processes, including sex determination, neurogenesis, and chondrogenesis. However, little is known about their potential functions in developing germline tissues. In Drosophila, the Sox protein Dichaete (a.k.a., Fish-hook) is a member of the SoxB subgroup whose HMG domain shares strong sequence similarity to that of vertebrate Sox2. Dichaete exhibits dynamic expression in embryonic and larval stages and has pleiotropic functions in a variety of tissues. In this study, we extend analyses of Dichaete function and show that expression of Dichaete protein is detected in the developing oocyte during early to mid stages of oogenesis. Strikingly, Dichaete exhibits cytoplasmic distribution and is not detected in the oocyte nucleus. Germline mosaic analyses revealed that the Dichaete gene has maternal functions that influence dorsal/ventral patterning of the egg chamber. Dichaete mutant eggs exhibit defects in formation of the dorsal appendages, differentiation of dorsal/anterior follicle cells, and mislocalization of Gurken protein and gurken mRNA. Dichaete protein was shown to possess RNA-binding capabilities, suggesting a direct post-transcriptional role in regulating RNA functions.


Lumbar disc herniation in a 15-year-old girl: A case report.
Lumbar disc herniation (LDH) is uncommon in the pediatric population. The lumbar spine biodynamics and architecture change with age, with adults being more susceptible to LDH than children. When conservative treatment fails for pediatric LDH, surgery may be considered. We described an unusual instance of pediatric lumbar disc herniation that was successfully treated with microdiscectomy. A 15-year-old patient presented with back discomfort and pain in her left leg that had been deteriorating for over 4 years. Conservative treatment with nonsteroidal anti-inflammatory medications and piriformis injection is ineffective. An MRI of her lumbosacral spine revealed that the left L4 root was compressed by a disc herniation at the L4/L5 level. A microdiscectomy was performed on the patient. Within 48 h of surgery, the patient was released home with significant alleviation in sciatic discomfort. In the pathogenesis of LDH, trauma and a sedentary lifestyle are important factors. Back pain and radiating pain are typical LDH symptoms. If conservative treatment does not result in a positive outcome, the microdiscectomy procedure is the surgical approach of choice. Long-term outcomes have demonstrated the efficacy and safety of this procedure. Every child who presents with back pain or radiculopathy should undergo a thorough evaluation for LDH especially if they have a high body mass index (BMI) or a history of trauma. Careful patient selection and preoperative evaluation result in extremely excellent surgery outcomes in pediatric LDH.


Convex weighting criteria for speaking rate estimation.
Speaking rate estimation directly from the speech waveform is a long-standing problem in speech signal processing. In this paper, we pose the speaking rate estimation problem as that of estimating a temporal density function whose integral over a given interval yields the speaking rate within that interval. In contrast to many existing methods, we avoid the more difficult task of detecting individual phonemes within the speech signal and we avoid heuristics such as thresholding the temporal envelope to estimate the number of vowels. Rather, the proposed method aims to learn an optimal weighting function that can be directly applied to time-frequency features in a speech signal to yield a temporal density function. We propose two convex cost functions for learning the weighting functions and an adaptation strategy to customize the approach to a particular speaker using minimal training. The algorithms are evaluated on the TIMIT corpus, on a dysarthric speech corpus, and on the ICSI Switchboard spontaneous speech corpus. Results show that the proposed methods outperform three competing methods on both healthy and dysarthric speech. In addition, for spontaneous speech rate estimation, the result show a high correlation between the estimated speaking rate and ground truth values.


Metabolic consequences of reduced gastric acidity.
A review of the effect on metabolism of antacids, anticholinergics and histamine H2-antagonists is given. It is stated that long-term treatment with antacids by a variety of mechanisms can cause severe metabolic complications such as the milk-alkali syndrome and phosphorus depletion. The interaction with other drugs can also be marked. There is very little known of the effect of anticholinergics on metabolism. Clinical experience has not indicated that any serious consequences will occur. The authors have investigated the effect continuous treatment with cimetidine 400 mg at night or twice daily for three years on weight, haemoglobin, plasma iron, plasma folate, plasma vitamin B12, albumin and plasma calcium. The only significant difference that occurred was a slight decrease of plasma calcium within the reference values. In conclusion it is stated that there is very little indication that the moderate and inconstant reduction of acidity over 24 hours which can be achieved by anticholinergics or twice daily administration of presently available H2-antagonists will result in metabolic consequences arising from reduced acidity. Higher doses given more frequently might give a risk for bacterial overgrowth with metabolic consequences.


[A fusion protein of rotavirus VP6 and cholera toxin B subunit: expression in Escherichia coli and analysis of biological activities].
Rotavirus infection is a major cause of dehydrating diarrhea in infants worldwide. The non-toxic cholera toxin B subunit(CTB), known as an immunomodulatory carrier, might help to stimulate mucosal immune response when coupled to rotavirus antigens in oral immunization. Here we report for the first time the construction of a translational fusion of CTB gene 5' to the VP6 gene of a human rotavirus A(field strain T114), and expression of the CTB-VP6 fusion protein in E. coli BL21(DE3). The expressed fusion protein has a molecular weight of 56 kD, as expected, and accounts for about 15% of the total E. coli protein. Western blottings with the hyperimmune serum against rotavirus strain WA and the antibody against cholera toxin indicated that the fusion protein retains the antigenicity identical to the native CTB and VP6. The GM1-ELISA analysis proves that the renatured CTB-VP6 has strong affinity for GM1 ganglioside.


