Maintenance of locomotor abilities following Laufband (treadmill) therapy in para- and tetraplegic persons: follow-up studies.
Recent reports indicate that walking capabilities in spinal cord damaged persons significantly improve--as compared to conventional rehabilitation therapy--after intensive training of aided (Laufband) treadmill-stepping. In the present report, follow up investigations on two collectives of spinal cord injured (sci) persons are described who had undergone (Laufband) treadmill therapy either during a period of renewed rehabilitation months or years after spinal cord injury (35 chronic patients) or during their first postacute rehabilitation period (41 acute patients). Among the initially chronic patients, 20 from 25 still wheelchair-bound before the onset of (Laufband) treadmill therapy, ie not capable of raising from the wheelchair and walking without help by other persons, became independent walkers after therapy. Assessment of voluntary muscle activity in resting position before and after the period of therapy had shown only small increases in most patients, indicating the involvement of motor automatisms and better utilisation of remaining muscle function during walking. Follow-up assessments performed 6 months to 6 1/2 years after discharge from the hospital revealed that the walking capabilities achieved by (Laufband) treadmill therapy in the 35 initially chronic patients were maintained in 31 persons, in three they had further improved, in only one it was reduced. These results indicate that the improvements achieved under clinical conditions can be maintained in every day life under domestic surroundings. From 41 initially acute patients, 15 had further improved and none had reduced his walking capability 6 months to 6 years after discharge from the hospital.


The pretreatment albumin to globulin ratio predicts chemotherapeutic outcomes in patients with unresectable metastatic colorectal cancer.
The pretreatment albumin to globulin ratio (AGR) has been reported to correlate with the long-term survival in patients with various cancers. However, there are no reports regarding the correlation between the pretreatment AGR and chemotherapeutic outcomes in patients with unresectable metastatic colorectal cancer. The aim of this study was to evaluate the prognostic significance of the pretreatment AGR in patients with unresectable metastatic colorectal cancer. A total of 66 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy for metastatic tumors were enrolled. The AGR was calculated as follows: Albumin/(Total protein - Albumin). The median pretreatment AGR was 1.254 (range: 0.849-1.840). We set 1.25 as the cut-off value based on the receiver operating characteristic curve. Based on the cut-off value of 1.25, 34 patients were classified into the high-AGR group and 32 patients were classified into the low-AGR group. The high-AGR group had a significantly higher chemotherapeutic disease control rate (p = 0.040) and better progression-free survival (p = 0.0171) and overall survival (p = 0.0360) rates than the low-AGR group. According to a multivariate analysis of survival, the AGR was identified to be an independent prognostic factor for progression-free survival (Hazard Ratio: 2.662, 95% Confidence Interval: 1.085-6.631, p = 0.033) and overall survival (Hazard Ratio: 2.247, 95% Confidence Interval: 1.069-4.722, p = 0.033). The pretreatment AGR is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy.


Non-ionic surfactants and membrane transport of thioridazine in goldfish.
Polysorbate 80, which has been widely used in studies of the effects of surfactants on drug absorption, increases the rate of absorption of some drugs at concentrations near its critical micelle concentration (cmc). To determine whether all non-ionic surfactants were capable of inducing this effect, the effects of six commercial non-ionic surfactants on thioridazine absorption in goldfish have been compared with the effect of polysorbate 80. The reciprocal death time (T-1) determined when the fish were immersed in the solution under study was the index of absoprtion rate used. Not all surfactants tested increased T-1. Cremophor EL (polyoxyethylated castor oil), Atlas G1295 (a polyoxyethylene fatty glyceride), Atlas G1300 (a polyoxyethylene glyceride ester) had no effect below their cmc's. Those surfactants that did increase T-1 [polysorbate 80 (a polyoxyethylene lanolin derivative), G2162 (a polyoxyethylene oxypropylene monosterate) and Renex 650 (a polyoxyethylene alkyl aryl ether)] display the concentration-dependent behaviour reported previously - a decrease in absorption rate when the surfactant concentration is increased above its cmc. The factor determining whether or not the surfactant will increas absorption rate appears to be the configuration of the surfactant molecule rather than its hydrophile-lipophile balance or its surface activity.


Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study.
To investigate the role of estrogen deprivation and replacement in amenorrheic and nonamenorrheic dancers on hormone therapy and calcium. Clinical, placebo-controlled, randomized trial study.Healthy volunteers in an academic research environment. Fifty-five dancers (mean age: 22.0 +/- 4.6, age at menarche: 14.7 +/- 2.3 years), including 24 amenorrheics. Amenorrheics were randomized in a controlled trial to receive placebo or Premarin, 0.625 mg for 25 days monthly, with Provera, 10 mg, for 10 of these 25 days (hormone therapy) for 2 years. These women were compared to normally menstruating controls. The study participants also received 1250 mg of calcium per day. Bone mineral density (BMD) measured at the foot, wrist, and lumbar spine. Our overall results showed no difference in BMD between the treated or placebo groups, indicating that hormone therapy did not change or normalize BMD when compared to normals. Five patients (all on placebo) who resumed menses during the study showed an increase in BMD without normalization. These findings suggest that mechanisms other than hypoestrogenism may be involved with the osteopenia associated with exercise-induced amenorrhea.


SRD5A1 and SRD5A2 are associated with treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic receptor antagonists.
Common treatments for benign prostatic hyperplasia include 5α-reductase inhibitors and α-adrenergic receptor antagonists. However, these treatments can only partially decrease the risk of benign prostatic hyperplasia progression. SRD5A1 and SRD5A2 are 5α-reductase inhibitor targets. We investigated the association between drug efficacy and single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a Chinese population. We genotyped 11 tagging single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a total of 426 benign prostatic hyperplasia cases and 1,008 controls from Xinhua Hospital, Shanghai, People's Republic of China. Cases were treated with type II 5α-reductase inhibitors and α-adrenergic receptor antagonists. We tested the association of tagging single nucleotide polymorphisms with benign prostatic hyperplasia risk/progression, clinical characteristics at baseline, including the I-PSS (International Prostate Symptom Score) and total prostate volume, and changes in clinical characteristics after treatment. The 11 tagging single nucleotide polymorphisms were not significantly associated with benign prostatic hyperplasia risk or progression (each p >0.05). In the SRD5A1 gene rs6884552 and rs3797177 were significantly associated with baseline I-PSS (p = 0.04 and 0.003, respectively). In the SRD5A2 gene rs523349 (V89L) and rs9332975 were significantly associated with baseline total prostate volume (p = 0.01 and 0.001, respectively). In SRD5A1 rs166050 was significantly associated with the posttreatment change in total prostate volume (p = 0.04). In SRD5A2 rs523349 and rs612224 were significantly associated with the posttreatment I-PSS change (p = 0.03 and 0.009, respectively). SRD5A1 and SRD5A2 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.


Risk assessment in electronic assembly workers: carpal tunnel syndrome.
Symptoms that develop in workers after repeated mechanical injury may be overlooked until the disability affects their productivity and safety. Modifications in the design of hand-operated tools or adaptations in production ergonomics may prevent further damage and permit affected workers to recover while avoiding the development of repetitive cumulative trauma in workers who are new to the job task. This article describes the results of an on-site survey, a biomechanical analysis, and a special neurologic assessment in an electronic assembly plant and provides a structured approach to worker surveillance and intervention to reduce the risk of carpal tunnel syndrome caused by repetitive motions.


Effect of a maternal cafeteria diet on the fatty acid composition of milk and offspring red blood cells.
Previous studies have demonstrated that exposure to a maternal cafeteria diet during the lactation period alone produces detrimental effects to offspring metabolic health comparable to exposure during the entire perinatal period. The present study used a rodent model to assess the effect of a maternal cafeteria diet on the fat content and fatty acid composition of the dams' milk, and to determine the degree to which this was related to the fatty acid status of offspring on postnatal day 1 (PND1), weaning and 3 weeks post-weaning onto a standard rodent diet. As expected, omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) content of both the milk and pup red blood cells (RBCs) was lower in the cafeteria (CAF) group on PND1. At 2 weeks post-partum, milk produced by CAF dams had a higher total fat, saturated fat and n-6 PUFA content, however these differences were modest in comparison with the differences in maternal intake between groups. Offspring suckled by CAF dams had a lower n-3 LCPUFA and n-6 PUFA status at weaning and higher trans fatty acid levels at both weaning and 6 weeks of age. These findings indicate that the fat content and fatty acid composition of the dam's milk is altered by exposure to a cafeteria diet. While it appears that the dam has a significant capacity to buffer the transfer of most dietary lipids into the milk, the trans fatty acids in particular appear to be readily transferred, resulting in persistent increases in trans fatty acid status of the offspring after weaning. The potential physiological implications of this warrants further examination.


Dantrolene and mepacrine antagonize the hemolysis of human red blood cells by halothane and bee venom phospholipase A2.
Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood cells. Phospholipase A2 (1 microM) alone caused less than 2% hemolysis, despite high levels (54%) of phosphatidylcholine hydrolysis. Incubation of red blood cells with halothane and phospholipase A2 caused 72% hemolysis. Halothane addition caused 100% hydrolysis of all diacylphosphoglycerides by phospholipase A2, suggesting a mutual potentiation. The major products of phospholipase A2 activity, arachidonic acid and lysophosphatidylcholine, when exogenously added, also greatly increased hemolysis induced by halothane, with arachidonic acid most closely resembling the synergism observed with phospholipase A2. Dantrolene (10 microM) and mepacrine (10 microM) significantly antagonized hemolysis induced by halothane and phospholipase A2 or halothane and exogenously added arachidonic acid and lysophosphatidylcholine. Dantrolene and mepacrine did not antagonize phospholipid hydrolysis or free fatty acid levels. Dantrolene and mepacrine antagonized the synergism between halothane and phospholipase A2 most likely by reducing the lytic action of halothane in the presence of arachidonic acid. The red blood cell is a useful model for studying the antagonism of halothane and phospholipase A2 toxicity by dantrolene and mepacrine.


