Treatment of obstructive sleep apnea with continuous nasal airflow delivered through nasal prongs.
We describe a new device for treating obstructive sleep apnea (OSA) which is similar to nasal CPAP, but less cumbersome. The device consists of a 7 mm diameter flexible tube terminating at one end in nasal prongs covered with foam cylinders. The foam cylinders are compressed, inserted into the nostrils and released, forming a tight seal. The other end of the catheter is attached to a compressor delivering between 7 and 15 L/min of air. We studied four men and two women with OSA, the first night without treatment and the following night with continuous nasal airflow. A desaturation index was calculated by multiplying the average number of desaturation episodes per hour of sleep times the average maximum desaturation per episode. With continuous nasal airflow there was a significant decrease in all parameters (p less than .025). We conclude that continuous nasal airflow decreased oxyhemoglobin desaturation in patients with OSA and may be useful in patients with mild-to-moderate OSA and in patients who do not tolerate nasal CPAP.


Photodamage to intact erythrocyte membranes at high laser intensities: methods of assay and suppression.
A simple hemolytic assay of the photodamage suffered by individual intact erythrocytes upon localized exposure to high laser intensities such as those encountered in fluorescence photobleaching recovery (FPR) experiments has been characterized. At incident beam powers over 100,000 W/cm2 at 514 or 568 nm, hemoglobin absorption induces thermal-shock lysis. Below the thermal-shock threshold, other intracellular chromophores appear to catalyze membrane contraction and lysis with linear dose kinetics in anaerobic preparations. A variety of chemical agents that inhibit photodamage to red cell ghost membranes at low intensities (less than 450 W/cm2) do not benefit intact cells at realistic FPR bleaching doses of 10,000 to 1,000,000 W/cm2. However, we find that sample deoxygenation dramatically photostabilizes erythrocytes, thus we have developed a physiologically compatible in situ deoxygenation method utilizing submitochondrial particles. The extent to which this and other deoxygenation procedures modify fluorophore photolability has been determined. FPR measurements become practical on intact erythrocytes when a combination of low bleach power, thorough deoxygenation, and long wavelength excitable (approximately 650 nm) fluorescence probes is employed; the equivalent of 60,000 photobleaches per cell can then be tolerated without detectable damage.


Impact of Variability in Portal Venous Phase Acquisition Timing in Tumor Density Measurement and Treatment Response Assessment: Metastatic Colorectal Cancer as a Paradigm.
New response patterns to anticancer drugs have led tumor size-based response criteria to shift to also include density measurements. Choi criteria, for instance, categorize antiangiogenic therapy response as a decrease in tumor density > 15% at the portal venous phase (PVP). We studied the effect that PVP timing has on measurement of the density of liver metastases (LM) from colorectal cancer (CRC). Pretreatment PVP computed tomography images from 291 patients with LM-CRC from the CRYSTAL trial (Cetuximab Combined With Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer; ClinicalTrials.gov identifier: NCT00154102) were included. Four radiologists independently scored the scans' timing according to a three-point scoring system: early, optimal, late PVP. Using this, we developed, by machine learning, a proprietary computer-aided quality-control algorithm to grade PVP timing. The reference standard was a computer-refined consensus. For each patient, we contoured target liver lesions and calculated their mean density. Contrast-product administration data were not recorded in the digital imaging and communications in medicine headers for injection volume (94%), type (93%), and route (76%). The PVP timing was early, optimal, and late in 52, 194, and 45 patients, respectively. The mean (95% CI) accuracy of the radiologists for detection of optimal PVP timing was 81.7% (78.3 to 85.2) and was outperformed by the 88.6% (84.8 to 92.4) computer accuracy. The mean ± standard deviation of LM-CRC density was 68 ± 15 Hounsfield units (HU) overall and 59.5 ± 14.9 HU, 71.4 ± 14.1 HU, 62.4 ± 12.5 HU at early, optimal, and late PVP timing, respectively. LM-CRC density was thus decreased at nonoptimal PVP timing by 14.8%: 16.7% at early PVP ( P < .001) and 12.6% at late PVP ( P < .001). Nonoptimal PVP timing should be identified because it significantly decreased tumor density by 14.8%. Our computer-aided quality-control system outperformed the accuracy, reproducibility, and speed of radiologists' visual scoring. PVP-timing scoring could improve the extraction of tumor quantitative imaging biomarkers and the monitoring of anticancer therapy efficacy at the patient and clinical trial levels.


[Gastrointestinal helminths of wild ruminants: observations on the chamois (Rupicapra rupicapra L.) in the Val Belviso reserve].
The results obtained in a survey on the gastrointestinal helminths of 32 chamois of the Riserva of Valbelviso on the Alpi Orobie are reported. All the animals were infested: the species identified with more frequence were O. circumcinta, M. marshalli, N. filicollis. Of great significance was the diffusion of N. filicollis, compared with other species of this genus, typical of the wild ruminants; Oe. radiatum, never previously observed in chamois, was also found. These results show that the promiscuity of wild and domestic ruminants in the pasture could interfere with the natural focality of the respective gastrointestinal nematodes.


Evolution of transcriptional control of antigenic variation and virulence in human and ape malaria parasites.
The most severe form of human malaria is caused by the protozoan parasite Plasmodium falciparum. This unicellular organism is a member of a subgenus of Plasmodium called the Laverania that infects apes, with P. falciparum being the only member that infects humans. The exceptional virulence of this species to humans can be largely attributed to a family of variant surface antigens placed by the parasites onto the surface of infected red blood cells that mediate adherence to the vascular endothelium. These proteins are encoded by a large, multicopy gene family called var, with each var gene encoding a different form of the protein. By changing which var gene is expressed, parasites avoid immune recognition, a process called antigenic variation that underlies the chronic nature of malaria infections. Here we show that the common ancestor of the branch of the Laverania lineage that includes the human parasite underwent a remarkable change in the organization and structure of elements linked to the complex transcriptional regulation displayed by the var gene family. Unlike the other members of the Laverania, the clade that gave rise to P. falciparum evolved distinct subsets of var genes distinguishable by different upstream transcriptional regulatory regions that have been associated with different expression profiles and virulence properties. In addition, two uniquely conserved var genes that have been proposed to play a role in coordinating transcriptional switching similarly arose uniquely within this clade. We hypothesize that these changes originated at a time of dramatic climatic change on the African continent that is predicted to have led to significant changes in transmission dynamics, thus selecting for patterns of antigenic variation that enabled lengthier, more chronic infections. These observations suggest that changes in transmission dynamics selected for significant alterations in the transcriptional regulatory mechanisms that mediate antigenic variation in the parasite lineage that includes P. falciparum. These changes likely underlie the chronic nature of these infections as well as their exceptional virulence.


A 10-Year Comparative Analysis Shows that Increasing Prevalence of Rifampin-Resistant Mycobacterium tuberculosis in China Is Associated with the Transmission of Strains Harboring Compensatory Mutations.
In this work, we conducted bacterial population profile studies to assess trends of rifampin (RIF) resistance of Mycobacterium tuberculosis isolates collected across China from 2005 to 2015. Totals of 273 and 269 randomly selected M. tuberculosis isolates from 2005 and 2015, respectively, were analyzed. The rates of RIF resistance (36.4%), isoniazid resistance (39.0%), and levofloxacin resistance (25.7%) in 2015 were significantly higher than those in 2005 (28.2%, 30.0%, and 15.4%, respectively; P < 0.05). Genotypic data revealed 256 (95.2%) Beijing-type isolates in 2015, a rate significantly higher than that in 2005 (86.4%) (P < 0.01). A higher proportion of mutations was identified within the rifampin resistance-determining region (RRDR) of rpoB in isolates from 2015 (99.0%) than in 2005 isolates (85.7%, P < 0.01). In addition, a significantly higher proportion of RIF-resistant isolates carrying compensatory mutations was observed in 2015 (31.6%) than in 2005 (7.8%). Notably, the great majority of these compensatory mutations (91.9%) were observed in isolates that harbored a mutation of codon 531 of the rpoB gene. In conclusion, our data demonstrate that resistance to RIF, isoniazid, and levofloxacin has become significantly more prevalent during the past decade. In addition, the prevalence of the Beijing genotype significantly increased from 2005 to 2015. Notably, a significantly increased frequency of strains with mutations in rpoC or rpoA is observed among those that have codon 531 mutations, which suggests that they may be compensatory and may play a role in facilitating transmission.


Probiotics in diverticular disease of the colon: an open label study.
To investigate the effectiveness and safety of a symbiotic mixture in preventing recurrence of constipation-related abdominal pain in patients with uncomplicated diverticular disease of the colon. Forty-six consecutive patients (10 men, 36 women, mean age 62.5 years, range 49 to 77 years), previously affected by symptomatic uncomplicated diverticular disease of the colon, were enrolled in a 6-month follow-up study in a prospective, randomized, open-label study. The following symptoms were assessed at entry and through follow-up by using a quantitative scale: constipation, diarrhoea and abdominal pain. After recruitment, the patients were assigned to the following treatment: SCM-III symbiotic mixture, 10 ml three times a day. The colonization of ingested Lactobacillus acidophilus 145 and Bifidobacterium spp. 420 was assessed by species-specific PCR. Forty-five patients completed the study (97%). Thirty-one patients (68%) were still symptom free after the 6th month of treatment. Treatment with SCM-III was regarded as "effective" or "very effective" in more than 78% of the patients altogether (p<0.01 vs baseline values). The microbiological study showed that, as compared to baseline values, SCM-III enabled a significant increase of the lactobacilli and bifidobacteria counting and a trend decrease of clostridia. Genomic analysis confirmed the survivability of the ingested strain as long as treatment was given. The present symbiotic mixture seems to be effective in preventing recurrence of symptomatic uncomplicated diverticular disease of the colon, especially in those patients with constipation-predominant features.


Effect of S. mutans combinations with bifidobacteria/lactobacilli on biofilm and enamel demineralization.
The present study evaluated the ability of Bifidobacterium and Lactobacillus species associated with streptococci to increase insoluble extracellular polysaccharide (EPS) production and initial caries lesion progression. Bovine enamel blocks (n = 190; 4 mm x 4 mm) were prepared, selected according to initial surface hardness (SH), and divided into two groups: a) double combinations: S. mutans with Bifidobacterium or Lactobacillus, and b) triple combinations: S. mutans and S. sobrinus with Bifidobacterium or Lactobacillus species. The blocks were exposed to the bacterial associations for 7 days. Subsequently, quantity of EPS from biofilms and caries lesion depth were determined by means of colorimetric and cross-sectional enamel hardness (ΔKHN) analysis. The data were submitted to one-way analysis of variance, followed by the Bonferroni test (p < 0.05). S. mutans with B. animalis or B. dentium produced a higher quantity of EPS; S. mutans + B. animalis led to the highest ∆KHN. S. mutans + S. sobrinus + B. longum induced greater EPS and ∆KHN values. In conclusion, associations of B. animalis and B. longum with streptococci promoted EPS production and caries lesion progression.