Cancer Risk Assessment for Workers Exposed to Pollution Source, a Petrochemical Company, Iran.
Air pollution have led to severe problem of adverse health effect in the world. This study aimed to conduct the health risk assessment, cancer risk analysis, and non-cancer risk for exposure to volatile organic compounds (VOCs) and hydrogen sulfide (H 2 S) in petrochemical industry. In this cross-sectional research, 123 samples were collected in the ambient air in Iran during winter 2016. For sampling and analysis of VOCs and H 2 S, 3 methods (numbers 1500, 1501, and 6013) presented by the National Institute of Occupational Safety and Health (NIOSH) were used. For determination of risk assessment of chemical pollutants, semi-quantitative method presented by the Occupational Safety and Health Division, Singapore was used. Finally, for calculation of cancer risk analysis, Chronic Daily Intake (CDI) and calculation of non-cancer risk, Exposure Concentration (EC) were used. Average concentration of benzene (2.12±0.95) in breathing zone of workers were higher than the Threshold Limit Values-Time Weighted Average (TLV-TWA) (P<0.05). Among chemical substance, benzene had very high rank of risk in petrochemical industry. Rank of risk for H 2 S, toluene, and xylene present in the breathing zone of workers was low. The mean cancer risk for workers exposed to benzene was estimated 8.78×10-3, in other words, 8.7 cancer per 1000 i.e. higher than the acceptable standard of 10-6. In our study, non-cancer risk for BTX was higher than the acceptable standard of 1. In particular, overall cancer and toxic risk can be associated with long term exposure to benzene.


Predictors of surgical outcome and their assessment.
The relatively high rate of failed back surgery has prompted the search for "risk factors" to predict the result of spinal surgery in a given individual. However, the literature reveals few unequivocal predictors and they often explain a relatively low proportion of variance in outcome. This suggests that we have a long way to go before being able to rest easily, having refused someone surgery on the basis of unfavourable baseline characteristics. The best recommendation is to ensure, firstly, that the indication for surgery is absolutely clear-cut (i.e. that surgically remediable pathology exists) and then to consider the various factors that may influence the "typical" outcome. Consistent risk factors for a poor outcome regarding return-to-work include long-term sick leave/receipt of disability benefit. Hence, every effort should be made to keep the individual in the workforce, despite the ongoing symptoms and plans for surgery. In patients with a particularly heavy job, consultation with occupational physicians might later ease the patient's way back into the workplace. Patients with degenerative disorders and/or comorbidity should be counselled that few of them will have complete/lasting pain relief or a complete return to pre-morbid function. Patients with a high level of distress may benefit from psychological treatment, before and/or accompanying the surgical treatment. The opportunity (time), encouragement (education and positive messages), and resources (referral to appropriate support services) to modify risk factors that are indeed modifiable should be offered, and realistic expectations should be discussed with the patient before the decision to operate is made.


Effector mechanisms in murine allograft rejection: comparison of skin and heart grafts in fully allogeneic and minor histocompatibility antigen-mismatched strain combinations.
Cytotoxic T lymphocytes (CTLs) and macrophage-mediated delayed-type hypersensitivity (DTH) responses may both mediate allograft rejection. Furthermore, although allograft rejection is classically considered a type [22, 23, 38, 50, 52] 1 cellular immune response, type-2 cytokines can support rejection. This study examines whether the immunogenicity of the transplanted tissue, as determined by type of tissue (skin versus heart) and degree of antigenic mismatch, influences recruitment of these effector mechanisms. Graft survival, histological appearance and intragraft gene expression (IL-2, IFN-gamma, IL-12 p40, IL-4, IL-10, perforin, Fas ligand (Fas L), iNOS and TNF-alpha) were compared for fully allogeneic, minor histocompatibility (mHC) antigen-mismatched and syngeneic skin and heart grafts. We found mRNA characteristic of CTLs and DTH responses in fully allogeneic and mHC antigen-mismatched skin and heart grafts. Concomitant type-1 and type-2 cytokine gene transcription was seen. These findings demonstrate that the tissue grafted and degree of antigenic disparity between donor and recipient do not restrict the repertoire of cellular immune responses involved in graft rejection. This finding has implications in the design of new immunosuppressive strategies for clinical transplantation.