Inflammation induces tau pathology in inclusion body myositis model via glycogen synthase kinase-3beta.
Inclusion body myositis (IBM) is an inflammatory muscle disease, although the role of inflammation remains to be elucidated. Here, we address the mechanisms by which inflammation modulates Abeta and tau, two hallmark features of this disease. A transgenic mouse model of IBM was utilized in which acute and chronic inflammation was induced via lipopolysaccharide. The effects of inflammation were assessed by analyzing the myopathological and the behavioral phenotype. Human IBM skeletal muscle biopsies were investigated to determine concordance with data from the animal model. Both acute and chronic lipopolysaccharide exposure augmented infiltration by CD8(+) cytotoxic T cells and increased amyloid precursor protein steady-state levels in skeletal muscle, whereas increased Abeta generation was observed only in chronically treated mice. Both acute and chronic inflammation enhanced tau phosphorylation in skeletal muscle. The mechanism underlying this effect was mediated by the tau kinase, glycogen synthase kinase-3beta (GSK-3beta). Suppression of GSK-3beta activity using either a specific inhibitor or lithium chloride significantly reduced tau phosphorylation and partially rescued motor impairment. In human IBM muscle, GSK-3beta and phospho-tau were colocalized, further supporting the pathogenic role of GSK-3beta in this disease. Using C2C12 myoblast cultures, we found that GSK-3beta was activated by proinflammatory cytokines (interleukin-1beta, interleukin-6, tumor necrosis factor-alpha), leading to enhanced tau phosphorylation. Our results identify a molecular mechanism by which proinflammatory stimuli affect tau pathology via the GSK-3beta signaling pathway in skeletal muscle.


Field conditions is a risk factor for traumatic injury in youth football-A joint venture of medicine and hydrology.
The risk of traumatic injury in football has been suggested to be affected by field conditions. This study, therefore, aimed to investigate whether near surface water content of the football field, influenced the risk of traumatic injuries during a youth football tournament. At Dana Cup, an annual international youth football tournament in Denmark, all injuries were registered and classified at the on-site emergency department over 7 years. The incidence rate of traumatic injury was computed. Meteorological data and soil characteristics were used to simulate near surface water content of the playing fields. The incidence rate ratio (IRR) between water content and injury incidence rate was analyzed using a multivariate Poisson regression, controlling for tournament stage and demographical parameters. About 2704 injuries were recorded corresponding to a risk time of 284 905 player hours. An inverse relation between water contents and the incidence rate of traumatic injury was found (IRR = 0.24 95% CI 0.1-0.7, p = 0.01). The incidence rate of traumatic injury increased with advancing tournament stage, that is, for the finals (IRR = 4.30 95% CI 2.8-6.6, p < 0.001). Also we found an interaction between dry fields and the final stage of tournament, further exacerbating this effect. Our data suggest that the incidence rate of traumatic injury is increased with drier field conditions and advanced tournament stages.


Transcription factors KANADI 1, MYB DOMAIN PROTEIN 44, and PHYTOCHROME INTERACTING FACTOR 4 regulate long intergenic noncoding RNAs expressed in Arabidopsis roots.
Thousands of long intergenic noncoding RNAs (lincRNAs) have been identified in plant genomes. While some lincRNAs have been characterized as important regulators in different biological processes, little is known about the transcriptional regulation for most plant lincRNAs. Through the integration of 8 annotation resources, we defined 6,599 high-confidence lincRNA loci in Arabidopsis (Arabidopsis thaliana). For lincRNAs belonging to different evolutionary age categories, we identified major differences in sequence and chromatin features, as well as in the level of conservation and purifying selection acting during evolution. Spatiotemporal gene expression profiles combined with transcription factor (TF) chromatin immunoprecipitation (ChIP) data were used to construct a TF-lincRNA regulatory network containing 2,659 lincRNAs and 15,686 interactions. We found that properties characterizing lincRNA expression, conservation, and regulation differ between plants and animals. Experimental validation confirmed the role of 3 TFs, KANADI 1, MYB DOMAIN PROTEIN 44, and PHYTOCHROME INTERACTING FACTOR 4, as key regulators controlling root-specific lincRNA expression, demonstrating the predictive power of our network. Furthermore, we identified 58 lincRNAs, regulated by these TFs, showing strong root cell type-specific expression or chromatin accessibility, which are linked with genome-wide association studies genetic associations related to root system development and growth. The multilevel genome-wide characterization covering chromatin state information, promoter conservation, and chromatin immunoprecipitation-based TF binding, for all detectable lincRNAs across 769 expression samples, permits rapidly defining the biological context and relevance of Arabidopsis lincRNAs through regulatory networks.


Selective catalytic reduction of NOx by hydrocarbons enhanced by hydrogen peroxide over silver/alumina catalysts.
It is shown that hydrogen peroxide enhances substantially selective reduction of NOx to nitrogen with hydrocarbons over Ag/alumina catalysts.


A versatile quantitation platform based on platinum nanoparticles incorporated volumetric bar-chart chip for highly sensitive assays.
Platinum nanoparticles incorporated volumetric bar-chart chip (PtNPs-V-Chip) is able to be used for point-of-care tests by providing quantitative and visualized readout without any assistance from instruments, data processing, or graphic plotting. To improve the sensitivity of PtNPs-V-Chip, hybridization chain reaction was employed in this quantitation platform for highly sensitive assays that can detect as low as 16 pM Ebola Virus DNA, 0.01ng/mL carcinoembryonic antigen (CEA), and the 10 HER2-expressing cancer cells. Based on this amplified strategy, a 100-fold decrease of detection limit was achieved for DNA by improving the number of platinum nanoparticle catalyst for the captured analyte. This quantitation platform can also distinguish single base mismatch of DNA hybridization and observe the concentration threshold of CEA. The new strategy lays the foundation for this quantitation platform to be applied in forensic analysis, biothreat detection, clinical diagnostics and drug screening.


Conversion therapy to everolimus in renal transplant recipients: results after one year.
Two new diagnoses have been causing graft loss during long-term follow-up, namely, chronic nephropathy and anticalcineurinic toxicity. The advent of the mammalian target of rapamycin (m-TOR) obviates anticalcineurine toxicity and reduces posttransplant malignancy incidence with good inmunosuppressive potential. We examinated the renal and metabolic behavior in renal transplant recipients who required conversion from an anticalcineurinic (cyclosporine or tacrolimus) to an m-TOR inhibitor (everolimus) as part of their immunosuppressive maintenance therapy. Twenty-one first renal transplant recipients had everolimus added to their inmunosuppressive therapy combined with an antimetabolite (mycophenolate mofetil or sodium mycophenolate). The mean age of the patients was 35 +/- 17 years (range, 6 to 65). The prevalence of male recipients was 57%; the overall mean weight, 64 kg (range, 48 to 95). All patients were hispanic with 15 transplants from cadaveric donors (71%). The mean follow-up posttransplant was 18 months (range, 3 to 40) and the mean follow-up on everolimus, 10 months (range, 2 to 22). There was no mortality or graft loss, but there were 3 (17%) biopsy-confirmed acute rejection episodes. There were no significant changes in metabolic function pre- or postconversion. Regarding renal function, the mean creatinine serum showed a trend to decline: preconversion 1.7 mg/dL; postconversion 1.5 mg/dL. In 10 patients, it was possible to discontinue at least one antihypertensive medication (48%). Everolimus was an effective medication to manage renal transplant patients. It produced metabolic stability and low myelotoxicity, despite combination with an antimetabolite (mycophenolic acid). Also, reduction of antihypertensive medications was an additional benefits for many patients.


Relocation of nonalbumin proteins after albumin resuscitation.
Prior work showed that albumin (5% A) resuscitation lowered serum globulins and coagulation protein activity levels compared to balanced electrolyte solution (BES) resuscitation. In this experiment, the effect of 1.25% A in BES (A-BES) on serum and lymphatic levels of nonalbumin proteins was studied in 20 splenectomized dogs subjected to reservoir shock and then treated with (a) BES or A-BES, (b) shed blood, and (c) autogenous bank blood. Serum levels of albumin, globulin, and coagulation protein activity were measured preshock, postshock, and daily for 3 days; skin lymph levels were measured on Day 3. Compared to BES, A-BES resuscitation significantly decreased serum globulins and coagulation protein activity of fibrinogen, Factor VIII, and antithrombin III. In contrast, skin lymph globulins and coagulation protein activity levels increased significantly with A-BES compared to BES resuscitation. These data suggest that the serum protein changes seen with albumin-supplemented resuscitation result from extravascular relocation of nonalbumin proteins, possibly, due to an oncotic homeostatic factor.


Device-guided slow-paced respiration for menopausal hot flushes: a randomized controlled trial.
To evaluate the efficacy of device-guided slow-paced respiration for reducing the frequency and severity of menopausal hot flushes. Perimenopausal or postmenopausal women reporting four or more hot flushes per day were recruited into a parallel-group, randomized trial of slow-paced respiration using a portable guided-breathing device. Women were randomly assigned to use a standard device to practice slowing their resting breathing rate to less than 10 breaths per minute for at least 15 minutes everyday or use an identical-appearing control device programmed to play relaxing nonrhythmic music while monitoring spontaneous breathing. The primary outcome, change in hot flush frequency over 12 weeks, was assessed using data from validated 7-day diaries abstracted by blinded analysts. Among the 123 participants, mean age was 53.4 (±3.4) years. Women reported an average of 8.5 (±3.5) hot flushes per day at baseline. After 12 weeks, women randomized to paced respiration (n=61) reported an average reduction of 1.8 (95% confidence interval [CI] 0.9-2.6) hot flushes per day (-21%) compared with 3.0 (95% CI 2.1-3.8) hot flushes per day (-35%) in the music-listening group (n=62) (P=.048). Paced respiration was associated with a 19% decrease in frequency of moderate-to-severe hot flushes compared with a 44% decrease with music listening (P=.02). In this randomized trial, women assigned to device-guided slow-paced respiration reported modest improvements in the frequency and severity of their hot flushes, but the paced respiration intervention was significantly less effective than a music-listening intervention in decreasing the frequency and severity of these symptoms. I.


De-facto marine protection from a Navy bombing range: Farallon De Medinilla, Mariana Archipelago, 1997 to 2012.
Fourteen surveys were conducted at Farallon De Medinilla (a U.S. Department of Defense bombing range in the Mariana Archipelago) between 1997 and 2012; annual surveys were conducted from 1999 through 2012. There was no evidence that the condition of the biological resources assessed had changed, or been adversely impacted to a significant degree by the training activities being conducted there. Restricted access has resulted in a de-facto preserve effect and outweighs minor negative impacts from training. The health, abundance and biomass of fishes, corals and other marine resources are comparable to or superior to those in similar habitats at other locations within the Mariana Archipelago. Our research suggests that the greatest threat to FDM's marine resources is from fishermen, not military training activities.