Radiation-induced hypomethylation triggers urokinase plasminogen activator transcription in meningioma cells.
Our previous studies have shown the role of radiation-induced urokinase plasminogen activator (uPA) expression in the progression of meningioma. In the present study, we investigated whether modulation of DNA methylation profiles could regulate uPA expression. Initially, radiation treatment was found to induce hypomethylation in meningioma cells with a decrease in DNA (cytosine-5)-methyltransferase 1 (DNMT1) and methyl-CpG binding domain protein (MBD) expression. However, oxidative damage by H(2)O(2) or pretreatment of irradiated cells with N-acetyl cysteine (NAC) did not show any influence on these proteins, thereby indicating a radiation-specific change in the methylation patterns among meningioma cells. Further, we identified that hypomethylation is coupled to an increase in uPA expression in these cells. Azacytidine treatment induced a dose-dependent surge of uPA expression, whereas pre-treatment with sodium butyrate inhibited radiation-induced uPA expression, which complemented our prior results. Methylation-specific polymerase chain reaction on bisulfite-treated genomic DNA revealed a diminished methylation of uPA promoter in irradiated cells. Transfection with small hairpin RNA (shRNA)-expressing plasmids targeting CpG islands of the uPA promoter showed a marked decline in uPA expression with subsequent decrease in invasion and proliferation of meningioma cells. Further, radiation treatment was found to recruit SP1 transcription factor, which was abrogated by shRNA treatment. Analysis on signaling events demonstrated the activation of MAP kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) in radiation-treated cells, while U0126 (MEK/ERK inhibitor) blocked hypomethylation, recruitment of SP1, and uPA expression. In agreement with our in vitro data, low DNMT1 levels and high uPA were found in intracranial tumors treated with radiation compared to untreated tumors. In conclusion, our data suggest that radiation-mediated hypomethylation triggers uPA expression in meningioma cells.


Molecular cloning and characterization of a novel putative carboxylesterase, present in human intestine and liver.
A full-length cDNA coding for a putative intestinal carboxylesterase (iCE) was isolated from a human small intestine cDNA library. The cDNA has an open reading frame of 559 amino acids with up to 65% homology to other carboxylesterases of different mammalian species. The deduced amino-acid sequence contains many structural features, that are highly conserved among all carboxylesterase isoenzymes, like the serine esterase active site, an ER-retention signal and one Asn-Xxx-Thr site for N-linked carbohydrate addition. Northern blot analysis revealed that the corresponding mRNA is 3.4-3.6 kb in size and is preferentially expressed in human intestine with a weak signal also in liver. Analysis of cells from the gastrointestinal tract unveiled site-specific, transcriptional regulation of iCE, with higher expression in small intestine and lower expression in colon and rectum. The high expression in small intestine is attributable to a higher expression in jejunum compared to duodenum and ileum.


Partial Substitution of Glucose with Xylitol Suppressed the Glycolysis and Selectively Inhibited the Proliferation of Oral Cancer Cells.
Suitable diet for cancer survivors remains an unresolved challenge. Increased glucose utilization is a hallmark of various cancers. Therefore, alternative carbohydrate supplying normal tissue but retarding cancer growth is needed. This study investigated the effect of sugar alcohols on the proliferation of oral cancer cells compared to nontransformed cells and explored the mechanism. Six oral squamous cell carcinoma (CAL-27, FaDu, SCC4, SCC9, SCC15, and SCC25) and one nontransformed oral keratinocyte (OKF6/TERT2) lines were cultured in media containing 1 mg/ml glucose and 5.8 mg/ml xylitol or sorbitol, yielding equal energy input to control group (4.5 mg/ml glucose). Partial substitution of glucose with sugar alcohols especially xylitol significantly suppressed proliferation of oral cancer but not nontransformed cells. Despite the addition of isocaloric quantities of the sugars, cancer cells exposed to low glucose plus xylitol had retarded ATP generation and decreased activity of phosphofructokinase (PFK), the rate-limiting enzyme in glycolysis. Furthermore, D-xylulose, its key metabolic intermediate, enhanced the anticancer effect of xylitol. These findings suggested a selective anticancer activity of xylitol and the potential mechanism involving inhibition of glucose utilization. Partial substitution of glucose with xylitol may be a proper nutrient for oral cancer survivors, deserving further investigation in animal and clinical settings.


The effect of a lifestyle intervention on metabolic health in young women.
With the increasing obesity rates in Western countries, an effective lifestyle intervention for fat reduction and metabolic benefits is needed. High-intensity intermittent exercise (HIIE), Mediterranean eating habits (Mediet), and fish oil (ω-3) consumption positively impact metabolic health and adiposity, although the combined effect has yet to be determined. A 12-week lifestyle intervention on adiposity, insulin resistance, and interleukin-6 (IL-6) levels of young overweight women was administered. Thirty women with a body mass index of 26.6±0.5 kg/m(2), blood pressure of 114/66±1.9/1.5 mmHg, and age of 22±0.8 years were randomly assigned to either an intervention group receiving Mediet advice, daily ω-3 supplementation, and HIIE 3 days/week for 12 weeks or a control group. The group receiving Mediet advice, daily ω-3 supplementation, and HIIE experienced a significant reduction in total body fat mass (P<0.001), abdominal adiposity (P<0.05), waist circumference (P<0.001), systolic blood pressure (P<0.05), fasting plasma insulin (P<0.05), IL-6 (P<0.001), and triglycerides (P<0.05). The greatest decreases in fasting plasma insulin (P<0.05) and IL-6 (P<0.001) occurred by week 6 of the intervention. Significant improvements in eating habits (P<0.05) and aerobic fitness (P<0.001) were also found following the intervention. A multifaceted 12-week lifestyle program comprising a Mediet, ω-3 supplementation, and HIIE induced significant improvements in fat loss, aerobic fitness, and insulin and IL-6 levels, positively influencing metabolic health.


A novel probe for measuring tissue bioelectrical impedance to enhance pedicle screw placement in spinal surgery.
Posterior spinal reconstruction with rods and pedicle screws has been widely used to corrects coliosis and other forms of degenerative spinal deformities. However, insertion of pedicle screwsis often clinically challenging, particularlyin patients with severe deformity. Bioelectrical impedance analysis is a technique that exploits the electrical properties of biological organs and tissues to indicate their compositions. Bioelectrical impedance measurement is non-invasive, simple, with adequate repeatability, and at a relatively low cost. In our study, we designed a bioelectrical impedance pedicle probe and use it to determine the bioelectrical impedance values in vitro and in vivo of different tissues relevant to pedicle screw insertion. We measured the bioelectrical impedance of different tissues relevant to pedicle screw placement in vitro and in vivo and explored the use of a prototype bioelectrical impedance pedicle probein guiding pedicle screw placement during spine surgery in animals. These data suggested that this novel bioelectrical impedance pedicle probe may be a new technique that has potential to offer accurate and safe placement of pedicle screws in spine surgery.


Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain.
Neuropeptides are structurally highly diverse messenger molecules that act as regulators of many physiological processes such as development, metabolism, reproduction or behavior in general. Differentiation of neuropeptidergic cells often corresponds with the presence of the transcription factor DIMMED. In the central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly occurs in neuroendocrine neurons that release peptides as neurohormones but also in interneurons with complex branching patterns. Fly strains with green fluorescence protein (GFP)-expressing dimmed cells make it possible to systematically analyze the processed neuropeptides in these cells. In this study, we mapped individual GFP-expressing neurons of adult D. melanogaster from the dimmed (c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types of dimmed neurons from the brain/gnathal ganglion. These cells included neuroendocrine cells with projection into the retrocerebral complex but also a number of large interneurons. Resulting mass spectra not only provided comprehensive data regarding mature products from 13 neuropeptide precursors but also evidence for the cellular co-localization of neuropeptides from different neuropeptide genes. The results can be implemented in a neuroanatomical map of the D. melanogaster brain. Graphical Abstract .


A haptic knob for rehabilitation of hand function.
This paper describes a novel two-degree-of-freedom robotic interface to train opening/closing of the hand and knob manipulation. The mechanical design, based on two parallelogram structures holding an exchangeable button, offers the possibility to adapt the interface to various hand sizes and finger orientations, as well as to right-handed or left-handed subjects. The interaction with the subject is measured by means of position encoders and four force sensors located close to the output measuring grasping and insertion forces. Various knobs can be mounted on the interface, including a cone mechanism to train a complete opening movement from a strongly contracted and closed hand to a large opened position. We describe the design based on measured biomechanics, the redundant safety mechanisms as well as the actuation and control architecture. Preliminary experiments show the performance of this interface and some of the possibilities it offers for the rehabilitation of hand function.


Evaluation of the Behavior of Spinal Deformities in Tuberculosis of the Spine in Adults.
A prospective clinical study. The objective of the present study was to evaluate the behavior of spinal deformities in tuberculosis (TB) of the spine during the initial 2 years and to suggest remedial measures. Spinal TB is the most common cause of a kyphotic deformity in many parts of the world. Treatment of the established deformity is difficult, hazardous and has a high complication rate. We followed 50 adult patients treated for spinal TB for a minimum of 2 years. Average values of vertebral body height loss (VBL), deformity angle, kyphosis angle, and lumbosacral joint angle at the final follow-up were compared with the values at initial presentation. The relationship between the amount of initial VBL and final kyphotic angle was analyzed. Average values of VBL, deformity angle, kyphosis angle, and lumbosacral joint angle at initial presentation were 0.26, 12.51°, 2.26°, and 12.3°, respectively; and the corresponding values at the final follow-up were 0.7, 17.8°, 5.64°, and 10.8°, respectively. The increase was extremely significant for the deformity angle (initial vs. 6th month, p=0.000; 6th month vs. 24th month, p=0.000) and kyphotic angle (initial vs. 6th month, p=0.003; 6th month vs. 24th month, p=0.000) in the thoracic and thoracolumbar regions during the first 2 years of the disease process. The increase in the deformity angle in the lumbar region was significant only in the initial 6 months (p=0.01). We could not find any correlation between the initial VBL and the final kyphotic angle (r=0.302, p>0.05). Different regions of the vertebral column respond differently to bony destruction caused by spinal TB. Deformity progression is more significant during the initial 6 months of the disease process, and this may be the best time to take remedial measures to prevent development/progression of the deformity. Kyphotic deformity keeps increasing even after 6 months of antituberculous treatment, and it does not correlate with the initial VBL in adults.