Synergic Catalysis of PdCu Alloy Nanoparticles within a Macroreticular Basic Resin for Hydrogen Production from Formic Acid.
Highly dispersed PdCu alloy nanoparticles have been successfully prepared within a macroreticular basic resin bearing N(CH3 )2 functional groups. This previously unappreciated combination of alloy is first proven to be responsible for the efficient production of high-purity H2 from formic acid (HCOOH) dehydrogenation for chemical hydrogen storage. By the addition of Cu, the electronically promoted Pd sites show significantly higher catalytic activity as well as a better tolerance towards CO poisoning as compared to their monometallic Pd counterparts. Experimental and DFT calculation studies revealed not only the synergic alloying effect but also cooperative action by the N(CH3 )2 groups within the resin play crucial roles in achieving exceptional catalytic performances. In addition to the advantages such as, facile preparation method, free of additives, recyclable without leaching of active component, and suppression of unfavorable CO formation less than 3 ppm, the present catalytic system is cost-effective because of the superior catalytic activity compared with that of well-established precious PdAg or PdAu catalysts. The present catalytic system is particularly desirable for an ideal hydrogen vector in terms of potential industrial application for fuel cells.


Improvement of cerebral arterial stenosis associated with Basedow's disease. Case report.
A 29-year-old female presented with Basedow's disease manifesting as sudden vomiting, diarrhea, fever over 38 degrees C, transient aphasia, and numbness in her extremities. These symptoms were considered due to cerebral ischemia at a local clinic. Magnetic resonance angiography indicated stenosis of the bilateral distal internal carotid arteries and the bilateral proximal anterior cerebral and middle cerebral arteries. Thyroid swelling and exophthalmos were observed. She was transferred to our hospital. Endocrine function tests showed hyperthyroidism. The diagnosis was Basedow's disease. Her symptoms disappeared after receiving intravenous drip infusion of fluid replacement, and antithyroid and antiplatelet medication. After she became euthyroid, cerebral angiography and magnetic resonance angiography revealed improvement of the stenosis of the cerebral arteries. Stenosis of the terminal portion of the internal carotid artery associated with Basedow's disease is extremely rare. Conservative treatment mainly including antithyroid medications for Basedow's disease, and antiplatelet drugs and intravenous replacement fluid for the ischemic manifestations should be the first choice of treatment unless immediate vascular reconstruction is necessary.


Estimating the instantaneous reproduction number (Rt) by using particle filter.
Monitoring the transmission of coronavirus disease 2019 (COVID-19) requires accurate estimation of the effective reproduction number (Rt). However, existing methods for calculating Rt may yield biased estimates if important real-world factors, such as delays in confirmation, pre-symptomatic transmissions, or imperfect data observation, are not considered. To include real-world factors, we expanded the susceptible-exposed-infectious-recovered (SEIR) model by incorporating pre-symptomatic (P) and asymptomatic (A) states, creating the SEPIAR model. By utilizing both stochastic and deterministic versions of the model, and incorporating predetermined time series of Rt, we generated simulated datasets that simulate real-world challenges in estimating Rt. We then compared the performance of our proposed particle filtering method for estimating Rt with the existing EpiEstim approach based on renewal equations. The particle filtering method accurately estimated Rt even in the presence of data with delays, pre-symptomatic transmission, and imperfect observation. When evaluating via the root mean square error (RMSE) metric, the performance of the particle filtering method was better in general and was comparable to the EpiEstim approach if perfectly deconvolved infection time series were provided, and substantially better when Rt exhibited short-term fluctuations and the data was right truncated. The SEPIAR model, in conjunction with the particle filtering method, offers a reliable tool for predicting the transmission trend of COVID-19 and assessing the impact of intervention strategies. This approach enables enhanced monitoring of COVID-19 transmission and can inform public health policies aimed at controlling the spread of the disease.


Manubrium sterni stress fracture: an unusual complication of non-contact sport.
Tremendous force is usually required to cause sternal fractures. Normally this is caused either by a direct blow to the chest or by an indirect injury from hyperflexion of the torso. A case is presented of a fracture of the manubrium sterni in a young man as a complication of body building exercises-a non-contact sport. It appears that this has not been reported before.


Use of IFN-Based Biotherapeutics to Harness the Host Against Foot-And-Mouth Disease.
Foot-and-mouth disease (FMD) is a highly contagious vesicular disease of cloven-hoofed animals that severely constrains international trade of livestock and animal products. Currently, disease control measures include broad surveillance, enforcement of sanitary policy, and use of an inactivated vaccine. While use of these measures has contributed to eliminating foot-and-mouth disease virus (FMDV) from a vast area of the world, the disease remains endemic in three continents, and outbreaks occasionally appear in previously declared FMD-free zones, causing economic and social devastation. Among others, a very fast rate of viral replication and the need for 7 days to achieve vaccine-induced protection are the main limitations in controlling the disease. New fast-acting antiviral strategies targeted to boost the innate immunity of the host to block viral replication are needed. Here we review the knowledge on the multiple strategies FMDV has evolved to block the host innate immunity, with particularly focus on the past and current research toward the development of interferon (IFN)-based biotherapeutics in relevant livestock species.


New molecular targets in angiogenic vessels of glioblastoma tumours.
Antiangiogenesis approaches have the potential to be particularly effective in the treatment of glioblastoma tumours. These tumours exhibit extremely high levels of neovascularisation, which may contribute to their extremely aggressive behaviour, not only by providing oxygenation and nutrition, but also by establishing a leaky vasculature that lacks a blood-brain barrier. This leaky vasculature enables migration of tumour cells, as well as the build up of fluid, which exacerbates tissue damage due to increased intracranial pressure. Here, we discuss the considerable progress that has been made in the identification of the pro- and antiangiogenic factors produced by glioblastoma tumours and the effects of these molecules in animal models of the disease. The safety and efficacy of some of these approaches have now been demonstrated in clinical trials. However, the ability of tumours to overcome these therapies and to re-establish angiogenesis requires further clinical research regarding potential multimodality therapies, as well as basic research into the regulation of angiogenesis by as yet unidentified factors. Optimisation of noninvasive procedures for monitoring of angiogenesis would greatly facilitate such research.


