Electrical stimulation therapy in chronic functional constipation: five years' experience in patients refractory to biofeedback therapy and with rectal hyposensitivity.
Biofeedback therapy (BFT) can be unsuccessful in constipated patients, even those with pelvic floor dysfunction. Electrical stimulation therapy (EST) has been introduced as a novel therapeutic modality in patients with chronic constipation, especially those who have rectal hyposensitivity. We evaluated the efficacy of EST based on five years' clinical experience. From January 2002 to February 2007, 159 patients underwent EST. After exclusion of 12 drop-outs, 147 (M:F = 61:86, 49 ± 17 years) finished all treatment sessions. Among them, 88 (M:F = 29:59, 49 ± 17 years) were refractory to BFT without rectal hyposensitivity (RH), and 59 (M:F = 32:27, 54 ± 17 years) were those with RH. The overall response to EST was 59.2% (87/147) by per-protocol analysis. In the EST-responsive group, overall satisfaction improved significantly (from 7.3 ± 3.0 to 4.3 ± 2.5, P < 0.05). Subgroup analysis showed that the response rate was 64.8% (57/88) in patients refractory to BFT without RH, and 50.8% (30/59) in those with RH. EST may have additional therapeutic efficacy in patients who are refractory to BFT. EST may also be effective in patients with RH, including restoration of rectal sensation. Therefore, EST could be considered as an alternative choice in patients refractory to BFT and with or without RH.


[Changes of monocyte and monocyte-platelet aggregates in different subgroups of thrombotic events in patients with acute myocardial infarction during PCI].
Objective To investigate the impact of thrombotic events on the alterations of monocyte and monocyte-platelet aggregates (MPAs) in patients with acute myocardial infarction (AMI) during percutaneous coronary intervention (PCI). Methods Blood was collected before PCI for flow cytometry. Monocyte subsets and MPAs were detected by four-color platform (CDl4-APC, CDl6-PE-Cy7, CD86-PE and CD41-Alexa FluorR488). According to the expression of the platelet surface marker CD41, the number of monocyte subsets and MPAs was analyzed using the fluorescent microspheres of absolute counting tube. The Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis were performed. Results CD14+CD16++ monocytes in intraprocedural thrombotic events (IPTE) group were significantly fewer than those in non-IPTE group, and the percentage in total mononuclear cells decreased. Compared with non-IPTE group, MPA binding ratio and monocyte subset MPA binding ratio were significantly higher in IPTE group. ROC analysis showed that MPA binding ratio and subgroup MPA binding ratio had a better predictive value for IPTE in patients with AMI. Conclusion The CD14+CD16++ monocytes in IPTE group were significantly fewer than those in the non-IPTE group. MPA binding ratio and MPA binding ratio of monocyte subsets were significantly higher in the IPTE group than in the non-IPTE group, so they have a good predictive value for IPTE in patients with AMI.


Correlation between micronuclei frequency in peripheral blood lymphocytes and retention of 131-I in thyroid cancer patients.
Differentiated thyroid cancers (DTCs) derive from thyroid follicular cells and include papillary and follicular cancers. In patients with DTCs, the initial treatment includes thyroidectomy and radioactive iodine (131-I) therapy. The objective of this study was to examine whether the intensity of DNA damage in peripheral blood lymphocytes (PBLs) of DTC patients depends on the amount of 131-I retained in the selected regions of interest (thyroid and abdominal region) as well as in the whole-body 72 hours after therapy. In addition, the possible influence of other factors that may affect micronuclei (MN) frequency, such as age, gender, smoking habits, and histological type of tumour was analyzed. The study population consisted of 22 DTC patients and 20 healthy donors. Data on the distribution of 131-I were obtained from the whole-body scans. MN frequency and cytokinesis-block proliferation index (CBPI) were measured using cytokinesis-block micronucleus assay. 131-I therapy significantly increased the MN frequency (19.50±6.90 vs. 27.10±19.50 MN) and significantly decreased the CBPI (1.52±0.20 vs. 1.38±0.17) in patients' lymphocytes. There was a clear correlation between the increased MN frequency and 131-I accumulation in the thyroid region in patients without metastases. The MN values did not differ in relation to the factors that could affect MN, such as age, gender, smoking habits, and histological type of tumour. In conclusion, the MN frequency in PBLs of DTC patients without metastases depends on the accumulation of 131-I in the thyroid region and does not depend on the other factors examined.


Meroterpenoids with BACE1 Inhibitory Activity from the Fruiting Body of Boletinus asiaticus.
BACE1 inhibitory activity-guided fractionation of an extract of the fruiting body of Boletinus asiaticus yielded five novel meroterpenoids (1-5) and one known compound (6; asiaticusin A). The structures of these compounds were determined by interpretation of NMR, MS, and IR spectral data. The five new compounds contain 4-hydroxybenzoic acid and geranylgeranoic acid units. Compounds 4-6 possessed BACE1 inhibitory activity (IC50 values: 14.7, 11.4, and 2.0 μM, respectively).


The Disgust Box: a novel approach to illustrate water contamination with feces.
Inadequate drinking water, sanitation, and hand hygiene are responsible for approximately 800,000 deaths per year in low- and middle-income countries. We evaluated the benefits of a behavior change communication method to motivate water treatment practices in urban low income communities in Dhaka, Bangladesh. To motivate people to chlorinate their water we used a device called the 'Disgust Box'. This box provides a vivid demonstration of how piped water is contaminated with feces. Most of the respondents were able to recall the Disgust Box demonstration at both 4-month and 1-year follow-up qualitative assessments. At 4 months, the majority of participants stated that they still felt disgusted by the demonstration and mentioned it as a motivator for water chlorination. However, after one year, despite being able to recall the demonstration, disgust was no longer mentioned as a motivator to chlorinate water. The Disgust Box has the potential to be an effective communication method and is more likely to work if it is part of an intervention that includes repeated presentations and a more attractive water treatment option.


An Adapted Optical Density-Based Microplate Assay for Characterizing Actinobacteriophage Infection.
Bacteriophages are a key part of natural environments, and they have a powerful ability to shape bacterial populations. To understand how individual phages interact with slow-growing bacterial hosts such as actinomycetes, an easy and reliable method for quantifying long-term bacterial growth in the presence of phages is needed. Spectrophotometric microplate readers allow for high-throughput repeated measurements, but incubating a small volume for an extended time can present technical challenges. This procedure adapts a standard 96-well microplate to allow for the co-culturing of phages and bacteria without sub-sampling for 96 h, with the bacterial growth recorded every 8 h using spectrophotometric absorbance values. These optical density values are analyzed using R to yield infection metrics, including the percent growth inhibition, relative virulence, and the Stacy-Ceballos index. The methods outlined here provide an effective way to conduct and analyze extended-duration microplate growth curve experiments and includes modifications to reduce evaporation and lid condensation. These protocols facilitate microplate-based assays of interactions between slow-growing bacterial hosts and their bacteriophages.


Neural correlates of adaptive cognitive control in working memory.
Conflicts in working memory (WM) can occur when retrieval cues activate competing items, which impairs the efficiency of retrieval. It has recently been shown that WM retrieval adapts similarly to these conflicts as predicted by conflict monitoring theory for selective attention tasks. Here, we utilized event-related potentials (ERPs) to investigate whether conflict and adaptive control in WM are reflected by the same neural markers that have previously been described for selective attention tasks. In our task, participants encoded two differently colored memory lists that contained four digits each (i.e., 2 5 7 1 and 4 5 9 1), and had to recognize whether a probe item from a specific list and position was correct or incorrect. Conflict during retrieval emerged when digits at corresponding positions (e.g., 2 and 5 at the first position) were different (incongruent), but not when these digits were the same (congruent). In behavioral data, we found a congruency sequence effect, that is, responses to incongruent probe items were slower, and this effect was reduced following trials with incongruent probe items. In ERPs, this behavioral marker of adaptive control was accompanied by two effects. First, congruency affected the amplitude of an N450, and this conflict effect was reduced after incongruent trials. Second, the posterior P3 amplitude varied with the congruency of the current and the previous trial. Both results resemble those found for the Stroop task and thus highlight the similarity between conflict and adaptive control in WM and selective attention tasks.


Comparison of periarticular anesthesia with liposomal bupivacaine with femoral nerve block for pain control after total knee arthroplasty: A PRISMA-compliant meta-analysis.
Periarticular anesthesia (PAI) with liposomal bupivacaine (LB) and femoral nerve block (FNB) were 2 common type of pain management after total knee arthroplasty (TKA). There is no consensus about PAI with LB shows better clinical outcome than FNB. Thus, we performed a systematic review and meta-analysis to compare the efficacy and safety of PAI with LB and FNB for patients prepared for TKA. Randomized controlled trials (RCTs) and non-RCTs from PubMed (1966-2017.2), EMBASE (1980-2017.2), and the Cochrane Central Register of Controlled Trials (CENTRAL, 2017.2), Web of Science (1966-2017.2), and Chinese Wanfang database (1980-2017.2) were searched. Continuous outcomes including visual analogue scale (VAS) at 24, 48, and 72 hours, total morphine consumption, length of hospital, and range of motion (ROM) were reported as the weighted mean difference with 95% and confidence interval (CI) and discontinuous outcomes (the occurrence of postoperative nausea and vomiting [PONV]) were presented as relative risk with 95% CI. Random-effects model was adopted to analyze the relevant data. According to the inclusion and exclusion criteria, 8 studies with 2407 patients were eligible and finally included in this meta-analysis (LB = 1114, FNB = 1293). There was no significant difference between VAS at 24, 4, and 72 hours, ROM, and the occurrence of PONV between PAI with LB group versus FNB group (P > 0.05). Compared with the FNB group, PAI with LB was associated with a significant decrease in length of hospital stay by 0.43 day (MD = -0.43; 95% CI -0.60 to -0.27; P = 0.001) and the total dose of total morphine consumption by (MD = -29.32; 95% CI -57.55 to -1.09; P = 0.042). The review of trials found that PAI with LB provided a significant beneficial effect over FNB in improving the pain or decreased the total morphine consumption in patients who underwent TKA. However, PAI with LB associated with less LOS than FNB. More high quality RCTs are still needed to identify the effects and optimal dose of LB for pain management after TKA.