[Medical disorders which interfere with pregnancy].
During pregnancy, the future mother can develop several different diseases. Most of them have a benign prognosis. Cyanotic heart disease, at least when it is accompanied by significant pulmonary hypertension or induces a functional class IV represents a contra-indication to pregnancy. Pregnancy cardiomyopathy generally carries a poor prognosis and may be responsible for the mother's death. Herpes virus pneumopathy can also be extremely dangerous. Lupus erythematosus represents a factor of guarded prognosis for the outcome of pregnancy; discontinuation of the latter should be seriously considered. Hepatic steatosis which is a rare diagnosis must be distinguished from Hellp syndrome in which the maternal prognosis is much better. In this review, we shall briefly discuss various medical diseases which may have a deleterious influence on the evolution of pregnancy or on the foetus. These deleterious influences can be direct, i.e. due to the disease, or indirect, i.e. due to the therapy. We shall successively consider several neurological, cardiological, pulmonary, dermatological and digestive diseases. We shall not take into account viral infections or infections in general, diabetes mellitus or the various vasculo-renal syndromes.


The Effect of Rapid Point-of-Care Respiratory Pathogen Testing on Antibiotic Prescriptions in Acute Infections-A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Rapid point-of-care testing for respiratory pathogens has gained increasing popularity, but its impact on antibiotic consumption is unclear. Thus, the aim of this systematic review and meta-analysis was to estimate the effect of rapid point-of-care testing on antibiotic prescriptions. The search for this systematic review with meta-analysis was performed in February 2023. Randomized controlled trials investigating the impact of testing for respiratory pathogens in all-aged patients were included regardless of the comparator. The main outcome was the antibiotic prescription rate. Analyses were stratified by test type, test setting, and patient age. A random-effects Mantel-Haenszel model was used to calculate risk ratios with 95% confidence intervals. Risk of bias was assessed for included studies, and the quality of the evidence was rated according to GRADE. A total of 754 abstracts were screened, and 10 studies were included in the analysis. Risk of bias was high in 2, low in 4, and had some concerns in 4 studies. Four studies analyzed influenza and respiratory syncytial virus tests, and 6 studies analyzed multiplex (viral and/or bacterial) testing. The prescription rate was 48.2% (496/1029) in the influenza and respiratory syncytial virus test group and 48.7% (540/1109) in the control group (risk ratio [RR], 0.97; 95% CI, 0.92-1.02; moderate-quality evidence). The prescription rate in the multiplex testing group was 54.3% (1554/2859), and it was 57.3% (1336/2326) in the control group (RR, 1.00; 95% CI, 0.96-1.04; moderate-quality evidence). In an age-stratified analysis, the prescription rates showed no evidence of a difference (children: RR, 1.03; 95% CI, 0.81-1.30; adults: RR, 0.98; 95% CI, 0.96-1.01; very low- and moderate-quality evidence). We found moderate-quality evidence that rapid point-of-care testing for respiratory pathogens does not decrease the antibiotic prescription rate.


Important region in the beta-spectrin C-terminus for spectrin tetramer formation.
Many hereditary hemolytic anemias are due to spectrin mutations at the C-terminal region of beta-spectrin (the betaC region) that destabilize spectrin tetramer formation. However, little is known about the betaC region of spectrin. We have prepared four recombinant beta-peptides of different lengths from human erythrocyte spectrin, all starting at position 1898 of the C-terminal region, but terminating at position 2070, 2071, 2072 or 2073. Native polyacrylamide gel electrophoresis showed that the two peptides terminating at positions 2070 and 2071 did not associate with an N-terminal region alpha-peptide (Spalpha1-156) in the micromolar range. However, the peptides that terminated at positions 2072 and 2073 associated with the alpha-peptide. Circular dichroism results showed that the unassociated helices in both alpha- and beta-peptides became associated, presumably to form a helical bundle, for those beta-peptides that formed an alphabeta complex, but not for those beta-peptides that did not form an alphabeta complex. In addition, upon association, an increase in the alpha-helical content was observed. These results showed that the beta-peptides ending prior to residue 2072 (Thr) would not associate with alpha-peptide, and that no helical bundling of the partial domains was observed. Thus, we suggest that the C-terminal segment of beta-spectrin, starting from residue 2073 (Thr), is not critical to spectrin tetramer formation. However, the C-terminal region ending with residue 2072 is important for its association with alpha-spectrin in forming tetramers.


Molecular cloning of cecropin B responsive endonucleases in Yersinia ruckeri.
We have previously demonstrated that Yersinia ruckeri resists cecropin B in an inducible manner. In this study, we sought to identify the molecular changes responsible for the inducible cecropin B resistance of Y. ruckeri. Differences in gene expression associated with the inducible resistance were investigated. Cultures of Y. ruckeri were exposed to a sublethal concentration of cecropin B and resultant changes in the messenger RNA population of the bacteria were assayed using the differential display reverse transcription polymerase chain reaction (DD-RT-PCR). A single band was consistently increased in intensity in all repeats of the experiment. The band was excised, cloned, sequenced, and used to screen a Y. ruckeri genomic DNA library. The DD-RT-PCR fragment shared 100% identity to the cDNA sequence of an ATP-dependent endonuclease of the overcome lysogenization defect (OLD) family of Y. ruckeri 29473. The genomic clone that was recovered was not identical to the DD-RT-PCR clone, but harbored a gene for a secreted endonuclease 1 (nucM) homologue. It was determined that transcription of the gene was upregulated following exposure to cecropin B via RT-PCR. Furthermore, an increase in the nuclease activity of culture supernatants of Y. ruckeri following exposure to cecropin B was demonstrated. These findings demonstrate that cecropin B exposure increases the expression of at least two endonucleases in Y. ruckeri. The production and secretion of an endonuclease by Y. ruckeri in response to an antimicrobial peptide indicates the involvement of both intracellular and extracellular DNA in the toxic effects of cecropin B.


[Role of myelinated and unmyelinated fibers of the vagus nerve in the development of ischemic fibrillation of the heart].
The effect of nn. vagi on ischemic heart arrhythmia was studied in acute experiments on cats. It was shown that thick myelinated fibers do not significantly alter the rate of onset of such arrhythmias. On the contrary, where the nn. vagi were cooled to 0 degree C, which entrained the block of non-myelinated fibers as well, the rate of ischemic heart arrhythmias (including heart fibrillation) drastically increased.


miR-1247-5p functions as a tumor suppressor in human hepatocellular carcinoma by targeting Wnt3.
Increasing evidence suggests that aberrant expression of certain microRNAs (miRNAs) may participate in the genesis and progression of tumors. Several studies have indicated that miR-1247-5p plays different roles in various types of cancer cells. The effects of miR-1247-5p on human hepatocellular carcinoma (HCC) cells are elusive. In the present study, we investigated the effects of miR-1247-5p on the progression of HCC. The transcript of miR-1247-5p was markedly downregulated in clinical samples of patients with HCC and HCC cell lines, and ectopic overexpression of miR‑1247-5p markedly inhibited the proliferation and invasion of HepG2 cells, induced cell apoptosis in vitro, and suppressed the growth of transplanted tumors in vivo. Wnt3 was found to be a potential target of miR-1247-5p and overexpression of miR-1247-5p was able to significantly downregulate the expression of Wnt3 by directly targeting the 3'UTR of this gene, which was verified by luciferase reporter assay and western blotting. Furthermore, we found that the miR-1247-5p gene was hypermethylated in HepG2 cells, and the transcript of miR-1247-5p was increased significantly after treatment with the demethylation drug 5-azacytidine. These findings demonstrated that miR-1247-5p functions as a tumor suppressor in human HCC by targeting Wnt3 and that the expression of miR-1247-5p can be regulated by DNA methylation, which indicates that miR-1247-5p has the potential to be a therapeutic target as well as a diagnostic marker of HCC.


Targeting and arginine-driven synergizing photodynamic therapy with nutritional immunotherapy nanosystems for combating MRSA biofilms.
The resistance and immune escape of methicillin-resistant Staphylococcus aureus (MRSA) biofilms cause recalcitrant infections. Here, we design a targeting and synergizing cascade PDT with nutritional immunotherapy nanosystems (Arg-PCN@Gel) containing PCN-224 as PDT platform for providing reactive oxygen species (ROS), incorporating arginine (Arg) as nitric oxide (NO) donor to cascade with ROS to produce more lethal ONOO- and promote immune response, and coating with gelatin as targeting agent and persistent Arg provider. The nanosystems adhered to the autolysin of MRSA and inhibited Arg metabolism by down-regulating icdA and icaA. It suppressed polysaccharide intercellular adhesin and extracellular DNA synthesis to prevent biofilm formation. The NO broke mature biofilms and helped ROS and ONOO- penetrate into biofilms to inactivate internal MRSA. Arg-PCN@Gel drove Arg to enhance immunity via inducible NO synthase/NO axis and arginase/polyamine axis and achieve efficient target treatment in MRSA biofilm infections. The targeting and cascading PDT synergized with nutritional immunotherapy provide an effective promising strategy for biofilm-associated infections.


Pigmented tumor in the nostril.
A 64-year-old man was noted to have a single pigmented lesion in the nostril of his nose. Clinical examination revealed a 5 mm nodular growth and brown lesion. With a presumed clinical diagnosis of malignant skin tumor, a biopsy was performed. The histological examination revealed the unexpected diagnosis of pigmented inverted follicular keratosis. The inverted follicular keratosis is an uncommon benign lesion that is usually diagnosed histologically rather than clinically. It commonly simulates other proliferative skin lesions.


Stress and Anxiety to Viral Epidemics-6 for Medical Students: Psychometric Properties of the Anxiety Measure for the COVID-19 Pandemic.
The aim of this study was to explore the psychometric properties and validity of Stress and Anxiety to Viral Epidemics-6 items (SAVE-6) among medical students who are at high risk of coronavirus disease 2019 (COVID-19) infection. A total of 212 medical students participated in the online anonymous survey that used SAVE-6, Coronavirus Anxiety Scale (CAS), Generalized Anxiety Disorder-7 items (GAD-7), and Work and Social Adjustment Scale (WSAS). We observed that the single-factor structure model of the SAVE-6 scale showed good internal consistency (Cronbach's alpha = 0.756) and a good convergent validity with GAD-7 (rho = 0.320, p < 0.001), CAS (rho = 0.229, p < 0.001), and WSAS (rho = 0.278, p < 0.001). The appropriate cut-off score of the SAVE-6 scale was determined as 15 points in accordance with at least a mild degree of generalized anxiety (GAD-7 score of 5) among medical students. In conclusion, the SAVE-6 scale can be applied to medical students as a reliable and valid rating scale to assess anxiety response to the present viral pandemic.