[Association of genetic polymorphism in plasminogen activator inhibitor-1 gene with endometrial hypoplasia in infertile women].
To investigate the relationship between the plasminogen activator inhibitor (PAI-1) polymorphisms and endometrial hypoplasia in infertile women. The study was conducted in 105 primary infertile patients with endometrial hypoplasia diagnosed by pathology and the thickness of endometrium by B-mode ultrasound and 85 controls who were not pregnant and had normal fertility. The -675 4G/5G polymorphism in the PAI-1 gene was detected by polymerase chain reaction-restriction fragment length polymerphim analysis. The frequencies of 4G/4G genotype and 4G allele of the PAI-1 gene were higher in the patient group (48.6% and 66.2%) than in the normal controls (22.4% and 47.1%) (P < 0.01). ThePAI-1 4G/4G genotype was significantly associated with endometrial hypoplasia in the infertile patients (OR=4.9, 95% CI: 2.10-10.12). The present findings suggest that the 4G/5G polymorphism of the PAI-1 gene was associated with endometrial hypoplasia in infertile patients.


The acute presentation of pulmonary thromboembolism: a retrospective viewpoint.
Acute pulmonary thromboembolism (PE) has been considered rare among Asians. We aim to describe the frequency and clinical features of this condition in a hospital in Singapore. Among patients admitted by the Emergency Department (ED), comparisons were made between those primarily diagnosed in the ED and those who were not. Retrospective review of all cases of radiologically proven acute PE over a 20-month period. Sixty-two patients were identified. The mean age was 61.5 +/- 18.0 years with a female to male ratio of 1.8:1. There were more Malays compared to other races. There were also more Caucasians, given the proximity of the hospital to the airport and the inclusion of tourists. The commonest symptoms were dyspnoea and chest pain, while the commonest signs were tachycardia and tachypnoea. Prolonged immobilisation was the commonest risk factor. Electrocardiographic S1Q3T3 pattern was seen in more patients compared to Western studies. Cardiomegaly was the commonest chest X-ray finding. Thirty-two patients were identified to have a source of embolisation. Overall mortality rate was 21%. The ED diagnosed 36% of the cases. Alternative admitting diagnoses were predominantly ischaemic heart disease and pneumonia. The group diagnosed in the ED were notably female (P = 0.044), Caucasian (P = 0.002) and had prolonged immobilisation (P = 0.025) prior to the onset of PE. Acute PE is not as rare here as previously thought. Clinical features reveal more similarities than differences compared to other studies in the literature. We advocate a high index of suspicion for earlier diagnosis in the ED.


NEONATAL HYPOGLYCAEMIA AT CAPE COAST TEACHING HOSPITAL.
Hypoglycaemia is an important metabolic condition in the neonate although there is no common consensus with regards to diagnosis, management and follow-up. It is common in preterm, small and large for gestational age and in birth asphyxia. Although the incidence of these predisposing factors is common among neonates in Ghana, the prevalence of neonatal hypoglycaemia (NH) has not been studied in this environment. To determine the prevalence of neonatal hypoglycaemia at the Cape Coast Teaching Hospital, Ghana. Cross sectional. Cape Coast Teaching Hospital, Ghana. Neonates between 3-24 hours of age delivered at the Cape Coast Teaching Hospital were included in the study. The blood glucose concentration was measured using Onetouch® Select TM Blood Glucose Monitoring System for 434 consecutively delivered neonates within 3-24 hours of birth. In addition the birth and delivery characteristics of the neonates were recorded. The overall prevalence of neonatal hypoglycaemia (NH) was 16 per 1000 births. The prevalence in appropriate weight for gestational age was 21 per 1000 births but none in small and large for gestational age group. The prevalence of NH in preterm, term and post-term neonates were 0, 18 and 15 per 1000 births respectively. The study showed that neonatal hypoglycaemia is common in Ghana although the expected result of high neonatal hypoglycaemia in preterm, small and large for gestational age groups was not recorded in this study.


An epidemiological analysis of the foot-and-mouth disease epidemic in Miyazaki, Japan, 2010.
An epidemic of foot-and-mouth disease occurred in Miyazaki, Japan, beginning in late March 2010. Here, we document the descriptive epidemiological features and investigate the between-farm transmission dynamics. As of 10 July 2010, a total of 292 infected premises have been confirmed with a cumulative incidence for cattle and pig herds of 8.5% and 36.4%, respectively, for the whole of Miyazaki prefecture. Pig herds were more likely to be infected than cattle herds (odds ratio = 4.3 [95% confidence interval (CI): 3.2, 5.7]). Modelling analysis suggested that the relative susceptibility of a cattle herd is 4.2 times greater than a typical pig herd (95% CI: 3.9, 4.5), while the relative infectiousness of a pig herd is estimated to be 8.0 times higher than a cattle herd (95% CI: 5.0, 13.6). The epidemic peak occurred around mid-May, after which the incidence started to decline and the effective reproduction numbers from late May were mostly less than unity, although a vaccination programme in late May could have masked symptoms in infected animals. The infected premises were geographically confined to limited areas in Miyazaki, but sporadic long-distance transmissions were seen within the prefecture. Given that multiple outbreaks in Far East Asian countries have occurred since early 2010, continued monitoring and surveillance is deemed essential.


