Clinical trials in cancer medicine.
The need for improvement in the results of all types of cancer treatment must be apparent to any practitioner who sees cancer patients. A number of clinical trials are in progress in this country to evaluate various cancer treatments, especially those using drugs. The purpose of this paper is to inform family physicians about the nature of some of these trials, and to provide some information about the drugs being investigated.


Evaluation of inferior right hepatic vein-preserving hepatectomy with resection of the superior right hepatic vein.
If the superior right hepatic vein (SRHV) is resected, segment 6 will be drained by the inferior right hepatic vein (IRHV) and congestion will not occur. However, early postoperative liver function and long-term regeneration of segment 6 after IRHV-preserving hepatectomy remains unclear. Three patients undergoing IRHV-preserving hepatectomy were examined. One (case 1) had liver metastasis from sigmoid colon cancer and two (cases 2 and 3) had hepatocellular carcinoma. Resection of segments 7 and 8 along with the SRHV was performed in cases 1 and 2. Anterior sectionectomy and resection of segment 4a along with the SRHV and middle hepatic vein (MHV) was performed in case 3. The volume of each sector was calculated by summation of each CT area. The warm ischemic time of the three cases was 50-78 min, operative blood loss was 496-914 g, and operating time was 4-7 h. There was no significant change in diameter of the IRHV and MHV before and after surgery. Intraoperative color Doppler ultrasonography was a useful technique for evaluating intrahepatic venous communication. Part of segment 6 had previously been resected in case 1, and at outpatient follow-up this segment was found to have become atrophic. In cases 2 and 3, the remnant posterior sector became hypertrophic. IRHV-preserving hepatectomy can retain a greater proportion of liver parenchyma than right hepatectomy. Postoperative liver function was well maintained in our patients and there were no serious complications. Long-term follow-up showed hypertrophy of the remnant posterior sector except in one case. To minimize surgical damage, for example in patients with poor liver function or preoperative complications, IRHV-preserving hepatectomy should be considered.


Examining Face Validity of Visual Stimuli Used in Preference Assessments for Older Adults With Communication Impairments.
Preference assessment is integral to person-centered treatment planning for older adults with communication impairments. There is a need to validate photographs used in preference assessment for this population. Therefore, this study aimed to establish preliminary face validity of photographs selected to enhance comprehension of questions from the Preferences for Everyday Living Inventory-Nursing Home (PELI-NH) and describe themes in older adults' recommendations for revising photographic stimuli. This qualitative, cognitive interviewing study included 21 participants with an average age of 75 years and no known cognitive or communication deficits. Photographic stimuli were randomized and evaluated across one to two interview sessions. Participants were asked to describe what the preference stimuli represented to them. Responses were scored to assess face validity. Participants were then shown the PELI-NH written prompt and asked to evaluate how well the photograph(s) represented the preference. A semideductive thematic analysis was conducted on interview transcripts to summarize themes in participant feedback. Forty-six (64%) stimuli achieved face validity criteria without revisions. Six (8%) stimuli achieved face validity after one partial revision. Twenty (28%) stimuli required multiple revisions and reached feedback saturation, requiring team review for finalization. Thematic analysis revealed challenges interpreting stimuli (e.g., multiple meanings) and participant preferences for improving photographs (e.g., aesthetics). Cognitive interviewing was useful for improving face validity of stimuli pertaining to personal care topics. Abstract and subjective preferences (e.g., cultural traditions) may be more challenging to represent. This study provides a framework for further testing with older adults with cognitive, communication, and hearing impairments.


Sleepiness and recovery in schedule change and the eighty-four hour workweek.
The aims were to evaluate sleepiness and recovery during a schedule change, and during an 84-hours workweek. The control group (16 men) stayed on a six-week schedule, whereas the intervention group (12 men) transferred to a seven-week schedule. Sleepiness was estimated, using the KSS-scale, four times during the first and the third night in the fifth or sixth shift week. Recovery was assessed through four estimations on days one, three and five during the week off. Statistical testing was carried out using repeated measurement ANOVA. Sleepiness at night was affected by night (F = 4.90, p < 0.05) and hour (F = 33.64, p < 0.001) in both groups. The intervention group was sleepier during the first recovery day compared to the control group (F = 4.02, p < 0.05). Analysis of the 84-hour-week showed an effect of night (F = 8.98, p < 0.05) and hour (F = 71.60, p < 0.001) on night work, and day (F = 22.49, p < 0.01) and hour (F = 6.66, p < 0.05) on recovery. Sleepiness was more pronounced on the first recovery day (F = 23.08, p < 0.01). The seven-week schedule showed no effect that differed from that of the control group on sleepiness during the night shift. After the 84-hour workweek the workers recovered in about three days. The new schedules may affect the first recovery day negatively.


Effects of meiotic inhibitors and gonadotrophins on porcine oocytes in vitro maturation, fertilization and development.
This study evaluated the effect of three reversible meiotic inhibitors (MINs) and their interaction with gonadotrophins (Gns) on the meiotic maturation and developmental competence of porcine oocytes. In experiment 1, the oocytes were matured for 22 hr in the presence or absence of dbcAMP (1 mM), cycloheximide (7 μM) or cilostamide (20 μM) with or without Gns, and for an additional 22 hr in the absence of MINs and Gns. At 22 hr of maturation, regardless of the presence of Gns, a higher proportion (p < .001) of oocytes cultured in the presence of MINs were effectively arrested at the germinal vesicle stage compared with the oocytes cultured without MINs. At 44 hr of maturation, the proportion of oocytes that reached MII was higher (p < .05) in groups with Gns compared with groups without Gns. In experiment 2, oocytes that were matured as in experiment 1 were inseminated and cultured for 7 days to evaluate fertilization parameters and blastocyst formation. Only oocytes from the dbcAMP + Gns group had higher (p < .05) efficiency of fertilization compared with the other treatment groups. The presence of dbcAMP during maturation also increased (p < .05) blastocyst formation and efficiency of blastocyst formation in both the presence and absence of Gns. These results indicate that the interaction of Gns with the tested MINs improved meiotic progression. In addition, regardless of supplementation with Gns, the presence of dbcAMP during the first maturation period increased and even doubled the capacity of oocytes to develop to the blastocyst stage.


Amelanotic melanoma of the palate: report of a case.
Primary amelanotic melanoma is an infrequent occurrence in the oral cavity. Owing to the high rate of local invasion and distant metastasis, oral amelanotic melanoma (OAM) carries a very poor prognosis. The absence of pathognomonic clinical and routine histological features in OAM is the reason for diagnosticdelay, which further worsens the prognosis. This case report discusses the masquerading nature of OAM that was clinically and histologically mimicking several malignant neoplasms. This case also demonstrates the poor prognosis of OAM. The objective of presenting this case is that the diagnostic delay of OAM can be avoided through enhanced clinical awareness and subsequent appropriate immunohistochemical investigations, in addition to the routine H&E-stained histopathological evaluation.


Immunoglobulin A monoclonal gammopathy in two horses with multiple myeloma.
The clinical findings in two horses with secretory multiple myeloma and secondary immunoglobulin A (IgA) monoclonal gammopathy were non-specific and included weight loss, pale mucous membranes, limb oedema and bacterial respiratory tract infection. Consistent laboratory abnormalities included hyperproteinaemia, hyperglobulinaemia, hypoalbuminaemia and hypercalcaemia. The diagnosis was based on the presence of IgA monoclonal gammopathy in serum and urine and bone marrow plasmacytosis (> 10 per cent). One horse was euthanased; it had neoplastic plasma cell infiltrates in its kidneys, spleen, liver, bone marrow, myocardium and adrenal glands. The other horse was treated for a bacterial pneumonia and was still alive six months after it was first examined.


Structural and biochemical insights into the 2'-O-methylation of pyrimidines 34 in tRNA.
tRNA molecules undergo extensive modifications during their maturation and these modifications play important cellular roles. TrmL is a tRNA-modification enzyme that catalyzes the transfer of a methyl group to the 2'-hydroxyl group of the pyrimidines at the wobble position 34 in two tRNALeu isoacceptors, but the mechanism remains elusive. In this study, we determined the crystal structure of TrmL from Thermus thermophilus (TtTrmL) to 1.7 Å. The enzyme contains only the conserved minimal SPOUT fold, but displays distinct biochemical behavior from its Escherichia coli counterpart, EcTrmL. Interestingly, a fortuitous ligand of 5'-methylthioadenosine was consistently found at the SAM-binding pocket in the crystal structures, which probably came from the expression host. Both TtTrmL and EcTrmL were capable of methylating each other's tRNA substrates, but the latter exhibited much higher activity than the former. Enzymatic activity assays showed that the reaction catalyzed by TtTrmL greatly depends on the reaction pH and is also affected by salt concentration. Via sequence alignment and structural superposition, we discovered that a universally conserved glutamate residue is likely to fulfill the role of the general base for the initial proton abstraction from the 2'-hydroxyl group of pyrimidines 34. Lastly, based on our structural and biochemical data, we proposed the dimer interface to be the tRNA-binding site for TtTrmL. The atomic coordinates and structural factors have been deposited in the Protein Data Bank with accession number 5CO4.