Histamine modulation of the basal ganglia circuitry in the development of pathological grooming.
Aberrant histaminergic function has been proposed as a cause of tic disorders. A rare mutation in the enzyme that produces histamine (HA), histidine decarboxylase (HDC), has been identified in patients with Tourette syndrome (TS). Hdc knockout mice exhibit repetitive behavioral pathology and neurochemical characteristics of TS, establishing them as a plausible model of tic pathophysiology. Where, when, and how HA deficiency produces these effects has remained unclear: whether the contribution of HA deficiency to pathogenesis is acute or developmental, and where in the brain the relevant consequences of HA deficiency occur. Here, we address these key pathophysiological questions, using anatomically and cellularly targeted manipulations in mice. We report that specific ablation or chemogenetic silencing of histaminergic neurons in the tuberomammillary nucleus (TMN) of the hypothalamus leads to markedly elevated grooming, a form of repetitive behavioral pathology, and to elevated markers of neuronal activity in both dorsal striatum and medial prefrontal cortex. Infusion of HA directly into the striatum reverses this behavioral pathology, confirming that acute HA deficiency mediates the effect. Bidirectional chemogenetic regulation reveals that dorsal striatum neurons activated after TMN silencing are both sufficient to produce repetitive behavioral pathology and necessary for the full expression of the effect. Chemogenetic activation of TMN-regulated medial prefrontal cortex neurons, in contrast, increases locomotion and not grooming. These data confirm the centrality of striatal regulation by neurotransmitter HA in the adult in the production of pathological grooming.


The Whitaker Index of Schizophrenic Thinking (WIST) and thirteen systems for diagnosing schizophrenia.
Developed the present study in conjunction with a project that evaluated the psychiatric diagnosis of schizophrenia (Landmark, 1982; Landmark & Leslie, 1982). This design, which included 13 different interview systems for diagnosing schizophrenic disorders, allowed for an in-depth analysis of the Whitaker Index of Schizophrenic Thinking (WIST). Eighty-five outpatients who were receiving long-term chemotherapy for schizophrenia at the Moditen Clinic of London Psychiatric Hospital were reassessed individually using each of the 13 systems, following a clinical interview format, and the WIST. Major statistical analysis evaluated the concurrent validity and discriminatory efficiency of the WIST in comparison to the 13 systems. The WIST was found to show a consistently high agreement with each of the 13 systems for an average WIST discriminatory efficiency of 70%. The WIST is suggested as a practical, easily administered, diagnostic tool that performs well in comparison to the interview systems.


Platelets actively sequester angiogenesis regulators.
Clinical trials with antiangiogenic agents have not been able to validate plasma or serum levels of angiogenesis regulators as reliable markers of cancer presence or therapeutic response. We recently reported that platelets contain numerous proteins that regulate angiogenesis. We now show that accumulation of angiogenesis regulators in platelets of animals bearing malignant tumors exceeds significantly their concentration in plasma or serum, as well as their levels in platelets from non-tumor-bearing animals. This process is selective, as platelets do not take up a proportional amount of other plasma proteins (eg, albumin), even though these may be present at higher concentrations. We also find that VEGF-enriched Matrigel pellets implanted subcutaneously into mice or the minute quantities of VEGF secreted by microscopic subcutaneous tumors (0.5-1 mm(3)) result in an elevation of VEGF levels in platelets, without any changes in its plasma levels. The profile of other angiogenesis regulatory proteins (eg, platelet-derived growth factor, basic fibroblast growth factor) sequestered by platelets also reflects the presence of tumors in vivo before they can be macroscopically evident. The ability of platelets to selectively take up angiogenesis regulators in cancer-bearing hosts may have implications for the diagnosis and management of many angiogenesis-related diseases and provide a guide for antiangiogenic therapies.


Effect of floating toes on knee and trunk acceleration during walking: a preliminary study.
[Purpose] This study investigated the effect of floating toes on knee and trunk acceleration during walking in experimental setting. [Subjects and Methods] Twelve healthy volunteers walked barefoot at a preferred speed along a linear pathway under 2 conditions: normal gait (control) condition and floating toes (FT) condition. In the latter, weight bearing by the toes was avoided using kinesiology tape applied along the toe extensors. Accelerations of the knee (Kn) and lumbar spine (Lx) were assessed using triaxial accelerometers mounted on the right fibular head and the spinous process of L3. Acceleration vectors were oriented such that the anterior, right, and cranial deviations were positive along the anteroposterior, lateral, and vertical axes, respectively. The root mean squares (RMSs; anteroposterior, RMSap; lateral, RMSl; vertical, RMSv) were calculated, and the mean values of 3 trials in each condition were determined. Differences between the conditions were assessed using the Wilcoxon signed-rank test. [Results] LxRMSap and LxRMSv were larger in the FT condition than in the control condition. KnRMSv tended to be higher in the FT condition than in the control condition. [Conclusion] Floating toes increase acceleration and might create mechanical stress on the lower back and knee during walking.


Effects of Fuel Aromatic Content on Nonvolatile Particulate Emissions of an In-Production Aircraft Gas Turbine.
Aircraft engines emit particulate matter (PM) that affects the air quality in the vicinity of airports and contributes to climate change. Nonvolatile PM (nvPM) emissions from aircraft turbine engines depend on fuel aromatic content, which varies globally by several percent. It is uncertain how this variability will affect future nvPM emission regulations and emission inventories. Here, we present black carbon (BC) mass and nvPM number emission indices (EIs) as a function of fuel aromatic content and thrust for an in-production aircraft gas turbine engine. The aromatics content was varied from 17.8% (v/v) in the neat fuel (Jet A-1) to up to 23.6% (v/v) by injecting two aromatic solvents into the engine fuel supply line. Fuel normalized BC mass and nvPM number EIs increased by up to 60% with increasing fuel aromatics content and decreasing engine thrust. The EIs also increased when fuel naphthalenes were changed from 0.78% (v/v) to 1.18% (v/v) while keeping the total aromatics constant. The EIs correlated best with fuel hydrogen mass content, leading to a simple model that could be used for correcting fuel effects in emission inventories and in future aircraft engine nvPM emission standards.


Alteration of DNA tertiary structure by physical and chemical carcinogens: involvement in DNA repair processes.
Parameters defining the topological state of DNA seem extremely important for describing the reactive state of the same DNA molecules. We have shown that physical and chemical DNA modifying agents alter the tertiary structure of DNA molecules. Variations in the tertiary structure of DNA were studied by one dimensional electrophoresis on an agarose gel of partially relaxed plasmid DNA topoisomers, a technique allowing the measurement of alterations in the degree of supercoiling equivalent to fractions of superhelical turns. Unwinding angles of -10.1 degrees or -8.7 degrees per pyrimidine or thymine dimer respectively, of -12 degrees per apurinic site, and of -3.4 degrees per methylated purine were obtained by titrating the number of damaged sites necessary to reduce the number of superhelical turns by one in each topoisomer. On the contrary, enzymatic methylation of the C-5 position of cytosine (a modified base present in prokaryotic and eukaryotic DNAs) did not alter the DNA tertiary structure. We have also shown that local alterations in DNA structure caused by UV-irradiation inhibit bacterial DNA topoisomerase I and DNA methylase, and that the topological state of DNA substrate influences the mode of methylation of Hpa II DNA methylase. These findings suggest that the natural topological state of DNA substrate (linear, relaxed, or covalently closed duplex DNA with varying degrees of supercoiling) influences the mode of action of enzymes possibly involved in DNA repair processes, while DNA structural alterations caused by DNA modifying agents might influence DNA repair processes in two ways: either by driving the interaction between repair enzymes and the modified sites of DNA, or by inhibiting or changing the mode of action of enzymes normally acting on unmodified DNA.


Long non-coding RNAs in non-small cell lung cancer: implications for EGFR-TKI resistance.
Non-small cell lung cancer (NSCLC) is one of the most common types of malignant tumors as well as the leading cause of cancer-related deaths in the world. The application of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has dramatically improved the prognosis of NSCLC patients who harbor EGFR mutations. However, despite an excellent initial response, NSCLC inevitably becomes resistant to EGFR-TKIs, leading to irreversible disease progression. Hence, it is of great significance to shed light on the molecular mechanisms underlying the EGFR-TKI resistance in NSCLC. Long non-coding RNAs (lncRNAs) are critical gene modulators that are able to act as oncogenes or tumor suppressors that modulate tumorigenesis, invasion, and metastasis. Recently, extensive evidence demonstrates that lncRNAs also have a significant function in modulating EGFR-TKI resistance in NSCLC. In this review, we present a comprehensive summary of the lncRNAs involved in EGFR-TKI resistance in NSCLC and focus on their detailed mechanisms of action, including activation of alternative bypass signaling pathways, phenotypic transformation, intercellular communication in the tumor microenvironment, competing endogenous RNAs (ceRNAs) networks, and epigenetic modifications. In addition, we briefly discuss the limitations and the clinical implications of current lncRNAs research in this field.


Alteration of neural tissue structure by expression of polysialic acid induced by viral delivery of PST polysialyltransferase.
The expression of polysialic acid (PSA) on neural cell adhesion molecule (NCAM) is known to attenuate cell-cell interactions. During neural development the widespread expression of PSA-NCAM creates permissive conditions for the migration of neuronal and glial precursors and the guidance and targeting of axons. NCAM polysialylation can occur via either of two specific sialyltransferases, ST8SiaII (STX) and ST8SiaIV (PST), and the purpose of this study was to determine if retroviral delivery of either PST or STX could induce PSA expression in vivo and thereby alter tissue plasticity. Retroviruses expressing GFP-PST or GFP-STX were injected into embryonic retina, and development was evaluated by examining neuroepithelial structure, the expression of markers for specific cell types, cellular proliferation, and apoptosis. Chick retina was chosen because it down-regulates PSA early in its development and has a highly stereotyped program of morphogenesis. Retroviral expression of PST induced PSA expression in retina and resulted in severe but localized alterations in retinal morphogenesis, including an early disruption of radial glial cell morphology, highly disorganized retinal layers, and invasion of pigmented cells into the neural retina. In contrast, retroviral delivery of STX did not induce PSA expression or affect morphogenesis. These findings demonstrate that expression of PSA is sufficient to promote morphological alterations in a relatively nonplastic neural tissue.