Heteroleptic iminopyrrolidinates of aluminium.
A series of iminopyrrolidine (ip) compounds were synthesized with excellent yields as potential ligands for novel organometallic precursors for atomic layer deposition. The idea behind these ligands was that carbodiimide (CDI) deinsertion would not occur as the quaternary carbon was tethered to one chelate nitrogen. To our advantage a melting point trend was evident within the ip ligands and reflected in the family of heteroleptic aluminium species when the ip ligands were reacted with TMA or TEA. The alkane elimination reaction occurred at room temperature yielding clean products with high yields. Crystal structures were collected for compounds 7 [ipipAlMe(2)], 12 [tbipAlMe(2)], and 14 [sbipAlEt(2)] demonstrating that the heteroleptic aluminium species were dimers. This was also evident in the mass spectra collected for each compound as the parent peak was that of the dimer minus a methyl. Thermolysis studies were carried out on all the ipAlMe(2) species to observe the decomposition at an isotherm over several days. The decay of the methyl peak was monitored as a ratio against TMS within the solution and was shown to be a first order decomposition. From these studies it was clear that nbip (9), iso-bip (10), and tbip (12) were the most stable complexes with half-lives of 24.8, 9.00, and 10.3 days, respectively.


Influence of Fluoride Varnish Application on Enamel Adhesion of a Universal Adhesive.
To study the effect of the varnish type, application time and surface polishing on the shear bond strength (SBS) of a universal adhesive in healthy and demineralized bovine enamel. 432 bovine primary central incisors were assigned to 18 groups according to enamel mineralization [healthy and demineralized], topical varnish [Clinpro White Varnish (CWV; 3M Oral Care) and Profluorid (PFV, Voco)], remineralization time [24 h or 21 days] and polishing or not of the enamel surface. Adhesion was tested using Futurabond M (Voco)+ and GrandioSO (Voco). Sheer bond strength (SBS) was measured and the fracture mode studied. The statistical analysis was performed using two-way ANOVA, Tukey's test, and Pearson's chi-squared test. In healthy bovine enamel, CWV reduced SBS at 24 h and 21 days; polishing significantly improved SBS. PFV increased SBS in healthy enamel at 21 days and demineralized enamel at 24 h and 21 days; polishing had no effect on SBS. The application time and polishing of the enamel surface affected the behavior of varnishes with respect to SBS. There was a correlation between the type of fracture and the degree of mineralization as well as the timepoint of varnish application. Remineralization of demineralized enamel with fluoride varnishes permits the recovery of the bond strength obtained in healthy enamel. Of the two varnishes studied, PFV had the highest SBS and more uniform behavior, regardless of the application timepoint, degree of mineralization, and surface treatment of the enamel..


Multicompetency needs in respiratory care: results of a survey of respiratory therapy alumni and hospital administrators.
I sought to determine (1) respiratory therapists' perceptions of their need for competencies normally associated with other professions, (2) hospital administrators' perceptions of functional combinations of health professions, and (3) the relationship of both sets of these perceptions to the hospital bed size of the employing hospital. I mailed pretested and validated survey instruments to all 1981-1984 graduates of The Wichita State University therapist program and a second, similar instrument to all hospital administrators in the state of Kansas. Both groups of respondents perceived a need for therapists to be competent in skills normally associated with other professions. This was true regardless of the size of the hospital concerned. Chi-square analysis revealed no significant difference between the responses of those completing and returning the written survey and the responses of a random sample of nonrespondents to the written survey who were contacted by telephone. Administrators most frequently identified as desirable nursing and physical therapy combinations with respiratory therapy. Respiratory therapists most frequently identified nursing, emergency medical technology, and medical technology as the professions in which they need additional competence. It would seem prudent for respiratory therapy educators to collaborate with other health care educators to identify a common professional core and to develop curricula that accommodate multicompetency needs.


A capitated payment system for involuntary mental health clients.
This DataWatch examines an outpatient capitated payment system, in the state of Oregon, designed to enhance community services for persons with chronic mental illness who had repeatedly been hospitalized involuntarily. Special state funds and Medicaid dollars were used to pay providers prospectively on a risk-adjusted basis for the delivery of outpatient mental health services. During the three-year study period clients were able to be discharged from the state hospital. Although the data are not straightforward, capitated clients' use of the state mental hospital seems to have declined somewhat more than that of comparison subjects. Outpatient service use was modest and appeared to have little relationship to a client's level of illness severity. Indeed, it was not possible to predict prospectively these clients' outpatient mental health services expenditures.