Diagnosis of skin cancer by correlation and complexity analyses of damaged DNA.
Skin cancer is a common, low-grade cancerous (malignant) growth of the skin. It starts from cells that begin as normal skin cells and transform into those with the potential to reproduce in an out-of-control manner. Cancer develops when DNA, the molecule found in cells that encodes genetic information, becomes damaged and the body cannot repair the damage. A DNA walk of a genome represents how the frequency of each nucleotide of a pairing nucleotide couple changes locally. In this research in order to diagnose the skin cancer, first DNA walk plots of genomes of patients with skin cancer were generated. Then, the data so obtained was checked for complexity by computing the fractal dimension. Furthermore, the Hurst exponent has been employed in order to study the correlation of damaged DNA. By analysing different samples it has been found that the damaged DNA sequences are exhibiting higher degree of complexity and less correlation compared to normal DNA sequences. This investigation confirms that this method can be used for diagnosis of skin cancer. The method discussed in this research is useful not only for diagnosis of skin cancer but can be applied for diagnosis and growth analysis of different types of cancers.


Are nanostructured lipid carriers (NLCs) better than solid lipid nanoparticles (SLNs): development, characterizations and comparative evaluations of clotrimazole-loaded SLNs and NLCs?
In recent years, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are among the popular research topics for the delivery of lipophilic drugs. Although SLNs have demonstrated several beneficial properties as drug-carrier, limited drug-loading and expulsion of drug during storage led to the development of NLCs. However, the superiority of NLCs over SLNs has not been fully established yet due to the contradictory results. In this study, SLNs and NLCs were developed using clotrimazole as model drug. Size, polydispersity index (PI), zeta potential (ZP), drug-loading (L), drug encapsulation efficiency (EE), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), drug release and stability of SLNs and NLCs were compared. Critical process parameters exhibited significant impact on the nanoparticles' properties. Size, PI, ZP and EE of the developed SLNs and NLCs were<100 nm, <0.17, <-22 mV and>82%, respectively. SEM images of SLNs and NLCs revealed spherical shaped particles (≈ 100 nm). DSC and XRD studies indicated slight difference between SLNs and NLCs as well as disappearance of the crystalline peak(s) of the encapsulated drug. NLCs demonstrated faster drug release than SLNs at low drug-loading, whereas there was no significant difference in drug release from SLNs and NLCs at high drug-loading. However, sustained/prolonged drug release was observed from both formulations. Furthermore, this study suggests that the drug release experiment should be designed considering the final application (topical/oral/parenteral) of the product. Regarding stability, NLCs showed better stability (in terms of size, PI, EE and L) than SLNs at 25°C. Moreover, there was no significant difference in drug release profile of NLCs after 3 months storage in compare to fresh NLCs, while significant change in drug release rate was observed in case of SLNs. Therefore, NLCs have an edge over SLNs.


Evolution and diversity of inherited viruses in the Nearctic phantom midge, Chaoborus americanus.
Inherited mutualists, parasites, and commensals occupy one of the most intimate ecological niches available to invertebrate-associated microbes. How this transmission environment influences microbial evolution is increasingly understood for inherited bacterial symbionts, but in viruses, research on the prevalence of vertical transmission and its effects on viral lineages is still maturing. The evolutionary stability of this strategy remains difficult to assess, although phylogenetic evidence of frequent host shifts and selective sweeps have been interpreted as strategies favoring parasite persistence. In this study, we describe and investigate a natural insect system in which species-wide sweeps have been restricted by the isolation of host populations. Previous work identified evidence of pronounced mitochondrial genetic structure among North American populations of the phantom midge, Chaoborus americanus. Here we take advantage of the geographical isolation in this species to investigate the diversity and persistence of its inherited virome. We identify eight novel RNA viruses from six families and use small RNA sequencing in reproductive tissues to provide evidence of vertical transmission. We report region-specific virus strains that mirror the continental phylogeography of the host, demonstrating that members of the inherited virome have independently persisted in parallel host lineages since they last shared a common ancestor in the Mid-Pleistocene. We find that the small interfering RNA pathway, a frontline of antiviral defense in insects, targets members of this inherited virome. Finally, our results suggest that the Piwi-mediated RNA silencing pathway is unlikely to function as a general antiviral defense in Chaoborus, in contrast to its role in some mosquitoes. However, we also report that this pathway generates abundant piRNAs from endogenous viral elements closely related to actively infecting inherited viruses, potentially helping to explain idiosyncratic patterns of virus-specific Piwi targeting in this insect.


Estimation of Multi-Species Leaf Area Index Based on Chinese GF-1 Satellite Data Using Look-Up Table and Gaussian Process Regression Methods.
Leaf area index (LAI) is an important biophysical parameter, which can be effectively applied in the estimation of vegetation growth status. At present, amounts of studies just focused on the LAI estimation of a single plant type, while plant types are usually mixed rather than single distribution. In this study, the suitability of GF-1 data for multi-species LAI estimation was evaluated by using Gaussian process regression (GPR), and a look-up table (LUT) combined with a PROSAIL radiative transfer model. Then, the performance of the LUT and GPR for multi-species LAI estimation was analyzed in term of 15 different band combinations and 10 published vegetation indices (VIs). Lastly, the effect of the different band combinations and published VIs on the accuracy of LAI estimation was discussed. The results indicated that GF-1 data exhibited a good potential for multi-species LAI retrieval. Then, GPR exhibited better performance than that of LUT for multi-species LAI estimation. What is more, modified soil adjusted vegetation index (MSAVI) was selected based on the GPR algorithm for multi-species LAI estimation with a lower root mean squared error (RMSE = 0.6448 m2/m2) compared to other band combinations and VIs. Then, this study can provide guidance for multi-species LAI estimation.


Perceptual demand and distraction interactions mediated by task-control networks.
Modulation of selective attention appears to be under the guidance of a cluster of distinct task-control networks, the frontroparietal (FPN) and cingulo-opercular (CON). Yet, their role in mediating the relationship between task perceptual load and presence/absence of distraction in the auditory modality is unclear. Here, we examined this interaction using functional magnetic resonance imaging (fMRI) and an auditory signal detection task. The auditory stimulus signal-to-noise ratio (SNR) was parametrically manipulated, by varying the amplitude of the Tone while holding the Noise constant, to create four perceptual load conditions presented in combination with or without acoustic distraction. Regions of the FPN (e.g., dorsolateral prefrontal cortex, inferior parietal lobule) and CON (e.g., dorsal anterior cingulate cortex/medial superior frontal cortex, anterior prefrontal cortex, anterior insula/frontal operculum) were modulated by perceptual load and distraction, such that lower loads induced a pattern of increased activity when there was no distraction. On the other hand, a trend of augmented activity was found in higher loads during distraction. These findings suggest a role for the FPN and CON in mediating the allocation of attentional resources to competing auditory information under varying degrees of perceptual demand.


Management of acute stroke. Ways to minimize damage and maximize recovery.
Brain infarctions due to atherothrombosis or cardiogenic emboli account for most cases of stroke. The remainder are caused by hemorrhages related to hypertension or subarachnoid bleeding. Management includes immediate measures to prevent further damage and rehabilitative measures by a multidisciplinary team. Efforts must also be directed toward preventing future strokes.


Inhibition of siderophore biosynthesis by 2-triazole substituted analogues of 5'-O-[N-(salicyl)sulfamoyl]adenosine: antibacterial nucleosides effective against Mycobacterium tuberculosis.
The synthesis, biochemical, and biological evaluation of a systematic series of 2-triazole derivatives of 5'-O-[N-(salicyl)sulfamoyl]adenosine (Sal-AMS) are described as inhibitors of aryl acid adenylating enzymes (AAAE) involved in siderophore biosynthesis by Mycobacterium tuberculosis. Structure-activity relationships revealed a remarkable ability to tolerate a wide range of substituents at the 4-position of the triazole moiety, and a majority of the compounds possessed subnanomolar apparent inhibition constants. However, the in vitro potency did not always translate into whole cell biological activity against M. tuberculosis, suggesting that intrinsic resistance plays an important role in the observed activities. Additionally, the well-known valence tautomerism between 2-azidopurines and their fused tetrazole counterparts led to an unexpected facile acylation of the purine N-6 amino group.


17beta-estradiol differentially activates mitogen-activated protein-kinases and improves survival following reperfusion injury of reduced-size liver in mice.
Ischemia-reperfusion injury (I/R-I), which is unavoidable in liver transplantation, impairs liver regeneration and predisposes to liver failure. The three major mitogen-activated protein-kinases (MAPKs): ERK, p38, and JNK, are critical in the transmission of signals triggered by proinflammatory cytokines, by stress, and by growth factors. JNK and p38alpha activation have been associated with apoptosis; p38beta with cell survival; and ERK with proliferation. Previous studies have demonstrated gender dimorphism in hepatocellular dysfunction after experimental trauma and hemorrhage. Female mice are protected to a much greater extent from I/R-I than male mice. We assessed the effects of 17beta-estradiol (17beta-E) on liver function, host survival, and cellular activation of MAPK in a murine model of I/R-I in reduced-size livers. C57BL/6 mice were subjected to 45 minutes of warm ischemia (70% of the liver mass). After reperfusion, the nonischemic lobes were excised. Vehicle, 17beta-E or the estrogen receptor antagonist ICI-182780, was delivered 1 hour before the injury. We evaluated AST and apoptosis as well as activation of JNK, p38, and ERK. Female mice showed a lower level of hepatocellular injury (AST = 445 +/- 82 IU/L) after I/R-I compared with male mice (AST = 1400 +/- 210). 17beta-E decreased the liver injury in male mice (AST = 522 +/- 77), an effect that was partially reversed by ICI-182,780 (910 +/- 92). A higher rate of apoptosis was observed in male animals given saline (enrichment factor = 7.22 +/- 0.8) versus those treated with 17beta-E (5.85 +/- 0.3, P < .05). A significant increase in liver regeneration, as assessed by the percentage of liver weight/body weight was demonstrated in females (184% +/- 24%) and male mice given 17beta-E (168% +/- 22%) compared with male mice given vehicle (9% +/- 4%). 17beta-E significantly down-regulated JNK and p38alpha activities, whereas I/R-I promoted p38beta and ERK activation. These results suggest that the cytoprotective effects of 17beta-E on I/R-I to reduced-size livers are associated with selective modulation of MAPK kinases.