Pharmacotherapy to protect the neuromuscular junction after acute organophosphorus pesticide poisoning.
Organophosphorus (OP) pesticide poisoning is a leading cause of morbidity and mortality in the developing world, affecting an estimated three million people annually. Much of the morbidity is directly related to muscle weakness, which develops 1-4 days after poisoning. This muscle weakness, termed the intermediate syndrome (IMS), leads to respiratory, bulbar, and proximal limb weakness and frequently necessitates the use of mechanical ventilation. While not entirely understood, the IMS is most likely due to persistently elevated acetylcholine (ACh), which activates nicotinic ACh receptors at the neuromuscular junction (NMJ). Thus, the NMJ is potentially a target-rich area for the development of new therapies for acute OP poisoning. In this manuscript, we discuss what is known about the IMS and studies investigating the use of nicotinic ACh receptor antagonists to prevent or mitigate NMJ dysfunction after acute OP poisoning.


Mathematical analysis of a lymphatic filariasis model with quarantine and treatment.
Lymphatic filariasis is a globally neglected tropical parasitic disease which affects individuals of all ages and leads to an altered lymphatic system and abnormal enlargement of body parts. A mathematical model of lymphatic filariaris with intervention strategies is developed and analyzed. Control of infections is analyzed within the model through medical treatment of infected-acute individuals and quarantine of infected-chronic individuals. We derive the effective reproduction number, [Formula: see text] and its interpretation/investigation suggests that treatment contributes to a reduction in lymphatic filariasis cases faster than quarantine. However, this reduction is greater when the two intervention approaches are applied concurrently. Numerical simulations are carried out to monitor the dynamics of the filariasis model sub-populations for various parameter values of the associated reproduction threshold. Lastly, sensitivity analysis on key parameters that drive the disease dynamics is performed in order to identify their relative importance on the disease transmission.


Reducing falls risk.
A multidisciplinary working group in a London hospital set up a questionnaire system to reduce patient falls. The framework it put in place is now a way of life at the hospital and could provide the basis for a wider Clinical Governance project.


Access to kidney transplantation: the limitations of our current understanding.
Since kidney transplantation (KTX) is the preferred means of treating kidney failure, ensuring that all patients who may benefit from KTX have equal access to this scarce resource is an important objective. Studies focusing on this issue will become increasingly important as the gap between the demand and supply of organs continues to increase, and changes to the United Network of Organ Sharing organ allocation policy are actively debated. However, it is clear that current methods used to study access to KTX have serious limitations. This review highlights the shortcomings of the methods currently used to assess access to KTX, and the limitations of registry data and national wait-list data as information sources to study patient access to KTX. The review also provides suggestions for research and analytical approaches that might be utilized to improve our future understanding of patient access to KTX. The information provided will aid the reader to critically assess issues related to patient access to KTX.


Synthetic High-Density Lipoprotein-Mediated Targeted Delivery of Liver X Receptors Agonist Promotes Atherosclerosis Regression.
Targeting at enhancing reverse cholesterol transport (RCT) is apromising strategy for treating atherosclerosis via infusion of reconstitute high density lipoprotein (HDL) as cholesterol acceptors or increase of cholesterol efflux by activation of macrophage liver X receptors (LXRs). However, systemic activation of LXRs triggers excessive lipogenesis in the liver and infusion of HDL downregulates cholesterol efflux from macrophages. Here we describe an enlightened strategy using phospholipid reconstituted apoA-I peptide (22A)-derived synthetic HDL (sHDL) to deliver LXR agonists to the atheroma and examine their effect on atherosclerosis regression in vivo. A synthetic LXR agonist, T0901317 (T1317) was encapsulated in sHDL nanoparticles (sHDL-T1317). Similar to the T1317 compound, the sHDL-T1317 nanoparticles upregulated the expression of ATP-binding cassette transporters and increased cholesterol efflux in macrophages in vitro and in vivo. The sHDL nanoparticles accumulated in the atherosclerotic plaques of ApoE-deficient mice. Moreover, a 6-week low-dose LXR agonist-sHDL treatment induced atherosclerosis regression while avoiding lipid accumulation in the liver. These findings identify LXR agonist loaded sHDL nanoparticles as a promising therapeutic approach to treat atherosclerosis by targeting RCT in a multifaceted manner: sHDL itself serving as both a drug carrier and cholesterol acceptor and the LXR agonist mediating upregulation of ABC transporters in the aorta.


Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein-Barr virus encoded latent membrane protein 1.
Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is essential for the immortalization of human B cells and is linked etiologically to several human tumors. LMP1 is an integral membrane protein which acts like a constitutively active receptor. It binds tumor necrosis factor (TNF)-receptor-associated factors (TRAFs), activates NFkappaB and triggers the transcription factor activating protein-1 (AP-1) via the c-Jun N-terminal kinase (JNK) cascade, but its specific contribution to AP-1 has not been elucidated fully. Members of AP-1 family, the Jun and fos related protein, have been shown to directly interact and form heterodimeric complexes. In this report, using a Tet-on LMP1 HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 in which could be regulated by Tet-on system, we show that Jun B can efficiently form a new heterodimeric complex with the c-Jun protein under the regulation of LMP1, phosphorylation of c-Jun (ser63, ser73) and Jun B involved in the process of the new heterodimeric form. We also find that this heterodimeric form can bind to the AP-1 consensus sequence. Transfection studies suggest that JNK interaction protein (JIP) could inhibit the heterodimer form of c-Jun and Jun B through blocking the AP-1 signaling pathway triggered by LMP1. The interaction and function between c-Jun protein and Jun B protein increase the repertoire of possible regulatory complexes by LMP1 that could play an important role in the regulation of transcription of specific cellular genes in the process of genesis of nasopharyngeal carcinoma.


Diagnostic value of MRI radiomics in differentiating high‑grade glioma from low‑grade glioma: A meta‑analysis.
No clear conclusions have yet been reached regarding the accuracy of magnetic resonance imaging (MRI) radiomics in distinguishing high-grade glioma (HGG) from low-grade glioma (LGG). In the present study, a meta-analysis was conducted to determine the diagnostic value of MRI radiomics in differentiating between HGG and LGG, in order to guide their clinical diagnosis. PubMed, Embase and the Cochrane Library databases were searched up to November 2022. The search included studies in which true positive, false positive, true negative and false negative values for the differentiation of HGG from LGG were reported or could be calculated by retrograde extrapolation. Duplicate publications, research without full text, studies with incomplete information or unextractable data, animal studies, reviews and systematic reviews were excluded. STATA 15.1 was used to analyze the data. The meta-analysis included 15 studies, which comprised a total of 1,124 patients, of which 701 had HGG and 423 had LGG. The pooled sensitivity and specificity of the studies overall were 0.92 (95% CI: 0.89-0.95) and 0.89 (95% CI: 0.85-0.92), respectively. The positive and negative likelihood ratios of the studies overall were 7.89 (95% CI: 6.01-10.37) and 0.09 (95% CI: 0.07-0.12), respectively. The pooled diagnostic odds ratio of the studies was 85.20 (95% CI: 54.52-133.14). The area under the summary receiver operating characteristic curve was 0.91. These findings indicate that radiomics may be an accurate tool for the differentiation of glioma grades. However, further research is needed to verify the most appropriate of these technologies.


Supramolecular organization of the subsarcolemmal cytoskeleton of adult skeletal muscle fibers. A review.
This review is focused on the composition and organization of the junctional subsarcolemmal cytoskeleton of adult muscle fibers. The cytoskeleton of muscle fibers is organized in functionally distinct compartments and the subsarcolemmal cytoskeleton itself can be broadly divided into junctional (myotendinous junction, neuromuscular junction and costameres) and non-junctional domains. In junctional zones three different multimolecular cytoskeletal complexes coexist: the focal adhesion-type, the spectrin-based and the dystrophin vs utrophin-based membrane skeleton systems. These complexes extend over several levels, from intracytoplasmic to subsarcolemmal and transmembranous; their common feature is the anchorage of actin filaments emanating from the intracytoplasmic level. The different cytoskeletal proteins, their putative roles and their interactions with various signaling pathways are presented here in detail. The subsarcolemmal cytoskeleton complexes are thought to play distinct physiological roles (membrane stabilization, force transmission to extracellular matrix, ionic channel anchorage, etc) but their colocalization on the three sarcolemmal junctional domains strongly suggests interrelated or common functions.


Reversal of Pacing-Induced Cardiomyopathy by Normal QRS Axis Pacing.
Right ventricular apical pacing has been a commonly used method for placement of permanent pacemaker, but it is known to be associated with ventricular dyssynchrony and may lead to heart failure. Septal pacing could be an alternative method to improve this complication but the results have been conflicting; hence, other strategies are needed. This case is about a patient with pacing-induced cardiomyopathy who showed much improvement after repositioning the leads to a site different from that of normally paced QRS axis.


Athermal design for the potassium titanyl phosphate electro-optical modulator.
An athermal design for the KTP electro-optical modulator is presented. By using the wave coupling theory of linear electro-optic effect and taking account of thermal expansion, the more accurate athermal static phase retardation (ASPR) directions in potassium titanyl phosphate (KTP) are found, and the optimized design for a transverse amplitude modulator at ASPR orientation is obtained. The numerical results show that the modulator with an athermal Soleil-Babinet compensator is of excellent thermal stability, and the acceptable error of the ASPR direction is less than 0.1 degrees.


[Shenxiong Glucose Injection inhibits H_2O_2-induced apoptosis of H9c2 cells by activating PI3K/AKT pathway].
The aim of this paper was to explore the mechanism of Shenxiong Glucose Injection antagonizing apoptosis of H9 c2 cells induced by H_2O_2. H9 c2 cells were pretreated with 1. 7%,3. 4% and 6. 8% Shenxiong Glucose Injection,and then H_2O_2 was introduced to induce apoptosis in vitro. Cell viability was detected by MTS assay,morphological changes of apoptosis were observed by AO/EB fluorescence staining,apoptosis rate was detected by Annexin/PI method,cell expression profile was detected by gene chip technology,the mRNA of PIK3 CA,Bcl-2,Bax,caspase-3 and GAPDH were detected by qRT-PCR,the protein expression levels of PIK3 CA,AKT,P-AKT,Bcl-2,Bax and caspase-3 were detected by Western blot,and the contents of LDH and MDA were detected by kit. The results showed that Shenxiong Glucose Injection of different concentrations significantly increased the viability of H9 c2 cells treated with H_2O_2( P<0. 01),and reversed H_2O_2-induced apoptosis( P< 0. 01). The microarray experiments showed that 138 genes were altered in H9 c2 cells after treatment with Shenxiong Glucose Injection. The differential expression fold of PIK3 CA associated with PI3 K/AKT pathway was 3. 59. The results of qRT-PCR and Western blot showed that Shenxiong Glucose Injection could down-regulate the mRNA and protein expression levels of caspase-3( P<0. 01),up-regulate the mRNA and protein expression level of PIK3 CA and Bcl-2( P<0. 01),and up-regulate the phosphorylation levels of AKT( P<0. 01) in H_2O_2-treated H9 c2 cells. The protective effect of Shenxiong Glucose Injection on H_2O_2 cells injury was significantly inhibited by LY294002,a PI3 K/AKT pathway inhibitor. The results suggested that Shenxiong Glucose Injection may inhibit H_2O_2-induced H9 c2 cells apoptosis by regulating PI3 K/AKT signaling pathway.