CD45 epitope mapping of human CD1a+ dendritic cells and peripheral blood dendritic cells.
The authors studied the pattern of leukocyte common antigen (CD45) epitope expression on dendritic cells in sections of human epidermis, tonsillar epithelium, dermatopathic lymph nodes, and in isolates from blood. The monoclonal antibodies (MAb) used were specific for all known CD45 epitopes, including the seven different CD45 common epitopes as well as the four known CD45R epitopes (two CD45RA, one CD45RB, and one CD45RO). Dendritic cells in all sites were uniformly reactive for the CD45 common epitopes tested except 2B11, which may recognize a CD45R rather than CD45 epitope. By single-label immunoperoxidase and double-label immunofluorescence epitope mapping of CD1a+ dendritic cells in tissue sections, it was generally difficult or impossible to detect expression of CD45RA, CD45RB, CD45RO, or 2B11. In blood dendritic cells, however, low levels of these CD45R epitopes were detected consistently using single-label immunoperoxidase staining of cytocentrifuge preparations. Monocytes were similar to blood dendritic cells except that the staining with MAb to CD45RO and 2B11 was slightly stronger. The authors conclude that dendritic cells differ from most subpopulations of lymphocytes in that CD45 common epitopes are readily detectable but the existing RA, RB, and RO epitopes are either undetectable or expressed at relatively low levels. These studies raise the possibility that CD1a+ dendritic cells may express a novel dominant CD45 isoform.


Distribution of uranium contamination in weathered fractured saprolite/shale and ground water.
The objective of this study was to determine how structure, stratigraphy, and weathering influence fate and transport of contaminants (particularly U) in the ground water and geologic material at the Department of Energy (DOE) Environmental Remediation Sciences Department (ERSD) Field Research Center (FRC). Several cores were collected near four former unlined adjoining waste disposal ponds. The cores were collected, described, analyzed for U, and compared with ground water geochemistry from surrounding multilevel wells. At some locations, acidic U-contaminated ground water was found to preferentially flow in small remnant fractures weathering the surrounding shale (nitric acid extractable U [U(NA)] usually < 50 mg kg(-1)) into thin (<25 cm) Fe oxide-rich clayey seams that retain U (U(NA) 239 to 375 mg kg(-1)). However, greatest contaminant transport occurs in a 2 to 3 m thick more permeable stratigraphic transition zone located between two less permeable, and generally less contaminated zones consisting of (i) overlying unconsolidated saprolite (U(NA) < 0.01 to 200 mg kg(-1)) and (ii) underlying less-weathered bedrock (U(NA) generally < 0.01 to 7 mg kg(-1)). In this transition zone, acidic (pH < 4) U-enriched ground water (U of 38 mg L(-1)) has weathered away calcite veins resulting in greater porosity, higher hydraulic conductivity, and higher U contamination (U(NA) 106 to 745 mg kg(-1)) of the weathered interbedded shale and sandstone. These characteristics of the transition zone produce an interval with a high flux of contaminants that could be targeted for remediation.


Methylphenidate and dextroamphetamine abuse in substance-abusing adolescents.
The prevalence of methylphenidate and dextroamphetamine misuse and abuse was examined in 450 adolescents referred for substance abuse treatment. Twenty three percent reported nonmedical use of these substances and six percent were diagnosed as methylphenidate or dextroamphetamine abusers. Abuse was more common in individuals who were out of school and had an eating disorder. Methylphenidate and dextroamphetamine abuse appears to be much less common than abuse of most other substances. It does occur, however, and parents and schools need to exert greater control over the dispensing of these medications. Physicians are advised to prescribe non-stimulant medications (eg, bupropion) when treating attention deficit hyperactivity disorder in substance-abusing individuals.


Strategies for inhibiting quorum sensing.
The ability of bacterial cells to synchronize their behaviour through quorum sensing (QS) regulatory networks enables bacterial populations to mount co-operative responses against competing micro-organisms and host immune defences and to adapt to environmental challenges. Since QS controls the ability of many pathogenic bacteria to cause disease, it is an attractive target for novel antibacterial agents that control infection through inhibition of virulence and by rendering biofilms more susceptible to conventional antibiotics and host clearance pathways. QS systems provide multiple druggable molecular targets for inhibitors (QSIs) that include the enzymes involved in QS signal molecule biosynthesis and the receptors involved in signal transduction. Considerable advances in our understanding of the chemical biology of QS systems and their inhibition have been made, some promising QS targets structurally characterized, QSI screens devised and inhibitors identified. However, much more work is required before any QSI 'hits' with the appropriate pharmacological and pharmacokinetic properties can enter human clinical trials. Indeed, the relative efficacy of QSIs alone or as prophylactics or therapeutics or as adjuvants in combination with conventional antibiotics still needs to be extensively evaluated in vivo. Particular attention must be given to the measurement of successful QSI therapy outcomes with respect to bacterial clearance, immune response and pathophysiology. Currently, our understanding of the potential of QS as a promising antibacterial target suggests that it is likely to be of value with respect to a limited number of major pathogens.