Probing prefrontal function in schizophrenia with neuropsychological paradigms.
In a recent series of studies we have attempted to clarify the nature of intellectual impairment in schizophrenia, and in particular, how patterns of dysfunction implicate specific neural systems. First, we found that acute psychotic adolescent patients displayed the same pattern of IQ scores (Performance less than Verbal) as adult chronic schizophrenic patients. We explored this deficit in problem solving by studying the performance of schizophrenic patients after receiving concrete and explicit instructions on how to do the Wisconsin Card Sorting Test, a task thought to be mediated by prefrontal cortex. We then studied the differential impact such a deficit in problem-solving strategies might have on a task thought to elicit both cognitive (prefrontal) and procedural or motor-skill (basal ganglia) processing. Procedural components appeared to be relatively more intact. We also addressed schizophrenic patients' ability to learn in other (extrafrontal) cognitive domains through verbal memory tasks and block design puzzles. Learning occurred under both conditions. We believe the overall pattern of deficit implicates primarily prefrontal neural systems, though a number of other neuropsychological functions are yet to be surveyed.


Stress responses of bacteria.
Bacteria, irrespective of natural habitat, are exposed to constant fluctuations in their growth conditions. Consequently they have developed sophisticated responses, modulated by the re-modelling of protein complexes and by phosphorylation-dependent signal transduction systems, to adapt to and to survive a variety of insults. Ultimately these signalling systems affect transcriptional regulons either by activating an alternative sigma factor subunit of RNA polymerase, for example, sigma E (sigma(E)) of Escherichia coli and sigma B (sigma(B)) and sigma F (sigma(F)) in Bacillus subtilis or by activating DNA-binding two-component response regulators. Recent structure determinations, and systems biology analysis of key regulators in well-characterised stress-responsive pathways, illustrate conserved and novel mechanisms in these representative model bacteria.


Paradoxical effect of supplementary progesterone between Day 3 and Day 7 on corpus luteum function and conceptus development in cattle.
The aim of the present study was to investigate the effect of short-term progesterone (P4) supplementation during the early metoestrous period on circulating P4 concentrations and conceptus development in cattle. The oestrous cycles of cross-bred beef heifers were synchronised using a 7-day P4-releasing intravaginal device (PRID® Delta; 1.55 g P4) treatment with administration of a prostaglandin F(2α) analogue (Enzaprost; CEVA Sante Animale) the day before PRID® Delta removal. Only those heifers recorded in standing oestrus (Day 0) were used. In Experiment 1, heifers were randomly assigned to one of five groups: (1) control: no treatment; (2) placebo: insertion of a blank device (no P4) from Day 3 to Day 7; (3) insertion of a PRID® Delta from Day 3 to Day 7; (4) insertion of a PRID® Delta from Day 3 to Day 5; or (5) insertion of a PRID® Delta from Day 5 to Day 7. In vitro-produced blastocysts were transferred to each heifer in Groups 2-5 on Day 7 (n=10 blastocysts per heifer) and conceptuses were recovered when heifers were killed on Day 14. Based on the outcome of Experiment 1, in Experiment 2 heifers were artificially inseminated at oestrus and randomly assigned to one of three treatment groups: (1) placebo; (2) PRID from Day 3 to Day 5; or (3) PRID from Day 3 to Day 7. All heifers were killed on Day 16 and recovered conceptuses were incubated in synthetic oviducal fluid medium for 24 h; spent media and uterine flushes were analysed for interferon-τ (IFNT). In both experiments, daily blood samples were taken to determined serum P4 concentrations. Data were analysed using the PROC MIXED procedure of SAS (SAS Institute, Cary, NC, USA). Insertion of a PRID resulted in an increase (P<0.05) in serum P4 that declined following removal. In Experiment 1, P4 supplementation from Day 3 to Day 5 (17.0±1.4 mm) or Day 3 to Day 7 (11.3±2.3 mm) increased conceptus length compared with placebo (2.1±1.8 mm). Serum P4 was significantly lower from Day 9 to Day 14 (P<0.05) and the weight of the Day 14 corpus luteum (CL) was lower in the PRID Day 3-7 group than the placebo or control groups. In Experiment 2, supplementation from Day 3 to Day 5 (94.0±18.8 mm) or Day 3 to Day 7 (143.6±20.6 mm) increased conceptus length on Day 16 compared with placebo (50.3±17.4 mm). Serum P4 was significantly lower in the two supplemented groups following PRID removal compared with placebo (P<0.05) and was associated with a lower CL weight in the Day 3-7 group. Conceptus length was strongly correlated with the IFNT concentration in the uterine flush (r=0.58; P=0.011) and spent culture medium (r=0.68; P<0.002). The findings of the present study highlight the somewhat paradoxical effects of P4 supplementation when given in the early metoestrous period in terms of its positive effect on conceptus development and its potentially negative effects on CL lifespan.


State trends in health risk factors and receipt of clinical preventive services among US adults during the 1990s.
Monitoring trends is essential for evaluating past activities and guiding current preventive health program and policy efforts. Although tracking progress toward national health goals is helpful, use of national estimates is limited because most preventive health care activities, policies, and other efforts occur at the state or community level. There may be important state trends that are obscured by national data. To estimate state-specific trends for 5 health risk factors and 6 clinical preventive services. Telephone surveys were conducted from 1991 through 2000 as part of the Behavioral Risk Factor Surveillance System. Randomly selected adults aged 18 years or older from 49 US states. Annual state sample sizes ranged from 1188 to 7543. Statistically significant changes (P<.01) in state prevalences of cigarette smoking, binge alcohol use, physical inactivity, obesity, safety belt use, and mammography; screening for cervical cancer, colorectal cancer, and cholesterol levels; and receipt of influenza and pneumococcal disease vaccination. There were statistically significant increases in safety belt use for 39 of 47 states and receipt of mammography in the past 2 years for women aged 40 years or older for 43 of 47 states. For persons aged 65 years or older, there were increases in receipt of influenza vaccination for 44 of 49 states and ever receiving pneumococcal vaccination for 48 of 49 states. State trends were mixed for binge alcohol use (increasing in 19 of 47 states and declining in 3), physical inactivity (increasing in 3 of 48 states and declining in 11), and cholesterol screening (increasing in 13 of 47 states and decreasing in 5). Obesity increased in all states and smoking increased in 14 of 47 states (declining only in Minnesota). Cervical cancer screening increased in 8 of 48 states and colorectal cancer screening increased in 13 of 49 states. New York experienced improvements for 8 of 11 measures, while 7 of 11 measures improved in Delaware, Kentucky, and Maryland; in contrast, Alaska experienced improvements for no measures and at least 4 of 11 measures worsened in Iowa, North Dakota, and South Dakota. Most states experienced increases in safety belt use, mammography, and adult vaccinations. Trends for smoking and binge alcohol use are disturbing, and obesity data support previous findings. Trend data are useful for targeting state preventive health efforts.


Effect of indomethacin on basal and histamine stimulated human gastric acid secretion.
The effect of acute administration of indomethacin over 24 hours on basal and histamine stimulated gastric acid secretion was evaluated in seven normal male volunteers. Augmented histamine tests (0.015 mg/kg/h) infused with the antihistamine diphenhydramine hydrochloride (25 mg/h) were performed before and after pretreatment with indomethacin or matching placebo capsules. The dose of indomethacin was 75 mg (sustained release capsules) taken 12 and 24 hours before and 50 mg taken one hour before a two hour histamine infusion test. Indomethacin enhanced basal gastric secretion from 3.5 +/- 0.5 to 6.4 +/- 0.6 mmol/h (p less than 0.01) and histamine stimulated secretion from 48 +/- 6 to 62 +/- 5 mmol/2 h (p less than 0.05). Indomethacin significantly inhibited systemic prostaglandin biosynthesis as measured by urinary excretion (87 +/- 12 vs 41 +/- 6 ng PGE/g creatinine/h) and the drug increased platelet aggregation time two, five, and six fold, respectively, induced by ADP, collagen, and adrenaline. The data indicate that therapeutic doses of indomethacin augmented basal and secretagogue stimulated gastric acid secretion in control subjects. The enhancement of gastric acid secretion by indomethacin may be because of reduced levels of endogenous prostaglandins. Diminished prostaglandin biosynthesis may play a role in indomethacin induced gastric mucosal damage observed in patients receiving the drug.


Evaluation of postural balance control in patients with multiple sclerosis - effect of different sensory conditions and arithmetic task execution. A pilot study.
The purpose of this study was to investigate the effect of concomitant cognitive task execution and different sensory conditions on balance control in patients with multiple sclerosis (MS). Thirty-two subjects with MS and 30 healthy age- and sex-matched control subjects were included in the study. Balance Performance Oriented Mobility Assessment was performed in all subjects. Their spontaneous sway characteristics while standing with different sensory conditions and during execution of a simple arithmetic task were analysed. Mean sway in the coronary and sagittal plane, as well as sway velocity, were measured. The values of all evaluated variables obtained in all tests were significantly higher in the MS group than in controls. In the MS group, more pronounced progression of changes in response to increased difficulty of the test was also observed. Analysis of risk of falls in MS revealed a significant increase of sway velocity and mean sway in the mediolateral and anteroposterior plane in the majority of tests. Postural stability in patients with MS is significantly decreased in comparison with the control group in all evaluated conditions. Stability deficit is enhanced in response to more difficult conditions of evaluation. Increased risk of falls is related to the increased postural sway velocity and length of mean sway; this association is most pronounced in the coronary plane.


[The late results of treatment with homeopathic agents in patients with prostatic adenoma].
The results of treatment with homeopathic remedies in dilutions 10(-400), 10(-2000), 10(-20000) are represented. The informative energetic hologramic conception of homeopathy is proposed. The homeopathic drugs are considered as holograms and the human organic as a biohologram. The resonance is a mode of their interaction with a wide therapeutic effect as a result.