Expression of Class I and Class II a/b Histone Deacetylase is Dysregulated in Hypertensive Animal Models.
Dysregulation of histone deacetylase expression and enzymatic activity is associated with a number of diseases. It has been reported that protein levels of histone deacetylase (HDAC)1 and HDAC5 increase during human pulmonary hypertension, and that the enzymatic activity of HDAC6 is induced in a chronic hypertensive animal model. This study investigated the protein expression profiles of class I and II a/b HDACs in three systemic hypertension models. We used three different hypertensive animal models: (i) Wistar-Kyoto rats (n=8) and spontaneously hypertensive rats (SHR; n=8), (ii) mice infused with saline or angiotensin II to induce hypertension, via osmotic mini-pump for 2 weeks, and (iii) mice that were allowed to drink L-NG-nitro-L-arginine methyl ester (L-NAME) to induce hypertension. SHR showed high systolic, diastolic, and mean blood pressures. Similar increases in systolic blood pressure were observed in angiotensin II or L-NAME-induced hypertensive mice. In SHR, class IIa HDAC (HDAC4, 5, and 7) and class IIb HDAC (HDAC6 and 10) protein expression were significantly increased. In addition, a HDAC3 protein expression was induced in SHR. However, in L-NAME mice, class IIa HDAC protein levels (HDAC4, 5, 7, and 9) were significantly reduced. HDAC8 protein levels were significantly reduced both in angiotensin II mice and in SHR. These results indicate that dysregulation of class I and class II HDAC protein is closely associated with chronic hypertension.


Ultrastructure and chemical analysis of the cell wall of Pythium debaryanum.
The ultrastructure and component polysaccharides of the cell wall of Pythium debaryanum IFO-5919 were investigated. From results obtained by means of acid, alkali, Schweitzer reagent and beta-1, 3-glucanase treatments and electron microscopy, it was concluded that 1) the acid-extracted fraction was a 1,3-linked branched glucan, 2) the alkali-extranded fraction was a mixture of 1,3-, 1,6-, and 1,3,6-linked highly branched two glucans, 3) the Schweitzer reagent-extracted fraction was a beta-1, 4-linked glucan, 4) the cell wall was constructed from two types of cullulosic microfibrils, as a frame and as a finer network, and amorphous beta-1, 3-glucan including beta-1, 6-linkage, 5) cellulosic microfibrils were covered by matrix material consisting of a mixture of amorphous beta-1, 3-linked and beta-1, 6-linked branching glucans.


Cytogenetic evolution following the transformation of myelodysplastic syndrome to acute myelogenous leukemia: implications on the overlap between the two diseases.
Cytogenetic evolution in the myelodysplastic syndrome (MDS) has been associated with an abrupt shift to acute myelogenous leukemia (AML). To investigate the 'evolution' of MDS to AML we compared the karyotypes of MDS patients at presentation and at development of AML. Of 170 patients with MDS who developed AML, 63 had banded karyotypes done at both time points. Fifteen patients had refractory anemia (RA) or RA with ringed sideroblasts (RARS), 27 had RA with excess blasts (RAEB), and 21 had RAEB in transformation (RAEBT). Patients had MDS for at least 12 weeks prior to developing AML. Thirty-one patients received cytotoxic therapy for MDS. Seventeen of 63 patients (27%) acquired a cytogenetic change when they developed AML. This percentage was significantly higher in RA/RARS patients compared to RAEB/RAEBT (53.3 vs. 18.8%, p < 0.01). Age, prior malignancy, cytotoxic therapy for MDS, and time to development of AML did not influence the probability of acquiring a cytogenetic change. The small number of patients did not allow testing for the effect of specific karyotypes on the incidence of cytogenetic change or the effect of this change on AML prognosis. The only recurring cytogenetic change was addition of chromosome 13 which occurred in four of 17 patients who changed. These data suggest that a cytogenetic change may be partly responsible for the transformation of RA/RARS, but not RAEB or RAEBT, to AML. This supports the concept that RAEB, RAEBT, and AML are different manifestations of the same disease, whereas RA/RARS are conditions that predispose to acute leukemia.


Virulence of Listeria monocytogenes isolates from humans and smoked salmon, peeled shrimp, and their processing environments.
The virulence of 82 Listeria monocytogenes isolates from human cases and cold-smoked salmon, cooked peeled shrimp, and their production environments was assessed using the plaque-forming assay and a subcutaneous inoculation test in mice. These isolates were previously typed using serotyping and pulsed-field gel electrophoresis. The isolates from food-production environments were collected in several surveys over the period of 5 years. Sixty-eight (99.8%) of 69 isolates tested from food and food-processing environments were considered virulent while only one was avirulent. All clinical isolates (13) were highly virulent. The isolates were from raw materials, final products, and the production environment. This stresses the importance of hygiene in the processing environment as well as among personnel to avoid contamination of the final product.


Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.
Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood. To assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations. PubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications. At least 2 reviewers identified 571 original, peer-reviewed English-language publications reporting genetic modifiers of human SCD phenotypes, wherein the outcome was not treatment response, and the comparison was not between SCD subtypes or including healthy controls. Data relevant to all genetic modifiers of SCD were extracted, evaluated, and presented following STREGA and PRISMA guidelines. Weighted z score meta-analyses and pathway analyses were conducted. Outcomes were aggregated into 25 categories, grouped as acute complications, chronic conditions, hematologic parameters or biomarkers, and general or mixed measures of SCD severity. The 571 included studies reported on 29 670 unique individuals (50% ≤ 18 years of age) from 43 countries. Of the 17 757 extracted results (4890 significant) in 1552 genes, 3675 results met the study criteria for meta-analysis: reported phenotype and genotype, association size and direction, variability measure, sample size, and statistical test. Only 173 results for 62 associations could be cross-study combined. The remaining associations could not be aggregated because they were only reported once or methods (eg, study design, reporting practice) and genotype or phenotype definitions were insufficiently harmonized. Gene variants regulating fetal hemoglobin and α-thalassemia (important markers for SCD severity) were frequently identified: 19 single-nucleotide variants in BCL11A, HBS1L-MYB, and HBG2 were significantly associated with fetal hemoglobin (absolute value of Z = 4.00 to 20.66; P = 8.63 × 10-95 to 6.19 × 10-5), and α-thalassemia deletions were significantly associated with increased hemoglobin level and reduced risk of albuminuria, abnormal transcranial Doppler velocity, and stroke (absolute value of Z = 3.43 to 5.16; P = 2.42 × 10-7 to 6.00 × 10-4). However, other associations remain unconfirmed. Pathway analyses of significant genes highlighted the importance of cellular adhesion, inflammation, oxidative and toxic stress, and blood vessel regulation in SCD (23 of the top 25 Gene Ontology pathways involve these processes) and suggested future research areas. The findings of this comprehensive systematic review and meta-analysis of all published genetic modifiers of SCD indicated that implementation of standardized phenotypes, statistical methods, and reporting practices should accelerate discovery and validation of genetic modifiers and development of clinically actionable genetic profiles.


LRP-1: functions, signaling and implications in kidney and other diseases.
Low-density lipoprotein (LDL)-related protein-1 (LRP-1) is a member of LDL receptor family that is implicated in lipoprotein metabolism and in the homeostasis of proteases and protease inhibitors. Expression of LRP-1 is ubiquitous. Up-regulation of LRP-1 has been reported in numerous human diseases. In addition to its function as a scavenger receptor for various ligands, LRP-1 has been shown to transduce multiple intracellular signal pathways including mitogen-activated protein kinase (MAPK), Akt, Rho, and the integrin signaling. LRP-1 signaling plays an important role in the regulation of diverse cellular process, such as cell proliferation, survival, motility, differentiation, and transdifferentiation, and thus participates in the pathogenesis of organ dysfunction and injury. In this review, we focus on the current understanding of LRP-1 signaling and its roles in the development and progression of kidney disease. The role and signaling of LRP-1 in the nervous and cardiovascular systems, as well as in carcinogenesis, are also briefly discussed.


Nanoparticles in Colorectal Cancer Therapy: Latest In Vivo Assays, Clinical Trials, and Patents.
Colorectal cancer (CRC) is the third most common cancer worldwide. Its poor response to current treatment options in advanced stages and the need for efficient diagnosis in early stages call for the development of new therapeutic and diagnostic strategies. Some of them are based on the use of nanometric materials as carriers and releasers of therapeutic agents and fluorescent molecules, or even on the utilization of magnetic materials that provide very interesting properties. These nanoformulations present several advantages compared with the free molecular cargo, including increased drug solubility, bioavailability, stability, and tumor specificity. Moreover, tumor multidrug resistance has been decreased in some cases, leading to improved treatment effectiveness by reducing drug dose and potential side effects. Here, we present an updated overview of the latest advances in clinical research, in vivo studies, and patents regarding the application of nanoformulations in the treatment of CRC. Based on the information gathered, a wide variety of nanomaterials are being investigated in clinical research, even in advanced phases, i.e., close to reaching the market. In sum, these novel materials can offer remarkable advantages with respect to current therapies, which could be complemented or even replaced by these nanosystems in the near future.