Examining validity of body mass index calculated using height and weight data from the US driver license.
Driver license departments in many US states collect data on individuals' height and weight. These data can be useful to researchers in epidemiological and public health studies. As height and weight on driver license are self-reported, they may be prone to reporting bias. We compare height and weight obtained from driver license records and clinically measured height and weight, as well as body mass index (BMI) values calculated using the two data sources for the same individual. We linked individual height and weight records obtained from the Driver License Division (DLD) in the Utah Department of Public Safety to clinical records from one of the largest healthcare providers in the state of Utah. We then calculated average differences between height, weight and BMI values separately for women and men in the sample, as well as discrepancies between the two sets of measures by age and BMI category. We examined how well self-reported height and weight from the driver licenses classify individuals into specific BMI categories based on clinical measures. Finally, we used two sets of BMI values to estimate individuals' relative risk of type II diabetes. Individuals, on average, tend to overestimate their height and underestimate their weight. Consequently, the value of BMI calculated using driver license records is lower than BMI calculated using clinical measurements. The discrepancy varies by age and by BMI category. Despite the discrepancy, BMI based on self-reported height and weight allows for accurate categorization of individuals at the higher end of the BMI scale, such as the obese. When used as predictors of relative risk of type II diabetes, both sets of BMI values yield similar risk estimates. Data on height and weight from driver license data can be a useful asset for monitoring population health in states where such information is collected, despite the degree of misreporting associated with self-report.


Backscatter-difference Measurements of Cancellous Bone Using an Ultrasonic Imaging System.
Backscatter-difference measurements may be used to detect changes in bone caused by osteoporosis. The backscatter-difference technique measures the power difference between two portions of an ultrasonic backscatter signal. The goal of this study is to evaluate the feasibility of using an ultrasonic imaging system to perform backscatter-difference measurements of bone. Ultrasonic images and backscatter signals were acquired from 24 specimens of human cancellous bone. The signals were analyzed in the frequency domain to determine the normalized mean backscatter-difference (nMBD) and in the time domain to determine the normalized backscatter amplitude ratio (nBAR). The images were analyzed to determine the normalized pixel value difference (nPVD), which measures the difference in average pixel brightness between regions of interest placed at two different depths in the image. All three parameters were found to increase with bone mineral density. The signal-based parameters, nMBD and nBAR, correlated well with bone mineral density, yielding linear correlation coefficients that ranged from 0.74 to 0.87. The image based parameter, nPVD, performed somewhat less well, yielding correlation coefficients that ranged from 0.42 to 0.81. These results suggest that ultrasonic imaging systems may be used to perform backscatter-difference measurements for the purpose of ultrasonic bone assessment.


Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration.
Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the number of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.


[Clinical outcomes of thoracoscopic esophagectomy after neoadjuvant chemotherapy].
With recent advances in multimodal therapy for esophageal cancer, neoadjuvant chemotherapy (NAC) followed by surgery has become the standard treatment for advanced resectable esophageal cancer. This study analyzed the feasibility and clinical outcomes of thoracoscopic esophagectomy (TE) after NAC. We retrospectively analyzed 129 patients who underwent TE with radical mediastinal lymph node dissection between January 2005 and December 2012. Of these patients, 54 received NAC( NAC+group) and 75 did not( NAC-group).The perioperative clinical outcomes, number of dissected nodes, and postoperative mortality were compared between the 2 groups. The operation time in the NAC+group was significantly longer than that in the NAC-group( p<0.01).However, the estimated blood loss was significantly less in the NAC+group( p<0.01).There was no significant difference in the number of dissected nodes and the frequency of postoperative complications between the 2 groups. TE can be safely adopted for the treatment of patients with advanced esophageal cancer after NAC.


The disruptive effects of pain on complex cognitive performance and executive control.
Pain interferes and disrupts attention. What is less clear is how pain affects performance on complex tasks, and the strategies used to ensure optimal outcomes. The aim of the current study was to examine the effect of pain on higher-order executive control processes involved in managing complex tasks. Sixty-two adult volunteers (40 female) completed two computer-based tasks: a breakfast making task and a word generation puzzle. Both were complex, involving executive control functions, including goal-directed planning and switching. Half of those recruited performed the tasks under conditions of thermal heat pain, and half with no accompanying pain. Whilst pain did not affect central performance on either task, it did have indirect effects. For the breakfast task, pain resulted in a decreased ability to multitask, with performance decrements found on the secondary task. However, no effects of pain were found on the processes thought to underpin this task. For the word generation puzzle, pain did not affect task performance, but did alter subjective accounts of the processes used to complete the task; pain affected the perceived allocation of time to the task, as well as switching perceptions. Sex differences were also found. When studying higher-order cognitive processes, pain-related interference effects are varied, and may result in subtle or indirect changes in cognition.


Health anxiety and its association with perceived subjective workload in psychiatric nurses during the COVID-19 outbreak: a correlational study.
Health care professionals, especially nurses, experience added workload, and psychological impact during the COVID-19 outbreak. This study aimed to investigate health anxiety and its association with perceived subjective workload in nurses working in psychiatric hospital wards. This descriptive correlational study was conducted on 206 nurses working in the psychiatric wards of Razi Psychiatry Hospital in Tabriz, Iran, in 2020-2021. Census sampling was applied and data were collected using the National Aeronautics and Space Administration Task Load Index, and the Health Anxiety Inventory. Data were analyzed using descriptive statistics, t-tests, and Pearson correlation in SPSS software version 16. The mean (SD) of health anxiety and workload of nurses was 23/22(6/86) score range of 0-54 and 71.46 (12.37) score range of 0-100, respectively. The correlation between the mean of health anxiety and workload was significant only in the temporary dimension. Given the high workload and moderate level of health anxiety and the significant correlation between health anxiety and the temporary dimension of workload and the important role of appropriate workload in the health of nurses and the quality of nursing care, organizations and nursing managers should provide some strategies, like stuff shortage management in psychiatric wards and creating a suitable organizational culture.


Physical activity and affect in elementary school children's daily lives.
A positive influence of physical activity (PA) on affect has been shown in numerous studies. However, this relationship has not yet been studied in the daily life of children. We present a part of the FLUX study that attempts to contribute to filling that gap. To this end, a proper way to measure PA and affect in the daily life of children is needed. In pre-studies of the FLUX study, we were able to show that affect can be measured in children with self-report items that are answered using smartphones. In the current article, we show that it is feasible to objectively measure children's PA with accelerometers for a period of several weeks and report descriptive information on the amount of activity of 51 children from 3rd and 4th grade. Additionally, we investigate the influence of daily PA on daily affect in children. Mixed effects models show no effect of PA on any of the four measured dimensions of affect. We discuss that this might be due to effects taking place at shorter time intervals, which can be investigated in future analyses.


Vascular lesions of parotid gland in adult patients: diagnosis with high-resolution ultrasound and MRI.
Three adult patients with rare vascular lesions in the parotid gland including pseudoaneurysm, arteriovenous fistula and haemangioma are discussed. All patients presented with non-specific unilateral parotid mass. In all cases high-resolution ultrasound and MRI allowed accurate diagnosis and delineation of the extent of lesion. Conventional angiogram was utilized for planning definitive surgical or endovascular treatment.


Sparing and sharing land for maintaining the multifunctionality of large floodplain rivers.
Large floodplain rivers (LFRs) are among the most threatened ecosystems on Earth and their utilization is expected to grow. Therefore, the need to develop more effective spatial prioritization tools to maintain their multifunctionality becomes increasingly important. We present a novel approach to land use design and conservation planning of LFRs and demonstrate its applicability using a case study for the Danube River, Central-Europe. Specifically, we use indicators of habitat naturalness and complexity to define four main land use functions for LFRs: (1) relatively intact areas with high habitat complexity, which are of high priority for conservation (C), (2) degraded and simplified areas, which are not suited for conservation, but for human utilization (HU), (3) relatively natural areas with low habitat complexity, which are suited both for conservation and for sustainable use of goods and services (LS), (4) degraded areas with relatively high habitat complexity potential, which should be used for rehabilitation (R). While C and HU spare land primarily for conservation and for human utilization, respectively, categories LS and R share land both for biodiversity conservation and for human use and well-being. Results of the case study show that the different land use functions did not clearly separate spatially along the evaluated segment, but distributed relatively equally. Area weighted indices highlighted the importance of large floodplains, while non-weighted indices indicated the importance of many smaller segments with narrow floodplain riparian zone, which can still be important for conservation or rehabilitation purposes. Our multiscale analysis revealed how land use categorizations depend on index use, index weightings and spatial resolution of land use function maps, which should be considered by management. The suggested methodology provides a transparent framework to any stakeholder groups on how to plan out management actions in the context of land conservation and ecosystem services delivery of LFRs.


Mechanisms that prevent catastrophic interactions between paternal chromosomes and the oocyte meiotic spindle.
Meiosis produces haploid gametes by accurately reducing chromosome ploidy through one round of DNA replication and two subsequent rounds of chromosome segregation and cell division. The cell divisions of female meiosis are highly asymmetric and give rise to a large egg and two very small polar bodies that do not contribute to development. These asymmetric divisions are driven by meiotic spindles that are small relative to the size of the egg and have one pole juxtaposed against the cell cortex to promote polar body extrusion. An additional unique feature of female meiosis is that fertilization occurs before extrusion of the second polar body in nearly all animal species. Thus sperm-derived chromosomes are present in the egg during female meiosis. Here, we explore the idea that the asymmetry of female meiosis spatially separates the sperm from the meiotic spindle to prevent detrimental interactions between the spindle and the paternal chromosomes.


Robotic Mitral Valve Surgery.
Growing interest in minimalizing surgical trauma during heart procedures stimulated the development of robotic mitral valve surgery in the late 1990s. Initially, the new technology was slowly adopted in clinical practice. However, following encouraging results by teams that adopted robotic heart surgery early on, a growing interest in implementation of robotic mitral valve surgery has emerged. Of importance are the technical developments and possibilities that accompany robotic surgery. Robotic arms feature unique characteristics, allowing unparalleled range of motion and allowing complex mitral valve repair techniques to be performed without limitations related to limited surgical incisions. High-quality three-dimensional vision effectively compensates for the lack of tactile feedback. Several technical solutions have been developed to facilitate mitral valve repair in minimal invasive setting, including chordal guiding systems, now available with various annuloplasty rings. On the other hand, precise vision and movements allows accurate determination of the length of implanted neochordae, facilitating precise determination of the length of implanted neochords even without the use of chordal-guiding systems. With robotic mitral valve surgery, leaflet resection techniques can be performed without limitations, ensuring that no compromises of the surgical strategy are made. Nevertheless, careful preoperative planning with appropriate work-up and imaging is of utmost importance to prevent complications. Moreover, the drawbacks of the initial learning curve and higher procedural costs are counterbalanced by less surgical trauma, lower utilization of blood products, and faster patient recovery. Robotic mitral valve surgery is still a young field and evolving technology that is bound to become an important tool in the toolbox of surgical mitral valve approaches.