Alternative Splicing of Three Genes Encoding Mechanotransduction-Complex Proteins in Auditory Hair Cells.
The mechanotransduction (MT) complex in auditory hair cells converts the mechanical stimulation of sound waves into neural signals. Recently, the MT complex has been suggested to contain at least four distinct integral membrane proteins: protocadherin 15 (PCDH15), transmembrane channel-like protein 1 (TMC1), lipoma HMGIC fusion partner-like 5 (LHFPL5), and transmembrane inner ear protein (TMIE). However, the composition, function, and regulation of the MT-complex proteins remain incompletely investigated. Here, we report previously undescribed splicing isoforms of TMC1, LHFPL5, and TMIE. We identified four alternative splicing events for the genes encoding these three proteins by analyzing RNA-seq libraries of auditory hair cells from adult mice [over postnatal day (P)28], and we then verified the alternative splicing events by using RT-PCR and Sanger sequencing. Moreover, we examined the tissue-specific distribution, developmental expression patterns, and tonotopic gradient of the splicing isoforms by performing semiquantitative and quantitative real-time PCR (qRT-PCR), and we found that the alternative splicing of TMC1 and LHFPL5 is cochlear-specific and occurs in both neonatal and adult mouse cochleae. Our findings not only reveal the potential complexity of the MT-complex composition, but also provide critical insights for guiding future research on the function, regulation, and trafficking of TMC1, LHFPL5, and TMIE and on the clinical diagnosis of hearing loss related to aberrant splicing of these three key genes in hearing.


Sources of Support and Information During Disease: An Exploratory Study, Comparing Migrant and Nonmigrant Colorectal Cancer Patients in Germany.
Introduction: The prevalence of cancer diseases among migrants is lower relative to nonmigrants, although this equalizes with increasing duration of residence. There are differences in the health behaviors and disease coping strategies between these two groups. The aim of this analysis is to compare migrant and nonmigrant colorectal cancer (CRC) patients in Germany regarding their sources of support and information during disease. Method: Data from 522 CRC patients, collected through a survey about satisfaction with care, were analyzed by descriptive and multivariate statistics. Results: Migrants and nonmigrants differed in two aspects: Migrants reported to receive the most relevant support during disease more often by nonmedical people, compared with nonmigrants, and they favored videos explaining the therapeutic steps of CRC more than nonmigrants. Discussion: Anticipating which types of support and information sources patients will access during their disease may help guide future diversity management across the field of cancer care.


Non-random distribution of extensive chromosome rearrangements in Brassica napus depends on genome organization.
Chromosome rearrangements are common, but their dynamics over time, mechanisms of occurrence and the genomic features that shape their distribution and rate are still poorly understood. We used allohaploid Brassica napus (AC, n = 19) as a model to analyze the effect of genomic features on the formation and diversity of meiotically driven chromosome rearrangements. We showed that allohaploid B. napus meiosis leads to extensive new structural diversity. Almost every allohaploid offspring carried a unique combination of multiple rearrangements throughout the genome, and was thus structurally differentiated from both its haploid parent and its sister plants. This large amount of genome reshuffling was remarkably well-tolerated in the heterozygous state, as neither male nor female fertility were strongly reduced, and meiosis behavior was normal in most cases. We also used a quantitative statistical model, which accounted for 75% of the observed variation in rearrangement rates, to show that the distribution of meiotically driven chromosome rearrangements was not random but was shaped by three principal genomic features. In descending order of importance, the rate of marker loss increased strongly with genetic distance from the centromere, the degree of collinearity between chromosomes, and the genome of origin (A < C). Overall, our results demonstrate that B. napus accumulates a large number of genetic changes, but these rearrangements are not randomly distributed in the genome. The structural genetic diversity produced by the allohaploid pathway and its role in the evolution of polyploid species compared to diploid meiosis are discussed.


Variability of spontaneous Ca2+ release between different rat ventricular myocytes is correlated with Na(+)-Ca2+ exchange and [Na+]i.
We have studied the factors responsible for the variation of the frequency of "waves" caused by spontaneous Ca2+ release in rat ventricular myocytes. The experiments were performed in isolated myocytes using the fluorescent indicators Indo-1 (to measure [Ca2+]i) and SBFI (to measure [Na+]i). After electrical stimulation (either with action potentials or voltage-clamp pulses), some cells showed spontaneous Ca2+ release. The frequency of this release, where present, was variable. The Ca2+ content of the sarcoplasmic reticulum (SR) was measured by applying caffeine (10 mmol/L). The resulting increase of [Ca2+]i activated the electrogenic Na(+)-Ca2+ exchange, and the integral of this current was used to estimate the Ca2+ content of the SR. The SR Ca2+ content was significantly higher in cells that oscillated at high rates ( > 10 . min-1) than in those that were quiescent. The rate of removal of Ca2+ from the cytoplasm by non-SR mechanisms was measured by adding caffeine (10 mmol/L) and measuring the rate constant of decay of the resulting increase of [Ca2+]i. Cells that had a high rate constant of decay of [Ca2+]i had a low frequency of oscillations. Measurements of [Na+]i showed a positive correlation between the frequency of spontaneous SR Ca2+ release and [Na+]i. After cessation of stimulation, there was a gradual decrease of [Na+]i, which was correlated with a parallel decrease of the frequency of oscillation rate. We conclude that the variability of frequency of spontaneous SR Ca2+ release is due to variations of the rate of Ca2+ removal from the cell, which are probably due to Na(+)-Ca2+ exchange. The variability of Na(+)- Ca2+ exchange rate, in turn, is likely to result from variations of [Na+]i.