[Principles and possibilities in the treatment of multiple injuries].
The authors describe the therapeutic results in 135 patients with multiple injuries hospitalized at the Surgical Clinic of the Third Medical Faculty, Charles University in 1981-1990. The authors analyze the procedure in the treatment of these patients which is provided by the most experienced surgeon in collaboration with his assistant. A stage-by-stage procedure and early indication of operation is the most important aspect of treatment.


A fate map of the murine pancreas buds reveals a multipotent ventral foregut organ progenitor.
The definitive endoderm is the embryonic germ layer that gives rise to the budding endodermal organs including the thyroid, lung, liver and pancreas as well as the remainder of the gut tube. DiI fate mapping and whole embryo culture were used to determine the endodermal origin of the 9.5 days post coitum (dpc) dorsal and ventral pancreas buds. Our results demonstrate that the progenitors of each bud occupy distinct endodermal territories. Dorsal bud progenitors are located in the medial endoderm overlying somites 2-4 between the 2 and 11 somite stage (SS). The endoderm forming the ventral pancreas bud is found in 2 distinct regions. One territory originates from the left and right lateral endoderm caudal to the anterior intestinal portal by the 6 SS and the second domain is derived from the ventral midline of the endoderm lip (VMEL). Unlike the laterally located ventral foregut progenitors, the VMEL population harbors a multipotent progenitor that contributes to the thyroid bud, the rostral cap of the liver bud, ventral midline of the liver bud and the midline of the ventral pancreas bud in a temporally restricted manner. This data suggests that the midline of the 9.5 dpc thyroid, liver and ventral pancreas buds originates from the same progenitor population, demonstrating a developmental link between all three ventral foregut buds. Taken together, these data define the location of the dorsal and ventral pancreas progenitors in the prespecified endodermal sheet and should lead to insights into the inductive events required for pancreas specification.


Macular retinal ganglion cell-inner plexiform layer thickness in patients on hydroxychloroquine therapy.
We evaluated macular ganglion cell-inner plexiform layer (GC-IPL) thickness using spectral-domain optical coherence tomography (SD-OCT) in patients with chronic exposure to hydroxychloroquine (HCQ). This study included 130 subjects, who were divided into three groups: Group 1A, 55 patients with HCQ use ≥5 years; Group 1B, 46 patients with HCQ use <5 years; and Group 2, 29 normal controls. In all patients with exposure to HCQ, fundus examination, automated threshold perimetry, fundus autofluorescence photography, SD-OCT, and GC-IPL thickness measurement using the Cirrus HD-OCT ganglion cell analysis algorithm were performed. Average and minimum macular GC-IPL thickness were compared between subjects groups, and correlations between GC-IPL thickness and duration or total dose of HCQ use were analyzed. Among the 101 patients of Group 1, six patients who showed clinically evident HCQ retinopathy also showed markedly thin macular GC-IPL. In addition, weak but significant negative correlations were observed between the average and minimum GC-IPL thickness of Group 1 patients and cumulative dose of HCQ, even when analyzing without the six patients with HCQ retinopathy. However, when analyzing after exclusion of patients with high cumulative doses (>1000 g), significant correlations were not observed. This study revealed that macular GC-IPL thickness did not show definite correlations with HCQ use. However, some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL.


Second malignancies in total therapy 2 and 3 for newly diagnosed multiple myeloma: influence of thalidomide and lenalidomide during maintenance.
Thalidomide and lenalidomide constitute an important part of effective myeloma therapy. Recent data from the Intergroup Francophone du Myélome, Cancer and Leukemia Group B, and Gruppo Italiano Malattie Ematologiche dell Adulto MM-015 trials suggest that lenalidomide maintenance therapy is associated with a higher incidence of second primary malignancies (SPMs), including both hematologic and solid malignancies. In the present study, we analyzed data from the Total Therapy 2 (TT2) trial, along with the 2 Total Therapy 3 (TT3) trials. TT2 patients were assigned randomly to either a control group (no thalidomide) or to the experimental group (thalidomide during induction, between transplantations, and during consolidation and maintenance). The 2 TT3 trials used thalidomide and bortezomib during induction, before and in consolidation after tandem melphalan-based transplantation; TT3A applied VTD (bortezomib, thalidomide, dexamethasone) in the first year of maintenance and TD for 2 more years, whereas TT3B used VRD (bortezomib, lenalidomide, dexamethasone) maintenance for 3 years. The cumulative incidence of SPMs did not differ significantly among the TT trial components when measured from enrollment (P = .78) or from initiation of maintenance (P = .82). However, a pairwise comparison of the TT2 arms suggested a lower incidence of hematologic SPMs in the thalidomide maintenance arm (hazard ratio = 0.38; P = .09). These trials are registered at www.clinicaltrials.gov as NCT00573391 (TT2), NCT00081939 (TT3A), and NCT00572169 (TT3B).


Presentation of self: being heard.
"Be yourself and you'll be fine." Sound advice but not so easy to achieve in pressure situations. How does one project oneself effectively? This article discusses ways to stop selling oneself short and to be heard.


Fluctuations and redundancy in optimal transport networks.
The structure of networks that provide optimal transport properties has been investigated in a variety of contexts. While many different formulations of this problem have been considered, it is recurrently found that optimal networks are trees. It is shown here that this result is contingent on the assumption of a stationary flow through the network. When time variations or fluctuations are allowed for, a different class of optimal structures is found, which share the hierarchical organization of trees yet contain loops. The transitions between different network topologies as the parameters of the problem vary are examined. These results may have strong implications for the structure and formation of natural networks, as is illustrated by the example of leaf venation networks.


Synthesis of well dispersed uniform sub-4 nm Y2O3:Eu3+ colloidal nanocrystals.
Well dispersed uniform sub-4 nm Y2O3:Eu colloidal nanocrystals have been synthesized through the non-hydrolytic high-temperature thermal decomposition technique. The as-synthesized nanocrystals can be stably dispersed in nonpolar solvents due to the capping organic ligands on their surface. Compared with bulk materials, the nanocrystals exhibited different luminescence features, including the intensity enhancement of the 5D0 --> 7F4 transition observed in the emission spectrum.


[Gunshot injuries of the gastroduodenal region].
The injuries of the abdomen and in the region of duodenum sustained through shooting, present a delicate and difficult problem in treatment. During the years 1970/74, 375 cases were treated in our clinic, out of which 38 patients were with abdominal injuries while 12 cases were with gastro-duodenal injuries all derived through shooting. Special delicate problems represent the treatment of pancreas injuries if only the tissue of the pancreas is only made with simple stitch. The difficulties represent the treatment of injuried principal duct. Every attempt of sewing the principal duct leads to mortal inflamation of the gland. The problem of treatment of this kind of injury, apart from using different methods which are recommended in the world literature still remains open and unsolved.


Prediction of manure and nutrient excretion from dairy cattle.
Accurate estimates of manure excretion are needed for planning manure storage facilities and for nutrient management. Data sets from metabolism studies conducted at several universities were compiled and evaluated for excretion of total manure, N, P, and K. Animal groups included calves weighing up to 204 kg, heifers weighing between 274 and 613 kg, nonlactating cows, and lactating cows. Regression equations were developed to predict excretion of total manure, total dry matter, N, P, and K. Predictors used in the regression equations for lactating cows included milk yield, percentages of protein and fat in milk, dietary concentrations of crude protein and neutral detergent fiber, and intakes of nutrients. The regression equations provide improved predictions of excretion and enable more accurate planning of manure storage and nutrients to be managed at the farm level.


CORRELATION OF EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AVERAGING VERSUS SINGLE-IMAGE QUANTITATIVE MEASUREMENTS WITH RETINAL VEIN OCCLUSION VISUAL OUTCOMES.
To demonstrate the effect of averaging multiple en face optical coherence tomography angiography images on the correlation between retinal microvasculature quantitative metrics and best-corrected visual acuity (BCVA) in eyes with retinal vein occlusion. A cross-sectional cohort with unilateral retinal vein occlusion was imaged in both eyes. Five 3 mm × 3-mm spectral domain optical coherence tomography angiography images were averaged, and quantitative parameters from averaged versus single images were correlated with logMAR BCVA. Regression analyses were performed to correlate quantitative metrics with BCVA. Ten patients (5 male, average age 64.3 years) were included. Among retinal vein occlusion eyes, vessel length density was significantly less in averaged versus a single image for both the superficial retinal layer (15.5 ± 2.5 vs. 17.8 ± 2.4/mm, P = 0.05) and deep retinal layer (16.2 ± 1.4 vs. 18.5 ± 1.6/mm, P = 0.003). Multivariate linear regression showed an increased R value with averaging (0.93 to 0.95, for single and averaged groups, respectively). Foveal avascular zone circularity was associated with BCVA on single images (coefficient = -0.96, P = 0.002), but not with averaged images (P = 0.063). Scan averaging of en face optical coherence tomography angiography images improves the clarity of vessels and may allow for more accurate quantification of vessel metrics. Quantitative metrics are significantly associated with BCVA, and averaging does not further improve this association compared with single-scan analysis.


PDE2 Inhibits PKA-Mediated Phosphorylation of TFAM to Promote Mitochondrial Ca2+-Induced Colorectal Cancer Growth.
Growing evidence indicates that the dysregulation of mitochondrial calcium (Ca2+) plays a critical role in the growth of tumor cells, including colorectal cancer (CRC). However, the underling mechanism is not fully elucidated. In this study, the regulatory effects of mitochondrial Ca2+ on phosphodiesterase 2 (PDE2)/cAMP/PKA axis and the phosphorylation of mitochondrial transcription factor A (TFAM) as well as the growth of CRC cells were systematically investigated both in vitro and in vivo. Our findings demonstrated that MCU-induced mitochondrial Ca2+ uptake activated mitochondrial PDE2 in CRC cells. Moreover, overexpression MCU in CRC led to a 1.9-fold increase in Ca2+ uptake compared to control cells. However, knockdown of MCU resulted in 1.5-fould decrease in Ca2+ uptake in mitochondria compared to the controls. Activation of mitochondrial PDE2 significantly inhibited the activity of mitochondrial protein kinase A (PKA), which subsequently leads to decreased phosphorylation of TFAM. Our data further revealed that PKA regulates the phosphorylation of TFAM and promotes the degradation of phosphorylated TFAM. Thus, TFAM protein levels accumulated in mitochondria when the activity of PKA was inhibited. Overall, this study showed that the overexpression of MCU enhanced CRC growth through promoting the accumulation of TFAM proteins in mitochondria. Conversely, knockdown of MCU in CRC cells resulted in decreased CRC growth. Collectively, these data suggest that the mitochondrial Ca2+-activated PDE2/cAMP/PKA axis plays a key role in regulating TFAM stability and the growth of CRC cells.