A history of the study of cerebral edema.
A brief review of the historical concepts underlying our present knowledge of cerebral edema is presented, together with the evolution of attempts to measure the edema.


Increased bladder wall thickness in diabetic and nondiabetic women with overactive bladder.
Bladder wall thickness has been reported to be associated with overactive bladder (OAB) in women. Diabetic women have an increased risk for OAB syndrome and may have an increased risk for bladder wall thickness. A total of 235 female patients aged 40 to 75 years were categorized into four groups. The first group consisted of women free of urgency or urge urinary incontinence. The second group included nondiabetic women with idiopathic OAB. The third group consisted of women with diabetes and clinical OAB, and women with diabetes but without OAB constituted the fourth group. Bladder wall thickness at the anterior wall was measured by ultrasound by the suprapubic approach with bladder filling over 250 mL. The diabetic (third group) and nondiabetic (second group) women with OAB had significantly greater bladder wall thickness at the anterior bladder wall than did the controls. However, the difference was not significant between the diabetic (third group) and the nondiabetic (second group) women with OAB. Women with diabetes but without OAB (fourth group) had greater bladder wall thickness than did the controls but this difference was not significant. Additionally, the difference in bladder wall thickness between diabetic women with (third group) and without (fourth group) OAB was not significant. This is the first study to show that bladder wall thickness is increased in diabetic women with and without OAB. Additionally, nondiabetic women with OAB had increased bladder wall thickness. Further studies may provide additional information for diabetic and nondiabetic women with OAB, in whom the etiopathogenesis of the disease may be similar.


Expression profiling identifies genes that continue to respond to insulin in adipocytes made insulin-resistant by treatment with tumor necrosis factor-alpha.
We have employed microarray technology using RNA from normal 3T3-L1 adipocytes and from 3T3-L1 adipocytes made insulin-resistant by treatment with tumor necrosis factor-alpha to identify a new class of insulin-responsive genes. These genes continued to respond normally to insulin even though the adipocytes themselves were metabolically insulin-resistant, i.e. they displayed a significantly decreased rate of insulin-stimulated glucose uptake. Approximately 12,000 genes/expressed sequence tags (ESTs) were screened. Of these, 40 genes/ESTs were identified that became insulin-resistant as expected (e.g. Socs-3, junB, and matrix metalloproteinase-11). However, 61 genes/ESTs continued to respond normally to insulin. Although some of these genes were previously shown to be regulated by insulin (e.g. Glut-1 and beta3-adrenergic receptor), other novel insulin-sensitive genes were also identified (e.g. Egr-1, epiregulin, Fra-1, and ABCA1). Real-time reverse transcription-PCR analysis confirmed the expression patterns of several of the differentially expressed genes. One gene that remained insulin-sensitive in the insulin-resistant adipocytes is the transcription factor Egr-1. Using an antisense strategy, we show that tissue factor and macrophage colony-stimulating factor, two cardiovascular risk factors, are downstream EGR-1 target genes in the adipocyte. Taken together, these data support the hypothesis that some signaling pathways remain insulin-sensitive in metabolically insulin-resistant adipocytes. These pathways may promote abnormal gene expression in hyperinsulinemic states like obesity and type II diabetes and thus may contribute to pathologies associated with these conditions.


Natural resistance to Marek's disease at hatching in chickens lacking maternal antibody, and relationship between this early resistance and resistance acquired with age.
Chickens of lines 6 and N, selected for resistance to Marek's disease (MD) and lacking maternal antibody, were resistant to MD mortality when exposed to pathogenic MD virus (MDV) at 1 day old. This finding indicated that natural resistance to MD is well developed at hatching in certain lines and is not dependent upon increasing age. Evidence obtained for lesion regression in early resistance and for possible genetic control of resistance acquired with age indicated that resistance at hatching and that acquired with age may be similar in character and may represent early and late manifestations of common natural resistance, possibly mediated through similar mechanisms.


Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect.
Duchenne muscular dystrophy (DMD) is characterized by the loss of a functional dystrophin protein; the muscles of DMD patients progressively degenerate as a result of mechanical stress during contractions, and the condition eventually leads to premature death. By means antisense oligonucleotides (AONs), it is possible to modulate pre-mRNA splicing eliminating mutated exons and restoring dystrophin open reading frame. To overcome the hurdles in using AONs for therapeutic interventions, we exerted engineered human DMD stem cells with a lentivirus, which permanently and efficiently delivered the cloned AONs. Here we describe for the first time the exosome-mediated release of AONs from engineered human DMD CD133+ stem cells allowing the rescue of murine dystrophin expression. Finally, upon release, AONs could be internalized by host cells suggesting a potential role of exosomes acting as vesicular carriers for DMD gene therapy.


Histamine induces KCNQ channel-dependent gamma oscillations in rat hippocampus via activation of the H1 receptor.
Histamine is an aminergic neurotransmitter, which regulates wakefulness, arousal and attention in the central nervous system. Histamine receptors have been the target of efforts to develop pro-cognitive drugs to treat disorders such as Alzheimer's disease and schizophrenia. Cognitive functions including attention are closely associated with gamma oscillations, a rhythmical electrical activity pattern in the 30-80 Hz range, which depends on the synchronized activity of excitatory pyramidal cells and inhibitory fast-spiking interneurons. We set out to explore whether histamine has a role in promoting gamma oscillations in the hippocampus. Using in-situ hybridization we demonstrate that histamine receptor subtypes 1, 2 and 3 are expressed in stratum pyramidale of area CA3 in rats. We show that both pyramidal cells and fast-spiking interneurons depolarize and increase action potential firing in response to histamine in vitro. The activation of histamine receptors generates dose-dependent, transient gamma oscillations in area CA3 of the hippocampus - the locus of the gamma rhythm generator. We also demonstrate that this histamine effect is independent of muscarinic receptors. Using specific antagonists we provide evidence that histamine gamma rhythmogenesis specifically depends on the H1 receptor. Histamine also depolarized both pyramidal cells and fast-spiking interneurons and increased membrane resistance in pyramidal cells. The increased membrane resistance is potentially mediated by the inhibition of potassium channels because application of the KCNQ channel opener ICA110381 abolished the oscillations. Taken together our data demonstrate a novel and physiological mechanism for generating gamma oscillations in hippocampus and suggest a role for KCNQ channels in this cognition-relevant brain activity.


2D Fe-doped NiO nanosheets with grain boundary defects for the advanced oxygen evolution reaction.
Two-dimensional (2D) nanomaterials with grain boundary defects are attractive to researchers in many fields, such as energy conversion and storage, sensing, catalysis and biological medicine. In this work, a nanostructure of 2D Fe-doped NiO nanosheets (NiFexO) with grain boundary defects was designed and applied in the electrocatalytic oxygen evolution reaction. This nanomaterial was synthesized through a solvothermal strategy followed by a thermally driven conversion process. In general, NiFexO electrocatalysts were fabricated with gradual morphological variation depending on the atomic ratio of Ni : Fe. It is surprising that the Fe content determines the electrocatalytic performance and the overpotential of water oxidation exhibits an inverted volcanic pattern. As expected, the as-prepared 2D NiFe0.1O nanosheets with grain boundary defects exhibit enhanced OER activity (274 mV@10 mA cm-2) compared with the oxide electrocatalyst reported in 1.0 M KOH owing to the advantages of abundant active sites. This work will shed light on the design and fabrication of novel-structured nanocatalysts.


Can Time Efficient Exercise Improve Cardiometabolic Risk Factors in Type 2 Diabetes? A Pilot Study.
Exercise is considered a cornerstone in the prevention and treatment of type 2 diabetes, but few individuals with type 2 diabetes exercise according to guidelines. We investigated the effect of two time efficient high intensity exercise interventions on exercise capacity, glycemic control and other cardiometabolic risk factors in patients with type 2 diabetes. Twenty-one individuals with type 2 diabetes were randomly assigned to low volume high intensity interval exercise (HIIE; 27 minutes/bout; 10x1-minute at 90 % of HRmax; n = 10) or extremely low volume sprint interval exercise (SIE; 10 minutes/bout; 2x20 seconds at maximum achievable intensity; n = 11) 3 days/week for 12 weeks. Aerobic exercise capacity (VO2peak), glycosylated hemoglobin (HbA1c), blood pressure and body composition were measured at baseline and post test. Both HIIE and SIE improved VO2peak (3.3 mL·min(-1)·kg(-1), 10.4 %), p < 0.01, and 1.4 mL·min(-1)·kg(-1) (4.6 %), p = 0.03, respectively). Only HIIE reduced body fat percentage (4.5 %, p = 0.04) and two minute heart rate recovery (11.0 bpm, p = 0.02). Neither HIIE nor SIE improved HbA1c. In conclusion, this study indicates that substantially lower exercise volumes than recommended in current guidelines can improve aerobic exercise capacity in individuals with type 2 diabetes. However, 12 weeks of time efficient high intensity exercise did not improve glycemic control, and interventions of longer duration should be investigated. Key pointsLow volume high-intensity interval exercise can improve peak oxygen uptake in previously sedentary individuals with type 2 diabetesThe weekly exercise volumes in the two intervention groups of 81 and 30 minutes respectively, is substantially lower than recommended in current exercise guidelines and could reduce the time-barrier associated with exercise among patients with type 2 diabetes.However, 12 weeks of structured, supervised low-volume exercise did not improve glycemic control, indicating a need for exercise volumes or longer intervention period.