[Spontaneous bacterial peritonitis in patients with cirrhosis].
Spontaneous bacterial peritonitis (SBP) is a severe complication occurring in patients with cirrhosis, and is associated with high mortality. Liver transplantation should be considered after a first episode of SBP. Gram-negative bacilli are the major cause of SBP, however there is an increasing trend of Gram-positive cocci related SBP. Management includes empirical antibiotic treatment and albumin infusion. The choice of antibiotics depends on the site of acquisition (community-acquired vs nosocomial or health-care associated infection) and local resistance profile, due to the emergence of drug-resistant bacteria. Secondary prophylaxis is recommended after resolution of SBP and reduces recurrence and mortality. Primary prophylaxis in patients with low protein ascites (<15 g/L) should be restricted to patients with severe cirrhosis awaiting for liver transplantation.


Direct cortical input modulates plasticity and spiking in CA1 pyramidal neurons.
The hippocampus is necessary for the acquisition and retrieval of declarative memories. The best-characterized sensory input to the hippocampus is the perforant path projection from layer II of entorhinal cortex (EC) to the dentate gyrus. Signals are then processed sequentially in the hippocampal CA fields before returning to the cortex via CA1 pyramidal neuron spikes. There is another EC input-the temporoammonic (TA) pathway-consisting of axons from layer III EC neurons that make synaptic contacts on the distal dendrites of CA1 neurons. Here we show that this pathway modulates both the plasticity and the output of the rat hippocampal formation. Bursts of TA activity can, depending on their timing, either increase or decrease the probability of Schaffer-collateral (SC)-evoked CA1 spikes. TA bursts can also significantly reduce the magnitude of synaptic potentiation at SC-CA1 synapses. The TA-CA1 synapse itself exhibits both long-term depression (LTD) and long-term potentiation (LTP). This capacity for bi-directional plasticity can, in turn, regulate the TA modulation of CA1 activity: LTP or LTD of the TA pathway either enhances or diminishes the gating of CA1 spikes and plasticity inhibition, respectively.


Sustainability and optimal control of an exploited prey predator system through provision of alternative food to predator.
In the present paper, we develop a simple two species prey-predator model in which the predator is partially coupled with alternative prey. The aim is to study the consequences of providing additional food to the predator as well as the effects of harvesting efforts applied to both the species. It is observed that the provision of alternative food to predator is not always beneficial to the system. A complete picture of the long run dynamics of the system is discussed based on the effort pair as control parameters. Optimal augmentations of prey and predator biomass at final time have been investigated by optimal control theory. Also the short and large time effects of the application of optimal control have been discussed. Finally, some numerical illustrations are given to verify our analytical results with the help of different sets of parameters.


Hysteroscopic assessment of abnormal uterine bleeding in users of the intrauterine contraceptive device.
Sixty users of the IUD who complained of abnormal menstrual blood loss were evaluated by hysteroscopy, and the findings were compared with a matched group who had this investigation for "missing strings". Submucous fibroids and endometritis were more frequent in the study group whereas malposition of the IUD was commoner in the controls (p < 0.05).


Carbonaceous nanomaterials immobilised mixed matrix membrane microextraction for the determination of polycyclic aromatic hydrocarbons in sewage pond water samples.
In this study, the potential for carbonaceous nanomaterials to be used as adsorbents for the mixed matrix membrane (MMM) microextraction and preconcentration of organic pollutants was demonstrated. For this method, multiwall carbon nanotubes (MWCNT) and single layer graphene (SLG) nanoparticles were individually incorporated through dispersion in a cellulose triacetate (CTA) polymer matrix to form a MWCNT-MMM and SLG-MMM, respectively. The prepared membranes were evaluated for the extraction of selected polycyclic aromatic hydrocarbons (PAHs) present in sewage pond water samples. The extraction was performed by dipping a small piece of membrane (7 mm × 7 mm) in a stirred 7.5 mL sample solution to initiate the analyte adsorption. This step was followed by an analyte desorption into 60 μL of methanol prior to high performance liquid chromatography (HPLC) analysis. When the optimum SLG-MMM microextraction technique was applied to spiked sewage pond water samples, the detection limit of the method for the PAHs were in the range of 0.02-0.09 ng/mL, with relative standard deviations of between 1.4% and 7.8%. Enrichment factors of 54-100 were achieved with relative recoveries of 99%-101%. A comparison was also made between the proposed approach and standard solid phase extraction using polymeric bonded octadecyl (C18) cartridges.


Neurotransmitter receptor alterations in hepatic encephalopathy: a review.
Hepatic encephalopathy (HE), a complex neuropsychiatric syndrome with symptoms ranging from subtle neuropsychiatric and motor disturbances to deep coma and death, is thought to be a clinical manifestation of a low-grade cerebral oedema associated with an altered neuron-astrocyte crosstalk and exacerbated by hyperammonemia and oxidative stress. These events are tightly coupled with alterations in neurotransmission, either in a causal or a causative manner, resulting in a net increase of inhibitory neurotransmission. Therefore, research focussed mainly on the potential role of γ-aminobutyric acid-(GABA) or glutamate-mediated neurotransmission in the pathophysiology of HE, though roles for other neurotransmitters (e.g. serotonin, dopamine, adenosine and histamine) or for neurosteroids or endogenous benzodiazepines have also been suggested. Therefore, we here review HE-related alterations in neurotransmission, focussing on changes in the levels of classical neurotransmitters and the neuromodulator adenosine, variations in the activity and/or concentrations of key enzymes involved in their metabolism, as well as in the densities of their receptors.


Minimally Invasive Advances in Deformity.
Adult spinal deformity is a major contributor to pain and disability. It is a degenerative disease with a rigid spine. Spinopelvic parameters have been identified that outline goals of operative intervention, as they have shown to significantly improve patient outcomes. Previously, this was accomplished with large, open fusions. Unfortunately, the adult spinal deformity population is often elderly with significant comorbidities. These extensive fusions have a high rate of morbidity and mortality. Technological advances have allowed minimally invasive approaches to be developed. These techniques have decreased operative morbidity without increasing health care spending.


Low-intensity ultrasound combined with allogenic adipose-derived mesenchymal stem cells (AdMSCs) in radiation-induced skin injury treatment.
Mesenchymal stem cells are mechano-sensitive cells with the potential to restore the function of damaged tissues. Low-intensity ultrasound has been increasingly considered as a bioactive therapeutic apparatus. Optimizing transplantation conditions is a critical aim for radiation-induced skin tissue injury. Therefore, the therapeutic function of adipose-derived mesenchymal stem cells to ultrasound stimulus was examined based on the mechanical index (MI). Mesenchymal stem cells were isolated from the adipose tissues of mature guinea pigs. An ultrasound system (US) was constructed with a 40 kHz frequency. The radiation-induced skin injury model was produced on the abdominal skin of guinea pigs by 60 Gy of radiation. Then, they were divided to 7 groups (n = 42): control, sham, US (MI = 0.7), AdMSCs injection, US AdMSCs (AdMSCs, under US with MI = 0.2), AdMSCs + US (AdMSCs transplantation and US with MI = 0.7) and US AdMSCs + US (combining the last two groups). The homing of stem cells was verified with fluorescence imaging. The groups were followed with serial photography, ultrasound imaging, tensiometry, and histology. The thickness of the skin was analyzed. Functional changes in skin tissue were evaluated with Young's modulus (kPa). One-way ANOVA tests were performed to analyze differences between treatment protocols (p < 0.05). The results of Kumar's score showed that radiation injury was significantly lower in the treatment groups of US AdMSCs and US AdMSCs + US than other groups after 14 days (p < 0.05). There was a significant difference in skin thickness between treatment groups with control, sham, and US groups after 60 Gy radiation and were closer to the thickness of healthy skin. Young's modulus in US AdMSCs + US, US AdMSCs, and AdMSCs + US groups demonstrated a significant difference with the other groups (p < 0.05). Young's modulus in US AdMSCs + US and US AdMSCs treatment groups were closer to Young's modulus of the healthy skin. The histological results confirmed the improvement of acute radiation damage in the combined treatment method, especially in US AdMSCs + US and US AdMSCs groups with increasing the epithelialization and formation of collagen. An ultrasonic treatment plan based on a mechanical index of the target medium could be used to enhance stem cell therapy.


Clinical and electrophysiologic features of idiopathic left ventricular aneurysm with sustained ventricular tachycardia.
We examined 10 patients with idiopathic left ventricular (LV) aneurysm with sustained ventricular tachycardia (VT) (Id-An group), and compared them with those in 16 age- and sex-matched patients who had postinfarction aneurysm and VT (MI-An group) to clarify detailed clinical and electrophysiologic characteristics of idiopathic LV aneurysm. The clinical and laboratory data and results of electrocardiography, electrophysiologic, and morphologic examinations in the two groups were compared. In the Id-An group, the LV aneurysms were located more often at the posterior and/or inferior wall, while in the MI-An group, they were more often located at the anterior and/or apical wall (P<0.001). The LV end-diastolic volume index was significantly smaller and the LV ejection fraction was significantly higher in the Id-An group (P<0.001). The size of the aneurysm and the area with abnormal electrograms in the Id-An group were significantly smaller than those in the MI-An group (P<0.005 and P<0.001, respectively). The inducibility of VT was high in both groups, and ventricular pacing during VT showed entrainment phenomenon in most of the patients. Thus, in both groups, the abnormal electrograms were closely associated with the wall motion abnormality, and reentry was suggested as the mechanism of VT. In the Id-An group, since the lesions were anatomically and electrophysiologically confined to the posterior and/or inferior wall, the global LV function was more well preserved compared with the MI-An group.


Cytoskyrins and cytosporones produced by Cytospora sp. CR200: taxonomy, fermentation and biological activities.
In screening endophytic fungi from Costa Rica for bioactivity, fungal culture CR200, isolated from a buttonwood tree, was found to contain compounds that initiate DNA damage in a test strain of E. coli (Biochemical Induction Assay, BIA) and inhibit growth of Gram-positive bacteria, including antibiotic-resistant strains. Two new bisanthraquinones (cytoskyrins A and B) and five new related octaketides (cytosporones A-E) were isolated from fermentation broths of this fungus. Cytoskyrin A exhibited potent in-vitro antibacterial (MICs against Gram-positive bacteria, 0.03-0.25 microg/mL) and DNA-damaging activities (10 ng/spot), whereas cytoskyrin B was inactive in these assays. Among the cytosporones, only D and E exhibited Gram-positive activity, but they were inactive in the BIA. Mechanistically, cytoskyrin A specifically inhibited DNA synthesis in E. coli imp at its MIC; however, it also moderately inhibited protein synthesis at 2x its MIC. Cytoskyrin A exhibited poor cytotoxicity against tumor cell lines (IC50>5 microg/mL) compared to known antitumor agents. The nuclear ribosomal internal transcribed spacer region of CR200 was found to share highest similarity (94-96%) with Cytospora spp. Micro- and macroscopic morphological observations of the conidia and conidiomata, respectively, also suggested this fungus to be a Cytospora sp.