ERCC1 gene polymorphism as a predictor for clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy.
Excision repair cross-complementation group 1 (ERCC1) is a highly conserved protein and an essential member of the nucleotide excision repair pathway. DNA repair is an important mechanism for resistance to platinum-based chemotherapy. Previous studies have shown that ERCC1 gene expression is associated with clinical outcome to platinum chemotherapy in a variety of cancers. Recently, 2 common polymorphisms in the ERCC1 gene have been described. The first is a single nucleotide polymorphism at codon 188 of the ERCC1 gene that causes a C-->T change but codes for the same amino acid, asparagine. This polymorphism may be associated with differential ERCC1 gene expression. The second is also a signal nucleotide polymorphism in the 3'-untranslated region and may affect MRNA stability. We hypothesized that these 2 polymorphisms may be associated with clinical outcome to platinum-based chemotherapy. We assessed the relationship between these ERCC1 gene polymorphism and clinical outcome to platinum-based chemotherapy in 106 patients with advanced refractory colorectal cancer. We found a significant associated between the ERCC1 codon 118 polymorphism and clinical outcome. Patients with the C/C genotype had a median survival of 15.3 months (95% CI, 6.0-12.1) and 11.1 months (95% CI, 5.8-16.2) for those with C/T and T/T genotypes, respectively. The ERCC1 codon 118 polymorphism may be a useful predictor of clinical outcome in advanced colorectal cancer patients treated with platinum-based chemotherapy.


Response Methodology Optimization and Artificial Neural Network Modeling for the Removal of Sulfamethoxazole Using an Ozone-Electrocoagulation Hybrid Process.
Removing antibiotics from water is critical to prevent the emergence and spread of antibiotic resistance, protect ecosystems, and maintain the effectiveness of these vital medications. The combination of ozone and electrocoagulation in wastewater treatment provides enhanced removal of contaminants, improved disinfection efficiency, and increased overall treatment effectiveness. In this work, the removal of sulfamethoxazole (SMX) from an aqueous solution using an ozone-electrocoagulation (O-EC) system was optimized and modeled. The experiments were designed according to the central composite design. The parameters, including current density, reaction time, pH, and ozone dose affecting the SMX removal efficiency of the OEC system, were optimized using a response surface methodology. The results show that the removal process was accurately predicted by the quadric model. The numerical optimization results show that the optimum conditions were a current density of 33.2 A/m2, a time of 37.8 min, pH of 8.4, and an ozone dose of 0.7 g/h. Under these conditions, the removal efficiency reached 99.65%. A three-layer artificial neural network (ANN) with logsig-purelin transfer functions was used to model the removal process. The data predicted by the ANN model matched well to the experimental data. The calculation of the relative importance showed that pH was the most influential factor, followed by current density, ozone dose, and time. The kinetics of the SMX removal process followed the first-order kinetic model with a rate constant of 0.12 (min-1). The removal mechanism involves various processes such as oxidation and reduction on the surface of electrodes, the reaction between ozone and ferrous ions, degradation of SMX molecules, formation of flocs, and adsorption of species on the flocs. The results obtained in this work indicate that the O-EC system is a potential approach for the removal of antibiotics from water.


What is an acceptable treatment outcome?
Nocturnal enuresis is a multifactorial condition and, as such, is accessible to a variety of treatment modalities. In order to evaluate and compare the efficacies of different treatments in patients with specific pathophysiologies, studies should describe fully the patient population under investigation. In addition, many of the studies conducted to date have applied different outcome measures, making comparisons difficult. Therefore, it is necessary to define standard outcome measures that should be used universally. These may relate to the effect of the treatment on the number of wet nights per week, the effect on the family economy of a reduction in the number of episodes of enuresis and the effect on the child's self esteem and/or quality of life.


Postural balance in young adults: the role of visual, vestibular and somatosensory systems.
The purpose of the study is to examine what sensory system predominates to maintain balance (e.g., visual, vestibular, and somatosensory) among people in their twenties and thirties. A subset of individuals from a larger descriptive cross-sectional study was assessed. A sample of 194 (males = 28%, females = 72%) young adults in the second and third decades of life had anthropometric measurements (height, weight, waist circumference, hip circumference, and leg length) taken and body mass index and waist-to-hip ratio were calculated. Balance was assessed using the NeuroCom Balance Master machine. There was a significant difference among the three sensory systems for postural balance among the young population, F (2, 576) = 111.741, p < .001. Post hoc Bonferroni tests were maintained at the 0.05 level which showed significance for the visual system compared to vestibular and somatosensory system: visual (M = 93.7, SD = 2.07); vestibular (M = 90.4, SD = 2.74); and somatosensory (M = 90.0, SD = 3.13). Based on the results, the visual system is the predominant sensory system used by young adults to maintained optimal postural balance. SIGNIFICANCE FOR PRACTICE: There is very little known about balance of younger adults. If balance issues are identified early in adult life it is possible to prevent exacerbation of balance decline as one age. If nurse practitioners are aware of what dominant sensory systems for balance young adults use, perhaps strategies to preserve these can avoid falls as they age.


Three new coumarin glycosides from the stems of Hydrangea paniculata.
Three new coumarin glycosides (1-3), together with three known compounds (4-6), have been obtained from the stems of Hydrangea paniculata Sieb. Their structures were elucidated based on spectroscopic data and chemical evidence. In addition, compounds 1-3 were screened for their neuroprotective effects against serum deprivation-induced PC12 cell damage, hepatoprotective activities against DL-galactosamine-induced toxicity in HL-7702 cells and their ability to inhibit LPS-induced nitric oxide production in the murine microglia BV2 cell line, but they were inactive.


The Impact of Cancer-Associated Fibroblasts on Drug Resistance, Stemness, and Epithelial-Mesenchymal Transition in Bladder Cancer: A Comparison between Recurrent and Non-Recurrent Patient-Derived CAFs.
This study comparatively evaluated the possible effects of recurrent and non-recurrent patient-derived Cancer-Associated Fibroblasts (CAFs-R and -NR) on the bladder cancer cell line, EJ138. Both groups of CAFs increased cisplatin resistance and altered cell cycle distribution alongside induced resistance to apoptosis. Later, the scratch assay confirmed the cell migration-inducing effects of CAFs on cells. Nonetheless, only CAFs-R managed to increase sphere-formation and clonogenic levels in EJ138 cells, which were later validated by upregulating pluripotency transcription factors. Besides, CAFs-R also affected the expression levels of some of the EMT markers. Our study suggests that CAFs-R had stronger pro-tumorigenic effects on EJ138 cells.


Acroplaxome, an F-actin-keratin-containing plate, anchors the acrosome to the nucleus during shaping of the spermatid head.
Nuclear shaping is a critical event during sperm development as demonstrated by the incidence of male infertility associated with abnormal sperm ad shaping. Herein, we demonstrate that mouse and rat spermatids assemble in the subacrosomal space a cytoskeletal scaffold containing F-actin and Sak57, a keratin ortholog. The cytoskeletal plate, designated acroplaxome, anchors the developing acrosome to the nuclear envelope. The acroplaxome consists of a marginal ring containing keratin 5 10-nm-thick filaments and F-actin. The ring is closely associated with the leading edge of the acrosome and to the nuclear envelope during the elongation of the spermatid head. Anchorage of the acroplaxome to the gradually shaping nucleus is not disrupted by hypotonic treatment and brief Triton X-100 extraction. By examining spermiogenesis in the azh mutant mouse, characterized by abnormal spermatid/sperm head shaping, we have determined that a deformity of the spermatid nucleus is restricted to the acroplaxome region. These findings lead to the suggestion that the acroplaxome nucleates an F-actin-keratin-containing assembly with the purpose of stabilizing and anchoring the developing acrosome during spermatid nuclear elongation. The acroplaxome may also provide a mechanical planar scaffold modulating external clutching forces generated by a stack of Sertoli cell F-actin-containing hoops encircling the elongating spermatid nucleus.


Enhancing the credibility of decisions based on scientific conclusions: transparency is imperative.
Transparency and documentation of the decision process are at the core of a credible risk assessment and, in addition, are essential in the presentation of a weight of evidence (WoE)-based approach. Lack of confidence in the risk assessment process (as the basis for a risk management decision), beginning with evaluation of raw data and continuing through the risk decision process, is largely because of issues surrounding transparency. There is a critical need to implement greater transparency throughout the risk assessment process, and although doing so will not guarantee the correctness of the risk assessment or that all risk assessors come up with the same conclusions, it will provide essential information on how a particular conclusion or decision was made, thereby increasing confidence in the conclusions. Recognizing this issue, the International Life Sciences Institute Health and Environmental Sciences Institute convened a multisector committee tasked with discussing this issue and examining existing guidance and recommendations related to transparency in risk assessment. The committee concluded that transparency is inextricably linked to credibility: credibility of the data, credibility of the risk assessment process, and credibility of the resulting decision making. To increase this credibility, existing guidance concerning criteria elements of transparency related to the risk assessment process must be more widely disseminated and applied, and raw data for studies used in human health and environmental risk assessment must be more widely available. Finally, the decision-making process in risk management must be better documented and a guidance framework established for both the process itself and its communication to the public.


Exercise in the menopause - an update.
One of the most important components of lifestyle relates to physical activity. Sedentary people fare less well than those who exercise regularly. The benefits of exercise can be demonstrated in many organs of the body. The most frequently studied effect of exercise is reduction in cardiovascular morbidity and mortality, but positive effects on the musculoskeletal system, breast cancer, mood and cognition, and quality of life have been recorded as well. In many cases, a dose-response was evident, and even a mild to moderate degree of activity, performed only a few times weekly, may carry significant merits. The following article reviews this topic and brings updated information on the benefits of exercise on postmenopausal health.