Intraoperative onychoscopy and histopathological correlation of red lunula in nail lichen planus: a case series.
The lunula is the white half-moon-shaped area located at the base of the fingernails and toenails, and is the only visible part of nail matrix. Red lunula can present as a complete form (the whole lunula is red), incomplete form (only the proximal lunula is red) or mottled form. Red lunula has been associated with a number of dermatological and systemic conditions. It is one of the less common manifestations of nail lichen planus (LP). However, the pathogenesis of the red lunula is not yet clear. We present a series of six patients with nail LP presenting with red lunula, and describe the findings of intraoperative onychoscopy and histopathology in an attempt to understand the pathogenesis underlying the condition.


A natural language understanding system combining syntactic and semantic techniques.
A large proportion of the medical record currently available in computerized medical information systems is in the form of free text reports. While the accessibility of this source of data is improved through inclusion in the computerized record, it remains unavailable for automated decision support, medical research, and management of medical delivery systems. Natural language understanding systems (NLUS) designed to encode free text reports represent one approach to making this information available for these uses. Below we describe an experimental NLUS designed to parse the reports of chest radiographs and store the clinical data extracted in a medical data base.


Translation regulation of intron-containing genes in chloroplasts.
The paper provides a short description of the originally developed algorithm for searching of the conservative protein-RNA binding sites. The algorithm is applied to analyze chloroplast genes. The candidate protein-RNA binding sites were detected upstream of atpF, petB, clpP, psaA, psbA, and psbB genes in many chloroplasts of algae and plants. We suggest that some of these sites are involved in suppressing translation until splicing is completed.


Cr(VI) removal from wastewater using nano zero-valent iron and chromium-reducing bacteria.
Significant global efforts are currently underway to alleviate the presence of toxic metals in water bodies, aiming to encourage a sustainable environment. Nevertheless, the scientific community has yet to methodically inspect the performance and mechanisms underlying the interaction between nanomaterials and microorganisms in this context. Therefore, this study seeks to address this knowledge gap by developing a novel system that integrates nano zero-valent iron (nZVI) with chromium-reducing bacteria (CrRB) to efficiently remove Cr(VI) from water sources. The combined use of RBC600 and CrRB resulted in a Cr(VI) removal rate of 77.73%, displaying a substantial improvement of 17.61% compared to the use of CrRB alone. The efficacy of Cr(VI) elimination was observed to be affected by several factors within the system, such as the pH value, the quantity of nZVI added, the degree of CrRB inoculation, and the initial concentration of Cr(VI) at the onset of the experiment. When the pH was adjusted to 5, the complete removal of 200 mg/L Cr(VI) was achieved within 36 h. Increasing the dosage of nZVI to above 2 g/L resulted in the complete elimination of Cr(VI) from the solution within 72 h. This can be attributed to the availability of more reaction sites for the reduction of Cr(VI), facilitated by the higher nZVI dose. Additionally, the increased dose of nZVI allowed for the dissolution of more reactive Fe(II) ions. The characterization analysis, high-throughput sequencing, and fluorescence quantitative PCR results have established that CrRB and its extracellular polymer effectively reduce and complex Cr(VI). This process facilitated the dissolution of the passivated layer on the surface of nZVI, thus significantly enhancing the efficiency of nZVI in responding to Cr(VI). Additionally, the presence of nZVI created a favorable living environment for CrRB, resulting in increased richness and diversity within the CrRB community. These findings provide valuable preliminary insights into the mechanism underlying Cr(VI) elimination by the synergistic interaction between nZVI and CrRB. Therefore, this study establishes a solid theoretical foundations for the application of nano-bio synergy in the remediation of Cr(VI).


Diagnostic packages can be assigned accurately in emergency departments. A multi-centre cohort study.
In the Region of Southern Denmark, the emergency departments categorise patients based on presenting symptoms and a proposed diagnostic package (n = 40) within each category. The diagnostic packages describe relevant clinical information and standard laboratory and other investigations to be performed. Allocation to the right diagnostic package is assumed to be associated with a higher quality. The aim of this study was to describe to which degree the assigned symptom-based diagnostic packages are related to relevant discharge diagnoses. This was a descriptive cohort study. The analysis was based on data on assigned diagnostic package, patient discharge diagnosis, hospital, gender, age, time of admission and discharge, length of stay, diagnostic package assigned, discharge diagnosis and co-morbidity. An acceptable standard for what would be an appropriate primarily diagnostic package was developed using a modified Delphi method. A total of 16,543 patient contacts were identified. Women constituted 52.2% (n = 8,925) of the patients. The median age was 64 years and the median length of stay was one day. All diagnostic packages were represented. A total of 68% of the included patients had been assigned an acceptable diagnostic package (95% confidence interval: 67.2-68.7). We found an appropriate use of one of 30 diagnostic packages in more than 50% of the cases. We found that 68% of the included patients were assigned an acceptable diagnostic package and that about 80% of all acute pathways were covered by 14 diagnostic packages. The study was funded by Region of Southern Denmark. The study was registered with the Danish Data Protection Agency (No. 2008-58-0035). No further approval was required.


Booming dune instability.
Sand avalanches flowing down the leeward face of some desert dunes spontaneously produce a loud sound with a characteristic vibrato around a well-defined frequency, a phenomenon called the "song of dunes." Here, we show through theory that a homogenous granular surface flow is linearly unstable towards growing elastic waves when a localized shear band forms at the interface between the avalanche and the static part of the dune. We unravel the nature of the acoustic amplifying mechanism at the origin of this booming instability. The dispersion relation and the shape of the most unstable modes are computed and compared to field measurements.


Green light stimulates early stem elongation, antagonizing light-mediated growth inhibition.
During the transition from darkness to light, the rate of hypocotyl elongation is determined from the integration of light signals sensed through the phototropin, cryptochrome, and phytochrome signaling pathways. In all light conditions studied, from UV to far-red, early hypocotyl growth is rapidly and robustly suppressed within minutes of illumination in a manner dependent upon light quality and quantity. In this study, it is shown that green light (GL) irradiation leads to a rapid increase in the growth rate of etiolated Arabidopsis seedlings. GL-mediated growth promotion was detected in response to constant irradiation or a short, single pulse of light with a similar time course. The response has a threshold between 10(-1) and 10(0) micromol m(-2), is saturated before 10(2) micromol m(-2) and obeys reciprocity. Genetic analyses indicate that the cryptochrome or phototropin photoreceptors do not participate in the response. The major phytochrome receptors influence the normal amplitude and timing of the GL response, yet the GL response is normal in seedlings grown for hours under constant dim-red light. Therefore, phytochrome activation enhances, but is not required for, the GL response. Seedlings grown under green, red, and blue light together are longer than those grown under red and blue alone. These data indicate that a novel GL-activated light sensor promotes early stem elongation that antagonizes growth inhibition.


Therapist adherence/competence and treatment outcome: A meta-analytic review.
The authors conducted a meta-analytic review of adherence-outcome and competence-outcome findings, and examined plausible moderators of these relations. A computerized search of the PsycINFO database was conducted. In addition, the reference sections of all obtained studies were examined for any additional relevant articles or review chapters. The literature search identified 36 studies that met the inclusion criteria. R-type effect size estimates were derived from 32 adherence-outcome and 17 competence-outcome findings. Neither the mean weighted adherence-outcome (r = .02) nor competence-outcome (r = .07) effect size estimates were found to be significantly different from zero. Significant heterogeneity was observed across both the adherence-outcome and competence-outcome effect size estimates, suggesting that the individual studies were not all drawn from the same population. Moderator analyses revealed that larger competence-outcome effect size estimates were associated with studies that either targeted depression or did not control for the influence of the therapeutic alliance. One explanation for these results is that, among the treatment modalities represented in this review, therapist adherence and competence play little role in determining symptom change. However, given the significant heterogeneity observed across findings, mean effect sizes must be interpreted with caution. Factors that may account for the nonsignificant adherence-outcome and competence-outcome findings reported within many of the studies reviewed are addressed. Finally, the implication of these results and directions for future process research are discussed.


Transcriptional analysis identifies major pathways as response components to Sporisorium scitamineum stress in sugarcane.
Sugarcane smut, which is caused by Sporisorium scitamineum, is a severe fungal disease affecting sugarcane. However, the major pathways involved in the interaction between sugarcane and S. scitamineum remains unclear. In the present study, suppression subtractive hybridization (SSH) library construction, together with reverse northern blotting, was conducted on the most prevalent sugarcane genotype ROC22 challenged with S. scitamineum. After alignment and homologous expressed sequence tag (EST) assembly, a total of 155 differentially expressed unigenes were identified from SSH libraries. Totally, 26 of 155 differentially expressed unigenes were analyzed by qRT-PCR in sugarcane smut-resistant genotype YC05-179 and susceptible genotype ROC22. Genes encoded two unknown protein (Q1 and Q11), serine/threonine kinase (Q2), fiber protein (Q3), eukaryotic translation initiation factor 5A (Q23), and Sc14-3-3-like protein (Q24) were induced in sugarcane smut-resistant genotype YC05-179 but inhibited in susceptible genotype ROC22. Based on the differential expression data achieved from SSH libraries and qRT-PCR, we found that, serine/threonine kinases, Ca2+ sensors, mitogen-activated protein genes and some NBS-LRR genes may involve in the signal recognition and transduction of smut fungus infection in sugarcane. While in the plant hormone signaling pathways, the genes related to auxin, abscisic acid, salicylic acid and ethylene were more apparently in response to smut fungus invasion. The hypersensitive response, protein metabolism, polyamine synthesis, and cell wall formation may play an important role in sugarcane defense against smut fungus colonization. Additionally, the Sc14-3-3 might serve as a molecular modulator in sugarcane being immune to smut disease by interacting with proteins like ScGAPN (Q10), which have been further verified by BiFC assay. The findings of the present study could provide a general view about gene pathways involving in sugarcane defense against smut disease and facilitate a better understanding of the molecular mechanism underlying sugarcane-S. scitamineum interaction.