Modulation by prostaglandins of the release of acetylcholine and noradrenaline in guinea-pig isolated ileum.
The effects of prostaglandin (PG) E2, PGF2alpha and indomethacin on the release of acetylcholine (ACh), noradrenaline (NA) and prostaglandin-like substances from the isolated guinea-pig ileum and its longitudinal muscle-myenteric plexus preparation were investigated. The output of ACh and PGs was determined by a bioassay and the output of NA by an isotope technique. The output of ACh, both resting and stimulated, was decreased by indomethacin (1 micron) especially after a longer exposure. The output of ACh was increased by PGE2 (6 nM) but not by PGF2alpha. This increase was inversely related to the initial level of ACh output; thus, it was marked only in the preparations with low initial output of ACh. Prostaglandin-like substances released from the ileum were mainly of the E type and their output only partially correlated with contractions and with the output of ACh. The stimulated outflow of NA at a frequency of 5 Hz was increased by indomethacin (50 micron) and decreased by PGE2 (30 nM). PGF2alpha had no effect. These results suggest that PGE2 might act physiologically as a modulator of cholinergic transmission whereas its effect on adrenergic transmission could be of a pharmacological nature.


Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition.
Iron-dependent oxidative stress, elevated levels of iron and of monoamine oxidase (MAO)-B activity, and depletion of antioxidants in the brain may be major pathogenic factors in Parkinson's disease, Alzheimer's disease and related neurodegenerative diseases. Accordingly, iron chelators, antioxidants and MAO-B inhibitors have shown efficacy in a variety of cellular and animal models of CNS injury. In searching for novel antioxidant iron chelators with potential MAO-B inhibitory activity, a series of new iron chelators has been designed, synthesized and investigated. In this study, the novel chelators were further examined for their activity as antioxidants, MAO-B inhibitors and neuroprotective agents in vitro. Three of the selected chelators (M30, HLA20 and M32) were the most effective in inhibiting iron-dependent lipid peroxidation in rat brain homogenates with IC50 values (12-16 microM), which is comparable with that of desferal, a prototype iron chelator that is not has orally active. Their antioxidant activities were further confirmed using electron paramagnetic resonance spectroscopy. In PC12 cell culture, the three novel chelators at 0.1 microM were able to attenuate cell death induced by serum deprivation and by 6-hydroxydopamine. M30 possessing propargyl, the MAO inhibitory moiety of the anti-Parkinson drug rasagiline, displayed greater neuroprotective potency than that of rasagiline. In addition, in vitro, M30 was a highly potent non-selective MAO-A and MAO-B inhibitor (IC50 < 0.1 microM). However, HLA20 was more selective for MAO-B but had poor MAO inhibition, with an IC50 value of 64.2 microM. The data suggest that M30 and HLA20 might serve as leads in developing drugs with multifunctional activities for the treatment of various neurodegenerative disorders.


Soft drink wastewater treatment by electrocoagulation-electrooxidation processes.
The aim of this work was to implement a coupled system, a monopolar Electrocoagulation (EC)-Electrooxidation (EO) processes, for the treatment of soft drink wastewater. For the EC test, Cu-Cu, anode-cathode were used at current densities of 17, 51 and 68 mA cm-2. Only 37.67% of chemical oxygen demand (COD) and 27% of total organic carbon (TOC) were removed at 20 min with an optimum pH of 8, this low efficiency can be associated with the high concentration of inorganic ions which inhibit the oxidation of organic matter due to their complexation with copper ions. Later EO treatment was performed with boron-doped diamond-Cu electrodes and a current density of 30 Am-2. The coupled EC-EO system was efficient to reduce organic pollutants from initial values of 1875 mg L-1 TOC and 4300 mg L-1 COD, the removal efficiencies were 75% and 85%, respectively. Electric energy consumption to degrade a kilogram of a pollutant in the soft drink wastewater using EC was 3.19 kWh kg-1 TOC and 6.66 kWh kg-1 COD. It was concluded that the coupled system EC-EO was effective for the soft drink wastewater treatment, reducing operating costs and residence time, and allowing its reuse in indirect contact with humans, thus contributing to the sustainable reuse as an effluent of industrial wastewater.


Effect of the use of combination uridine triphosphate, cytidine monophosphate, and hydroxycobalamin on the recovery of neurosensory disturbance after bilateral sagittal split osteotomy: a randomized, double-blind trial.
The change in neurosensory lesions that develop after bilateral sagittal split osteotomy (BSSO) was explored, and the influence of the application of combination uridine triphosphate (UTP), cytidine monophosphate (CMP), and hydroxycobalamin (vitamin B12) on patient outcomes was assessed. This was a randomized, controlled, double-blind trial. The study sample comprised 12 patients, each evaluated on both sides (thus 24 sides). All patients fulfilled defined selection criteria. Changes in the lesions were measured both subjectively and objectively. The sample was divided into two patient groups: an experimental group receiving medication and a control group receiving placebo. The statistical analysis was performed using SPSS software. Lesions in both groups improved and no statistically significant difference between the groups was observed at any time. 'Severe' injuries in the experimental group were more likely to exhibit a significant improvement after 6 months. Based on the results of the present study, it is concluded that the combination UTP, CMP, and hydroxycobalamin did not influence recovery from neurosensory disorders.


T-cell quality in memory and protection: implications for vaccine design.
T cells mediate effector functions through a variety of mechanisms. Recently, multiparameter flow cytometry has allowed a simultaneous assessment of the phenotype and multiple effector functions of single T cells; the delineation of T cells into distinct functional populations defines the quality of the response. New evidence suggests that the quality of T-cell responses is crucial for determining the disease outcome to various infections. This Review highlights the importance of using multiparameter flow cytometry to better understand the functional capacity of effector and memory T-cell responses, thereby enabling the development of preventative and therapeutic vaccine strategies for infections.


Forty-four-year longitudinal study of stroke incidence and risk factors - the Prospective Population Study of Women in Gothenburg.
To assess stroke incidence over 44 years and association with risk factors. To study total stroke incidence at 60-82 years of age and risk factors. Prospective population study. Gothenburg, Sweden, with ∼450,000 inhabitants. A representative sample of a general population of women (1462 in total) in 5 age strata aged 38-60 years in 1968-1969 (the Population Study of Women in Gothenburg, PSWG) were followed up to the ages of 82-104 years in 2012. Further, analysis was also performed for the age interval 60-82 years. Incidence of total stroke (TS), ischaemic (IS), haemorrhagic (HS), non-specified (NS) and fatal (FS) strokes and association with baseline classic risk factors (such as hypertension, atrial fibrillation, low physical activity, diabetes, high waist-hip-ratio, hyperlipidaemia, smoking), low education, mental stress, pre-eclampsia and oral health as expressed by loss of teeth and bone score. Blood pressure in levels 1-3 according to modern guidelines. Associations with atrial fibrillation, diabetes and myocardial infarction shown in survival analyses. The five cohorts contributed to risk time data concerning associations with TS in the 60-82 age interval from the examination performed when they were 60. Three hundred and thirty-seven (23%) women had a first-ever stroke, 64 (19%) fatal. TS was associated with physical inactivity, high triglycerides and low education in multivariable analysis. The main sub-type IS was associated with systolic blood pressure, physical inactivity and low education. Pre-eclampsia showed association with IS only in the univariable analysis. FS was associated with systolic blood pressure and smoking. During 60-82 years of age, having <20 teeth (HR 1.74, CI 1.25-2.42), diabetes (HR 2.28 CI 1.09-4.76), WHR (HR 1.29 per 0.1 units CI 1.01-1.63), systolic blood pressure (HR 1.11 per 10 units CI 1.04-1.18) and smoking (HR 1.57, CI 1.14-2.16), were associated with TS in the combined five cohorts. Several classic risk factors showed independent associations with stroke. Vulnerability factors as low education and oral health, reflected by loss of teeth, also showed association with stroke. All these factors are possible to target in primary care preventive interventions.Key PointsStroke is a common disease and the risk of stroke is a key issue demanding preventive strategies in primary health care. The present prospective population study of women showsOut of 1460 women, almost a quarter got a stroke. The stroke incidence 60-82 years of age was rather stable between the first four age cohorts but somewhat lower in the latest cohort, born 1930.Hypertension, low physical activity, low education and high triglyceride levels but not cholesterol were associated with stroke in women.Low education and loss of teeth are vulnerability factors that should need particular attention.


Tissue locations for the turnover of radioactively labeled rat orosomucoid in vivo.
Tissues involved in the turnover of rat serum orosomucoid were identified by methods designed to cause lysosomal trapping of radiolabel at the sites of glycoprotein degradation. 125I-, [3H]Raffinose-, and [1-14C]glucosamine-labeled orosomucoid exhibited serum half-lives of 20, 20, and 27 h when injected intravenously into rats. As expected, the asialo derivative of [3H]raffinose-labeled rat orosomucoid was lost very rapidly from the circulation and recovered quantitatively in the liver within 30 min. At 50 h after injection of [3H]raffinose-asialo-orosomucoid the liver retained 38% of the radioactivity while the remainder was found in the gastrointestinal tract and urine. Chromatography of the urine on Bio-Gel P-4 revealed a single radioactive product that eluted similar to raffinose-lysine. The same material was found in the liver. This ability of the [3H]raffinose label to resist metabolic disposal was used to evaluate tissue catabolism of native rat orosomucoid. Comparison of the tissue radioactivity in experiments using 125I- and [3H]raffinose-labeled derivatives of the nondesialylated glycoprotein showed kidney, liver, and muscle to be most active in 3H accumulation. However, the [3H]raffinose metabolites excreted in the urine was markedly different from those produced from asialo-orosomucoid and in contrast there was minimal loss of label to the gastrointestinal tract from the native substrate. Leupeptin, an inhibitor of lysosomal thiol cathespins, was administered continuously to rats by a subcutaneous osmotic pump. At 24 h after injection of 125I-orosomucoid, leupeptin-treated rats showed a net 16% increase in tissue radioactivity above sham-operated animals and a corresponding decrease occurred in the radioactivity associated with the gastrointestinal tract and urine. Tissues that exhibited increases in radioactivity were kidney, muscle, liver, and hide. The different behavior of labeled native and asialo-orosomucoids suggests that the hepatic galactose receptor system plays, at most, a limited role in maintaining homeostasis of the native glycoprotein.