Chromosomes from testicular preparations of lepidoptera.
Typical elongate, beaded chromosomes have been observed in squash preparations of testicular tissue of the butterfly Speyeria aphrodite (Fabricius), the first demonstration of relatively uncondensed chromosomes in the Lepidoptera.


Overexpression of AIOLOS inhibits cell proliferation and suppresses apoptosis in Nalm-6 cells.
The AIOLOS gene is important in the control of mature B-lymphocyte differentiation and proliferation. Previous research has shown that deregulated AIOLOS expression is associated with adult B-cell acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia in human patients. However, the function of AIOLOS in childhood B-cell precursor (BCP)-ALL is not fully understood. In the present study, Nalm-6 cells were divided into three groups: the untransfected control (UT), the lentiviral vector control (Lenti-Mock) and the AIOLOS-overexpressing (Lenti-AIOLOS) group. Lenti-AIOLOS Nalm-6 cells were constructed by lentiviral transduction, followed by cell proliferation assay, cell-cycle analysis and apoptosis assay, to evaluate the effects of AIOLOS on proliferation, cell cycle distribution and apoptosis of Nalm-6 cells in vitro. Moreover, the expression levels of genes associated with apoptosis and the cell cycle, as well as the transcription factors IKZF1 and NF-κB, were investigated by quantitative reverse transcription-polymerase chain reaction and western blot analysis. The results showed that the proliferation of Nalm-6 cells in the Lenti-AIOLOS group was reduced by 16% on day 8 compared with cells in the UT group (P>0.05). The reduction peaked at 29% on day 10 (P<0.05). The percentage of Nalm-6 cells in the G0/G1 phase increased from 70.4 (UT) to 84.1% (Lenti-AIOLOS) (P<0.01), and the S-phase cells decreased from 20.3 (UT) to 11.7% (Lenti-AIOLOS) (P<0.01). Total apoptotic cells significantly decreased in AIOLOS-transfected Nalm-6 cells (10.75%) compared with those in the Lenti-Mock (17.00%) or UT group (19.05%) (P<0.01). In particular, the difference between the groups in the percentage of late apoptotic cells was significant (2.85 vs. 7.95%; P<0.01). In addition, overexpression of AIOLOS resulted in upregulation of BCL-2 and downregulation of CCND3, BAX, IKZF1 and NF-κB. No changes were detected on C-MYC and P27. Our findings indicate that lentivirus-mediated overexpression of AIOLOS in Nalm-6 cells could inhibit cell proliferation, suppress cell apoptosis and arrest the cell cycle at the G0/G1 phase in vitro.


Two cases of asymptomatic Teflon granulomas following microvascular decompression mimicking cerebellopontine angle tumours: lessons learnt in the neuro-oncology multidisciplinary team.
We present the cases of two patients with asymptomatic Teflon granulomas which were incidentally found years after microvascular decompression and presented to the neuro-oncology multidisciplinary team as possible cerebellopontine angle tumours. Teflon granulomas can be asymptomatic and they can radiologically resemble cerebellopontine angle tumours. It is important that all relevant information is available to the neuro-oncology multidisciplinary team for adequate assessment and appropriate treatment recommendations.


Chlamydia trachomatis serovar distribution and Neisseria gonorrhoeae coinfection in male patients with urethritis in Greece.
The distribution of Chlamydia trachomatis serovars and Neisseria gonorrhoeae coinfection was studied in a group of 100 C. trachomatis-positive males with urethritis in Greece. The serovar distribution revealed that apart from the predominant worldwide types E and F, the relatively uncommon type G is also prevalent. Gonococcal coinfection was frequent (30%) and was associated with genovariant Ja (75%, P = 0.008).


An Analysis of Young Driver Crash Types and the Associated Lifetime Care Cost in Victoria, Australia.
The elevated crash involvement rate of young drivers is well documented. Given the higher crash risk of young drivers and the need for innovative policy and programs, it remains important to fully understand the type of crashes young drivers are involved in, and knowledge of the lifetime care cost of crashes can support effective policy development. The aim of this article is to document the number and type of young driver crashes, as well as the associated lifetime care cost over a 9-year period (2005-2013) in Victoria, Australia. In Victoria, Australia, the Transport Accident Commission (TAC) has legislated responsibility for road safety and the care of persons injured in road crashes, irrespective of fault. TAC claims data for the period 2005-2013 were used to document the number and type of young driver crashes. Lifetime care costs (past and future payment liabilities) were calculated by Taylor Fry actuarial consultancy. License and population data were used to define the crash involvement rate of young drivers. Over the 9-year period, 16,817 claims were lodged to the TAC by drivers 18-25 years of age following a crash. There were 646 fewer drivers aged 18-25 killed and injured in 2013, compared to 2005, representing an unadjusted change of -28.7% (-29.8% males; -28.4% females). The total lifetime care cost of young drivers killed and injured in Victoria for the period 2005-2013 was estimated to be AU$634 million (US$493 million). Differences between males and females, single- and multivehicle crashes, and fatalities and injuries were found to be statistically significant. Run-off-road crashes and crashes from opposing direction were overrepresented in the lifetime care costs for young driver claimants. Twenty-eight injured drivers were classified as high-severity claims. These 28 claimants require additional long-term care, which was estimated to be AU$219 million; of these 28, 24 were male (85.7%). The long-term care costs for these 28 drivers (0.16%) accounts for 34.5% of the total lifetime care cost of all 18- to 25-year-old injured drivers. By using no-fault lifetime care costs that account for medical and like expenses, rehabilitation, and social reintegration costs, a more accurate understanding of the cost of young driver crashes can be determined. Application of these costs to specific crash types highlights new priorities and opportunities for developing programs to reduce young driver crashes.


[Acute appendicitis in Crakow population].
In spite of decreasing morbidity, acute appendicitis (AA) is still found the most frequent cause of so called acute abdomen. This study presents the retrospective estimation of 1515 patients treated surgically in ten years period, admitted to hospital with the initial diagnosis of AA. In 1339 patients the initial diagnosis was confirmed during surgery. This group was divided into three subgroups: 1. Without perforation, 2. With perforation or abscess presence, 3. With diffuse peritonitis. In our study 60% of patients were male, however in the group aged over 70 we found the majority were females. The mean age was 16.7 years and in half of the cases patients were under 20. The incidence for Cracow population was 61.6 new cases in group of 100,000 inhabitants per one year (74.7 for males and 49.7 for females). The risk of appendix perforation or diffuse peritonitis was higher in extreme age groups. Mortality rate we found as 0.9%, but the risk of death was significantly higher in patients with advanced AA, or in the group over 70. Percentage of missed diagnoses was found as 11.6, and there was an advantage of female (female 19.2%, male 5.7%). Wound infection was dominant with the frequency rising along with the progression of AA. 1. The morbidity of AA in Cracow population in years 1989-1998, was 61.6/100,000/year on average and showed decreasing trend. 2. General mortality in AA remains at a stable and does not exceed 1%. It is most frequent in patients over 70 irrespectively of the form of AA.


An unusual presentation of primary renal hypokalemia-hypomagnesemia (Gitelman's syndrome).
Gitelman's syndrome, or congenital hypokalemic hypomagnesemic hypocalciuria with metabolic alkalosis, is widely described as a benign or milder variant of Bartter's syndrome and most commonly presents with transient periods of weakness and fatigue, presyncope, vertigo, ataxia, and blurred vision, though aborted sudden cardiac death has also been rarely reported. Despite this there are limited data in the literature regarding the formal cardiac evaluation of patients with Gitelman's syndrome. We present the case of a gentleman with Gitelman's syndrome who initially presented to his primary physician with symptoms suggestive of an upper respiratory tract infection and subsequently survived a ventricular fibrillation (VF) cardiac arrest in the community. We review the literature regarding possible life-threatening cardiac complications in these patients.


The Outliers: Metal-Mediated Radical Reagents for Biological Substrate Degradation.
The predictable and controllable interaction of small organic or peptidic molecules with biological substrates is the primary reason most pharmaceuticals are narrowly decorated carbon frameworks. The inhibition or activation binding models are measurable and without side reactions that can cause pathological angst. Yet many diseases, especially those involving rapid proliferation of cells (i.e., cancer) or aggregation of peptides (e.g., heart disease, Alzheimer's disease) have not yet been cured by inhibition therapeutics. Additionally, interventional medicine is often required to alleviate such maladies by physical removal first, followed by molecular-level therapy as a second stage. Thus, there appears to be a niche for more aggressive therapeutics that may employ harsher chemical processes to realize clinical efficacy, albeit without causing catastrophic side effects. Molecules that may be considered for this challenge are not typically biomimetic, nor do they fit the traditional pharmaceutical paradigm. They may have unusual modes of action or undesired reactivity that can be lethal if not controlled. These are the outliers; potential pharmacophores that biology does not know how to manage or adapt to. This is why they may be an intriguing class of agents that needs continuous development. In this Account, we connect the under-developed enediyne family of compounds and our metalloenediyne derivatives to existing radical-based therapeutics such as bleomycin and doxorubicin to illustrate that controlled diradical reactivity, although an outlier mechanism, has a place in the therapeutic portfolio. This is self-evident in that of the 11 natural product enediynes known, 2 have clinical impact, a strong ratio. We expand on the chemical diversity of potential enediyne constructs and focus on the accessible trigger mechanisms to activate diradical formation as a method to control toxicity. Moreover, we further illustrate how electromagnetic fields can be employed to activate both molecular and larger nanomaterial constructs that carry highly concentrated payloads of reactive reagent. Finally, we describe how controlled diradical reactivity can reach beyond traditional therapeutic targets such as DNA, to peptide aggregates found in blood clots, neural fibrils, and membrane scaffolds. It is our belief that cleverly constructed frameworks with well-designed and controlled activation/reaction schemes can lead to novel therapeutics that can challenge evolving viral and bacterial invaders. From this evangelical perspective, our hope is that the conceptual framework, if not the specific designs in this Account, stimulate the readership to develop out-of-the-box therapeutic designs that may combat resistant disease targets.