Genetic Modification of T Cells.
Gene transfer technology and its application to human gene therapy greatly expanded in the last decade. One area of investigation that appears particularly promising is the transfer of new genetic material into T cells for the potential treatment of cancer. Herein, we describe several core technologies that now yield high-efficiency gene transfer into primary human T cells. These gene transfer techniques include viral-based gene transfer methods based on modified Retroviridae and non-viral methods such as DNA-based transposons and direct transfer of mRNA by electroporation. Where specific examples are cited, we emphasize the transfer of chimeric antigen receptors (CARs) to T cells, which permits engineered T cells to recognize potential tumor antigens.


Amniotic membrane transplantation in ocular rosacea.
A 40-year-old patient with the diagnosis of acne rosacea presented with perforated peripheral corneal ulcer. Three applications of cyanoacrylate glue along with bandage contact lens failed to seal the perforation. Two months after the presentation, corneal perforation was successfully managed with amniotic membrane transplantation. The final best corrected visual acuity of 6/6 was achieved.


Effective Treatment of Simultaneous Distal Radius and Scaphoid Fractures.
Background There is an increasing trend for most surgeons to choose open reduction and internal fixation of simultaneous distal radius and scaphoid fractures; however, it is not clear if there is any evidence to support this. Case Description The purpose of this systematic review was to investigate the evidence for management of simultaneous distal radius and scaphoid fractures. Literature Review We performed searches of the EMBASE and MEDLINE databases (CRD42020167403). We included a total of 20 studies, involving 178 patients with 182 simultaneous fractures of the distal radius and scaphoid. The distal radius fractures were mostly intra-articular (112/182). The scaphoid fractures were mostly undisplaced (120/148) and at the scaphoid waist (152/178). All distal radius fractures went on to unite, and just 2 of 182 scaphoid fractures went on to nonunion. All included studies were retrospective case series, and therefore all were found to have a critical risk of bias due to confounding. The union rate for both the distal radius and scaphoid fractures is high with both operative and nonoperative treatments. Clinical Relevance Although there are no comparative studies to evaluate the most effective treatment, there is evidence to support operative management. Level of Evidence This is a Level IV, systematic review study.


Halo congenital nevus.
A 24-year-old woman noted a depigmented halo around a pigmented lesion that had been present on her abdomen since birth. The halo and the central pigmented zone showed no change during the following year. Light and electron microscopic studies disclosed an uninflamed nevus extending to the deep reticular dermis; peripherally, the basal layer of the epidermis was depigmented. These findings indicate that a halo may develop about an uninflamed nevus that does not involute, and that the nevus may show the specific histopathology of congenital nevus.


Medial transport of the fibula using the Ilizarov device for reconstruction of a massive defect of the tibia in two children.
We present two children with massive defects of the tibia and an associated active infection who were treated by medial transport of the fibula using the Ilizarov device. The first child had chronic discharging osteomyelitis which affected the whole tibial shaft. The second had sustained bilateral grade-IIIB open tibial fractures in a motor-car accident. The first child was followed up for three years and the second for two years. Both achieved solid union between the proximal and distal stumps of the tibia and the fibula, with hypertrophy of the fibula. The first child had a normal range of movement at the knee, ankle and foot but there was shortening of 1.5 cm. The second had persistent anterior angulation at the proximal tibiofibular junction and the ankle was stiff in equinus.


Recombinant H22(scFv) blocks CD64 and prevents the capture of anti-TNF monoclonal antibody. A potential strategy to enhance anti-TNF therapy.
Tumor necrosis factor (TNF) is a pro-inflammatory cytokine that plays a critical role in many inflammatory diseases. Soluble TNF can be neutralized by monoclonal antibodies (mAbs), and this is a widely-used therapeutic approach. However, some patients do not respond to anti-TNF therapy due to the increased expression of CD64 on monocytes and macrophages. A recent study has shown that CD64 captures anti-TNF mAbs via their Fcγ domain, which induces the transcription of pro-inflammatory genes. Specific blocking of CD64 could therefore be a promising strategy to improve the response to anti-TNF therapy. We used the CD64-specific antibody fragment H22(scFv) and tested its activity against the human CD64(+) cell line HL-60. When stimulated with interferon gamma (IFN-γ), these cells represent a pro-inflammatory phenotype of the monocyte/macrophage lineage. We found that H22(scFv) binds selectively to and blocks CD64, preventing the capture of anti-TNF mAb. Importantly, H22(scFv) itself does not induce CD64 activation. We also found that transmembrane TNF on HL-60 cells stimulated with IFN-γ also contributes to the capture of anti-TNF mAb, although via their Fab domain. In conclusion, the specific blocking of CD64 by H22(scFv) could be used a possible anti-inflammatory mechanism for potentiating the effect of anti-TNF antibodies.


[Hemolymphangioma of the orbit in a young girl: a clinical observation].
We report the clinical observation of an 8-year-old girl, admitted for a supermedial swelling of the eyelid associated with acute exophthalmia. The anatomical-pathological examination and the X-ray of the orbit provided the diagnosis of hemolymphangioma in a country where investigative resources are very limited (tomodensitometry, magnetic resonance imaging, and color Doppler). Most authors emphasize the advantages of MRI, which can show whether the ocular muscles in contact with the tumor are intact, rule out other causes of orbital tumors responsible for exophthalmia, and can help adjust treatment.


Recruitment of pregnant women to an exercise-intervention study.
We share here our experience of recruiting pregnant women into an exercise intervention study. Recruitment challenges were anticipated owing to the study design, which required four hospital visits for cardiovascular assessment, a long-term (nine-month) commitment, and adherence to a 20-week exercise programme. Fifty-three women were assigned to one of three groups (no-exercise, land exercise or water exercise) using a 2 × 2 × 2 flexible randomisation design. Seven hundred forty-four women were screened at an antenatal clinic, of whom 501 were eligible to participate in the study. One hundred forty-five women were subsequently approached: 46 (32%) of whom agreed to participate, 42 (29%) were interested but then declined and 57 (39%) declined outright. Our study design helped recruit pregnant women as it allowed them some choice of group membership. We also noted that the participant-researcher relationship is important in reducing attrition. Our experience provides indications of likely recruitment and attrition rates for future randomised controlled trials of this type.


Case Report: A Novel Heterozygous Mutation of CD2AP in a Chinese Family With Proteinuria Leads to Focal Segmental Glomerulosclerosis.
Idiopathic focal segmental glomerulosclerosis (FSGS) is a relatively frequent kidney disorder that manifest clinically as proteinuria and progressive loss of renal function. Genetic factors play a dominant role in the occurrence of FSGS. CD2-associated protein (CD2AP) is an adapter molecule and is essential for the slit-diaphragm assembly and function. Mutations in the CD2AP gene can contribute to FSGS development. Here, we describe a Chinese family of four generations with unexplained proteinuria. The proband, a 12-year-old boy, was diagnosed as FSGS. Whole-exome sequencing (WES) revealed an unknown frameshift insertion mutation (p.K579Efs*7) of CD2AP gene that leads to a truncation of CD2AP protein. Bioinformatics strategies predicted that the novel mutation was pathogenic. The mutation was absent in either healthy family members or our 200 healthy controls. In summary, we used WES to explore the genetic lesion of FSGS patients and identified a novel mutation in CD2AP gene. This work broadens the mutation spectrum of CD2AP gene and provides data for genetic counseling to additional FSGS patients.


[Long-term efficacy and safety of electroacupuncture on improving MMSE in patients with Alzheimer's disease].
To observe the efficacy and safety of electroacupuncture (EA) on improving mini-mental state examination (MMSE) in patients with Alzheimer's disease (AD), and to evaluate the efficacy during follow-up visit. Forty patients were randomly divided into a treatment group and a control group, 20 patients in each one (3 patients dropped off in the treatment group and 4 patients in the control group). The patients in the treatment group were treated with acupuncture at Baihui (GV 20), Fengfu (GV 16), Shenting (GV 24), Taiyang (EX-HN 5), Shangyintang (Extra 3) and Dazhong (KI 14); besides, EA was applied at Taiyang (EX-HN 5), Baihui (GV 20) and Shenting (GV 24) with dilatational wave, 10 Hz/50 Hz in frequency, 0.5 to 5.0 mA in intensity, once every two days, three treatments per week. The patients in the control group were treated with oral administration of donepezil hydrochloride tablets, once a day, taken before sleep. The treatment was given for 12 weeks in the two groups. The MMSE was evaluated before treatment, 12 weeks±3 days into treatment, and 24 weeks±7 days after treatment, respectively. The difference of total score of MMSE before and 12 weeks±3 days into treatment was not significant between the two groups (P>0.05); the total score of MMSE after treatment was higher than that before treatment (both P<0.05); compared before treatment, the short-term memory score was increased in the treatment group (P<0.05), and the increasing range was superior to that in the control group (P<0.05). Compared before treatment, the total score of MMSE in the two groups were reduced 24 weeks ±7 days after treatment (both P<0.05), and the reduction in the treatment group was less than that in the control group (P<0.05); the differences of short-term memory score before and after treatment was significant between the two groups (P<0.05). No adverse reaction occurred in the two groups. The effect of EA on improving MMSE in patients with AD is similar to donepezil supported by evidence-based medicine. The effect of EA may have a certain continuous effect, and may have advantages in instantaneous memory. In addition, the EA is safe.