Newly Diagnosed Infection After Admission for Acute Heart Failure: From the KCHF Registry.
Background No studies have explored the association between newly diagnosed infections after admission and clinical outcomes in patients with acute heart failure. We aimed to explore the factors associated with newly diagnosed infection after admission for acute heart failure, and its association with in-hospital and post-discharge clinical outcomes. Methods and Results Among 4056 patients enrolled in the Kyoto Congestive Heart Failure registry, 2399 patients without any obvious infectious disease upon admission were analyzed. The major in-hospital and post-discharge outcome measures were all-cause deaths. There were 215 patients (9.0%) with newly diagnosed infections during hospitalization, and 2184 patients (91.0%) without infection during hospitalization. The factors independently associated with a newly diagnosed infection were age ≥80 years, acute coronary syndrome, non-ambulatory status, hyponatremia, anemia, intubation, and patients who were not on loop diuretics as outpatients. The newly diagnosed infection group was associated with a higher incidence of in-hospital mortality (16.3% and 3.2%, P<0.001) and excess adjusted risk of in-hospital mortality (odds ratio, 6.07 [95% CI, 3.61-10.19], P<0.001) compared with the non-infection group. The newly diagnosed infection group was also associated with a higher 1-year incidence of post-discharge mortality (19.3% in the newly diagnosed infection group and 13.6% in the non-infection group, P<0.001) and excess adjusted risk of post-discharge mortality (hazard ratio, 1.49 [95% CI, 1.08-2.07], P=0.02) compared with the non-infection group. Conclusions Elderly patients with multiple comorbidities were associated with the development of newly diagnosed infections after admission for acute heart failure. Newly diagnosed infections after admission were associated with higher in-hospital and post-discharge mortality in patients with acute heart failure. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT02334891.


Symptomatic ductal carcinoma in situ (DCIS): Upstaging risk and predictors.
To estimate the upstaging risk of symptomatic ductal carcinoma in situ (DCIS) to invasive disease and to identify features related to upstaging risk. This retrospective investigation includes symptomatic women with DCIS at core needle biopsy from January 2007 to December 2016 at a large academic institution. Patient characteristics, findings at imaging, core needle biopsy histopathology results, and final surgical histopathology results were retrieved from the medical records. Using standard statistical tests, patient, imaging, and pathology features were compared between DCIS cases that were upstaged to invasive disease at surgery versus cases that were not upstaged. From 2007 to 2016, fewer than 5% (63/1399) of women diagnosed with DCIS presented with symptoms. Therefore, 63 women (mean age, 51; range, 27-88 years) comprised the study cohort. 84.1% (n = 53) presented with an area of clinical concern, and 15.9% (n = 10) presented with pathologic nipple discharge. The most common finding at mammography was calcifications with or without an associated asymmetry or mass (74.1%, 40/54). The upstaging rate of symptomatic DCIS to invasive disease was 34.9% (22/63). Imaging modality used for biopsy was associated with higher upstaging risk, with cases that were biopsied under MRI guidance accounting for 22.7% of upstaged cases versus 4.9% of non-upstaged cases (p = 0.03). Women with DCIS uncommonly present with symptoms, and the upstaging rate of symptomatic DCIS is high at nearly 35%. Biopsy modality type of MRI is associated with higher upstaging risk.


Impact of herbal medicines on physical impairment.
The usefulness of recording physical impairment during intervention studies in chronic low back patients has been questioned. A re-analysis of all of our studies investigating aqueous extracts of Harpagophytum procumbens and a proprietary ethanolic Salix extract for chronic non-specific low back pain revealed that the "physical impairment" component of the Arhus low back pain index changed very little during treatment despite appreciable changes in the other two components, "pain" and "disability", over time. For comparison, we also extracted data from the literature on the topical use of capsaicin, which showed the same thing. There may be little to lose from omitting the time-consuming assessments of "physical impairment" in studies of the (primarily analgesic) effectiveness of herbal preparations.


[Results of a combined glaucoma- and cataract-operation (author's transl)].
106 eyes with glaucoma and cataract have been operated simultaneously with a combined cataract-extraction (cryoextraction) and trephining with scleral flap (Elliot-Fronimopoulos). In 95 eyes intraocular pressure was compensated without local therapy (about 90%).


Composite-veneered amalgam restorations.
A procedure is described for the construction of composite resin veneers for large amalgam restorations. The resulting restoration combines the physical qualities of amalgam with the esthetic benefits of composite resins. Among the 14 restorations that have been studied for 2 years, none failed mechanically and minor surface discolorations have been satisfactorily corrected by polishing.


Role of the pineal gland in immunity. III. Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism.
We have recently demonstrated that the pineal neurohormone melatonin exerts important immunoregulatory functions. We now report that exogenous melatonin counteracts completely the effect of acute anxiety-restraint stress on thymus weight and antibody response to sheep red blood cells (SRBC). In addition, administration of melatonin in the evening prevented paralysis and death of mice infected with sublethal doses of encephalomyocarditis virus (EMCV) after acute stress. The anti-stress activity of melatonin was present in mice injected with T-dependent antigens, and it was abolished by the contemporary administration of the specific opioid-antagonist naltrexone. This suggests that melatonin exerts its remarkable anti-stress effect on antigen-activated cells via an opiatergic mechanism. These findings have important implications at both basic and clinical levels. They provide a new approach to a possible physiological 'up-regulation' of the immune response under virus- and/or stress-related immunosuppression.


Crystal Structure of the Wild-Type Human GlyRS Bound with tRNA(Gly) in a Productive Conformation.
Aminoacyl-tRNA synthetases are essential components of the protein translational machinery in all living species, among which the human glycyl-tRNA synthetase (hGlyRS) is of great research interest because of its unique species-specific aminoacylation properties and noncanonical roles in the Charcot-Marie-Tooth neurological disease. However, the molecular mechanisms of how the enzyme carries out its classical and alternative functions are not well understood. Here, we report a complex structure of the wild-type hGlyRS bound with tRNA(Gly) at 2.95Å. In the complex, the flexible Whep-TRS domain is visible in one of the subunits of the enzyme dimer, and the tRNA molecule is also completely resolved. At the active site, a glycyl-AMP molecule is synthesized and is waiting for the transfer of the glycyl moiety to occur. This cocrystal structure provides us with new details about the recognition mechanism in the intermediate stage during glycylation, which was not well elucidated in the previous crystal structures where the inhibitor AMPPNP was used for crystallization. More importantly, the structural and biochemical work conducted in the current and previous studies allows us to build a model of the full-length hGlyRS in complex with tRNA(Gly), which greatly helps us to understand the roles that insertions and the Whep-TRS domain play in the tRNA-binding process. Finally, through structure comparison with other class II aminoacyl-tRNA synthetases bound with their tRNA substrates, we found some commonalities of the aminoacylation mechanism between these enzymes.


Chemoreflexsensitivity among patients with paroxysmal atrial fibrillation.
Atrial fibrillation is the most common cardiac arrhythmia with typical complications of thromboembolisms. The autonomic nervous system is an important factor for the initiation of arrhythmias. A vagally or adrenergically hyperfunction could cause the initiation of paroxysmal atrial fibrillation (PAF). We measured the chemoreflexsensitivity (CHRS) among 110 patients to determine a disturbed autonomic function as risk factor for PAF. We examined 45 patients with PAF (group A), 45 patients with sinus rhythm (group B) and 20 young volunteers (group C). The ratio between the difference of RR intervals in ECG and venous pO(2) was measured for the determination of CHRS. The margin of the CHRS was 3 ms/mmHg. Patients of group A had a significantly lower CHRS compared to group B (1.56+/-1.46 vs 6.29+/-3.71 ms/mmHg, p<0.0008) or group C (1.56+/-1.46 vs 6.35+/-4.29 ms/ mmHg, p<0.0003). A significant difference between group B and C could not be observed (6.29+/-3.71 vs. 6.35+/-4.29 ms/mmHg, p = n.s.). A specificity of 74% and a sensitivity of 71% was achieved for identifying patients with PAF by using a margin of 3 ms/mmHg for the CHRS. An analysis of CHRS seems to be an appropriate method to demonstrate a neurovegetative imbalance which might be one possible trigger mechanism of PAF. The predictive power has to be examined by prospective investigations of a larger patient population.


Motivation behind running among older adult runners.
Recreational running has greatly increased over the last decade, and different research has tried to understand the motivation that leads these amateur athletes to run. However, most research has focused on adult athletes, while the motivation behind older adult athletes has been overlooked. The aim of this research was to analyse the motivational aspects of amateur runners aged over 50 years, and to consider the influence that years of practice, type of participation and some socio-demographical variables have on these older adults' motivation behind running. 244 older adult amateur athletes in total completed an online survey with the 56 items contained in the motivation of marathoners scales (MOMS), 108 of whom were female (44%), and 136 were male runners (56%). Athletes were asked about their years' running experience (< 1 year, 1-5 years, 6-10 years, > 10 years), their participation in running events (recreationally, half marathon, marathon, ultramarathon) and age (ranges 50-60, more than 60 years), gender (male, female), family life (whether in a relationship or not), and whether they had children (yes, no). The results showed statistical differences in the nine MOMS dimensions in terms of years' running experience and participation in different running events. Moreover, older adult runners' gender and age subsequently showed statistical differences with five and six motivational factors respectively, while athletes that did not have children were more likely to run regarding competition and showing recognition. Family life did not show any statistical association with any of the dimensions on the scale in this population, while regression analyses showed that, mainly, years' running experience and participation were positively predicted, together with most motivational dimensions, while having children was negatively predicted in some of them. This study showed that older adult runners' reasons for participating differ from those obtained in previous studies, especially regarding training experience and participation in events. Therefore, the older adult population should be specifically addressed.