[The roles of Kupffer cells in the development and regression of liver fibrosis].
Hepatic fibrosis results from iterative hepatic injury with sustained inflammation, formation of scar tissue, loss of tissue architecture and organ failure. There is no doubt, from both human and animal studies, that too much or too protracted inflammation in the liver leads to excess scarring. During liver injury, Kupffer cells can quickly flood the hepatic milieu with soluble mediators, including oxidants, cytokines, and proteinases, which can affect stellate cell proliferation, migration, and differentiation. On the other hand, the contribution of Kupffer cells to regression of hepatic fibrosis has been demonstrated. These findings underscore the potential importance of hepatic macrophages in regulating both stellate cell biology and extracellular material degradation during regression of hepatic fibrosis. Therefore, biological characterization of Kupffer cells, their interactions with stellate cells in the cytokine environment are essential to understand the mechanisms underlying the progressive development of excessive scarring in the liver as well as the ability of the liver for tissue repair and recovery.


Functional study and epigenetic targets analyses of SIRT1 in intramuscular preadipocytes via ChIP-seq and mRNA-seq.
The SIRT1 epigenetic regulator is involved in hepatic lipid homoeostasis. However, the role of SIRT1 in regulating intramuscular fat deposition as well as the pathways and potential epigenetic targets involved remain unknown. Herein, we investigate SIRT1 function, its genome-wide epigenetic target profile, and transcriptomic changes under SIRT1 overexpression during yak intramuscular preadipocytes differentiation. To this end, we analysed the relationship between SIRT1 and intramuscular fat content as well as lipid metabolism-related genes in longissimus dorsi tissue. We found that SIRT1 expression negatively correlates with intramuscular fat content as well as with the expression of genes related to lipid synthesis, while positively correlating with that of fatty acid oxidation-involved genes. SIRT1 overexpression in intramuscular preadipocytes significantly reduced adipose differentiation marker expression, intracellular triacylglycerol content, and lipid deposition. Chromatin immunoprecipitation coupled with high-throughput sequencing of H3K4ac (a known direct target of SIRT1) and high-throughput mRNA sequencing results revealed that SIRT1 may regulate intramuscular fat deposition via three potential new transcription factors (NRF1, NKX3.1, and EGR1) and four genes (MAPK1, RXRA, AGPAT1, and HADH) implicated in protein processing within the endoplasmic reticulum pathway and the MAPK signalling pathway in yaks. Our study provides novel insights into the role of SIRT1 in regulating yak intramuscular fat deposition and may help clarify the mechanistic determinants of yak meat characteristics.


[Changes in Plasma Amyloid-β Level and Their Relationship With White Matter Microstructure in Patients With Mild Cognitive Impairment].
Objective To investigate the changes in plasma amyloid-β (Aβ) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aβ42 and Aβ40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aβ42,Aβ40,and Aβ42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aβ42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aβ42 level showed no significant difference among the three groups (P=0.227).The plasma Aβ40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aβ42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aβ42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aβ42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aβ42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aβ levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aβ levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.


Citrullination regulates the expression of insulin-like growth factor-binding protein 1 (IGFBP1) in ovine uterine luminal epithelial cells.
There are five peptidylarginine deiminase (PAD) isozymes designated as PADs 1, 2, 3, 4 and 6, and many are expressed in female reproductive tissues. These enzymes post-translationally convert positively charged arginine amino acids into neutral citrulline residues. Targets for PAD-catalyzed citrullination include arginine residues on histone tails, which results in chromatin decondensation and changes in gene expression. Some of the first studies examining PADs found that they are localized to rodent uterine epithelial cells. Despite these findings, the function of PAD-catalyzed citrullination in uterine epithelial cells is still unknown. To address this, we first examined PAD expression in uterine cross-sections from pregnant ewes on gestation day 25 (d25). Immunohistochemistry revealed that the levels of PADs 2 and 4 are robust in luminal and glandular epithelia compared with those of PADs 1 and 3. As PADs 2 and 4 have well-characterized roles in histone citrullination, we next hypothesized that PADs citrullinate histones in these uterine cells. Examination of caruncle lysates from pregnant ewes on gestation d25 and an ovine luminal epithelial (OLE) cell line shows that histone H3 arginine residues 2, 8, 17 and 26 are citrullinated, but histone H4 arginine 3 is not. Using a pan-PAD inhibitor, we next attenuated histone citrullination in OLE cells, which resulted in a significant decrease in the expression of insulin-like growth factor-binding protein 1 (IGFBP1) mRNA. As IGFBP1 is important for the migration and attachment of the trophectoderm to uterine endometrium, our results suggest that PAD-catalyzed citrullination may be an important post-translational mechanism for the establishment of pregnancy in ewes.


Endothelin-1 potentiates ADP-induced platelet aggregation in chronic renal failure.
The effect of preincubation of heparinized whole blood with endothelin-1 (ET-1) on the ADP (adenosine diphosphate) and epinephrine-induced platelet aggregation was examined in 20 healthy donors compared with 20 patients with chronic renal failure (CRF). ET-1 significantly stimulated ADP-induced aggregation in CRF: EC (effective concentration)25 = 2.3 +/- 0.20 with ET-1 vs. 2.7 +/- 0.22 mumol/L without ET-1; EC50: 3.8 +/- 0.18 with ET-1 vs. 4.4 +/- 0.24 mumol/L without ET-1; and EC75: 5.7 +/- 0.22 with ET-1 vs. 6.4 +/- 0.21 mumol/L without ET-1). In healthy donors only the EC25 was significantly increased: EC25 = 2.5 +/- 0.13 with ET-1 vs. 2.8 +/- 0.20 mumol/L without ET-1. No significant influence of ET-1 in epinephrine-induced aggregation was observed in CRF or in healthy donors. The basal values of determined ET-1 were significantly elevated in CRF: 6.99 +/- 0.29 pmol/mL vs. 5.65 +/- 0.33 pmol/mL in healthy donors. The high endogenous level of ET-1 in CRF patients together with an observed higher endogenous plasma level of cAMP (58 +/- 5.2 nmol/L compared to 29 +/- 2.0 nmol/L in healthy donors) may explain the enhanced pharmacological interaction of ET-1 and ADP in CRF patients. The data suggest that positive agonist interaction between ET-1 and ADP may result from effects on the concentrations of cAMP within the platelet rather than from direct interaction on the membrane receptors or the transmembrane coupling mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)


Superhydrophobic surfaces with photocatalytic self-cleaning properties by nanocomposite coating of TiO(2) and polytetrafluoroethylene.
Superhydrophobic surfaces with photocatalytic self-cleaning properties are designed through coating a nanocomposite TiO(2) photocatalyst and hydrophobic polytetrafluoroethylene onto a structured substrate by applying a co-deposition technique. This coating realizes adequate photocatalytic activity for self-cleaning and inducing unique surface wettability changes. The nanocomposite can contain multiple functions, enabling energy-saving and maintenance-free characteristics.


Spectrum of common Hodgkin lymphoma and non-Hodgkin lymphomas subtypes in Zambia: a 3-year records review.
Lymphomas usually present with different occurrence patterns across different geographical locations, but their epidemiology in Zambia is yet to be extensively explored. To study the spectrum of lymphoma subtypes prevalent within the Zambian population. Histopathological records with suspected lymphoma at the University Teaching Hospital (UTH) in Lusaka from the year 2014 to 2016, diagnosed based on the 2008 World Health Organization (WHO) criteria were reviewed. The analysis was done in terms of type, sex, age, and site of biopsy; and Fisher's exact test was used for significance testing. During the study period (2014-2016), there were more B cell neoplasms {222 (92.5%)} than T cell neoplasms {18 (7.5%)}. Non-Hodgkin's lymphoma (NHL) was seen in 191 (79.6%) whereas classic Hodgkin's lymphoma (CHL) was seen in 39 (16.3%). Burkitt's lymphoma (BL) and diffuse large B cell lymphoma (DLBCL) showed equal proportions {17.5% of all lymphoma cases (42/240) each}, as the most prevalent subtypes of NHL whereas marginal zone B cell lymphoma was the rarest subtype with 1.4% (4/240). For CHL, mixed cellularity and lymphocyte rich subtypes (4.6% of all lymphoma cases) were the most common subtypes. There was a statistically significant difference in the occurrences of lymphoma subtypes across different age categories (p = 0.002). Zambia has a diverse lymphoma subtypes population, affecting a relatively young population. The data from this study will serve as a baseline for improved health care provision and more robust future studies.


Morphological studies of fiber types of striated muscle fibers of the cremaster in the guinea pig.
THe fine structure of the striated muscle fibers of the cremaster of the guinea pig was studied using the cholinesterase technique and light and electron microscopy. Under light microscopy, isolated single muscle fibers showed two types of nerve endings: the first one presented elliptic or oval areas having digit-like structures inside, some of the borders of which were heavily stained. These fibers had only one end-plate. The second type presented elongated clear areas with most of the density located on the borders. Several nerve endings were apparent in these fibers. By electron microscopy, the former had large and numerous sarcolemmal foldings and these characteristics were also observed in unstained fibers. In the latter, the foldings were scanty or absent. At the ultrastructural level, the fibers having only one end-plate presented a regular array of fibrils with an abundant sarcoplasmic reticulum ('Fibrillenstruktur' type) in contrast to the multi-innervated fiber with an irregular distribution pattern of fibrils and a scarce sarcoplasmic reticulum ('Felderstruktur' type). The striated muscle fiber layer of the cremaster probably contains both fast and slow fibers. The possible functional role for the slow striated muscle fibers is discussed.


Studying plant-pollinator interactions facing climate change and changing environments.
Plant-pollinator interactions are essential for successful plant reproduction in both natural and agricultural systems. These interactions are negatively impacted by recent large-scale alterations of the environments, particularly climate change. The responses of plants and pollinators to changing abiotic conditions that vary seasonally and geographically are often uncoordinated, potentially leading to the breakdown of this interaction. The complexity of the responses of plants and pollinators to our changing climate necessitates creative approaches. The six articles in this special issue directly address this need by providing a variety of key methods and reviews of current methodology. The articles include: DNA barcoding methods for use on pollen collected from visiting bees; methods for assessment of plant attraction traits (nectar and review of floral volatiles methods); a field sampling method for ground nesting bees; a review of using spatial and temporal transplants for addressing changing dynamics of plant-pollinator interactions; and a review of approaches used to assess potential shifts in phenology of plants and pollinators. Collectively, these articles illustrate some of the breadth of approaches needed to address the changing dynamics of plant-pollinator interactions.