Potassium acetate by fermentation with Clostridium thermoaceticum.
Potassium acetate is currently made by reacting petroleum-based acetic acid with potassium hydroxide. An alternate process, anaerobic fermentation of dextrose with Clostridium thermoaceticum, could be used and could possibly be cheaper. Growth characteristics and productivity of the fermentation were optimized to maximize acetate concentration in the broth. The effects of pH, type, and concentrations of nutrients and reducing agents were also evaluated. Corn steep liquor and stillage from an ethanol plant were effective and much cheaper substitutes for yeast extract. Preconcentrating the cells by ultrafiltration improved productivity, resulting in an acetic acid concentration of 53.6 g/L in 50 h at pH 6.5 using corn steep liquor. Sodium sulfide could be substituted for cysteine as the reducing agent with yields greater than 0.9 g acetic acid/g glucose.


Cellular prion protein (PrPC) in the development of Merlin-deficient tumours.
Loss of function mutations in the neurofibromatosis Type 2 (NF2) gene, coding for a tumour suppressor, Merlin, cause multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas. These tumours may occur sporadically or as part of the hereditary condition neurofibromatosis Type 2 (NF2). Current treatment is confined to (radio) surgery and no targeted drug therapies exist. NF2 mutations and/or Merlin inactivation are also seen in other cancers including some mesothelioma, breast cancer, colorectal carcinoma, melanoma and glioblastoma. To study the relationship between Merlin deficiency and tumourigenesis, we have developed an in vitro model comprising human primary schwannoma cells, the most common Merlin-deficient tumour and the hallmark for NF2. Using this model, we show increased expression of cellular prion protein (PrPC) in schwannoma cells and tissues. In addition, a strong overexpression of PrPC is observed in human Merlin-deficient mesothelioma cell line TRA and in human Merlin-deficient meningiomas. PrPC contributes to increased proliferation, cell-matrix adhesion and survival in schwannoma cells acting via 37/67 kDa non-integrin laminin receptor (LR/37/67 kDa) and downstream ERK1/2, PI3K/AKT and FAK signalling pathways. PrPC protein is also strongly released from schwannoma cells via exosomes and as a free peptide suggesting that it may act in an autocrine and/or paracrine manner. We suggest that PrPC and its interactor, LR/37/67 kDa, could be potential therapeutic targets for schwannomas and other Merlin-deficient tumours.


Thermotherapy-induced reduction in glioma invasiveness is mediated by tumor necrosis factor-alpha.
Thermotherapy has been proven to be effective for the treatment of various tumors, including glioma. We determined whether tumor necrosis factor-alpha (TNF-α) is involved in the regulation of the biological processes of glioma development. Reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry were used to investigate the levels of TNF-α mRNA and heat shock factor-1 (HSF1) protein, respectively, in glioma cells. Radioimmunoassay was used to dynamically monitor the contents of TNF-α in the nutrient fluid of C6 cells after thermotherapy treatment. Crystal violet staining was used to determine glioma invasiveness. The most obvious increases in HSF1 protein and TNF-α mRNA in C6 cells were observed at 30 and 60 min after thermotherapy, respectively. In addition, the radioactivity of TNF-α in the culture fluid of the C6 cells reached a peak after 120 min of thermotherapy. In addition, glioma invasiveness decreased and the concentration of TNF-α reached a maximum after 120 min of thermotherapy. Our results show that the decrease in thermotherapy-mediated glioma invasiveness is due to the accelerated release of TNF-α, which could promote the release of HSF1 from neurospongioma cells.


Conductance of graphene flakes contacted at their corners.
Linear conductance of junctions formed by graphene flakes with the order of the nanometer-thick electrodes attached at the corners of the flakes is studied. The explored structures have sizes up to 20,000 atoms and the conductance is studied as a function of applied gate voltage varied around the Fermi level. The finding, obtained computationally, is that junctions formed by armchair-edge flakes with the electrodes connected at the acute-angle corners block the electron transport while only junctions with such electrodes at the obtuse-angle corners tend to provide the high electrical conductance typical for metallic GNRs. The finding in the case of zig-zag edges is similar with the exception of a relatively narrow gate voltage interval in which each studied junction is highly conductive as mediated by the edge states. The contrast between the conductive and insulating setups is typically several orders of magnitude in terms of ratio of their conductances. The main results of the paper also remain to a large extent valid in the presence of edge disorder.


[Medical record--insufficient source of information about patients treated for stroke].
The complete hospital notes made by physicians, nurses and paramedics for 123 patients diagnosed with stroke were studied in order to assess whether the information was sufficient for transfer to a new caregiver. A checklist was designed to include information of importance for the planning of subsequent medical care, rehabilitation and prevention. The questions covered the following areas: social situation, next of kin, current status and physical condition, risk factors, information to the patient, contact with social services, medication and planning. The results revealed missing as well as duplicated information. Apart from the notes written by physicians, additional information was not found to be of use, with the exception of information on next of kin, current status and physical condition.


A revised Fasanella-Servat ptosis operation.
The Fasanella-Servat operation for ptosis has had several modifications of suture placement. The present method utilized 5-0 nylon which traverses the cut edges as a running mattress suture. The ends of the suture are fixed on the skin surface with rubber bolsters. The suture is removed in 10 days. The advantages are: (1) no suture knots on the corneal surface; (2) ease of placement; (3) minimal tissue reaction; (4) the suture is removed; and (5) ease of suture removal.


Evidence supporting broader access to safe legal abortion.
Unsafe abortion continues to be a major cause of maternal death; it accounts for 14.5% of all maternal deaths globally and almost all of these deaths occur in countries with restrictive abortion laws. A strong body of accumulated evidence shows that the simple means to drastically reduce unsafe abortion-related maternal deaths and morbidity is to make abortion legal and institutional termination of pregnancy broadly accessible. Despite this evidence, abortion is denied even when the legal condition for abortion is met. The present article aims to contribute to a better understanding that one can be in favor of greater access to safe abortion services, while at the same time not be "in favor of abortion," by reviewing the evidence that indicates that criminalization of abortion only increases mortality and morbidity without decreasing the incidence of induced abortion, and that decriminalization rapidly reduces abortion-related mortality and does not increase abortion rates.


Characterization of Cg10062 from Corynebacterium glutamicum: implications for the evolution of cis-3-chloroacrylic acid dehalogenase activity in the tautomerase superfamily.
A 149-amino acid protein designated Cg10062 is encoded by a gene from Corynebacterium glutamicum. The physiological function of Cg10062 is unknown, and the gene encoding this protein has no obvious genomic context. Sequence analysis links Cg10062 to the cis-3-chloroacrylic acid dehalogenase ( cis-CaaD) family, one of the five known families of the tautomerase superfamily. The characterized tautomerase superfamily members have two distinctive characteristics: a beta-alpha-beta structure motif and a catalytic amino-terminal proline. Pro-1 is present in the Cg10062 amino acid sequence along with His-28, Arg-70, Arg-73, Tyr-103, and Glu-114, all of which have been implicated as critical residues for cis-CaaD activity. The gene for Cg10062 has been cloned and the protein overproduced, purified, and subjected to kinetic and mechanistic characterization. Like cis-CaaD, Cg10062 functions as a hydratase: it converts 2-oxo-3-pentynoate to acetopyruvate and processes 3-bromopropiolate to a species that inactivates the enzyme by acylation of Pro-1. Kinetic and (1)H NMR spectroscopic studies also show that Cg10062 processes both isomers of 3-chloroacrylic acid at low levels with a clear preference for the cis isomer. Pro-1 is critical for the dehalogenase and hydratase activities because the P1A mutant no longer catalyzes either reaction. The presence of the six key catalytic residues and the hydratase activity coupled with the absence of an efficient cis-CaaD activity and the lack of isomer specificity implicate factors beyond this core set of residues in cis-CaaD catalysis and specificity. This work sets the stage for in-depth mechanistic and structural studies of Cg10062, which could identify the additional features necessary for a fully active and highly specific cis-CaaD. Such results will also shed light on how cis-CaaD emerged in the tautomerase superfamily because Cg10062 could be characteristic of an intermediate along the evolutionary pathway for this dehalogenase.


Piercing and tatooing in high school students of Veneto region: prevalence and perception of infectious releated risk.
Body piercing (P) and tattoo (T) is a growing social phenomenon over recent years. Nowadays in Italy little is known about the prevalence, the attitude, the medical and social consequences of these activities. The purpose of this study is to examine the prevalence distribution and the attitude towards P and T and the perception of the risk for infections, in a sample of high school students living in the four Provinces of the Veneto Region (Italy). An anonymous, self administrate multiple-choice questionnaire about piercing and tattoo practices was distributed during the 2009-2010 academic year to a sample of randomly extracted grades to obtain information about sociodemographic characteristics, family educational level, personal attitude, prevalence and perception of the importance of the sanitary, technical and artistic competence of the operator. The correctly compiled questionnaires were 2712 (95.4%). Males and females were respectively 46.2% and 53.8% (mean age 17 +/- 1.7 years). The 20.2% and the 6.4% of all the students had already experienced respectively P and T and resulted "very interested" the 46.7% to P and the 57.4% to T. Esthetical motivations are the main ones referred to use body art. The most part of interviewed subjects (81.6%) think that it is possible to have an infection, but only about 50% of students reported to know specific information about transmission of HIV, Viral Hepatitis and skin infections. The parents' educational levels do not influence the perception of the risk of infection. The majority of interviewed subjects (88.0%) prefers to undergo body art practices in a qualified center. Only the 30% of students recur to a medical help to solve problem of infection. The piercing and tattoo prevalence rate in our study (P: 20.2% and T:6.4%) resulted similar to other Italian ones (range reported: P: 20.3-35.1%, T: 4.8-8.6%), showing an increasing trend with age. Since a high rate of interviewed students referred a substantial ignorance about the risk of transmission of body art related infectious diseases, it is suitable to promote as soon as possible among the youth educational interventions and counseling.