Investigation of Antioxidant Markers in Diabetic Patients.
Hyperglycemia is a characteristic of diabetes mellitus, one of the most common metabolic illnesses in the world, and is caused by either reduced insulin secretion or insulin resistance. Diabetes mellitus in adults has been on the rise in recent decades, and it is now the world's fifth-biggest cause of mortality. Diabetes mellitus will affect 592 million people worldwide by 2035, according to the International Diabetes Mellitus Federation, and diabetic complications are divided into two groups of acute and chronic types. Diabetic ketoacidosis, nonketotic hyperosmolar coma, and hypoglycemia are some examples of acute problems, whereas chronic complications include injuries to the small vessels (microvascular issues) and large blood arteries (macrovascular complications). Diabetic neuropathy, retinopathy, and nephropathy all have microvascular consequences, and on the other hand, macrovascular problems have a role in the etiology of cardiovascular disorders such as coronary, cerebrovascular, and peripheral artery diseases. This study aimed to estimate some antioxidant markers, including total protein, albumin, globulin, albumin/globulin ratio (AGR), free amino, free amino/total protein, thiol, thiol/total protein, carbonyl, as well as carbonyl/total protein levels in the plasma of diabetic complications compared to healthy subjects, and investigate the correlations between them. The present study included 120 plasma samples divided into 80 samples as patients with diabetic complications; 26, 26, and 28 samples had diabetic kidney disease, diabetic retinopathy, and diabetic neuropathy, respectively, with the age range between 20-60. Moreover, a total of 40 healthy subjects were included in the study as the control group with the same age ranges. The results showed that there was not any significant difference in carbonyl; however, significant differences were recorded in the total protein, albumin, globulin, AGR, free amino, free amino/total protein, thiol and thiol/total protein, as well as carbonyl/total protein levels in all studied groups. The correlation outcomes indicated that there were significant positive relationships between total protein-globulin, AGR-albumin, and free amine-albumin. In contrast, significant negative correlations were recorded between total protein-AGR and AGR-globulin in diabetic complications. Finally, it was concluded that oxidation markers might play a role in monitoring diabetic complications.


Application of a likelihood ratio test based method for safety signal detection to left ventricular assist devices.
Effective post-market safety surveillance of medical devices is critical for public health. However, many current statistical methods for safety signal detection do not control for type I error when assessing multiple device and adverse event (AE) combinations. This can result in increased false signals, underscoring the need for more robust statistical methods. Moreover, the duration of medical device use can be an important factor to consider in safety surveillance. In this study, we adapted a likelihood ratio test (LRT) based method, which was initially developed and applied to drugs, to identify safety signals for left ventricular assist devices (LVAD). Among patients with chronic, advanced left ventricular failure, we analyzed AE data for HeartWare and HeartMate II patients during a two-year period and further incorporated person-years (henceforth exposure-time). The novel modified LRT and conventional Z-test with p-values adjusted by the Benjamini-Hochberg (BH) procedure were used to explore safety signals by comparing HeartWare and HeartMate II patients in the presence of multiple adverse events. Both methods identified greater incidence of stroke among HeartWare as compared to HeartMate II patients without exposure-time (p = .025 for LRT and p = .027 for Z-test with BH) and with exposure-time (p = .002 for LRT and p = .005 for Z-test with BH). By using improved statistical methods for safety signal detection, potential safety issues can be identified and addressed in a more timely manner to enhance public safety.


Standard thermodynamic properties of H3PO4(aq) over a wide range of temperatures and pressures.
The densities and heat capacities of solutions of phosphoric acid, 0.05 to 1 mol kg-1, were measured using flow vibrating tube densitometry and differential Picker-type calorimetry at temperatures up to 623 K and at pressures up to 28 MPa. The standard molar volumes and heat capacities of molecular H3PO4(aq) were obtained, via the apparent molar properties corrected for partial dissociation, by extrapolation to infinite dilution. The data on standard derivative properties were correlated simultaneously with the dissociation constants of phosphoric acid from the literature using the theoretically founded SOCW model. This made it possible to describe the standard thermodynamic properties, particularly the standard chemical potential, of both molecular and ionized phosphoric acid at temperatures up to at least 623 K and at pressures up to 200 MPa. This representation allows one to easily calculate the first-degree dissociation constant of H3PO4(aq). The performance of the SOCW model was compared with the other approaches for calculating the high-temperature dissociation constant of the phosphoric acid. Using the standard derivative properties, sensitively reflecting the interactions between the solute and the solvent, the high-temperature behavior of H3PO4(aq) is compared with that of other weak acids.


Collecting a set of psoriasis family material through a patient organisation; clinical characterisation and presence of additional disorders.
The aim of the present study was to describe the clinical characteristics of a population of psoriatics sampled from a patient organisation and not from hospitals or out-patient clinics. Furthermore, we wanted to compare siblings with and without psoriasis regarding the occurrence of other diseases. At the end of 1991, we initiated a project which aimed to study genetic factors leading to psoriasis. Firstly, we sent questionnaires to all the members of the Swedish Psoriasis Association. We then examined 1,217 individuals (570 with psoriasis) from 310 families, in their homes in the southern part of Sweden. All the available family members were examined clinically and asked about the course of the skin disease and the occurrence of other diseases. The eight hundred members of the proband generation were divided into two groups, with or without psoriasis, and their clinical features were compared. Most individuals in this study population had a mild form of psoriasis. The siblings with psoriasis had joint complaints significantly more frequently than their siblings without the skin disease and those with joint complaints had more widespread skin disease. Among the other studied concomitant diseases (iritis, heart or hypertension disease, endocrine disease, inflammatory bowel disease and neurological disease), we were not able to find any difference. Seventy-seven of 570 persons were found to be in remission (13.5%). Females had a mean onset 2.5 years earlier than males. We were not able to find any correlation between the extent of the skin disease and age at onset. Twice as many persons with joint complaints were found among those with psoriasis than among those without, 28% versus 13%. Almost half (48%) the psoriatics who also had joint complaints had psoriasis lesions on their nails. Endocrine disorders were found in 9% of those without any allele for Cw6, but only in 1% of those who had Cw6. In fact, none of 183 Cw6 carriers had diabetes, as compared to the population prevalence of 3-5% in Sweden. With the exception of joint complaints, persons with psoriasis, collected from a patient organisation, did not have an increased frequency of (studied) co-existing diseases.


Laser induced fluorescence studies of iodine oxide chemistry. Part II. The reactions of IO with CH3O2, CF3O2 and O3.
The technique of pulsed laser photolysis was coupled to laser induced fluorescence detection of iodine oxide (IO) to measure rate coefficients, k for the reactions IO + CH(3)O(2)--> products (R1, 30-318 Torr N(2)), IO + CF(3)O(2)--> products (R2, 70-80 Torr N(2)), and IO + O(3)--> OIO + O(2) (R3a). Values of k(1) = (2 +/- 1) x 10(-12) cm(3) molecule(-1) s(-1), k(2) = (3.6 +/- 0.8) x 10(-11) cm(3) molecule(-1) s(-1), and k(3a) <5 x 10(-16) cm(3) molecule(-1) s(-1) were obtained at T = 298 K. In the course of this work, the product yield of IO from the reaction of CH(3)O(2) with I was determined to be close to zero, whereas CH(3)OOI was formed efficiently at 70 Torr N(2). Similarly, no evidence was found for IO formation in the CF(3)O(2) + I reaction. An estimate of the rate coefficients k(CH(3)O(2) + I) = 2 x 10(-11) cm(3) molecule(-1) s(-1) and k(CH(3)OOI + I) = 1.5 x 10(-10) cm(3) molecule(-1) s(-1) was also obtained. The results on k(1)-k(3) are compared to the limited number of previous investigations and the implications for the chemistry of the marine boundary layer are briefly discussed.


Synthesis of CulnS2, CulnSe2, and Cu(InxGa(1-x))Se2 (CIGS) nanocrystal "inks" for printable photovoltaics.
Chalcopyrite copper indium sulfide (CuInS2) and copper indium gallium selenide (Cu(InxGa(1-x))-Se2; CIGS) nanocrystals ranging from approximately 5 to approximately 25 nm in diameter were synthesized by arrested precipitation in solution. The In/Ga ratio in the CIGS nanocrystals could be controlled by varying the In/Ga reactant ratio in the reaction, and the optical properties of the CulnS2 and CIGS nanocrystals correspond to those of the respective bulk materials. Using methods developed to produce uniform, crack-free micrometer-thick films, CulnSe2 nanocrystals were tested in prototype photovoltaic devices. As a proof-of-concept, the nanocrystal-based devices exhibited a reproducible photovoltaic response.


Single-Walled Carbon Nanotubes Enhance the Efficiency and Stability of Mesoscopic Perovskite Solar Cells.
Carbon nanotubes are 1D nanocarbons with excellent properties and have been extensively used in various electronic and optoelectronic device applications including solar cells. Herein, we report a significant enhancement in the efficiency and stability of perovskite solar cells (PSCs) by employing single-walled carbon nanotubes (SWCNTs) in the mesoporous photoelectrode. It was found that SWCNTs provide both rapid electron transfer and advantageously shifts the conduction band minimum of the TiO2 photoelectrode and thus enhances all photovoltaic parameters of PSCs. The TiO2-SWCNTs photoelectrode based PSC device exhibited a power conversion efficiency (PCE) of up to 16.11%, while the device fabricated without SWCNTs displayed an efficiency of 13.53%. More importantly, we found that the SWCNTs in the TiO2 nanoparticles (TiO2 NPs) based photoelectrode suppress the hysteresis behavior and significantly enhance both the light and long-term storage stability of the PSC devices. The present work provides important guidance for future investigations in utilizing carbonaceous materials for solar cells.


Breeding migrations by bighorn sheep males are driven by mating opportunities.
In some species where male mating success largely depends on intrasexual competition, males can adopt migratory or resident strategies to seek breeding opportunities. The resulting mixture of resident and migrant tactics within a population can have important ecological, genetic, and evolutionary consequences for metapopulations. Bighorn sheep Ovis canadensis males establish a linear dominance hierarchy that influences their mating tactics. Some males perform breeding migrations during the pre-rut and rut to seek mating opportunities, but little is known about these seasonal movements. We analyzed presence/absence data for 62 marked bighorn males during six mating seasons (20-32 males/year) in the Sheep River Provincial Park, Alberta, Canada, where hunting was not allowed. On average, about half of males left their natal population to rut elsewhere. The proportion of males leaving (yearly range 15%-69%) increased as the number of resident mature males increased and the populational sex ratio decreased, with fewer females during the pre-rut. Among those leaving the park, 24% did so in October, while the trophy sheep hunting season was open. Detailed monitoring of breeding migrations in protected populations could inform management strategies to limit evolutionary impacts of hunting, which can alter size-dependent mortality and create artificial pressures driving changes on heritable traits.