Age at death of major cardiovascular diseases in 13 cohorts. The seven countries study of cardiovascular diseases 45-year follow-up.
To explore age at death (AD) for major cardiovascular diseases (CVD) and their risk factors in originally middle-aged men followed nearly to extinction in the Seven Countries Study. Thirteen cohorts of men aged 40-59 years (N = 10,628) in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) were enrolled in late 1950s and early 1960s and were followed 45 years for mortality. AD was computed for coronary heart disease (CHD), stroke (STR), heart disease of uncertain aetiology (HDUE) and for all-causes. AD was compared across CHD-HDUE-STR. Cox models were computed for each end-point using baseline age, cigarettes smoking, systolic blood pressure and serum cholesterol. After 45 years 92.9% of men had died. The most common CVD death was CHD in most cohorts except some Mediterranean and Japanese cohorts where STR or HDUE were most prevalent. In 13 cohorts mean AD was 74.5, 73.5, 75.7 and 79.1 years, respectively, for all-cause, CHD, STR and HDUE mortality (all possible differences were significant). The difference, across cohorts, between the highest and the lowest mean AD was 12.9, 9.0 and 4.7 years for CHD, HDUE and STR mortality, respectively. Risk factors explored were significant predictors of all three CVD end-points, except serum cholesterol, specific to CHD mortality. AD is a useful indicator of previous health and aging populations. STR and HDUE are diseases appearing later in life, thus being associated with a higher AD compared with CHD mortality.


Mouse cathepsin K: cDNA cloning and predominant expression of the gene in osteoclasts, and in some hypertrophying chondrocytes during mouse development.
We have constructed cDNA clones covering the entire coding region of mouse, human and rabbit preprocathepsin K mRNA for studies on bone turnover. The clone pMCatK-1 for mouse cathepsin K shares 87% nucleotide homology with the corresponding human and rabbit sequences. Analysis of a panel of mouse tissues for tissue distribution of cathepsin K mRNA revealed the highest levels in musculoskeletal tissues: bone, cartilage and skeletal muscle. In situ hybridization of developing mouse embryos was performed to identify the cellular source of cathepsin K mRNA. The strongest mRNA signal was detected in osteoclasts of bone, identified in serial sections by positive TRAP staining. Cathepsin K mRNA was also observed in some hypertrophic chondrocytes of growth cartilages. Association of cathepsin K production with degradation of bone and cartilage matrix suggests that this enzyme and its mRNA levels could serve as markers for matrix degradation in diseases affecting these tissues.


Autopsy pathology of pediatric posttransplant lymphoproliferative disorder.
Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality, is related to Epstein-Barr virus (EBV) infection, and is more common in children than in adults. We reviewed autopsies of children who died with PTLD to compare postmortem with antemortem PTLD histology, to assess the extent of PTLD, to document associated pathology, and to identify cause of death. Postmortem examinations were performed on 7 patients after bone marrow (n = 3) or liver (n = 4) transplant. PTLD was classified histologically as hyperplasia or lymphoma. In situ hybridization for EBER1 messenger RNA was performed on tissue samples from all cases. EBV serologies were used to categorize infections as negative, primary, or reactive. PTLD was diagnosed in 5 children 12 to 35 (mean: 22) days before death, and 1.5 to 4 (mean: 3) months after transplant; PTLD was diagnosed in 2 cases at autopsy 2.5 and 4 months after transplant. Postmortem PTLD histology resembled antemortem histology; 5 PTLDs were lymphoma, 1 was hyperplasia, and 1 contained both lymphoma and hyperplasia. EBER1 messenger RNA was detected in 6 B-cell PTLDs, including lesions from patients who did not have EBV serology that indicated active infection. Complete autopsy of 4 patients who died with biopsy-proven PTLD revealed widely disseminated disease, and lymph node, brain, gastrointestinal tract, and kidney were involved in all 4 patients. Cases diagnosed at autopsy were 1 widely disseminated PTLD that had been suspected but not proven antemortem, and 1 PTLD confined to abdominal lymph nodes that was not suspected antemortem. Severe organ dysfunction (renal failure, gastrointestinal hemorrhage) was caused by massive PTLD infiltration in 2 patients. The conditions other than PTLD that contributed to morbidity and death were organ infection (5 cases), infarcts (4 cases), and diffuse alveolar damage (3 cases). PTLD may occur within weeks after transplant in children. The distribution of PTLD comprises a spectrum from localized and subclinical to widely disseminated and symptomatic. PTLD may cause demise quickly after the onset of signs and symptoms, through massive organ infiltration or associated conditions, such as diffuse alveolar damage. EBV serology may not accurately reflect the presence or extent of PTLD. Autopsy studies of transplant patients are necessary to identify the true incidence, natural history, and response to treatment of PTLD.