Suppressing the X-Y coupling effect in compact electron storage rings.
The x-y coupling effect, especially the tilt of the beam profiles, in the Super-ALIS compact electron storage ring has been effectively eliminated. The main feature of this method is the suppression of the most harmful Fourier components of the skew-quadrupole perturbation by using just one thin skew-quadrupole magnet. Therefore, the method should be simple and effective for coupling suppression in compact storage rings that have little space for correction instruments.


Novel Approach to Reduction of an Incarcerated Uterus.
Incarceration of the pregnant uterus is a rare condition and can lead to bladder obstruction, renal failure, or uterine rupture. We present a novel, noninvasive technique to reduce an incarcerated uterus. With conscious sedation, the patient was placed in all-fours position. The physician's hands were placed on the patient's abdomen and pressure applied until the uterine fundus was palpated. Gentle, steady fundal pressure on both sides was directed toward the maternal chest (bilateral mediocephalad pressure) elevating the uterus out of the pelvis. This approach successfully reduced the gravid incarcerated uterus and was well tolerated by the patient and fetus. The author's experience with this method is limited to this case. Prior experience with reduction of the incarcerated uterus has been with methods previously described in the literature. In conjunction with conscious sedation and all-fours positioning, transabdominal manipulation of the uterine fundus with bilateral mediocephalad pressure may facilitate reduction of an incarcerated uterus. This method may obviate the need for more invasive procedures.


A common source foodborne outbreak of cholera in Singapore.
An epidemiological investigation of an outbreak of Vibrio cholerae 01, biotype El Tor, serotype Ogawa, phage type 1, confined to a group of foreign construction workers in Singapore is described. A total of 22 workers were confirmed to have cholera and another 15 had asymptomatic Vibrio cholerae 01 infection between 3 November and 11 November 1982. The source of infection was traced to contaminated seafood prepared at the construction site canteen where two food handlers were found to be infected with V. cholerae 01 (one symptomatic and the other asymptomatic). The incubation period of cholera in this outbreak ranged from 4 to 203 hours with a median of 38 hours. Only two workers had moderate to severe dehydration and required intravenous therapy. Early recognition of the outbreak and prompt implementation of control measures prevented the outbreak from spreading to other parts of Singapore.


Anxiolytic-like effect of 5-HT(2) ligands and benzodiazepines co-administration: comparison of two animal models of anxiety (the four-plate test and the elevated plus maze).
Animal models of anxiety remain a useful tool for evaluating the anxiolytic-like effect of new treatments. Even though many tests are similarly based on exploration tasks, using more than one animal model is all the more recommended since there are qualitative differences between such tests. Furthermore, although many tests are excellent tool for detecting benzodiazepines/GABA compounds, inconsistent results have been reported for 5-HT ligands. Here, two animal models have been chosen, the elevated plus maze (EPM) based on the natural aversion of rodents for open spaces and the four-plates test (FPT) a models involving the animal's conditioned response to stressful events. In a recent study, we have demonstrated that the 5-HT(2A/2C) agonist DOI and the 5-HT(2B) agonist BW 723C86 were shown to produce an anxiolytic-like effect in both tests. This study aimed to evaluate a putative interaction between benzodiazepine and 5-HT(2) ligands in the FPT and the EPM. Indeed, close distribution of GABA(A) and 5-HT(2) receptors was found in brain structures leading to functional interrelation. In the FPT, sub-active doses of alprazolam and diazepam were strongly potentiated by DOI. BW 723C86, also potentiated the anxiolytic-like effect of the two benzodiazepines with a weaker effect. In the same way, DOI and benzodiazepines administration induced an increase in the anxiolytic-like parameters in the EPM with a strongest effect observed with alprazolam. Regardless of anxiety models used in this study, 5-HT(2A) ligands exerted facilitatory influence upon GABAergic system. Therefore, the FPT and the EPM might implicate the same kind of anxiety.


[Factorial structure of mutural cognition between parents and child].
Tsujioka's Children's Report of Parental Behavior Inventory (EICA) and its modification adapted to the parents were administered to the high school students (75 boys and 63 girls) and their parents. The results were analyzed by means of the Cliff's Procrustian factor analysis. In the first-order factor analysis, very congruent eight primary factors were obtained in two kinds of samples (boy-parents sample and girl-parents sample). These factors were 1. Acceptance in mother, 2. Autonomy in parents, 3. Identification in child, 4. Acceptance in father, 5. Autonomy in child, 6. Control in father, 7. Control in mother, and 8. Emotional support in child. Sex differences in children were examined in terms of the means and the standard deviations.


Effectiveness of aluminum hydroxide timing administration in relation to meals in controlling hyperphosphatemia in dialysis patients.
Phosphate binder compounds contribute to the control of hyperphosphatemia in hemodialysis (HD) patients. However, the most effective schedule of administration of phosphate binders in relation to meals is not well documented. We examined the effectiveness of aluminum hydroxide intake as the sole phosphate binder in relation to meals. Eighty-five patients on regular HD (45 male, 40 female), age 21-72 years, with a duration of 6-216 months HD participated in the study. In all patients, phosphate binders were discontinued for a one month period. Thereafter, and according to the protocol, all patients were advised to take aluminum hydroxide [Al(OH)3 ] 30 min before, during and 30 min after meals for 3 periods of one month each, in a random order. One month washout period preceded the periods of Al(OH)3 ingestion. When Al(OH)3 was administered 30 min prior to the meals, serum phosphate decreased by 7.0% (0.59 mg/dL), while when administrated with or 30 min after meals, it decreased statistically significantly by 28.5% (2.08 mg/dL), and 16% (1.29 mg/dL) respectively. Our results suggest that the efficacy of Al(OH)3 to bind phosphate salts and thus to prevent the hyperphosphatemia in HD patients is higher when this drug is taken with meals.


Cortical blindness following bacterial meningitis: a case report with reassessment of prognosis and aetiology.
A case of cortical blindness is presented which developed during H. influenzae type B meningitis. Cortical blindness may appear late in the course of bacterial meningitis, during a period of clinical improvement, and recovery can be expected in 50 per cent of cases. In contrast, when the cause is ischaemic the onset of blindness is immediate and usually recovery is complete. Radiological evidence is presented for the pathological process in meningitis.


Educ@dom: comparative study of the telemonitoring of patients with type 2 diabetes versus standard monitoring-study protocol for a randomized controlled study.
The global prevalence of type 2 diabetes is considerable. To avoid or delay its chronic complications, patients with type 2 diabetes should improve blood glucose management by adapting their life style. This involves changing the way in which diabetes is controlled. We believe that, thanks to technological innovations in connected health-monitoring devices, the telemonitoring of type 2 diabetes patients using therapeutic educational tools is likely to help them adapt their treatment and lifestyle habits, and therefore improve blood glucose management. This is a multicenter, randomized, controlled, prospective study. The primary objective is to compare the efficacy of telemonitoring to standard monitoring in terms of changes in glycated hemoglobin levels (HbA1c) after a 1 year follow-up period. The secondary objectives are clinical (changes in knowledge, physical activity, weight, etc.) and medical-economic. 282 patients are required (141 patients in each group) to satisfy the primary objective. For patients in the intervention group, the device will be given to them for 1 year and then withdrawn during the second year of follow-up. The anticipated benefits of this research are an improvement in blood glucose management in patients with type 2 diabetes by improving their lifestyle whilst rationalizing recourse to consultations in order to reduce the incidence of complications and cost in the long term. If the results of this study show that management of type 2 diabetes by tele monitoring is clinically effective and economical, this device could then be made available to a larger diabetic patient cohort.


Effects of gross motor function and manual function levels on performance-based ADL motor skills of children with spastic cerebral palsy.
[Purpose] The purpose of this study was to determine effects of Gross Motor Function Classification System and Manual Ability Classification System levels on performance-based motor skills of children with spastic cerebral palsy. [Subjects and Methods] Twenty-three children with cerebral palsy were included. The Assessment of Motor and Process Skills was used to evaluate performance-based motor skills in daily life. Gross motor function was assessed using Gross Motor Function Classification Systems, and manual function was measured using the Manual Ability Classification System. [Results] Motor skills in daily activities were significantly different on Gross Motor Function Classification System level and Manual Ability Classification System level. According to the results of multiple regression analysis, children categorized as Gross Motor Function Classification System level III scored lower in terms of performance based motor skills than Gross Motor Function Classification System level I children. Also, when analyzed with respect to Manual Ability Classification System level, level II was lower than level I, and level III was lower than level II in terms of performance based motor skills. [Conclusion] The results of this study indicate that performance-based motor skills differ among children categorized based on Gross Motor Function Classification System and Manual Ability Classification System levels of cerebral palsy.


Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease.
Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed.


[Modified technique for correction of the orbital hypertelorism].
To explore the possibility of para-orbital soft-tissue expansion, before orbital osteotomy and medial translocation procedures with a combined intracranial-extracranial approach. Tissue expansion in the region of the zygomatic and temporal has been undergone for 3 weeks before the traditional intracranial-extracranial approach for orbital osteotomy and medial translocation in two patients. The healing between the orbital bone was studied with measurement of interorbital distance and three-dimensional CT. The inter-orbital distance of the two patients decreased from 4.4 cm and 3.2 cm to 2.0 cm and 1.4 cm. The intercanthal distance decreased from 6.7 cm and 4.8 cm to 5.0 cm and 3.8 cm. The para-orbital soft-tissue expansion technique may be an effective technique for the stability of the corrected interorbital distance in orbital hypertelorism.