Molar-incisor hypomineralization in a cohort of individuals born with cleft lip and palate.
This study aimed to investigate the frequency of molar-incisor hypomineralization (MIH) in individuals born with cleft lip and or cleft palate. Three hundred eighty-six individuals born with cleft lip and/or palate before orthodontic treatment. All the individuals were submitted to a clinical examination and intraoral standardized photos. The registration of MIH was taken by two orthodontists and analysed in association with the cleft type and laterality. The Kruskal-Wallis test and the regression test were used to compare the frequency of molars and incisors affected according to cleft type and laterality, sex and age. We found a frequency of 67.87% of MIH in the studied sample. The frequency varied from 25% (in individuals born with cleft palate) to 77% in individuals born with bilateral cleft lip and palate). The number of affected molars was statistically different depending on cleft type and laterality (P < .001- Kruskal-Wallis test). Differences were found between individuals born with unilateral cleft lip and palate and unilateral cleft lip and alveolus (P = .03), and with isolated cleft palate (P = .03), and between individuals born with bilateral cleft lip and palate and born with unilateral cleft lip and alveolus (P = .01), and cleft palate (P = .01). Sex (P = .21) and age (P = .36) had no influence on the frequency of MIH. A positive correlation was found between the number of molars affected and incisors affected (P < .001). Individuals born with cleft lip and palate have a higher frequency of MIH, and the complexity of cleft type was associated with the number of affected molars.


The characterization and phosphorylation of an actin-like protein in synaptosomal membranes.
A protein of 43,000 daltons, named protein 'C', is a component of synaptosomal plasma membranes, vesicular and microsomal membranes, as well as synaptosomal and cellular cytoplasm. Protein 'C' undergoes endogeneous phosphorylation in synaptosomal plasma membranes but not in other subcellular fractions. This phosphorylation is stimulated by papaverine and calcium, inhibited by magnesium and not affected by cyclic nucleotides. Protein 'C' and muscle actin were shown to be very similar by isoelectric focusing, two dimensional gel electrophoresis, and by peptide mapping. This suggests that protein 'C' is an actin-like protein which undergoes endogenous phosphorylation specifically in synaptosomal plasma membranes. Phosphorylation of protein 'C' may be involved in neurotransmitter release.


Prolactin and 3-methylcholanthrene induced cervical carcinoma. Effect of bromocriptine.
Female mice of the NMRI strain were injected with estradil for the first five days after birth (estrogenized animals) and ovariectomized at the ages of 6-9 weeks. One week later, a cotton thread impregnated with 3-methylcholanthrene was inserted into the uterine cervix. Starting on the day of insertion of the thread, and for a further 6 days, the females were injected with estradiol (E2), ovine prolactin (P), or 2-bromo-alpha-ergokryptine mesylate (bromocriptine). Controls were injected with vehicles only. The animals were killed 4 or 8 weeks after insertion of the thread, and the uterine cervix was serially sectioned. A combined treatment with E2 and P resulted in an increased incidence of invasive epithelial lesions in the uterine cervix. This incidence was higher than in controls or females injected with either hormone separately. Bromocriptine reduced the incidence of invasions, and this reduction with either hormone separately. Bromocriptine reduced the incidence of invasion, and this reduction could not be restored to the contrl level by a simultaneous treatment with E2 anrogenized females was higher than that reported in an earlied study using non-estrogpenized females.


Sequence specific DNA binding of Ets-1 transcription factor: molecular dynamics study on the Ets domain--DNA complexes.
Molecular dynamics (MD) simulations for Ets-1 ETS domain-DNA complexes were performed to investigate the mechanism of sequence-specific recognition of the GGAA DNA core by the ETS domain. Employing the crystal structure of the Ets-1 ETS domain-DNA complex as a starting structure we carried out MD simulations of: (i). the complex between Ets-1 ETS domain and a 14 base-pair DNA containing GGAA core sequence (ETS-GGAA); (ii). the complex between the ETS domain and a DNA having single base-pair mutation, GGAG sequence (ETS-GGAG); and (iii). the 14 base-pair DNA alone (GGAA). Comparative analyses of the MD structures of ETS-GGAA and ETS-GGAG reveal that the DNA bending angles and the ETS domain-DNA phosphate interactions are similar in these complexes. These results support that the GGAA core sequence is distinguished from the mutated GGAG sequence by a direct readout mechanism in the Ets-1 ETS domain-DNA complex. Further analyses of the direct contacts in the interface between the helix-3 region of Ets-1 and the major groove of the core DNA sequence clearly show that the highly conserved arginine residues, Arg391 and Arg394, play a critical role in binding to the GGAA core sequence. These arginine residues make bidentate contacts with the nucleobases of GG dinucleotides in GGAA core sequence. In ETS-GGAA, the hydroxyl group of Tyr395 is hydrogen bonded to N7 nitrogen of A(3) (the third adenosine in the GGAA core), while the hydroxyl group makes a contact with N4 nitrogen of C(4') (the complementary nucleotide of the fourth guanosine G(4) in the GGAG sequence) in the ETS-GGAG complex. We have found that this difference in behavior of Tyr395 results in the relatively large motion of helix-3 in the ETS-GGAG complex, causing the collapse of bidentate contacts between Arg391/Arg394 and the GG dinucleotides in the GGAG sequence.


Breast stimulation for cervical ripening and induction of labour.
Breast stimulation has been suggested as a means of inducing labour. It is a non-medical intervention allowing women greater control over the induction process. This is one of a series of reviews of methods of cervical ripening and labour induction using a standardised methodology. To determine the effectiveness of breast stimulation for third trimester cervical ripening or induction of labour in comparison with placebo/no intervention or other methods of induction of labour. The Cochrane Pregnancy and Childbirth Group Trials Register (March 2004) and bibliographies of relevant papers. Clinical trials of breast stimulation for third trimester cervical ripening or labour induction. A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. Six trials (719 women) were included. Analysis of trials comparing breast stimulation with no intervention found a significant reduction in the number of women not in labour at 72 hours (62.7% versus 93.6%, relative risk (RR) 0.67, 95% confidence interval (CI) 0.60 to 0.74). This result was not significant in women with an unfavourable cervix. A major reduction in the rate of postpartum haemorrhage was reported (0.7% versus 6%, RR 0.16, 95% CI 0.03 to 0.87). No significant difference was detected in the caesarean section rate (9% versus 10%, RR 0.90, 95% CI 0.38 to 2.12) or rates of meconium staining. There were no instances of uterine hyperstimulation. Three perinatal deaths were reported (1.8% versus 0%, RR 8.17, 95% CI 0.45 to 147.77). When comparing breast stimulation with oxytocin alone the analysis found no difference in caesarean section rates (28% versus 47%, RR 0.60, 95% CI 0.31 to 1.18). No difference was detected in the number of women not in labour after 72 hours (58.8% versus 25%, RR 2.35, 95% CI 1.00 to 5.54) or rates of meconium staining. There were four perinatal deaths (17.6% versus 5%, RR 3.53, 95% CI 0.40 to 30.88). Breast stimulation appears beneficial in relation to the number of women not in labour after 72 hours, and reduced postpartum haemorrhage rates. Until safety issues have been fully evaluated it should not be used in high-risk women. Further research is required to evaluate its safety, and should seek data on postpartum haemorrhage rates, number of women not in labour at 72 hours and maternal satisfaction.


Changes in health-related quality of life of oral cancer patients treated with curative intent: experience of a developing country.
This study aimed to assess changes in oral cancer patients' health-related quality of life (HRQOL) and the impact of disease stage on HRQOL scores. HRQOL data were collected from seven hospital-based centres using the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) version 4.0 instrument. The independent samples t-test, χ2 test, and paired samples t-test were used to analyse the data. A total of 300 patients were recruited. The most common oral cancer sub-site was tongue and floor of mouth (42.6%). Surgical intervention (41.1%) was the most common treatment modality. Significant differences in ethnicity and treatment modality were observed between early and late stage patients. Pre-treatment HRQOL scores were significantly lower for late than early stage patients. At 1 month post-treatment, the functional and head and neck domains and the FACT-H&N (TOI) summary scores showed significant deterioration in both early and late stage patients. In contrast, the emotional domain showed a significant improvement for early and late stage patients at 1, 3, and 6 months post-treatment. Although HRQOL deterioration was still observed among early and late stage patients at 6 months post-treatment, this was not statistically significant. In conclusion, advanced disease is associated with poorer HRQOL. Although ethnic differences were observed across different disease stages, the influence of ethnicity on patient HRQOL was not evident in this study.


Bacterial decomposition of insects post-Metarhizium infection: Possible influence on plant growth.
Strains of entomopathogenic fungi may have substantial differences in their final stages of mycosis. Insect cadavers are usually overgrown with mycelium after colonization of the insect body, but in many cases, bacterial decomposition of the colonized hosts occurs. We used two Metarhizium robertsii strains in the work: Mak-1 (cadavers become overgrown with mycelium and conidia) and P-72 (cadavers decay after fungal colonization). We conducted a comparative analysis of gut and cadaver microbiota in Colorado potato beetle larvae using 16S rRNA gene sequencing after infection with these strains. In addition, we estimated the content of different forms of nitrogen in cadavers and the influence of cadavers on the growth of Solanum lycopersicum on sand substrates under laboratory conditions. It was shown that infections did not lead to a significant shift in the midgut bacterial communities of infected insects compared to those of untreated insects. Importantly, bacterial communities were similar in both types of cadaver, with predominantly enterobacteria. Decomposing cadavers (P-72) were characterized by increased nitrate and ammonium, and they had a stronger growth-promoting effect on plants compared to cadavers overgrown with mycelium and conidia (Mak-1). We also estimated the colonization and growth of plants after treatment with conidia of both strains cultivated on artificial medium. Both cultures successfully colonized plants, but strain P-72 showed stronger growth promotion than Mak-1. We propose that the use of deviant strains that are unable to sporulate on cadavers leads to a faster (though only passive) flow of nitrogen from killed insects to plants.


Fatty degeneration of myocardial cells as a sign of death due to hypothermia versus degenerative deposition of lipofuscin.
Lipid-deposits in internal organs, e.g. nephrons, are discussed as reliable marker to determine hypothermia as cause of death. While investigations concerning lipid vacuoles in the epithelium of the renal tubules are already published, there is no systematic information available about hypothermia and lipid deposits in cardiomyocytes. Therefore, this retrospective study presents the first results of lipid-stainings of myocardial samples taken by autopsies in hypothermia-cases in comparison to samples from a control group. It was the aim of the study to clarify the conceivable causal relationship between death due to hypothermia and lipid-deposits apart from lipofuscin and fatty degeneration, respectively, in cardiomyocytes.