[T-cell granular lymphocyte-proliferative disorder without severe infection for 13 years despite severe neutropenia].
A 68-year-old woman was referred to Oami Hospital for severe leukocytopenia. Laboratory data revealed severe leukocytopenia (0.8x10(9)/l), severe neutropenia (0.22x10(9)/l) and IgM-kappa monoclonal gammopathy. Granular lymphocytes accounted for more than 90% of leukocytes. Surface marker analysis revealed that these lymphocytes were CD3+, CD4-, CD8+ and CD16+, and monoclonal rearrangement of T-cell receptor genes was seen on Southern blot hybridization analysis. She was diagnosed with T-cell lineage granular lymphocyte proliferative disorder (T-GLPD). During 13-year follow-up without granulocyte-colony stimulating factor (G-CSF) administration, except for one hospitalization because of bacterial pneumonia, she has not experienced severe infection, despite severe neutropenia. T-GLPD should be kept in mind as a cause of leukocytopenia with or without monoclonal gammopathy, and surface marker or Southern blot hybridization analysis should be considered for determining the diagnosis. There are many reports about Caucasian patients with T-GLPD suffering from recurrent infections and dying of severe infection, but in Japanese T-GLPD patients, severe infection is very rare, as shown in the present case report.


Autologous cord blood transfusion in preterm infants - could its humoral effect be the kez to control prematurity-related complications? A preliminary study.
Umbilical cord blood (UCB), rich in stem/progenitor cells, is partially eliminated from the bloodstream during childbirth because the cord is immediately clamped. We hypothesize that transfusion of autologous UCB to premature infants after delivery could serve as an adjuvant modality for preventing the development of prematurity-related complications. We randomly enrolled 20 preterm infants born before 32 weeks of gestational age (GA), all of whom developed anemia, necessitating transfusion of red blood cells (RBCs). Two groups, matched for GA, were selected: (1) infants (n = 5) who underwent UCB transfusion once within 5 days of birth (mean ± standard deviation, 3.2 ± 1.9 days) and (2) infants (n = 15) from whom UCB was not collected (e.g., lack of consent). The latter served as controls and received allogeneic RBC transfusions (7.8 ± 3.9 days after birth). Selected prematurity-related complications were monitored. Two weeks after UCB/RBC transfusion, peripheral blood samples were collected, and the concentrations of 41 selected growth factors and their receptors were analyzed using a multiplex protein array. UCB transfusions were found to be both feasible and tolerable. Intraventricular haemorrhage was diagnosed in two of five (40%) UCB recipients, but was found in thirteen of fifteen RBC recipients (86.7%). Twenty-two plasma proteins (e.g., insulin-like growth factors, stem cell factor, epidermal growth factors) were found with significantly different concentrations in UCB recipients compared to controls. Results demonstrate safety and feasibility of UCB transfusion in a small group of very premature neonates and should be interpreted as preliminary speculation. Transfusion of UCB could induce a specific humoral effects, and this could serve as an adjuvant modality for prevention of prematurity complications.


Five-year survey of cefotaxime resistance in Spain.
During 1991-1995 a Spain collaborative study group surveyed the resistance to cefotaxime both in community as well as in hospital isolates of bacteria. The isolates tested during the study period of 5 years were 813, 875, 3631, 3184, and 3050 strains, respectively. Antimicrobial activity of cefotaxime was assayed by broth or agar microdilution, in accordance with criteria of the National Committee of Clinical Laboratory Standards (NCCLS). Cefotaxime resistance included 2.5% of all isolates: 2.6% Enterobacteriaceae, 1.7% Streptococcus pneumoniae, 0.5% Haemophilus influenzae, 0.0% Haemophilus spp., and 0.0% Moraxella catarrhalis. The overall incidence of resistance to cefotaxime decreased fro member of Enterobacteriaceae from 3.6% in 1991 to 2.5% in 1995. The incidence of resistance varied with the species and was highest in Enterobacter and in Citrobacter freundii.


Insulin treatment and myocardial function in isolated, perfused heart from diabetic rat.
Difficulty of some patients to maintain adequate cardiac output following the termination of cardiopulmonary bypass remains a significant problem in cardiac surgery. The patients with diabetes mellitus frequently fail to respond to therapy after the cardiopulmonary bypass. However, little is known about the relationship between the control of diabetes mellitus and myocardial performance. The purpose of the present study was to look at the effect of diabetes and insulin treatment upon ventricular function and myocardial microcirculation in isolated perfused rat heart. Experimental diabetes was induced by injecting streptozotocin and some of them were treated by insulin injection. Severe form of ischemia was induced in heart from acute form of diabetes and functional recovery was compared among the control, diabetic and insulin treated groups. In chronic form of diabetes, myocardial function and microcirculation which was measured by local H2 generation method were studied during aerobic perfusion and mild form of ischemic perfusion. The hearts from experimental diabetes were more susceptible to ischemia and insulin pretreatment protected the functional alterations. This beneficial effect of insulin was associated with improved glucose and fatty acid metabolism. Myocardial microcirculation in hearts from diabetes was significantly less than in control, however, this was not correctable by the insulin treatment.


Age-related changes of the innate immune system of the palatine tonsil in a healthy cohort.
Although tonsillectomy is performed frequently, the role of palatine tonsils in life long immune protection or tolerance is still debated and the consequences of their removal for the immune system are of general interest. We analysed the tonsillar myeloid compartment in healthy subjects across a wide range of age (64% male; age range: 3 - 85 years) and compared its composition to the peripheral blood. We could observe a strong accumulation of all granulocyte subsets in the aging tonsil, which was most pronounced for basophils and mast cells. On functional level, an increase of CD163 and CD206 expression among monocytes and an increase of neutrophils expressing the inhibitory FcγRIIb correlated with increasing age. While the age-related shift of the leukocyte composition towards monocytes in blood is not reflected in tonsils, the increasing immunoregulatory phenotype of tonsilar monocytes is potentially counteracting the phenomenon of inflammaging at higher age.


A quantitative analysis of microalgal lipids for optimization of biodiesel and omega-3 production.
The lipid characteristics of microalgae are known to differ between species and change with growth conditions. This work provides a methodology for lipid characterization that enables selection of the optimal strain, cultivation conditions, and processing pathway for commercial biodiesel production from microalgae. Two different microalgal species, Nannochloropsis sp. and Chlorella sp., were cultivated under both nitrogen replete and nitrogen depleted conditions. Lipids were extracted and fractionated into three major classes and quantified gravimetrically. The fatty acid profile of each fraction was analyzed using GC-MS. The resulting quantitative lipid data for each of the cultures is discussed in the context of biodiesel and omega-3 production. This approach illustrates how the growth conditions greatly affect the distribution of fatty acid present in the major lipid classes and therefore the suitability of the lipid extracts for biodiesel and other secondary products.


Five new species of Bryaxis Kugelann (Coleoptera, Staphylinidae, Pselaphinae) from Korea and a nomenclatural note on Bryaxismahunkai Löbl.
The genus Bryaxis Kugelann (Goniaceritae: Bythinini) is the most species-rich genus of the subfamily Pselaphinae and is mainly distributed in the Palearctic region. Although previous studies have documented 14 species in the Korean Peninsula, the true diversity, ecology, and immature stages of the genus are still inadequately known. In this study, five new Korean species are described: B.grandinodussp. nov., B.uljinensissp. nov., B.fabaiformissp. nov., B.girinensissp. nov., and B.nemorosussp. nov. Illustrations of the habitus and other morphological details, and a distribution map are provided. In addition, Bryaxisleechanyoungi Nomura & Lee, 1993 is proposed as a new synonym of B.mahunkai Löbl, 1975 based on the original description and illustrations of diagnostic characters.


Key considerations and current perspectives of epidemiological studies on human papillomavirus persistence, the intermediate phenotype to cervical cancer.
Persistent infection with human papillomavirus (HPV) causes essentially all precancerous cervical lesions and cervical cancer in females and thus is an important intermediate phenotype to cervical cancer. A majority of infected individuals naturally clear HPV viral infection, but the virus persists in a subset of infected hosts and the mechanism for this differential outcome is not well described. Most of the epidemiological studies have been cross-sectional in nature, and even with longitudinal studies, the definition of HPV persistence or clearance has not been well defined. There is no consensus on the correct time interval between HPV DNA tests, or how to utilize HPV persistence information in clinical management because there is no treatment for HPV. While most studies are performed with the endpoint of cancer, the intermediate phenotype has been overlooked. Epidemiological studies of HPV persistence suffer with several challenges in definitions, study designs, and analyses that undermine its importance in identifying and understanding the interactions between the viral and host genomes in the process of HPV infection pathogenesis. We have evaluated the current status of HPV persistence and provide perspectives on how the field would benefit from a research focus on intermediate phenotype in epidemiological studies.


A novel classification for atypical Hangman fractures and its application: A retrospective observational study.
Atypical Hangman fractures (AHF) were first formally reported and considered to be more often associated with neurologic deficit in 1993. However, there is a paucity of literature focusing on these fractures. The purpose of the retrospective study was to introduce a new classification scheme for AHF and its application.Sixty-two patients with Hangman fractures were identified. There were 46 (74.2%, 46/62) AHF patients, including 29 type I, 9 type II, 5 type IIa, and 3 type III fractures (Levine-Edwards classification). Based on fracture patterns, incidence, and their impact on neurologic status, a primary classification for AHF was devised. The clinical features of AHF were observed, and a new classification was introduced. The appropriate treatment strategy of AHF was discussed.Of 46 AHF patients, 27 underwent surgical treatment (24 with posterior approach with screw-rod fixation and fusion, 1 with anterior approach by C2/3 discectomy and fusion, and 2 with anterior and posterior approach), and the remaining 19 patients underwent nonoperative treatment. No patient complained severe neck pain at final follow-up. Neurologic status improved 1 to 2 grade in 12 cases with neurologic deficit. All patients achieved bony fusion within the follow-up period.AHF should be recognized as a distinct fracture subtype. The new classification for AHF is based on the feature of fracture patterns, injury mechanism, incidence, and their impact on neurologic deficit. And the new classification is complementary to Levine-Edwards.