Repeatable Photodynamic Therapy with Triggered Signaling Pathways of Fibroblast Cell Proliferation and Differentiation To Promote Bacteria-Accompanied Wound Healing.
Despite the development of advanced antibacterial materials, bacterial infection is still a serious problem for wound healing because it usually induces severe complications and cannot be eradicated completely. Most current materials cannot simultaneously provide antibacterial activity, reusability, and biocompatibility as well as participate in stimulating cell behaviors to promote bacteria-accompanied wound healing. This work fabricated a hybrid hydrogel embedded with two-dimensional (2D) few-layer black phosphorus nanosheets (BPs) via simple electrostatic interaction. Within 10 min, 98.90% Escherichia coli and 99.51% Staphylococcus aureus can be killed rapidly by this hybrid, due to its powerful ability to produce singlet oxygen (1O2) under simulated visible light. In addition, this hydrogel also shows a high repeatability; that is, the antibacterial efficacy can still reach up to 95.6 and 94.58% against E. coli and S. aureus, respectively, even after challenging bacteria up to four times repeatedly. In vitro and in vivo results reveal that BPs in this hybrid hydrogel can promote the formation of the fibrinogen at the early stages during the tissue reconstruction process for accelerated incrustation. In addition, BPs can also trigger phosphoinositide 3-kinase (PI3K), phosphorylation of protein kinase B (Akt), and extracellular signal-regulated kinase (ERK1/2) signaling pathways for enhanced cellular proliferation and differentiation. Moreover, the hydrogel causes no appreciable abnormalities or damage to major organs (heart, liver, spleen, lung, and kidney) in rats during the wound healing process. Therefore, this BP-based hydrogel will have great potential as a safe multimodal therapeutic system for active wound healing and sterilization.


"If sex hurts, am I still a woman?" the subjective experience of vulvodynia in hetero-sexual women.
Vulvodynia has recently been recognized as a significant health problem among women, with a considerable proportion experiencing psychological distress and sexual dysfunction for many years. This study used a material-discursive framework and a qualitative methodology to investigate women's subjective experience of vulvodynia within the context of a hetero-sexual relationship, and their negotiation of coitus, commonly associated with vulvar pain. Seven women, who had experienced vulvodynia between 2 and 10 years, took part in in-depth interviews. Thematic decomposition drawing on a Foucauldian framework for interpretation identified that six of the seven women took up subject positions of "inadequate woman" and "inadequate partner," positioning themselves as failures for experiencing pain during coitus, which they interpreted as affecting their ability to satisfy their partners sexually, resulting in feelings of shame, guilt, and a decreased desire for sexual contact. This was interpreted in relation to dominant discourses of femininity and hetero-sexuality, which conflate a woman's sexuality with her need to be romantically attached to a man, position men as having a driven need for sex, and uphold coitus as the organizing feature of hetero-sex. Only one woman positioned herself as an "adequate woman/partner," associated with having renegotiated the coital imperative and the male sex drive discourse within her relationship. These positions, along with women's agentic attempts to resist them, were discussed in relation to their impact on hetero-sexual women's negotiation of vulvodynia. Implications for future research and vulvodynia treatment regimes are also raised.


Induction of thaumatin-like proteins (TLPs) in Rhizoctonia solani-infected rice and characterization of two new cDNA clones.
Thaumatin-like proteins (TLPs) were shown to be induced in rice plants (cv. IR58) that were infected with the sheath blight fungus, Rhizoctonia solani. Western blot analysis revealed the presence of two TLPs with sizes of 25 and 24 kDa which are different from a previously reported TLP with a size of 15.6 kDa from rice plants infiltrated with the non-pathogenic bacterium, Pseudomonas syringae pv. syringae. By probing a cDNA expression library prepared from RNA isolated from R. solani-infected rice plants with a TLP antibody, several putative TLP cDNA clones were isolated and sequenced. The cDNA clones appeared to be derived from two different genes which shared only 77% sequence identity with each other and a lower percentage of sequence identity with the previously reported TLP cDNA clone. Southern blot analysis with the two TLP cDNAs revealed different rice genomic DNA fragments. Northern blot analysis also confirmed that a 1.1-kb RNA detectable by the TLP cDNA inserts was induced by fungal infection. Thus rice TLPs are encoded by a family of at least three genes which are differentially expressed in responses to bacterial or fungal pathogens.


Autophagy: An Emerging Target for Developing Effective Analgesics.
Inadequate treatment of acute and chronic pain causes depression, anxiety, sleep disturbances, and increased mortality. Abuse and overdose of opioids and the side effects associated with chronic use of NSAID illustrate the need for development of safer and effective pain medication. Working toward this end, an in silico tool based on an emergent intelligence analytical platform that examines interactions between protein networks was used to identify molecular mechanisms involved in regulating the body's response to painful stimuli and drug treatments. Examining interactions between protein networks associated with the expression of over 20 different pain types suggests that the regulation of autophagy plays a central role in modulation of pain symptoms (see Materials and Methods). Using the topology of this regulatory scheme as an in silico screening tool, we identified that combinations of functions targeted by cannabidiol, myo-inositol, and fish oils with varying ratios of eicosapentaenoic and docosahexaenoic acids are projected to produce superior analgesia. For validating this prediction, we administered combinations of cannabidiol, myo-inositol, and fish oils to rats that received formalin injections in hind paws, prior to substance administration, and showed that analgesic effects produced by these combinations were comparable or superior to known NSAID analgesics, which suggests that these combinations have potential in treatment of pain.


Multiple forms of H4 histone mRNA in human cells.
Two species of H4 histone mRNA were isolated from the polysomes of S phase HeLa S3 cells. Electrophoresis under denaturing and nondenaturing conditions indicates that the two H4 mRNAs differ in size. Both mRNAs translate H4 histones in vitro, lack poly(A) at their 3' termini, and are capped at their 5' termini. Polyacrylamide gel electrophoresis and tryptic peptide analysis suggest that the polypeptides synthesized by the two mRNAs are indistinguishable.


Astaxanthin Attenuates Hypertensive Vascular Remodeling by Protecting Vascular Smooth Muscle Cells from Oxidative Stress-Induced Mitochondrial Dysfunction.
Oxidative stress aggravates mitochondrial injuries and accelerates the proliferation of vascular smooth muscle cells (VSMCs), which are important mechanisms contributing to vascular remodeling in hypertension. We put forward the hypothesis that Astaxanthin (ATX), known to possess strong features of antioxidant, could attenuate vascular remodeling by inhibiting VSMC proliferation and improving mitochondrial function. The potential effects of ATX were tested on spontaneously hypertensive rats (SHRs) and cultured VSMCs that injured by angiotensin II (Ang II). The results showed that ATX lowered blood pressure, reduced aortic wall thickness and fibrosis, and decreased the level of reactive oxygen species (ROS) and H2O2 in tunica media. Moreover, ATX decreased the expression of proliferating cell nuclear antigen (PCNA) and ki67 in aortic VSMCs. In vitro, ATX mitigated VSMC proliferation and migration, decreased the level of cellular ROS, and balanced the activities of ROS-related enzymes including NADPH oxidase, xanthine oxidase, and superoxide dismutase (SOD). Besides, ATX mitigated Ca2+ overload, the overproduction of mitochondrial ROS (mtROS), mitochondrial dysfunction, mitochondrial fission, and Drp1 phosphorylation at Ser616. In addition, ATX enhanced mitophagy and mitochondrial biosynthesis by increasing the expression of PINK, parkin, mtDNA, mitochondrial transcription factor A (Tfam), and PGC-1α. The present study indicated that ATX could efficiently treat vascular remodeling through restraining VSMC proliferation and restoring mitochondrial function. Inhibiting mitochondrial fission by decreasing the phosphorylation of Drp1 and stimulating mitochondrial autophagy and biosynthesis via increasing the expression of PINK, parkin, Tfam, and PGC-1α may be part of its underlying mechanisms.


Direct 17O dynamic nuclear polarization of single-site heterogeneous catalysts.
We utilize direct 17O DNP for the characterization of non-protonated oxygens in heterogeneous catalysts. The optimal sample preparation and population transfer approach for 17O direct DNP experiments performed on silica surfaces is determined and applied to the characterization of Zr- and Y-based mesoporous silica-supported single-site catalysts.


Novel approaches for quantifying protein biomarkers in gliomas: benefits and pitfalls.
The therapeutic paradigm of gliomas is changing from a general approach towards an individualized and targeted approach. Accordingly, the search for prognostic and predictive biomarkers, as well as the demand for quantitative, feasible and robust methods for biomarker analysis increases. We find that software classifiers can identify and quantify the expression of a given biomarker within different subcellular compartments and that such classifiers can exclude frequently occurring nontumor cells, thereby avoiding potential bias. The use of a quantitative approach provides a continuous measurement of the expression, allowing establishment of new cut-points and identification of patients with specific prognoses. However, some pitfalls must be noted. This article focuses on benefits and pitfalls of novel approaches for quantifying protein biomarkers in gliomas.


Mechanisms underlying the control of responses to predator odours in aquatic prey.
In aquatic systems, chemical cues are a major source of information through which animals are able to assess the current state of their environment to gain information about local predation risk. Prey use chemicals released by predators (including cues from a predator's diet) and other prey (such as alarm cues and disturbance cues) to mediate a range of behavioural, morphological and life-history antipredator defences. Despite the wealth of knowledge on the ecology of antipredator defences, we know surprisingly little about the physiological mechanisms that control the expression of these defensive traits. Here, we summarise the current literature on the mechanisms known to specifically mediate responses to predator odours, including dietary cues. Interestingly, these studies suggest that independent pathways may control predator-specific responses, highlighting the need for greater focus on predator-derived cues when looking at the mechanistic control of responses. Thus, we urge researchers to tease apart the effects of predator-specific cues (i.e. chemicals representing a predator's identity) from those of diet-mediated cues (i.e. chemicals released from a predator's diet), which are known to mediate different ecological endpoints. Finally, we suggest some key areas of research that would greatly benefit from a more mechanistic approach.