Sonographic measurement of renal length in children: Variation associated with body position.
We ultrasonographically measured renal length in the major axis in children. Here we discuss the differences in measured lengths in the supine and prone positions. In study 1, which included 214 children, more than 60 percent of the kidneys measured longer in the supine than in the prone position. The difference (S-P: length in the supine position minus length in the prone position) was substantially greater in the left kidney. In study 2, we observed the relation between the kidney and the liver or spleen in 60 children prospectively to determine if artifacts had contributed to the observed differences. When the location of the liver or spleen was above the ki dney, which may induce velocity displacement and renal duplication artifacts, the kidney tended to measure longer. We conclude that kidneys tend to measure longer in the supine than in the prone position. Difference in renal length in different positions was greater in the left kidney than in the right kidney. Sonographic artifacts are presumed to contribute to differences in measured length.


Incidentally discovered adrenal masses.
It is becoming increasingly common to discover adrenal masses incidentally on radiologic imaging studies. Adrenal masses are also occasionally found unexpectedly during operation. Herein, we review 10 cases of incidentally discovered adrenal masses which illustrate the experience with the treatment of these lesions in the past 8 years. A management plan based on this experience and a review of previously published data are discussed.


[Chemotherapy with paclitaxel leads to microRNA release].
During recent years, microRNAs (Greek: micros = small; miRNA) have become more important. miRNAs are highly conserved, noncoding, single-stranded RNA molecules 17–28 nucleotide in length. Secreted by tumor cells, miRNAs regulate many biological processes and are also involved in chemoresistance. Classical forms of cancer treatment lead to miRNA release. Which miRNAs are correlated to head and neck squamous cell carcinomas (HNSCC) and their chemoresistance to paclitaxel remains unknown. Identification of miRNAs expressed in HNSCC and elucidation of those involved in conferring chemoresistance to paclitaxel. To identify changes in gene expression, HNSCC cell lines were treated with 10 μM paclitaxel for 48 h and analyzed by microarray analysis. Thereafter, changed in expression of single miRNAs (miR221*, miR222 and miR222*) following paclitaxel treatment were analyzed using a quantitative real-time polymerase chain reaction (qRT-PCR). Under treatment with paclitaxel, miRNAs were released. The dominant change is upregulation of MIR222 gene expression. Regulation of miR222* expression under paclitaxel treatment seems to be different in human papillomavirus (HPV)-negative and HPV-positive HNSCC cell lines. Expression of mirR221/222 is correlated to cell cycle regulation, carcinogenesis, and chemoresistance. Detailed knowledge of the molecular mechanisms and effects ofmiRNAs is important for identifying miRNAs as cancermarkers, as well as for increasing the efficiency of cancer therapeutics.


Characterization of Rab32- and Rab38-positive lysosome-related organelles in osteoclasts and macrophages.
Both the biogenesis and functions of osteoclasts and macrophages involves dynamic membrane traffic. We screened transcript levels for Rab family small GTPases related to osteoclasts and identified Rab38. Rab38 expression is upregulated during osteoclast differentiation and maturation. In osteoclasts, both Rab38 and its paralog, Rab32, colocalize to lysosome-related organelles (LROs). In macrophages, Rab32 is also found in LROs. LROs are part of the endocytic pathway but are distinct from lysosomes. After receptor activator of NF-κB ligand stimulation, LROs contain cathepsin K and tartrate-resistant acid phosphatase inside and help both proteins to accumulate around bone resorption pits. After osteoclast maturation, these enzymes are hardly found within LROs. In macrophages derived from Rab32 and Rab38 double knockout mice, both acidification and V-ATPase a3 localization were severely compromised. Both the double knockout macrophage and bafilomycin-treated wildtype macrophage show an increase in Lamp1-positive organelles, implying that biogenesis of lysosomes and LROs are related. These results indicate that Rab32 and Rab38 both play a crucial role in LRO biogenesis in macrophages and in osteoclasts.


Radiation therapy for chloroma (granulocytic sarcoma).
Chloroma (granulocytic sarcoma) is a rare, extramedullary tumor of immature myeloid cells related to acute nonlymphocytic leukemia or myelodysplastic syndrome. Radiation therapy (RT) is often used in the treatment of chloromas; however, modern studies of RT are lacking. We reviewed our experience to analyze treatment response, disease control, and toxicity associated with RT to develop treatment algorithm recommendations for patients with chloroma. Thirty-eight patients who underwent treatment for chloromas at our institution between February 1990 and June 2010 were identified and their medical records were reviewed and analyzed. The majority of patients that presented with chloroma at the time of initial leukemia diagnosis (78%) have not received RT because it regressed after initial chemotherapy. Yet most patients that relapsed or remained with chloroma after chemotherapy are in the RT cohort (90%). Thirty-three courses of RT were administered to 22 patients. Radiation subsite breakdown was: 39% head and neck, 24% extremity, 9% spine, 9% brain, 6% genitourinary, 6% breast, 3% pelvis, and 3% genitourinary. Median dose was 20 (6-36) Gy. Kaplan-Meier estimates of progression-free survival and overall survival in the RT cohort were 39% and 43%, respectively, at 5 years. At a median follow-up of 11 months since RT, only 1 patient developed progressive disease at the irradiated site and 4 patients developed chloromas at other sites. RT was well tolerated without significant acute or late effects and provided symptom relief in 95% of cases. The majority of patients with chloromas were referred for RT when there was extramedullary progression, marrow relapse, or rapid symptom relief required. RT resulted in excellent local disease control and palliation of symptoms without significant toxicity. We recommend irradiating chloromas to at least 20 Gy, and propose 24 Gy in 12 fractions as an appropriate regimen.


Acetylation of Bombyx mori silk fibroin and their characterization in the dry and hydrated states using 13C solid-state NMR.
Acetylation of Bombyx mori silk fibroin (SF) was accomplished by chemical reaction of the side chain OH groups in Ser and Tyr residues with acetic anhydrate to increase hydrophobic character of SF. A combination of three kinds of 13C solid-state NMR techniques was used to elucidate the effect of acetylation in the dry and hydrated states for [3-13C]Ser, [3-13C]Tyr and [3-13C]Ala enriched-SF powder. The mobilities of Tyr and Ala residues in the amorphous region of acetylated 13C-labeled SF powder increased slightly and only very small amounts of the Ala residue with high mobility was observed by hydration. On the other hand, there are essentially no effect of water on the β-sheet region of these residues and acetylated Ser residues. A similar tendency toward the effect of hydration for acetylated SF powder was observed for acetylated SF fiber. The remarkable improvement of the dimensional stability in water was attained although the tensile strengths of fibers were slightly lower by the acetylation of SF fiber. Thus, acetylation proved very effective to achieve water-proofing of SF materials and the effect of acetylation on the local structure and dynamics of SF could be clarified using 13C solid-state NMR.


Acute overdose with controlled-release levodopa-carbidopa.
Reports of acute levodopa-carbidopa overdose are rare and no case of an acute overdose with a controlled-release formulation has been described. We describe such a case in which serial concentrations of catecholamines were measured. A 55-year-old man ingested 89 tablets of Sinemet 50/200 (17.8 g of levodopa, 4.45 g of carbidopa). Clinical effects and plasma concentrations of dopamine, noradrenaline and adrenalin were assessed over 66 hours. On admission 2.5 hours after the ingestion, his physical examination was normal except for mydriasis and urine retention. Five hours post-ingestion he had psychomotor agitation, delirium with logorrhea, joviality, visual hallucinations, regular sinus tachycardia and xerostomia. The clinical course included two episodes hypotension and four of transient tachycardia. Treatment was symptomatic and supportive. Clinical toxicity reappeared 48 hours after the intoxication. The patient was discharged at the end of the fourth day with amnesia for the event. Dopamine showed an initial plasma concentration peak 14 hours after the toxic ingestion, followed by a second peak 38 hours after the ingestion. The initial peak of noradrenaline occurred 20 hours post-ingestion with a second lower peak at 38 hours. There were no elevations in adrenalin concentrations. There appeared to be no correlation between the intensity of the clinical signs and the blood concentrations of dopamine and noradrenaline, although the resolution of the clinical signs did correspond to these catecholamines return to normal values. Patients who ingest controlled-release formulations need to be observed until after the second catecholamine peak.


Characteristics of the alkylphenol and bisphenol A distributions in marine organisms and implications for human health: A case study of the East China Sea.
The distributions of alkylphenol (AP) and bisphenol A (BPA) in marine organisms, including fish, prawns and molluscs, could reflect the exposure of AP and BPA directly and effectively. This paper provides the first report on the species-dependent distribution and the human health risks of four APs (4-t-octylphenol, 4-t-OP; 4-octylphenol, 4-OP;4-nonylphenol, 4-NP; 4-n-nonylphenol, 4-n-NP) and BPA in 95 wild and 88 processed marine biota samples from the East China Sea of the Yangtze River Delta area. 4-NP was the predominant compound with the highest detected concentration of 19,890.50ng/g ww. Significant pollution was observed in Taizhou, Shanghai and Ningbo. The species-dependent distribution was related to food habits, living patterns and trophic transfer. Higher residual concentrations of 4-t-OP, 4-OP, 4-n-NP and BPA were observed in fish species that consumed benthic organisms or demersal fish species, whereas 4-NP showed different results due to trophic dilution. The trophic magnification factors (TMFs) of the linear APs (4-OP and 4-n-NP) (1.22-2.93) were higher than those of the branched ones (4-t-OP and 4-NP) (0.72-0.90), indicating the relative metabolism stability of linear APs. 4-NP has the lowest TMF value of 0.72, and its trophic dilution might be observed because the branched carbon chain exhibits the lowest dispersion force compared to that of the other APs. As for the health risk, 7-year old children may be exposed to the highest health risk of 4-NP with 95th percentile values of the hazard quotient of 0.22 to 0.23; however, the risks of the other chemicals were relatively low.


Optimal management of ulnar collateral ligament injury in baseball pitchers.
The ulnar collateral ligament stabilizes the elbow joint from valgus stress associated with the throwing motion. During baseball pitching, this ligament is subjected to tremendous stress and injury if the force on the ulnar collateral ligament during pitching exceeds the physiological limits of the ligament. Injuries to the throwing elbow in baseball pitchers result in significant time loss and typically surgical intervention. The purpose of this paper is to provide a review of current information to sports medicine clinicians on injury epidemiology, injury mechanics, injury risk factors, injury prevention, surgical interventions, nonsurgical interventions, rehabilitation, and return to play outcomes in baseball pitchers of all levels.