Preoperative Botulinum toxin A enabling defect closure and laparoscopic repair of complex ventral hernia.
Operative management of complex ventral hernia still remains a significant challenge for surgeons. Closure of large defects in the unprepared abdomen has serious pathophysiological consequences due to chronic contraction and retraction of the lateral abdominal wall muscles. We report outcomes of 56 consecutive patients who had preoperative Botulinum toxin A (BTA) abdominal wall relaxation facilitating closure and repair. This was a prospective observational study of 56 patients who underwent ultrasound-guided BTA into the lateral abdominal oblique muscles prior to elective ventral hernia repair between November 2012 and January 2017. Serial non-contrast abdominal CT imaging was performed to evaluate changes in lateral oblique muscle length and thickness. All hernias were repaired laparoscopically, or laparoscopic-open-laparoscopic (LOL) using intraperitoneal onlay mesh. 56 patients received BTA injections at predetermined sites to the lateral oblique muscles, which were well tolerated. Mean patient age was 59.7 years, and mean BMI was 30.9 kg/m2 (range 21.8-54.0). Maximum defect size was 24 × 27 cm. A subset of 18 patients underwent preoperative pneumoperitoneum as an adjunct procedure. A comparison of pre-BTA to post-BTA imaging demonstrated an increase in mean lateral abdominal wall length from 16.1 cm to 20.1 cm per side, a mean gain of 4.0 cm/side (range 1.0-11.7 cm/side) (p < 0.0001). This corresponds to an unstretched mean length gain of 8.0 cm of the lateral abdominal wall. Laparoscopic/LOL primary closure was achieved in all cases, with no clinical evidence of raised intra-abdominal pressures. One patient presented with a new fascial defect 26 months post-operative. Preoperative BTA to the lateral abdominal wall muscles is a safe and effective technique for the preparation of patients prior to operative management of complex ventral hernias. BTA temporary flaccid paralysis relaxes, elongates and thins the chronically contracted abdominal musculature. This in turn reduces lateral traction forces facilitating laparoscopic repair and fascial closure of large defects under minimal tension.


Event-related potential indicators of text integration across sentence boundaries.
An event-related potentials (ERPs) study examined word-to-text integration processes across sentence boundaries. In a two-sentence passage, the accessibility of a referent for the first content word of the second sentence (the target word) was varied by the wording of the first sentence in one of the following ways: lexically (explicitly using a form of the target word); conceptually (using a paraphrase of the target word), and situationally (encouraging an inference concerning the referent of the target word). A baseline condition had no coreference between the two sentences. ERP results on the target word indicated multiple effects related to word identification and word-to-referent mapping processes. Both the explicit and paraphrase conditions, but not the inference condition, showed a reduced N400 relative to the baseline condition, consistent with immediate integration by lexico-semantic processes. A 300-ms effect (P300) was found in the paraphrase condition. The results were consistent with an immediate integration hypothesis and furthermore differentiated a lexical (N200), a conceptual (P300), and a situational (N400) component for this integration. The conceptual basis appears not to extend to predictive inferences.


Multi-camera field monitoring reveals costs of learning for parasitoid foraging behaviour.
Dynamic conditions in nature have led to the evolution of behavioural traits that allow animals to use information on local circumstances and adjust their behaviour accordingly, for example through learning. Although learning can improve foraging efficiency, the learned information can become unreliable as the environment continues to change. This could lead to potential fitness costs when memories holding such unreliable information persist. Indeed, persistent unreliable memory was found to reduce the foraging efficiency of the parasitoid Cotesia glomerata under laboratory conditions. Here, we evaluated the effect of such persistent unreliable memory on the foraging behaviour of C. glomerata in the field. This is a critical step in studies of foraging theory, since animal behaviour evolved under the complex conditions present in nature. Existing methods provide little detail on how parasitoids interact with their environment in the field, therefore we developed a novel multi-camera system that allowed us to trace parasitoid foraging behaviour in detail. With this multi-camera system, we studied how persistent unreliable memory affected the foraging behaviour of C. glomerata when these memories led parasitoids to plants infested with non-host caterpillars in a semi-field set-up. Our results demonstrate that persistent unreliable memory can lead to maladaptive foraging behaviour in C. glomerata under field conditions and increased the likelihood of oviposition in the non-host caterpillar Mamestra brassica. Furthermore, these time- and egg-related costs can be context dependent, since they rely on the plant species used. These results provide us with new insight on how animals use previously obtained information in naturally complex and dynamic foraging situations and confirm that costs and benefits of learning depend on the environment animals forage in. Although behavioural studies of small animals in natural habitats remain challenging, novel methods such as our multi-camera system contribute to understanding the nuances of animal foraging behaviour.


Computed tomography and positron emission tomography/computed tomography surveillance after combined modality treatment of supradiaphragmatic Hodgkin lymphoma: a clinical and economic perspective.
We studied the clinical benefits of radiological imaging, in the follow-up of patients after combined modality treatment for stage I/II classical supradiaphragmatic Hodgkin lymphoma (HL). Imaging data were collected for 78 adults treated during 1996-2008. Median follow-up was 4.6 years. Six of the nine relapses were detected clinically. On average, 31 imaging studies/patient were performed, with an estimated cost of $12 608/patient. Chest computed tomography (CT) scans accounted for 25%, abdominopelvic CT scans 41% and positron emission tomography (PET) or PET/CT scans 22% of this expense. Only one patient recurred infradiaphragmatically. The estimated radiation dose from imaging was 399 mSv and 229 mSv per patient, in relapse and non-relapse groups, respectively. CT scans contributed over 80% of the imaging radiation exposure. The routine use of CT scans in the surveillance of patients with HL after curative treatment adds to healthcare costs and total body radiation exposure with a low yield. History and physical examination remain effective tools for the follow-up of patients.


The potential of transcranial magnetic stimulation for population-based application: a region-based illustrated brief overview.
The awareness of the global trends in neuroscience study, especially in the cognitive neuroscience field, should be increased. One notable approach is the use of transcranial magnetic stimulation (TMS) not only as a research tool but also as a choice for treatment and rehabilitation in neurological disorders, such as post-stroke hemiplegia, visuospatial neglect syndrome, Alzheimer's disease (AD) and psychiatric conditions such as major depression and schizophrenia. All of these occur in significant numbers in highly populated regions. This paper briefly discusses the basic protocols and potential benefits of using TMS with the aim of providing insight that is useful in the design of future public health strategies in highly populated regions with a large neurocognitive burden of disease where this technique is currently underemployed.


The Prevalence and Associated Factors of Alcohol Consumption: A Cross-Sectional Study in Khon Kaen, Thailand.
Knowledge of the situation and risk factors associated with alcohol consumption are essential for prevention and control measures of health consequences. This study aims to explore the prevalence of alcohol consumption and the factors associated with alcohol consumption in the population aged 12-65 years. This was a descriptive study. This survey used multi-stage sampling and face-to-face interviews, carried out in both urban and rural areas. Those interviewed were a representative sample of 876 people in the ratio ofone male and one female to represent the household. Data were collected by interviewers between 1 January and 28 February 2012. The data were analyzed by frequency, percentage, mean, standard deviation, Chi-square, multiple logistic regression, OR and 95% CI of OR. This study was approved by the ethics and research institutional review board of Khon Kaen University No. HE53121. The mean age of the respondents was 41.7 years (SD 13.6). The majority of the respondents were the head of the family (33.9%), those educated to primary school level (44.6%), living in rural areas (55.9%), who were married (70.7%), and who were farmers (35.3%). The prevalence of alcohol consumption during the previous week was 6.3% (95% CI: 4.7 to 7.9), during the previous month was 35.2% (95% CI: 32.0 to 38.3), and during the previous year was 41.0% (95% CI: 37.7 to 44.2). The factors associated with alcohol consumption were gender (male/female) AOR 6.5 (95% CI 4.4 to 8.9, p-value < 0.001) age group (25-44/45-65) AOR 1.6 (95% CI 1.1 to 2.4, p-value = 0.011) location (rural/urban) AOR 1.7 (95% C1 1.3 to 2.4, p-value < 0.001) educational attainment (bachelor or master degree/primary school) AOR 1.7 (95% CI 1.1 to 2.8, p-value = 0.031) and the occupation (laborer) AOR 1.6 (95% CI 1.1 to 2.4, p-value = 0.015). Knowing the prevalence and factors associated with alcohol consumption are essential to understanding the situation, solving related problems and using the information in the campaign for the prevention and control of alcohol consumption


Reduction of opiate withdrawal symptoms with use of clonidine in a county jail.
Increasingly, addicted inmates admitted to jail in New Mexico are in the process of opiate withdrawal. While the standard for opiate detoxification is a narcotic taper, correctional policy restricts opiate use for safety reasons. An alternative for withdrawal is a supportive intervention with clonidine, a non-opiate. Could clonidine be beneficial for acute opiate withdrawal symptoms in this population? Fifty-five inmates (37 male and 18 female) volunteered to participate in assessing clonidine for the reduction of withdrawal symptoms. Symptoms were assessed with the Subjective Opiate Withdrawal Scale and treated with a standard clonidine protocol. Clonidine significantly decreased the mean scores at 1 and 4 hours after medication use. Clonidine for opiate withdrawal reduces symptoms when opiate-assisted detoxification is not available.


Polymorphism in chromosome 4.
Chromosomal analyses were performed on 302 individuals, using QFQ banding techniques to determine the occurrence of heteromorphism of chromosome 4. Two type of heteromorphism were observed, one showing an intensely fluorescent band in the centromere region and the other an intensely fluorescent band in the proximal area of the short arm. No one individual possessed both type of heteromorphism. A higher frequency of chromosome 4 heteromorphism was found in patients with schizophrenia, mental retardation, hyperactivity, developmental delay and speech impediments than in normal individuals.


[Synthesis and characteristics of integrated bionic mandibular condylar scaffold].
OBJECTIVE This study aims to construct a chitosan (CS)-polycaprolactone (PCL)-hydroxyapatite (HA) composite biomimetic scaffold to replace condyle and to explore the tissue engineering applications of condylar. A resin mold of the mandibular condyle was prepared by using rapid prototyping techniques. A mandibular condylar integrated biomimetic scaffold model was prepared by solution casting-ice Lek. PCL and CS were mixed at a ratio of 4:1. HA at quality ratios of 40%, 50%, 60%, and 70% was added to groups a, b, c, and d, respectively. The microscopic morphology, porosity, infrared spectra, X-ray diffraction pattern, and mechanical properties of the scaffold were observed. The scaffold that includes both upper and lower parts displayed the same features (i.e., shape, yellow-white appearance, and hard texture) as the mandibular condyle. Scanning electron microscopy showed that the composite scaffold had a 3D network spatial structure, 70%-85% porosity, and 10-200 µm pore size. Infrared spectra showed that the peak intensity reduced with decreasing HA content. X-ray diffraction showed that the diffraction peak decreased with increasing HA content. Suitable tensile and compressive and flexural strength were discovered in the presence of 50% HA. The scaffold prepared by solution casting-ice Lek shows favorable comprehensive features and is expected to replace human condylar.