Simple high-performance liquid chromatographic method for the measurement of toloxatone in rabbit cerebrospinal fluid and plasma.
A simplified, rapid high-performance liquid chromatographic procedure has been developed for the measurement of toloxatone in rabbit plasma and cerebrospinal fluid. The method involves a single-step extraction of the alkalinized sample with diethyl ether and analysis of the evaporated extract on a C8 column. Detection was performed by ultraviolet absorbance monitored at 240 nm. The overall run-time of the assay was 8 min at a flow-rate of 1 ml min-1. The sensitivity limit of toloxatone was 70 ng ml-1 at a signal-to-noise ratio of 3:1 in rabbit cerebrospinal fluid and plasma. The assay has been used to define plasma toloxatone concentration-time profiles and to quantitate cerebrospinal fluid toloxatone levels after a single intravenous injection in rabbits.


Ultrasonic evaluation of the physical and mechanical properties of granites.
Masonry is the oldest building material that survived until today, being used all over the world and being present in the most impressive historical structures as an evidence of spirit of enterprise of ancient cultures. Conservation, rehabilitation and strengthening of the built heritage and protection of human lives are clear demands of modern societies. In this process, the use of nondestructive methods has become much common in the diagnosis of structural integrity of masonry elements. With respect to the evaluation of the stone condition, the ultrasonic pulse velocity is a simple and economical tool. Thus, the central issue of the present paper concerns the evaluation of the suitability of the ultrasonic pulse velocity method for describing the mechanical and physical properties of granites (range size between 0.1-4.0 mm and 0.3-16.5 mm) and for the assessment of its weathering state. The mechanical properties encompass the compressive and tensile strength and modulus of elasticity, and the physical properties include the density and porosity. For this purpose, measurements of the longitudinal ultrasonic pulse velocity with distinct natural frequency of the transducers were carried out on specimens with different size and shape. A discussion of the factors that induce variations on the ultrasonic velocity is also provided. Additionally, statistical correlations between ultrasonic pulse velocity and mechanical and physical properties of granites are presented and discussed. The major output of the work is the confirmation that ultrasonic pulse velocity can be effectively used as a simple and economical nondestructive method for a preliminary prediction of mechanical and physical properties, as well as a tool for the assessment of the weathering changes of granites that occur during the serviceable life. This is of much interest due to the usual difficulties in removing specimens for mechanical characterization.


Involvement of AMPA receptor desensitization in short-term synaptic depression at the calyx of Held in developing rats.
Paired-pulse facilitation (PPF) and depression (PPD) are forms of short-term plasticity that are generally thought to reflect changes in transmitter release probability. However, desensitization of postsynaptic AMPA receptors (AMPARs) significantly contributes to PPD at many glutamatergic synapses. To clarify the involvement of AMPAR desensitization in synaptic PPD, we compared PPD with AMPAR desensitization, induced by paired-pulse glutamate application in patches excised from postsynaptic cells at the calyx of Held synapse of developing rats. We found that AMPAR desensitization contributed significantly to PPD before the onset of hearing (P10-12), but that its contribution became negligible after hearing onset. During postnatal development (P7-21) the recovery of AMPARs from desensitization became faster. Concomitantly, glutamate sensitivity of AMPAR desensitization declined. Single-cell reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated a developmental decline of GluR1 expression that correlated with speeding of the recovery of AMPARs from desensitization. Transmitter release probability declined during the second postnatal week (P7-14). Manipulation of the extracellular Ca2+/Mg2+ ratio, to match release probability at P7-8 and P13-15 synapses, revealed that the release probability is also an important factor determining the involvement of AMPAR desensitization in PPD. We conclude that the extent of involvement of AMPAR desensitization in short-term synaptic depression is determined by both pre- and postsynaptic mechanisms.


Serum alkaline phosphatase (Al-Pase) isozyme in gastric and colonic cancer (using a simple thin layer polyacrylamide gel electrophoresis).
Using the simple thin layer polyacrylamide gel electrophoresis, serum alkaline phosphatase could be separated 5 isozyme bands in various digestive diseases, consisting of 54 cases of gastric cancer, 11 of colonic cancer, 12 of hepatoma, 4 of cholangioma, 14 of pancreatic cancer, 81 of benign hepatobilliary diseases, 13 of cancers of other organs and 61 of control. The obtained results were as follows: 1) The electrophoretic analysis of serum alkaline phosphatase showed the specific band remaining at the origin, already reported as "alkaline phosphatase O", in primary and metastatic cancer of the liver and cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cholelithiasis. On the contrary, alkaline phosphatase O was never found in gastric and colonic cancer without cancerous metastasis to the liver, and it was also inclined to be positive with the progress of liver metastasis among them. 2) Intestinal alkaline phosphatase was usually found in higher frequency in blood group B and O than in the others, and it was apt to disappear in gastric or colonic cancer with an exacerbation of its cancerous lesions. 3) Heat-stable alkaline phosphatase was found in 10% of gastric or colonic cancer, all of which were histologically proved to be well differentiated adenocarcinoma.


Openness to Experience is associated with neural and performance measures of memory in older adults.
Age-related decline in episodic memory performance is a well-replicated finding across numerous studies. Recent studies focusing on aging and individual differences found that the Big Five personality trait Openness to Experience (hereafter: Openness) is associated with better episodic memory performance in older adults, but the associated neural mechanisms are largely unclear. Here, we investigated the relationship between Openness and memory network function in a sample of 352 participants (143 older adults, 50-80 years; 209 young adults, 18-35 years). Participants underwent functional magnetic resonance imaging (fMRI) during a visual memory encoding task. Functional memory brain-network integrity was assessed using the similarity of activations during memory encoding (SAME) scores, which reflect the similarity of a participant's memory network activity compared to prototypical fMRI activity patterns of young adults. Openness was assessed using the NEO Five-Factor Inventory. Older vs young adults showed lower memory performance and higher deviation of fMRI activity patterns (i.e. lower SAME scores). Specifically in older adults, high Openness was associated with better memory performance, and mediation analysis showed that this relationship was partially mediated by higher SAME scores. Our results suggest that trait Openness may constitute a protective factor in cognitive aging by better preservation of the brain's memory network.


p53-based therapeutics for head and neck squamous cell carcinoma.
Inactivation of the tumor suppressor p53 is a pathogenetic event in the development of head and neck squamous cell carcinoma (HNSCC). In the absence of functional wildtype p53, HNSCC cells have increased resistance to standard chemotherapeutics and radiation. Numerous approaches to restore p53 function in cancer cells have been developed over the past several decades. This review article focuses on viral approaches to deliver wildtype p53 to HNSCC cells, a designer virus that selectively eliminates mutant p53 HNSCC cells, and chemical approaches to reactivate p53 function in HNSCC cells. These promising studies provide evidence that p53 therapeutics may prove useful alone or in combination with conventional chemotherapy and/or radiation for the management of HNSCC patients.


Necessity of routine ipsilateral hemithyroidectomy during laryngopharyngectomy for pyriform sinus cancer.
The aim of this study was to revisit the role of hemithyroidectomy in the treatment of pyriform sinus cancer by determining the incidence of thyroid gland invasion by the tumor. Medical records of 27 patients with pyriform sinus cancer who underwent laryngopharyngectomy with ipsilateral hemithyroidectomy from 1999 to 2010 at a National Cancer Institute-designated comprehensive cancer center were retrospectively reviewed. Computed tomographic scans of the neck, operative notes, and surgical specimens were examined to determine the presence of thyroid gland invasion by imaging, clinical appearance, and pathology. There were 19 male and 8 female patients (age range, 44-79 years; mean, 59.9 years). Most of the cases (85%) had advanced-stage disease. Extralaryngeal spread of tumor with thyroid cartilage invasion was noted in the computed tomographic scans of 5 patients; however, there was no radiologic evidence of thyroid gland invasion in any patient. No gross thyroid gland invasion by the tumor was appreciated in any patient during surgery. No histologic evidence of tumoral invasion of the thyroid gland was found in any of 27 surgical specimens. Results of this study suggest that thyroid gland invasion by pyriform sinus cancer is not common. Therefore, a routine ipsilateral hemithyroidectomy may not be necessary in the treatment of every patient with pyriform sinus cancer, unless there is evidence of thyroid gland invasion.


Making the T-type even tinier: corticotropin-releasing factor-mediated inhibition of low-voltage-activated calcium channel activity.
T-type calcium channels are important for a variety of physiological processes such as brain and heart function. Proper regulation of these channels by second messengers is fundamental; however, our knowledge of the molecular pathways that regulate T-type calcium channels is limited in comparison with other voltage-dependent calcium channels. In this issue of Molecular Pharmacology, Tao et al. (p. 1596) demonstrate that Cav3.2 is regulated by activation of the corticotropin-releasing factor receptor 1 in a Gbetagamma-dependent manner.


Ultrastructural pathology of aortic dissections in patients with Marfan syndrome: Comparison with dissections in patients without Marfan syndrome.
Despite the discovery in 1990 that mutations in the fibrillin-1 gene cause the Marfan syndrome, the pathogenesis of the life-threatening dissections associated with this disease is far from elucidated. Both the massive number of known fibrillin-1 mutations that result in a heterogeneous patient population and the strongly heterogeneous histology of patients' aortae presumably contribute to this lack of knowledge. We performed a detailed ultrastructural immunoelectron microscopic and histochemical analysis of the dissected media of ascending aortae of 10 patients with Marfan syndrome and compared them with those of 6 patients without Marfan syndrome and 77 individuals without known aortic disease. Relatively similar abnormalities were found in both patient groups, although they were more numerous and more diffusely spread in the patients with Marfan syndrome than in the patients without Marfan syndrome. The most conspicuous ultrastructural defects were the formation of abrupt transverse tears in thick and compact elastic lamellae and the local breaking up of smooth muscle cell-elastic lamella connections (that largely consist of microfibrils and elastic extensions, protruding from the elastic lamellae). This breaking up was characterized by a strongly reduced number of microfibrils and a severe shortening of the elastic extensions. Finally, the elastic extensions detached from the lamellae to ultimately degenerate and disappear. These changes were found mainly in the oldest group of patients with Marfan syndrome, indicating that they represented a loss of previously normally developed structures. We also compared our findings with those from a recently developed murine Marfan model (Pereira L, Lee SY, Gayraud B, Andrilopoulos K, Shapiro SD, Bunton T, Biery NJ, Dietz HC, Sakai LY, Ramirez F. Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1. Proc Natl Acad Sci. U. S. A. 1999: 96: 3819-3823). Next to similarities, several striking differences existed, demonstrating that this model is not fully representative of the human Marfan syndrome.